Efficacy of Protocol-Based Pharmacotherapy Management in Switching of Antibiotic Administration Routes and Dose Adjustment Based on Renal Function: A Before-After Study

Efficacy of Protocol-Based Pharmacotherapy Management in Switching of Antibiotic Administration Routes and Dose Adjustment Based on Renal Function: A Before-After Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy of Protocol-Based Pharmacotherapy Management in Switching of Antibiotic Administration Routes and Dose Adjustment Based on Renal Function: A Before-After Study Yuki Sato, Yudai Takatani, Shunsaku Nakagawa, Yoshiki Katada, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7429703/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Dec, 2025 Read the published version in Journal of Pharmaceutical Health Care and Sciences → Version 1 posted You are reading this latest preprint version Abstract Background: Antibiotics are crucial for treating infectious diseases, but their appropriate use is essential to minimize adverse reactions and resistance. This study evaluated the effectiveness of protocol-based pharmacotherapy management (PBPM) based on renal function in adjusting antibiotic dosage and implementing an intravenous-to-oral switch in older patients at high risk of drug-related adverse events. The study compared antibiotic treatment outcomes before and after PBPM implementation at Kyoto University Hospital. Method: This before-and-after study included patients aged ≥65 years diagnosed with community-acquired pneumonia or uncomplicated pyelonephritis at Kyoto University Hospital. The control group (January to December 2021) received conventional antibiotic treatment, whereas the PBPM group (June 2022 to May 2023) received treatment based on a protocol developed by pharmacists, emergency physicians, and infectious disease specialists. Primary and secondary outcomes included antibiotic administration duration, clinical response, adverse reactions, and costs. Results: The study included 78 patients (40 control, 38 PBPM). The PBPM group showed a significantly shorter total antibiotic treatment duration (9.6 ± 4.4 vs. 7.5 ± 2.4 days, p < 0.05) and intravenous administration duration (7.1 ± 2.8 vs. 5.6 ± 2.2 days, p < 0.01) compared with the control group. The PBPM group also demonstrated lower clinical treatment failure rates and reduced incidences of acute kidney injury and alanine aminotransferase elevation. Antibiotic costs per patient were 13% lower in the PBPM group. There were no significant differences in early clinical response, readmission rates, or mortality between groups. Conclusions: PBPM, conducted collaboratively by pharmacists and physicians, effectively optimized antibiotic use, reduced adverse event risks, shortened treatment duration, and lowered healthcare costs without compromising clinical outcomes. These findings support PBPM implementation to improve antibiotic stewardship in older patients with common infections. Clinical trial number: not applicable. protocol-based pharmacotherapy management antibiotic stewardship dosage adjustment renal function intravenous-to-oral switch K-COGaI criteria Figures Figure 1 1. Introduction Antibiotics are essential for the treatment of infectious diseases, and their efficacy is widely recognized. However, appropriate use of these drugs is crucial for minimizing adverse reactions and the emergence of resistance [ 1 , 2 ]. Therefore, maximizing the efficacy of antibiotics while minimizing their side effects, specifically toxicity and the emergence of resistance, is recommended [ 3 ]. In addition, many patients hospitalized with infectious diseases receive antibiotics intravenously (IV), which is more expensive than oral administration (PO) and also incurs indirect costs associated with preparation and administration [ 4 ]. Indirect costs have been reported to exceed the cost of the drug itself by 13–113% [ 5 ]. One approach to antibiotic use is dose optimization based on the pharmacokinetics (PK)/pharmacodynamics (PD) theory for IV antibiotics. The second approach is switching from IV to PO administration as soon as the patient is clinically stable. Such interventions, including dose adjustments and changes in administration routes, have been reported to have multiple benefits, including fewer adverse reactions, reduced risk of infection, shorter hospital stays, and reduced associated costs [ 4 , 6 – 13 ]. In particular, several randomized controlled trials have shown that early switching to oral antibiotics is safe while maintaining efficacy in common infections such as pneumonia, uncomplicated pyelonephritis, and intra-abdominal infections [ 7 , 14 , 15 ]. Therefore, when using antibiotics, a prompt transition from IV to PO is strongly recommended once patients are clinically stable. This recommendation is outlined in the 2007 American Thoracic Society and Infectious Diseases Society of America (IDSA) Community-Acquired Pneumonia Guidelines and the 2016 IDSA Antibiotic Stewardship Guidelines [ 16 , 17 ]. Cooperation by a multidisciplinary team is essential in promoting appropriate antibiotic use, and the intervention of pharmacists is particularly effective. The IDSA and the Society for Healthcare Epidemiology of America recommend that pharmacists play an active role in antibiotic stewardship programs as part of their routine practice [ 16 ]. In particular, pharmacist-initiated intravenous-to-oral switch (IVOS) after symptom improvement has been reported to be beneficial, leading to shorter antibiotic treatment durations and reduced medical costs [ 6 ]. Furthermore, it would be clinically useful for pharmacists to intervene comprehensively, not only by initiating IVOS but also by adjusting antibiotic dosages based on the PK/PD theory. However, no examples of such practices or their clinical significance have been reported thus far. In addition, depending on local regulations, it may be difficult for pharmacists to adjust the antibiotic dosage independently or on behalf of physicians; therefore, establishing predefined protocols that enable pharmacists to intervene in antibiotic treatment would be beneficial. At Kyoto University Hospital, doctors and pharmacists have collaborated to implement protocol-based pharmacotherapy management (PBPM) for antibiotic treatment in emergency patients [ 18 ]. This approach is expected to provide safe drug therapy while maintaining clinical outcomes. In this study, we retrospectively examined the effectiveness of PBPM in adjusting antibiotic dosages and implementing IVOS based on renal function in older patients at high risk of drug-related adverse events, including renal dysfunction. 2. Methods 2.1 Study design This before-and-after study aimed to evaluate the efficacy of PBPM in antibiotic treatment. As PBPM was implemented for antibiotic treatment at Kyoto University Hospital in January 2022, we compared older patients who received antibiotic treatment before and PBPM initiation. The control group comprised patients treated from January 2021 to December 2021, and the PBPM group comprised patients treated from June 2022 to May 2023. The period from January to May 2022 was excluded because it represented a transition period before the implementation of PBPM. 2.2 Study participants The study participants were patients aged 65 years or older diagnosed with community-acquired pneumonia or uncomplicated pyelonephritis during the study period, admitted to the emergency intensive care unit or ward in the Department of Primary Care and Emergency Medicine at Kyoto University Hospital, and initiated IV antibiotic therapy. Patients with bacteremia often require longer treatment periods; therefore, they were excluded to ensure comparable conditions. In addition, patients hospitalized due to complicated infections (e.g., empyema, lung abscess, renal abscess, perinephric abscess), those who completed IV antibiotic treatment within 48 hours of initiation, those who began antibiotic treatment before hospitalization, and those transferred to another ward or hospital before completing antibiotic treatment were also excluded. 2.3 Antibiotic treatment using PBPM When implementing PBPM, pharmacists, emergency physicians, and infectious disease physicians created a protocol for adjusting antibiotic dosages based on renal function (Supplementary Tables 1 and 2), referencing The Sanford Guide to Antimicrobial Therapy ( https://www.sanfordguide.com/ ). Additionally, referencing the COMS criteria—guidelines for the IVOS of antibiotic therapy reported by the University of Nottingham in 2010—a flowchart for performing IVOS tailored to the clinical setting in Japan was created, which we named the K-COGaI criteria (Supplementary Fig. 1). Within PBPM, doctors selected the initial antibiotics for each patient and asked pharmacists to adjust the dosage based on renal function and evaluate IVOS eligibility. Considering the patient’s age, physical constitution, renal function, and the severity of the infection, the pharmacist proposed an antibiotic prescription (including dosage, volume of dissolving solution, infusion time, and administration route) based on the protocols (Supplementary Tables 1 and 2 and Supplementary Fig. 1). The pharmacist regularly reviewed the blood test results and proposed dosage adjustments when necessary. In addition, when a patient receiving antibiotics met all K-COGaI criteria, the pharmacist recommended IVOS to the attending physician. In either case, the pharmacist’s proposal was recorded in the electronic medical record and shared with the doctors and nurses. During weekday shifts (8:30–17:15), pharmacists proactively proposed antibiotic dosage adjustments and IVOS. At other times, physicians determined the dosage and timing of IVOS by referring to the dosage adjustment protocol based on renal function. Patients in the control group received antibiotics before the protocol was established, and the antibiotic dosage and timing of IVOS were determined based on the emergency physician’s knowledge and experience. 