Clinical and pharmacoeconomic evaluation of fidaxomicin in patients over 65 years of age and immunocompromised patients with recurrent and refractory Clostridioides difficile infection

Clinical and pharmacoeconomic evaluation of fidaxomicin in patients over 65 years of age and immunocompromised patients with recurrent and refractory Clostridioides difficile infection | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical and pharmacoeconomic evaluation of fidaxomicin in patients over 65 years of age and immunocompromised patients with recurrent and refractory Clostridioides difficile infection Isabella Alram, Sebastian M. Wingen-Heimann, Marie Engelhard, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7445823/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Jan, 2026 Read the published version in BMC Infectious Diseases → Version 1 posted 10 You are reading this latest preprint version Abstract Background Recurrent or refractory Clostridioides difficile infection (CDI) often affects older and immunocompromised patients, posing clinical and economic challenges. While fidaxomicin has shown lower recurrence rates than vancomycin in the general population, evidence in this population remains limited. Methods This retrospective, multicentre case-control study compared patients aged > 65 years or immunocompromised patients receiving fidaxomicin (case group) with those treated with vancomycin (control group) for recurrent or refractory CDI. A microcosting approach was used to assess direct treatment costs. Results A total of 344 patients were included (172 per group). Compared to the control group, the fidaxomicin group presented a significantly higher rate of symptom reduction on day 10 (n = 163, 95% vs. n = 147, 86%; p = 0.004) and lower CDI recurrence rates (n = 36, 21% vs. n = 63, 37%; p = 0.001). While the mean CDI treatment costs per patient were significantly higher in the fidaxomicin group (p < 0.001), the hospitalisation and overall treatment costs were comparable (€19,898, 95% CI €16,151-€23,645 vs. €20,469, 95% CI €16,837-€24,101, p = 0.811; €17,798, 95% CI €14,620-€20,975 vs. €17,300, 95% CI €14,199-€20,400, p = 0.840). Key cost drivers were hospitalisation, intensive care unit treatment, and severe initial CDI. Conclusions Despite higher drug acquisition costs of fidaxomicin, overall treatment costs were comparable between the two groups with better clinical outcomes in patients treated with fidaxomicin. Fidaxomicin Clostridioides difficile Infection Disease Recurrence Healthcare Resource Utilization Observational Study Figures Figure 1 Introduction Clostridioides difficile infection (CDI) is a common cause of hospital-acquired infectious diarrhoea in hospitalised patients. Its severity ranges from asymptomatic carriage or diarrhoea to life-threatening pseudomembranous colitis. It is often a complication of broad-spectrum antibiotic treatment [ 1 ]. The incidence of and mortality due to CDI is higher in immunocompromised patients compared to the general population – including haematological/oncological patients and patients after solid-organ transplantation [ 2 – 5 ]. This also includes the population of geriatric patients [ 6 ]. In these vulnerable patient populations, especially after intensive chemotherapy and under immunosuppressive therapy, a disruption of the gut microbiome is associated with worsened clinical outcomes, including increased infection rates, treatment-related complications, and mortality [ 7 – 9 ]. Fidaxomicin is recommended as first-line treatment for initial CDI in the standard of care setting as well as for patients with a high risk of recurrence [ 10 ]. The occurrence of recurrent and refractory CDI is an additional burden for patients, clinicians, and healthcare systems [ 11 , 12 ]. If a first CDI recurrence occurs, fidaxomicin is recommended if patients are treated with vancomycin during the initial CDI episode [ 10 ]. Controversy, however, exists regarding the clinical and health economic impact of fidaxomicin in the context of recurrent and refractory disease [ 13 ]. To date, the clinical impact of fidaxomicin has been tested in randomised controlled trials [ 14 – 19 ], whereas the clinical and health economic outcomes have been examined in some single-centre, real-world studies regarding the treatment of mostly initial CDI [ 20 – 24 ]. Studies that specifically investigated patients with recurrent CDI demonstrated that fidaxomicin was associated with significantly lower recurrence rates compared to vancomycin or metronidazole [ 25 , 26 ]. Although evidence exists regarding the efficacy of fidaxomicin in treating recurrent or refractory CDI, comprehensive real-world data remain limited, especially in immunocompromised patients and patients at advanced age. Moreover, despite its recommendation as first-line therapy in recent guidelines, the use of fidaxomicin remains limited in practice, mainly due to financial constraints which take precedence over clinical prioritisation. We therefore performed a retrospective case-control study at two tertiary-care hospitals in Germany to observe and evaluate clinical and health economic experiences with fidaxomicin for treating recurrent or refractory CDI in immunocompromised patients and patients aged over 65 years compared to vancomycin-treated controls. Patients and Methods Study design and study population We performed a retrospective, multicentre case-control study at two German university hospitals (Cologne and Frankfurt am Main). We included adult patients with recurrent or refractory CDI receiving fidaxomicin (case group) or vancomycin (control group), respectively, between January 2013 and December 2023. For inclusion, they needed to present with at least one of the following inclusion criteria: (i) haematological or oncological underlying disease, (ii) diseases requiring immunosuppressive therapy, such as autoimmune disorders or post-organ transplantation status, and (iii) age 65 years or older. The follow-up period was 90 days. Matching of control patients from the same participating study site was performed by using a nearest neighbour approach based on the following criteria: age, sex, in- or outpatient status, underlying disease, year of inpatient stay, and if treated in an intensive care unit (ICU) the APACHE score. Only patients who were alive after at least ten days following treatment initiation with fidaxomicin or vancomycin were included. Definitions Diarrhoea was defined as three or more unformed stools per day. CDI was defined primarily as clinical findings consistent with CDI and microbiological evidence of C. difficile toxins by enzyme immunoassay. In addition, cases were identified based on a clinical presentation consistent with CDI in combination with a positive nucleic acid amplification test (NAAT), preferably with a low cycle threshold, or a positive toxigenic C. difficile culture, if there was no evidence of another cause of diarrhoea. Furthermore, cases of pseudomembranous colitis confirmed by endoscopy, post colectomy, or autopsy were included, if accompanied by a positive test for the presence of toxigenic C. difficile . Recurrence of CDI was defined as a new CDI after initial response to treatment within a period of 90 days. Response to treatment was defined as the absence of diarrhoea for two consecutive days, with improvement continuing throughout the duration of the CDI treatment and no further treatment of CDI required from the second day after completion of the treatment. Refractory CDI was defined as persistence of diarrhoea beyond day 5 of CDI antibiotic treatment or recurrence of diarrhoea on days 5 to 10 of CDI antibiotic treatment after initial cessation of diarrhoea. Study objectives and hypotheses We evaluated the clinical effectiveness of fidaxomicin in treating recurrent and refractory CDI, along with associated healthcare resource utilization and costs. In addition, we examined further outcomes, including time to cure, number of recurrent CDI episodes, and overall length of hospital stay (LOS) in patients treated with fidaxomicin compared with control patients. Data documentation Patient data were collected anonymously into a web-based eCRF, accessible via www.clinicalsurveys.net , after conclusion of the 90-day observation period or after death of the patient. Under the supervision of experienced internal medicine specialists, medical documentation specialists carried out the documentation at the respective study site. The leading study site University Hospital Cologne handled the data monitoring and query management. Healthcare resource utilization and cost analysis The healthcare resource utilization and cost analysis was performed from the perspective of the German healthcare system [ 27 ]. It contained direct treatment cost factors that included costs for hospital treatment and costs for CDI medication. Costs for treatment on hospital ward were calculated based on the German Diagnosis Related Groups (G-DRG) systematic provided by Institute for the Hospital Renumeration System für das Entgeltsystem im Krankenhaus (InEK - Institut für das Entgeltsystem im Krankenhaus) and represented personnel and material costs from the years 2013 to 2023 [ 28 ]. Costs for CDI medication were calculated by using the pharmacy retail price from 2024 extracted from the Rote Liste®, a comprehensive drug directory in Germany [ 29 ]. To ensure comparability of hospitalisation and drug acquisition costs, the microcosting approach used year 2024 values expressed in Euros (€). Indirect cost factors, such as productivity losses due to illness-related disability or death before retirement age, were disregarded because of the complex underlying diseases or retirement age. Statistical analysis The data were processed and analysed using R (R version 4.5.0) [ 30 ]. Patient characteristics and outcomes are presented as percentages (absolute numbers) for categorical variables and means (95% confidence interval = 95% CI) for continuous variables. Age and treatment durations are reported as medians (range/inter quartile range). Statistical significance was determined via Pearson’s chi-squared test, Mann-Whitney U Test, Fisher’s exact test or Student’s t-test (two-sided), as appropriate, with p < 0.05 as the significance level. Logistic regression and Cox regression analyses were performed via maximum likelihood estimation. A multivariable generalised linear model (GLM) with a gamma distribution and log-link was conducted to assess variables that influence direct treatment costs. Regression analyses included independent patient characteristics and risk factors as well as the underlying CDI treatment. Prior to multivariable analyses, univariate analyses were performed, and all variables with p < 0.1 were included in the model. The multivariable analyses reported odds ratios (OR) for logistic regression and GLM or hazard ratios (HR) for Cox regression and 95% CIs; the level of significance was set at p < 0.05. Survival analysis was conducted via the Kaplan-Meier method to estimate the cumulative probability of death over time. In accordance with the real-world design of this study, patients with missing values were excluded for the respective analysis step (complete case analysis), if data were missing completely at random. Results Study population Following the screening of 5,600 potential cases within the inclusion period in both centres, a total of 344 patients met the eligibility criteria and were therefore enrolled in the study. The patient characteristics are demonstrated in Table 1 . Approximately one third of the patients presented with refractory CDI and two thirds with recurrent CDI. The most common risk factors were haematological disease, age over 65 years, and a previous hospitalisation within 90 days prior to CDI diagnosis. Almost all patients suffered from mild to moderate CDI, with hospital-acquired infections observed in 42% (n = 73) of the fidaxomicin group and 45% (n = 78) of the vancomycin group. We found no significant differences between the patient characteristics of the fidaxomicin- and vancomycin-treated patients. For five patients in the fidaxomicin group, it was not possible to find suitable controls, such that matching was carried out across study sites. Table 1 Characteristics of patients with recurrent or refractory Clostridioides difficile infection Fidaxomicin (n = 172) Vancomycin (n = 172) p value Female , n (%) 92 (54) 78 (45) 0.131 a Age , median (range) 66 (19–85) 67 (19–84) 0.878 b Body mass index , mean (95% CI) 23.6 (20.0–26.0) 24.6 (21.0-27.8) 0.083 c Caucasian , n (%) 169 (98) 168 (98) 0.703 a Risk factors , n (%) Haematological disease 62 (36) 56 (33) 0.496 a Oncological disease 28 (16) 31 (18) 0.668 a Kidney transplantation 24 (14) 22 (13) 0.284 a Liver transplantation 6 (4) 3 (2) 0.295 d Other underlying disease with immunosuppression 15 (9) 22 (13) 0.330 a Geriatric patient > = 65 years 47 (27) 46 (27) 0.903 a >= 2 CDI episodes 90 days before current CDI diagnosis 19 (11) 15 (9) 0.463 a Previous CDI recurrence within 90 days prior to diagnosis 22 (13) 13 (8) 0.109 a Previous hospitalisation within 90 days prior to diagnosis 122 (71) 116 (67) 0.484 a Severe first CDI episode 16 (9) 11 (6) 0.316 a Other comorbidities , n (%) Cardiovascular disease 114 (66) 116 (67) 0.819 a Endocrinological disease 68 (40) 59 (34) 0.315 a Gastroenterological disease (except of CDI) 50 (29) 52 (30) 0.813 a Nephrological disease 66 (38) 61 (36) 0.576 a Psychiatric disease 20 (12) 27 (16) 0.272 a Pulmonary disease 39 (23) 27 (16) 0.100 a Type of CDI , n (%) Recurrent CDI 110 (64) 112 (65) 0.822 a Refractory CDI 62 (36) 61 (35) 0.910 a Severity of recurrent/refractory CDI , n (%) Mild to moderate 170 (99) 171 (99) 1.000 d Severe 1 (1) 1 (1) 1.000 d Severe, complicated 1 (1) 0 (0) 1.000 d Number of episodes of recurrent/refractory CDI, n (%) 1 172 (100) 172 (100) 1.000 a 2 36 (21) 63 (37) 0.001 a 3 1 (1) 10 (6) 0.157 d 4 - 2 (1) 0.007 d Type of CDI acquisition , n (%) 0.556 a Community-acquired CDI 28 (16) 32 (19) Hospital-acquired CDI 73 (42) 78 (45) Health system-acquired CDI 59 (34) 50 (29) Unknown 12 (7) 12 (7) Abbreviations: CI, confidence interval, CDI, Clostridioides difficile infection a Pearson’s chi-squared test, b Mann-Whitney-U test, c Student’s t-test, d Fisher’s exact test Treatment types and durations In the fidaxomicin group, 63% of the patients (n = 108) were treated as inpatients, 15% (n = 26) as outpatients and 22% (n = 38) in an in- and outpatient setting. In the vancomycin group, 58% (n = 100) of the patients were inpatients, 14% (n = 24) were outpatients, and 28% (n = 48) were in- and outpatients. In the inpatient setting of fidaxomicin-treated patients, 96% (n = 140) received fidaxomicin standard dose (200 mg twice a day), whereas 2% (n = 3) were treated with fidaxomicin extended-pulsed therapy. In 1% (n = 1) of the patients, bezlotoxumab or faecal microbiota transfer (FMT) was added to the fidaxomicin treatment, respectively. Outpatients were treated with fidaxomicin standard dose (77%, n = 20) or fidaxomicin extended-pulsed therapy (12%, n = 3), while bezlotoxumab was added in 15% (n = 4) and FMT in 4% (n = 1) of patients. There were no statistically significant differences in the duration of treatment between the groups (Table 2 ). Across all recurrent and refractory CDI episodes, fidaxomicin was given orally for a median duration of 11 days (fidaxomicin group: IQR 11–15; vancomycin group: IQR 10–13) in both groups (p = 0.367), whereas vancomycin was given orally for a