Impact of the Combination of Daptomycin and Trimethoprim-Sulfamethoxazole on Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Infections

Complicated Staphylococcus aureus infections, including bacteremia, are often associated with treatment failures, prolonged hospital stays, and the emergence of resistance to primary and even secondary therapies. Daptomycin is commonly used as salvage therapy after vancomycin failure for the treatment of methicillin-resistant S. aureus (MRSA) infections. Unfortunately, the emergence of daptomycin resistance, especially in deep-seated infections, has been reported, prompting the need for alternative or combination therapy. Numerous antibiotic combinations with daptomycin have been investigated clinically and in vitro. Of interest, the combination of daptomycin and trimethoprim-sulfamethoxazole (TMP-SMX) has proved to be rapidly bactericidal in vitro to strains that are both susceptible and nonsusceptible to daptomycin. However, to date, there is limited clinical evidence supporting the use of this combination. This was a multicenter, retrospective case series of patients treated with the combination of daptomycin and TMP-SMX for at least 72 h. The objective of this study was to describe the safety and effectiveness of this regimen in clinical practice. The most commonly stated reason that TMP-SMX was added to daptomycin was persistent bacteremia and/or progressive signs and symptoms of infection. After the initiation of combination therapy, the median time to clearance of bacteremia was 2.5 days. Microbiological eradication was demonstrated in 24 out of 28 patients, and in vitro synergy was demonstrated in 17 of the 17 recovered isolates. Further research with this combination is necessary to describe the optimal role and its impact on patient outcomes.