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Outcomes of Carbapenem-Resistant Klebsiella pneumoniae Infection and the Impact of Antimicrobial and Adjunctive Therapies

Published online by Cambridge University Press:  02 January 2015

Gopi Patel
Affiliation:
Department of Medicine, Mount Sinai School of Medicine, New York, New York
Shirish Huprikar
Affiliation:
Department of Medicine, Mount Sinai School of Medicine, New York, New York
Stephanie H. Factor
Affiliation:
Department of Medicine, Mount Sinai School of Medicine, New York, New York
Stephen G. Jenkins
Affiliation:
Department of Medicine, Mount Sinai School of Medicine, New York, New York Department of Pathology, Mount Sinai School of Medicine, New York, New York
David P. Calfee*
Affiliation:
Department of Medicine, Mount Sinai School of Medicine, New York, New York
*
Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1151, New York, NY 10029 ([email protected])

Abstract

Background.

Carbapenem-resistant Klebsiella pneumoniae is an emerging healthcare-associated pathogen.

Objective.

To describe the epidemiology of and clinical outcomes associated with carbapenem-resistant K. pneumoniae infection and to identify risk factors associated with mortality among patients with this type of infection.

Setting.

Mount Sinai Hospital, a 1,171-bed tertiary care teaching hospital in New York City.

Design.

Two matched case-control studies.

Methods.

In the first matched case-control study, case patients with carbapenem-resistant K. pneumoniae infection were compared with control patients with carbapenem-susceptible K. pneumoniae infection. In the second case-control study, patients who survived carbapenem-resistant K. pneumoniae infection were compared with those who did not survive, to identify risk factors associated with mortality among patients with carbapenem-resistant K. pneumoniae infection.

Results.

There were 99 case patients and 99 control patients identified. Carbapenem-resistant K. pneumoniae infection was independently associated with recent organ or stem-cell transplantation (P = .008), receipt of mechanical ventilation (P = .04), longer length of stay before infection (P = .01), and exposure to cephalosporins (P = .02) and carbapenems (P < .001). Case patients were more likely than control patients to die during hospitalization (48% vs 20%; P < .001) and to die from infection (38% vs 12%; P < .001). Removal of the focus of infection (ie, debridement) was independently associated with patient survival (P = .002). The timely administration of antibiotics with in vitro activity against carbapenem-resistant K. pneumoniae was not associated with patient survival.

Conclusions.

Carbapenem-resistant K. pneumoniae infection is associated with numerous healthcare-related risk factors and with high mortality. The mortality rate associated with carbapenem-resistant K. pneumoniae infection and the limited antimicrobial options for treatment of carbapenem-resistant K. pneumoniae infection highlight the need for improved detection of carbapenem-resistant K. pneumoniae infection, identification of effective preventive measures, and development of novel agents with reliable clinical efficacy against carbapenem-resistant K. pneumoniae.

