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Synergy study of vancomycin or teicoplanin plus gentamicin against enterococci, Staphylococcus aureus and
1Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Abstract:
We conducted a time-kill study comparing the combination of vancomycin plus gentamicin versus teicoplanin plus gentamicin against 20 clinical isolates each, of enterococci, S. aureus and coagulase-negative staphylococci. The concentrations of vancomycin and teicoplanin were selected so that cultures containing these drugs alone contained 10(3) to 10(6) cfu/ml after 24 hr, mostly 2 to 4 times the MIC for each isolate. In this way we could be certain that synergism or antagonism would not go undetected. One-fourth of the gentamicin MIC for each isolate was used throughout the study. In vitro bactericidal synergy was considered to be present when vancomycin plus gentamicin or teicoplanin plus gentamicin yielded at least a 2 log 10 decline in cfu/ml compared to vancomycin or teicoplanin alone. There was no significant difference between the two antibiotic combinations against these gram-positive cocci. The antibiotic combinations showed synergy against 75 per cent of enterococcal isolates, 70 per cent of S. aureus isolates and 50 per cent of coagulase-negative staphylococcal isolates when measured at 24 hr of incubation. Five (25%) enterococcal strains resistant to the synergistic effect of the antibiotic combinations had gentamicin MICs greater than 64 mg/L. For staphylococcal isolates, no association was found between synergy and gentamicin susceptibility, methicillin resistance, or tolerance to vancomycin or teicoplanin.
Insights
Vancomycin plus gentamicin and teicoplanin plus gentamicin showed similar efficacy against gram-positive cocci. Synergy was observed in most enterococcal and S. aureus isolates, but less frequently in coagulase-negative staphylococci.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Antibiotic resistance is a growing threat, necessitating evaluation of combination therapies.
- Vancomycin and teicoplanin are key antibiotics for treating infections caused by Gram-positive cocci.
- Gentamicin is often used in combination with cell-wall active agents to achieve synergistic killing.
Purpose of the Study:
- To compare the in vitro bactericidal synergy of vancomycin plus gentamicin versus teicoplanin plus gentamicin.
- To evaluate the efficacy of these combinations against clinical isolates of enterococci, Staphylococcus aureus, and coagulase-negative staphylococci.
Main Methods:
- A time-kill study design was employed.
- Bactericidal synergy was defined as a ≥2 log10 decline in colony-forming units (cfu)/mL compared to monotherapy at 24 hours.
- Antibiotic concentrations were set relative to the minimum inhibitory concentration (MIC) for each isolate.
Main Results:
- No significant difference in efficacy was observed between vancomycin-gentamicin and teicoplanin-gentamicin combinations.
- Synergy was demonstrated against 75% of enterococcal, 70% of S. aureus, and 50% of coagulase-negative staphylococcal isolates.
- Enterococcal isolates resistant to synergy had high gentamicin MICs (>64 mg/L).
Conclusions:
- Both vancomycin-gentamicin and teicoplanin-gentamicin combinations are effective against a majority of enterococcal and S. aureus isolates.
- The synergistic effect against staphylococcal isolates was not associated with gentamicin susceptibility, methicillin resistance, or tolerance.
- High gentamicin MICs may predict resistance to synergistic killing in enterococci.