median duration of 13 days (IQR 10–20) in the fidaxomicin group and 12 days (IQR 11–21) in the vancomycin group (p = 0.876). Table 2 Treatment details of patients with recurrent or refractory Clostridioides difficile infection Fidaxomicin group (n = 172) Vancomycin group (n = 172) p value Treatment of recurrent/refractory CDI, n (%) 172 (100) 169 (98) 0.248 c Fidaxomicin, n (%) 165 (96) 10 (6) < 0.001 a Duration (days), Median (IQR) 11 (11–15) 11 (10–13) 0.367 b Fidaxomicin extended pulsed therapy, n (%) 7 (4) 1 (1) 0.067 c Duration (days), Median (IQR) 26 (26–27) 13 (na) 0.163 b Vancomycin, n (%) 4 (2) 165 (96) < 0.001 c Duration (days), Median (IQR) 13 (10–20) 12 (11–21) 0.876 b Vancomycin tapered pulsed therapy, n (%) - 12 (7) - Duration (days), Median (IQR) - 49 (36–56) - Metronidazole, n (%) - 8 (5) - Duration (days), Median (IQR) - 11 (10–14) - Bezlotoxumab, n (%) 5 (3) - - Duration (days), Median (IQR) 26 (11–26) - - Additional antibiotic treatment during CDI treatment, n (%) 95 (55) 105 (61) 0.274 a after CDI treatment, n (%) 95 (55) 93 (54) 0.829 a Hospital visits Inpatient treatment, n (%) 146 (85) 148 (86) 0.760 a Number of hospitalisations, Median (Range) 1 (1–5) 1 (1–6) 0.689 b Length of initial hospital stay, Median (IQR) 31 (13–55) 33 (14–52) 0.845 b Overall hospital length of stay, Median (IQR) 36 (19–55) 37 (19–59) 0.956 b Outpatient treatment, n (%) 64 (37) 72 (42) 0.378 a Number of visits, Median (Range) 1 (1–3) 1 (1–3) 0.025 b Abbreviations: CI, confidence interval; IQR, interquartile range; LOS, length of stay; CDI, Clostridioides difficile infection; na, not applicable a Pearson’s chi-squared test, b Mann-Whitney-U test, c Fisher’s exact test With a median of 31 days (IQR 13–55) and 33 days (IQR 14–52) the hospital length of stay of the initial hospitalisation was comparable in the fidaxomicin and vancomycin group (p = 0.845) with a similar amount of CDI treatment as the reason for hospitalisation (44%, n = 64 vs. 45%, n = 67; p = 0.845). No significant differences were detected between both groups regarding the number of patients treated in the intermediate care unit (24%, n = 35 vs. 24%, n = 36; p = 0.894) or the ICU (23%, n = 34 vs. 22%, n = 33; p = 0.892) during the observation period. Patients in both groups had a median of one outpatient visit, with significantly more outpatient visits in the vancomycin group than in the fidaxomicin group (p = 0.025). Overall effectiveness of fidaxomicin Symptom reduction on day 10 was reached in significantly more fidaxomicin-treated patients (95%, n = 163) than in vancomycin-treated patients (86%, n = 147, p = 0.004). Univariate logistic regression analysis revealed that fidaxomicin as CDI therapy was the only independent variable with an impact on the symptom reduction on day 10 (OR 3.080, p = 0.005; Table 3 ). The median number of days with CDI-associated diarrhoea was similar in both groups (fidaxomicin group: 5 days, IQR 3–8 days; vancomycin group: 4 days, IQR 3–9 days; p = 0.817). A new CDI recurrence within 90 days occurred in significantly more vancomycin-treated patients (37%, n = 63) than in fidaxomicin-treated patients (21%, n = 36; p = 0.001). Overall, there were more recurrent than refractory CDIs (Table 1 ). The multivariable logistic regression analysis demonstrated that CDI therapy with fidaxomicin significantly reduced the risk of CDI recurrence within the 90-day observational period (OR 0.443, p = 0.001), while additional antibiotic treatment after CDI therapy was significantly associated with an increased risk of CDI recurrence (OR 2.221, p = 0.002; Table 4 ). Table 3 Univariate logistic regression analyses of independent variables with impact on Clostridioides difficile infection-associated symptom reduction on day 10 based on risk factors for Clostridioides difficile infection and Clostridioides difficile infection therapy Variable p value (univariate) Odds ratio 95% CI Age 0.493 1.008 0.985–1.029 Fidaxomicin as CDI therapy 0.005 3.080 1.440–7.176 Previous CDI recurrence a 0.136 0.482 0.194–1.371 Previous hospitalisation a 0.326 1.444 0.678–2.975 Severe first CDI episode 0.655 1.404 0.392–8.973 Inpatient treatment 0.630 0.765 0.220–2.054 Additional antibiotic treatment during CDI treatment 0.415 0.736 0.341–1.516 Abbreviations: CDI, Clostridioides difficile infection; CI, confidence interval a within 90 days prior to diagnosis Table 4 Uni- and multivariable logistic regression analyses of independent variables with impact on the occurrence of a new Clostridioides difficile infection recurrence within the 90-day observational period based on risk factors for Clostridioides difficile infection and Clostridioides difficile infection therapy Variable p value (uni-variate) Odds ratio 95% CI p value (multi-variate) Odds ratio 95% CI Age 0.687 1.003 0.988–1.019 - - - Fidaxomicin as CDI therapy 0.001 0.458 0.281–0.737 0.001 0.443 0.270–0.719 Previous CDI recurrence a 0.252 1.532 0.722–3.141 - - - Previous hospitalisation a 0.520 0.849 0.517–1.408 - - - Severe first CDI episode 0.587 1.261 0.523–2.846 - - - Inpatient treatment 0.587 0.836 0.444–1.629 - - - Additional antibiotic treatment during CDI treatment 0.284 1.299 0.808–2.110 - - - Additional antibiotic treatment after CDI treatment 0.002 2.146 1.323–3.534 0.002 2.221 1.360–3.691 Abbreviations: CDI, Clostridioides difficile infection; CI, confidence interval a within 90 days prior to diagnosis Overall, 13% of all patients (n = 46) died within the 90-day observational period, with no significant difference between the groups (fidaxomicin group: 15%, n = 25; vancomycin group: 12%, n = 21; p = 0.483; Fig. 1 ). In one fidaxomicin-treated patient, death was attributable to CDI complications and in another patient, death was partially attributable to CDI whereas in the vancomycin group no deaths were attributable to CDI. The death from CDI in the two fidaxomicin-treated patients was associated with another episode of CDI after the successful treatment of the first recurrence with fidaxomicin. In the subgroup of patients with recurrent CDI, we found similar clinical outcomes ( Table S1 ). In contrast, in the subgroup of patients with refractory CDI, no significant differences in symptom reduction on day 10 or in the rate of recurrence were detected ( Table S3 ). Costs for hospitalisation and CDI treatment Direct treatment costs for recurrent and refractory CDI patients, including hospitalisation and drug acquisition costs, are described in Table 5 . For the 294 patients treated in the inpatient and combined in- and outpatient setting, DRG data were available for 91% (n = 268) and were therefore used to calculate hospitalisation costs. Mean overall hospitalisation costs were comparable between both groups with €19,898 per patient (95% CI 16,151 − 23,645) in the fidaxomicin group and €20,469 per patient (95% CI 16,837 − 24,101) in the control group (p = 0.811). Over 85% of those expenses could be assigned to the initial hospitalisation in both groups, amounting to €17,300 per patient (95% CI 13,596 − 21,005) in the fidaxomicin group and €17,520 per patient (95% CI 13,958 − 21,082) in the control group (p = 0.969). Expenses for patients that were hospitalised due to recurrent or refractory CDI were an average of €4,000 higher in the fidaxomicin group compared with the vancomycin group (€8,552 per patient, 95% CI 5,717 − 11,386; €12,578 per patient, 95% CI 9,066 − 16,089, p = 0.071). Table 5 Direct treatment costs for patients with recurrent or refractory Clostridioides difficile infection in Euro Fidaxomicin group (n = 172) Vancomycin group (n = 172) p value Hospitalisation costs I, b , n (%) 133 (77) 135 (78) 0.795 d Costs per patient, mean (95% CI) 19,406 (15,215 − 23,597) 19,300 (15,534 − 23,067) 0.990 a Hospitalisation costs I , n (%) (Year 2024) 133 (77) 135 (78) 0.795 d Costs per patient, mean (95% CI) 19,898 (16,151 − 23,645) 20,469 (16,837 − 24,101) 0.811 a Drug acquisition costs for first recurrent or refractory CDI c Fidaxomicin, n (%) 165 (96) - - Costs per patient, mean (95% CI) 2,020 (1,952 − 20,091) - - Fidaxomicin extended pulsed therapy, n (%) 7 (4) - - Costs per patient, mean (95% CI) 1,706 (1,647-1,761) - - Vancomycin, n (%) - 165 (96) - Costs per patient, mean (95% CI) - 976 (837-1,130) - Vancomycin tapered pulsed therapy, n (%) - 9 (5) - Costs per patient, mean (95% CI) - 1,272 (730-2,063) - Metronidazole, n (%) - 1 (1) - Costs per patient, mean (95% CI) - 77 - Bezlotoxumab, n (%) 3 (2) - - Costs per patient, mean (95% CI) 2,228 (1,800-2,479) - - Drug acquisition costs for second recurrent or refractory CDI c Fidaxomicin, n (%) 27 (16) 19 (11) 0.002 d Costs per patient, mean (95% CI) 2,147 (1,835-2,561) 2,059 (1,806-2,364) 0.699 a Fidaxomicin extended pulsed therapy, n (%) - 1 (1) - Costs per patient, mean (95% CI) - 1,147 - Vancomycin, n (%) 4 (2) 18 (10) 0.002 d Costs per patient, mean (95% CI) 1,220 (423-2,766) 510 (401–641) 0.161 a Vancomycin tapered pulsed therapy, n (%) - 2 (1) - Costs per patient, mean (95% CI) - 582 (384–779) - Metronidazole, n (%) - 6 (3) - Costs per patient, mean (95% CI) - 42 (37–47) - Drug acquisition costs for third recurrent or refractory CDI c Vancomycin, n (%) - 2 (1) - Costs per patient, mean (95% CI) - 2,919 (538-5,301) - Vancomycin tapered pulsed therapy, n (%) - 2 (1) - Costs per patient, mean (95% CI) - 850 (818–882) - Metronidazole, n (%) - 1 (1) - Costs per patient, mean (95% CI) - 24 - Overall recurrent/ refractory CDI drug acquisition costs c , n (%) 172 (100) 169 (98) 0.248 e Costs per patient, mean (95% CI) 2,412 (2,254-2,594) 1,256 (1,074 − 1,453) < 0.001 a Overall direct treatment costs b, c , n (%) 172 (100) 172 (100) - Costs per patient, mean (95% CI) 17,417 (13,935 − 20,899) 16,382 (13,220 − 19,545) 0.676 a Overall direct treatment costs, n (%) (Year 2024) 172 (100) 172 (100) - Costs per patient, mean (95% CI) 17,798 (14,620 − 20,975) 17,300 (14,199 − 20,400) 0.840 a Abbreviations: CI, Confidence interval; CDI, Clostridioides difficile infection I n-values differ due to missing data; a Bootstrapped t-test (independent samples, two sided); b Based on G-DRGs from 2013 to 2023; c Based on Rote Liste® prices from 2024; d Pearson chi-square test (two-tailed); e Fisher´s exact test Costs for CDI treatment with fidaxomicin and vancomycin were calculated stratified by CDI episode. For initial recurrent or refractory CDI treatment, a mean of €2,020 (95% CI 1,952 − 20,091) and €1,706 (95% CI 1,647-1,761) per patient was spent on fidaxomicin and fidaxomicin extended pulsed therapy. Overall, CDI drug acquisition costs were significantly higher in the fidaxomicin group, with a mean cost of €2,412 per patient (95% CI 2,254-2,594), compared with the vancomycin group, with a mean cost of €1,256 per patient (95% CI 1,074 − 1,453, p < 0.001). With regard to the overall direct treatment costs, expenses were similar in both groups (fidaxomicin group: €17,417 per patient, 95% CI 13,935 − 20,899; vancomycin group: €17,300, 95% CI 14,199 − 20,400; p = 0.840). Expenses of €2,180 (95% CI 1,933-2,486) and €1,928 (95% CI 1,487-2,405) per patient in the fidaxomicin and vancomycin groups were associated with drug acquisition costs in the outpatient setting (p = 0.367). For inpatient treatment and in- and outpatient treatment, significantly higher mean costs per patient were spent for CDI drug acquisition in the fidaxomicin group (€2,453, 95% CI 2,270-2,656) compared with the vancomycin group (€1,145, 95% CI 956-1,354; p < 0.001). When the direct cost parameters were separated for recurrent or refractory CDI patients, the results were comparable to those of the total study cohort ( Table S2, Table S4 ). Variables influencing overall direct treatment costs of recurrent or refractory CDI patients are given in Table 6 . The multivariable GLM revealed that inpatient treatment (OR 4.944, p < 0.001), ICU treatment (OR 2.119, p < 0.001), hospital-acquired CDI (OR 1.802, p < 0.001), rehospitalisations (OR 1.576, p < 0.001) and a severe first CDI episode within 90 days prior to recurrent or refractory CDI diagnosis (OR 1.452, p = 0.038), were associated with higher overall direct treatment costs. Older age, CDI therapy, type of CDI, subsequent CDI episodes and symptom reduction on day 10 were not found to influence overall costs. Table 6 Generalised linear model of variables influencing overall treatment costs in patients with recurrent or refractory Clostridioides difficile infection Overall treatment costs Univariate GLM Multivariable GLM p OR 95% CI p OR 95% CI Age 0.311 0.996 0.987–1.005 - - - CDI therapy (Reference = Vancomycin group) Fidaxomicin 0.825 1.029 0.800–1.323 - - - Inpatient treatment (Reference = Outpatient treatment) < 0.001 9.801 7.181–13.094 < 0.001 4.944 3.552–6.802 Severe first CDI episode < 0.001 2.205 1.438–3.586 0.038 1.452 1.038–2.093 Refractory CDI (Reference = Recurrent CDI) 0.162 1.213 0.929–1.594 - - - Type of CDI acquisition (Reference = Community-acquired CDI) Hospital-acquired CDI < 0.001 3.197 2.292–4.392 < 0.001 1.802 1.333–2.412 Health system-acquired CDI 0.018 1.514 1.069–2.121 0.388 1.127 0.846–1.492 Treatment on intensive care unit < 0.001 2.932 2.246–3.885 < 0.001 2.119 1.645 − 2.752 Rehospitalisation 0.036 1.405 1.033–1.946 < 0.001 1.576 1.256 − 1.992 Subsequent CDI episode 0.465 1.108 0.846–1.465 - - - Symptom reduction at day 10 0.281 1.258 0.809–1.870 - - - Note: n = 320; Akaike information criterium: 6,703; Bayes information criterium: 6,733; deviation: 218; likelihood quotient chi-square: 228.2 (p < 0.001) Abbreviations: CI, confidence interval; GLM, generalised linear model; OR, Odds ratio; CDI, Clostridioides difficile infection Discussion In this retrospective case-control study we analysed the clinical and health economic impact of fidaxomicin in immunocompromised patients with recurrent and refractory CDI treated in an in- and outpatient setting in Germany. With regard to the clinical outcomes, we found a significantly higher rate of symptom resolution at day 10 of CDI therapy as well as a significantly lower rate of CDI recurrences in the fidaxomicin group compared with the vancomycin group. While costs for CDI therapy were significantly higher in the fidaxomicin group, hospitalisation and overall direct treatment costs were comparable in both groups. In the fidaxomicin registration trials, the clinical efficacy of fidaxomicin compared with that of vancomycin at the end of therapy did not differ significantly in the subgroup of patients with previous episodes of CDI [ 14 ]. Cornely et al. reported similar clinical cure rates in a general population [ 16 ], as did Rao et al. in hospitalised patients receiving concomitant antibiotics for concurrent infections [ 31 ]. In our study, we observed a significantly higher rate of symptom reduction on day 10 in patients treated with fidaxomicin than in those treated with vancomycin – indicating that fidaxomicin is more effective than vancomycin in patients with relevant pre-existing conditions, older age and current refractory or recurrent CDI. Corresponding to our results, a recent retrospective single-centre, real-world study investigating treatment failure based on a combined outcome defined as clinical failure, recurrent CDI within 30 days after the end of initial CDI treatment, or death attributable to CDI, reported that fidaxomicin was associated with a risk reduction of 63% in comparison with vancomycin [ 22 ]. Consistent with our findings, treatment with fidaxomicin was associated with significantly lower rates of CDI recurrence than vancomycin, as demonstrated in the