Cross-resistance of Pseudomonas aeruginosa to ciprofloxacin, extended-spectrum beta-lactams, and aminoglycosides and susceptibility to antibiotic combinations

Abstract

The susceptibilities of 270 clinical isolates of Pseudomonas aeruginosa from diverse sources (82 burn patients, 76 cystic fibrosis [CF] patients, and 112 other sources) to ciprofloxacin and three other quinolones, nine extended-spectrum beta-lactams, and three aminoglycosides were determined by an agar dilution method in cation-supplemented Mueller-Hinton medium. Ciprofloxacin, ceftazidime, imipenem, and aztreonam were the most active. MICs for burn isolates were consistently higher than those for other isolates for most antibiotics, whereas those for CF strains were consistently lower. Multidrug resistance to aminoglycosides and beta-lactams occurred in 21% of the burn isolates, 2.6% of the CF isolates, and 8.9% of the other isolates. Ninety percent of these strains remained susceptible to ciprofloxacin. Seven percent of the isolates were resistant to ciprofloxacin (MIC, greater than or equal to 2 micrograms/ml). Concurrent resistance to ciprofloxacin and beta-lactams or aminoglycosides was rare (1.8 to 4%). Analysis by Spearman rank correlation revealed a high degree of correlation of MICs among antibiotics within the same class, except for imipenem. An inoculum effect was observed for all antibiotics between 10(6) and 10(4) CFU (P less than 0.05), with those for piperacillin and cefoperazone being the most pronounced (16-fold and 8-fold differences, respectively), and was least apparent for the quinolones, aminoglycosides, imipenem, and aztreonam (twofold differences). Selected strains for which there were high MICs of ciprofloxacin (greater than or equal to 1 micrograms/ml) were tested against ciprofloxacin in combination with other agents in a checkerboard agar dilution assay. Synergistic (summated fractional inhibitory concentration, </=0.5) interactions at clinically achievable concentrations were most frequent with mezlocillin (33%), piperacillin (21%), and (7.6%), aztreonam (3.7%), and the aminoglycosides (3.7%). Antagonism (summated fractional inhibitory concentration, >/= 4) was observed in only one instance (with gentamicin).