Effects of vancomycin versus nafcillin in enhancing killing of methicillin-susceptible Staphylococcus aureus causing bacteremia by human cathelicidin LL-37

J Le; Q Dam; M Schweizer; W Thienphrapa; V Nizet; G Sakoulas

doi:10.1007/s10096-016-2682-0

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Effects of vancomycin versus nafcillin in enhancing killing of methicillin-susceptible Staphylococcus aureus causing bacteremia by human cathelicidin LL-37

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Peer reviewed

Effects of vancomycin versus nafcillin in enhancing killing of methicillin-susceptible Staphylococcus aureus causing bacteremia by human cathelicidin LL-37

J Le, Q Dam, M Schweizer, W Thienphrapa, V Nizet and G Sakoulas

European journal of clinical microbiology & infectious diseases, Vol.35(9), pp.1441-1447

09/2016

DOI: 10.1007/s10096-016-2682-0

PMCID: PMC4983239

PMID: 27234592

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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.

Bacteriolysis - drug effects

Microbial Viability - drug effects

Staphylococcus aureus - isolation & purification

Staphylococcus aureus - physiology

Humans

Antimicrobial Cationic Peptides - pharmacology

Bacteremia - microbiology

Microbial Sensitivity Tests

Drug Interactions

Vancomycin - pharmacology

Anti-Bacterial Agents - pharmacology

Staphylococcal Infections - microbiology

Staphylococcus aureus - drug effects

Nafcillin - pharmacology

Details

Title: Subtitle: Effects of vancomycin versus nafcillin in enhancing killing of methicillin-susceptible Staphylococcus aureus causing bacteremia by human cathelicidin LL-37
Creators: J Le - 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
Q Dam - University of California San Diego School of Medicine, La Jolla, CA, USA
M Schweizer - University of Iowa Carver College of Medicine, Iowa City, IA, USA
W Thienphrapa - University of California San Diego School of Medicine, La Jolla, CA, USA
V Nizet - University of California San Diego School of Medicine, La Jolla, CA, USA
G Sakoulas - University of California San Diego School of Medicine, La Jolla, CA, USA
Resource Type: Journal article
Publication Details: European journal of clinical microbiology & infectious diseases, Vol.35(9), pp.1441-1447
DOI: 10.1007/s10096-016-2682-0
PMID: 27234592
PMCID: PMC4983239
NLM abbreviation: Eur J Clin Microbiol Infect Dis
ISSN: 0934-9723
eISSN: 1435-4373
Grant note: R37 AI052453 / NIAID NIH HHS K23 AI089978 / NIAID NIH HHS P50 HD090259 / NICHD NIH HHS U54 AI057153 / NIAID NIH HHS U54 HD071600 / NICHD NIH HHS
Language: English
Date published: 09/2016
Academic Unit: Epidemiology; General Internal Medicine; Internal Medicine
Record Identifier: 9984094329902771

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