Markowitz S M, Wells V D, Williams D S, Stuart C G, Coudron P E, Wong E S
Medical Service, Hunter Holmes McGuire, Department of Veterans Affairs Medical Center, Richmond, Virginia 23249.
Antimicrob Agents Chemother. 1991 Jun;35(6):1075-80. doi: 10.1128/AAC.35.6.1075.
beta-Lactamase-producing (BL+), aminoglycoside-resistant (AR) Enterococcus faecalis is endemic in our hospital, having caused widespread colonization and infection. Suitable therapy for infections caused by these organisms has been problematic. We compared the antimicrobial and bactericidal activities, by broth macrodilution and time-kill methods, of several antibiotics, alone and in combination, against BL+, AR isolates of E. faecalis and determined the transmissibility of antibiotic resistance markers. Ampicillin-sulbactam, imipenem, daptomycin, and ciprofloxacin were the most active antibiotics with MICs for 90% of isolates tested of 2, 1, 2, and 1 microgram/ml, respectively, against inocula of 10(3) and 10(5) CFU/ml. Little inoculum effect was noted with imipenem, vancomycin, daptomycin, or ciprofloxacin, while the addition of sulbactam to ampicillin partially inhibited the effect of the increased inoculum. Penicillin-sulbactam and ampicillin-sulbactam combinations in a 2:1 ratio were most frequently bactericidal (greater than or equal to 3-log10-unit decrease in bacterial titers at 24 h for 13 of 20 isolates), followed by daptomycin (8 of 20 isolates) and ciprofloxacin (2 of 20 isolates). Bactericidal activity was not demonstrated for imipenem or teicoplanin. beta-Lactamase production and aminoglycoside resistance were associated with a 60- to 65-MDa plasmid which was easily transferred to a plasmid-free E. faecalis recipient. The 840-bp beta-lactamase gene probe hybridized to purified plasmid DNA from BL+ donor isolates of E. faecalis and transconjugants but not from BL- isolates. Ampicillin-sulbactam and daptomycin (an investigational antibiotic) seem to be reasonable choices for the empiric therapy of presumed enterococcal infections in hospitals in which BL+, AR E. faecalis strains are isolated. Their use should ideally be supported by tests for bactericidal activity.
产β-内酰胺酶（BL+）、耐氨基糖苷类（AR）的粪肠球菌在我院呈地方流行，已导致广泛定植和感染。针对这些微生物引起的感染，合适的治疗方法一直存在问题。我们采用肉汤稀释法和时间杀菌法，比较了几种抗生素单独及联合使用时对产BL+、AR的粪肠球菌分离株的抗菌和杀菌活性，并测定了抗生素耐药标记的可传递性。氨苄西林-舒巴坦、亚胺培南、达托霉素和环丙沙星是活性最强的抗生素，对90%受试分离株的MICs（接种量为10³和10⁵CFU/ml时）分别为2、1、2和1μg/ml。亚胺培南、万古霉素、达托霉素或环丙沙星几乎没有接种量效应，而氨苄西林添加舒巴坦可部分抑制接种量增加的效应。2:1比例的青霉素-舒巴坦和氨苄西林-舒巴坦组合最常具有杀菌作用（20株分离株中有13株在24小时时细菌滴度下降≥3个对数10单位），其次是达托霉素（20株分离株中有8株）和环丙沙星（20株分离株中有2株）。亚胺培南或替考拉宁未显示出杀菌活性。产β-内酰胺酶和耐氨基糖苷类与一个60至65MDa的质粒相关，该质粒很容易转移至无质粒的粪肠球菌受体菌。840bp的β-内酰胺酶基因探针与产BL+的粪肠球菌供体分离株及转接合子的纯化质粒DNA杂交，但不与BL-分离株杂交。在分离出产BL+、AR粪肠球菌菌株的医院中，氨苄西林-舒巴坦和达托霉素（一种研究用抗生素）似乎是经验性治疗疑似肠球菌感染的合理选择。理想情况下，它们的使用应以杀菌活性检测为依据。
