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Comparative in vitro activity of nafcillin, oxacillin, and methicillin in combination with gentamicin and tobramycin
Abstract:
The in vitro activity of nafcillin, oxacillin, and methicillin alone and in combination with gentamicin and tobramycin against 30 strains of enterococci was investigated. The penicillinase-resistant penicillins were less active than penicillin and ampicillin against the enterococci. Nafcillin was more active than oxacillin and methicillin. Sixty-six percent of strains were inhibited by nafcillin at 6.25 mug/ml, but none was inhibited by oxacillin and methicillin at the same concentration. At 12.5 mug/ml, 83, 16, and 0% were inhibited by nafcillin, oxacillin, and methicillin, respectively. By using a variety of criteria and analyses, it was shown that none of the antibiotic combinations studied demonstrated enhanced killing of all strains of enterococci. Nafcillin-gentamicin was the best combination, and enhanced killing was demonstrated against most strains. Oxacillin was more effective than methicillin when combined with gentamicin. Tobramycin was probably less effective than gentamicin in combination with the penicillinase-resistant penicillins against enterococci.
Insights
Penicillinase-resistant penicillins like nafcillin showed limited in vitro activity against enterococci. Nafcillin-gentamicin combination demonstrated enhanced killing against most strains, outperforming other combinations.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Enterococci are significant pathogens, often requiring combination antibiotic therapy.
- Penicillinase-resistant penicillins (PRPs) are typically used for Staphylococcus infections, but their activity against enterococci is less understood.
Purpose of the Study:
- To evaluate the in vitro activity of nafcillin, oxacillin, and methicillin against enterococci.
- To assess the synergistic or additive effects of combining these PRPs with gentamicin or tobramycin.
Main Methods:
- In vitro susceptibility testing of 30 enterococcal strains against nafcillin, oxacillin, and methicillin.
- Evaluation of antibiotic combinations including nafcillin-gentamicin, nafcillin-tobramycin, oxacillin-gentamicin, oxacillin-tobramycin, methicillin-gentamicin, and methicillin-tobramycin.
Main Results:
- Nafcillin demonstrated greater in vitro activity than oxacillin and methicillin against enterococci.
- Sixty-six percent of strains were inhibited by nafcillin at 6.25 µg/ml, while oxacillin and methicillin showed minimal activity.
- The nafcillin-gentamicin combination exhibited enhanced killing against most enterococcal strains, outperforming other PRP-aminoglycoside combinations.
Conclusions:
- Penicillinase-resistant penicillins exhibit limited intrinsic activity against enterococci compared to penicillin or ampicillin.
- Nafcillin-gentamicin is the most effective combination tested for enhanced enterococcal killing in vitro.
- Gentamicin appears more effective than tobramycin in combination with PRPs against enterococci.