Emergence of Antibiotic-Resistant Pseudomonas Aeruginosa
Abstract & Commentary Source: Carmeli Y, et al. Emergence of antibiotic-resistant Pseudomonas aeruginosa: Comparison of risks associated with different antipseudomonal agents. Antimicrob Agents Chemother 1999;43:1379-1382.Many medical centers are plagued with growing resistance in strains of Pseudomonas aeruginosa. At the Deaconess Hospital, a Harvard teaching hospital, Carmeli and colleagues asked the question, "Use of which antipseudomonal antimicrobial was most likely to lead to resistance?" Carmeli et al studied ceftazidime, ciprofloxacin, imipenem, and piperacillin (or infrequently used piperacillin-tazobactam). The study progressed from August 1994 through July 1996. The baseline isolate of P. aeruginosa had to be susceptible to the antibiotic administered in order for the patient to be included in the study. Several other variables were analyzed in addition to the study drugs such as underlying disease and weighted comorbidities (Charlson comorbidity score).
The results were somewhat surprising. In the 271 patients studied, ceftazidime (46%) was the most commonly used agent, followed by ciprofloxacin (36%), piperacillin (33%), and finally, imipenem (14%). Subsequent isolates resistant to at least one of the study drugs occurred in 28 (10.2%), at a rate of 7.4 per 1000 patient days. The median time for emergence of resistance was 14 days (range, 2-65 days). Of the nine pairs of isolates available for molecular typing, all showed identical DNA patterns.
The factors associated with emergence were imipenem usage (2.9 hazard ratio), the frequency of microbiological culturing, and the length of hospital stay before entry into the cohort. The hazard ratios for the other studied agents included ceftazidime 0.7, ciprofloxacin 0.8, and piperacillin 1.7. Imipenem had the highest likelihood of emergence of resistance to itself whereas ceftazidime had the lowest. Even though ciprofloxacin had a low likelihood of emerging resistance overall, when compared to ceftazidime, its use was associated with a significant chance of resistance emerging to itself.
The use of aminoglycosides in combinations with other antipseudomonal agents has been thought to reduce the emergence of resistance. In this study, it did not, although there was some confounding due to the fact that their patients were assumed to be at greater risk for producing resistant strains, and were more likely to receive aminoglycosides.
Comment by Joseph F. John, MD
It was reassuring that commonly used anti-pseudomonal agents like ceftazidime and ciprofloxacin had low rates of eliciting resistance. Carmeli and colleagues point out that the tendency of a particular agent to encourage emergence of resistance in the infecting strain should not be confused with the overall rates of resistance in an institution. Those overall rates are more closely associated with the overall volume of use of the particular agent.
Imipenem and its cousin, meropenem, retain excellent susceptibility profiles against most Enterobacteriaceae. Yet, Carmeli et al advise that the most prudent use of the carbepenems would be in polymicrobial infections, particularly those suspected of having an anerobic component. When imipenem is used to treat infections due to P. aeruginosa, there should be attention paid to frequent follow-up cultures to ensure resistance is not emerging in the infecting strain. The mechanism by which imipenem may be associated with an increased risk of emergence of resistance is uncertain. The answer may be as trivial as that of adequate dosing—a variable not examined by Carmeli et al. v
What antipseudomonal antibacterial agent is most associated with emergence of resistance in the infecting strain of Pseudomonas aeruginosa?
a. Ciprofloxacin
b. Ceftazidime
c. Imipenem
d. Pipercillin
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