Department of Pharmacy Practice, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York, USA.
Department of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York, USA.
Microbiol Spectr. 2022 Aug 31;10(4):e0062122. doi: 10.1128/spectrum.00621-22. Epub 2022 Jun 15.
Penicillin plus ceftriaxone is a promising alternative to ampicillin plus ceftriaxone for the treatment of Enterococcus faecalis infective endocarditis. Limited data is available supporting the utilization of penicillin plus ceftriaxone. A total of 20 E. faecalis isolates; one wild-type strain (JH2-2) and 19 clinical blood strains were assessed for penicillin plus ceftriaxone and ampicillin plus ceftriaxone synergy using a 24-h time-kill experiment. Susceptibility was determined by broth microdilution. Differences in bactericidal, bacteriostatic, or inactivity, as well as synergy between treatments were assessed by chi-square or Fisher exact test. All E. faecalis isolates were considered susceptible to ampicillin and penicillin. Ampicillin plus ceftriaxone versus penicillin plus ceftriaxone similarly demonstrated synergy. Bactericidal activity was more commonly observed for ampicillin plus ceftriaxone versus penicillin plus ceftriaxone. Among isolates with a penicillin MIC of 4 μg/mL ( = 7), synergistic activity for both combinations was less common compared to isolates with a penicillin MIC ≤ 2 μg/mL ( = 13). Ampicillin plus ceftriaxone and penicillin plus ceftriaxone demonstrate similar synergistic potential against E. faecalis clinical blood isolates, but strains with higher penicillin and ceftriaxone MICs less frequently demonstrated synergy. Further research is warranted to determine the role of the penicillin plus ceftriaxone therapy and the penicillin MIC in clinical practice. Penicillin plus ceftriaxone demonstrates similar synergistic activity against to ampicillin plus ceftriaxone. Isolates with a penicillin MIC of 4 mg/L and a ceftriaxone MIC of 512 or higher, lack penicillin plus ceftriaxone synergy despite the penicillin susceptibility MIC breakpoint of 8 mg/L.
青霉素联合头孢曲松治疗粪肠球菌感染性心内膜炎有较好的应用前景，替代氨苄西林联合头孢曲松。但目前仅有少量数据支持使用青霉素联合头孢曲松。本研究采用 24 小时时间杀伤实验，评估了 20 株粪肠球菌分离株，包括 1 株野生型菌株（JH2-2）和 19 株临床血分离株，以评估青霉素联合头孢曲松和氨苄西林联合头孢曲松的协同作用。采用肉汤微量稀释法测定药敏性。采用卡方检验或 Fisher 确切概率法评估处理之间杀菌、抑菌或无活性的差异以及协同作用。所有粪肠球菌分离株对氨苄西林和青霉素均敏感。氨苄西林联合头孢曲松与青霉素联合头孢曲松同样表现出协同作用。与青霉素联合头孢曲松相比，氨苄西林联合头孢曲松的杀菌活性更常见。对于青霉素 MIC 为 4 μg/ml（ = 7）的分离株，与青霉素 MIC ≤ 2 μg/ml（ = 13）的分离株相比，两种联合用药的协同活性更少见。青霉素联合头孢曲松和氨苄西林联合头孢曲松对粪肠球菌临床血分离株具有相似的协同作用潜力，但青霉素和头孢曲松 MIC 较高的菌株较少表现出协同作用。需要进一步研究以确定青霉素联合头孢曲松治疗的作用以及临床实践中青霉素 MIC 的作用。青霉素联合头孢曲松对粪肠球菌的协同作用与氨苄西林联合头孢曲松相似。尽管青霉素的药敏 MIC 折点为 8 mg/L，但青霉素 MIC 为 4 mg/L 且头孢曲松 MIC 为 512 或更高的分离株缺乏青霉素联合头孢曲松协同作用。
