Pharmacodynamic evaluation of the activity of antibiotics against hemin- and menadione-dependent small-colony variants of Staphylococcus aureus in models of extracellular (broth) and intracellular (THP-1 monocytes) infections.

Antimicrobial Agents and Chemotherapy
Laetitia G GarciaFrançoise Van Bambeke

Abstract

Staphylococcus aureus small-colony variants (SCVs) persist intracellularly, which may contribute to persistence/recurrence of infections and antibiotic failure. We have studied the intracellular fate of menD and hemB mutants (corresponding to menadione- and hemin-dependent SCVs, respectively) of the COL methicillin-resistant S. aureus (MRSA) strain and the antibiotic pharmacodynamic profile against extracellular (broth) and intracellular (human THP-1 monocytes) bacteria. Compared to the parental strain, SCVs showed slower extracellular growth (restored upon medium supplementation with menadione or hemin), reduced phagocytosis, and, for the menD SCV, lower intracellular counts at 24 h postinfection. Against extracellular bacteria, daptomycin, gentamicin, rifampin, moxifloxacin, and oritavancin showed similar profiles of activity against all strains, with a static effect obtained at concentrations close to their MICs and complete eradication as maximal effect. In contrast, vancomycin was not bactericidal against SCVs. Against intracellular bacteria, concentration-effect curves fitted sigmoidal regressions for vancomycin, daptomycin, gentamicin, and rifampin (with maximal effects lower than a 2-log decrease in CFU) but biphasic re...Continue Reading

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Citations

Mar 15, 2013·The Journal of Antimicrobial Chemotherapy·Laetitia G GarciaFrançoise Van Bambeke
Jun 1, 2013·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Barbara C Kahl
May 11, 2016·Future Microbiology·Achim J Kaasch, Harald Seifert
Jan 31, 2018·Antimicrobial Agents and Chemotherapy·Evgeny A IdelevichKarsten Becker
Jan 22, 2015·Antimicrobial Agents and Chemotherapy·Florent ValourFrédéric Laurent
Dec 3, 2014·Antimicrobial Agents and Chemotherapy·Justin R LenhardBrian T Tsuji
Mar 11, 2016·Clinical Microbiology Reviews·Barbara C KahlBettina Löffler
Jun 15, 2019·Microbiology Spectrum·Richard Proctor

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