The treatment of resistant staphylococcal infections

Abstract

Staphylococcus aureus of the many staphylococcal species is the most common cause of both skin and soft tissue infection and severe staphylococcal infections including Staphylococcus aureus bacteremia (SAB). Many antibiotics are active against the staphylococci, yet over the last 40 years antibiotic resistance, particularly resistance to beta-lactam antibiotics, has plagued antimicrobial therapy. The term “methicillin resistance” is a historic term and now refers to the ability of staphylococci, in particular methicillin-resistant Staphylococcus aureus (MRSA), to resist the action of beta-lactam antibiotics. This resistance is encoded by the mecA gene carried in a complex genetic cassette, SCCmec. Vancomycin and old antibiotics remain the keystone of treatment for resistant staphylococci. Other newer agents, and some older agents, show good activity against resistant staphylococci which are the focus of this review: trimethoprim-sulfamethoxazole, ceftaroline, daptomycin, fosfomycin, linezolid, dalbavancin, televancin, and omadacycline. Other agents with novel mechanisms of action are under development, for use as single anti-staphylococcal agents or for combination use to augment the action of the primary anti-staphylococcal agent. Vancomycin therapy carries specific risks, particularly renal dysfunction, but despite its foibles, vancomycin remains the standard of care for the treatment of resistant staphylococcal infections. Some clinicians implement an early switch from vancomycin at the earliest signs of renal dysfunction. The near horizon holds promise also of augmentation of both cellular and humoral responses to staphylococcal infection. Pending newer clinical trials that show clear superiority of one anti-staphylococcal agent over another or over vancomycin, it will remain to expert clinical judgment in determining antibiotic choice and duration of anti-staphylococcal therapy.