Georges B, Conil J M, Cougot P, Decun J F, Archambaud M, Seguin T, Chabanon G, Virenque C, Houin G, Saivin S
Anesthesia Reanimation, CHU Rangueil, UMR 181 Experimental Physiopathology and Toxicology (UPTE INRA-ENVT), Faculty of Pharmaceutic Sciences, Toulouse, France.
Int J Clin Pharmacol Ther. 2005 Aug;43(8):360-9. doi: 10.5414/cpp43360.
The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters of a continuous infusion of cefepime vs. an intermittent regimen in critically ill adult patients with Gram-negative bacilli infection. The prospective randomized parallel study was carried out in 50 patients with severe pneumonia (n = 41) or bacteremia (n = 9). They received cefepime 4 g/d either as a continuous infusion or intermittent administration 2 x 2 g in combination with amikacin. Patient characteristics and the minimal inhibitory concentration (MIC) of the isolated bacteria were comparable. Clinical outcomes were assessed along with pharmacodynamic indices and compared in both groups (chi2 and Mann-Whitney U-tests). Mechanical ventilation, clinical outcome and bacteriological eradication did not significantly differ between the two groups. Also, the area under the plasma cefepime concentration curve at steady state (AUCss: 612 +/- 369 vs. 623 +/- 319 mg x 1(-1) x h), AUCss > MIC (595 +/- 364 vs. 606 +/- 316 mg x 1(-1) x h) and the area under the inhibitory concentration curve (AUICss: 4258 +/- 5819 vs. 5194 +/- 7465 mg x 1(-1) x h) were similar. If the time above MIC (t > MIC) was not significantly higher in Group 1 (100 +/- 0%) than in Group 2 (90 +/- 11%), t > five-fold MIC in Group 1 (100 +/- 0%) was significantly higher (p < 0.01) than in Group 2 (82 +/- 25%). The mean time over the French breakpoint (4 mg/l) was 100 +/- 0% and 72 +/- 27% in Group 1 and 2 (p < 0.001), respectively. In contrast to intermittent cefepime administration, continuous infusion of cefepime consistently maintained a serum concentration > 5 x the MIC of typical Gram-negative nosocomial pathogens. This results in greater bactericidal activity against organisms with a higher (2 mg/l) cefepime breakpoint even if the clinical outcome is not significantly modified.
本研究的目的是比较在患有革兰氏阴性杆菌感染的成年重症患者中，持续输注头孢吡肟与间歇给药方案的药代动力学和药效学参数。这项前瞻性随机平行研究在50例严重肺炎患者（n = 41）或菌血症患者（n = 9）中进行。他们接受4g/d的头孢吡肟，要么持续输注，要么与阿米卡星联合间歇给药2次，每次2g。患者特征和分离细菌的最低抑菌浓度（MIC）具有可比性。评估临床结局以及药效学指标，并在两组之间进行比较（卡方检验和曼-惠特尼U检验）。两组之间的机械通气、临床结局和细菌学清除情况无显著差异。此外，稳态时血浆头孢吡肟浓度曲线下面积（AUCss：612±369 vs. 623±319mg·1⁻¹·h）、AUCss＞MIC（595±364 vs. 606±316mg·1⁻¹·h）以及抑菌浓度曲线下面积（AUICss：4258±5819 vs. 5194±7465mg·1⁻¹·h）相似。如果第1组高于MIC的时间（t＞MIC）（100±0%）并不显著高于第2组（90±11%），那么第1组高于5倍MIC的时间（t＞5倍MIC）（100±0%）则显著高于（p＜0.01）第2组（82±25%）。第1组和第2组超过法国断点（4mg/l）的平均时间分别为100±0%和72±27%（p＜0.001）。与头孢吡肟间歇给药相比，持续输注头孢吡肟始终能维持血清浓度＞5倍典型革兰氏阴性医院感染病原体的MIC。这导致对头孢吡肟断点较高（2mg/l）的微生物具有更强的杀菌活性，即使临床结局没有显著改善。
