Comparison of flucloxacillin and cefazolin in methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia

Evidence and Economic review 

Published May 2026

Background: 

In Scotland, flucloxacillin is currently the first-line antibiotic recommended for treating methicillin-sensitive MSSA bacteraemia, however flucloxacillin is associated with increased risk of acute kidney injury (AKI). For this reason, the Scottish Antimicrobial Prescribing Group (SAPG) assessed the clinical efficacy, safety and cost implications associated with switching from flucloxacillin to cefazolin in MSSA bacteraemia. This publication reports findings from the clinical evidence review and economic evaluation.

Method:

A search of databases and grey literature was conducted. The cost-comparison reviewed acquisition costs, administration costs and costs associated with AKI.

Results:

Clinical efficacy: Cefazolin was found to be non-inferior when compared to flucloxacillin or cloxacillin for all-cause mortality at 90 days, therapeutic success and survival at day 90.

Adverse events: Patients treated with cefazolin reported fewer serious adverse events and lower AKI rates compared to flucloxacillin or cloxacillin.

Cost comparisons: Economic evaluation showed that switching from flucloxacillin to cefazolin will increase the net medicines cost in patients with MSSA bacteraemia when compared with flucloxacillin. However, when considering the cost of administration and AKIs, cefazolin is expected to result in cost savings.

Recommendation:

SAPG Committee endorsed cefazolin as first-line antibiotic in the treatment of adults with MSSA bacteraemia.

SAPG Staphylococcus aureus bacteraemia (SAB) quality of care indicators to be updated to reflect change.

The full report is now available to read: Evidence and economic review: Comparison of flucloxacillin and cefazolin in methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia.