Antimicrobial activity of gentamicin in experimental enterococcal endocarditis

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Gentamicin resistance in Streptococcus faecalis can complicate treatment.
• In vitro assays may not fully predict in vivo antibiotic efficacy.

Purpose of the Study:

• To compare the in vitro activity of gentamicin with its therapeutic efficacy in a rabbit model of Streptococcus faecalis endocarditis.
• To investigate the influence of serum on gentamicin's anti-enterococcal activity.

Main Methods:

• Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined in Mueller-Hinton broth with and without rabbit serum.
• Time-kill studies were performed to assess gentamicin's activity.
• Experimental endocarditis was induced in rabbits and treated with gentamicin or ampicillin.

Main Results:

• The test strain of Streptococcus faecalis was resistant to gentamicin in vitro based on MICs and MBCs.
• Gentamicin showed limited activity in broth-based time-kill studies without serum.
• Supplementation with rabbit serum enhanced gentamicin's in vitro activity.
• In vivo, gentamicin alone demonstrated significant anti-enterococcal activity in experimental endocarditis, comparable to ampicillin.
• Vegetation titers were significantly reduced in gentamicin-treated rabbits compared to controls.

Conclusions:

• Gentamicin exhibits in vivo anti-enterococcal activity against Streptococcus faecalis endocarditis, even when the organism displays in vitro resistance.
• Serum factors can enhance gentamicin's efficacy.
• In vitro susceptibility testing may not always correlate with therapeutic outcomes in complex infections like endocarditis.