Risk factors and outcome of Pseudomonas aeruginosa bloodstream infections (PABSI) in hematological patients: A single center retrospective cohort study

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Vehreschild, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5212591/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Dec, 2024 Read the published version in Infection → Version 1 posted 13 You are reading this latest preprint version Abstract Purpose: Bloodstream infections caused by Pseudomonas aeruginosa (PABSI) in hematological patients are associated with high morbidity and mortality. We investigated the epidemiology, risk factors, and outcomes of PABSI at our center. Methods: All adult hematological patients with PABSI between January 2013 and July 2023 were included. Demographic and clinical characteristics, antimicrobial susceptibilities, antibiotic therapy, fluoroquinolone-prophylaxis, source of infection, and 30-day outcome were recorded. Descriptive statistics, tests for difference, and logistic regression models were performed. Results: Fifty patients with PABSI were identified with a median age of 58.5 years (range 24-78). 37 patients (74%) had severe neutropenia, 20 (40%) received allogeneic HSCT, and 29 (58%) had acute leukemia. A total of 34 (68%) had received timely appropriate anti-pseudomonal antibiotic therapy. The most common presumed cause of PABSI was mucositis (n=16, 32%), followed by pneumonia (8, 16%) and skin and soft tissue infections (n=6, 12%). Empirical combination therapy was used in 16 (32%) patients, while targeted combination therapies were used in 27 (54%) patients. P. aeruginosa detection led to treatment change in 31 (62%) cases. The overall 30-day survival rate was 78% (n=39). Carbapenem-resistance occurred in 34% (n=17), and multidrug-resistance (MDR) in 20% (n=10). Prior antibiotic exposure was associated with resistance. Appropriate antibiotic therapy was associated with survival, whereas antibiotic resistance and organ infection were associated with a fatal outcome. Conclusion: Prior antibiotic exposure in hematological patients is associated with resistance in PABSI, a major risk factor for a fatal outcome. Antibiotic stewardship efforts should be intensified and fluoroquinolone prophylaxis needs to be reconsidered. Pseudomonas aeruginosa bloodstream infections antibiotic resistance fluoroquinolone-prophylaxis hematological patients antimicrobial stewardship Introduction Bloodstream infections (BSI) caused by gram-negative bacteria are of particular concern in hematological patients. Pseudomonas aeruginosa is a major threat, due to its inherited antibiotic resistance. P. aeruginosa -associated bloodstream infections (PABSI) in particular are associated with high morbidity and mortality. [ 1 , 2 ]. The unique characteristics of hematological inpatients include a compromised immune system, a mucosal barrier disturbance due to mucositis, central venous catheters and frequent exposure to health care settings, making them particularly susceptible to nosocomial infections including PABSI. In particular in hematological patients, we previously demonstrated that BSIs caused by non-fermenters including P. aeruginosa are associated with a worse outcome compared to Enterobacterales BSIs [ 3 , 4 ]. Antibiotic therapy with a beta-lactam antibiotic with anti-pseudomonal activity is strongly recommended in febrile neutropenia to adequately cover BSI caused by P. aeruginosa [ 5 ]. Sources of PABSI are sometimes found in the inpatient environment, such as hospital water systems [ 6 ]. P. aeruginosa can cause a variety of infectious diseases, including pneumonia, skin and soft tissue infections, wound infections and urinary tract infections, which can lead to BSI thorough bacterial translocation or in the context of central venous catheter-associated infections [ 7 , 8 ]. It has been demonstrated that infections caused by multidrug-resistant (MDR) P. aeruginosa are associated with prior quinolone use and previous hospitalization, particularly at intensive care units [ 9 ]. These risk factors often apply to hematological patients. Understanding the risk factors and outcome of PABSI in this patient population is crucial for optimizing patient management and improving outcomes. Methods A retrospective study was conducted at the hematological department (67 beds) of the University Hospital Frankfurt. The medical records of all adult patients admitted and treated on hematology wards for a malignant hematological disease or myeloproliferative disorder, and diagnosed with PABSI between January 2013 and July 2023, were reviewed. Data on patient demographics, clinical characteristics, the results of microbiological susceptibility tests, antibiotic therapy and previous antibiotic use, the potential source of infection and patient outcomes at day 30 after detection of BSI were recorded. Data was processed and analyzed using SPSS (IBM SPSS version 29). Univariate comparisons were conducted by using the x 2 or the Fisher exact test for categorical variables. Variables with a P value < 0.05 in univariate analysis could be included in the multivariate analysis. All tests were two-tailed, with the significance level set at 0.05. The study was approved by the local ethics committee (#2021 − 370). Definitions The onset of BSI was defined as the date of collection of the positive blood culture sample. Severe neutropenia (grade IV) was defined as an absolute neutrophil count of less than 0.5 x 10 9 cells/liter. Carbapenem resistance was defined as either imipenem and/or meropenem resistance, fluoroquinolone resistance was defined as levofloxacin and/or ciprofloxacin resistance according to the respective available EUCAST definitions. The "I" category was interpreted as resistant in all isolates tested as “intermediate” prior to January 2020 (CLSI) [ 10 , 11 ].and interpreted as susceptible in all isolates tested “susceptible increased exposure” from 1 January 2020 (EUCAST) [ 11 ]. The term "multi-drug resistance" was defined as resistance in three or more of the following antimicrobial classes, namely penicillins (piperacillin/tazobactam), cephalosporins (ceftazidime or cefepime), carbapenems (imipenem or meropenem), and fluoroquinolones (ciprofloxacin). Empirical antibiotic therapy was defined as any antibiotic treatment administered for suspected BSI prior to the availability of definite susceptibility results from blood cultures. Any antibiotic treatment initiated following the availability of susceptibility results was defined as targeted therapy. Pseudomonas -directed monotherapy was defined as the administration of one in vitro active anti-pseudomonal agent, whereas the administration of two or more in vitro active antibiotics was defined as combination therapy. Therapy extension was defined as either a change to combination therapy from monotherapy, or the use of any of the new beta-lactam/beta-lactamase inhibitor combinations ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam, or cefiderocol, or colistin. Appropriate therapy was defined as the use of one or more Pseudomonas -active agents, tested as susceptible in vitro. Antibiotic pre-exposure was defined as prescription of the respective antibiotic drug for at least 48hrs within the last three months before the diagnosis of PABSI. Acute kidney injury was defined according to the KDIGO [ 12 ] criteria as an increase in serum creatinine ≥0,3 mg/dl within 48 hrs or an increase in serum creatinine to at least 1.5 times the known or assumed baseline value within seven days or a drop in urine volume to < 0.5 ml/kg bw/h for at least six hours. Cases receiving an allogeneic stem cell transplantation (SCT) included patients hospitalized prior to or after having received conditioning chemotherapy and up to day 100 after SCT. Results A total of 50 patients were included into the analysis, with a median age of 58.5 years and a slight male predominance (64% were male). The majority of patients (n = 25, 50%) had acute myeloid leukemia (AML), (n = 8, 16%) acute lymphoblastic leukemia (ALL), and (n = 8, 16%) non-Hodgkin lymphoma. Among 29 patients (58%) who underwent hematopoietic stem cell transplantation (HSCT), 20 (40%) underwent allogeneic HSCT. Most patients were in a good (ECOG 0, 28%) or slightly reduced (ECOG 1, 38%) performance status at the time of admission. A total of 11 patients (22%) died within 30 days after onset of PABSI. Of these, 10 deaths could be defined as sepsis-associated. The most common suspected sources of PABSI were mucositis (n = 16, 32%), skin and soft tissue infections (n = 10, 20%), among those four perianal abscesses (8%), further pneumonia (n = 8, 16%), and urinary tract infections (n = 5, 10%). Additionally, catheter-related infections and complicated intraabdominal infections were observed in three cases each (6% each). One case of malignant otitis externa was identified. In five cases (10%), no potential source of infection could be identified, four patients (8%) had more than one potential source of infection. In most cases (n = 45, 90%), fever triggered the collection of blood cultures, which then provided evidence of PABSI. In five cases, deterioration of the general condition and/or increased inflammation values led to the sampling of blood cultures. Table 1 Patient characteristics Characteristics All patients (n = 50) Age (years; median, range) 58.5 (24–78) Female sex, n (%) 18 (36) BMI (median; range) 24.5 (16.8–45.5) Hematological disease, n (%) AML 21 (42) ALL 8 (16) MDS/AML 4 (8) MDS 1 (2) CLL 1 (2) CML 1(2) CMML 1 (2) MM 3 (6) OMF 1 (2) B-NHL 6 (12) M. Hodgkin 1 (2) NHL (other) 2 (4) HSCT, n (%) No 21 (42) Yes 29 (58) Allogeneic SCT 100d 7 (14) ECOG, n (%) 0 14 (28) 1 19 (38) 2 5 (10) n.a. 12 (24) Reason for BC sampling n (%) Fever 45 (90) Suspected systemic infection without fever 5 (10) Neutropenia grade IV 38 (76) Length of stay (days; median, range) 30 (1-149) Suspected source of PABSI, n (%) Mucositis 16 (32) SSTI including perianal abscess 10 (20) Pneumonia 8 (16) UTI 5 (10) Inraabdominal infection 3 (6) Catheter