2.4 Outcomes The primary endpoint was the duration of antibiotic administration (days). The secondary endpoints were early clinical response (ECR), clinical treatment failure rate, readmission rate within 28 days after discharge, 28-day mortality, length of hospital stay, rate of adverse reactions, antibiotic cost, and compliance with the dosage adjustment protocol based on renal function. ECR was defined as meeting all of the following three criteria: i) no clinical deterioration or death within 96 hours; ii) a decrease of ≥ 30% in white blood cell count or C-reactive protein compared with baseline; and iii) a decrease in body temperature of 0.3°C for 2 consecutive days from treatment initiation. Clinical treatment failure was defined as a change in broad-spectrum antibiotic use or relapse. Adverse reactions were defined as grade 1 or higher events that occurred during antibiotic use. Acute kidney injury (AKI) was assessed according to the Kidney Disease Improving Global Outcomes clinical practice guidelines [ 19 ]. Elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and diarrhea were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Compliance with the dosage adjustment protocol based on renal function was calculated as the proportion of patients who adhered to the protocol (Supplementary Tables 1 and 2). 2.5 Other Measurements Causative bacteria detected in sputum and urine were identified by an infectious disease specialist. Information on other variables, including age, sex, and reasons why IVOS could not be performed, was collected from electronic medical records. 2.6 Statistical Analysis Fisher’s exact test was used to compare nominal variables between the two groups, and Student’s t-test was used to compare continuous variables. A risk level of ≤ 5% (P < 0.05) was considered statistically significant. GraphPad PRISM (GraphPad Software Inc., San Diego, CA) was used for the analysis. 3. Results 3 − 1. Patients’ demographic and clinical characteristics Among 85 patients admitted to the emergency department with community-acquired pneumonia or uncomplicated pyelonephritis, 78 were included in the final analysis (40 control, 38 PBPM) (Fig. 1 ). Seven patients were excluded for the following reasons: i) admitted due to bacteremia (n = 3), ii) admission due to empyema (n = 1), iii) competion of IV antibiotics within 48 hours of initiation (n = 1), iv) initiation of antibiotics before admission (n = 1), and v) transfer to another ward or hospital before completion of antibiotic treatment (n = 1). There were no significant differences between the two groups regarding their demographic and clinical characteristics (Table 1 ). Table 1 Patients’ demographic and clinical characteristics Control group (n = 40) PBPM group (n = 38) Sex, female, n (%) 19 (47.5) 16 (42.1) Age (years), mean ± SD 83.9 ± 9.1 82.1 ± 14.6 Body weight (kg), mean ± SD 52.6 ± 12.1 54.4 ± 14.4 Creatinine clearance (mL/min), mean ± SD 34.6 ± 23.9 39.5 ± 26.5 CRP (mg/dL), mean ± SD 12.1 ± 7.7 10.6 ± 8.3 WBC (×10 3 /µL), mean ± SD 12.3 ± 5.3 11.5 ± 5.4 Body temperature (℃), mean ± SD 37.8 ± 0.9 37.9 ± 0.7 Underlying disease, n (%) Diabetes mellitus 14 (35.0) 16 (42.1) Ischemic heart disease 7 (17.5) 12 (31.6) Chronic respiratory disease 1 (2.5) 1 (2.6) Malignant tumor 0 (0) 4 (10.5) Others 19 (47.5) 18 (47.4) Charlson Comorbidity Index, mean ± SD 6.0 ± 1.4 6.1 ± 2.2 Pitt Bacteremia Score, mean ± SD 1.3 ± 1.7 1.9 ± 1.8 Type of infection, n (%) Pneumonia 25 (62.5) 28 (73.7) Pyelonephritis 15 (37.5) 10 (26.3) Causative organisms in pneumonia, n (%) * Haemophilus influenzae 1 (4.0) 0 (0) Klebsiella pneumoniae 4 (16.0) 1 (3.6) Moraxella catarrhalis 0 (0) 2 (7.1) Pseudomonas aeruginosa 3 (12.0) 0 (0) MSSA 1 (4.0) 2 (7.1) MRSA 1 (4.0) 0 (0) Others 2 (8.0) 1 (3.6) Unknown 15 (60.0) 23 (82.1) Causative organisms in uncomplicated pyelonephritis, n (%) * Enterobacter cloacae complex 2 (13.3) 0 (0) Escherichia coli 9 (60.0) 7 (70.0) Klebsiella oxytoca 1 (6.7) 1 (10.0) Klebsiella pneumoniae 2 (13.3) 1 (10.0) Pseudomonas aeruginosa 1 (6.7) 0 (0) Proteus mirabilis 1 (6.7) 0 (0) Others 3 (20.0) 3 (30.0) Unknown 1 (6.7) 0 (0) Empiric therapy, n (%) Ampicillin/Sulbactam 16 (40.0) 14 (36.8) Piperacillin/Tazobactam 6 (15.0) 8 (21.1) Ceftriaxone 12 (30.0) 14 (36.8) Meropenem 3 (7.5) 2 (5.3) Others 3 (7.5) 0 (0) Data are expressed either as means ± standard deviations or numbers with percentages in parentheses. Continuous variables were compared using Student’s t-test. Categorical variables were compared using Fisher’s exact test. *One patient can have more than two indications. Highest value within 24 hours of admission. Creatinine clearance was calculated using the Cockcroft–Gault formula. Protocol-based pharmacotherapy management: PBPM, standard deviation: SD, C-reactive protein: CRP, white blood cell: WBC, Methicillin-susceptible Staphylococcus aureus : MSSA, Methicillin-resistant Staphylococcus aureus : MRSA. 3 − 2. Association between IVOS and PBPM The proportion of patients who underwent IVOS was 42.5% (17/40) and 39.5% (15/38) in the control and PBPM groups, respectively, with no significant difference (Table 2 ). Similarly, when categorized into pneumonia and uncomplicated pyelonephritis, there was no significant difference between the groups in the proportion of patients who underwent IVOS. However, when IVOS was performed, the time to switch to oral antibiotics was 6.1 ± 2.3 days (mean ± standard deviation) and 4.2 ± 1.1 days in the control and PBPM groups, respectively, significantly shorter in the PBPM group. In the control group, two patients returned to IV administration after switching to oral antibiotics, whereas no such cases occurred in the PBPM group. Reasons for not performing IVOS included lack of clinical improvement, absence of oral antimicrobial agents effective against the causative bacteria, inability to administer oral antibiotics due to gastrointestinal bleeding or other reasons, and patient intubation (Supplementary Table 3). Table 2 Effect of PBPM on intravenous-to-oral switch Control group (n = 40) PBPM group (n = 38) Cases switched from intravenous to oral treatment, n (%) 17 (42.5) 15 (39.5) Pneumonia 7 (28.0) 7 (25.0) Uncomplicated pyelonephritis 10 (66.7) 8 (80.0) Time to switch (days), mean ± SD 6.1 ± 2.3 4.2 ± 1.1** Data are expressed either as means ± standard deviations or numbers with percentages in parentheses. Continuous variables were compared using Student’s t-test. Categorical variables were compared using Fisher’s exact test. ** P < 0.01, significantly different from the control group. Protocol-based pharmacotherapy management: PBPM, standard deviation: SD. 3–3. Antibiotic administration duration in the control and PBPM groups The antibiotic administration duration in the control and PBPM groups is shown in Table 3 . The total antibiotic treatment duration (regardless of administration route) was 9.6 ± 4.4 days and 7.5 ± 2.4 days in the control and PBPM groups, respectively, with the PBPM group showing a significant reduction in treatment duration. The duration of IV administration was also significantly reduced in the PBPM group compared to the control group (control, 7.1 ± 2.8 days; PBPM, 5.6 ± 2.0 days). The duration of PO was not significantly different between the two groups (control, 6.1 ± 4.2 days; PBPM, 4.8 ± 2.4 days). Regarding pneumonia alone, there was a significant difference between the two groups in the total antibiotic treatment period (control, 8.8 ± 4.4 days; PBPM, 6.9 ± 2.2 days), but no significant difference in the duration of IV administration (control, 7.3 ± 3.1 days; PBPM, 5.8 ± 2.2 days) or PO (control, 5.6 ± 4.3 days; PBPM, 4.4 ± 2.4 days). When limited to uncomplicated pyelonephritis, the total antibiotic treatment period (control, 10.9 ± 4.3 days; PBPM, 9.0 ± 2.5 days) and the IV administration period (control, 6.7 ± 2.1 days; PBPM, 4.9 ± 1.5 days) were significantly different between the two groups, but there was no significant difference in PO duration (control, 6.4 ± 4.3 days; PBPM, 5.1 ± 2.6 days). Table 3 Effect of PBPM on the duration of antibiotic treatment Total patients Control group (n = 40) PBPM group (n = 38) Days of intravenous plus oral treatment 9.6 ± 4.4 7.5 ± 2.4* Days of intravenous treatment 7.1 ± 2.8 5.6 ± 2.2** Days of oral treatment 6.1 ± 4.2 4.8 ± 2.4 Patients with pneumonia Control group (n = 25) PBPM group (n = 28) Days of intravenous plus oral treatment 8.8 ± 4.4 6.9 ± 2.2* Days of intravenous treatment 7.3 ± 3.1 5.8 ± 2.2* Days of oral treatment 5.6 ± 4.3 4.4 ± 2.4 Patients with uncomplicated pyelonephritis Control group (n = 15) PBPM group (n = 10) Days of intravenous plus oral treatment 10.9 ± 4.3 9.0 ± 2.5 Days of intravenous treatment 6.7 ± 2.1 4.9 ± 1.5* Days of oral treatment 6.4 ± 4.3 5.1 ± 2.6 Data are expressed as means ± standard deviations. Continuous variables were compared using Student’s t-test. * P < 0.05, ** P < 0.01, significantly different from the control group. Protocol-based pharmacotherapy management: PBPM. 3–4. Secondary outcomes in the control and PBPM groups The secondary outcomes are listed in Table 4 . Among the treatment outcomes, the clinical treatment failure rate was significantly lower in the PBPM group than in the control group. There were no significant differences between the two groups