Using fosfomycin to prevent infection following ureterorenoscopy in response to shortage of cephalosporins: a retrospective preliminary study.

BACKGROUND: In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy. METHODS: The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative urinary catheter use, and preoperative antibiotic treatment. RESULTS: The fosfomycin and cefotiam groups (n = 69 per group) exhibited no significant differences in terms of patients' median age, operative duration, preoperative urine white blood cell count, preoperative urine bacterial count, and the rate of preoperative antibiotic treatment. In the fosfomycin and cefotiam groups, the median duration of postoperative hospital stay was 3 and 4 days, respectively; the median maximum postoperative temperature was 37.3 °C and 37.2 °C, respectively. The fosfomycin group had lower postoperative C-reactive protein levels and white blood cell count than the cefotiam group. However, the frequency of fever > 38 °C requiring additional antibiotic administration was similar. CONCLUSIONS: During cefotiam shortage, fosfomycin administration enabled surgeons to continue performing ureterorenoscopies without increasing the complication rate.

Evaluation of target area under the concentration-time curve of vancomycin in an initial dosing design: a retrospective cohort study.

OBJECTIVES: Area under the concentration-time curve (AUC)-guided dosing of vancomycin was introduced in a clinical setting; however, the target range of non-steady-state AUCs, such as Day 1 AUC and Day 2 AUC, remains controversial. Therefore, we sought to determine pharmacokinetic parameter thresholds and identify independent risk factors associated with acute kidney injury (AKI) to establish a safe initial dosing design for vancomycin administration. METHODS: A single-centre, retrospective, cohort study of hospitalized patients treated with vancomycin was conducted to determine the threshold of both non-steady-state AUCs (Day 1 and 2 AUCs) and trough levels at the first blood sampling point (therapeutic drug monitoring, TDM). In addition, independent risk factors associated with AKI were evaluated using univariate and multivariate logistic regression analyses. RESULTS: The thresholds for predicting AKI were estimated as 456.6 mg·h/L for AUC0-24h, 554.8 mg·h/L for AUC24-48h, 1080.8 mg·h/L for AUC0-48h and 14.0 µg/mL for measured trough levels, respectively. In a multivariate analysis, Day 2 AUC ≥ 554.8 mg·h/L [adjusted odds ratio (OR), 57.16; 95% confidence interval (CI), 11.95-504.05], piperacillin/tazobactam (adjusted OR, 15.84; 95% CI, 2.73-127.70) and diuretics (adjusted OR, 4.72; 95% CI, 1.13-21.01) were identified as risk factors for AKI. CONCLUSIONS: We identified thresholds for both AUCs in the non-steady-state and trough levels at the first TDM. Our results highlight the importance of monitoring not only the AUC but also trough levels during vancomycin treatment to reduce the likelihood of AKI.

Clinical Usefulness of the "MN Criteria" - the Clostridioides difficile Infection Severity Scoring System - in the Japanese Setting.

Objective The severity of Clostridioides difficile infection (CDI) is an important prognostic factor. The "MN criteria," proposed in Japan in 2017, attempted to remedy the shortfalls in the reported guidelines proposed globally to determine CDI severity. We therefore assessed the accuracy of the MN criteria and validated the important factors associated with predicting CDI severity. Methods Sixty-six CDI cases were investigated retrospectively at a Japanese University Hospital from January 2015 to December 2018. The fulminant cases were screened out, and the non-fulminant cases were classified according to their severity stages using the nine variables included in the MN criteria. Clinical events, such as death within 28 days, colectomy, and admission to the intensive care unit, were evaluated. First, the sensitivity and specificity of the MN criteria for predicting clinical events were determined. The relationships between clinical events and the explanatory variables were then evaluated through univariate and multivariate analyses. Results The screening of the fulminant cases and classification of the non-fulminant cases into mild/moderate and severe/super severe cases resulted in a sensitivity of 1.00 and a specificity of 0.89. Univariate and multivariate analyses revealed a significant association of the serum albumin (Alb) level as well as white blood cell (WBC) count with clinical events. Conclusion The findings provide evidence supporting the accuracy of the MN criteria in predicting CDI severity and show that the Alb and WBC are important variables in predicting CDI severity.

Development and Evaluation of a Novel Software Program, SAKURA-TDM, for Area Under the Concentration-Time Curve-Guided Vancomycin Dosing: A Short Communication.

