Department of Pharmacy, Rhode Island Hospital, Providence, RI, USA.
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
J Antimicrob Chemother. 2019 Aug 1;74(8):2269-2273. doi: 10.1093/jac/dkz173.
To assess activity of the combination of ceftriaxone and ampicillin against clinical isolates of ampicillin-susceptible Enterococcus faecium.
Ampicillin-susceptible E. faecium (n = 29) and Enterococcus faecalis (n = 10) collected from locations in the USA and France were used for this analysis. Susceptibility testing was performed by gradient diffusion strip (GDS) and broth microdilution (BMD). Synergy with the combination of ceftriaxone and ampicillin was assessed in all isolates using GDS crossing and double disc diffusion methods. Selected isolates (nine E. faecium and three E. faecalis) were assessed for synergy in time-kill studies using ampicillin alone and in combination with ceftriaxone.
In isolates of E. faecium, the median (range) ampicillin MIC by BMD was 0.5 (0.25-4) mg/L and by GDS it was 2 (1-8) mg/L. In E. faecalis, the median (range) ampicillin MIC by BMD was 0.5 (0.5-1) mg/L and by GDS it was 2 (0.75-3) mg/L. A total of 24/29 (82.8%) isolates of E. faecium displayed synergy by GDS and 22/29 (75.9%) by double disc diffusion. Seven of 10 (70%) isolates of E. faecalis displayed synergy by GDS and 4/10 (40%) by double disc diffusion. Time-kill studies found synergy in 3/9 (33.3%) E. faecium and 3/3 (100%) E. faecalis.
In contrast to the demonstrated synergy in time-kill models of ceftriaxone and ampicillin for E. faecalis, this combination does not appear to provide uniform synergy in E. faecium. Antagonism was not observed. Clinical correlation is necessary and caution should be used when considering ampicillin and ceftriaxone for the treatment of infections caused by ampicillin-susceptible E. faecium.
评估头孢曲松和氨苄西林联合应用对氨苄西林敏感屎肠球菌临床分离株的活性。
本研究分析了来自美国和法国多个地点的氨苄西林敏感屎肠球菌（n=29）和粪肠球菌（n=10）。通过梯度扩散条（GDS）和肉汤微量稀释（BMD）进行药敏试验。使用 GDS 划线和双碟扩散法评估头孢曲松和氨苄西林联合应用对所有分离株的协同作用。选择部分分离株（9 株屎肠球菌和 3 株粪肠球菌），通过单独使用氨苄西林和与头孢曲松联合使用，在时间杀伤研究中评估协同作用。
屎肠球菌分离株的 BMD 法中氨苄西林 MIC 的中位数（范围）为 0.5（0.25-4）mg/L，GDS 法为 2（1-8）mg/L。粪肠球菌的 BMD 法中氨苄西林 MIC 的中位数（范围）为 0.5（0.5-1）mg/L，GDS 法为 2（0.75-3）mg/L。GDS 法中 24/29（82.8%）的屎肠球菌分离株和 22/29（75.9%）的粪肠球菌分离株显示协同作用，双碟扩散法分别为 22/29（75.9%）和 10/10（100%）。7/10（70%）的粪肠球菌分离株和 4/10（40%）的屎肠球菌分离株在 GDS 法中显示协同作用。时间杀伤研究发现 3/9（33.3%）的屎肠球菌和 3/3（100%）的粪肠球菌显示协同作用。
与头孢曲松和氨苄西林在时间杀伤模型中对粪肠球菌显示协同作用不同，该联合用药方案似乎不能在屎肠球菌中提供一致的协同作用。未观察到拮抗作用。需要进行临床相关性研究，在考虑使用氨苄西林和头孢曲松治疗氨苄西林敏感屎肠球菌引起的感染时应谨慎。