in terms of ECR, rehospitalization rate, 28-day mortality, or length of hospital stay. A comparison of the incidence of antibiotic-related adverse events during antibiotic treatment showed that the incidences of AKI and ALT elevation were significantly lower in the PBPM group than in the control group. There were no significant differences in the incidences of AST elevation, diarrhea, or Clostridioides difficile infection between the two groups. The total antibiotic costs were 522,105 yen (13,517 yen per patient) and 457,205 yen (11,787 yen per patient) for the control and PBPM groups, respectively. Therefore, the cost per patient was 13% lower in the PBPM group than in the control group. A comparison of the adherence rates to the antibiotic dosage adjustment protocol based on renal function before and after PBPM implementation showed that they were 77.5% (31/40) and 97.4% (37/38) in the control and PBPM groups, respectively, with a significantly higher rate in the PBPM group. Table 4 Secondary outcomes for antibiotic treatment Control group (n = 40) PBPM group (n = 38) Treatment success, n (%) Early clinical response 18 (45.0) 23 (60.1) Clinical treatment failures 9 (22.5) 2 (5.6)* Readmission within 1 month 2 (5.0) 0 (0) 28-day mortality, n (%) 0 (0) 0 (0) Length of hospital stay (days), mean ± SD 10.4 ± 4.7 10.6 ± 6.2 Adverse events, n (%) Nephrotoxicity a 6 (15.0) 0 (0)* Hematologic abnormality b 0 (0) 0 (0) Hepatobiliary abnormality b 13 (32.5) 4 (10.5)* Aspartate aminotransferase increased 11 (27.5) 4 (10.5) Alanine aminotransferase increased 9 (22.5) 2 (5.3)* Total bilirubin increased 0 (0) 0 (0) Non- Clostridioides difficile -associated diarrhea 10 (25.0) 14 (36.8) Clostridioides difficile infection 0 (0) 0 (0) Cost of antibiotics (yen), mean ± SD 13,517 ± 10,462 11,787 ± 6,798 Compliance with renal dosage adjustment protocol for antibiotics Yes, n (%) 31 (77.5) 37 (97.4)* No (overdose), n (%) 3 (7.5) 1 (2.63) No (underdose), n (%) 6 (15.0) 0 (0)* Data are expressed either as means ± standard deviations or numbers with percentages in parentheses. Continuous variables were compared using Student’s t-test. Categorical variables were compared using Fisher’s exact test. a Classified according to the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines. b Classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 clinical practice guidelines. * P < 0.05, significantly different from the control group. Protocol-based pharmacotherapy management: PBPM, standard deviation: SD. 4. Discussion This study examined the effectiveness of PBPM in implementing IVOS and antibiotic dose adjustment based on renal function. The results showed that PBPM shortened the duration of IV antibiotic administration, reduced the risk of adverse events, and lowered pharmaceutical costs without negatively affecting clinical outcomes compared to conventional treatment mainly performed by physicians. The effectiveness of IVOS in PBPM is consistent with the results of a previous study that evaluated the usefulness of IVOS of antibiotics using Collaborative Drug Therapy Management [ 20 ]. However, this is the first study to apply a protocol that standardizes the process of IVOS and antibiotic dose adjustment based on renal function, offering advantages different from those of existing studies. No differences were observed between the control and PBPM groups in ECR, 28-day mortality, readmission within 1 month, proportion of Clostridioides difficile infection cases, and length of hospitalization. In addition, during the period in which PBPM was implemented, there were no deaths within 28 days, no rehospitalizations within 1 month, and no cases of Clostridioides difficile infection, suggesting that the implementation of PBPM does not worsen clinical outcomes. A meta-analysis reported that IVOS was as effective as continued IV administration in terms of clinical outcomes in community-acquired pneumonia [ 10 ]. Therefore, the antimicrobial stewardship program recommended by the IDSA and Society for Healthcare Epidemiology of America strongly recommends that IV antibiotics used in initial treatment should be switched to oral antibiotics at the appropriate time [ 16 ]. Therefore, in the case of uncomplicated infections, it is clinically appropriate to actively switch the route of antibiotic administration via PBPM. The implementation of PBPM by pharmacists in this study was shown to be an effective method for shortening both the total and IV antibiotic administration periods. The duration of IV antibiotic administration was also shortened across different types of infections. There was a difference in the rate of IVOS between patients with pneumonia and those with uncomplicated pyelonephritis. This may be due to the high risk of aspiration and difficulty with oral intake in patients with pneumonia, which may have led to a slower switch to PO (Supplementary Table 3). Nevertheless, the implementation of PBPM could still lead to an appropriate treatment duration, even in patients with limited options. This study, however, did not find any association between the implementation of PBPM and a shortened length of hospital stay. Many patients had difficulty being discharged home; some were not immediately discharged after switching to PO, while others underwent a period of observation after switching. Although future larger studies are needed to confirm its validity, this study suggests that the implementation of PBPM contributes to a shortened antibiotic administration period in both patients with community-acquired pneumonia and uncomplicated pyelonephritis. Adverse events associated with antibiotic administration occurred in 22.3% of patients, and the risk of adverse events increased by 3% for every 10 days of antibiotic use [ 21 , 22 ]. Therefore, regular reviews of the dosage and necessity of antibiotics are expected to reduce the risk of adverse events. In this study, the rates of AKI and ALT elevation during the antibiotic administration period significantly decreased after the implementation of PBPM compared to before its implementation. Although compliance with the antibiotic dosage adjustment protocol based on renal function improved after the implementation of PBPM, the rate of overdosing remained unchanged. Therefore, the decrease in adverse events is likely due to the shortened antibiotic administration period facilitated by PBPM. This study had some limitations. First, the patients in the PBPM and control groups were admitted at different times, introducing potential confounding effects. For instance, the increased knowledge and ability of doctors and pharmacists due to the establishment of the dosage adjustment protocol and IVOS flowchart for PBPM may have indirectly influenced the results. In addition, this study was conducted at a single institution with a small sample size; therefore, caution is required when generalizing the effectiveness of PBPM. 5. Conclusions The results of this study suggest that PBPM, when conducted collaboratively by pharmacists and physicians, is an effective method to optimize antibiotic use, reduce the risk of adverse events, and shorten treatment duration, thereby lowering healthcare costs. We believe that these findings will contribute to the improvement of guidelines for the appropriate use of antibiotics. It is also important to evaluate the effectiveness of PBPM in a wider range of patient groups and infectious diseases and to expand its scope of application in future studies. When introducing and implementing PBPM, it is necessary to develop protocols that consider local regulations and restrictions and ensure their appropriate application. Declarations Ethics approval and consent to participate This study was conducted with the approval of the Ethics Committee of the Graduate School of Medicine and Faculty of Medicine, Kyoto University, and Kyoto University Hospital (No. R0545-2). The Ethics Committee of Kyoto University Graduate School and Faculty of Medicine, which approved the study, waived the requirement for informed consent due to its retrospective nature. Nonetheless, general information about the study was made available on hospital bulletin boards and the website. It was clearly stated that if potential participants chose to decline enrollment, they would not be included in the study. Ultimately, no one opted out. The study was conducted in accordance with the Declaration of Helsinki. Consent for publication Not applicable. Competing interests All the authors declare that there are no competing interests relevant to this study. Funding This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors. Author Contribution YS wrote the initial drafts of the manuscript. Y Takatani designed and conceived this study. YS, Y Tsuchido, and M Saigo collected the data. M Saigo supported statistical analyses. YK, M Sugimoto, and MK contributed to the development of antibiotic protocols. Y Takatani, SN, YK, Y Tsuchido, MT, SO, and TT interpreted the results and critically revised the manuscript. All authors read and approved the final manuscript. Acknowledgement We would like to thank all the doctors at the Department of Primary Care and Emergency Medicine at Kyoto University Hospital for their generous cooperation in preparing this paper. 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Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial. BMJ. 2006;333:7580. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Diseases: official publication Infect Dis Soc Am. 2007;44(Suppl 2):S27–72. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Diseases: official publication Infect Dis Soc Am. 2016;62(10):e51–77. Katada Y, Nakagawa S, Minakata K, et al. Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery. J Clin Pharm Ther. 2017;42(5):591–7. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179–84. Algargoosh M, Ritchie S, Duffy E, Van der Werf B, Thomas M, Martini N. The impact of a pharmacist-led intravenous to oral switch of metronidazole: a before-and-after study. Antibiotics. 2022;11(10):1303. Kokado R, Hagiya H, Koyama T, et al. Antibiotic-associated adverse drug events at a Japanese academic hospital. J Infect Chemotherapy: Official J Japan Soc Chemother. 2019;25(5):392–5. Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med. 2017;177(9):1308–15. Additional Declarations No competing interests reported. Supplementary Files PBPMSuppleFigureforsubmission250821.pptx PBPMSupplymentaryTableforsubmission250822finalversion.docx Cite Share Download PDF Status: Published Journal Publication published 24 Dec, 2025 Read the published version in Journal of Pharmaceutical Health Care and Sciences → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7429703","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":506602418,"identity":"576fdfe3-40a2-4917-b95b-57742f914ca9","order_by":0,"name":"Yuki Sato","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Sato","suffix":""},{"id":506602420,"identity":"6e493cc6-6c1d-492a-82a0-10b3a0cae1b1","order_by":1,"name":"Yudai Takatani","email":"data:image/png;base64,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","orcid":"","institution":"Kyoto University","correspondingAuthor":true,"prefix":"","firstName":"Yudai","middleName":"","lastName":"Takatani","suffix":""},{"id":506602422,"identity":"4a84cfe3-d1fa-4b5a-b272-316846029887","order_by":2,"name":"Shunsaku Nakagawa","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shunsaku","middleName":"","lastName":"Nakagawa","suffix":""},{"id":506602424,"identity":"fe588baa-8e85-472c-b837-ddab216c2ab7","order_by":3,"name":"Yoshiki Katada","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yoshiki","middleName":"","lastName":"Katada","suffix":""},{"id":506602426,"identity":"98f2d06a-34a1-410a-ae9f-7255aa505e31","order_by":4,"name":"Yasuhiro Tsuchido","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yasuhiro","middleName":"","lastName":"Tsuchido","suffix":""},{"id":506602428,"identity":"0559b4dc-8fa4-4a7e-bcfa-d8ce9f2db17f","order_by":5,"name":"Mitsuhiro Sugimoto","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mitsuhiro","middleName":"","lastName":"Sugimoto","suffix":""},{"id":506602430,"identity":"2064d3bb-9124-40ed-bda7-bf3f7af83677","order_by":6,"name":"Masanori Kimata","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Masanori","middleName":"","lastName":"Kimata","suffix":""},{"id":506602432,"identity":"e3fc2923-c969-4398-a9bb-78457cb5300f","order_by":7,"name":"Mamiko Saigo","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mamiko","middleName":"","lastName":"Saigo","suffix":""},{"id":506602434,"identity":"cfa8249b-3711-49a3-b35d-1dd26de0c3b1","order_by":8,"name":"Masahiro Tsuda","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Masahiro","middleName":"","lastName":"Tsuda","suffix":""},{"id":506602437,"identity":"21055c98-b537-4c0b-893e-6265eb55906d","order_by":9,"name":"Shigeru Ohtsuru","email":"","orcid":"","institution":"Kyoto University","correspondingAuthor":false,"prefix":"","firstName":"Shigeru","middleName":"","lastName":"Ohtsuru","suffix":""},{"id":506602438,"identity":"35c9e3da-850d-46d2-9c38-2fa506eaf668","order_by":10,"name":"Tomohiro Terada","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomohiro","middleName":"","lastName":"Terada","suffix":""}],"badges":[],"createdAt":"2025-08-22 01:08:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7429703/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7429703/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40780-025-00512-8","type":"published","date":"2025-12-24T15:58:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90469806,"identity":"8db6b122-0739-4069-860f-e66282f98e8e","added_by":"auto","created_at":"2025-09-03 06:12:17","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":494478,"visible":true,"origin":"","legend":"\u003cp\u003ePatient flow diagram. Protocol-based pharmacotherapy management: PBPM.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7429703/v1/67b7bda2e351b15feef3f05f.jpeg"},{"id":99172392,"identity":"f283feaf-8524-4726-ade6-9bab29f593a9","added_by":"auto","created_at":"2025-12-29 16:08:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1405287,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7429703/v1/0df9d0b3-f788-48a8-873f-58f04c291dcb.pdf"},{"id":90471030,"identity":"dfb69d59-fd95-48c0-ba1b-2a1d394dc73f","added_by":"auto","created_at":"2025-09-03 06:20:16","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":70732,"visible":true,"origin":"","legend":"","description":"","filename":"PBPMSuppleFigureforsubmission250821.pptx","url":"https://assets-eu.researchsquare.com/files/rs-7429703/v1/f142f99984a841d063f174d1.pptx"},{"id":90469796,"identity":"4259de50-7157-4dd2-bb0c-2ae8b3e455f3","added_by":"auto","created_at":"2025-09-03 06:12:16","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":37744,"visible":true,"origin":"","legend":"","description":"","filename":"PBPMSupplymentaryTableforsubmission250822finalversion.docx","url":"https://assets-eu.researchsquare.com/files/rs-7429703/v1/ee2475fc9d65f77d3905bf45.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of Protocol-Based Pharmacotherapy Management in Switching of Antibiotic Administration Routes and Dose Adjustment Based on Renal Function: A Before-After Study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAntibiotics are essential for the treatment of infectious diseases, and their efficacy is widely recognized. However, appropriate use of these drugs is crucial for minimizing adverse reactions and the emergence of resistance [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Therefore, maximizing the efficacy of antibiotics while minimizing their side effects, specifically toxicity and the emergence of resistance, is recommended [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In addition, many patients hospitalized with infectious diseases receive antibiotics intravenously (IV), which is more expensive than oral administration (PO) and also incurs indirect costs associated with preparation and administration [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Indirect costs have been reported to exceed the cost of the drug itself by 13\u0026ndash;113% [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. One approach to antibiotic use is dose optimization based on the pharmacokinetics (PK)/pharmacodynamics (PD) theory for IV antibiotics. The second approach is switching from IV to PO administration as soon as the patient is clinically stable. Such interventions, including dose adjustments and changes in administration routes, have been reported to have multiple benefits, including fewer adverse reactions, reduced risk of infection, shorter hospital stays, and reduced associated costs [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In particular, several randomized controlled trials have shown that early switching to oral antibiotics is safe while maintaining efficacy in common infections such as pneumonia, uncomplicated pyelonephritis, and intra-abdominal infections [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Therefore, when using antibiotics, a prompt transition from IV to PO is strongly recommended once patients are clinically stable. This recommendation is outlined in the 2007 American Thoracic Society and Infectious Diseases Society of America (IDSA) Community-Acquired Pneumonia Guidelines and the 2016 IDSA Antibiotic Stewardship Guidelines [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCooperation by a multidisciplinary team is essential in promoting appropriate antibiotic use, and the intervention of pharmacists is particularly effective. The IDSA and the Society for Healthcare Epidemiology of America recommend that pharmacists play an active role in antibiotic stewardship programs as part of their routine practice [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In particular, pharmacist-initiated intravenous-to-oral switch (IVOS) after symptom improvement has been reported to be beneficial, leading to shorter antibiotic treatment durations and reduced medical costs [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Furthermore, it would be clinically useful for pharmacists to intervene comprehensively, not only by initiating IVOS but also by adjusting antibiotic dosages based on the PK/PD theory. However, no examples of such practices or their clinical significance have been reported thus far. In addition, depending on local regulations, it may be difficult for pharmacists to adjust the antibiotic dosage independently or on behalf of physicians; therefore, establishing predefined protocols that enable pharmacists to intervene in antibiotic treatment would be beneficial. At Kyoto University Hospital, doctors and pharmacists have collaborated to implement protocol-based pharmacotherapy management (PBPM) for antibiotic treatment in emergency patients [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This approach is expected to provide safe drug therapy while maintaining clinical outcomes. In this study, we retrospectively examined the effectiveness of PBPM in adjusting antibiotic dosages and implementing IVOS based on renal function in older patients at high risk of drug-related adverse events, including renal dysfunction.