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Bactericidal activity of gentamicin against Enterococcus faecalis in vitro and in vivo
1Institut National de la Santé et de la Recherche Médicale, EMI 9933, Hôpital Bichat-Claude Bernard, Paris, France.
Abstract:
The activity of gentamicin at various concentrations against two strains of Enterococcus faecalis was investigated in vitro and in a rabbit model of aortic endocarditis. In vitro, gentamicin at 0.5 to 4 times the MIC failed to reduce the number of bacteria at 24 h. Rabbit or human serum dramatically increased gentamicin activity, leading to a >/=3-log(10) CFU/ml decrease in bacterial counts when the drug concentration exceeded the MIC. Susceptibility testing in the presence of serum was predictive of in vivo activity, since gentamicin alone significantly reduced the number of surviving bacteria in the vegetations if the peak-to-MIC ratio was greater than 1. However, gentamicin selected resistant mutants in rabbits. The intrinsic activity of gentamicin should be taken into account in evaluation of combinations of gentamicin and cell wall-active agents against enterococci.
Insights
Gentamicin alone showed limited activity against Enterococcus faecalis infections in rabbits. However, its effectiveness significantly improved in the presence of serum, though resistant strains emerged.
Area of Science:
- Pharmacology and Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Enterococcus faecalis is a significant cause of healthcare-associated infections, particularly endocarditis.
- Gentamicin is an aminoglycoside antibiotic often used in combination therapy for enterococcal infections.
- Understanding gentamicin's intrinsic activity and factors influencing its efficacy is crucial for optimizing treatment strategies.
Purpose of the Study:
- To evaluate the in vitro and in vivo activity of gentamicin against Enterococcus faecalis.
- To investigate the impact of serum on gentamicin's efficacy.
- To assess the predictive value of susceptibility testing in serum for in vivo outcomes and the emergence of resistance.
Main Methods:
- In vitro testing of gentamicin against two Enterococcus faecalis strains at various concentrations relative to the Minimum Inhibitory Concentration (MIC).
- In vivo study using a rabbit model of aortic endocarditis.
- Assessment of bacterial counts in vegetations and susceptibility testing in the presence of rabbit or human serum.
Main Results:
- In vitro, gentamicin alone (0.5-4x MIC) did not reduce bacterial numbers at 24 hours.
- Presence of rabbit or human serum significantly enhanced gentamicin activity, achieving a >/=3-log(10) CFU/ml decrease when drug concentration exceeded MIC.
- Gentamicin alone significantly reduced bacteria in vivo if the peak-to-MIC ratio was >1, but selected for resistant mutants in rabbits.
Conclusions:
- Serum dramatically potentiates gentamicin activity against Enterococcus faecalis, making serum-based susceptibility testing a valuable predictor of in vivo efficacy.
- Despite its enhanced activity in serum, gentamicin monotherapy can lead to the development of resistant strains in vivo.
- The intrinsic activity of gentamicin must be considered when evaluating combination therapies with cell wall-active agents for enterococcal infections.