studies by Louie et al. and Cornely et al. [ 14 , 16 ], as well as in a subgroup analysis of Cornely et al. with patients with recurrent CDI [ 25 ]. A recent study demonstrated that fidaxomicin was significantly more effective in treating patients with CDI recurrence after the initial CDI episode and preventing subsequent CDI episodes in comparison with vancomycin, metronidazole or the combination of vancomycin and metronidazole [ 26 ]. Notably, our study stands out by demonstrating that these favourable outcomes were confirmed not only in patients with recurrent or refractory CDI, but also in patients aged over 65 years and in immunocompromised patients. We were further able to show that treatment with fidaxomicin significantly reduced the risk of a new CDI recurrence, whereas additional antibiotic treatment after CDI therapy had a significant effect on recurrence. Rao et al. demonstrated that patients receiving antibiotics simultaneously with CDI treatment had non-significantly higher rates of treatment response with fidaxomicin than vancomycin [ 31 ]. While the clinical findings of our total study cohort correspond to those of the subgroup of patients with recurrent CDI, the results could not be replicated in the subgroup of refractory CDI patients. This may be explained by the fact that this subgroup consisted of a smaller sample size as well as possible interactions of the premedication preceding the change in antibiotic treatment. In this context, it is also noteworthy that we observed a higher percentage of inpatient treatment as well as a longer median length of hospitalisation in the refractory CDI subgroup than in the recurrent CDI subgroup. While in our cohort, fidaxomicin and vancomycin were given for a median duration of 11 and 12 days, Rao et al. reported longer durations of 15 and 17 days in a cohort of patients with initial CDI treated with other non-CDI concomitant antibiotics [ 31 ]. Recurrent and refractory CDI not only represent a remarkable clinical burden but also entail a considerable economic burden on the healthcare system, which increases with each additional episode [ 32 – 35 ]. According to the ESCMID guideline, fidaxomicin treatment is recommended as 200 mg twice a day for ten days, resulting in costs of €1,700 per patient [ 10 ]. In our study population, the mean costs exceeded this value by €320. In the control group, mean costs for vancomycin and vancomycin tapered pulsed therapy were €976 (95% CI 838-1,130) and €1,272 (95% CI 730-2,063) per patient. The guideline recommends vancomycin 125 mg four times daily for ten days for the treatment of recurrent or refractory CDI which results in €384 [ 10 ]. When the costs of standard treatment were compared with those in our study population, mean costs in our study cohort were approximately €592 higher. The overall drug acquisition costs of fidaxomicin for recurrent or refractory CDI amounted to €2,412 and were significantly higher compared with the costs of €1,256 for vancomycin. This result was to be expected, as fidaxomicin is still under patent. In contrast, the hospitalisation costs as well as overall direct treatment costs were comparable between the two groups. This is in line with similar durations of hospitalisation. Nevertheless, overall direct treatment costs were higher in the subgroup of patients with refractory CDI than in those with recurrent CDI. These findings may be due to the longer hospital stays in the refractory group. Our findings are consistent with those of a study assessing the cost-effectiveness and budget impact of fidaxomicin in comparison with vancomycin in patients with an increased risk of recurrence in Germany. The authors concluded that, even though the costs were higher, fidaxomicin was more effective than vancomycin because of lower rates of recurrence, especially in subgroups such as cancer patients, geriatric patients, and patients with previous CDI [ 32 ]. Similarly, Okumura et al. evaluated patients after treatment failure with metronidazole and showed that fidaxomicin, in comparison with vancomycin, was associated with higher acquisition costs, which were compensated for by reduced hospitalisation costs on the basis of lower recurrence rates and reduced costs of complications [ 36 ]. Similar results were found in further studies in Spain [ 37 ] and the United Kingdom [ 20 ]. Our multivariable GLM identified inpatient treatment, treatment in ICU, hospital-acquired CDI, rehospitalisation as well as a severe first episode of CDI as cost drivers affecting the overall direct treatment cost of recurrent/ refractory CDI. In comparison, a systematic review evaluating economic assessments of fidaxomicin, vancomycin and metronidazole identified cure rate, recurrence rate, the duration of hospitalisation, as well as drug and associated costs as essential cost drivers [ 38 ]. There are several limitations to our study, including its retrospective design, which is prone to errors due to missing data, even though patients with incomplete medical records were not included in this study. Furthermore, we cannot exclude the possibility that unmeasured comorbidities or temporal trends outside the scope of the study may have influenced the results – limitations that are well-recognised in retrospective case-control studies [ 39 ]. As the study period covered a period of 11 years, there were changes in the guidelines for the treatment of CDI during this time. By matching patients on the basis of the year of CDI diagnosis, we aimed to minimise potential bias related to temporal variations in treatment practices and disease management. Furthermore, hospitalisation and drug acquisition costs were difficult to compare across studies due to differences in healthcare systems, reimbursement policies, and pricing structures between countries as well as varying methods for the calculation of the hospitalisation costs. Additionally, no data are available on the costs associated with CDI treatment for patients treated exclusively in an outpatient setting. Consequently, we could analyse only the number of outpatient visits as an indicator of healthcare resource utilization. Our study has several strengths. First, our study has a multicentre, matched, real-world cohort design, which enabled robust and valid comparisons between the two groups. Second, we focused on a high-risk group of patients, including haematological, oncological, immunocompromised, and geriatric patients, which is still a poorly assessed group of patients, especially regarding recurrent and refractory CDI. Third, to the best of our knowledge, this study is the first to examine the health economic impact of fidaxomicin in high-risk patients with recurrent or refractory CDI and to identify major cost drivers. Conclusions In conclusion, our study demonstrated that patients with advanced age and immunocompromised patients with recurrent and refractory CDI treated with fidaxomicin as first-line treatment had improved clinical outcomes compared with patients treated with vancomycin, with similar hospitalisation and overall treatment costs. Treatment costs of refractory CDI patients were higher than those of recurrent CDI patients. Future studies should focus on effective approaches to minimise identified cost drivers while optimizing treatment strategies for recurrent and refractory CDI, especially in at-risk patients. Declarations Acknowledgements Data sharing The authors are not permitted to disclose the study data beyond the research team. However, the data can be accessed through direct request to the corresponding author, and R scripts used to analyse the data can be made available on reasonable request. Funding This study was supported by an unrestricted research grant from Tillotts Pharma GmbH, Kurfürstendamm 170, 10707 Berlin, Germany. It was designed, planned, and performed by the academic authors of the University Hospitals Cologne and Frankfurt am Main, Germany. Ethical statement A primary ethics vote was obtained at the Ethics Committee of the Department of Medicine at the University of Cologne on 2023-04-24 (local ethics ID approval 23–1143-retro), as the University Hospital Cologne was the leading study site. The participating study site received their local ethics vote at the respective ethics commission. Since documentation was retrospective and anonymised, no signed consent was required from individual patients. CRediT authorship contribution statement IA: Writing – original draft, Conceptualization, Data collection. SMWH: Writing – review & editing, Conceptualization, Investigation, Methodology, Project administration, Funding acquisition. ME: Writing – original draft, Formal analysis. NP: Conceptualization, Data collection, Writing – review & editing. JJV: Writing – review & editing, Investigation. MJGTV: Conceptualization, Investigation, Methodology, Writing – review & editing. SMP: Writing – original draft, Conceptualization, Investigation, Methodology, Formal analysis, Project administration, Funding acquisition. Conflicts of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SMWH has received research and travel grants from Astellas, MSD, and Tillotts; research grants from Basilea, Gilead, and 3M, travel grants from Pfizer, and lecture honoraria from Astellas, MSD, and Tillotts. ME received travel grants from Tillotts. JJV has received research grants from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zentrum für Luft- und Raumfahrt (DLR), University of Bristol, Rigshospitalet Copenhagen, German Network University Medicine, German Cancer Consortium (DKTK), German Federal Ministry of Health (BMG), European Union, lecture honoraria from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), University Hospital Freiburg/ Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), Ärztekammer Nordrhein, Ärztekammer Hessen, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine (DGIM), Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, APOGEPHA, German Cancer Consortium (DKTK), University Hospital Oldenburg, meeting and travel support from German Centre for Infection Research (DZIF), University Manchester, German Society for Infectious Diseases (DGI), University Hospital Aachen, German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, German Cancer Consortium (DKTK), and advisory board fees from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, Janssen, Biontech. MJGTV has received research grants from MSD, Heel, Roche and Tillotts, consulting fees from GILEAD, Tillotts, Pfizer, Bioaster, GSK, Ecraid, and lecture honoraria from Akademie für Infektionsmedizin, Astra Zeneca, bioMerieux, DGI, European Society of Neurogastroenterology, Falk Foundation, FomF GmbH, GILEAD, GSK, Helios Kliniken, Hessisches Landessozialgericht, Infektio Forum, Janssen Cilag GmbH, Klinikum Kassel, Landesärztekammer Hessen, LMU Kliniken, MSD, Pfizer, Streamed up, St. Vincent Hospital, Tillotts. SMP received travel grants and lecture honoraria from Tillotts. IA and NP have no conflicts of interest. Data Availability The authors are not permitted to disclose the study data beyond the research team. However, the data can be accessed through direct request to the corresponding author, and R scripts used to analyse the data can be made available on reasonable request. References P. Eze, E. Balsells, M.H. Kyaw, H. 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Watt, A Systematic Literature Review of Economic Evaluations of Antibiotic Treatments for Clostridium difficile Infection, Pharmacoeconomics 35(11) (2017) 1123-1140. https://doi.org/10.1007/s40273-017-0540-2. T.R. Frieden, Evidence for Health Decision Making - Beyond Randomized, Controlled Trials, N Engl J Med 377(5) (2017) 465-475. https://doi.org/10.1056/NEJMra1614394. Additional Declarations Competing interest reported. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SMWH has received research and travel grants from Astellas, MSD, and Tillotts; research grants from Basilea, Gilead, and 3M, travel grants from Pfizer, and lecture honoraria from Astellas, MSD, and Tillotts. ME received travel grants from Tillotts. JJV has received research grants from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zentrum für Luft- und Raumfahrt (DLR), University of Bristol, Rigshospitalet Copenhagen, German Network University Medicine, German Cancer Consortium (DKTK), German Federal Ministry of Health (BMG), European Union, lecture honoraria from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), University Hospital Freiburg/ Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), Ärztekammer Nordrhein, Ärztekammer Hessen, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine (DGIM), Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, APOGEPHA, German Cancer Consortium (DKTK), University Hospital Oldenburg, meeting and travel support from German Centre for Infection Research (DZIF), University Manchester, German Society for Infectious Diseases (DGI), University Hospital Aachen, German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, German Cancer Consortium (DKTK), and advisory board fees from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, Janssen, Biontech. MJGTV has received research grants from MSD, Heel, Roche and Tillotts, consulting fees from GILEAD, Tillotts, Pfizer, Bioaster, GSK, Ecraid, and lecture honoraria from Akademie für Infektionsmedizin, Astra Zeneca, bioMerieux, DGI, European Society of Neurogastroenterology, Falk Foundation, FomF GmbH, GILEAD, GSK, Helios Kliniken, Hessisches Landessozialgericht, Infektio Forum, Janssen Cilag GmbH, Klinikum Kassel, Landesärztekammer Hessen, LMU Kliniken, MSD, Pfizer, Streamed up, St. Vincent Hospital, Tillotts. SMP received travel grants and lecture honoraria from Tillotts. IA and NP have no conflicts of interest. Supplementary Files SupplementaryMaterialFidaxomicinVancomycin.pdf Cite Share Download PDF Status: Published Journal Publication published 29 Jan, 2026 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 23 Oct, 2025 Reviews received at journal 05 Oct, 2025 Reviews received at journal 29 Sep, 2025 Reviewers agreed at journal 20 Sep, 2025 Reviewers agreed at journal 17 Sep, 2025 Reviewers invited by journal 17 Sep, 2025 Editor invited by journal 26 Aug, 2025 Editor assigned by journal 25 Aug, 2025 Submission checks completed at journal 25 Aug, 2025 First submitted to journal 24 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7445823","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":520192483,"identity":"88fb76e6-4f84-4e41-9c20-c2e55b0010e9","order_by":0,"name":"Isabella Alram","email":"","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Isabella","middleName":"","lastName":"Alram","suffix":""},{"id":520192484,"identity":"b302158a-bd34-4436-a5e5-81ebbfa3f3c3","order_by":1,"name":"Sebastian M. Wingen-Heimann","email":"","orcid":"","institution":"University Hospital Cologne, University of Cologne","correspondingAuthor":false,"prefix":"","firstName":"Sebastian","middleName":"M.","lastName":"Wingen-Heimann","suffix":""},{"id":520192486,"identity":"3fa031ef-1fc9-495f-b88b-5c5da6cea5d7","order_by":2,"name":"Marie Engelhard","email":"","orcid":"","institution":"University of Cologne, University Hospital Cologne","correspondingAuthor":false,"prefix":"","firstName":"Marie","middleName":"","lastName":"Engelhard","suffix":""},{"id":520192487,"identity":"f7453d29-95c1-4ac7-975b-a5d7a3bc4667","order_by":3,"name":"Nele Pfeiffer","email":"","orcid":"","institution":"University of Cologne, University Hospital