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Study design\u003c/h2\u003e\u003cp\u003eThis before-and-after study aimed to evaluate the efficacy of PBPM in antibiotic treatment. As PBPM was implemented for antibiotic treatment at Kyoto University Hospital in January 2022, we compared older patients who received antibiotic treatment before and PBPM initiation. The control group comprised patients treated from January 2021 to December 2021, and the PBPM group comprised patients treated from June 2022 to May 2023. The period from January to May 2022 was excluded because it represented a transition period before the implementation of PBPM.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Study participants\u003c/h2\u003e\u003cp\u003eThe study participants were patients aged 65 years or older diagnosed with community-acquired pneumonia or uncomplicated pyelonephritis during the study period, admitted to the emergency intensive care unit or ward in the Department of Primary Care and Emergency Medicine at Kyoto University Hospital, and initiated IV antibiotic therapy. Patients with bacteremia often require longer treatment periods; therefore, they were excluded to ensure comparable conditions. In addition, patients hospitalized due to complicated infections (e.g., empyema, lung abscess, renal abscess, perinephric abscess), those who completed IV antibiotic treatment within 48 hours of initiation, those who began antibiotic treatment before hospitalization, and those transferred to another ward or hospital before completing antibiotic treatment were also excluded.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Antibiotic treatment using PBPM\u003c/h2\u003e\u003cp\u003eWhen implementing PBPM, pharmacists, emergency physicians, and infectious disease physicians created a protocol for adjusting antibiotic dosages based on renal function (Supplementary Tables\u0026nbsp;1 and 2), referencing The Sanford Guide to Antimicrobial Therapy (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.sanfordguide.com/\u003c/span\u003e\u003cspan address=\"https://www.sanfordguide.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Additionally, referencing the COMS criteria\u0026mdash;guidelines for the IVOS of antibiotic therapy reported by the University of Nottingham in 2010\u0026mdash;a flowchart for performing IVOS tailored to the clinical setting in Japan was created, which we named the K-COGaI criteria (Supplementary Fig.\u0026nbsp;1). Within PBPM, doctors selected the initial antibiotics for each patient and asked pharmacists to adjust the dosage based on renal function and evaluate IVOS eligibility. Considering the patient\u0026rsquo;s age, physical constitution, renal function, and the severity of the infection, the pharmacist proposed an antibiotic prescription (including dosage, volume of dissolving solution, infusion time, and administration route) based on the protocols (Supplementary Tables\u0026nbsp;1 and 2 and Supplementary Fig.\u0026nbsp;1). The pharmacist regularly reviewed the blood test results and proposed dosage adjustments when necessary. In addition, when a patient receiving antibiotics met all K-COGaI criteria, the pharmacist recommended IVOS to the attending physician. In either case, the pharmacist\u0026rsquo;s proposal was recorded in the electronic medical record and shared with the doctors and nurses. During weekday shifts (8:30\u0026ndash;17:15), pharmacists proactively proposed antibiotic dosage adjustments and IVOS. At other times, physicians determined the dosage and timing of IVOS by referring to the dosage adjustment protocol based on renal function. Patients in the control group received antibiotics before the protocol was established, and the antibiotic dosage and timing of IVOS were determined based on the emergency physician\u0026rsquo;s knowledge and experience.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Outcomes\u003c/h2\u003e\u003cp\u003eThe primary endpoint was the duration of antibiotic administration (days). The secondary endpoints were early clinical response (ECR), clinical treatment failure rate, readmission rate within 28 days after discharge, 28-day mortality, length of hospital stay, rate of adverse reactions, antibiotic cost, and compliance with the dosage adjustment protocol based on renal function. ECR was defined as meeting all of the following three criteria: i) no clinical deterioration or death within 96 hours; ii) a decrease of \u0026ge;\u0026thinsp;30% in white blood cell count or C-reactive protein compared with baseline; and iii) a decrease in body temperature of 0.3\u0026deg;C for 2 consecutive days from treatment initiation. Clinical treatment failure was defined as a change in broad-spectrum antibiotic use or relapse. Adverse reactions were defined as grade 1 or higher events that occurred during antibiotic use. Acute kidney injury (AKI) was assessed according to the Kidney Disease Improving Global Outcomes clinical practice guidelines [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and diarrhea were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Compliance with the dosage adjustment protocol based on renal function was calculated as the proportion of patients who adhered to the protocol (Supplementary Tables\u0026nbsp;1 and 2).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Other Measurements\u003c/h2\u003e\u003cp\u003eCausative bacteria detected in sputum and urine were identified by an infectious disease specialist. Information on other variables, including age, sex, and reasons why IVOS could not be performed, was collected from electronic medical records.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6 Statistical Analysis\u003c/h2\u003e\u003cp\u003eFisher\u0026rsquo;s exact test was used to compare nominal variables between the two groups, and Student\u0026rsquo;s t-test was used to compare continuous variables. A risk level of \u0026le;\u0026thinsp;5% (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) was considered statistically significant. GraphPad PRISM (GraphPad Software Inc., San Diego, CA) was used for the analysis.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cb\u003e3\u0026thinsp;\u0026minus;\u0026thinsp;1. Patients\u0026rsquo; demographic and clinical characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAmong 85 patients admitted to the emergency department with community-acquired pneumonia or uncomplicated pyelonephritis, 78 were included in the final analysis (40 control, 38 PBPM) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Seven patients were excluded for the following reasons: i) admitted due to bacteremia (n\u0026thinsp;=\u0026thinsp;3), ii) admission due to empyema (n\u0026thinsp;=\u0026thinsp;1), iii) competion of IV antibiotics within 48 hours of initiation (n\u0026thinsp;=\u0026thinsp;1), iv) initiation of antibiotics before admission (n\u0026thinsp;=\u0026thinsp;1), and v) transfer to another ward or hospital before completion of antibiotic treatment (n\u0026thinsp;=\u0026thinsp;1). There were no significant differences between the two groups regarding their demographic and clinical characteristics (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\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\u003ePatients\u0026rsquo; demographic and clinical 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\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePBPM group \u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, female, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (47.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (42.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e82.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody weight (kg), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54.4\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine clearance (mL/min), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34.6\u0026thinsp;\u0026plusmn;\u0026thinsp;23.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.5\u0026thinsp;\u0026plusmn;\u0026thinsp;26.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCRP (mg/dL), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC (\u0026times;10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody temperature (℃), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnderlying disease, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (35.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (42.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic heart disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (17.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (31.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic respiratory disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (2.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMalignant tumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (10.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (47.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (47.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharlson Comorbidity Index, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePitt Bacteremia Score, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType of infection, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePneumonia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (73.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePyelonephritis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (26.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCausative organisms in pneumonia, n (%) *\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eHaemophilus influenzae\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (16.