Ingram Paul R, Ng Jacinta, Mathieson Claire, Mowlaboccus Shakeel, Coombs Geoffrey, Raby Edward, Dyer John
Department Infectious Diseases, Fiona Stanley Hospital, Perth, Australia.
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
JAC Antimicrob Resist. 2021 Aug 7;3(3):dlab128. doi: 10.1093/jacamr/dlab128. eCollection 2021 Sep.
Amoxicillin plus ceftriaxone combination therapy is now standard of care for enterococcal endocarditis. Due to amoxicillin instability in infusion devices, benzylpenicillin plus ceftriaxone may be substituted to facilitate outpatient parenteral antimicrobial therapy (OPAT) delivery, despite lack of guideline endorsement.
To assess the clinical efficacy of benzylpenicillin plus ceftriaxone for the management of enterococcal endovascular infections, in addition to assessing this combination's synergy.
Retrospective cohort study assessing unplanned readmissions, relapses and mortality for 20 patients with endovascular infections treated with benzylpenicillin plus ceftriaxone delivered via OPAT. For a subset of isolates, synergism for both amoxicillin and benzylpenicillin in combination with ceftriaxone was calculated using a chequerboard method.
Patients had endovascular infections of native cardiac valves (11), mechanical or bioprosthetic cardiac valves (7), pacemaker leads (1) or left ventricular assistant devices (1). The median duration of OPAT was 22 days, and the most frequent antimicrobial regimen was benzylpenicillin 14 g/day via continuous infusion and ceftriaxone 4 g once daily via short infusion. Rates of unplanned readmissions were high (30%), although rates of relapsed bacteraemia (5%) and 1 year mortality (15%) were comparable to the published literature. Benzylpenicillin less frequently displayed a synergistic interaction with ceftriaxone when compared with amoxicillin (3 versus 4 out of 6 isolates).
Lower rates of synergistic antimicrobial interaction and a significant proportion of unplanned readmissions suggest clinicians should exercise caution when treating enterococcal endovascular infection utilizing a combination of benzylpenicillin and ceftriaxone via OPAT.
阿莫西林联合头孢曲松的联合疗法目前是肠球菌性心内膜炎的标准治疗方案。由于阿莫西林在输液装置中不稳定，尽管缺乏指南认可，但苄星青霉素联合头孢曲松可作为替代方案，以促进门诊胃肠外抗菌治疗（OPAT）的实施。
评估苄星青霉素联合头孢曲松治疗肠球菌性血管内感染的临床疗效，并评估该联合用药的协同作用。
回顾性队列研究，评估20例接受通过OPAT给予苄星青霉素联合头孢曲松治疗的血管内感染患者的非计划再入院、复发和死亡率。对于部分分离株，采用棋盘法计算阿莫西林和苄星青霉素与头孢曲松联合使用时的协同作用。
患者的血管内感染累及天然心脏瓣膜（11例）、机械或生物人工心脏瓣膜（7例）、起搏器导线（1例）或左心室辅助装置（1例）。OPAT的中位持续时间为22天，最常用的抗菌方案是持续输注苄星青霉素14g/天，短时间输注头孢曲松4g/天。非计划再入院率较高（30%），尽管菌血症复发率（5%）和1年死亡率（15%）与已发表文献相当。与阿莫西林相比，苄星青霉素与头孢曲松显示协同相互作用的频率较低（6株分离株中分别为3株和4株）。
抗菌协同作用率较低以及相当比例的非计划再入院表明，临床医生在通过OPAT使用苄星青霉素和头孢曲松联合治疗肠球菌性血管内感染时应谨慎行事。
