Lavoie S R, Wong E S, Coudron P E, Williams D S, Markowitz S M
Infectious Diseases Section, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia 23249.
Antimicrob Agents Chemother. 1993 Jul;37(7):1447-51. doi: 10.1128/AAC.37.7.1447.
Increasing antibiotic resistance in the enterococci, including the capacity for beta-lactamase production and the development of high-level aminoglycoside resistance, has complicated the treatment of serious enterococcal infections, which often require synergistic antibiotic combinations for cure. We utilized the rabbit model of aortic valve endocarditis to investigate the effects of various antibiotics, alone and in combination, against a multiply antibiotic-resistant isolate of Enterococcus faecalis. Female New Zealand White rabbits were infected with either a beta-lactamase-producing, gentamicin-resistant isolate of E. faecalis or a non-beta-lactamase-producing, aminoglycoside-susceptible isolate, and the mean log10 CFU per gram of vegetation were determined. The most active agents were low-dose ampicillin-sulbactam (200 mg/kg of body weight per day), high-dose ampicillin-sulbactam (400 mg/kg of body weight per day), and vancomycin (150 mg/kg of body weight per day), which reduced the titers of bacteria by 2.27, 2.76, and 2.85 log10 (CFU/g, respectively, compared with controls. While ampicillin-sulbactam and vancomycin were equally efficacious in reducing titers of bacteria in vegetations, no animals were cured (defined as < 2 log10 CFU/g of vegetation) by either agent, whether treatment was continued for 3 or 7 days. The addition of gentamicin was not associated with increased killing in rabbits infected with the aminoglycoside-resistant isolate. Both high-dose ampicillin-sulbactam and vancomycin regimens demonstrated significant, continued reduction in bacterial titers with the longer periods of treatment (P < or = 0.05); 7-day treatment with high-dose ampicillin-sulbactam produced a greater reduction in bacterial titers in vegetation than 7-day treatment with vancomycin (P < or = 0.05). We conclude that ampicillin-sulbactam and vancomycin are equally effective in the treatment of experimental endocarditis due to beta-lactamase-producing, highly gentamicin-resistant E. faecalis. The optimum therapy for such infections in humans is not known.
肠球菌的抗生素耐药性不断增加，包括产生β-内酰胺酶的能力以及高水平氨基糖苷类耐药性的出现，使得严重肠球菌感染的治疗变得复杂，这类感染通常需要联合使用具有协同作用的抗生素才能治愈。我们利用兔主动脉瓣心内膜炎模型，研究了各种抗生素单独使用及联合使用时，对一株多重耐药粪肠球菌分离株的影响。雌性新西兰白兔分别感染一株产β-内酰胺酶、对庆大霉素耐药的粪肠球菌分离株或一株不产β-内酰胺酶、对氨基糖苷类敏感的分离株，然后测定每克赘生物中的平均log10 CFU。最有效的药物是低剂量氨苄西林-舒巴坦（每天200mg/kg体重）、高剂量氨苄西林-舒巴坦（每天400mg/kg体重）和万古霉素（每天150mg/kg体重），与对照组相比，它们分别使细菌滴度降低了2.27、2.76和2.85 log10（CFU/g）。虽然氨苄西林-舒巴坦和万古霉素在降低赘生物中细菌滴度方面同样有效，但无论是治疗3天还是7天，两种药物均未使任何动物治愈（定义为每克赘生物中<2 log10 CFU）。对于感染了氨基糖苷类耐药分离株的兔子，添加庆大霉素并未增强杀菌效果。高剂量氨苄西林-舒巴坦和万古霉素治疗方案在较长治疗期内均显示细菌滴度持续显著降低（P≤0.05）；高剂量氨苄西林-舒巴坦治疗7天比万古霉素治疗7天能使赘生物中的细菌滴度降低得更多（P≤'0.05）。我们得出结论，氨苄西林-舒巴坦和万古霉素在治疗由产β-内酰胺酶、对庆大霉素高度耐药的粪肠球菌引起的实验性心内膜炎方面同样有效。目前尚不清楚人类此类感染的最佳治疗方法。