related 3 (6) Otitis externa 1 (2) Empirical antibiotic therapy, n (%) Combination therapy 16 (32) Monotherapy 34 (68) Regimen containing agents, n (%) Piperacillin/Tazobactam 17 (34) Meropenem 22 (44) Imipenem 9 (18) Levofloxacin 3 (6) Ciprofloxacin 5 (10) Ceftazidime/Avibactam 1 (2) Amikacin 6 (12) Tobramycin 1 (2) Colistin 4 (8) Targeted antibiotic therapy, n (%) Combination 33 (66) Extension 31 (62) Step-down 4 (8) 30-day-mortality, n (%) 11 (22) Death (sepsis-related), n (%) 10 (20) One-third of the patients (n = 16, 32%) received an empirical anti-pseudomonal combination therapy. Meropenem was the most frequently prescribed antibiotic (n = 22, 44%), followed by piperacillin/tazobactam (n = 17, 34%) and imipenem (n = 9, 18%). Fluoroquinolones were added in seven cases (14%) as part of a combination therapy, and in one case prescribed as an empirical monotherapy, aminoglycosides were only prescribed as combination partners to antipseudomonal beta lactam-antibiotics. Four patients (8%) were treated with colistin as part of a combination therapy, and in one case (2%), ceftazidime/avibactam was prescribed on an empirical basis for a known colonization with MDR P. aeruginosa. In 37 (74%) cases, the detection of PABSI led to a treatment modification. Two thirds (n = 33, 66%) received targeted anti-pseudomonal combination therapy, in 31 cases (62%) a treatment extension (broader spectrum agent and/or combination therapy) was carried out. To identify potential risk factors for fatal outcome, we conducted a comparison of the characteristics of 30-day survivors and non-survivors. Appropriate empirical therapy within 24 hrs was significantly more frequent in cases with a favorable outcome. There was no difference in survival if either empirical or targeted combination therapy was administered. There were also no differences regarding previous Pseudomonas -active antibiotic therapies and prophylaxis. Patients with infections of internal organs (lung or intraabdominal infection) had a significantly worse outcome (p < 0.001) compared to cases with bacterial translocation favored by mucositis, or cases with UTI or other sources of PABSI (Table 2 ). Acute kidney injury according to KDIGO criteria was also significantly more frequent in cases with fatal outcome. Resistant Pseudomonas isolates were more common in patients who had a poor 30-day outcome. Table 2 Risk factors of fatal outcome at day 30 in PABSI Characteristics Overall N = 50 (%) Survivors N = 39 (%) Non-survivors N = 11 (%) p-value 1 Appropriate antibiotic therapy within 24 hrs 35 (70) 31 (79) 4 (36) 0.01 Empirical combination therapy 16 (32) 13 (33) 3 (28) 1.0 Change to modified targeted therapy 37 (74) 28 (72) 9 (82) 0.70 Combination 33 (66) 27 (69) 6 (55) 0.36 Extension 31 (62) 23 (59) 8 (73) 0.50 Step-down 4 (8) 4 (10) 0 (0) 0.56 Suspected source of PABSI Pneumonia 8 (16) 4 (10) 4 (36) 0.059 Perianal abscess 4 (8) 4 (10) 0 (0) 0.56 Mucositis 16 (32) 14 (36) 2 (18) 0.47 Catheter related 3 (6) 3 (8) 0 (0) 1.0 SSTI 6 (12) 4 (10) 2 (18) 0.60 UTI 5 (10) 5 (13) 0 (0) 0.57 Otitis externa 1 (2) 1 (3) 0 (0) 1.0 Intraabdominal infection 3 (6) 0 (0) 3 (28) 0.008 Internal organ infection (Pneumonia or cIAI) 4 (10) 7 (64) < 0.001 Neutropenia grade IV 38 (76) 30 (77) 8 (73) 1.0 Acute kidney injury 15 (30) 4 (10) 11 (100) < 0.001 PA-active antibiotic therapy within 3 months prior PABSI 36 (72) 28 (72) 8 (73) 1.0 PA-active antibiotic prophylaxis within 3 months prior PABSI 28 (56) 19 (49) 9 (82) 0.085 Resistance Carbapenems 17 (34) 11 (28) 6 (54) 0.15 Piperacillin/ Tazobactam 16 (32) 9 (23) 7 (64) 0.024 Fluoroquinolones 11 (22) 5 (13) 6 (54) 0.008 Cephalosporins 12 (24) 5 (13) 7 (64) 0.002 MDR 10 (20) 4 (10) 6 (54) 0.004 Aminoglycosides 4 (8) 1 (3) 3 (27) 0.029 PA: P. aeruginosa 1 Chi-Square-Test or Fisher´s exact Test Table 3 Regression analysis resistance and antibiotic pre-exposure Unadjusted OR (95%CI) Univariate p-value Unadjusted OR (95%CI) Univariate p-value Unadjusted OR (95%CI) Univariate p-value Unadjusted OR (95%CI) Univariate p-value CP-R PT-R FQ-R Ceph-R CP-E 5.5 (1.53–19.86) < 0.01 3.06 (0.89–10.48) 0.08 4.76 (1.09–20.91) 0.04 1.38 (0.37–5.06) 0.63 PT-E 0.95 (0.29–3.11) 0.93 1.62 (0.49–5.36) 0.433 1.20 (0.31–4.61) 0.79 1.53 (0.42–5.66) 0.52 FQ-E 1.19 (0.35–4.02) 0.78 7.0 (1.38–35.62) 0.02 8.57 (0.99–73.58) 0.05 9.90 (1.16–84.47) 0.04 Ceph-E* n.a. n.a. n.a. n.a. n.a. n.a. n.a. n.a. CP-E = Carbapenem exposure, PT-E = Piperacillin/Tazobactam exposure, FQ-E = Fluoroquinolone exposure, Cef-E = Cephalosporin exposure, CP-R = Carbapenem-resistance, PT-R = Piperacillin/Tazobactam-resistance, FQ-R = Fluoroquinolone-resistance, Ceph-R = Cephalosporin-resistance * no patients were exposed to Pseudomonas -active cephalosporins (ceftazidime/cefepime) within three months prior to PABSI The association between fluoroquinolone exposure (FQ-E) and fluoroquinolone resistance was at the margin of statistical significance, while the associations between either FQ-E and piperacillin/tazobactam resistance (PT-R) or FQ-E and cephalosporin resistance (Ceph-R) were statistically significant. Furthermore, previous therapies with carbapenems were found to be associated with carbapenem resistance. As there were no cases with cephalosporin-exposure, no associations for co-resistance could be statistically determined (Table 3 ). Table 4 Co-resistance of PABSI isolates No of isolates Resistance to Co-resistance with antibiotic n (%) P/T CP Cipro PA-Ceph AG 16 P/T 10 (63)* 6 (38) 9 (56) 2 (13) 17 CP 10 (59) 8 (47) 8 (47) 4 (24) 11 Cipro 7 (64) 8 (73) 7 (64) 3 (28) 12 PA-Ceph * 10 (83) 8 (67) 7 (58) 3 (25) 4 AG 2 (50) 4 (100) 3 (75) 3 (75) P/T= Piperacillin/Tazobactam; CP= Carbapenem (Imipenem or Meropenem); Cipro= Ciprofloxacin; PA-Ceph= Pseudomonas -active Cephalosporins (Ceftazidime or Cefepime); AG= Aminoglycosides *Co-resistance rates of >50% are marked in bold The PABSI isolates in our study showed a significant rate of co-resistance. PT-R isolates were often also carbapenem or cephalosporin resistant (63% and 56%, respectively). CP-R isolates were often also PT-R. FQ-R isolates were also predominantly carbapenem-, piperacillin/tazobactam, or cephalosporin-resistant (73%, 64%, and 64%, respectively). Aminoglycoside resistance (AS-R) was rare, with only 4 (8%) of isolates tested resistant. Conversely, when aminoglycoside resistance was present, CP-R, FQ-R and Ceph-R was also present in 100%, 75% and 75%, respectively (Table 4 ). Table 5 Risk factors of fatal outcome at day 30 in PABSI by univariate regression analysis. Characteristics Unadjusted OR (95%CI) Univariate p-value OR Multivariate p-value Appropriate antibiotic therapy within 24 hrs 6.78 (1.58-29.0) 0.01 5.07 (1.07–24.07) 0.04 Internal organ infection (Pneumonia or cIAI) 0.07 (0.01–0.33) < 0.001 Piperacillin/Tazobactam resistance 0.17 (0.041–0.721) 0.02 Carbapenem-resistance 0.33 (0.08–1.30) 0.11 Fluoroquinolone-resistance 0.12 (0.03–0.56) < 0.01 0.17 (0.03–0.83) 0.03 Cephalosporin-resistance 0.08 (0.02–0.39) < 0.01 Aminoglycoside-resistance 0.07 (0.01–0.76) 0.03 Multidrug resistance 0.10 (0.02–0.46) < 0.01 In the univariate regression analysis, FQ-R, P/T-R, Ceph-R, AG-R and MDR, but not CP-R were found to be associated with increased 30-day mortality (Table 5 ). Since there were no survivors among patients with intraabdominal infections, regression analysis could not be performed. Taken together, cases with internal organ infection (lung or intraabdominal infection) exhibited a significantly elevated risk of fatal outcome, as in case of patients who did not receive adequate therapy within 24 hrs after the onset of fever. In the multivariable analysis, FQ-R and lack of adequate therapy within 24 hrs were significantly associated with unfavorable outcome (Table 5 ). Discussion In this monocentric retrospective study, we analyzed the risk factors and outcomes of adult hematological patients with BSI due to P. aeruginosa (PABSI) over nearly ten years. We found that antibiotic drug resistance is a main risk factor for increased mortality, most likely due to inadequate empirical therapy. The inadequacy of antibiotic therapy and the development of antibiotic resistance have been identified as risk factors for a fatal outcome in neutropenic patients with sepsis in previous studies [ 13 ]. These observations are consistent with those of other studies about PABSI caused by multidrug-resistant, sometimes hypervirulent isolates of P. aeruginosa in hematologic patients [ 14 – 16 ]. BSIs due to P. aeruginosa are associated with high rates of morbidity and mortality, with estimated mortality rates of 43.2–58.8% [ 8 ], which is considerably higher than the 30-day mortality in our cohort (22%), especially in view of a relatively high resistance rate in our cohort [ 2 , 13 ]. In our cohort, as in other studies, previous antibiotic exposure was associated with occurrence of resistant P. aeruginosa [ 16 , 17 ]. Of note, carbapenem exposure was associated with both carbapenem-resistance and fluoroquinolone-resistance in P. aeruginosa. Fluoroquinolone exposure was associated with both, cephalosporin-resistance and piperacillin/tazobactam resistance, whereas the association with fluoroquinolone-resistance remained at the margin of significance. We found higher rates of co-resistance compared to other studies [ 18 ]. P. aeruginosa has numerous intrinsic resistance mechanisms such as porin loss, efflux pumps and inactivating enzymes. It can also acquire resistance mechanisms, e.g. through mutation or horizontal gene transfer (e.g. of metallo-betalactamases) [ 19 ]. The mechanism cannot be deduced from the resistance phenotype and since our strains were not available for whole genome sequencing, the causes for the observed resistance remain speculative. It has been demonstrated that in patients with leukemia, the pathogen responsible for the BSI frequently dominates or colonizes the microbiota of the gastrointestinal (GI) tract [ 20 ]. Conversely, avoiding colonization, especially by multidrug-resistant P. aeruginosa strains, could potentially reduce the risk