title: Reduced glycopeptide and lipopeptide susceptibility in Staphylococcus aureus and the "seesaw effect": Taking advantage of the back door left open?
abstract: 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.
authors.affiliation: Detroit Receiving Hospital, Detroit Medical Center, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Ortwine
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Werth
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D006020:Glycopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D046915:Penicillin-Binding Proteins / Q000235:genetics / Q000378:metabolism; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D020713:Vancomycin Resistance; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006020:Glycopeptides; D055666:Lipopeptides; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; C478699:penicillin-binding protein 2a, Streptococcus; D010453:Peptide Synthases; D017576:Daptomycin
keywords: Combination therapy; Daptomycin nonsusceptible; MRSA; Seesaw effect; hVISA/VISA/VRSA