Combination therapy does not decrease 30-day mortality but increases antibiotic consumption in methicillin-sensitive S. aureus bacteraemia.

Purpose: The study aimed to compare the impact of combination and monotherapy on mortality, antibiotic consumption using 'Days of Therapy (DOT)', and antibiotic-related adverse events in patients with methicillin-susceptible S. aureus (MSSA) bacteraemia.

Methods: This retrospective study included all adult patients (>18 years) with MSSA bacteraemia who received either monotherapy (beta-lactam alone) or combination therapy (beta-lactam plus teicoplanin or daptomycin or linezolid) between 2018 and 2023. Mortality, antibiotic consumption, and factors predicting mortality were analysed. Groups were compared for 30-d mortality with survival analysis. Logistic regression models were used to identify risk factors for mortality. Antibiotic consumption was calculated by DOT.

Results: Among 395 patients screened, 185 patients who had an MSSA bacteraemia received either monotherapy (n = 73, 39.5%) or combination therapy (n = 112, 60.5%). The 30-d mortality rate was similar between groups (%15.1 vs. 21.4, P = 0.280). Time to bacterial clearance was also similar (median (IQR): 4 (3-7) vs. 4 (3-7) d, P = 0.699). DOT per 1000 patient days was significantly higher in the combination therapy group than in the monotherapy group (median, IQR: 1420, 827-1836 vs. 933, 732-1000), P < 0.001). The 30-d mortality rate was 18.9% (n = 35/185), and the PITT bacteraemia score was the only independent predictor of mortality (median, IQR: 1506, 1.264-1.794, P < 0.001).

Conclusions: Our findings indicate that combination therapy does not confer a survival benefit over monotherapy in patients with MSSA bacteraemia. However, combination therapy was associated with a significant increase in antibiotic consumption. Therefore, our results do not support the routine use of combination therapy for MSSA bacteraemia in this patient population.