of invasive infection. As about sixty percent of leukemia patients develop neutropenic fever and the prompt initiation of an empirical and Pseudomonas -active therapy is strongly recommended, most patients are extensively exposed to antibiotics and antibiotic selection pressure is a relevant problem [ 5 , 21 ]. To minimize selection pressure and damage to the microbiota, antibiotic therapies should be prescribed for as long as necessary, but as short as possible. By deciding in favor of monotherapy versus combination therapy and a rational duration of treatment, antibiotic usage and thus selection pressure can be reduced. The superiority of combination therapy over monotherapy in PABSI is a subject of ongoing controversy. A meta-analysis showed no difference in terms of mortality, although data on infections with antibiotic resistant P. aeruginosa -BSI are scarce. For this reason, the current ESCMID guidelines do not include a recommendation for or against targeted combination therapy for infections caused by carbapenem-resistant P. aeruginosa [ 22 ]. In severe infections (sepsis), a combination is recommended, if monotherapy is based on either fosfomycin, a polymyxin or an aminoglycoside [ 22 ]. In line with this, the IDSA does not recommend combination therapy for PABSI, if one of the new beta-lactam/beta-lactamase inhibitor combinations (ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam) or cefiderocol have been tested susceptible [ 23 ]. Current AGIHO guidelines strongly recommend the use of single-agent broad-spectrum Pseudomonas -active antibiotics such as piperacillin/tazobactam, ceftazidime, cefepime, meropenem or imipenem/cilastatin as first line antibiotic therapy [ 24 ]. However, in our cohort, 32% of patients received an empirical combination therapy, due to local treatment policy. With regard to the duration of therapy, it has been shown that the duration of treatment for febrile neutropenia, which is often determined by the time of regeneration, can be shortened in view of a 72 hours fever-free status and clinical response, without any negative impact on clinical outcome [ 25 ]. Furthermore, a multicenter-study in onco-hematology patients with PABSI could show, that short-courses (7–11 days) of therapy were non-inferior in terms of clinical outcomes compared to prolonged courses (12-21days) [ 26 ]. The benefits of fluoroquinolone prophylaxis (FQP) have also been the subject of controversial debate for years. In the meantime, it has been repeatedly demonstrated that, although the omission of an FQP is associated with an increase in BSI, it is not associated with increased mortality [ 27 , 28 ]. The effects of FQP on resistance selection were shown not only for P. aeruginosa infections, but also for both viridans streptococci and Enterobacterales [ 29 ] which in turn leads to reduced effectiveness of prophylaxis [ 30 ]. The empirical use of fluoroquinolones for combination therapy in neutropenic patients with sepsis can therefore not be recommended in centers where FQP is widely used or if colonization with a FQ-R pathogen such as P. aeruginosa or Enterobacterales is documented. These observations compelled other centers to leave the FQP [ 31 , 32 ]. Discontinuation of FQP has been shown to decrease FQ-R and 3rd generation cephalosporin resistance due to ESBL-producing Enterobacterales , without the increase of serious infectious complications [ 33 ]. At our center, FQP has been largely discontinued in the stem cell unit but is still in place in patients undergoing intensive chemotherapy for acute leukemia. As a result, potentially resistant pathogens, including P. aeruginosa , may be already selected prior to stem cell transplantation. Antibiotic stewardship in hematology may therefore contribute to reducing infections caused by multi-resistant pathogens and the maintainance of a protective microbiota, thereby improving patient outcomes [ 34 ]. As a consequence of our study, we would like to strengthen antibiotic stewardship efforts on hematology wards. In the light of the observed increase in mortality associated with FQR, the use of FQP in patients with acute leucemia under intensive chemotherapy should be reconsidered. Limitations: It should be noted that this study has some limitations. First, this is a retrospective study, which means that not all relevant data was available. Second, the evaluation is monocentric, and BSIs with P. aeruginosa are not very frequent, resulting in a relatively low number of cases, with only 50 patients included. Consequently, our conclusions need to be tested in large, multicenter and potentially interventional studies. Declarations Competing Interests The authors declare that they have no conflict of interest. Funding The authors have no relevant financial or non-financial interests to disclose. Author Contribution Conception, data collection and data analysis were performed by JK and MH. The first draft of the manuscript was written by JK. MH reviewed and edited the manuscript- FL, GB and BS were closely involved in patient care. MV, HS, SW, SS, BS, GB and FL were involved in planning and conducting the study. EH advised on the statistics. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgement We would like to thank Ms. Langhans for providing the microbiological data. We would also like to thank all persons involved in the clinical care of the PABSI patients. References J. T. Thaden, L. P. Park, S. A. Maskarinec, F. 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Cheng, “Antibiotic resistance in Pseudomonas aeruginosa : mechanisms and alternative therapeutic strategies,” Biotechnol. Adv. , vol. 37, no. 1, pp. 177–192, Jan. 2019, doi: 10.1016/j.biotechadv.2018.11.013. S. McMahon et al. , “Contribution of the Oral and Gastrointestinal Microbiomes to Bloodstream Infections in Leukemia Patients,” Microbiol. Spectr. , vol. 11, no. 3, p. e0041523, Jun. 2023, doi: 10.1128/spectrum.00415-23. S. S. Makhani et al. , “Inpatient Burden and Clinical Outcomes of Febrile Neutropenia in Cancer Patients: A National Inpatient Sample Database Analysis,” Blood , vol. 140, no. Supplement 1, pp. 5154–5155, Nov. 2022, doi: 10.1182/blood-2022-165527. M. Paul et al. , “European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine),” Clin. Microbiol. Infect. , vol. 28, no. 4, pp. 521–547, Apr. 2022, doi: 10.1016/j.cmi.2021.11.025. Clinical Infectious Diseases rel="noopener"> [email protected] . ciad428, https://doi org/10 1093/cid/ciad428 Published: 18 July 2023   Pranita D. Tamma*, Samuel L. Aitken, Robert A. Bonomo, Amy J. Mathers, David van Duin, Cornelius J. Clancy *Corresponding Author Please submit your feedback and comments on the AMR Guidance by emailing <a href="mailto:practiceguidelines@idsociety org" target="_blank", “AMR Guidance.” Accessed: Jul. 08, 2024. [Online]. Available: https://www.idsociety.org/practice-guideline/amr-guidance/ M. Christopeit et al. , “Prophylaxis, diagnosis and therapy of infections in patients undergoing high-dose chemotherapy and autologous haematopoietic stem cell transplantation. 2020 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO),” Ann. Hematol. , vol. 100, no. 2, pp. 321–336, Feb. 2021, doi: 10.1007/s00277-020-04297-8. M. Aguilar-Guisado et al. , “Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial,” Lancet Haematol. , vol. 4, no. 12, pp. e573–e583, Dec. 2017, doi: 10.1016/S2352-3026(17)30211-9. X. Feng et al. , “Is Short-Course Antibiotic Therapy Suitable for Pseudomonas aeruginosa Bloodstream Infections in Onco-hematology Patients With Febrile Neutropenia? Results of a Multi-institutional Analysis,” Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. , vol. 78, no. 3, pp. 518–525, Mar. 2024, doi: 10.1093/cid/ciad605. M. Cullen et al. , “Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas,” N. Engl. J. Med. , vol. 353, no. 10, pp. 988–998, Sep. 2005, doi: 10.1056/NEJMoa050078. G. Bucaneve et al. , “Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia,” N. Engl. J. Med. , vol. 353, no. 10, pp. 977–987, Sep. 2005, doi: 10.1056/NEJMoa044097. R. M. Prabhu, K. E. Piper, M. R. Litzow, J. M. Steckelberg, and R. Patel, “Emergence of quinolone resistance among viridans group streptococci isolated from the oropharynx of neutropenic peripheral blood stem cell transplant patients receiving quinolone antimicrobial prophylaxis,” Eur. J. Clin. Microbiol. Infect. Dis. Off. Publ. Eur. Soc. Clin. Microbiol. , vol. 24, no. 12, pp. 832–838, Dec. 2005, doi: 10.1007/s10096-005-0037-3. M. J. Satlin et al. , “Colonization With Fluoroquinolone-Resistant Enterobacterales Decreases the Effectiveness of Fluoroquinolone Prophylaxis in Hematopoietic Cell Transplant Recipients,” Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. , vol. 73, no. 7, pp. 1257–1265, Oct. 2021, doi: 10.1093/cid/ciab404. E. Eryilmaz-Eren, F. Izci, Z. Ture, P. Sagiroglu, L. Kaynar, and A. Ulu-Kilic, “Bacteremia in Hematopoietic Stem Cell Recipients Receiving Fluoroquinolone Prophylaxis: Incidence, Resistance, and Risk Factors,” Infect. Chemother. , vol. 54, no. 3, pp. 446–455, Sep. 2022, doi: 10.3947/ic.2022.0005. L. Caldwell et al. , “Cessation of Ciprofloxacin Prophylaxis in Hemato-Oncology Patients,” Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. , vol. 75, no. 1, pp. 178–179, Jan. 2022, doi: 10.1093/cid/ciab1000. A. Verlinden et al. , “Clinical and microbiological impact of discontinuation of fluoroquinolone prophylaxis in patients with prolonged profound neutropenia,” Eur. J. Haematol. , vol. 93, no. 4, pp. 302–308, Oct. 2014, doi: 10.1111/ejh.12345. A. Contejean et al. , “Antimicrobial stewardship in high-risk febrile neutropenia patients,” Antimicrob. Resist. Infect. Control , vol. 11, no. 1, p. 52, Mar. 2022, doi: 10.1186/s13756-022-01084-0. Additional Declarations No competing interests reported. 