Ionic binding, adaptive resistance and post-antibiotic effect of netilmicin and ciprofloxacin

Ionic binding, post-antibiotic effect (PAE) and adaptive resistance to netilmicin and ciprofloxacin were investigated in 11 distinct clinical isolates. Both netilmicin and ciprofloxacin showed concentration dependent kill and PAE when bacteria were exposed to these antibiotics at 37 degrees C. The effects of netilmicin were maintained at 4 degrees C, when there is no energy dependent cell uptake of antibiotic, but were partially inhibited by exposure to NaCl and EDTA although not by Ca++. This supports the concept that ionic binding to the bacterial cell wall is important in the initial uptake of netilmicin. Ciprofloxacin showed no such effects at 4 degrees C. Adaptive resistance (reduced bacterial kill on second exposure) occurred with both netilmicin and ciprofloxacin but was seen more frequently with netilmicin. It persisted longer than classical PAE but, even after continuous exposure, was not enough to suggest a loss of kill with a twice daily dosing regimen of netilmicin or ciprofloxacin.