β-内酰胺类、β-内酰胺酶抑制剂和利福平联合用药对小鼠肺炎模型中鲍曼不动杆菌的体内疗效。
In vivo efficacies of combinations of beta-lactams, beta-lactamase inhibitors, and rifampin against Acinetobacter baumannii in a mouse pneumonia model.
作者信息
Wolff M, Joly-Guillou M L, Farinotti R, Carbon C
机构信息
Clinique de Réanimation des Maladies Infectieuses, Hôpital Bichat-Claude Bernard, 75018 Paris, France.
出版信息
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。
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