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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-5212591","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":376960843,"identity":"eb0dda15-d0cb-4043-aefd-d3961d2705ed","order_by":0,"name":"Johanna Kessel","email":"data:image/png;base64,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","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":true,"prefix":"","firstName":"Johanna","middleName":"","lastName":"Kessel","suffix":""},{"id":376960844,"identity":"54511d1f-0d23-49a9-b8c2-3a4608cc95ea","order_by":1,"name":"Gesine Bug","email":"","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Gesine","middleName":"","lastName":"Bug","suffix":""},{"id":376960845,"identity":"10204717-3a49-454c-80df-b76c19eeafb8","order_by":2,"name":"Björn Steffen","email":"","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Björn","middleName":"","lastName":"Steffen","suffix":""},{"id":376960846,"identity":"5ee232f1-b423-4788-94c1-90d1f01edf1e","order_by":3,"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":376960847,"identity":"d9b32c5e-62c4-47cd-9884-af4e4c3409e0","order_by":4,"name":"Sarah Weber","email":"","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Weber","suffix":""},{"id":376960848,"identity":"4346c3d5-7e9f-47f5-8f33-e19dcfcb01de","order_by":5,"name":"Sebastian Scheich","email":"","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Sebastian","middleName":"","lastName":"Scheich","suffix":""},{"id":376960849,"identity":"b68dfd9f-9205-47ad-b969-12a8ce92fe05","order_by":6,"name":"Fabian Lang","email":"","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Fabian","middleName":"","lastName":"Lang","suffix":""},{"id":376960850,"identity":"7e14a08e-83c2-4ead-9662-f422c27850a2","order_by":7,"name":"Hubert Serve","email":"","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Hubert","middleName":"","lastName":"Serve","suffix":""},{"id":376960851,"identity":"fffa0aef-d543-4135-b90f-3fad5da3bdb0","order_by":8,"name":"Eva Herrmann","email":"","orcid":"","institution":"Goethe University Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Eva","middleName":"","lastName":"Herrmann","suffix":""},{"id":376960852,"identity":"85cefa2c-bb73-463c-b236-736f9c6f41c0","order_by":9,"name":"Michael Hogardt","email":"","orcid":"","institution":"Goethe University Frankfurt, University Hospital Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Hogardt","suffix":""}],"badges":[],"createdAt":"2024-10-06 11:23:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5212591/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5212591/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s15010-024-02453-0","type":"published","date":"2024-12-19T15:58:37+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":72202601,"identity":"cccd2d13-455f-4d2e-bf60-acfc29a3e951","added_by":"auto","created_at":"2024-12-23 16:15:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":851271,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5212591/v1/df0d2429-f759-46d2-9d6b-e86cefc492ff.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk factors and outcome of Pseudomonas aeruginosa bloodstream infections (PABSI) in hematological patients: A single center retrospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBloodstream infections (BSI) caused by gram-negative bacteria are of particular concern in hematological patients. \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e is a major threat, due to its inherited antibiotic resistance. \u003cem\u003eP. aeruginosa\u003c/em\u003e-associated bloodstream infections (PABSI) in particular are associated with high morbidity and mortality. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The unique characteristics of hematological inpatients include a compromised immune system, a mucosal barrier disturbance due to mucositis, central venous catheters and frequent exposure to health care settings, making them particularly susceptible to nosocomial infections including PABSI. In particular in hematological patients, we previously demonstrated that BSIs caused by non-fermenters including \u003cem\u003eP. aeruginosa\u003c/em\u003e are associated with a worse outcome compared to \u003cem\u003eEnterobacterales BSIs\u003c/em\u003e [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Antibiotic therapy with a beta-lactam antibiotic with anti-pseudomonal activity is strongly recommended in febrile neutropenia to adequately cover BSI caused by \u003cem\u003eP. aeruginosa\u003c/em\u003e [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Sources of PABSI are sometimes found in the inpatient environment, such as hospital water systems [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. \u003cem\u003eP. aeruginosa\u003c/em\u003e can cause a variety of infectious diseases, including pneumonia, skin and soft tissue infections, wound infections and urinary tract infections, which can lead to BSI thorough bacterial translocation or in the context of central venous catheter-associated infections [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It has been demonstrated that infections caused by multidrug-resistant (MDR) \u003cem\u003eP. aeruginosa\u003c/em\u003e are associated with prior quinolone use and previous hospitalization, particularly at intensive care units [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. These risk factors often apply to hematological patients. Understanding the risk factors and outcome of PABSI in this patient population is crucial for optimizing patient management and improving outcomes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA retrospective study was conducted at the hematological department (67 beds) of the University Hospital Frankfurt. The medical records of all adult patients admitted and treated on hematology wards for a malignant hematological disease or myeloproliferative disorder, and diagnosed with PABSI between January 2013 and July 2023, were reviewed. Data on patient demographics, clinical characteristics, the results of microbiological susceptibility tests, antibiotic therapy and previous antibiotic use, the potential source of infection and patient outcomes at day 30 after detection of BSI were recorded. Data was processed and analyzed using SPSS (IBM SPSS version 29). Univariate comparisons were conducted by using the \u003cem\u003ex\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e or the Fisher exact test for categorical variables. Variables with a \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in univariate analysis could be included in the multivariate analysis. All tests were two-tailed, with the significance level set at 0.05. The study was approved by the local ethics committee (#2021\u0026thinsp;\u0026minus;\u0026thinsp;370).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions\u003c/h2\u003e \u003cp\u003eThe onset of BSI was defined as the date of collection of the positive blood culture sample. Severe neutropenia (grade IV) was defined as an absolute neutrophil count of less than 0.5 x 10\u003csup\u003e9\u003c/sup\u003e cells/liter. Carbapenem resistance was defined as either imipenem and/or meropenem resistance, fluoroquinolone resistance was defined as levofloxacin and/or ciprofloxacin resistance according to the respective available EUCAST definitions. The \"I\" category was interpreted as resistant in all isolates tested as \u0026ldquo;intermediate\u0026rdquo; prior to January 2020 (CLSI) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].and interpreted as susceptible in all isolates tested \u0026ldquo;susceptible increased exposure\u0026rdquo; from 1 January 2020 (EUCAST) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The term \"multi-drug resistance\" was defined as resistance in three or more of the following antimicrobial classes, namely penicillins (piperacillin/tazobactam), cephalosporins (ceftazidime or cefepime), carbapenems (imipenem or meropenem), and fluoroquinolones (ciprofloxacin). Empirical antibiotic therapy was defined as any antibiotic treatment administered for suspected BSI prior to the availability of definite susceptibility results from blood cultures. Any antibiotic treatment initiated following the availability of susceptibility results was defined as targeted therapy. \u003cem\u003ePseudomonas\u003c/em\u003e-directed monotherapy was defined as the administration of one in vitro active anti-pseudomonal agent, whereas the administration of two or more in vitro active antibiotics was defined as combination therapy. Therapy extension was defined as either a change to combination therapy from monotherapy, or the use of any of the new beta-lactam/beta-lactamase inhibitor combinations ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam, or cefiderocol, or colistin. Appropriate therapy was defined as the use of one or more \u003cem\u003ePseudomonas\u003c/em\u003e-active agents, tested as susceptible in vitro. Antibiotic pre-exposure was defined as prescription of the respective antibiotic drug for at least 48hrs within the last three months before the diagnosis of PABSI. Acute kidney injury was defined according to the KDIGO [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] criteria as an increase in serum creatinine \u0026ge;0,3 mg/dl within 48 hrs or an increase in serum creatinine to at least 1.5 times the known or assumed baseline value within seven days or a drop in urine volume to \u0026lt;\u0026thinsp;0.5 ml/kg bw/h for at least six hours. Cases receiving an allogeneic stem cell transplantation (SCT) included patients hospitalized prior to or after having received conditioning chemotherapy and up to day 100 after SCT.