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Risk Factors and Clinical Impact of Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae

Published online by Cambridge University Press:  02 January 2015

Leanne B. Gasink*
Affiliation:
Division of Infectious Diseases of the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Paul H. Edelstein
Affiliation:
Division of Infectious Diseases of the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Ebbing Lautenbach
Affiliation:
Division of Infectious Diseases of the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Marie Synnestvedt
Affiliation:
Office of Human Research, School of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Neil O. Fishman
Affiliation:
Division of Infectious Diseases of the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
*
FOC NW2 652 1800 Concord Pike, Wilmington, DE 19803-2902 ([email protected])

Abstract

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.

Type
Original Articles
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2009

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References

1.Neuhauser, MM, Weinstein, RA, Rydman, R, Danziger, LH, Karam, G, Quinn, JRAntibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA 2003;289:885888.CrossRefGoogle ScholarPubMed
2.Streit, JM, Jones, RN, Sader, HS, Fritsche, TR. Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001). Int J Antimicrob Agents 2004;24:111118.CrossRefGoogle ScholarPubMed
3.Falagas, ME, Bliziotis, IA. Pandrug-resistant gram-negative bacteria: the dawn of the post-antibiotic era? Int J Antimicrob Agents 2007;29:630636.CrossRefGoogle ScholarPubMed
4. National Nosocomial Infections Surveillance S. 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.CrossRefGoogle Scholar
5.MacKenzie, FM, Forbes, KJ, Dorai-John, T, Amyes, SG, Gould, IM. Emergence of a carbapenem-resistant Klebsiella pneumoniae. Lancet 1997;350:783.CrossRefGoogle ScholarPubMed
6.Bradford, PA, Bratu, S, Urban, C, et al.Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactamases in New York City. Clin Infect Dis 2004;39:5560.CrossRefGoogle Scholar
7.Leavitt, A, Navon-Venezia, S, Chmelnitsky, I, Schwaber, MJ, Carmeli, Y. Emergence of KPC-2 and KPC-3 in carbapenem-resistant Klebsiella pneumoniae strains in an Israeli hospital. Antimicrob Agents Chemother 2007;51:30263029.CrossRefGoogle Scholar
8.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
9.Pope, J, Adams, J, Doi, Y, Szabo, D, Paterson, DL. KPC type beta-lactamase, rural Pennsylvania. Emerg Infect Dis 2006;12:16131614.CrossRefGoogle ScholarPubMed
10.Villegas, MV, Lolans, K, Correa, A, et al.First detection of the plasmid-mediated class A carbapenemase KPC-2 in clinical isolates of Klebsiella pneumoniae from South America. Antimicrob Agents Chemother 2006;50:28802882.CrossRefGoogle Scholar
11.Zhang, R, Zhou, HW, Cai, JC, Chen, GX. Plasmid-mediated carbapenem-hydrolysing beta-lactamase KPC-2 in carbapenem-resistant Serratia mar-cescens isolates from Hangzhou, China. J Antimicrob Chemother 2007;59:574576.CrossRefGoogle ScholarPubMed
12.Tenover, FC, Kalsi, RK, Williams, PP, et al.Carbapenem resistance in Klebsiella pneumoniae not detected by automated susceptibility testing. Emerg Infect Dis 2006;12:12091213.CrossRefGoogle Scholar
13.Bratu, S, Landman, D, Haag, R, et al.Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium. Arch Intern Med 2005;165:14301435.CrossRefGoogle ScholarPubMed
14.Schwaber, MJ, 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.CrossRefGoogle ScholarPubMed
15.Falagas, ME, Rafailidis, PI, Kofteridis, D, et al.Risk factors of carbapenem-resistant Klebsiella pneumoniae infections: a matched case control study. J Antimicrob Chemother 2007;60:11241130.CrossRefGoogle ScholarPubMed
16.Kwak, YG, Choi, SH, Choo, EJ, et al.Risk factors for the acquisition of carbapenem-resistant Klebsiella pneumoniae among hospitalized patients. Microb Drug Resist 2005;11:165169.CrossRefGoogle ScholarPubMed
