Gil-Navarro M V, Lopez-Cortes L E, Luque-Marquez R, Galvez-Acebal J, de Alarcon-Gonzalez A
Unidad Clínica de Farmacia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio, Sevilla, Spain.
Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Instituto de Biomedicina de Sevilla (IBiS), Universidad de Sevilla/Centro Superior de Investigaciones Científicas, Sevilla, Spain.
J Clin Pharm Ther. 2018 Apr;43(2):220-223. doi: 10.1111/jcpt.12635. Epub 2017 Oct 13.
Enterococcus faecalis is the third most common causal agent of infective endocarditis. Currently, the treatment recommended is a combination of ampicillin (2 g/4 h) plus ceftriaxone (2 g/12 h), so patients must remain hospitalized for almost 6 weeks to receive the treatment. They are not generally included in outpatient parenteral antimicrobial therapy programs because 2 different electronic pumps are required to administer these 2 antibiotics. To enable the treatment of patients with E. faecalis IE at home, we designed a continuation combination regimen of ceftriaxone 4 g once daily in a short infusion plus ampicillin 2 g/4 h using a programmable pump.
We analyzed a cohort of patients attended in an outpatient parenteral antimicrobial therapy program that has been working since 2012 in 2 tertiary hospitals. We selected patients attended in this program for E. faecalis IE treated with a continuation regimen of ampicillin 12 g daily (2 g/4 h) and ceftriaxone 4 g every 24 hours between July 2012 and March 2017.
Of the 720 patients included in the outpatient parenteral antimicrobial therapy program, 42 had infective endocarditis, and 4 (9.52%) were treated using the combination regimen described above. All patients were men, and all had left-sided native-valve infective endocarditis. All 4 patients received ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours in hospital, for a median duration of 25 days (IQR 15-32). Thereafter, in the program, they received the following regimen: a 30-minute infusion of ceftriaxone 4 g in 250 mL of saline solution, followed by ampicillin 12 g daily in 500 mL of saline solution delivered by a pump programmed to administer 2 g every 4 hours. Patients received this treatment at home for a median of 22.5 days (IQR 13-32). All patients achieved clinical and microbiological cure with no recurrences or complications after a lengthy follow-up period (median 365 days, IQR 221-406). No drug-related adverse events or problems with the pump system were reported.
Use of ceftriaxone 4 g in a single dose yields a mean plasma concentration of 30 μg/mL. Ceftriaxone also has a high plasma protein binding capability, and once this binding is saturated, there is no reason to administer higher doses. Therefore, it seems reasonable to use a dose of 4 g of ceftriaxone once daily to have a synergist effect with ampicillin within the vegetation, and enable the treatment of patients with E. faecalis infective endocarditis at home. In conclusion, the administration of ampicillin (2 g/4 h) plus ceftriaxone (4 g/24 h) as a continuation regimen in an outpatient parenteral antimicrobial therapy program may be as effective and safe as the usual lengthy in-hospital regimen (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) in patients with E. faecalis infective endocarditis.
粪肠球菌是感染性心内膜炎的第三大常见致病原。目前推荐的治疗方案是氨苄西林（2g/4小时）加头孢曲松（2g/12小时）联合使用，因此患者必须住院近6周才能接受该治疗。由于需要使用2种不同的电子泵来输注这2种抗生素，所以患者一般不被纳入门诊胃肠外抗菌治疗项目。为了使粪肠球菌感染性心内膜炎患者能够在家中接受治疗，我们设计了一种延续性联合治疗方案，即使用可编程泵，每日1次短时间输注4g头孢曲松加每4小时输注2g氨苄西林。
我们分析了自2012年起在2家三级医院开展的门诊胃肠外抗菌治疗项目中收治的一组患者。我们选取了在该项目中接受治疗的粪肠球菌感染性心内膜炎患者，这些患者在2012年7月至2017年3月期间采用每日12g氨苄西林（2g/4小时）和每24小时4g头孢曲松的延续性治疗方案。
在门诊胃肠外抗菌治疗项目纳入的720例患者中，42例患有感染性心内膜炎，其中4例（9.52%）采用上述联合治疗方案。所有患者均为男性，均患有左侧原发性瓣膜感染性心内膜炎。所有4例患者在医院均接受每4小时2g氨苄西林和每12小时2g头孢曲松治疗，中位疗程为25天（四分位间距15 - 32天）。此后，在该项目中，他们接受以下治疗方案：在250mL盐溶液中30分钟输注4g头孢曲松，随后通过编程为每4小时输注2g的泵在500mL盐溶液中每日输注12g氨苄西林。患者在家中接受该治疗的中位时间为22.5天（四分位间距13 - 32天）。经过长时间随访（中位365天，四分位间距221 - 406天），所有患者均实现临床和微生物学治愈且无复发或并发症。未报告与药物相关的不良事件或泵系统问题。
单次剂量使用4g头孢曲松可使血浆平均浓度达到30μg/mL。头孢曲松还具有较高的血浆蛋白结合能力，一旦这种结合饱和，就没有理由给予更高剂量。因此，每日使用1次4g头孢曲松剂量似乎合理，可在赘生物内与氨苄西林产生协同作用，并使粪肠球菌感染性心内膜炎患者能够在家中接受治疗。总之，在门诊胃肠外抗菌治疗项目中，将氨苄西林（2g/4小时）加头孢曲松（4g/24小时）作为延续性治疗方案，对于粪肠球菌感染性心内膜炎患者可能与常规的长时间住院治疗方案（氨苄西林2g/4小时和头孢曲松2g/12小时）一样有效且安全。