Cologne","correspondingAuthor":false,"prefix":"","firstName":"Nele","middleName":"","lastName":"Pfeiffer","suffix":""},{"id":520192489,"identity":"e5b62bc3-4dac-4ba9-870c-73ae761625fb","order_by":4,"name":"J. Janne Vehreschild","email":"","orcid":"","institution":"Goethe University Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"J.","middleName":"Janne","lastName":"Vehreschild","suffix":""},{"id":520192491,"identity":"50dc0849-63c6-4050-bc1b-c4f990780db7","order_by":5,"name":"Maria J.G.T. Vehreschild","email":"","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"J.G.T.","lastName":"Vehreschild","suffix":""},{"id":520192493,"identity":"408370a0-17ae-480a-bb02-1ba8c26eca7e","order_by":6,"name":"Sina M. Pütz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIie2PsYrCQBRF3zAQm5ekzTTxFyID4rLF/koGQRs/IIWgIGgzYruFH5FK7DYysNVsv9sljZWFNstWYrIiguDE0mJO9ZrDOxfAYnlG6PXKyBhigEZ54yMKghOfFVqnXEDA6DGlOXM3e7JW4Zuvf9k79EKfuhnskvtKpLxuQLTiCF8rlsKAs4kXk6U2KBSjgEyVkGS+YsUxEanCiLpTQ9gE+V+pjCTFLcshER//ytEwRmG7+hKjg04VJlJaKWPTFmx3hO63pHb4SzmfB+WXzfLTELbQ/Puwfm02Fqr4kdAN/Zls5buhIaxC3GZkNQIAMZRbLBaLBU77CEcsSJ9QswAAAABJRU5ErkJggg==","orcid":"","institution":"University of Cologne, University Hospital Cologne","correspondingAuthor":true,"prefix":"","firstName":"Sina","middleName":"M.","lastName":"Pütz","suffix":""}],"badges":[],"createdAt":"2025-08-24 11:23:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7445823/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7445823/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-026-12611-4","type":"published","date":"2026-01-29T15:58:35+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":92274864,"identity":"cfa2aa59-1481-4295-b08f-c9a1264261d5","added_by":"auto","created_at":"2025-09-26 15:27:42","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":317630,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptFidaxomicinVancomycinV2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/8effdde05d98cd51642ddaf0.docx"},{"id":92274935,"identity":"ddc23b3e-8055-4fa7-94a6-75b21bc29bdb","added_by":"auto","created_at":"2025-09-26 15:27:48","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":11308,"visible":true,"origin":"","legend":"","description":"","filename":"df5d2776d2934857a00c938d80867101.json","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/cde20a97da64a31e008c979d.json"},{"id":92274938,"identity":"b584096a-2744-4efd-a46b-162277b4fce8","added_by":"auto","created_at":"2025-09-26 15:27:49","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":165511,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialFidaxomicinVancomycin.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/1b151ebd3ecb4a381da33697.pdf"},{"id":92274828,"identity":"79b1e339-2548-4baf-acbb-529650a7fccd","added_by":"auto","created_at":"2025-09-26 15:27:40","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":193278,"visible":true,"origin":"","legend":"","description":"","filename":"df5d2776d2934857a00c938d808671011enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/0c3be3d3843749e4aea6bb47.xml"},{"id":92274880,"identity":"26d73011-15fc-434a-8d22-bbf6b92411fe","added_by":"auto","created_at":"2025-09-26 15:27:43","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":94451,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/85074c6cfb3fd8fa5f1d1520.png"},{"id":92274877,"identity":"5daf415d-2185-4961-9e46-a996383902f3","added_by":"auto","created_at":"2025-09-26 15:27:43","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":56710,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/88273e57222c89dcb512cceb.png"},{"id":92274814,"identity":"eda7cf89-5dda-4c9f-bc0d-023d19c00110","added_by":"auto","created_at":"2025-09-26 15:27:40","extension":"xml","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":186577,"visible":true,"origin":"","legend":"","description":"","filename":"df5d2776d2934857a00c938d808671011structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/17ef69edf5d99d2c1f7122f5.xml"},{"id":92274928,"identity":"6b59d2c0-db4f-4dcd-8b4e-8e48648cc3fe","added_by":"auto","created_at":"2025-09-26 15:27:46","extension":"html","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":200139,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/176d2d67f3fa4e7a8a0b2c65.html"},{"id":92274842,"identity":"02f2ffe6-2f25-4514-9361-e9dfae16a8aa","added_by":"auto","created_at":"2025-09-26 15:27:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":377087,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival of the observed groups. Kaplan-Meier plot shows overall survival rate (in %) until day 90 after therapy initiation with fidaxomicin (blue line) and vancomycin (red line, HR = 0.816, 95% CI: 0.457-1.458, log-rank test: p = 0.483). Abbreviations: rCDI, recurrent or refractory \u003cem\u003eClostridioides difficile\u003c/em\u003e infection.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/32c5c617f639e2539dc771f2.png"},{"id":101691063,"identity":"e742b4a2-65fc-4666-95bd-fe9c6503f74f","added_by":"auto","created_at":"2026-02-02 16:11:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2357875,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/da013f6a-8690-49b7-8b09-2dde8dc971bd.pdf"},{"id":92274936,"identity":"12b6e9c3-fa5c-40fe-aa8c-c87b2ff8631a","added_by":"auto","created_at":"2025-09-26 15:27:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":165511,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialFidaxomicinVancomycin.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7445823/v1/29f9e68f5a415a508c48d4f6.pdf"}],"financialInterests":"Competing interest reported. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:\nSMWH has received research and travel grants from Astellas, MSD, and Tillotts; research grants from Basilea, Gilead, and 3M, travel grants from Pfizer, and lecture honoraria from Astellas, MSD, and Tillotts. ME received travel grants from Tillotts. JJV has received research grants from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zentrum für Luft- und Raumfahrt (DLR), University of Bristol, Rigshospitalet Copenhagen, German Network University Medicine, German Cancer Consortium (DKTK), German Federal Ministry of Health (BMG), European Union, lecture honoraria from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), University Hospital Freiburg/ Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), Ärztekammer Nordrhein, Ärztekammer Hessen, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine (DGIM), Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, APOGEPHA, German Cancer Consortium (DKTK), University Hospital Oldenburg, meeting and travel support from German Centre for Infection Research (DZIF), University Manchester, German Society for Infectious Diseases (DGI), University Hospital Aachen, German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, German Cancer Consortium (DKTK), and advisory board fees from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, Janssen, Biontech. MJGTV has received research grants from MSD, Heel, Roche and Tillotts, consulting fees from GILEAD, Tillotts, Pfizer, Bioaster, GSK, Ecraid, and lecture honoraria from Akademie für Infektionsmedizin, Astra Zeneca, bioMerieux, DGI, European Society of Neurogastroenterology, Falk Foundation, FomF GmbH, GILEAD, GSK, Helios Kliniken, Hessisches Landessozialgericht, Infektio Forum, Janssen Cilag GmbH, Klinikum Kassel, Landesärztekammer Hessen, LMU Kliniken, MSD, Pfizer, Streamed up, St. Vincent Hospital, Tillotts. SMP received travel grants and lecture honoraria from Tillotts. IA and NP have no conflicts of interest.","formattedTitle":"Clinical and pharmacoeconomic evaluation of fidaxomicin in patients over 65 years of age and immunocompromised patients with recurrent and refractory Clostridioides difficile infection","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cem\u003eClostridioides difficile\u003c/em\u003e infection (CDI) is a common cause of hospital-acquired infectious diarrhoea in hospitalised patients. Its severity ranges from asymptomatic carriage or diarrhoea to life-threatening pseudomembranous colitis. It is often a complication of broad-spectrum antibiotic treatment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The incidence of and mortality due to CDI is higher in immunocompromised patients compared to the general population \u0026ndash; including haematological/oncological patients and patients after solid-organ transplantation [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This also includes the population of geriatric patients [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In these vulnerable patient populations, especially after intensive chemotherapy and under immunosuppressive therapy, a disruption of the gut microbiome is associated with worsened clinical outcomes, including increased infection rates, treatment-related complications, and mortality [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFidaxomicin is recommended as first-line treatment for initial CDI in the standard of care setting as well as for patients with a high risk of recurrence [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The occurrence of recurrent and refractory CDI is an additional burden for patients, clinicians, and healthcare systems [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. If a first CDI recurrence occurs, fidaxomicin is recommended if patients are treated with vancomycin during the initial CDI episode [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Controversy, however, exists regarding the clinical and health economic impact of fidaxomicin in the context of recurrent and refractory disease [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. To date, the clinical impact of fidaxomicin has been tested in randomised controlled trials [\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], whereas the clinical and health economic outcomes have been examined in some single-centre, real-world studies regarding the treatment of mostly initial CDI [\u003cspan additionalcitationids=\"CR21 CR22 CR23\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Studies that specifically investigated patients with recurrent CDI demonstrated that fidaxomicin was associated with significantly lower recurrence rates compared to vancomycin or metronidazole [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Although evidence exists regarding the efficacy of fidaxomicin in treating recurrent or refractory CDI, comprehensive real-world data remain limited, especially in immunocompromised patients and patients at advanced age. Moreover, despite its recommendation as first-line therapy in recent guidelines, the use of fidaxomicin remains limited in practice, mainly due to financial constraints which take precedence over clinical prioritisation. We therefore performed a retrospective case-control study at two tertiary-care hospitals in Germany to observe and evaluate clinical and health economic experiences with fidaxomicin for treating recurrent or refractory CDI in immunocompromised patients and patients aged over 65 years compared to vancomycin-treated controls.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and study population\u003c/h2\u003e\u003cp\u003eWe performed a retrospective, multicentre case-control study at two German university hospitals (Cologne and Frankfurt am Main). We included adult patients with recurrent or refractory CDI receiving fidaxomicin (case group) or vancomycin (control group), respectively, between January 2013 and December 2023. For inclusion, they needed to present with at least one of the following inclusion criteria: (i) haematological or oncological underlying disease, (ii) diseases requiring immunosuppressive therapy, such as autoimmune disorders or post-organ transplantation status, and (iii) age 65 years or older. The follow-up period was 90 days. Matching of control patients from the same participating study site was performed by using a nearest neighbour approach based on the following criteria: age, sex, in- or outpatient status, underlying disease, year of inpatient stay, and if treated in an intensive care unit (ICU) the APACHE score. Only patients who were alive after at least ten days following treatment initiation with fidaxomicin or vancomycin were included.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDefinitions\u003c/h3\u003e\n\u003cp\u003eDiarrhoea was defined as three or more unformed stools per day. CDI was defined primarily as clinical findings consistent with CDI and microbiological evidence of \u003cem\u003eC. difficile\u003c/em\u003e toxins by enzyme immunoassay. In addition, cases were identified based on a clinical presentation consistent with CDI in combination with a positive nucleic acid amplification test (NAAT), preferably with a low cycle threshold, or a positive toxigenic \u003cem\u003eC. difficile\u003c/em\u003e culture, if there was no evidence of another cause of diarrhoea. Furthermore, cases of pseudomembranous colitis confirmed by endoscopy, post colectomy, or autopsy were included, if accompanied by a positive test for the presence of toxigenic \u003cem\u003eC. difficile\u003c/em\u003e. Recurrence of CDI was defined as a new CDI after initial response to treatment within a period of 90 days. Response to treatment was defined as the absence of diarrhoea for two consecutive days, with improvement continuing throughout the duration of the CDI treatment and no further treatment of CDI required from the second day after completion of the treatment. Refractory CDI was defined as persistence of diarrhoea beyond day 5 of CDI antibiotic treatment or recurrence of diarrhoea on days 5 to 10 of CDI antibiotic treatment after initial cessation of diarrhoea.\u003c/p\u003e\n\u003ch3\u003eStudy objectives and hypotheses\u003c/h3\u003e\n\u003cp\u003eWe evaluated the clinical effectiveness of fidaxomicin in treating recurrent and refractory CDI, along with associated healthcare resource utilization and costs. In addition, we examined further outcomes, including time to cure, number of recurrent CDI episodes, and overall length of hospital stay (LOS) in patients treated with fidaxomicin compared with control patients.\u003c/p\u003e\n\u003ch3\u003eData documentation\u003c/h3\u003e\n\u003cp\u003ePatient data were collected anonymously into a web-based eCRF, accessible via \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.clinicalsurveys.net\" target=\"_blank\"\u003ewww.clinicalsurveys.net\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.clinicalsurveys.net\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, after conclusion of the 90-day observation period or after death of the patient. Under the supervision of experienced internal medicine specialists, medical documentation specialists carried out the documentation at the respective study site. The leading study site University Hospital Cologne handled the data monitoring and query management.