Effectiveness of penicillin, dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia: a retrospective, propensity-score-adjusted case-control and cohort analysis

Abstract

Objectives: Penicillin-susceptible Staphylococcus aureus isolates account for a fifth of cases of S. aureus bacteraemia (SAB) in Denmark, but little is known about treatment outcomes with penicillins or other antimicrobials. Here we compare penicillin, dicloxacillin and cefuroxime as definitive treatments in relation to 30 day mortality.

Methods: A retrospective chart review of 588 penicillin-susceptible S. aureus cases at five centres from January 1995 to December 2010. Data on demographics, antimicrobial treatment, clinical signs and symptoms, and mortality at day 30 were collected. Hazard ratios (HRs) with 95% CIs associated with mortality were modelled using propensity-score-adjusted Cox proportional hazards regression analysis. Propensity-score-matched case-control studies were carried out.

Results: Definitive therapy with cefuroxime was associated with an increased risk of 30 day mortality compared with penicillin (adjusted HR 2.54, 95% CI 1.49-4.32). Other variables that were statistically significantly associated with 30 day mortality included increasing age, disease severity and a primary respiratory focus. Osteomyelitis/arthritis was associated with a lower risk of death than were other secondary manifestations. Propensity-score-matched case-control studies confirmed an increased risk of 30 day mortality: cefuroxime treatment (39%) versus penicillin treatment (20%), P = 0.037; and cefuroxime treatment (38%) versus dicloxacillin treatment (10%), P = 0.004.

Conclusions: Definitive therapy for penicillin-susceptible SAB with cefuroxime was associated with a significantly higher mortality than was seen with therapy with penicillin or dicloxacillin.

Keywords: epidemiology; sepsis; survival analysis.