BACKGROUND: The area under the concentration-time curve (AUC)-guided dosing of vancomycin has been introduced in Japan; however, the optimal dosing method remains controversial. Here, a novel software program was developed for AUC-guided vancomycin dosing and to estimate the theoretical threshold of the steady-state AUC 24 that could reduce the risk of renal injury. METHODS: A single-center, retrospective, observational study was conducted to develop a novel software program (SAKURA-TDM ver.1.0) for AUC-guided dosing. The estimation accuracy of pharmacokinetic parameters determined using SAKURA-TDM was compared with that of clinically available software programs and assessed with Bland-Altman analysis. In addition, theoretical cutoff points of the steady-state AUC 24 and the predicted trough values were estimated using Youden J statistic approach. RESULTS: The estimation accuracy of pharmacokinetic parameters and AUC determined using SAKURA-TDM was comparable to that of other TDM software programs. Of note, despite a good relationship between the predicted AUC 24 and trough values, the correlation between the predicted AUC 24 and measured trough values was not strong. The cutoff values of the steady-state AUC 24 and the predicted trough value for reducing the probability of a measured trough value of >20 mcg/mL were 513.1 mg·h/L and 15.6 mcg/mL, respectively. CONCLUSIONS: We demonstrated the equivalence of the estimated PK parameters between SAKURA-TDM and other TDM software programs available in Japan. Considering the threshold of both trough values and the steady-state AUC and monitoring of the AUC in a non-steady state, it would be possible to reduce the risk of vancomycin-associated renal injury.

Efficacy of fosfomycin in preventing infection after endoscopic combined intrarenal surgery in periods of limited supply of first- and second-generation cephalosporins.

OBJECTIVES: In March 2019, cefazolin was unavailable owing to difficulty in procuring the active ingredient. Furthermore, the supply of alternative drugs, such as cefotiam and cefmetazole, was limited. In the Department of Nephro-Urology, fosfomycin-based drugs are used as substitutes for cefazolin, which is a perioperative prophylactic antibacterial drug. Herein, we investigated the effectiveness of fosfomycin sodium and cefotiam in preventing infection after endoscopic combined intrarenal surgery as a retrospective preliminary study. METHODS: A total of 200 patients who underwent endoscopic combined intrarenal surgery at our department between August 2017 and January 2021 were included. The patients were administered cefotiam (n = 95) or fosfomycin (n = 105) as perioperative antibacterial agents. There were no significant differences in the median age or surgery time between the cefotiam and fosfomycin groups. Propensity score matching was performed to match the preoperative urine bacterial counts of both groups. Sixty-eight patients were selected from each group. RESULTS: The median postoperative hospital stay duration was 4 days for the two groups. The median maximum postoperative temperatures were 37.5 and 37.4°C, respectively. There were no significant differences between the maximum postoperative temperatures in both groups. Furthermore, there were no differences between the groups regarding the white blood cell counts, C-reactive protein levels, and aspartate aminotransferase and alanine aminotransferase levels postoperatively, as well as in terms of postoperative fever requiring additional antibiotics. CONCLUSIONS: During a period of difficulty in acquiring cefazolin and cefotiam, the use of fosfomycin allowed us to continue with the procedure without increased clinical complications.

Efficacy of fosfomycin in the prevention of postoperative infection following transurethral resection of bladder tumor during periods of limited cefazolin, cefotiam, and cefmetazole supply.

INTRODUCTION: In March 2019, cefazolin availability was limited owing to the contamination of the drug substance. In addition, there was a difficulty in supplying drugs alternative to cefazolin, such as cefotiam and cefmetazole. In our Department of Nephro-urology, we used fosfomycin-based drugs to substitute cefazolin as perioperative preventive antibacterial drugs. In this study, we aimed to evaluate the usage status of perioperative prophylactic antibacterial drugs before and after the period of limited cefazolin supply and to investigate the efficacy and safety of fosfomycin sodium in preventing infections following transurethral resection of bladder tumor. METHODS: We enrolled 346 patients who underwent transurethral resection of bladder tumor in our department from April 2018 to August 2020. The patients received the following perioperative antibacterial agents: cefotiam (n = 146), fosfomycin (n = 166), and other antibacterial agents (n = 34). There was no significant difference in the median age or surgery time. RESULTS: The median length of hospital stay was 6, 5, and 5 days in the cefotiam, fosfomycin, and other antibacterial groups, respectively, with significant difference. The median maximum postoperative temperature was 37.1 °C in all groups, with no significant difference. There were no differences in C-reactive protein, aspartate aminotransferase, and alanine aminotransferase levels determined by postoperative blood tests; preoperative and postoperative urinary white blood cell counts; preoperative urine bacterial counts; and surgery-related infection requiring additional antibiotic treatments among the groups. CONCLUSIONS: The use of fosfomycin-based agents helped overcome the limited supply of cefazolin without worsening clinical outcomes.