Antimicrobial activity of cefepime tested against ceftazidime-resistant Gram-negative clinical strains from North American Hospitals: report from the SENTRY Antimicrobial Surveillance Program (1998-2004).

To assess the effect of ceftazidime resistance on the activity of other antimicrobial agents, 3030 ceftazidime-resistant Gram-negative bacilli (GNB) isolates (of a total of 42061 GNB) were tested against a panel of more than 30 agents. Ceftazidime resistance was observed in 40.3% of Acinetobacter spp., 16.9% of Pseudomonas aeruginosa, and 5.7% of Enterobacteriaceae isolates. The highest rates of ceftazidime resistance among the enteric GNB were observed with Enterobacter spp. (20.9%) >Citrobacter spp. (15.3%) > indole-positive Proteae (10.1%). Overall, 90% of ceftazidime-resistant Enterobacteriaceae and 30% of ceftazidime-resistant P. aeruginosa remained susceptible to the "4th-generation" cephalosporin, cefepime. The activities (% susceptible) of other antimicrobials tested against ceftazidime-resistant Enterobacteriaceae and P. aeruginosa, respectively, were as follows: amikacin, 90% and 88%; ciprofloxacin, 63% and 46%; gentamicin, 59% and 67%, imipenem, 99% and 65%; levofloxacin, 69% and 44%; and piperacillin/tazobactam only 40% and 12%. Ceftazidime-resistant GNB exhibited high rates of resistance to other antimicrobials. Cefepime was very active against ceftazidime-resistant enteric GNB (AmpC enzyme producers), especially Enterobacter spp. (94.3% susceptible), Citrobacter spp. (96.7% susceptible), and indole-positive Proteae (89.6% susceptible), and showed activity similar to that of ceftazidime against all P. aeruginosa and Acinetobacter spp. isolated in North American medical centers. Continued resistances surveillance monitoring will be necessary to assess the effectiveness of widely used broad-spectrum antimicrobials as novel resistance mechanisms emerge.