Resistance mechanisms selected after in vitro exposure to 12 quinolones were analyzed for Pseudomonas aeruginosa. Efflux-type mutants were predominant. Quinolones differed in their ability to select a particular efflux system. While the newer fluoroquinolones favored the MexCD-OprJ system, the older quinolones selected exclusively the MexEF-OprN or MexAB-OprM systems. A protonable C-7 substituent in combination with a C-6 fluorine atom is a structural determinant of quinolones involved in efflux pump substrate specificity.

The ability of six antibiotics to produce resistance by stepwise selection on agar medium was assessed in 24 gram-negative rods. Escherichia coli was the strain least prone to selection of resistance, whereas Pseudomonas aeruginosa frequently developed resistance to all antibiotics. When used alone, ciprofloxacin, pefloxacin, amikacin, ceftazidime and cefpirome were associated with a comparable risk of acquired resistance (in 14 to 17 out of 24 strains); imipenem selected resistant strains in 10/24 isolates (5/18 in non-pseudomonas strains). The number of strains exhibiting cross resistance with structurally unrelated antibiotics was 11 after pefloxacin treatment, eight after exposure to ciprofloxacin, six after ceftazidime, and one after imipenem or cefpirome. The combination of ciprofloxacin with amikacin was less efficient in reducing acquisition of resistance than the combination of ciprofloxacin with a beta-lactam: ciprofloxacin plus cefpirome was especially potent in this respect.