Although Markowitz et al165 showed that trimethoprim- sulfamethoxazole was inferior to vancomycin in the treat- ment of invasive S aureus infections, it is sometimes used in salvage situations. Interestingly, all treatment failures with trimethoprim-sulfamethoxazole occurred in patients infected with MSSA in that report,165 whereas patients with MRSA infection were uniformly cured. The efficacy of trimethoprim- sulfamethoxazole and other folate antagonists may be attenu- ated by thymidine release from damaged host cells (eg, at sites of tissue damage such as abscesses).166 In an in vitro study,167 the addition of trimethoprim-sulfamethoxazole to daptomy- cin was rapidly bactericidal for a daptomycin-nonsusceptible strain compared with daptomycin monotherapy. The com- bination of daptomycin and a -lactam antibiotic has been reported to be effective in treating a limited number of patients with persistent MRSA bacteremia.168 The potential effective- ness of this combination may be due in part to the capacity of the -lactam agent to alter the surface charge of the organism in a nonbactericidal mechanism, allowing enhanced surface binding of daptomycin.169 171 Linezolid was reported to be effective in the treatment of persistent MRSA bacteremia,172 but this study had important study design weaknesses.173 Patient outcomes with linezolid therapy for S aureus left-sided IE have generally been poor.174 176 have been used successfully as salvage ther- apy in selected patients with MRSA IE who clinically failed vancomycin therapy. Ceftaroline received FDA registrational indications for acute bacterial skin and soft tissue infections caused by both MRSA and MSSA, as well as community-acquired pneu- monia caused by MSSA. Several case series suggest that it may have utility in complicated S aureus infections, including These promising observations should be verified with appropriately designed clinical studies before ceftaroline can be recommended for widespread use in such off-label settings. Recommendations 1. 