Comparative effectiveness of β-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study

Abstract

Objectives Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia Methods We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. Results In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2–3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0–3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73–1.60 and HR 1.22, 95% CI 0.88–1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42–4.52 and sHR 1.93, 95% CI 0.67–5.60]. Conclusions In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.

Clinical Effectiveness of Continuous Infusion Flucloxacillin in the Outpatient Parenteral Antimicrobial Therapy (OPAT) Setting in a UK Hospital: A Service Evaluation

“…Prior to the introduction of continuous intravenous infusions (CIVs), administration of flucloxacillin for serious Methicillin Sensitive Staphylococcus aureus (MSSA) infection was not logistically practical in the OPAT setting, due to its required dosing frequency of every 4-6 hours to ensure pharmacokinetic/pharmacodynamic (PK-PD) parameters are achieved [1]. Other once daily treatment options, namely ceftriaxone, are not favoured as a first-line treatment option for MSSA bacteraemia compared to anti-staphylococcal penicillins, given concerns of higher risk of treatment failure and conflicting results relating to efficacy in the OPAT setting [2,3]. Continuous antimicrobial infusions are advised within the OPAT good practice recommendations [4] to be used where there are robust drug stability data, such data is published for flucloxacillin [5].…”