Evolution of Staphylococcus aureus under vancomycin selective pressure: the role of the small-colony variant phenotype - PubMed (original) (raw)

Evolution of Staphylococcus aureus under vancomycin selective pressure: the role of the small-colony variant phenotype

Justin R Lenhard et al. Antimicrob Agents Chemother. 2015 Feb.

Abstract

Staphylococcus aureus small-colony variants (SCVs) often persist despite antibiotic therapy. Against a 10(8)-CFU/ml methicillin-resistant S. aureus (MRSA) (strain COL) population of which 0%, 1%, 10%, 50%, or 100% was an isogenic hemB knockout (Ia48) subpopulation displaying the SCV phenotype, vancomycin achieved maximal reductions of 4.99, 5.39, 4.50, 3.28, and 1.66 log10 CFU/ml over 48 h. Vancomycin at ≥16 mg/liter shifted a population from 50% SCV cells at 0 h to 100% SCV cells at 48 h, which was well characterized by a Hill-type model (R2>0.90).

Copyright © 2015, American Society for Microbiology. All Rights Reserved.

PubMed Disclaimer

Figures

FIG 1

FIG 1

Vancomycin time-kill experiments involving exclusively strains of the NP at an inoculum of 0% SCV/100% NP cells (A) and exclusively strains of the SCV phenotype at an inoculum of 100% SCV/0% NP cells (B), as well as three mixed-population experiments consisting of 1% SCV/99% NP (C), 10% SCV/90% NP (D), and 50% SCV/50% NP (E) cell inoculums. The pharmacodynamic relationship between log ratio area and vancomycin concentration are also displayed for 0% SCV/100% NP (F), 100% SCV/0% NP (G), 1% SCV/99% NP (H), 10% SCV/90% NP (I), and 50% SCV/50% NP (J) cells. _R_2, _E_max, and EC50s are listed next to the corresponding Hill plots (percent standard errors are listed parenthetically).

FIG 2

FIG 2

Colony counts used to track SCV subpopulations. In mixed-culture experiments, samples were plated on plain BHI agar as well as BHI containing 2.0 mg/liter gentamicin. Gentamicin plates permitted only the growth of SCVs, and the corresponding CFU plots derived from the drug plates are displayed for 1% SCV/99% NP (A), 10% SCV/90% NP (B), and 50% SCV/50% NP (C) cell inoculums. Additionally, the maximum percentages of the SCV detected over 48 h for each vancomycin concentration are plotted and fit to a Hill-type function for 1% SCV/99% NP (D), 10% SCV/90% NP (E), and 50% SCV/50% NP (F) cell inoculums.

Similar articles

Cited by

References

    1. Hiramatsu K. 1998. Vancomycin resistance in staphylococci. Drug Resist Updat 1:135–150. doi:10.1016/S1368-7646(98)80029-0. - DOI - PubMed
    1. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF. 2011. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 52:e18–55. doi:10.1093/cid/ciq146. - DOI - PubMed
    1. Lodise TP, Lomaestro B, Graves J, Drusano GL. 2008. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother 52:1330–1336. doi:10.1128/AAC.01602-07. - DOI - PMC - PubMed
    1. Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A. 2006. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med 166:2138–2144. doi:10.1001/archinte.166.19.2138. - DOI - PubMed
    1. Cui L, Iwamoto A, Lian JQ, Neoh HM, Maruyama T, Horikawa Y, Hiramatsu K. 2006. Novel mechanism of antibiotic resistance originating in vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother 50:428–438. doi:10.1128/AAC.50.2.428-438.2006. - DOI - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources