The Current and Future Impact of Antimicrobial Resistance Among Nosocomial Bacterial Pathogens

The selection of drug-resistant microorganisms has generally been associated with the widespread use of antimicrobial agents. The emergence of these antimicrobial resistance has an undesirable impact that often severely limits the use of these drugs that could have otherwise been identified as "drugs of first choice." Among the most serious drug-resistance problems, the chromosomally mediated type -I beta-lactamase mechanism has become more common among the infecting Gram-negative bacteria. Type-I beta-lactamases are routinely identified in Enterobacter spp., Citrobacter freundii, Proteus vulgaris, Pseudomonas spp., Providencia spp., Morganella spp., Serratia spp., and various nonfermenters, including Acinetobacter spp., and can be induced to high production when exposed to certain beta-lactam antibiotics (for example, ceftazidime or cefoxitin). These organisms can also undergo spontaneous mutations to become high-level constitutive beta-lactamase producers, thus remaining resistant to most beta-lactam antibiotics. This has been the most common event at our medical center since 1986. Plasmid-mediated beta-lactamases and bacterial cell membrane protein alterations also confer resistance, resulting in clinically important challenges. At the University of Iowa Hospitals and Clinics, beta-lactam-resistant Pseudomonas, Citrobacter, and Enterobacter were observed over a 2-year period, an event that correlated with the introduction of the "third-generation" cephalosporin ceftazidime to the formulary. As ceftazidime use increased from 1986 to 1988, the minimal inhibitory concentrations (MICs) for not only ceftazidime but also some other "third-generation" cephems increased for Pseudomonas aeruginosa. Similarly, susceptibility of Citrobacter spp. and Enterobacter spp. declined during this period for ceftazidime and, to a lesser extent, the unrelated broad-spectrum penicillin, piperacillin.(ABSTRACT TRUNCATED AT 250 WORDS)