Treatment of ciprofloxacin- and ceftizoxime-induced resistant gram-negative bacilli

Gram-negative bacilli that had been selected for resistance to either ciprofloxacin or ceftizoxime as a result of previous exposure to these agents were inoculated into semipermeable subcutaneous chambers in rabbits, modeling a locally neutropenic closed-space infection. Five resistant organisms, one Serratia marcescens (157) and four Pseudomonas aeruginosa (864, 876, 913, and 915) strains, were selected by previous therapy with ciprofloxacin, and six Pseudomonas strains (833, 845, 864, 876, 913, and 915) were selected by previous therapy with ceftizoxime. Animals were treated with either single antibiotics or combinations of antibiotics for four days, and the response was determined by quantitative bacterial count measurements. The selected (induced) resistance was stable for at least four days, both in vivo and in vitro, but was limited to the antibiotic class of the agent used for induction. Four of five isolates for which resistance had been induced by ciprofloxacin returned to preinduction susceptibility by the eight day of subculture. Organisms that were selected for resistance to ciprofloxacin were successfully treated by a combination of azlocillin and amikacin, and were as sensitive to that regimen as were the parent, uninduced strains. Organisms selected for resistance by pretreatment with ceftizoxime were successfully treated by the combination of ciprofloxacin plus azlocillin, and this regimen was also equally active against the selected strains as it was against the parental isolates. Although selection or induction of resistance is a potential problem with all new potent antimicrobial agents, it appears that infections due to these isolates can still be treated successfully through the use of appropriate combination chemotherapy.