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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%; P = .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.

Background: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is an emerging pathogen with serious clinical and infection control implications. To our knowledge, no study has specifically examined risk factors for KPC-producing K. pneumoniae or its impact on mortality., Methods: To identify risk factors for infection or colonization with KPC-producing K. pneumoniae, a case-control study was performed. Case patients with KPC-producing K. pneumoniae were compared with control subjects with carbapenem-susceptible K. pneumoniae. A cohort study evaluated the association between KPC-producing K. pneumoniae and in-hospital mortality., Results: Fifty-six case patients and 863 control subjects were identified. In multivariable analysis, independent risk factors for KPC-producing K. pneumoniae were (1) severe illness (adjusted odds ratio [AOR], 4.31; 95% confidence interval [CI], 2.25-8.25), (2) prior fluoroquinolone use (AOR, 3.39; 95% CI, 1.50, 7.66), and (3) prior extended-spectrum cephalosporin use (AOR, 2.55; 95% CI, 1.18, 5.52). Compared with samples from other anatomic locations, K. pneumoniae isolates from blood samples were less likely to harbor KPC (AOR, 0.33; 95% CI, 0.12, 0.86). KPC-producing K. pneumoniae was independently associated with in-hospital mortality (AOR, 3.60; 95% CI, 1.87-6.91)., Conclusions: KPC-producing K. pneumoniae is an emerging pathogen associated with significant mortality. Our findings highlight the urgent need to develop strategies for prevention and infection control. Limiting use of certain antimicrobials, specifically fluoroquinolones and cephalosporins, use may be effective strategies.

Background: Acinetobacter baumannii is an emerging gram-negative pathogen that can cause healthcare-acquired infections among patients. Treatment is complicated for cases of healthcare-acquired infection with A. baumannii resistant to imipenem., Objective: To elucidate the risk factors for imipenem-resistant A. baumannii (IRAB) infection or colonization and to identify the effect of resistance on clinical and economic outcomes., Methods: We analyzed data from 2 medical centers of the University of Pennsylvania. Longitudinal trends in the prevalence of IRAB clinical isolates were characterized during the period from 1989 through 2004. For A. baumannii isolates obtained from 2001 through 2006, a case-control study was conducted to investigate the association between prior carbapenem use and IRAB infection or colonization, and a cohort study was performed to identify the effect of IRAB infection or colonization on mortality, length of stay after culture, and hospital cost after culture., Results: From 1989 through 2004, the annual prevalence of IRAB isolates ranged from 0% to 21%. During the period from 2001 through 2006, there were 386 unique patients with A. baumannii isolates, and 89 (23.1%) had IRAB isolates. Prior carbapenem use was independently associated with IRAB infection or colonization (adjusted odds ratio, 3.04 [95% confidence interval, 1.07-8.65]). There was a borderline significant association between IRAB infection or colonization and mortality, although this association was limited to isolates recovered from blood samples (adjusted odds ratio, 5.30 [95% confidence interval, 0.81-34.59]). Compared with patients with imipenem-susceptible A. baumannii infection or colonization, patients with IRAB infection or colonization had a longer hospital stay after culture (median, 21 vs 16 days; P = .07) and greater hospital charges after culture (mean, $334,516 vs $276,059; P = .03). After controlling for patient location in an intensive care unit, transfer from another facility, and length of hospital stay before culture, there was no longer an independent association between IRAB infection or colonization and higher cost after culture and length of stay after positive culture result., Conclusions: Many A. baumannii isolates exhibit imipenem resistance, which is strongly associated with prior use of carbapenems. Given the high mortality rate associated with A. baumannii infection or colonization, interventions to curb further emergence of cases of IRAB infection and strategies to optimize therapy are needed.

Coadministration of oral divalent or trivalent cation-containing compounds with oral fluoroquinolones may impair fluoroquinolone absorption. Among 3,134 patients who received a course of oral levofloxacin, coadministration was significantly associated with subsequent identification of a levofloxacin-resistant isolate. Strategies to curb the emergence of fluoroquinolone resistance should include avoiding the coadministration of divalent or trivalent cation-containing compounds and fluoroquinolone.