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 50 patients were included into the analysis, with a median age of 58.5 years and a slight male predominance (64% were male). The majority of patients (n\u0026thinsp;=\u0026thinsp;25, 50%) had acute myeloid leukemia (AML), (n\u0026thinsp;=\u0026thinsp;8, 16%) acute lymphoblastic leukemia (ALL), and (n\u0026thinsp;=\u0026thinsp;8, 16%) non-Hodgkin lymphoma. Among 29 patients (58%) who underwent hematopoietic stem cell transplantation (HSCT), 20 (40%) underwent allogeneic HSCT. Most patients were in a good (ECOG 0, 28%) or slightly reduced (ECOG 1, 38%) performance status at the time of admission. A total of 11 patients (22%) died within 30 days after onset of PABSI. Of these, 10 deaths could be defined as sepsis-associated. The most common suspected sources of PABSI were mucositis (n\u0026thinsp;=\u0026thinsp;16, 32%), skin and soft tissue infections (n\u0026thinsp;=\u0026thinsp;10, 20%), among those four perianal abscesses (8%), further pneumonia (n\u0026thinsp;=\u0026thinsp;8, 16%), and urinary tract infections (n\u0026thinsp;=\u0026thinsp;5, 10%). Additionally, catheter-related infections and complicated intraabdominal infections were observed in three cases each (6% each). One case of malignant otitis externa was identified. In five cases (10%), no potential source of infection could be identified, four patients (8%) had more than one potential source of infection. In most cases (n\u0026thinsp;=\u0026thinsp;45, 90%), fever triggered the collection of blood cultures, which then provided evidence of PABSI. In five cases, deterioration of the general condition and/or increased inflammation values led to the sampling of blood cultures.\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\u003ePatient characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAll patients (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years; median, range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.5 (24\u0026ndash;78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (median; range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.5 (16.8\u0026ndash;45.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematological disease,\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAML\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDS/AML\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCML\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCMML\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB-NHL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM. Hodgkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNHL (other)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSCT, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAllogeneic SCT\u0026thinsp;\u0026lt;\u0026thinsp;100d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAutologous SCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAllogeneic SCT\u0026thinsp;\u0026gt;\u0026thinsp;100d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReason for BC sampling n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuspected systemic infection without fever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutropenia grade IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of stay (days; median, range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (1-149)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspected source of PABSI, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMucositis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSSTI including perianal abscess\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInraabdominal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCatheter related\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOtitis externa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmpirical antibiotic therapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCombination therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMonotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegimen containing agents, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePiperacillin/Tazobactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeropenem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eImipenem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCiprofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCeftazidime/Avibactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmikacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTobramycin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eColistin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTargeted antibiotic therapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCombination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExtension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (62)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStep-down\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day-mortality, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath (sepsis-related),\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (20)\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\u003eOne-third of the patients (n\u0026thinsp;=\u0026thinsp;16, 32%) received an empirical anti-pseudomonal combination therapy. Meropenem was the most frequently prescribed antibiotic (n\u0026thinsp;=\u0026thinsp;22, 44%), followed by piperacillin/tazobactam (n\u0026thinsp;=\u0026thinsp;17, 34%) and imipenem (n\u0026thinsp;=\u0026thinsp;9, 18%). Fluoroquinolones were added in seven cases (14%) as part of a combination therapy, and in one case prescribed as an empirical monotherapy, aminoglycosides were only prescribed as combination partners to antipseudomonal beta lactam-antibiotics. Four patients (8%) were treated with colistin as part of a combination therapy, and in one case (2%), ceftazidime/avibactam was prescribed on an empirical basis for a known colonization with MDR \u003cem\u003eP. aeruginosa.\u003c/em\u003e In 37 (74%) cases, the detection of PABSI led to a treatment modification. Two thirds (n\u0026thinsp;=\u0026thinsp;33, 66%) received targeted anti-pseudomonal combination therapy, in 31 cases (62%) a treatment extension (broader spectrum agent and/or combination therapy) was carried out.\u003c/p\u003e \u003cp\u003eTo identify potential risk factors for fatal outcome, we conducted a comparison of the characteristics of 30-day survivors and non-survivors.\u003c/p\u003e \u003cp\u003eAppropriate empirical therapy within 24 hrs was significantly more frequent in cases with a favorable outcome. There was no difference in survival if either empirical or targeted combination therapy was administered. There were also no differences regarding previous \u003cem\u003ePseudomonas\u003c/em\u003e-active antibiotic therapies and prophylaxis. Patients with infections of internal organs (lung or intraabdominal infection) had a significantly worse outcome (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to cases with bacterial translocation favored by mucositis, or cases with UTI or other sources of PABSI (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Acute kidney injury according to KDIGO criteria was also significantly more frequent in cases with fatal outcome. Resistant \u003cem\u003ePseudomonas\u003c/em\u003e isolates were more common in patients who had a poor 30-day outcome.\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\u003eRisk factors of fatal outcome at day 30 in PABSI\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;50 (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSurvivors\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;39 (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNon-survivors\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;11 (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAppropriate antibiotic therapy within 24 hrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmpirical combination therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange to modified targeted therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCombination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExtension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStep-down\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspected source of PABSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.059\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerianal abscess\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMucositis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCatheter related\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSSTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOtitis externa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntraabdominal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInternal organ infection (Pneumonia or cIAI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutropenia grade IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute kidney injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA-active antibiotic therapy within 3 months prior PABSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA-active antibiotic prophylaxis within 3 months prior PABSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCarbapenems\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePiperacillin/\u003c/p\u003e \u003cp\u003eTazobactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFluoroquinolones\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCephalosporins\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAminoglycosides\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.029\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003ePA: \u003cem\u003eP. aeruginosa\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e1\u003c/sup\u003e Chi-Square-Test or Fisher\u0026acute;s exact Test\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=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRegression analysis resistance and antibiotic pre-exposure\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\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\u003eUnadjusted OR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnivariate p-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnadjusted OR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUnivariate p-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnadjusted OR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnivariate p-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUnadjusted OR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eUnivariate p-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCP-R\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ePT-R\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eFQ-R\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eCeph-R\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\u003eCP-E\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003cp\u003e(1.53\u0026ndash;19.