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMoraxella catarrhalis\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (7.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMSSA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (7.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMRSA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (8.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (82.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCausative organisms in uncomplicated pyelonephritis, n (%) *\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eEnterobacter cloacae complex\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (70.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eKlebsiella oxytoca\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (10.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (10.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eProteus mirabilis\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (30.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmpiric therapy, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAmpicillin/Sulbactam\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (36.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePiperacillin/Tazobactam\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (15.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (21.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCeftriaxone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (30.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (36.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeropenem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eData are expressed either as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations or numbers with percentages in parentheses. Continuous variables were compared using Student\u0026rsquo;s t-test. Categorical variables were compared using Fisher\u0026rsquo;s exact test. *One patient can have more than two indications. Highest value within 24 hours of admission. Creatinine clearance was calculated using the Cockcroft\u0026ndash;Gault formula. Protocol-based pharmacotherapy management: PBPM, standard deviation: SD, C-reactive protein: CRP, white blood cell: WBC, Methicillin-susceptible \u003cem\u003eStaphylococcus aureus\u003c/em\u003e: MSSA, Methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e: MRSA.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003e3 − 2. Association between IVOS and PBPM\u003c/h3\u003e\n\u003cp\u003eThe proportion of patients who underwent IVOS was 42.5% (17/40) and 39.5% (15/38) in the control and PBPM groups, respectively, with no significant difference (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Similarly, when categorized into pneumonia and uncomplicated pyelonephritis, there was no significant difference between the groups in the proportion of patients who underwent IVOS. However, when IVOS was performed, the time to switch to oral antibiotics was 6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 days (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation) and 4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 days in the control and PBPM groups, respectively, significantly shorter in the PBPM group. In the control group, two patients returned to IV administration after switching to oral antibiotics, whereas no such cases occurred in the PBPM group. Reasons for not performing IVOS included lack of clinical improvement, absence of oral antimicrobial agents effective against the causative bacteria, inability to administer oral antibiotics due to gastrointestinal bleeding or other reasons, and patient intubation (Supplementary Table\u0026nbsp;3).\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\u003eEffect of PBPM on intravenous-to-oral switch\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\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\u003eControl group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePBPM group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCases switched from intravenous to oral treatment, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e17 (42.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15 (39.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePneumonia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7 (28.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (25.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUncomplicated pyelonephritis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10 (66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8 (80.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime to switch (days), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1**\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eData are expressed either as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations or numbers with percentages in parentheses. Continuous variables were compared using Student\u0026rsquo;s t-test. Categorical variables were compared using Fisher\u0026rsquo;s exact test. **\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01, significantly different from the control group. Protocol-based pharmacotherapy management: PBPM, standard deviation: SD.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003e3–3. Antibiotic administration duration in the control and PBPM groups\u003c/h3\u003e\n\u003cp\u003eThe antibiotic administration duration in the control and PBPM groups is shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The total antibiotic treatment duration (regardless of administration route) was 9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4 days and 7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 days in the control and PBPM groups, respectively, with the PBPM group showing a significant reduction in treatment duration. The duration of IV administration was also significantly reduced in the PBPM group compared to the control group (control, 7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 days; PBPM, 5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0 days). The duration of PO was not significantly different between the two groups (control, 6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2 days; PBPM, 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 days). Regarding pneumonia alone, there was a significant difference between the two groups in the total antibiotic treatment period (control, 8.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4 days; PBPM, 6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2 days), but no significant difference in the duration of IV administration (control, 7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 days; PBPM, 5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2 days) or PO (control, 5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 days; PBPM, 4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 days). When limited to uncomplicated pyelonephritis, the total antibiotic treatment period (control, 10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 days; PBPM, 9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 days) and the IV administration period (control, 6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 days; PBPM, 4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 days) were significantly different between the two groups, but there was no significant difference in PO duration (control, 6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 days; PBPM, 5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 days).\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\u003eEffect of PBPM on the duration of antibiotic treatment\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\u003eTotal patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePBPM group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays of intravenous plus oral treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays of intravenous treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2**\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays of oral treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients with pneumonia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePBPM group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays of intravenous plus oral treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays of intravenous treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays of oral treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients with uncomplicated pyelonephritis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePBPM group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays of intravenous plus oral treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays of intravenous treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays of oral treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eData are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations. Continuous variables were compared using Student\u0026rsquo;s t-test. *\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01, significantly different from the control group. Protocol-based pharmacotherapy management: PBPM.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003e3–4. Secondary outcomes in the control and PBPM groups\u003c/h3\u003e\n\u003cp\u003eThe secondary outcomes are listed in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Among the treatment outcomes, the clinical treatment failure rate was significantly lower in the PBPM group than in the control group. There were no significant differences between the two groups in terms of ECR, rehospitalization rate, 28-day mortality, or length of hospital stay. A comparison of the incidence of antibiotic-related adverse events during antibiotic treatment showed that the incidences of AKI and ALT elevation were significantly lower in the PBPM group than in the control group. There were no significant differences in the incidences of AST elevation, diarrhea, or \u003cem\u003eClostridioides difficile\u003c/em\u003e infection between the two groups. The total antibiotic costs were 522,105 yen (13,517 yen per patient) and 457,205 yen (11,787 yen per patient) for the control and PBPM groups, respectively. Therefore, the cost per patient was 13% lower in the PBPM group than in the control group. A comparison of the adherence rates to the antibiotic dosage adjustment protocol based on renal function before and after PBPM implementation showed that they were 77.5% (31/40) and 97.4% (37/38) in the control and PBPM groups, respectively, with a significantly higher rate in the PBPM group.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSecondary outcomes for antibiotic treatment\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\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePBPM group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment success, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEarly clinical response\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (45.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (60.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical treatment failures\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (22.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5.6)*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReadmission within 1 month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (5.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e28-day mortality, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLength of hospital stay (days), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse events, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNephrotoxicity \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (15.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHematologic abnormality \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary abnormality \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (32.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (10.5)*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAspartate aminotransferase increased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (27.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (10.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlanine aminotransferase increased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (22.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5.3)*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal bilirubin\u0026nbsp;increased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-\u003cem\u003eClostridioides difficile\u003c/em\u003e-associated diarrhea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (36.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eClostridioides difficile\u003c/em\u003e infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCost of antibiotics (yen), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13,517\u0026thinsp;\u0026plusmn;\u0026thinsp;10,462\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11,787\u0026thinsp;\u0026plusmn;\u0026thinsp;6,798\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCompliance with renal dosage adjustment protocol for antibiotics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31 (77.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (97.4)*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo (overdose), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (2.63)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo (underdose), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (15.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eData are expressed either as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations or numbers with percentages in parentheses. Continuous variables were compared using Student\u0026rsquo;s t-test. Categorical variables were compared using Fisher\u0026rsquo;s exact test. \u003csup\u003ea\u003c/sup\u003e Classified according to the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines. \u003csup\u003eb\u003c/sup\u003e Classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 clinical practice guidelines. *\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, significantly different from the control group. Protocol-based pharmacotherapy management: PBPM, standard deviation: SD.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study examined the effectiveness of PBPM in implementing IVOS and antibiotic dose adjustment based on renal function. The results showed that PBPM shortened the duration of IV antibiotic administration, reduced the risk of adverse events, and lowered pharmaceutical costs without negatively affecting clinical outcomes compared to conventional treatment mainly performed by physicians. The effectiveness of IVOS in PBPM is consistent with the results of a previous study that evaluated the usefulness of IVOS of antibiotics using Collaborative Drug Therapy Management [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, this is the first study to apply a protocol that standardizes the process of IVOS and antibiotic dose adjustment based on renal function, offering advantages different from those of existing studies.\u003c/p\u003e\u003cp\u003eNo differences were observed between the control and PBPM groups in ECR, 28-day mortality, readmission within 1 month, proportion of \u003cem\u003eClostridioides difficile\u003c/em\u003e infection cases, and length of hospitalization. In addition, during the period in which PBPM was implemented, there were no deaths within 28 days, no rehospitalizations within 1 month, and no cases of \u003cem\u003eClostridioides difficile\u003c/em\u003e infection, suggesting that the implementation of PBPM does not worsen clinical outcomes. A meta-analysis reported that IVOS was as effective as continued IV administration in terms of clinical outcomes in community-acquired pneumonia [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, the antimicrobial stewardship program recommended by the IDSA and Society for Healthcare Epidemiology of America strongly recommends that IV antibiotics used in initial treatment should be switched to oral antibiotics at the appropriate time [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, in the case of uncomplicated infections, it is clinically appropriate to actively switch the route of antibiotic administration via PBPM.\u003c/p\u003e\u003cp\u003eThe implementation of PBPM by pharmacists in this study was shown to be an effective method for shortening both the total and IV antibiotic administration periods. The duration of IV antibiotic administration was also shortened across different types of infections. There was a difference in the rate of IVOS between patients with pneumonia and those with uncomplicated pyelonephritis. This may be due to the high risk of aspiration and difficulty with oral intake in patients with pneumonia, which may have led to a slower switch to PO (Supplementary Table\u0026nbsp;3). Nevertheless, the implementation of PBPM could still lead to an appropriate treatment duration, even in patients with limited options. This study, however, did not find any association between the implementation of PBPM and a shortened length of hospital stay. Many patients had difficulty being discharged home; some were not immediately discharged after switching to PO, while others underwent a period of observation after switching. Although future larger studies are needed to confirm its validity, this study suggests that the implementation of PBPM contributes to a shortened antibiotic administration period in both patients with community-acquired pneumonia and uncomplicated pyelonephritis.\u003c/p\u003e\u003cp\u003eAdverse events associated with antibiotic administration occurred in 22.3% of patients, and the risk of adverse events increased by 3% for every 10 days of antibiotic use [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Therefore, regular reviews of the dosage and necessity of antibiotics are expected to reduce the risk of adverse events. In this study, the rates of AKI and ALT elevation during the antibiotic administration period significantly decreased after the implementation of PBPM compared to before its implementation. Although compliance with the antibiotic dosage adjustment protocol based on renal function improved after the implementation of PBPM, the rate of overdosing remained unchanged. Therefore, the decrease in adverse events is likely due to the shortened antibiotic administration period facilitated by PBPM.\u003c/p\u003e\u003cp\u003eThis study had some limitations. First, the patients in the PBPM and control groups were admitted at different times, introducing potential confounding effects. For instance, the increased knowledge and ability of doctors and pharmacists due to the establishment of the dosage adjustment protocol and IVOS flowchart for PBPM may have indirectly influenced the results. In addition, this study was conducted at a single institution with a small sample size; therefore, caution is required when generalizing the effectiveness of PBPM.