Wolff M, Joly-Guillou M L, Farinotti R, Carbon C
Clinique de Réanimation des Maladies Infectieuses, Hôpital Bichat-Claude Bernard, 75018 Paris, France.
Antimicrob Agents Chemother. 1999 Jun;43(6):1406-11. doi: 10.1128/AAC.43.6.1406.
The effects of various regimens containing combinations of beta-lactams, beta-lactam inhibitor(s), and rifampin were assessed in a recently described mouse model of Acinetobacter baumannii pneumonia (M. L. Joly-Guillou, M. Wolff, J. J. Pocidalo, F. Walker, and C. Carbon, Antimicrob. Agents Chemother. 41:345-351, 1997). Two aspects of the therapeutic response were studied: the kinetics of the bactericidal effect (treatment was initiated 3 h after intratracheal inoculation, and bacterial counts were determined over a 24-h period) and survival (treatment was initiated 8 h after inoculation, and the cumulative mortality rate was assessed on day 5). Two clinical strains were used: a cephalosporinase-producing strain (SAN-94040) and a multiresistant strain (RCH-69). For SAN-94040 and RCH-69, MICs and MBCs (milligrams per liter) were as follows: ticarcillin, 32, 64, 256, and >256, respectively; ticarcillin-clavulanate, 32, 64, and 512, and >512, respectively; imipenem, 0.5, 0.5, 8, and 32, respectively; sulbactam, 0.5, 0.5, 8, and 8, respectively; and rifampin, 8, 8, 4, and 4, respectively. Against SAN-94040, four regimens, i.e., imipenem, sulbactam, imipenem-rifampin, and ticarcillin-clavulanate (at a 25/1 ratio)-sulbactam produced a true bactericidal effect (>/=3-log10 reduction of CFU/g of lung). The best survival rate (i.e., 93%) was obtained with the combination of ticarcillin-clavulanate-sulbactam, and regimens containing rifampin provided a survival rate of >/=65%. Against RCH-69, only regimens containing rifampin and the combination of imipenem-sulbactam had a true bactericidal effect. The best survival rates (>/=80%) were obtained with regimens containing rifampin and sulbactam. These results suggest that nonclassical combinations of beta-lactams, beta-lactamase inhibitors, and rifampin should be considered for the treatment of nosocomial pneumonia due to A. baumannii.
在最近描述的鲍曼不动杆菌肺炎小鼠模型中(M. L. Joly - Guillou、M. Wolff、J. J. Pocidalo、F. Walker和C. Carbon,《抗菌药物与化疗》41:345 - 351,1997年),评估了含β - 内酰胺类、β - 内酰胺酶抑制剂和利福平组合的各种治疗方案的效果。研究了治疗反应的两个方面:杀菌作用的动力学(气管内接种后3小时开始治疗,并在24小时内测定细菌数量)和存活率(接种后8小时开始治疗,并在第5天评估累积死亡率)。使用了两株临床菌株:一株产头孢菌素酶菌株(SAN - 94040)和一株多重耐药菌株(RCH - 69)。对于SAN - 94040和RCH - 69,其最低抑菌浓度(MICs)和最低杀菌浓度(MBCs,毫克/升)如下:替卡西林分别为32、64、256和>256;替卡西林 - 克拉维酸分别为32、64和512以及>512;亚胺培南分别为0.5、0.5、8和32;舒巴坦分别为0.5、0.5、8和8;利福平分别为8、8、4和4。针对SAN - 94040,四种治疗方案,即亚胺培南、舒巴坦、亚胺培南 - 利福平以及替卡西林 - 克拉维酸(25/1比例) - 舒巴坦产生了真正的杀菌效果(肺组织中CFU/g减少≥3个对数10)。替卡西林 - 克拉维酸 - 舒巴坦组合获得了最佳存活率(即93%),含利福平的治疗方案存活率≥65%。针对RCH - 69,只有含利福平的治疗方案以及亚胺培南 - 舒巴坦组合有真正的杀菌效果。含利福平和舒巴坦的治疗方案获得了最佳存活率(≥80%)。这些结果表明,对于鲍曼不动杆菌引起的医院获得性肺炎的治疗,应考虑β - 内酰胺类、β - 内酰胺酶抑制剂和利福平的非经典组合。