Different aminoglycoside-resistant phenotypes in a rabbit Staphylococcus aureus endocarditis infection model

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Aminoglycosides are crucial antibiotics for bacterial infections.
• Enzymatic resistance can limit the efficacy of aminoglycosides.
• Staphylococcus aureus infections pose a significant clinical challenge.

Purpose of the Study:

• To evaluate the in vivo antibacterial activity of amikacin, gentamicin, and netilmicin against Staphylococcus aureus strains with varying enzymatic resistance.
• To determine the clinical relevance of enzymatic resistance in predicting aminoglycoside efficacy.
• To identify the most effective aminoglycoside for treating staphylococcal infections in a relevant animal model.

Main Methods:

• Utilized a rabbit endocarditis model to simulate Staphylococcus aureus infections.
• Administered amikacin, gentamicin, and netilmicin to mimic human dosing regimens (single daily dose).
• Tested four strains of Staphylococcus aureus, including kanamycin-resistant variants, assessing in vivo activity.

Main Results:

• Amikacin demonstrated no efficacy against three kanamycin-resistant Staphylococcus aureus strains, despite in vitro susceptibility.
• Gentamicin exhibited significant antibacterial activity in the endocarditis model.
• Netilmicin's efficacy was not explicitly detailed but implied to be less favorable than gentamicin.

Conclusions:

• Enzymatic resistance mechanisms, particularly those conferring kanamycin resistance, significantly compromise amikacin's in vivo activity.
• Gentamicin is identified as a potentially preferable aminoglycoside for treating Staphylococcus aureus infections, even in the presence of certain resistance mechanisms.
• Disk diffusion tests may not accurately predict in vivo aminoglycoside efficacy in the context of specific enzymatic resistance profiles.