Pajot O, Burdet C, Couffignal C, Massias L, Armand-Lefevre L, Foucrier A, Da Silva D, Lasocki S, Laouénan C, Mentec H, Mentré F, Wolff M
Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, France
AP-HP, Bichat Hospital, Biostatistics Department, F-75018 Paris, France IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France.
J Antimicrob Chemother. 2015 May;70(5):1487-94. doi: 10.1093/jac/dku569. Epub 2015 Jan 27.
Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients.
Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a ≥10(3) cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment.
Thirty-nine patients [median (min-max) age = 60 years (28-84) and median SAPS2 at inclusion = 40 (19-73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094-16) and 2 mg/L (1-32), respectively. Median times over MIC and over 5× MIC for imipenem were 100% (8-100) and 74% (3-100), respectively. The median C1/MIC ratio for amikacin was 23 (1-76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/MIC was significantly higher in the microbiological success group: 26 (1-76) versus 11 (3-26) (P = 0.004).
In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C1/MIC ratio than previously described might be necessary.
尽管最近取得了进展，但重症监护病房（ICU）患者呼吸机相关性肺炎（VAP）的抗生素治疗仍然具有挑战性。我们评估了亚胺培南和美罗培南的药代动力学和药效学参数对这些患者微生物学结局的影响。
前瞻性纳入革兰氏阴性杆菌（GNB）VAP患者。在经验性给予每日三次亚胺培南联合单次剂量美罗培南后，采集血样进行药代动力学分析。对从呼吸道样本中分离出的每种GNB进行最低抑菌浓度（MIC）测定。微生物学成功定义为定量培养中细菌计数从基线到治疗第3天减少≥10³cfu/mL。
纳入39例患者[年龄中位数（最小值 - 最大值）= 60岁（28 - 84岁），纳入时SAPS2中位数 = 40（19 - 73）]。亚胺培南和美罗培南的MIC中位数分别为0.25mg/L（0.094 - 16）和2mg/L（1 - 32）。亚胺培南高于MIC和高于5×MIC的时间中位数分别为100%（8 - 100）和74%（3 - 100）。美罗培南的C1/MIC比值中位数为23（1 - 76）；34例患者（87%）的C1/MIC≥10。29例患者（74%）实现了微生物学成功。没有亚胺培南药效学参数与微生物学成功显著相关。对于美罗培南，微生物学成功组的C1/MIC显著更高：26（1 - 76）对11（3 - 26）（P = 0.004）。
在患有VAP的ICU患者中，常规给药方案很容易达到经典的亚胺培南药效学靶点。在此背景下，对于美罗培南，可能需要比先前描述的更高的C1/MIC比值。
