Comparative synergistic activity of nafcillin, oxacillin, and methicillin in combination with gentamicin against

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Enterococci are significant causes of nosocomial infections.
• Penicillinase-resistant penicillins are used to treat infections caused by penicillinase-producing bacteria.
• Gentamicin is an aminoglycoside antibiotic often used in combination therapy.

Purpose of the Study:

• To evaluate the in vitro effectiveness of nafcillin, oxacillin, and methicillin, alone and in combination with gentamicin, against clinical isolates of enterococci.
• To determine the synergistic potential of these antibiotic combinations against enterococci.

Main Methods:

• Minimal inhibitory concentrations (MICs) were determined for three semisynthetic, penicillinase-resistant penicillins (nafcillin, oxacillin, methicillin) against 29 clinical enterococcal isolates.
• The effectiveness of these penicillins, alone and in combination with gentamicin, was assessed at clinically achievable concentrations.
• Synergy was evaluated using stringent criteria.

Main Results:

• Nafcillin exhibited lower MICs compared to oxacillin and methicillin, but higher than penicillin.
• The combination of nafcillin and gentamicin demonstrated enhanced killing against 13 of 14 strains and synergy against 10 of 14 strains.
• Combinations of oxacillin-gentamicin and methicillin-gentamicin showed significantly less synergy, with only 3 and 1 strains, respectively, exhibiting synergistic killing.

Conclusions:

• Nafcillin, particularly in combination with gentamicin, offers a promising therapeutic option for enterococcal infections.
• The synergistic effect of nafcillin-gentamicin highlights the importance of combination therapy selection in combating enterococcal infections.
• Oxacillin and methicillin in combination with gentamicin are less effective against these enterococcal isolates.