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.06\u003c/p\u003e \u003cp\u003e(0.89\u0026ndash;10.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.76\u003c/p\u003e \u003cp\u003e(1.09\u0026ndash;20.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.38 (0.37\u0026ndash;5.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePT-E\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003cp\u003e(0.29\u0026ndash;3.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.62\u003c/p\u003e \u003cp\u003e(0.49\u0026ndash;5.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.433\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.20\u003c/p\u003e \u003cp\u003e(0.31\u0026ndash;4.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.53\u003c/p\u003e \u003cp\u003e(0.42\u0026ndash;5.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFQ-E\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.19\u003c/p\u003e \u003cp\u003e(0.35\u0026ndash;4.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.0\u003c/p\u003e \u003cp\u003e(1.38\u0026ndash;35.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.57\u003c/p\u003e \u003cp\u003e(0.99\u0026ndash;73.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.90 (1.16\u0026ndash;84.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCeph-E*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003en.a.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eCP-E\u0026thinsp;=\u0026thinsp;Carbapenem exposure, PT-E\u0026thinsp;=\u0026thinsp;Piperacillin/Tazobactam exposure, FQ-E\u0026thinsp;=\u0026thinsp;Fluoroquinolone exposure, Cef-E\u0026thinsp;=\u0026thinsp;Cephalosporin exposure, CP-R\u0026thinsp;=\u0026thinsp;Carbapenem-resistance, PT-R\u0026thinsp;=\u0026thinsp;Piperacillin/Tazobactam-resistance, FQ-R\u0026thinsp;=\u0026thinsp;Fluoroquinolone-resistance, Ceph-R\u0026thinsp;=\u0026thinsp;Cephalosporin-resistance\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e* no patients were exposed to \u003cem\u003ePseudomonas\u003c/em\u003e-active cephalosporins (ceftazidime/cefepime) within three months prior to PABSI\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe association between fluoroquinolone exposure (FQ-E) and fluoroquinolone resistance was at the margin of statistical significance, while the associations between either FQ-E and piperacillin/tazobactam resistance (PT-R) or FQ-E and cephalosporin resistance (Ceph-R) were statistically significant. Furthermore, previous therapies with carbapenems were found to be associated with carbapenem resistance. As there were no cases with cephalosporin-exposure, no associations for co-resistance could be statistically determined (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 4 Co-resistance of PABSI isolates\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width:100.0%;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.64%;border: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eNo of isolates\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: 1pt solid windowtext;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-image: initial;border-left: none;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eResistance to\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 70.3%;border-top: 1pt solid windowtext;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-image: initial;border-left: none;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eCo-resistance with antibiotic n (%)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.64%;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 27.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 27.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 27.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eP/T\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 27.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eCP\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 27.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eCipro\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 27.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003ePA-Ceph\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 27.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eAG\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.64%;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eP/T\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e10 \u003cstrong\u003e(63)*\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e6 (38)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e9 \u003cstrong\u003e(56)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e2 (13)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.64%;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e17\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eCP\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e10 \u003cstrong\u003e(59)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e8 (47)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e8 (47)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e4 (24)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.64%;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eCipro\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e7 \u003cstrong\u003e(64)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e8 \u003cstrong\u003e(73)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e7 \u003cstrong\u003e(64)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e3 (28)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.64%;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003ePA-Ceph *\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e10 \u003cstrong\u003e(83)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e8 \u003cstrong\u003e(67)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e7 \u003cstrong\u003e(58)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e3 (25)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.64%;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eAG\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e2 (50)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e4 \u003cstrong\u003e(100)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e3 \u003cstrong\u003e(75)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e3 \u003cstrong\u003e(75)\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.06%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: rgb(231, 230, 230);padding: 0in 5.4pt;height: 28.35pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003eP/T= Piperacillin/Tazobactam; CP= Carbapenem (Imipenem or Meropenem); Cipro= Ciprofloxacin; PA-Ceph=\u003cem\u003ePseudomonas\u003c/em\u003e-active Cephalosporins (Ceftazidime or Cefepime); AG= Aminoglycosides\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;font-size:16px;font-family:\"Calibri\",sans-serif;line-height:200%;'\u003e\u003cspan style='font-size:12px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e*Co-resistance rates of \u0026gt;50% are marked in bold\u003c/span\u003e\u003c/p\u003e\u003cp\u003eThe PABSI isolates in our study showed a significant rate of co-resistance. PT-R isolates were often also carbapenem or cephalosporin resistant (63% and 56%, respectively). CP-R isolates were often also PT-R. FQ-R isolates were also predominantly carbapenem-, piperacillin/tazobactam, or cephalosporin-resistant (73%, 64%, and 64%, respectively). Aminoglycoside resistance (AS-R) was rare, with only 4 (8%) of isolates tested resistant. Conversely, when aminoglycoside resistance was present, CP-R, FQ-R and Ceph-R was also present in 100%, 75% and 75%, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\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\u003eRisk factors of fatal outcome at day 30 in PABSI by univariate regression analysis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnadjusted OR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnivariate p-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMultivariate p-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAppropriate antibiotic therapy within 24 hrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.78 (1.58-29.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e5.07 (1.07\u0026ndash;24.07)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternal organ infection (Pneumonia or cIAI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.07 (0.01\u0026ndash;0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePiperacillin/Tazobactam resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.17 (0.041\u0026ndash;0.721)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCarbapenem-resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.33 (0.08\u0026ndash;1.