title: Effects of vancomycin versus nafcillin in enhancing killing of methicillin-susceptible Staphylococcus aureus causing bacteremia by human cathelicidin LL-37.
abstract: Recent studies have demonstrated that anti-staphylococcal beta-lactam antibiotics, like nafcillin, render methicillin-resistant Staphylococcus aureus (MRSA) more susceptible to killing by innate host defense peptides (HDPs), such as cathelicidin LL-37. We compared the effects of growth in 1/4 minimum inhibitory concentration (MIC) of nafcillin or vancomycin on the LL-37 killing of 92 methicillin-susceptible S. aureus (MSSA) isolates. For three randomly selected strains among these, we examined the effects of nafcillin, vancomycin, daptomycin, or linezolid on LL-37 killing and autolysis. Growth in the presence of subinhibitory nafcillin significantly enhanced LL-37 killing of MSSA compared to vancomycin and antibiotic-free controls. Nafcillin also reduced MSSA production of the golden staphylococcal pigment staphyloxanthin in 39 % of pigmented strains vs. 14 % for vancomycin. Among the antibiotics tested, only nafcillin resulted in significantly increased MSSA autolysis. These studies point to additional mechanisms of anti-staphylococcal activity of nafcillin beyond direct bactericidal activity, properties that vancomycin and other antibiotic classes do not exhibit. The ability of nafcillin to enhance sensitivity to innate HDPs may contribute to its superior effectiveness against MSSA, as suggested by studies comparing clinical outcomes to vancomycin treatment.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, MC 0714, La Jolla, CA, 92093-0714, USA. jenle@ucsd.edu.
authors.forename: J
authors.initials: J
authors.lastname: Le
authors.affiliation: University of California San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Dam
authors.affiliation: Iowa City VA Health Care System, Iowa City, IA, USA.|University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Schweizer
authors.affiliation: University of California San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Thienphrapa
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, MC 0714, La Jolla, CA, 92093-0714, USA.|University of California San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Nizet
authors.affiliation: University of California San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Sakoulas
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology*; D001433:Bacteriolysis / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D009254:Nafcillin / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D014640:Vancomycin / Q000494:pharmacology*; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D009254:Nafcillin; D014640:Vancomycin; D054804:Cathelicidins