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThe results of this study suggest that PBPM, when conducted collaboratively by pharmacists and physicians, is an effective method to optimize antibiotic use, reduce the risk of adverse events, and shorten treatment duration, thereby lowering healthcare costs. We believe that these findings will contribute to the improvement of guidelines for the appropriate use of antibiotics. It is also important to evaluate the effectiveness of PBPM in a wider range of patient groups and infectious diseases and to expand its scope of application in future studies. When introducing and implementing PBPM, it is necessary to develop protocols that consider local regulations and restrictions and ensure their appropriate application.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cp\u003e This study was conducted with the approval of the Ethics Committee of the Graduate School of Medicine and Faculty of Medicine, Kyoto University, and Kyoto University Hospital (No. R0545-2). The Ethics Committee of Kyoto University Graduate School and Faculty of Medicine, which approved the study, waived the requirement for informed consent due to its retrospective nature. Nonetheless, general information about the study was made available on hospital bulletin boards and the website. It was clearly stated that if potential participants chose to decline enrollment, they would not be included in the study. Ultimately, no one opted out. The study was conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eAll the authors declare that there are no competing interests relevant to this study.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis research received no grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYS wrote the initial drafts of the manuscript. Y Takatani designed and conceived this study. YS, Y Tsuchido, and M Saigo collected the data. M Saigo supported statistical analyses. YK, M Sugimoto, and MK contributed to the development of antibiotic protocols. Y Takatani, SN, YK, Y Tsuchido, MT, SO, and TT interpreted the results and critically revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003e We would like to thank all the doctors at the Department of Primary Care and Emergency Medicine at Kyoto University Hospital for their generous cooperation in preparing this paper.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNational Institute for Health and Care Excellence (Great Britain). Bpacnz Guideline: Antimicrobial Stewardship: Systems and Processes for Effective Antimicrobial Medicine Use within Human Health and Healthcare in New Zealand. NICE; London, UK, 2017. 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Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Diseases: official publication Infect Dis Soc Am. 2007;44(2):159\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSevin\u0026ccedil; F, Prins JM, Koopmans RP, et al. Early switch from intravenous to oral antibiotics: guidelines and implementation in a large teaching hospital. J Antimicrob Chemother. 1999;43(4):601\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Zanten AR, Engelfriet PM, van Dillen K, van Veen M, Nuijten MJ, Polderman KH. Importance of nondrug costs of intravenous antibiotic therapy. Crit Care. 2003;7(6):R184\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMertz D, Koller M, Haller P, et al. Outcomes of early switching from intravenous to oral antibiotics on medical wards. 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J Antimicrob Chemother. 1998;42(1):107\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRhew DC, Tu GS, Ofman J, Henning JM, Richards MS, Weingarten SR. Early switch and early discharge strategies in patients with community-acquired pneumonia: a meta-analysis. Arch Intern Med. 2001;161(5):722\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evon Gunten V, Amos V, Sidler AL, Beney J, Troillet N, Reymond JP. Hospital pharmacists' reinforcement of guidelines for switching from parenteral to oral antibiotics: a pilot study. Pharm World Sci. 2003;25(2):52\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcLaughlin CM, Bodasing N, Boyter AC, Fenelon C, Fox JG, Seaton RA. Pharmacy-implemented guidelines on switching from intravenous to oral antibiotics: an intervention study. QJM: Monthly J Association Physicians. 2005;98(10):745\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMacGregor RR, Graziani AL. Oral administration of antibiotics: a rational alternative to the parenteral route. Clin Infect Diseases: official publication Infect Dis Soc Am. 1997;24(3):457\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarrie TJ, Lau CY, Wheeler SL, Wong CJ, Vandervoort MK, Feagan BG. A controlled trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL study investigators. Community-acquired pneumonia intervention trial assessing levofloxacin. JAMA. 2000;283(6):749\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOosterheert JJ, Bonten MJ, Schneider MM, et al. Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial. BMJ. 2006;333:7580.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Diseases: official publication Infect Dis Soc Am. 2007;44(Suppl 2):S27\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Diseases: official publication Infect Dis Soc Am. 2016;62(10):e51\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKatada Y, Nakagawa S, Minakata K, et al. Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery. J Clin Pharm Ther. 2017;42(5):591\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlgargoosh M, Ritchie S, Duffy E, Van der Werf B, Thomas M, Martini N. The impact of a pharmacist-led intravenous to oral switch of metronidazole: a before-and-after study. Antibiotics. 2022;11(10):1303.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKokado R, Hagiya H, Koyama T, et al. Antibiotic-associated adverse drug events at a Japanese academic hospital. J Infect Chemotherapy: Official J Japan Soc Chemother. 2019;25(5):392\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med. 2017;177(9):1308\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"protocol-based pharmacotherapy management, antibiotic stewardship, dosage adjustment, renal function, intravenous-to-oral switch, K-COGaI criteria","lastPublishedDoi":"10.21203/rs.3.rs-7429703/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7429703/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/em\u003e Antibiotics are crucial for treating infectious diseases, but their appropriate use is essential to minimize adverse reactions and resistance. This study evaluated the effectiveness of protocol-based pharmacotherapy management (PBPM) based on renal function in adjusting antibiotic dosage and implementing an intravenous-to-oral switch in older patients at high risk of drug-related adverse events. The study compared antibiotic treatment outcomes before and after PBPM implementation at Kyoto University Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e\u003c/em\u003e This before-and-after study included patients aged ≥65 years diagnosed with community-acquired pneumonia or uncomplicated pyelonephritis at Kyoto University Hospital. The control group (January to December 2021) received conventional antibiotic treatment, whereas the PBPM group (June 2022 to May 2023) received treatment based on a protocol developed by pharmacists, emergency physicians, and infectious disease specialists. Primary and secondary outcomes included antibiotic administration duration, clinical response, adverse reactions, and costs.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/em\u003e The study included 78 patients (40 control, 38 PBPM). The PBPM group showed a significantly shorter total antibiotic treatment duration (9.6 ± 4.4 vs. 7.5 ± 2.4 days, p \u0026lt; 0.05) and intravenous administration duration (7.1 ± 2.8 vs. 5.6 ± 2.2 days, p \u0026lt; 0.01) compared with the control group. The PBPM group also demonstrated lower clinical treatment failure rates and reduced incidences of acute kidney injury and alanine aminotransferase elevation. Antibiotic costs per patient were 13% lower in the PBPM group. There were no significant differences in early clinical response, readmission rates, or mortality between groups.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/em\u003e PBPM, conducted collaboratively by pharmacists and physicians, effectively optimized antibiotic use, reduced adverse event risks, shortened treatment duration, and lowered healthcare costs without compromising clinical outcomes. These findings support PBPM implementation to improve antibiotic stewardship in older patients with common infections.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eClinical trial number:\u003c/strong\u003e\u003c/em\u003e not applicable.\u003c/p\u003e","manuscriptTitle":"Efficacy of Protocol-Based Pharmacotherapy Management in Switching of Antibiotic Administration Routes and Dose Adjustment Based on Renal Function: A Before-After Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-03 06:12:11","doi":"10.21203/rs.3.rs-7429703/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4de4e7bc-ac03-4ce5-8ac7-ef176bd78b25","owner":[],"postedDate":"September 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-29T16:03:33+00:00","versionOfRecord":{"articleIdentity":"rs-7429703","link":"https://doi.org/10.1186/s40780-025-00512-8","journal":{"identity":"journal-of-pharmaceutical-health-care-and-sciences","isVorOnly":false,"title":"Journal of Pharmaceutical Health Care and Sciences"},"publishedOn":"2025-12-24 15:58:30","publishedOnDateReadable":"December 24th, 2025"},"versionCreatedAt":"2025-09-03 06:12:11","video":"","vorDoi":"10.1186/s40780-025-00512-8","vorDoiUrl":"https://doi.org/10.1186/s40780-025-00512-8","workflowStages":[]},"version":"v1","identity":"rs-7429703","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7429703","identity":"rs-7429703","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}