Limitations of antibiotic options for invasive infections caused by methicillin-resistant Staphylococcus aureus: is combination therapy the answer?

Invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA), particularly those involving persistent bacteraemia, necrotizing pneumonia, osteomyelitis and other deep-seated sites of infections, are associated with high mortality and are often difficult to treat. The response to treatment of severe MRSA infection with currently available antibiotics active against MRSA is often unsatisfactory, leading some physicians to resort to combination antibiotic therapy. Now, with the emergence of community-associated MRSA (CA-MRSA) clones that display enhanced virulence potentially related to up-regulated toxin production, the use of adjuvant protein synthesis-inhibiting antibiotics to reduce toxin production also has been advocated by some experts. In this review, we discuss the limitations of antibiotics currently available for the treatment of serious invasive MRSA infections and review the existing literature that examines the potential role of combination therapy in these infections.