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Antimicrobial susceptibility changes in Enterococcus faecalis following various penicillin exposure regimens
T L Hodges1, S Zighelboim-Daum, G M Eliopoulos
1Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts.
Antimicrobial Agents and Chemotherapy
|January 11, 1992
Summary
Different penicillin exposure methods in vitro can select for Enterococcus faecalis strains with increased resistance or tolerance. Understanding these changes is crucial for optimizing penicillin dosing regimens in treating enterococcal infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Enterococcus faecalis is a common cause of healthcare-associated infections.
- Penicillin is a primary antibiotic for treating enterococcal infections, often used in combination with aminoglycosides.
- Antibiotic resistance and tolerance in E. faecalis pose significant challenges to effective treatment.
Purpose of the Study:
- To investigate how different in vitro penicillin exposure strategies affect the resistance and tolerance of penicillin-naive Enterococcus faecalis strains.
- To identify the mechanisms underlying changes in penicillin susceptibility, including alterations in penicillin-binding proteins.
- To inform the development of optimal penicillin dosing regimens for enterococcal infections.
Main Methods:
- Penicillin-naive Enterococcus faecalis strains were exposed in vitro to penicillin using three regimens: repeated pulses, stepwise increasing concentrations, and sustained single concentrations.
- Changes in penicillin resistance were assessed using Minimum Inhibitory Concentrations (MICs).
- Tolerance to bactericidal effects was evaluated through time-kill studies, and alterations in penicillin-binding proteins were examined in selected clones.
Main Results:
- Repeated penicillin pulses induced tolerance without increasing resistance.
- Stepwise increasing concentrations led to both increased resistance and tolerance.
- Sustained exposure to a fixed concentration resulted in minimal resistance increase but retained a non-tolerant response.
- Acquired tolerance without resistance changes showed no alteration in penicillin-binding protein patterns.
- Increased penicillin resistance, whether tolerant or non-tolerant, correlated with altered penicillin-binding protein labeling.
Conclusions:
- In vitro exposure of Enterococcus faecalis to penicillin, via pulsing, graded, or sustained concentrations, can select for clones with enhanced resistance or tolerance.
- The specific exposure regimen influences the type and extent of resistance and tolerance developed.
- These findings have implications for designing effective penicillin-based treatment strategies for enterococcal infections, particularly when standard synergistic combinations are not achievable.