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Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial Activity
The empirical combination of both a beta-lactam and glycopeptide to counter potential staphylococcal pathogens may improve the clinical outcomes for cases of Staphylococcus aureus bacteremia. We reported comparative in vitro studies of combination effects of different cephalosporins (i.e., cefazolin...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435797/ https://www.ncbi.nlm.nih.gov/pubmed/28572795 http://dx.doi.org/10.3389/fmicb.2017.00884 |
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author | Tang, Hung-Jen Lai, Chih-Cheng Chen, Chi-Chung Zhang, Chun-Cheng Weng, Tzu-Chieh Yu, Wen-Liang Chen, Hung-Jui Chiu, Yu-Hsin Ko, Wen-Chien Chuang, Yin-Ching |
author_facet | Tang, Hung-Jen Lai, Chih-Cheng Chen, Chi-Chung Zhang, Chun-Cheng Weng, Tzu-Chieh Yu, Wen-Liang Chen, Hung-Jui Chiu, Yu-Hsin Ko, Wen-Chien Chuang, Yin-Ching |
author_sort | Tang, Hung-Jen |
collection | PubMed |
description | The empirical combination of both a beta-lactam and glycopeptide to counter potential staphylococcal pathogens may improve the clinical outcomes for cases of Staphylococcus aureus bacteremia. We reported comparative in vitro studies of combination effects of different cephalosporins (i.e., cefazolin, cefmetazole, cefotaxime, and cefepime) combined with glycopeptides for 34 randomly selected methicillin-resistant S. aureus (MRSA) isolates by three methods, including the checkerboard, time-killing, and combination MIC measurement methods. Thirteen SCCmec type III isolates with a cefazolin MIC of ≥ 128 μg/mL were classified as the high-cefazolin MIC (HCM) group, whereas 13 SCCmec type IV and 8 SCCmec type V isolates were classified as the low-cefazolin MIC (LCM) group. With the checkerboard method, synergism was present for vancomycin-based combinations at 30.8–69.2 and 13.6–66.7%, as well as teicoplanin-based combinations of 38.5–84.6 and 0–47.6%, of the HCM and LCM isolates, respectively. No antagonism was noted. The in vitro inhibitory activity was evident even at a low concentration of 1/512x MIC of cephalosporin combined with sub-inhibitory concentrations (1/2x MIC) of a glycopeptide. With time-killing assays, synergism was noted at 1/2x or 1x susceptible breakpoint concentrations (SBCs) of a cephalosporin combined with 1/4 or 1/2 MIC of a glycopeptide. In the presence of 1/2 SBC of a cephalosporin, vancomycin or teicoplanin MICs decreased an average of 2.0- to 6.6- or 1.6- to 5.5-fold, respectively. With 8 μg/mL cephalosporin, the decline of glycopeptide MICs was most obvious in the presence of cefmetazole. In conclusion, cephalosporin-glycopeptide combinations at clinically achievable concentrations can exhibit in vitro synergistic antibacterial activity against clinical MRSA isolates. Such combinations require more clinical data to support their application for use in human MRSA infections. |
format | Online Article Text |
id | pubmed-5435797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54357972017-06-01 Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial Activity Tang, Hung-Jen Lai, Chih-Cheng Chen, Chi-Chung Zhang, Chun-Cheng Weng, Tzu-Chieh Yu, Wen-Liang Chen, Hung-Jui Chiu, Yu-Hsin Ko, Wen-Chien Chuang, Yin-Ching Front Microbiol Microbiology The empirical combination of both a beta-lactam and glycopeptide to counter potential staphylococcal pathogens may improve the clinical outcomes for cases of Staphylococcus aureus bacteremia. We reported comparative in vitro studies of combination effects of different cephalosporins (i.e., cefazolin, cefmetazole, cefotaxime, and cefepime) combined with glycopeptides for 34 randomly selected methicillin-resistant S. aureus (MRSA) isolates by three methods, including the checkerboard, time-killing, and combination MIC measurement methods. Thirteen SCCmec type III isolates with a cefazolin MIC of ≥ 128 μg/mL were classified as the high-cefazolin MIC (HCM) group, whereas 13 SCCmec type IV and 8 SCCmec type V isolates were classified as the low-cefazolin MIC (LCM) group. With the checkerboard method, synergism was present for vancomycin-based combinations at 30.8–69.2 and 13.6–66.7%, as well as teicoplanin-based combinations of 38.5–84.6 and 0–47.6%, of the HCM and LCM isolates, respectively. No antagonism was noted. The in vitro inhibitory activity was evident even at a low concentration of 1/512x MIC of cephalosporin combined with sub-inhibitory concentrations (1/2x MIC) of a glycopeptide. With time-killing assays, synergism was noted at 1/2x or 1x susceptible breakpoint concentrations (SBCs) of a cephalosporin combined with 1/4 or 1/2 MIC of a glycopeptide. In the presence of 1/2 SBC of a cephalosporin, vancomycin or teicoplanin MICs decreased an average of 2.0- to 6.6- or 1.6- to 5.5-fold, respectively. With 8 μg/mL cephalosporin, the decline of glycopeptide MICs was most obvious in the presence of cefmetazole. In conclusion, cephalosporin-glycopeptide combinations at clinically achievable concentrations can exhibit in vitro synergistic antibacterial activity against clinical MRSA isolates. Such combinations require more clinical data to support their application for use in human MRSA infections. Frontiers Media S.A. 2017-05-18 /pmc/articles/PMC5435797/ /pubmed/28572795 http://dx.doi.org/10.3389/fmicb.2017.00884 Text en Copyright © 2017 Tang, Lai, Chen, Zhang, Weng, Yu, Chen, Chiu, Ko and Chuang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Tang, Hung-Jen Lai, Chih-Cheng Chen, Chi-Chung Zhang, Chun-Cheng Weng, Tzu-Chieh Yu, Wen-Liang Chen, Hung-Jui Chiu, Yu-Hsin Ko, Wen-Chien Chuang, Yin-Ching Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial Activity |
title | Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial Activity |
title_full | Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial Activity |
title_fullStr | Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial Activity |
title_full_unstemmed | Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial Activity |
title_short | Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial Activity |
title_sort | cephalosporin-glycopeptide combinations for use against clinical methicillin-resistant staphylococcus aureus isolates: enhanced in vitro antibacterial activity |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435797/ https://www.ncbi.nlm.nih.gov/pubmed/28572795 http://dx.doi.org/10.3389/fmicb.2017.00884 |
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