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluoroquinolone-resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.12 (0.03\u0026ndash;0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.17 (0.03\u0026ndash;0.83)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCephalosporin-resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.08 (0.02\u0026ndash;0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAminoglycoside-resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.07 (0.01\u0026ndash;0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultidrug resistance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.10 (0.02\u0026ndash;0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the univariate regression analysis, FQ-R, P/T-R, Ceph-R, AG-R and MDR, but not CP-R were found to be associated with increased 30-day mortality (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Since there were no survivors among patients with intraabdominal infections, regression analysis could not be performed. Taken together, cases with internal organ infection (lung or intraabdominal infection) exhibited a significantly elevated risk of fatal outcome, as in case of patients who did not receive adequate therapy within 24 hrs after the onset of fever. In the multivariable analysis, FQ-R and lack of adequate therapy within 24 hrs were significantly associated with unfavorable outcome (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this monocentric retrospective study, we analyzed the risk factors and outcomes of adult hematological patients with BSI due to \u003cem\u003eP. aeruginosa\u003c/em\u003e (PABSI) over nearly ten years. We found that antibiotic drug resistance is a main risk factor for increased mortality, most likely due to inadequate empirical therapy. The inadequacy of antibiotic therapy and the development of antibiotic resistance have been identified as risk factors for a fatal outcome in neutropenic patients with sepsis in previous studies [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These observations are consistent with those of other studies about PABSI caused by multidrug-resistant, sometimes hypervirulent isolates of \u003cem\u003eP. aeruginosa\u003c/em\u003e in hematologic patients [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. BSIs due to \u003cem\u003eP. aeruginosa\u003c/em\u003e are associated with high rates of morbidity and mortality, with estimated mortality rates of 43.2\u0026ndash;58.8% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], which is considerably higher than the 30-day mortality in our cohort (22%), especially in view of a relatively high resistance rate in our cohort [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In our cohort, as in other studies, previous antibiotic exposure was associated with occurrence of resistant \u003cem\u003eP. aeruginosa\u003c/em\u003e [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Of note, carbapenem exposure was associated with both carbapenem-resistance and fluoroquinolone-resistance in \u003cem\u003eP. aeruginosa.\u003c/em\u003e Fluoroquinolone exposure was associated with both, cephalosporin-resistance and piperacillin/tazobactam resistance, whereas the association with fluoroquinolone-resistance remained at the margin of significance. We found higher rates of co-resistance compared to other studies [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. \u003cem\u003eP. aeruginosa\u003c/em\u003e has numerous intrinsic resistance mechanisms such as porin loss, efflux pumps and inactivating enzymes. It can also acquire resistance mechanisms, e.g. through mutation or horizontal gene transfer (e.g. of metallo-betalactamases) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The mechanism cannot be deduced from the resistance phenotype and since our strains were not available for whole genome sequencing, the causes for the observed resistance remain speculative.\u003c/p\u003e \u003cp\u003eIt has been demonstrated that in patients with leukemia, the pathogen responsible for the BSI frequently dominates or colonizes the microbiota of the gastrointestinal (GI) tract [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Conversely, avoiding colonization, especially by multidrug-resistant \u003cem\u003eP. aeruginosa\u003c/em\u003e strains, could potentially reduce the risk of invasive infection.\u003c/p\u003e \u003cp\u003eAs about sixty percent of leukemia patients develop neutropenic fever and the prompt initiation of an empirical and \u003cem\u003ePseudomonas\u003c/em\u003e-active therapy is strongly recommended, most patients are extensively exposed to antibiotics and antibiotic selection pressure is a relevant problem [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. To minimize selection pressure and damage to the microbiota, antibiotic therapies should be prescribed for as long as necessary, but as short as possible. By deciding in favor of monotherapy versus combination therapy and a rational duration of treatment, antibiotic usage and thus selection pressure can be reduced. The superiority of combination therapy over monotherapy in PABSI is a subject of ongoing controversy. A meta-analysis showed no difference in terms of mortality, although data on infections with antibiotic resistant \u003cem\u003eP. aeruginosa\u003c/em\u003e-BSI are scarce. For this reason, the current ESCMID guidelines do not include a recommendation for or against targeted combination therapy for infections caused by carbapenem-resistant \u003cem\u003eP. aeruginosa\u003c/em\u003e [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In severe infections (sepsis), a combination is recommended, if monotherapy is based on either fosfomycin, a polymyxin or an aminoglycoside [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In line with this, the IDSA does not recommend combination therapy for PABSI, if one of the new beta-lactam/beta-lactamase inhibitor combinations (ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam) or cefiderocol have been tested susceptible [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Current AGIHO guidelines strongly recommend the use of single-agent broad-spectrum \u003cem\u003ePseudomonas\u003c/em\u003e-active antibiotics such as piperacillin/tazobactam, ceftazidime, cefepime, meropenem or imipenem/cilastatin as first line antibiotic therapy [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, in our cohort, 32% of patients received an empirical combination therapy, due to local treatment policy. With regard to the duration of therapy, it has been shown that the duration of treatment for febrile neutropenia, which is often determined by the time of regeneration, can be shortened in view of a 72 hours fever-free status and clinical response, without any negative impact on clinical outcome [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Furthermore, a multicenter-study in onco-hematology patients with PABSI could show, that short-courses (7\u0026ndash;11 days) of therapy were non-inferior in terms of clinical outcomes compared to prolonged courses (12-21days) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe benefits of fluoroquinolone prophylaxis (FQP) have also been the subject of controversial debate for years. In the meantime, it has been repeatedly demonstrated that, although the omission of an FQP is associated with an increase in BSI, it is not associated with increased mortality [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe effects of FQP on resistance selection were shown not only for \u003cem\u003eP. aeruginosa\u003c/em\u003e infections, but also for both viridans \u003cem\u003estreptococci\u003c/em\u003e and \u003cem\u003eEnterobacterales\u003c/em\u003e [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] which in turn leads to reduced effectiveness of prophylaxis [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The empirical use of fluoroquinolones for combination therapy in neutropenic patients with sepsis can therefore not be recommended in centers where FQP is widely used or if colonization with a FQ-R pathogen such as \u003cem\u003eP. aeruginosa\u003c/em\u003e or \u003cem\u003eEnterobacterales\u003c/em\u003e is documented.\u003c/p\u003e \u003cp\u003eThese observations compelled other centers to leave the FQP [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Discontinuation of FQP has been shown to decrease FQ-R and 3rd generation cephalosporin resistance due to ESBL-producing \u003cem\u003eEnterobacterales\u003c/em\u003e, without the increase of serious infectious complications [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAt our center, FQP has been largely discontinued in the stem cell unit but is still in place in patients undergoing intensive chemotherapy for acute leukemia. As a result, potentially resistant pathogens, including \u003cem\u003eP. aeruginosa\u003c/em\u003e, may be already selected prior to stem cell transplantation.\u003c/p\u003e \u003cp\u003eAntibiotic stewardship in hematology may therefore contribute to reducing infections caused by multi-resistant pathogens and the maintainance of a protective microbiota, thereby improving patient outcomes [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs a consequence of our study, we would like to strengthen antibiotic stewardship efforts on hematology wards. In the light of the observed increase in mortality associated with FQR, the use of FQP in patients with acute leucemia under intensive chemotherapy should be reconsidered.\u003c/p\u003e\n\u003ch3\u003eLimitations:\u003c/h3\u003e\n\u003cp\u003eIt should be noted that this study has some limitations. First, this is a retrospective study, which means that not all relevant data was available. Second, the evaluation is monocentric, and BSIs with \u003cem\u003eP. aeruginosa\u003c/em\u003e are not very frequent, resulting in a relatively low number of cases, with only 50 patients included.\u003c/p\u003e \u003cp\u003eConsequently, our conclusions need to be tested in large, multicenter and potentially interventional studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConception, data collection and data analysis were performed by JK and MH. The first draft of the manuscript was written by JK. MH reviewed and edited the manuscript- FL, GB and BS were closely involved in patient care. MV, HS, SW, SS, BS, GB and FL were involved in planning and conducting the study. EH advised on the statistics. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to thank Ms. Langhans for providing the microbiological data. We would also like to thank all persons involved in the clinical care of the PABSI patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJ. T. Thaden, L. P. Park, S. A. Maskarinec, F. Ruffin, V. G. Fowler, and D. van Duin, \u0026ldquo;Results from a 13-Year Prospective Cohort Study Show Increased Mortality Associated with Bloodstream Infections Caused by Pseudomonas aeruginosa Compared to Other Bacteria,\u0026rdquo; \u003cem\u003eAntimicrob. 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Paul \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine),\u0026rdquo; \u003cem\u003eClin. Microbiol. Infect.\u003c/em\u003e, vol. 28, no. 4, pp. 521\u0026ndash;547, Apr. 2022, doi: 10.1016/j.cmi.2021.11.025.