Extracorporeal membrane oxygenation may decrease the plasma concentration of remdesivir in a patient with severe coronavirus disease 2019.

Remdesivir is an antiviral drug that results in clinical improvement after five days of treatment and accelerates recovery by 31%. No studies have discussed the pharmacokinetic analysis of remdesivir in patients with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO). A 63-year-old American man who underwent mechanical ventilation and ECMO for severe COVID-19 was administered remdesivir for ten days. The loading dosage was 200 mg at 7 PM on day 12 and 100 mg daily at 0:00 PM from day 13-21, administered within 1 h. The pharmacokinetic analysis was performed. The serum creatinine concentration was within the normal range of 0.5-0.7 mg/dL during treatment. According to the pharmacokinetic analysis, the plasma concentrations of remdesivir and GS-441524 4 h after administration (C4) were 662 ng/mL and 58 ng/mL, respectively, and the concentrations 18 h after administration (C18) were 32 ng/mL and 44 ng/mL, respectively. Therefore, the half-life of remdesivir and GS-441524 was 3.2 and 35.1 h, respectively. Monitoring the plasma concentrations of remdesivir and GS-441524 in patients undergoing ECMO may be necessary.

Retrospective evaluation of appropriate dosing of cefmetazole for invasive urinary tract infection due to extended-spectrum ß-lactamase-producing Escherichia coli.

INTRODUCTION: The frequency of urinary tract infections (UTIs) caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales is steadily increasing worldwide. Therefore, we aimed to evaluate the efficacy and appropriate dosing of cefmetazole (CMZ) in invasive urinary tract infection (iUTI) caused by ESBL-producing Escherichia coli (ESBLEC). METHODS: Patients who developed ESBLEC iUTI and received CMZ between January 2007 and December 2018 were identified, and their medical records were reviewed. The time above minimum inhibitory concentration (MIC) (TAM) was calculated using the MIC value obtained from each patient and its simulated CMZ concentration. RESULTS: Thirty-nine patients were included in the study. The median TAM was 92.6% (interquartile range [IQR], 67.6-100). CMZ was clinically efficacious in 38 (97.4%) patients overall and in 11 out of 12 (91.7%) patients with normal renal function who received CMZ at 1 g every 8 h. CONCLUSIONS: In normal renal function, 1 g CMZ infused for over 1 h every 8 h is an efficacious treatment for iUTI caused by ESBLEC with MIC =< 4 mg/L.

Nucleos(t)ide reverse transcriptase inhibitor-sparing regimens in the era of standard 3-drug combination therapies for HIV-1 infection.

Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens have often been selected as antiretroviral therapy (ART) for HIV-1 infection recently, but data for characteristics have been lacking. This study aimed to document the current status of NRTI-sparing regimens in the era of standard 3-drug combination therapies. We cross-sectionally compared characteristics of patients treated with NRTI-sparing regimens (NRTI-sparing group) with dolutegravir plus tenofovir alafenamide fumarate/emtricitabine as a standard ART group in 2018. The NRTI-sparing and the standard ART groups included 61 and 469 patients, respectively. The mean (± standard deviation) age and serum creatinine of the NRTI-sparing group were significantly higher than those of the standard ART group (57.6 ± 12.8 years vs 42.8 ± 10.4 years (p < 0.05) and 2.09 ± 3.10 mg/dL vs. 0.93 ± 0.19 mg/dL (p < 0.05), respectively. The percentage of patients with NRTI-sparing regimens increased with age; with less than 5% in their 50s or younger, 8.4% in their 60s, and 14.1% aged ≥ 70 years. The primary reason for switching to the NRTI-sparing regimen was due to reduced renal function. According to the limited data, viral suppression was achieved at week 48 in all patients in the NRTI-sparing group. No patient had treatment failure nor developed drug resistance. The use of NRTI-sparing regimens increased with age. They were more frequently used in patients aged ≥ 60 years and those with decreased renal function.

Eight-Year Experience of Antimicrobial Stewardship Program and the Trend of Carbapenem Use at a Tertiary Acute-Care Hospital in Japan-The Impact of Postprescription Review and Feedback.

OBJECTIVE: We implemented a stepwise antimicrobial stewardship program (ASP). This study evaluated the effect of each intervention and the overall economic impact on carbapenem (CAR) use. METHOD: Carbapenem days of therapy (CAR-DOT) were calculated to assess the effect of each intervention, and antipseudomonal DOT were calculated to assess changes in use of broad-spectrum antibiotics. We carried out segmented regression analysis of studies with interrupted time series for 3 periods: Phase 1 (infectious disease [ID] consultation service only), Phase 2 (adding monitoring and e-mail feedback), and Phase 3 (adding postprescription review and feedback [PPRF] led by ID specialist doctors and pharmacists). We also estimated cost savings over the study period due to decreased CAR use. RESULTS: The median monthly CAR-DOT, per month per 100 patient-days, during Phase 1, Phase 2, and Phase 3 was 5.46, 3.69, and 2.78, respectively. The CAR-DOT decreased significantly immediately after the start of Phase 2, but a major decrease was not observed during this period. Although the immediate change was not apparent after Phase 3 started, CAR-DOT decreased significantly over this period. Furthermore, the monthly DOT of 3 alternative antipseudomonal agents also decreased significantly over the study period, but the incidence of antimicrobial resistance did not decrease. Cost savings over the study period, due to decreased CAR use, was estimated to be US $150 000. CONCLUSIONS: Adding PPRF on the conventional ASP may accelerate antimicrobial stewardship. Our CAR stewardship program has had positive results, and implementation is ongoing.

Comparison of knowledge to antimicrobial stewardship institution policies targeting Staphylococcus aureus bacteremia and candidemia between medical doctors and pharmacists in an academic teaching hospital in Japan.

Staphylococcus aureus bacteremia (SAB) and candidemia have significant impacts on mortality. Both have important implications for antimicrobial stewardship programs (ASPs). However, there are limited data regarding who should be educated and what components should be considered for the ASPs. Hence, we investigated the possibility of the key elements for implications of SAB and candidemia managements for ASPs. We conducted a cross-sectional study on the knowledge of antimicrobial stewardship institution policies targeting SAB and candidemia for all medical doctors (MDs) and pharmacists to using an E-learning system. To compare the differences in proportions of appropriate knowledge between junior residents and other MDs, and all MDs and pharmacists, we performed bivariate analyses using Fisher's exact test and χ2 test with odds ratios (ORs) with 95% confidence intervals (CIs). In total, all 395 MDs (71 junior residents, 137 senior residents and fellows, and 187 attending doctors) and all 63 pharmacists including 4 antimicrobial stewardship teams pharmacists responded to survey. MDs other than junior residents responded significantly inappropriately to the questions on the candidemia than junior residents (OR = 0.6, 95% CI: 0.4-1.0). Pharmacists had a significantly lower proportion of appropriate knowledge to the candidemia than MDs (OR = 0.4, 95% CI: 0.2-0.8). The major pitfall was failure to consult an ophthalmologist (82.5%). Next step, we will conduct educational intervention about institution policies, and evaluate whether to improve the knowledges and practices by pre-post test and chart review.