\u003c/p\u003e\n\u003ch3\u003eHealthcare resource utilization and cost analysis\u003c/h3\u003e\n\u003cp\u003eThe healthcare resource utilization and cost analysis was performed from the perspective of the German healthcare system [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. It contained direct treatment cost factors that included costs for hospital treatment and costs for CDI medication. Costs for treatment on hospital ward were calculated based on the German Diagnosis Related Groups (G-DRG) systematic provided by Institute for the Hospital Renumeration System f\u0026uuml;r das Entgeltsystem im Krankenhaus (InEK - Institut f\u0026uuml;r das Entgeltsystem im Krankenhaus) and represented personnel and material costs from the years 2013 to 2023 [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Costs for CDI medication were calculated by using the pharmacy retail price from 2024 extracted from the Rote Liste\u0026reg;, a comprehensive drug directory in Germany [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. To ensure comparability of hospitalisation and drug acquisition costs, the microcosting approach used year 2024 values expressed in Euros (\u0026euro;). Indirect cost factors, such as productivity losses due to illness-related disability or death before retirement age, were disregarded because of the complex underlying diseases or retirement age.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe data were processed and analysed using R (R version 4.5.0) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Patient characteristics and outcomes are presented as percentages (absolute numbers) for categorical variables and means (95% confidence interval\u0026thinsp;=\u0026thinsp;95% CI) for continuous variables. Age and treatment durations are reported as medians (range/inter quartile range). Statistical significance was determined via Pearson\u0026rsquo;s chi-squared test, Mann-Whitney U Test, Fisher\u0026rsquo;s exact test or Student\u0026rsquo;s t-test (two-sided), as appropriate, with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 as the significance level. Logistic regression and Cox regression analyses were performed via maximum likelihood estimation. A multivariable generalised linear model (GLM) with a gamma distribution and log-link was conducted to assess variables that influence direct treatment costs. Regression analyses included independent patient characteristics and risk factors as well as the underlying CDI treatment. Prior to multivariable analyses, univariate analyses were performed, and all variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.1 were included in the model. The multivariable analyses reported odds ratios (OR) for logistic regression and GLM or hazard ratios (HR) for Cox regression and 95% CIs; the level of significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Survival analysis was conducted via the Kaplan-Meier method to estimate the cumulative probability of death over time. In accordance with the real-world design of this study, patients with missing values were excluded for the respective analysis step (complete case analysis), if data were missing completely at random.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eStudy population\u003c/h2\u003e\u003cp\u003eFollowing the screening of 5,600 potential cases within the inclusion period in both centres, a total of 344 patients met the eligibility criteria and were therefore enrolled in the study. The patient characteristics are demonstrated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Approximately one third of the patients presented with refractory CDI and two thirds with recurrent CDI. The most common risk factors were haematological disease, age over 65 years, and a previous hospitalisation within 90 days prior to CDI diagnosis. Almost all patients suffered from mild to moderate CDI, with hospital-acquired infections observed in 42% (n\u0026thinsp;=\u0026thinsp;73) of the fidaxomicin group and 45% (n\u0026thinsp;=\u0026thinsp;78) of the vancomycin group. We found no significant differences between the patient characteristics of the fidaxomicin- and vancomycin-treated patients. For five patients in the fidaxomicin group, it was not possible to find suitable controls, such that matching was carried out across study sites.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of patients with recurrent or refractory \u003cem\u003eClostridioides difficile\u003c/em\u003e infection\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFidaxomicin\u003c/p\u003e\u003cp\u003e(n\u0026nbsp;=\u0026nbsp;172)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eVancomycin\u003c/p\u003e\u003cp\u003e(n\u0026nbsp;=\u0026nbsp;172)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e92 (54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78 (45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.131\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e, median (range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66 (19\u0026ndash;85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67 (19\u0026ndash;84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.878\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBody mass index\u003c/b\u003e, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.6 (20.0\u0026ndash;26.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.6 (21.0-27.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.083\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCaucasian\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e169 (98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e168 (98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.703\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRisk factors\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHaematological disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.496\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOncological disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.668\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKidney transplantation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.284\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver transplantation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.295\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther underlying disease with immunosuppression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.330\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeriatric patient\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;65 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47 (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46 (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.903\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;= 2 CDI episodes 90 days before current CDI diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.463\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious CDI recurrence within 90 days prior to diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.109\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious hospitalisation within 90 days prior to diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e122 (71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e116 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.484\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere first CDI episode\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.316\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOther comorbidities\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiovascular disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e114 (66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e116 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.819\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrinological disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68 (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59 (34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.315\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastroenterological disease (except of CDI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50 (29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.813\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNephrological disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.576\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePsychiatric disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.272\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePulmonary disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.100\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eType of CDI\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecurrent CDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e110 (64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e112 (65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.822\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRefractory CDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.910\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSeverity of recurrent/refractory CDI\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMild to moderate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e170 (99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e171 (99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere, complicated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of episodes of recurrent/refractory CDI, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e172 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e172 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63 (37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.157\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eType of CDI acquisition\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.556\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCommunity-acquired CDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital-acquired CDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78 (45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHealth system-acquired CDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59 (34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50 (29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eAbbreviations: CI, confidence interval, CDI, \u003cem\u003eClostridioides difficile\u003c/em\u003e infection\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Pearson\u0026rsquo;s chi-squared test, \u003csup\u003eb\u003c/sup\u003e Mann-Whitney-U test, \u003csup\u003ec\u003c/sup\u003e Student\u0026rsquo;s t-test, \u003csup\u003ed\u003c/sup\u003e Fisher\u0026rsquo;s exact test\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eTreatment types and durations\u003c/h2\u003e\u003cp\u003eIn the fidaxomicin group, 63% of the patients (n\u0026thinsp;=\u0026thinsp;108) were treated as inpatients, 15% (n\u0026thinsp;=\u0026thinsp;26) as outpatients and 22% (n\u0026thinsp;=\u0026thinsp;38) in an in- and outpatient setting. In the vancomycin group, 58% (n\u0026thinsp;=\u0026thinsp;100) of the patients were inpatients, 14% (n\u0026thinsp;=\u0026thinsp;24) were outpatients, and 28% (n\u0026thinsp;=\u0026thinsp;48) were in- and outpatients. In the inpatient setting of fidaxomicin-treated patients, 96% (n\u0026thinsp;=\u0026thinsp;140) received fidaxomicin standard dose (200 mg twice a day), whereas 2% (n\u0026thinsp;=\u0026thinsp;3) were treated with fidaxomicin extended-pulsed therapy. In 1% (n\u0026thinsp;=\u0026thinsp;1) of the patients, bezlotoxumab or faecal microbiota transfer (FMT) was added to the fidaxomicin treatment, respectively. Outpatients were treated with fidaxomicin standard dose (77%, n\u0026thinsp;=\u0026thinsp;20) or fidaxomicin extended-pulsed therapy (12%, n\u0026thinsp;=\u0026thinsp;3), while bezlotoxumab was added in 15% (n\u0026thinsp;=\u0026thinsp;4) and FMT in 4% (n\u0026thinsp;=\u0026thinsp;1) of patients. There were no statistically significant differences in the duration of treatment between the groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Across all recurrent and refractory CDI episodes, fidaxomicin was given orally for a median duration of 11 days (fidaxomicin group: IQR 11\u0026ndash;15; vancomycin group: IQR 10\u0026ndash;13) in both groups (p\u0026thinsp;=\u0026thinsp;0.367), whereas vancomycin was given orally for a median duration of 13 days (IQR 10\u0026ndash;20) in the fidaxomicin group and 12 days (IQR 11\u0026ndash;21) in the vancomycin group (p\u0026thinsp;=\u0026thinsp;0.876).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTreatment details of patients with recurrent or refractory \u003cem\u003eClostridioides difficile\u003c/em\u003e infection\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFidaxomicin group (n\u0026thinsp;=\u0026thinsp;172)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eVancomycin group (n\u0026thinsp;=\u0026thinsp;172)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTreatment of recurrent/refractory CDI, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e172 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e169 (98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.248\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFidaxomicin, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e165 (96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration (days), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (11\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (10\u0026ndash;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.367\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFidaxomicin extended pulsed therapy, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.067\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration (days), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (26\u0026ndash;27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (na)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.163\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVancomycin, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e165 (96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration (days), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (10\u0026ndash;20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (11\u0026ndash;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.876\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVancomycin tapered pulsed therapy, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration (days), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49 (36\u0026ndash;56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMetronidazole, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration (days), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (10\u0026ndash;14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBezlotoxumab, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration (days), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (11\u0026ndash;26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAdditional antibiotic treatment\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eduring CDI treatment, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e95 (55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e105 (61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.274\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eafter CDI treatment, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e95 (55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93 (54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.829\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHospital visits\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInpatient treatment, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e146 (85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e148 (86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.760\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of hospitalisations, Median (Range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1\u0026ndash;6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.689\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLength of initial hospital