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Bacteremia caused by  Staphylococcus aureus  is common. Cases caused by methicillin-resistant  S. aureus  (MRSA) are particularly formidable and often lethal. The mortality associated with MRSA bacteremia has not significantly decreased over the past couple of decades and concerns regarding efficacy and toxicity of standard therapy highlight the need for novel agents and new therapeutic approaches. This paper explores clinical trials investigating novel therapeutic approaches to  S. aureus  bacteremia. There is a special focus on MRSA bacteremia. Monotherapy and combination therapies and novel antimicrobials and adjunctive therapies that are only recently being established for therapeutic use are discussed. The unfavorable safety profile of combination antimicrobial therapy in clinical trials has outweighed its benefits. Therefore, future investigation should focus on optimizing duration and de-escalation protocols. Antibody and bacteriophage lysin-based candidates have mostly been limited to safety trials, but progress with these agents is demonstrated through a lysin-based agent receiving a phase III trial. Antibiotics indicated for use in treating MRSA skin infections see continued investigation as treatments for MRSA bacteremia despite the difficulty of completing trials in this patient population. Promising agents include dalbavancin, ceftobiprole, ceftaroline, and exebacase.

Investigational agents for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia: progress in clinical trials