17.Patel, G, Huprikar, S, Factor, S, Jenkins, S, Calfee, D. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008;29:10991106.CrossRefGoogle ScholarPubMed
18.McGettigan, SE, Adreaecchio, K, Edelstein, PH. Specificity of ertapenem susceptibility screening for the detection of Klebsiella pneumoniae carbapenemases (KPC). J Clin Microbiol 2009;47:785786.CrossRefGoogle Scholar
19.Lomaestro, BM, Tobin, EH, Shang, W, Gootz, T. The spread of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae to upstate New York. Clin Infect Dis 2006;43:e26e28.CrossRefGoogle ScholarPubMed
20.Anderson, KF, Lonsway, DR, Rasheed, JK, et al.Evaluation of methods to identify the Klebsiella pneumoniae carbapenemase in Enterobacteriaceae. J Clin Microbiol 2007;45:27232725.CrossRefGoogle ScholarPubMed
21.Harris, AD, Karchmer, TB, 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
22.Gasink, LB, Fishman, NO, Nachamkin, I, Bilker, WB, Lautenbach, E. Risk factors for and impact of infection or colonization with aztreonam-resistant Pseudomonas aeruginosa. Infect Control Hosp Epidemiol 2007; 28:11751180.CrossRefGoogle ScholarPubMed
23. 3M Health Information Systems. All-patient refined diagnosis related groups (APR-DRGs) methodology overview, version 20. Wallingford, CT:3M Health Information Systems; 2003.Google Scholar
24.Mendes, RE, Bell, JM, Turnidge, JD, et al.Carbapenem-resistant isolates of Klebsiella pneumoniae in China and detection of a conjugative plasmid (blaKPC-2 plus qnrB4) and a blaIMP-4 gene. Antimicrob Agents Chemother 2008;52:798799.CrossRefGoogle Scholar
25.Endimiani, A, Carias, LL, Hujer, AM, et al.Presence of plasmid-mediated quinolone resistance in Klebsiella pneumoniae isolates possessing blaKPC in the United States. Antimicrob Agents Chemother 2008;52:26802682.CrossRefGoogle ScholarPubMed
26.Rice, LB, Carias, LL, Hutton, RA, Rudin, SD, Endimiani, A, Bonomo, RA. The KQ element, a complex genetic region conferring transferable resistance to carbapenems, aminoglycosides, and fluoroquinolones in Klebsiella pneumoniae. Antimicrob Agents Chemother 2008;52:34273429.CrossRefGoogle ScholarPubMed
27.Naas, T, Cuzon, G, Villegas, MV, Lartigue, MF, Quinn, JP, Nordmann, P. Genetic structures at the origin of acquisition of the beta-lactamase bla KPC gene. Antimicrob Agents Chemother 2008;52:12571263.CrossRefGoogle ScholarPubMed
28.Linder, JA, Huang, ES, Steinman, MA, Gonzales, R, Stafford, RS. Fluoroquinolone prescribing in the United States: 1995 to 2002. Am J Med 2005;118:259268.CrossRefGoogle ScholarPubMed
29.Gould, CV, Fishman, NO, Nachamkin, I, Lautenbach, E. Chloramphenicol resistance in vancomycin-resistant enterococcal bacteremia: impact of prior fluoroquinolone use? Infect Control Hosp Epidemiol 2004;25:138145.CrossRefGoogle ScholarPubMed
30.Wiener, J, Quinn, JP, Bradford, PA, et al.Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes. JAMA 1999;281:517523.CrossRefGoogle ScholarPubMed
31.Lautenbach, E, Weiner, MG, Nachamkin, I, Bilker, WB, Sheridan, A, Fishman, NO. Imipenem resistance among Pseudomonas aeruginosa: risk factors for emergence and impact of resistance on clinical and economic outcomes. Infect Control Hosp Epidemiol 2006;27:893900.CrossRefGoogle ScholarPubMed
32.Paramythiotou, E, Lucet, JC, Timsit, JF, et al.Acquisition of multidrug-resistant Pseudomonas aeruginosa in patients in intensive care units: role of antibiotics with antipseudomonal activity. Clin Infect Dis 2004;38:670677.CrossRefGoogle ScholarPubMed
33.Jacoby, GA. Mechanisms of resistance to quinolones. Clin Infect Dis 2005;41(Suppl 2):S120S126.CrossRefGoogle ScholarPubMed
34.Woodford, N, Tierno, PM Jr, Young, K, et al.Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A beta-lactamase, KPC-3, in a New York Medical Center. Antimicrob Agents Chemother 2004;48:47934799.CrossRefGoogle Scholar
35.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