stay, Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31 (13\u0026ndash;55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (14\u0026ndash;52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.845\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverall hospital length of stay, Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (19\u0026ndash;55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (19\u0026ndash;59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.956\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOutpatient treatment, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64 (37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.378\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of visits, Median (Range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1\u0026ndash;3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1\u0026ndash;3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.025\u003c/b\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eAbbreviations: CI, confidence interval; IQR, interquartile range; LOS, length of stay; CDI, \u003cem\u003eClostridioides difficile\u003c/em\u003e infection; na, not applicable\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Pearson\u0026rsquo;s chi-squared test, \u003csup\u003eb\u003c/sup\u003e Mann-Whitney-U test, \u003csup\u003ec\u003c/sup\u003e Fisher\u0026rsquo;s exact test\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWith a median of 31 days (IQR 13\u0026ndash;55) and 33 days (IQR 14\u0026ndash;52) the hospital length of stay of the initial hospitalisation was comparable in the fidaxomicin and vancomycin group (p\u0026thinsp;=\u0026thinsp;0.845) with a similar amount of CDI treatment as the reason for hospitalisation (44%, n\u0026thinsp;=\u0026thinsp;64 vs. 45%, n\u0026thinsp;=\u0026thinsp;67; p\u0026thinsp;=\u0026thinsp;0.845). No significant differences were detected between both groups regarding the number of patients treated in the intermediate care unit (24%, n\u0026thinsp;=\u0026thinsp;35 vs. 24%, n\u0026thinsp;=\u0026thinsp;36; p\u0026thinsp;=\u0026thinsp;0.894) or the ICU (23%, n\u0026thinsp;=\u0026thinsp;34 vs. 22%, n\u0026thinsp;=\u0026thinsp;33; p\u0026thinsp;=\u0026thinsp;0.892) during the observation period. Patients in both groups had a median of one outpatient visit, with significantly more outpatient visits in the vancomycin group than in the fidaxomicin group (p\u0026thinsp;=\u0026thinsp;0.025).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eOverall effectiveness of fidaxomicin\u003c/h2\u003e\u003cp\u003eSymptom reduction on day 10 was reached in significantly more fidaxomicin-treated patients (95%, n\u0026thinsp;=\u0026thinsp;163) than in vancomycin-treated patients (86%, n\u0026thinsp;=\u0026thinsp;147, p\u0026thinsp;=\u0026thinsp;0.004). Univariate logistic regression analysis revealed that fidaxomicin as CDI therapy was the only independent variable with an impact on the symptom reduction on day 10 (OR 3.080, p\u0026thinsp;=\u0026thinsp;0.005; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The median number of days with CDI-associated diarrhoea was similar in both groups (fidaxomicin group: 5 days, IQR 3\u0026ndash;8 days; vancomycin group: 4 days, IQR 3\u0026ndash;9 days; p\u0026thinsp;=\u0026thinsp;0.817). A new CDI recurrence within 90 days occurred in significantly more vancomycin-treated patients (37%, n\u0026thinsp;=\u0026thinsp;63) than in fidaxomicin-treated patients (21%, n\u0026thinsp;=\u0026thinsp;36; p\u0026thinsp;=\u0026thinsp;0.001). Overall, there were more recurrent than refractory CDIs (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The multivariable logistic regression analysis demonstrated that CDI therapy with fidaxomicin significantly reduced the risk of CDI recurrence within the 90-day observational period (OR 0.443, p\u0026thinsp;=\u0026thinsp;0.001), while additional antibiotic treatment after CDI therapy was significantly associated with an increased risk of CDI recurrence (OR 2.221, p\u0026thinsp;=\u0026thinsp;0.002; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate logistic regression analyses of independent variables with impact on \u003cem\u003eClostridioides difficile\u003c/em\u003e infection-associated symptom reduction on day 10 based on risk factors for \u003cem\u003eClostridioides difficile\u003c/em\u003e infection and \u003cem\u003eClostridioides difficile\u003c/em\u003e infection therapy\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026nbsp;value\u003c/p\u003e\u003cp\u003e(univariate)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOdds ratio\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.493\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.985\u0026ndash;1.029\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFidaxomicin as CDI therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.080\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.440\u0026ndash;7.176\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious CDI recurrence\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.136\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.482\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.194\u0026ndash;1.371\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious hospitalisation\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.326\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.444\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.678\u0026ndash;2.975\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere first CDI episode\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.655\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.404\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.392\u0026ndash;8.973\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInpatient treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.630\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.765\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.220\u0026ndash;2.054\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdditional antibiotic treatment during CDI treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.415\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.736\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.341\u0026ndash;1.516\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: CDI, \u003cem\u003eClostridioides difficile\u003c/em\u003e infection; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e within 90 days prior to diagnosis\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUni- and multivariable logistic regression analyses of independent variables with impact on the occurrence of a new \u003cem\u003eClostridioides difficile\u003c/em\u003e infection recurrence within the 90-day observational period based on risk factors for \u003cem\u003eClostridioides difficile\u003c/em\u003e infection and \u003cem\u003eClostridioides difficile\u003c/em\u003e infection therapy\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026nbsp;value\u003c/p\u003e\u003cp\u003e(uni-variate)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOdds ratio\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026nbsp;value\u003c/p\u003e\u003cp\u003e(multi-variate)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eOdds ratio\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.687\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.988\u0026ndash;1.019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFidaxomicin as CDI therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.458\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.281\u0026ndash;0.737\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.443\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.270\u0026ndash;0.719\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious CDI recurrence\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.252\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.532\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.722\u0026ndash;3.141\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious hospitalisation\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.520\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.849\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.517\u0026ndash;1.408\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere first CDI episode\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.587\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.261\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.523\u0026ndash;2.846\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInpatient treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.587\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.836\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.444\u0026ndash;1.629\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdditional antibiotic treatment during CDI treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.284\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.299\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.808\u0026ndash;2.110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdditional antibiotic treatment after CDI treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.146\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.323\u0026ndash;3.534\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.221\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.360\u0026ndash;3.691\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: CDI, \u003cem\u003eClostridioides difficile\u003c/em\u003e infection; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003ea\u003c/sup\u003e within 90 days prior to diagnosis\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eOverall, 13% of all patients (n\u0026thinsp;=\u0026thinsp;46) died within the 90-day observational period, with no significant difference between the groups (fidaxomicin group: 15%, n\u0026thinsp;=\u0026thinsp;25; vancomycin group: 12%, n\u0026thinsp;=\u0026thinsp;21; p\u0026thinsp;=\u0026thinsp;0.483; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In one fidaxomicin-treated patient, death was attributable to CDI complications and in another patient, death was partially attributable to CDI whereas in the vancomycin group no deaths were attributable to CDI. The death from CDI in the two fidaxomicin-treated patients was associated with another episode of CDI after the successful treatment of the first recurrence with fidaxomicin.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn the subgroup of patients with recurrent CDI, we found similar clinical outcomes (\u003cb\u003eTable \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e). In contrast, in the subgroup of patients with refractory CDI, no significant differences in symptom reduction on day 10 or in the rate of recurrence were detected (\u003cb\u003eTable S3\u003c/b\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eCosts for hospitalisation and CDI treatment\u003c/h2\u003e\u003cp\u003eDirect treatment costs for recurrent and refractory CDI patients, including hospitalisation and drug acquisition costs, are described in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. For the 294 patients treated in the inpatient and combined in- and outpatient setting, DRG data were available for 91% (n\u0026thinsp;=\u0026thinsp;268) and were therefore used to calculate hospitalisation costs. Mean overall hospitalisation costs were comparable between both groups with \u0026euro;19,898 per patient (95% CI 16,151\u0026thinsp;\u0026minus;\u0026thinsp;23,645) in the fidaxomicin group and \u0026euro;20,469 per patient (95% CI 16,837\u0026thinsp;\u0026minus;\u0026thinsp;24,101) in the control group (p\u0026thinsp;=\u0026thinsp;0.811). Over 85% of those expenses could be assigned to the initial hospitalisation in both groups, amounting to \u0026euro;17,300 per patient (95% CI 13,596\u0026thinsp;\u0026minus;\u0026thinsp;21,005) in the fidaxomicin group and \u0026euro;17,520 per patient (95% CI 13,958\u0026thinsp;\u0026minus;\u0026thinsp;21,082) in the control group (p\u0026thinsp;=\u0026thinsp;0.969). Expenses for patients that were hospitalised due to recurrent or refractory CDI were an average of \u0026euro;4,000 higher in the fidaxomicin group compared with the vancomycin group (\u0026euro;8,552 per patient, 95% CI 5,717\u0026thinsp;\u0026minus;\u0026thinsp;11,386; \u0026euro;12,578 per patient, 95% CI 9,066\u0026thinsp;\u0026minus;\u0026thinsp;16,089, p\u0026thinsp;=\u0026thinsp;0.071).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDirect treatment costs for patients with recurrent or refractory \u003cem\u003eClostridioides difficile\u003c/em\u003e infection in Euro\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFidaxomicin group (n\u0026thinsp;=\u0026thinsp;172)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eVancomycin group (n\u0026thinsp;=\u0026thinsp;172)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHospitalisation costs\u003c/b\u003e\u003csup\u003e\u003cb\u003eI, b\u003c/b\u003e\u003c/sup\u003e, \u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e133 (77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e135 (78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.795\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19,406 (15,215\u0026thinsp;\u0026minus;\u0026thinsp;23,597)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19,300 (15,534\u0026thinsp;\u0026minus;\u0026thinsp;23,067)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.990\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHospitalisation costs\u003c/b\u003e\u003csup\u003e\u003cb\u003eI\u003c/b\u003e\u003c/sup\u003e, \u003cb\u003en (%) (Year 2024)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e133 (77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e135 (78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.795\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19,898 (16,151\u0026thinsp;\u0026minus;\u0026thinsp;23,645)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20,469 (16,837\u0026thinsp;\u0026minus;\u0026thinsp;24,101)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.811\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDrug acquisition costs for first recurrent or refractory CDI\u003c/b\u003e\u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFidaxomicin, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e165 (96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,020 (1,952\u0026thinsp;\u0026minus;\u0026thinsp;20,091)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFidaxomicin extended pulsed therapy, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,706 (1,647-1,761)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVancomycin, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e165 (96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e976 (837-1,130)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVancomycin tapered pulsed therapy, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,272 (730-2,063)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMetronidazole, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBezlotoxumab, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,228 (1,800-2,479)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDrug acquisition costs for second recurrent or refractory CDI\u003c/b\u003e\u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFidaxomicin, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27 (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003csup\u003e\u003cb\u003ed\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,147 (1,835-2,561)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2,059 (1,806-2,364)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.699\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFidaxomicin extended pulsed therapy, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,147\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVancomycin, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003csup\u003e\u003cb\u003ed\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,220 (423-2,766)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e510 (401\u0026ndash;641)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.161\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVancomycin tapered pulsed therapy, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e582 (384\u0026ndash;779)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMetronidazole, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42 (37\u0026ndash;47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDrug acquisition costs for third recurrent or refractory CDI\u003c/b\u003e\u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVancomycin, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2,919 (538-5,301)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVancomycin tapered pulsed therapy, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e850 (818\u0026ndash;882)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMetronidazole, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOverall recurrent/ refractory CDI drug acquisition costs\u003c/b\u003e\u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e, \u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e172 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e169 (98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.248\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,412 (2,254-2,594)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,256 (1,074\u0026thinsp;\u0026minus;\u0026thinsp;1,453)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOverall direct treatment costs\u003c/b\u003e\u003csup\u003e\u003cb\u003eb, c\u003c/b\u003e\u003c/sup\u003e, \u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e172 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e172 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17,417 (13,935\u0026thinsp;\u0026minus;\u0026thinsp;20,899)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16,382 (13,220\u0026thinsp;\u0026minus;\u0026thinsp;19,545)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.676\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOverall direct treatment costs, n (%) (Year 2024)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e172 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e172 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCosts per patient, mean (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17,798 (14,620\u0026thinsp;\u0026minus;\u0026thinsp;20,975)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17,300 (14,199\u0026thinsp;\u0026minus;\u0026thinsp;20,400)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.840\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: CI, Confidence interval; CDI, \u003cem\u003eClostridioides difficile\u003c/em\u003e infection\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003eI\u003c/sup\u003e n-values differ due to missing data; \u003csup\u003ea\u003c/sup\u003e Bootstrapped t-test (independent samples, two sided); \u003csup\u003eb\u003c/sup\u003e Based on G-DRGs from 2013 to 2023; \u003csup\u003ec\u003c/sup\u003e Based on Rote Liste\u0026reg; prices from 2024; \u003csup\u003ed\u003c/sup\u003e Pearson chi-square test (two-tailed); \u003csup\u003ee\u003c/sup\u003e Fisher\u0026acute;s exact test\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eCosts for CDI treatment with fidaxomicin and vancomycin were calculated stratified by CDI episode. For initial recurrent or refractory CDI treatment, a mean of \u0026euro;2,020 (95% CI 1,952\u0026thinsp;\u0026minus;\u0026thinsp;20,091) and \u0026euro;1,706 (95% CI 1,647-1,761) per patient was spent on fidaxomicin and fidaxomicin extended pulsed therapy. Overall, CDI drug acquisition costs were significantly higher in the fidaxomicin group, with a mean cost of \u0026euro;2,412 per patient (95% CI 2,254-2,594), compared with the vancomycin group, with a mean cost of \u0026euro;1,256 per patient (95% CI 1,074\u0026thinsp;\u0026minus;\u0026thinsp;1,453, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). With regard to the overall direct treatment costs, expenses were similar in both groups (fidaxomicin group: \u0026euro;17,417 per patient, 95% CI 13,935\u0026thinsp;\u0026minus;\u0026thinsp;20,899; vancomycin group: \u0026euro;17,300, 95% CI 14,199\u0026thinsp;\u0026minus;\u0026thinsp;20,400; p\u0026thinsp;=\u0026thinsp;0.840).\u003c/p\u003e\u003cp\u003eExpenses of \u0026euro;2,180 (95% CI 1,933-2,486) and \u0026euro;1,928 (95% CI 1,487-2,405) per patient in the fidaxomicin and vancomycin groups were associated with drug acquisition costs in the outpatient setting (p\u0026thinsp;=\u0026thinsp;0.367). For inpatient treatment and in- and outpatient treatment, significantly higher mean costs per patient were spent for CDI drug acquisition in the fidaxomicin group (\u0026euro;2,453, 95% CI 2,270-2,656) compared with the vancomycin group (\u0026euro;1,145, 95% CI 956-1,354; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). When the direct cost parameters were separated for recurrent or refractory CDI patients, the results were comparable to those of the total study cohort (\u003cb\u003eTable S2, Table S4\u003c/b\u003e).\u003c/p\u003e\u003cp\u003eVariables influencing overall direct treatment costs of recurrent or refractory CDI patients are given in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. The multivariable GLM revealed that inpatient treatment (OR 4.944, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), ICU treatment (OR 2.119, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), hospital-acquired CDI (OR 1.802, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), rehospitalisations (OR 1.576, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a severe first CDI episode within 90 days prior to recurrent or refractory CDI diagnosis (OR 1.452, p\u0026thinsp;=\u0026thinsp;0.038), were associated with higher overall direct treatment costs. Older age, CDI therapy, type of CDI, subsequent CDI episodes and symptom reduction on day 10 were not found to influence overall costs.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGeneralised linear model of variables influencing overall treatment costs in patients with recurrent or refractory \u003cem\u003eClostridioides difficile\u003c/em\u003e infection\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverall treatment costs\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eUnivariate GLM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eMultivariable GLM\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.311\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.996\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.987\u0026ndash;1.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCDI therapy\u003c/b\u003e (Reference\u0026thinsp;=\u0026thinsp;Vancomycin group)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFidaxomicin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.825\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.029\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.800\u0026ndash;1.323\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInpatient treatment\u003c/b\u003e (Reference\u0026thinsp;=\u0026thinsp;Outpatient treatment)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.801\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.181\u0026ndash;13.094\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.944\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.552\u0026ndash;6.802\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSevere first CDI episode\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.205\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.438\u0026ndash;3.586\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.452\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.038\u0026ndash;2.093\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRefractory CDI\u003c/b\u003e (Reference\u0026thinsp;=\u0026thinsp;Recurrent CDI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.162\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.213\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.929\u0026ndash;1.594\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eType of CDI acquisition\u003c/b\u003e (Reference\u0026thinsp;=\u0026thinsp;Community-acquired CDI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital-acquired CDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.197\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.292\u0026ndash;4.392\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.802\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.333\u0026ndash;2.412\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHealth system-acquired CDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.018\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.514\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.069\u0026ndash;2.121\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.388\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.846\u0026ndash;1.492\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTreatment on intensive care unit\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.932\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.246\u0026ndash;3.885\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.119\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.645 \u0026minus;\u0026thinsp;2.752\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRehospitalisation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.036\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.405\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.033\u0026ndash;1.946\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.576\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.256 \u0026minus;\u0026thinsp;1.992\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSubsequent CDI episode\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.465\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.108\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.846\u0026ndash;1.465\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSymptom reduction at day 10\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.281\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.258\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.809\u0026ndash;1.870\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eNote: n\u0026thinsp;=\u0026thinsp;320; Akaike information criterium: 6,703; Bayes information criterium: 6,733; deviation: 218; likelihood quotient chi-square: 228.2 (p\u0026nbsp;\u0026lt;\u0026nbsp;0.001)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eAbbreviations: CI, confidence interval; GLM, generalised linear model; OR, Odds ratio; CDI, \u003cem\u003eClostridioides difficile\u003c/em\u003e infection\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective case-control study we analysed the clinical and health economic impact of fidaxomicin in immunocompromised patients with recurrent and refractory CDI treated in an in- and outpatient setting in Germany. With regard to the clinical outcomes, we found a significantly higher rate of symptom resolution at day 10 of CDI therapy as well as a significantly lower rate of CDI recurrences in the fidaxomicin group compared with the vancomycin group. While costs for CDI therapy were significantly higher in the fidaxomicin group, hospitalisation and overall direct treatment costs were comparable in both groups.\u003c/p\u003e\u003cp\u003eIn the fidaxomicin registration trials, the clinical efficacy of fidaxomicin compared with that of vancomycin at the end of therapy did not differ significantly in the subgroup of patients with previous episodes of CDI [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Cornely et al. reported similar clinical cure rates in a general population [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], as did Rao et al. in hospitalised patients receiving concomitant antibiotics for concurrent infections [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In our study, we observed a significantly higher rate of symptom reduction on day 10 in patients treated with fidaxomicin than in those treated with vancomycin \u0026ndash; indicating that fidaxomicin is more effective than vancomycin in patients with relevant pre-existing conditions, older age and current refractory or recurrent CDI. Corresponding to our results, a recent retrospective single-centre, real-world study investigating treatment failure based on a combined outcome defined as clinical failure, recurrent CDI within 30 days after the end of initial CDI treatment, or death attributable to CDI, reported that fidaxomicin was associated with a risk reduction of 63% in comparison with vancomycin [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Consistent with our findings, treatment with fidaxomicin was associated with significantly lower rates of CDI recurrence than vancomycin, as demonstrated in the studies by Louie et al. and Cornely et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], as well as in a subgroup analysis of Cornely et al. with patients with recurrent CDI [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. A recent study demonstrated that fidaxomicin was significantly more effective in treating patients with CDI recurrence after the initial CDI episode and preventing subsequent CDI episodes in comparison with vancomycin, metronidazole or the combination of vancomycin and metronidazole [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Notably, our study stands out by demonstrating that these favourable outcomes were confirmed not only in patients with recurrent or refractory CDI, but also in patients aged over 65 years and in immunocompromised patients. We were further able to show that treatment with fidaxomicin significantly reduced the risk of a new CDI recurrence, whereas additional antibiotic treatment after CDI therapy had a significant effect on recurrence. Rao et al. demonstrated that patients receiving antibiotics simultaneously with CDI treatment had non-significantly higher rates of treatment response with fidaxomicin than vancomycin [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. While the clinical findings of our total study cohort correspond to those of the subgroup of patients with recurrent CDI, the results could not be replicated in the subgroup of refractory CDI patients. This may be explained by the fact that this subgroup consisted of a smaller sample size as well as possible interactions of the premedication preceding the change in antibiotic treatment. In this context, it is also noteworthy that we observed a higher percentage of inpatient treatment as well as a longer median length of hospitalisation in the refractory CDI subgroup than in the recurrent CDI subgroup. While in our cohort, fidaxomicin and vancomycin were given for a median duration of 11 and 12 days, Rao et al. reported longer durations of 15 and 17 days in a cohort of patients with initial CDI treated