\u003c/li\u003e\n\u003cli\u003e\u0026lt;div class=\u0026quot;pub-history-row clearfix\u0026quot;\u0026gt; \u0026lt;div class=\u0026quot;ww-citation-primary\u0026quot;\u0026gt;\u0026lt;em\u0026gt;Clinical Infectious Diseases\u0026lt;/em\u0026gt; rel=\u0026quot;noopener\u0026quot;\u0026gt;[email protected]\u0026lt;/a\u0026gt;\u0026lt;/span\u0026gt;.\u0026lt;/strong\u0026gt;\u0026lt;/em\u0026gt;\u0026lt;/h4\u0026gt; ciad428,\u0026amp;nbsp;\u0026lt;a href=\u0026quot;https://doi org/10 1093/cid/ciad428\u0026quot; data-google-interstitial=\u0026quot;false\u0026quot;\u0026gt;https://doi org/10 1093/cid/ciad428\u0026lt;/a\u0026gt;\u0026lt;/div\u0026gt; \u0026lt;/div\u0026gt; \u0026lt;div class=\u0026quot;pub-history-row clearfix\u0026quot;\u0026gt; \u0026lt;div class=\u0026quot;ww-citation-date-wrap\u0026quot;\u0026gt; \u0026lt;div class=\u0026quot;citation-label\u0026quot;\u0026gt;\u0026lt;strong\u0026gt;Published\u0026lt;/strong\u0026gt;: 18 July 2023\u0026lt;/div\u0026gt; \u0026lt;/div\u0026gt; \u0026lt;/div\u0026gt; \u0026lt;p\u0026gt;\u0026amp;nbsp;\u0026lt;/p\u0026gt; \u0026lt;p\u0026gt;Pranita D. Tamma*, Samuel L. Aitken, Robert A. Bonomo, Amy J. Mathers, David van Duin, Cornelius J. Clancy\u0026lt;/p\u0026gt; \u0026lt;p\u0026gt;\u0026lt;em\u0026gt;*Corresponding Author\u0026lt;/em\u0026gt;\u0026lt;/p\u0026gt; \u0026lt;h4\u0026gt;\u0026lt;em\u0026gt;\u0026lt;strong\u0026gt;Please submit your feedback and comments on the AMR Guidance by emailing\u0026amp;nbsp;\u0026lt;span style=\u0026quot;text-decoration: underline;\u0026quot;\u0026gt;\u0026lt;a href=\u0026quot;mailto:practiceguidelines@idsociety org\u0026quot; target=\u0026quot;_blank\u0026quot;, \u0026ldquo;AMR Guidance.\u0026rdquo; Accessed: Jul. 08, 2024. [Online]. Available: https://www.idsociety.org/practice-guideline/amr-guidance/\u003c/li\u003e\n\u003cli\u003eM. Christopeit \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Prophylaxis, diagnosis and therapy of infections in patients undergoing high-dose chemotherapy and autologous haematopoietic stem cell transplantation. 2020 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO),\u0026rdquo; \u003cem\u003eAnn. Hematol.\u003c/em\u003e, vol. 100, no. 2, pp. 321\u0026ndash;336, Feb. 2021, doi: 10.1007/s00277-020-04297-8.\u003c/li\u003e\n\u003cli\u003eM. Aguilar-Guisado \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial,\u0026rdquo; \u003cem\u003eLancet Haematol.\u003c/em\u003e, vol. 4, no. 12, pp. e573\u0026ndash;e583, Dec. 2017, doi: 10.1016/S2352-3026(17)30211-9.\u003c/li\u003e\n\u003cli\u003eX. Feng \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Is Short-Course Antibiotic Therapy Suitable for Pseudomonas aeruginosa Bloodstream Infections in Onco-hematology Patients With Febrile Neutropenia? Results of a Multi-institutional Analysis,\u0026rdquo; \u003cem\u003eClin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am.\u003c/em\u003e, vol. 78, no. 3, pp. 518\u0026ndash;525, Mar. 2024, doi: 10.1093/cid/ciad605.\u003c/li\u003e\n\u003cli\u003eM. Cullen \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas,\u0026rdquo; \u003cem\u003eN. Engl. J. Med.\u003c/em\u003e, vol. 353, no. 10, pp. 988\u0026ndash;998, Sep. 2005, doi: 10.1056/NEJMoa050078.\u003c/li\u003e\n\u003cli\u003eG. Bucaneve \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia,\u0026rdquo; \u003cem\u003eN. Engl. J. Med.\u003c/em\u003e, vol. 353, no. 10, pp. 977\u0026ndash;987, Sep. 2005, doi: 10.1056/NEJMoa044097.\u003c/li\u003e\n\u003cli\u003eR. M. Prabhu, K. E. Piper, M. R. Litzow, J. M. Steckelberg, and R. Patel, \u0026ldquo;Emergence of quinolone resistance among viridans group streptococci isolated from the oropharynx of neutropenic peripheral blood stem cell transplant patients receiving quinolone antimicrobial prophylaxis,\u0026rdquo; \u003cem\u003eEur. J. Clin. Microbiol. Infect. Dis. Off. Publ. Eur. Soc. Clin. Microbiol.\u003c/em\u003e, vol. 24, no. 12, pp. 832\u0026ndash;838, Dec. 2005, doi: 10.1007/s10096-005-0037-3.\u003c/li\u003e\n\u003cli\u003eM. J. Satlin \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Colonization With Fluoroquinolone-Resistant Enterobacterales Decreases the Effectiveness of Fluoroquinolone Prophylaxis in Hematopoietic Cell Transplant Recipients,\u0026rdquo; \u003cem\u003eClin. Infect. Dis. Off. Publ. Infect. Dis. Soc. 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Verlinden \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Clinical and microbiological impact of discontinuation of fluoroquinolone prophylaxis in patients with prolonged profound neutropenia,\u0026rdquo; \u003cem\u003eEur. J. Haematol.\u003c/em\u003e, vol. 93, no. 4, pp. 302\u0026ndash;308, Oct. 2014, doi: 10.1111/ejh.12345.\u003c/li\u003e\n\u003cli\u003eA. Contejean \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Antimicrobial stewardship in high-risk febrile neutropenia patients,\u0026rdquo; \u003cem\u003eAntimicrob. \u003c/em\u003e\u003cem\u003eResist. Infect. Control\u003c/em\u003e, vol. 11, no. 1, p. 52, Mar. 2022, doi: 10.1186/s13756-022-01084-0.\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":"infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infe","sideBox":"Learn more about [Infection](http://link.springer.com/journal/15010)","snPcode":"15010","submissionUrl":"https://submission.nature.com/new-submission/15010/3","title":"Infection","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pseudomonas aeruginosa, bloodstream infections, antibiotic resistance, fluoroquinolone-prophylaxis, hematological patients, antimicrobial stewardship","lastPublishedDoi":"10.21203/rs.3.rs-5212591/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5212591/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eBloodstream infections caused by \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (PABSI) in hematological patients are associated with high morbidity and mortality. We investigated the epidemiology, risk factors, and outcomes of PABSI at our center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll adult hematological patients with PABSI between January 2013 and July 2023 were included. Demographic and clinical characteristics, antimicrobial susceptibilities, antibiotic therapy, fluoroquinolone-prophylaxis, source of infection, and 30-day outcome were recorded. Descriptive statistics, tests for difference, and logistic regression models were performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eFifty patients with PABSI were identified with a median age of 58.5 years (range 24-78). 37 patients (74%) had severe neutropenia, 20 (40%) received allogeneic HSCT, and 29 (58%) had acute leukemia. A total of 34 (68%) had received timely appropriate anti-pseudomonal antibiotic therapy. The most common presumed cause of PABSI was mucositis (n=16, 32%), followed by pneumonia (8, 16%) and skin and soft tissue infections (n=6, 12%). Empirical combination therapy was used in 16 (32%) patients, while targeted combination therapies were used in 27 (54%) patients. \u003cem\u003eP. aeruginosa\u003c/em\u003e detection led to treatment change in 31 (62%) cases. The overall 30-day survival rate was 78% (n=39). Carbapenem-resistance occurred in 34% (n=17), and multidrug-resistance (MDR) in 20% (n=10). Prior antibiotic exposure was associated with resistance. Appropriate antibiotic therapy was associated with survival, whereas antibiotic resistance and organ infection were associated with a fatal outcome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrior antibiotic exposure in hematological patients is associated with resistance in PABSI, a major risk factor for a fatal outcome. Antibiotic stewardship efforts should be intensified and fluoroquinolone prophylaxis needs to be reconsidered.\u003c/p\u003e","manuscriptTitle":"Risk factors and outcome of Pseudomonas aeruginosa bloodstream infections (PABSI) in hematological patients: A single center retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-11 17:53:38","doi":"10.21203/rs.3.rs-5212591/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-12T05:08:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-12T04:05:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-11T16:28:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-09T15:06:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-05T11:42:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"290687438104841770434765032594462585388","date":"2024-11-01T15:17:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"180651768127802286244779870145169981238","date":"2024-10-30T11:31:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99431981460298136327465861861455165009","date":"2024-10-30T06:54:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"194756812735905304578833078954387041362","date":"2024-10-15T11:51:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-14T14:36:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-08T04:15:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-07T05:31:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Infection","date":"2024-10-06T11:18:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infe","sideBox":"Learn more about [Infection](http://link.springer.com/journal/15010)","snPcode":"15010","submissionUrl":"https://submission.nature.com/new-submission/15010/3","title":"Infection","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"39d6cad2-0b4e-4a83-b52e-3f3d3a38d710","owner":[],"postedDate":"December 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-23T16:09:13+00:00","versionOfRecord":{"articleIdentity":"rs-5212591","link":"https://doi.org/10.1007/s15010-024-02453-0","journal":{"identity":"infection","isVorOnly":false,"title":"Infection"},"publishedOn":"2024-12-19 15:58:37","publishedOnDateReadable":"December 19th, 2024"},"versionCreatedAt":"2024-12-11 17:53:38","video":"","vorDoi":"10.1007/s15010-024-02453-0","vorDoiUrl":"https://doi.org/10.1007/s15010-024-02453-0","workflowStages":[]},"version":"v1","identity":"rs-5212591","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5212591","identity":"rs-5212591","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}