Imipenem Resistance in Pseudomonas aeruginosa: Emergence, Epidemiology, and Impact on Clinical and Economic Outcomes

BACKGROUND. Pseudomonas aeruginosa is one of the most common gram-negative hospital-acquired pathogens. Resistance of this organism to imipenem complicates treatment. OBJECTIVE. To elucidate the risk factors for imipenem-resistant P. aeruginosa (IRPA) infection or colonization and to identify the effect of resistance on clinical and economic outcomes. METHODS. Longitudinal trends in prevalence of IRPA from 2 centers were characterized during the period from 1989 through 2006. For P. aeruginosa isolates obtained during the period from 2001 through 2006, a case-control study was conducted to investigate the association between prior carbapenem use and IRPA infection or colonization, and a cohort study was performed to identify the effect of IRPA infection or colonization on mortality, length of stay after culture, and hospital cost after culture. RESULTS. From 1989 through 2006, the proportion of P. aeruginosa isolates demonstrating resistance to imipenem increased from 13% to 20% (P < .001, trend). During the period from 2001 through 2006, there were 2,542 unique patients with P. aeruginosa isolates, and 253 (10.0%) had IRPA isolates. Prior carbapenem use was independently associated with IRPA infection or colonization (adjusted odds ratio [OR], 7.92 [95% confidence interval {CI}, 4.78-13.11]). Patients with an IRPA isolate recovered had higher in-hospital mortality than did patients with an imipenem-susceptible P. aeruginosa isolate (17.4% vs 13.4%; Pp. 01). IRPA infection or colonization was an independent risk factor for mortality among patients with isolates recovered from blood (adjusted OR, 5.43 [95% CI, 1.72-17.10]; P = .004) but not among patients with isolates recovered from other anatomic sites (adjusted OR, 0.78 [95% CI, 0.51-1.21]; P = .27). Isolation of IRPA was associated with longer hospital stay after culture (P < .001) and greater hospital cost after culture (P < .001) than was isolation of an imipenem-susceptible strain. In multivariable analysis, IRPA infection or colonization remained an independent risk factor for both longer hospital stay after culture (coefficient, 0.20 [95% CI, 0.04-0.36]; P = .02) and greater hospital cost after culture (coefficient, 0.30 [95% CI, 0.06-0.54]; P = .02). CONCLUSIONS. The prevalence of IRPA infection or colonization has increased significantly, with important implications for both clinical and economic outcomes. Interventions to curb this continued increase and strategies to optimize therapy are urgently needed.