Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Int J Antimicrob Agents. 2013 Jan;41(1):47-51. doi: 10.1016/j.ijantimicag.2012.09.007. Epub 2012 Nov 3.
Carbapenems are increasingly being utilised owing to the escalating prevalence of antimicrobial-resistant Gram-negative bacteria from community and hospital settings. In this study, pharmacodynamic profiles of doripenem, imipenem and meropenem were evaluated against Gram-negative bacteria isolated from hospitalised patients. MICs for carbapenems were determined for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii obtained from the COMPACT II programme conducted in the Asia-Pacific region. Monte Carlo simulations were undertaken to assess the pharmacodynamic profile of carbapenems against each of the pathogens. All carbapenem regimens achieved optimal exposures [cumulative fraction of response (CFR) ≥90%] against E. coli and K. pneumoniae. Against P. aeruginosa, doripenem achieved 81.3-95.3% CFR, imipenem achieved 55.2-77.9% CFR and meropenem achieved 71.9-91.3% CFR; only doripenem regimens of 4-h infusion of 1000 mg every 8h (q8h) and 1-h and 4-h infusion of 2000 mg q8h and a meropenem regimen of 3-h infusion of 2000 mg q8h obtained optimal exposures; all carbapenem regimens showed slight (1-7%) improvement in CFRs in favour of isolates collected from ICU sources. Against A. baumannii, CFRs were much lower (25.9-46.7% CFR) and no carbapenem regimens achieved optimal exposure in or outside the ICU. Owing to the high potency of carbapenems against these Enterobacteriaceae populations, standard regimens are likely to perform well in the Asia-Pacific region. However, larger doses combined with prolonged infusions will be required to increase the CFR for these carbapenems against resistant non-fermenting Gram-negatives such as P. aeruginosa and A. baumannii that are prevalent in these countries.
由于社区和医院环境中抗微生物革兰氏阴性菌的流行率不断上升，碳青霉烯类药物的使用越来越多。在这项研究中，评估了多利培南、亚胺培南和美罗培南对住院患者分离的革兰氏阴性菌的药效学特征。从亚太地区进行的 COMPACT II 计划中获得的大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌的碳青霉烯类药物 MIC 进行了测定。进行了蒙特卡罗模拟，以评估碳青霉烯类药物对每种病原体的药效学特征。所有碳青霉烯类药物方案对大肠杆菌和肺炎克雷伯菌均达到了最佳暴露[累积反应分数（CFR）≥90%]。对于铜绿假单胞菌，多利培南达到 81.3-95.3%的 CFR，亚胺培南达到 55.2-77.9%的 CFR，美罗培南达到 71.9-91.3%的 CFR；只有多利培南 4 小时输注 1000mg，每 8 小时（q8h）和 1 小时和 4 小时输注 2000mg，q8h 的方案以及美罗培南 3 小时输注 2000mg，q8h 的方案才能获得最佳暴露；所有碳青霉烯类药物方案在 ICU 来源的分离株中，CFR 略有改善（1-7%）。对于鲍曼不动杆菌，CFR 低得多（25.9-46.7%的 CFR），在 ICU 内外，没有碳青霉烯类药物方案达到最佳暴露。由于碳青霉烯类药物对这些肠杆菌科细菌的高活性，标准方案在亚太地区可能表现良好。然而，为了增加这些碳青霉烯类药物对这些在这些国家流行的耐药非发酵革兰氏阴性菌（如铜绿假单胞菌和鲍曼不动杆菌）的 CFR，需要使用更大剂量并延长输注时间。
