Efficacy of ciprofloxacin in stationary-phase bacteria in vivo

The granuloma pouch model in mice infected with Escherichia coli or Pseudomonas aeruginosa was used to investigate the bactericidal effect of ciprofloxacin in vivo on bacteria in the stationary growth phase. Ciprofloxacin caused a rapid decline in the number of colony-forming units (cfu) of E. coli shortly after initiation of therapy (40 mg/kg, intraperitoneally). Ciprofloxacin was more effective than norfloxacin or pefloxacin and comparable in efficacy to ofloxacin. The drugs penetrated well into the pouch exudate, exceeding the minimal inhibitory concentrations (MICs) of the infecting organisms. The concentrations of pefloxacin or ofloxacin were higher than those of norfloxacin or ciprofloxacin. Ciprofloxacin also showed good killing effects in pouches infected with one strain of P. aeruginosa (ICB 7453, MIC of 0.06 micrograms/ml). However, with another P. aeruginosa strain (ICB 7933), which has a MIC of 0.5 micrograms/ml, killing of stationary cells in vivo was not very pronounced. Electron microscopic evaluation of the pouch exudate revealed that phagocytosed and non-phagocytosed E. coli cells were severely damaged in comparison with untreated control cells. The earliest ultrastructural changes could be observed 15 minutes after initiation of therapy. The results demonstrate that ciprofloxacin is effective in mice for the treatment of a local inflammatory abscess harboring a stationary population of E. coli or P. aeruginosa. This specific kind of killing occurs in vivo when drug concentrations are at least eight to 10 times higher than the MIC.