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...
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| Format: | Article |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2017.00884/full |
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| author | Hung-Jen Tang Hung-Jen Tang Chih-Cheng Lai Chi-Chung Chen Chun-Cheng Zhang Tzu-Chieh Weng Wen-Liang Yu Wen-Liang Yu Hung-Jui Chen Yu-Hsin Chiu Wen-Chien Ko Wen-Chien Ko Yin-Ching Chuang Yin-Ching Chuang |
| author_facet | Hung-Jen Tang Hung-Jen Tang Chih-Cheng Lai Chi-Chung Chen Chun-Cheng Zhang Tzu-Chieh Weng Wen-Liang Yu Wen-Liang Yu Hung-Jui Chen Yu-Hsin Chiu Wen-Chien Ko Wen-Chien Ko Yin-Ching Chuang Yin-Ching Chuang |
| author_sort | Hung-Jen Tang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T19:59:41Z |
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| id | doaj.art-e5145037b2fa46f6a081e01c265d334d |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-12T19:59:41Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-e5145037b2fa46f6a081e01c265d334d2022-12-22T00:13:47ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-05-01810.3389/fmicb.2017.00884234078Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial ActivityHung-Jen Tang0Hung-Jen Tang1Chih-Cheng Lai2Chi-Chung Chen3Chun-Cheng Zhang4Tzu-Chieh Weng5Wen-Liang Yu6Wen-Liang Yu7Hung-Jui Chen8Yu-Hsin Chiu9Wen-Chien Ko10Wen-Chien Ko11Yin-Ching Chuang12Yin-Ching Chuang13Department of Medicine, Chi Mei Medical CenterTainan, TaiwanDepartment of Health and Nutrition, Chia Nan University of Pharmacy and ScienceTainan, TaiwanDepartment of Intensive Care Medicine, Chi Mei Hospital—Liou YingTainan, TaiwanMedical Research, Chi Mei Medical CenterTainan, TaiwanDepartment of Medicine, Chi Mei Medical CenterTainan, TaiwanDepartment of Medicine, Chi Mei Medical CenterTainan, TaiwanDepartment of Medicine, Chi Mei Medical CenterTainan, TaiwanMedical Research, Chi Mei Medical CenterTainan, TaiwanDepartment of Medicine, Chi Mei Medical CenterTainan, TaiwanMedicine, Chi Mei Hospital—Liou YingTainan, TaiwanDepartment of Internal Medicine and Center of Infection Control, National Cheng Kung University HospitalTainan, TaiwanDepartment of Medicine, College of Medicine, National Cheng Kung UniversityTainan, TaiwanDepartment of Health and Nutrition, Chia Nan University of Pharmacy and ScienceTainan, TaiwanMedicine, Chi Mei Hospital—Liou YingTainan, TaiwanThe 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.http://journal.frontiersin.org/article/10.3389/fmicb.2017.00884/fullglycopeptidescefazolincefmetazolecefotaximecefepimecombination therapy |
| spellingShingle | Hung-Jen Tang Hung-Jen Tang Chih-Cheng Lai Chi-Chung Chen Chun-Cheng Zhang Tzu-Chieh Weng Wen-Liang Yu Wen-Liang Yu Hung-Jui Chen Yu-Hsin Chiu Wen-Chien Ko Wen-Chien Ko Yin-Ching Chuang Yin-Ching Chuang Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Staphylococcus aureus Isolates: Enhanced In vitro Antibacterial Activity Frontiers in Microbiology glycopeptides cefazolin cefmetazole cefotaxime cefepime combination therapy |
| 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 | glycopeptides cefazolin cefmetazole cefotaxime cefepime combination therapy |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2017.00884/full |
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