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Antimicrobial activity and interaction of pefloxacin and its principal metabolites. Collaborative Antimicrobial
1Clinical Microbiology Institute, Tualatin, Oregon 97062.
Abstract:
The in vitro antimicrobial activity of pefloxacin and its major metabolites was determined and the interaction of pefloxacin and N-demethyl pefloxacin (norfloxacin) assessed at the ratio naturally occurring in urine (1:2). Pefloxacin and N-demethyl pefloxacin had approximately the same spectrum but were markedly more active than N-oxide pefloxacin (MIC90s greater than or equal to 64 micrograms/ml) against 867 stock strains. When combined with N-demethyl pefloxacin, pefloxacin had greater potency and a broader spectrum in tests against 5869 fresh clinical organisms. For approximately 10% more strains pefloxacin MICs were less than or equal to 2 micrograms/ml when pefloxacin was combined with 2 parts (4 micrograms/ml) of N-demethyl pefloxacin. The most significant extension of the pefloxacin spectrum was to include non-enteric gram-negative bacilli (inhibition of 67% versus 88%) and enterococci-streptococci (inhibition of 33% versus 86%). These results are similar to those previously noted for enoxacin plus 3-oxo-enoxacin, and potentially achievable with other newer fluoro-quinolones undergoing significant metabolism.
Insights
Pefloxacin combined with its metabolite N-demethyl pefloxacin (norfloxacin) showed enhanced antimicrobial activity and a broader spectrum against clinical bacteria. This combination therapy may improve treatment outcomes for infections caused by resistant pathogens.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Pefloxacin is a fluoroquinolone antibiotic.
- Its major metabolites include N-demethyl pefloxacin (norfloxacin) and N-oxide pefloxacin.
- The interaction of pefloxacin and its metabolites in antimicrobial activity is not fully understood.
Purpose of the Study:
- To determine the in vitro antimicrobial activity of pefloxacin and its major metabolites.
- To assess the interaction between pefloxacin and N-demethyl pefloxacin (norfloxacin) at a clinically relevant ratio.
- To evaluate the potential for synergistic or additive effects in combination therapy.
Main Methods:
- In vitro antimicrobial susceptibility testing was performed.
- Pefloxacin, N-demethyl pefloxacin, and N-oxide pefloxacin were tested individually and in combination.
- Minimum inhibitory concentrations (MICs) were determined against stock strains and fresh clinical isolates.
- The ratio of pefloxacin to N-demethyl pefloxacin mimicked that found in urine (1:2).
Main Results:
- Pefloxacin and N-demethyl pefloxacin exhibited similar antimicrobial spectra, both more potent than N-oxide pefloxacin.
- Combining pefloxacin with N-demethyl pefloxacin significantly enhanced its potency and broadened its spectrum against clinical organisms.
- The combination therapy led to a notable increase in susceptibility for non-enteric gram-negative bacilli and enterococci-streptococci.
Conclusions:
- N-demethyl pefloxacin (norfloxacin) potentiates the antimicrobial activity of pefloxacin.
- Combination therapy with pefloxacin and N-demethyl pefloxacin offers a broader spectrum of activity compared to pefloxacin alone.
- These findings suggest potential therapeutic benefits for fluoroquinolone combination therapies involving active metabolites.