Zhanel George G, Derkatch Sheldon, Laing Nancy, Noreddin Ayman M, Hoban Daryl J
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, 820 Sherbrook Street, Winnipeg, R3A 1R9, Canada.
J Antimicrob Chemother. 2007 Jan;59(1):144-7. doi: 10.1093/jac/dkl433. Epub 2006 Nov 1.
Ertapenem is a novel carbapenem with activity against both penicillin-susceptible (MIC < or = 0.06 mg/L) and penicillin-non-susceptible (MIC > or = 0.12 mg/L) Streptococcus pneumoniae. This study assessed the pharmacodynamic activity of ertapenem against penicillin-susceptible and penicillin-non-susceptible S. pneumoniae using an in vitro pharmacodynamic model.
Fifteen S. pneumoniae strains including 3 penicillin-susceptible and 12 penicillin-non-susceptible [4 penicillin-intermediate (MIC 0.12-1 mg/L) and 8 penicillin-resistant (MIC > or = 2 mg/L); with different resistance phenotypes including erythromycin-resistant (MIC > or = 1 mg/L), ciprofloxacin-resistant (MIC > or = 4 mg/L) and doxycycline-resistant (MIC > or = 8 mg/L)] were studied. The in vitro pharmacodynamic model was inoculated with 1 x 10(6) cfu/mL and ertapenem was dosed once daily at 0 and 24 h to simulate f (free) Cmax and t(1/2) obtained after a standard 1 g intravenous once daily dose in healthy volunteers (fCmax 15 mg/L, t(1/2) 4 h). Sampling was performed for 48 h to assess viable growth.
Ertapenem T(> MIC) > or = 80% (ertapenem MICs < or = 0.5 mg/L) resulted in bactericidal (> or = 3 log10 killing) activity at 12, 24 and 48 h with complete eradication of penicillin-susceptible and penicillin-non-susceptible S. pneumoniae from the model with no regrowth over the 48 h study period. Ertapenem T(> MIC) < or = 63% (ertapenem MIC > or = 1 mg/L) resulted in bactericidal activity at 12 h with regrowth at 24 and 48 h. The observed MICs for S. pneumoniae of ertapenem studied in the in vitro model did not change during the 48 h period, even for strains where regrowth occurred.
Ertapenem is bactericidal against both penicillin-susceptible and penicillin-non-susceptible S. pneumoniae (ertapenem MICs < or = 0.5 mg/L) when simulating free drug after 1 g intravenous once daily dosing.
厄他培南是一种新型碳青霉烯类抗生素，对青霉素敏感（MIC≤0.06mg/L）和青霉素不敏感（MIC≥0.12mg/L）的肺炎链球菌均有活性。本研究使用体外药效学模型评估了厄他培南对青霉素敏感和青霉素不敏感肺炎链球菌的药效学活性。
研究了15株肺炎链球菌，其中包括3株青霉素敏感株和12株青霉素不敏感株[4株青霉素中介株（MIC 0.12 - 1mg/L）和8株青霉素耐药株（MIC≥2mg/L）；具有不同耐药表型，包括红霉素耐药（MIC≥1mg/L）、环丙沙星耐药（MIC≥4mg/L）和强力霉素耐药（MIC≥8mg/L）]。体外药效学模型接种浓度为1×10⁶cfu/mL，厄他培南在0和24小时每日给药一次，以模拟健康志愿者每日一次静脉注射1g标准剂量后获得的游离Cmax和t(1/2)（游离Cmax 15mg/L，t(1/2) 4小时）。进行48小时采样以评估活菌生长情况。
当厄他培南T(> MIC)≥80%（厄他培南MIC≤0.5mg/L）时，在12、24和48小时产生杀菌（≥3 log₁₀杀灭）活性，模型中的青霉素敏感和青霉素不敏感肺炎链球菌被完全清除，在48小时研究期内无再生长。当厄他培南T(> MIC)≤63%（厄他培南MIC≥1mg/L）时，在12小时产生杀菌活性，但在24和48小时有再生长。在体外模型中研究的肺炎链球菌对厄他培南的观察MIC在48小时内未发生变化，即使是有再生长的菌株。
在模拟每日一次静脉注射1g后游离药物的情况下，厄他培南对青霉素敏感和青霉素不敏感的肺炎链球菌（厄他培南MIC≤0.5mg/L）均有杀菌作用。
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