Antimicrobial activity and interaction of pefloxacin and its principal metabolites

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≥64 µg/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 ≤2 µg/ml when pefloxacin was combined with 2 parts (4 µg/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.