Type
Original Articles
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2008

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References

1. National Nosocomial Infections Surveillance (NNIS) system report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004;32:470485.Google Scholar
2. Cosgrove, S, Sakoulas, G, Perencevich, E, Schwaber, M, Karchmer, A, Carmeli, Y. Comparison of mortality with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 2003;36:5359.Google Scholar
3. Cosgrove, S, Qi, Y, Kaye, K, Harbarth, S, Karchmer, A, Carmeli, Y. The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges. Infect Control Hosp Epidemiol 2005;26:166174.CrossRefGoogle ScholarPubMed
4. Engemann, J, Carmeli, Y, Cosgrove, S, et al. Adverse clinical and epidemiologic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection. Clin Infect Dis 2003;36:592598.CrossRefGoogle Scholar
5. Reed, S, Friedman, J, Engemann, J, et al. Costs and outcomes among hemodialysis-dependent patients with methicillin-resistant or methicillin-susceptible Staphylococcus aureus bacteremia. Infect Control Hosp Epidemiol 2005;26:175183.CrossRefGoogle ScholarPubMed
6. Lautenbach, E, Patel, J, Bilker, W, Edelstein, P, Fishman, NO. Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clin Infect Dis 2001;32:11621171.CrossRefGoogle ScholarPubMed
7. Lee, S, Kotapati, S, Kuti, J, Nightingale, C, Nicolau, DP. Impact of extended-spectrum β-lactamase-producing Escherichia coil and Klebsiella species on clinical outcomes and hospital costs: a matched cohort study. Infect Control Hosp Epidemiol 2006;27:12261232.CrossRefGoogle Scholar
8. Paterson, D, Doi, Y. A step closer to extreme drug resistance in gram-negative bacilli. Clin Infect Dis 2007;45:11791181.Google Scholar
9. Chow, J, Shlaes, DM. Imipenem resistance associated with the loss of a 40-kDa outer membrane protein in Enterobacter aerogenes . J Antimicrob Chemother 1991;28:499504.CrossRefGoogle Scholar
10. Bradford, , PA, , Urban, C, Mariano, N, Projan, S, Rahal, J, Bush, K. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC β-lactamase, and the loss of an outer membrane protein. Antimicrob Agents Chemother 1997;41:563569.Google Scholar
11. MacKenzie, F, Forbes, K, Dorai-John, T, Amyes, S, Gould, IM. Emergence of a carbapenem-resistant Klebsiella pneumoniae . Lancet 1997;350:783.CrossRefGoogle ScholarPubMed
12. Deshpande, L, Jones, R, Fritsche, T, Sader, HS. Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000-2004). Mi-crob Drug Resist 2006;12:223230.Google Scholar
13. Bratu, S, Mooty, M, Nichani, S, et al. Emergence of KPC-possessing Klebsiella pneumoniae in Brooklyn, New York: epidemiology and recommendations for detection. Antimicrob Agents Chemother 2005;49:30183020.CrossRefGoogle ScholarPubMed
14. Schwaber, M, Klarfeld-Lidji, S, Navon-Venezia, S, Schwartz, D, Leavitt, A, Carmeli, Y. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults, and effect of acquisition on mortality. Antimicrob Agents Chemother 2008;52:10281033.Google Scholar
15. Landman, D, Bratu, S, Kochar, S, et al. Evolution of antimicrobial resistance among Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in Brooklyn, NY. J Antimicrob Chemother 2007;60:7882.Google Scholar
16. Falagas, M, Rafailidis, P, Kofteridis, D, et al. Risk factors of carbapenem-resistant Klebsiella pneumoniae infections: a matched case-control study. J Antimicrob Chemother 2007;60:11241130.Google Scholar
17. Horan, T, Gaynes, RP. Surveillance of nosocomial infections. In: Mayhall, C, ed. Hospital Epidemiology and Infection Control. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:16591702.Google Scholar
18. CLSI. Performance standards for antimicrobial susceptibilities testing: 16th informational supplement. Approved standard; CLSI document. Wayne, PA: CLSI, 2006;M100S16.Google Scholar
19. Tygacil (tigecycline IV) [package insert]. Madison, NJ: Wyeth Pharmaceuticals; 2008.Google Scholar
20. Kuhar, D, Calfee, DP. Risk factors for colonization and/or infection with carbapenem-resistant Klebsiella pneumoniae . In: 17th Annual Scientific Meeting of the Society for Healthcare Epidemiology of America; Baltimore, MD; April 14-17, 2007. Abstract 251.Google Scholar
21. Ahmad, M, Urban, C, Mariano, N, et al. Clinical characteristics and molecular epidemiology associated with imipenem-resistant Klebsiella pneumoniae. Clin Infect Dis 1999;29:352355.CrossRefGoogle ScholarPubMed
22. Kwak, Y, Choi, S, Choo, E, et al. Risk factors for the acquisition of carbapenem-resistant Klebsiella pneumoniae among hospitalized patients. Microb Drug Resist 2005;11:165169.Google Scholar
23. Singh, N, Wagener, M, Obman, A, Cacciarelli, T, de Vera, M, Gayowski, T. Bacteremias in liver transplant recipients: shift toward gram-negative bacteria as predominant pathogens. Liver Transpl 2004;10:844849.CrossRefGoogle ScholarPubMed
24. Bratu, S, Tolaney, P, Karumudi, U, et al. Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents. J Antimicrob Chemother 2005;56:128132.CrossRefGoogle ScholarPubMed
25. Karabinis, A, Paramythiotou, E, Myonia-Petropoulou, D, et al. Colistin for Klebsiella pneumoniae-associated sepsis. Clin Infect Dis 2004;38:e79.CrossRefGoogle ScholarPubMed
26. Daly, M, Riddle, D, Ledeboer, N, Dunne, W, Ritchie, DJ. Tigecycline for the treatment of pneumonia and empyema caused by carbapenemase-producing Klebsiella pneumoniae . Pharmacotherapy 2007;27:10521057.CrossRefGoogle ScholarPubMed
27. Patel, G, Arvelakis, A, Sauter, B, Gondolesi, G, Caplivski, D, Huprikar, S. Strongyloides hyperinfection syndrome after intestinal transplantation. Transpl Infect Dis 2007;10:137141.CrossRefGoogle ScholarPubMed
28. Harris, A, Karchmer, T, Carmeli, Y, Samore, MH. Methodological principles of case-control studies that analyzed risk factors for antibiotic resistance: a systematic review. Clin Infect Dis 2001;32:10551061.CrossRefGoogle ScholarPubMed
29. Tenover, F, Kalsi, R, Williams, P, et al. Carbapenem resistance in Klebsiella pneumoniae not detected by automated susceptibility testing. Emerg Infect Dis 2006;12:12091213.CrossRefGoogle Scholar