Reduced glycopeptide and lipopeptide susceptibility in Staphylococcus aureus and the “seesaw effect”: Taking advantage of the back door left open?

Methicillin-resistant S. aureus (MRSA) constitutes approximately 50% of clinical S. aureus isolates and is most commonly the result of production of a mutated pencillin-binding protein, PBP2a, which is able to carry out essential cell wall synthesis functions while maintaining a low-affinity for nearly all beta-lactam antibiotics. Decreased susceptibility to glycopeptides, typically considered first-line MRSA agents, has also been documented. Interestingly, among MRSA isolates, an increase in beta-lactam susceptibility has been documented in the presence of declining lipo- and glycopeptide susceptibility. This phenomenon, termed the “seesaw effect” has been documented both in vitro and in vivo. In the era of increasing antimicrobial resistance and few new drugs to treat these organisms, this phenomenon may provide novel ways to use our current antimicrobials in a new, and more effective, manner.