with other non-CDI concomitant antibiotics [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecurrent and refractory CDI not only represent a remarkable clinical burden but also entail a considerable economic burden on the healthcare system, which increases with each additional episode [\u003cspan additionalcitationids=\"CR33 CR34\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. According to the ESCMID guideline, fidaxomicin treatment is recommended as 200 mg twice a day for ten days, resulting in costs of \u0026euro;1,700 per patient [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In our study population, the mean costs exceeded this value by \u0026euro;320. In the control group, mean costs for vancomycin and vancomycin tapered pulsed therapy were \u0026euro;976 (95% CI 838-1,130) and \u0026euro;1,272 (95% CI 730-2,063) per patient. The guideline recommends vancomycin 125 mg four times daily for ten days for the treatment of recurrent or refractory CDI which results in \u0026euro;384 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. When the costs of standard treatment were compared with those in our study population, mean costs in our study cohort were approximately \u0026euro;592 higher. The overall drug acquisition costs of fidaxomicin for recurrent or refractory CDI amounted to \u0026euro;2,412 and were significantly higher compared with the costs of \u0026euro;1,256 for vancomycin. This result was to be expected, as fidaxomicin is still under patent. In contrast, the hospitalisation costs as well as overall direct treatment costs were comparable between the two groups. This is in line with similar durations of hospitalisation. Nevertheless, overall direct treatment costs were higher in the subgroup of patients with refractory CDI than in those with recurrent CDI. These findings may be due to the longer hospital stays in the refractory group. Our findings are consistent with those of a study assessing the cost-effectiveness and budget impact of fidaxomicin in comparison with vancomycin in patients with an increased risk of recurrence in Germany. The authors concluded that, even though the costs were higher, fidaxomicin was more effective than vancomycin because of lower rates of recurrence, especially in subgroups such as cancer patients, geriatric patients, and patients with previous CDI [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Similarly, Okumura et al. evaluated patients after treatment failure with metronidazole and showed that fidaxomicin, in comparison with vancomycin, was associated with higher acquisition costs, which were compensated for by reduced hospitalisation costs on the basis of lower recurrence rates and reduced costs of complications [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Similar results were found in further studies in Spain [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] and the United Kingdom [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur multivariable GLM identified inpatient treatment, treatment in ICU, hospital-acquired CDI, rehospitalisation as well as a severe first episode of CDI as cost drivers affecting the overall direct treatment cost of recurrent/ refractory CDI. In comparison, a systematic review evaluating economic assessments of fidaxomicin, vancomycin and metronidazole identified cure rate, recurrence rate, the duration of hospitalisation, as well as drug and associated costs as essential cost drivers [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThere are several limitations to our study, including its retrospective design, which is prone to errors due to missing data, even though patients with incomplete medical records were not included in this study. Furthermore, we cannot exclude the possibility that unmeasured comorbidities or temporal trends outside the scope of the study may have influenced the results \u0026ndash; limitations that are well-recognised in retrospective case-control studies [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. As the study period covered a period of 11 years, there were changes in the guidelines for the treatment of CDI during this time. By matching patients on the basis of the year of CDI diagnosis, we aimed to minimise potential bias related to temporal variations in treatment practices and disease management. Furthermore, hospitalisation and drug acquisition costs were difficult to compare across studies due to differences in healthcare systems, reimbursement policies, and pricing structures between countries as well as varying methods for the calculation of the hospitalisation costs. Additionally, no data are available on the costs associated with CDI treatment for patients treated exclusively in an outpatient setting. Consequently, we could analyse only the number of outpatient visits as an indicator of healthcare resource utilization.\u003c/p\u003e\u003cp\u003eOur study has several strengths. First, our study has a multicentre, matched, real-world cohort design, which enabled robust and valid comparisons between the two groups. Second, we focused on a high-risk group of patients, including haematological, oncological, immunocompromised, and geriatric patients, which is still a poorly assessed group of patients, especially regarding recurrent and refractory CDI. Third, to the best of our knowledge, this study is the first to examine the health economic impact of fidaxomicin in high-risk patients with recurrent or refractory CDI and to identify major cost drivers.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, our study demonstrated that patients with advanced age and immunocompromised patients with recurrent and refractory CDI treated with fidaxomicin as first-line treatment had improved clinical outcomes compared with patients treated with vancomycin, with similar hospitalisation and overall treatment costs. Treatment costs of refractory CDI patients were higher than those of recurrent CDI patients. Future studies should focus on effective approaches to minimise identified cost drivers while optimizing treatment strategies for recurrent and refractory CDI, especially in at-risk patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData sharing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are not permitted to disclose the study data beyond the research team. However, the data can be accessed through direct request to the corresponding author, and R scripts used to analyse the data can be made available on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by an unrestricted research grant from Tillotts Pharma GmbH, Kurfürstendamm 170, 10707 Berlin, Germany. It was designed, planned, and performed by the academic authors of the University Hospitals Cologne and Frankfurt am Main, Germany.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA primary ethics vote was obtained at the Ethics Committee of the Department of Medicine at the University of Cologne on 2023-04-24 (local ethics ID approval 23–1143-retro), as the University Hospital Cologne was the leading study site. The participating study site received their local ethics vote at the respective ethics commission. Since documentation was retrospective and anonymised, no signed consent was required from individual patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT authorship contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIA: Writing – original draft, Conceptualization, Data collection. SMWH: Writing – review \u0026amp; editing, Conceptualization, Investigation, Methodology, Project administration, Funding acquisition. ME: Writing – original draft, Formal analysis. NP: Conceptualization, Data collection, Writing – review \u0026amp; editing. JJV: Writing – review \u0026amp; editing, Investigation. MJGTV: Conceptualization, Investigation, Methodology, Writing – review \u0026amp; editing. SMP: Writing – original draft, Conceptualization, Investigation, Methodology, Formal analysis, Project administration, Funding acquisition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare the following financial interests/personal relationships which may be considered as potential competing interests:\u003c/p\u003e\n\u003cp\u003eSMWH has received research and travel grants from Astellas, MSD, and Tillotts; research grants from Basilea, Gilead, and 3M, travel grants from Pfizer, and lecture honoraria from Astellas, MSD, and Tillotts. ME received travel grants from Tillotts. JJV has received research grants from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zentrum für Luft- und Raumfahrt (DLR), University of Bristol, Rigshospitalet Copenhagen, German Network University Medicine, German Cancer Consortium (DKTK), German Federal Ministry of Health (BMG), European Union, lecture honoraria from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), University Hospital Freiburg/ Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), Ärztekammer Nordrhein, Ärztekammer Hessen, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine (DGIM), Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, APOGEPHA, German Cancer Consortium (DKTK), University Hospital Oldenburg, meeting and travel support from German Centre for Infection Research (DZIF), University Manchester, German Society for Infectious Diseases (DGI), University Hospital Aachen, German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, German Cancer Consortium (DKTK), and advisory board fees from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, Janssen, Biontech. MJGTV has received research grants from MSD, Heel, Roche and Tillotts, consulting fees from GILEAD, Tillotts, Pfizer, Bioaster, GSK, Ecraid, and lecture honoraria from Akademie für Infektionsmedizin, Astra Zeneca, bioMerieux, DGI, European Society of Neurogastroenterology, Falk Foundation, FomF GmbH, GILEAD, GSK, Helios Kliniken, Hessisches Landessozialgericht, Infektio Forum, Janssen Cilag GmbH, Klinikum Kassel, Landesärztekammer Hessen, LMU Kliniken, MSD, Pfizer, Streamed up, St. Vincent Hospital, Tillotts. SMP received travel grants and lecture honoraria from Tillotts. IA and NP have no conflicts of interest.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe authors are not permitted to disclose the study data beyond the research team. However, the data can be accessed through direct request to the corresponding author, and R scripts used to analyse the data can be made available on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eP. Eze, E. Balsells, M.H. Kyaw, H. Nair, Risk factors for Clostridium difficile infections - an overview of the evidence base and challenges in data synthesis, J Glob Health 7(1) (2017) 010417. https://doi.org/10.7189/jogh.07.010417.\u003c/li\u003e\n\u003cli\u003eS.L. Revolinski, L.S. Munoz-Price, Clostridium difficile in Immunocompromised Hosts: A Review of Epidemiology, Risk Factors, Treatment, and Prevention, Clin Infect Dis 68(12) (2019) 2144-2153. https://doi.org/10.1093/cid/ciy845.\u003c/li\u003e\n\u003cli\u003eD. Neofytos, K. Kobayashi, C.D. Alonso, J. Cady-Reh, D. Lepley, M. Harris, N. Desai, E. Kraus, A. Subramanian, S. Treadway, D. Ostrander, C. Thompson, K. 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Frieden, Evidence for Health Decision Making - Beyond Randomized, Controlled Trials, N Engl J Med 377(5) (2017) 465-475. https://doi.org/10.1056/NEJMra1614394.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Fidaxomicin, Clostridioides difficile Infection, Disease Recurrence, Healthcare Resource Utilization, Observational Study","lastPublishedDoi":"10.21203/rs.3.rs-7445823/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7445823/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eRecurrent or refractory \u003cem\u003eClostridioides difficile\u003c/em\u003e infection (CDI) often affects older and immunocompromised patients, posing clinical and economic challenges. While fidaxomicin has shown lower recurrence rates than vancomycin in the general population, evidence in this population remains limited.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis retrospective, multicentre case-control study compared patients aged\u0026thinsp;\u0026gt;\u0026thinsp;65 years or immunocompromised patients receiving fidaxomicin (case group) with those treated with vancomycin (control group) for recurrent or refractory CDI. A microcosting approach was used to assess direct treatment costs.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 344 patients were included (172 per group). Compared to the control group, the fidaxomicin group presented a significantly higher rate of symptom reduction on day 10 (n\u0026thinsp;=\u0026thinsp;163, 95% vs. n\u0026thinsp;=\u0026thinsp;147, 86%; p\u0026thinsp;=\u0026thinsp;0.004) and lower CDI recurrence rates (n\u0026thinsp;=\u0026thinsp;36, 21% vs. n\u0026thinsp;=\u0026thinsp;63, 37%; p\u0026thinsp;=\u0026thinsp;0.001). While the mean CDI treatment costs per patient were significantly higher in the fidaxomicin group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), the hospitalisation and overall treatment costs were comparable (\u0026euro;19,898, 95% CI \u0026euro;16,151-\u0026euro;23,645 vs. \u0026euro;20,469, 95% CI \u0026euro;16,837-\u0026euro;24,101, p\u0026thinsp;=\u0026thinsp;0.811; \u0026euro;17,798, 95% CI \u0026euro;14,620-\u0026euro;20,975 vs. \u0026euro;17,300, 95% CI \u0026euro;14,199-\u0026euro;20,400, p\u0026thinsp;=\u0026thinsp;0.840). Key cost drivers were hospitalisation, intensive care unit treatment, and severe initial CDI.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eDespite higher drug acquisition costs of fidaxomicin, overall treatment costs were comparable between the two groups with better clinical outcomes in patients treated with fidaxomicin.\u003c/p\u003e","manuscriptTitle":"Clinical and pharmacoeconomic evaluation of fidaxomicin in patients over 65 years of age and immunocompromised patients with recurrent and refractory Clostridioides difficile infection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-26 15:06:14","doi":"10.21203/rs.3.rs-7445823/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-23T19:51:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-05T16:33:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-29T15:15:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"184810343807127199393699517507455078563","date":"2025-09-20T09:49:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222937421394696796098253808617087466125","date":"2025-09-17T18:47:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-17T18:09:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-26T05:54:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-26T00:09:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-26T00:08:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-08-24T11:12:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5308baeb-fba5-4914-9fd7-7eededffac8f","owner":[],"postedDate":"September 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:07:18+00:00","versionOfRecord":{"articleIdentity":"rs-7445823","link":"https://doi.org/10.1186/s12879-026-12611-4","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2026-01-29 15:58:35","publishedOnDateReadable":"January 29th, 2026"},"versionCreatedAt":"2025-09-26 15:06:14","video":"","vorDoi":"10.1186/s12879-026-12611-4","vorDoiUrl":"https://doi.org/10.1186/s12879-026-12611-4","workflowStages":[]},"version":"v1","identity":"rs-7445823","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7445823","identity":"rs-7445823","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}