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.