A large retrospective cohort study of cefazolin compared with flucloxacillin for methicillin-susceptible Staphylococcus aureus bacteraemia

Background and objectives: Antistaphylococcal penicillins (ASPs) are recommended as first-line treatment for invasive infections caused by methicillin-susceptible Staphylococcus aureus (MSSA). Cefazolin is an alternative option, but there is theoretical concern about its use as some MSSA strains produce beta-lactamases active against cefazolin. The study compared the outcomes in patients with MSSA infections treated with flucloxacillin and cefazolin. 

Methods: We analysed data from The Australia and New Zealand Co-operative Outcomes of Staphylococcal Sepsis (ANZCOSS) observational study, which included all consecutive unique episodes of Staphylococcus aureus bacteraemia from 27 hospital-based or independent microbiology laboratories from January 2007 to September 2013. In this retrospective analysis of prospectively collected data, we compared 30-day all-cause mortality in patients with MSSA bacteraemia treated with flucloxacillin to that in patients treated with cefazolin. 

Results: We included data from 7312 episodes of MSSA bacteremia and found no difference in 30-day mortality in those treated with flucloxacillin (731/6520 [11.2%, 95% CI 10.9–12.5%]) compared to cefazolin (83/792 [10.7%, 95% CI 8.4–12.8%]), OR 0.93 (95% CI 0.72–1.17). In a propensity-adjusted analysis, mortality remained non-significantly lower in the cefazolin group (aOR 0.86 [95% CI 0.65–1.14]). 

Conclusions: This study supports the results from previous observational studies from other regions, while extending them to Australasia and to a much larger number of patients. Although this observational study indicates cefazolin is likely to have equivalent or superior outcomes to ASPs for MSSA bacteraemia, this can only be convincingly proven by a properly designed randomised controlled trial.