PMID- 31190908 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1178-6973 (Print) IS - 1178-6973 (Electronic) IS - 1178-6973 (Linking) VI - 12 DP - 2019 TI - Simulating moxalactam dosage for extended-spectrum beta-lactamase-producing Enterobacteriaceae using blood antimicrobial surveillance network data. PG - 1199-1208 LID - 10.2147/IDR.S193712 [doi] AB - Objectives: Monte Carlo simulation (MCS) was used to evaluate optimal dosage for cefepime (FEP), moxalactam (MOX), and cefperazone/sulbactam (CFZ/SBT) against extended-spectrum beta-lactamase (ESBL) producers isolated from the Blood Bacterial Resistant Investigation Collaborative System. Methods: Minimum inhibitory concentration (MIC) was tested by agar dilution, and ESBL producers were identified by modified Clinical and Laboratory Standards Institute tests. Pharmacokinetic parameters were derived from data on healthy individuals, and probability of target attainment (PTA) and cumulative fraction of response (CFR) %fT >MIC values were estimated by MCS. Results: A total of 2032 Escherichia coli (875 ESBL-producing) and Klebsiella pneumoniae (157 ESBL-producing) strains, and 371 other Enterobacteriaceae strains, were isolated from patients with bloodstream infections (BSIs). MIC(90) values for FEP, MOX, and CFZ/SBT against ESBL-producing E. coli and K. pneumoniae were 64/64 mg/L, 2/32 mg/L, and 64/128 mg/L, respectively. Conventional MOX and CFZ/SBT doses failed to reach 90% PTA against isolates with MICs >/=8 mg/L and >/=4 mg/L, respectively. Against ESBL producers, neither FEP nor CFZ/SBT achieved >/=90% CFR, while CFRs for MOX (1 g iv q6h, 2 g iv q12h, and 2 g iv q8h) exceeded 90% against ESBL-producing E. coli. Simulated CFRs for FEP and MOX were similar (>90%) against non-ESBL-producing Enterobacteriaceae, and higher than CFRs for CFZ/SBT. Conclusion: ESBL producers from BSIs were highly susceptible to MOX, and PTA values were generally higher for MOX than FEP or CFZ/SBT for conventional dosing regimens. This large MCS analysis shows that MOX but not FEP or CFZ/SBT can be used empirically to treat BSIs caused by ESBL-producing E. coli strains. FAU - Huang, Chen AU - Huang C AD - State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. AD - Department of Respiratory Medicine, Lihuili Hospital, Ningbo Medical Center, Ningbo, People's Republic of China. FAU - Shi, Qingyi AU - Shi Q AD - State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. FAU - Zheng, Beiwen AU - Zheng B AD - State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. FAU - Ji, Jinru AU - Ji J AD - State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. FAU - Ying, Chaoqun AU - Ying C AD - State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. FAU - Yu, Xiao AU - Yu X AD - State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. FAU - Wang, Hui AU - Wang H AD - Department of Respiratory Medicine, Lihuili Hospital, Ningbo Medical Center, Ningbo, People's Republic of China. FAU - Xiao, Yonghong AU - Xiao Y AD - State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China. LA - eng PT - Journal Article DEP - 20190508 PL - New Zealand TA - Infect Drug Resist JT - Infection and drug resistance JID - 101550216 PMC - PMC6522843 OTO - NOTNLM OT - Enterobacteriaceae OT - Monte Carlo simulation OT - cefepime OT - cefperazone/sulbactam OT - extended-spectrum beta-lactamase OT - moxalactam COIS- The authors reported no conflicts of interest in this work. EDAT- 2019/06/14 06:00 MHDA- 2019/06/14 06:01 PMCR- 2019/05/08 CRDT- 2019/06/14 06:00 PHST- 2018/11/07 00:00 [received] PHST- 2019/02/11 00:00 [accepted] PHST- 2019/06/14 06:00 [entrez] PHST- 2019/06/14 06:00 [pubmed] PHST- 2019/06/14 06:01 [medline] PHST- 2019/05/08 00:00 [pmc-release] AID - 193712 [pii] AID - 10.2147/IDR.S193712 [doi] PST - epublish SO - Infect Drug Resist. 2019 May 8;12:1199-1208. doi: 10.2147/IDR.S193712. eCollection 2019.