Lomefloxacin-induced modification of the kinetics of growth of Gram-negative bacteria and susceptibility to phagocytic killing by human neutrophils

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Abstract
The post-antibiotic effect (PAE) of lomefloxacin against Escherichia coli and Pseudomonas aeruginosa was determined and compared with various other antibiotics. All the quinolones tested, and chloramphenicol and gentamicin, possessed PAE activity. At 10 × MIC and 30min exposure, the PAEs against E. coli were 1·6, 1·3, and 1·8 h for lomefloxacin, ciprofloxacin and norfloxacin respectively, and for P. aeruginosa the equivalent PAEs were 1·1, 1 and 0·5 h. The lomefloxacin PAE was dose-dependent and exposure for 5min was sufficient to give optimal PAE at high concentrations of lomefloxacin. Such brief exposure rapidly blocked bacterial nucleic acid biosynthesis. Lomefloxacin pretreated bacteria were more susceptible to killing by PMN than untreated bacteria. Optimum enhancement of phagocytic killing of E. coli occurred when exposure to lomefloxacin was associated with an 80% decrease in cfu during pretreatment. Maximum PMN activity against P. aeruginosa occurred when bacteria were exposed to lomefloxacin producing change in cfu of + 0·2 log10 to –0·7 log10. These results indicate that phenotypic changes of P. aeruginosa and E. coli exposed to lomefloxacin render the bacteria more susceptible to phagocytic killing.

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