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Health outcomes attributable to carbapenemase-producing Enterobacteriaceae infections: A systematic review and meta-analysis

Published online by Cambridge University Press:  22 October 2019

Dalton R. Budhram ,
Stephen Mac ,
Joanna M. Bielecki ,
Samir N. Patel  and
Beate Sander
Dalton R. Budhram*
Affiliation:
Department of Medicine, Queen’s University, Kingston, Ontario, Canada
Stephen Mac
Affiliation:
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network, Toronto, Ontario, Canada
Joanna M. Bielecki
Affiliation:
Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network, Toronto, Ontario, Canada
Samir N. Patel
Affiliation:
Public Health Ontario Laboratory, Public Health Ontario, 661 University Ave, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Beate Sander
Affiliation:
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network, Toronto, Ontario, Canada Public Health Ontario Laboratory, Public Health Ontario, 661 University Ave, Toronto, Ontario, Canada Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
*
Author for correspondence: Dalton R. Budhram, Email: [email protected]
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Abstract

Background:

Carbapenemase-producing Enterobacteriaceae (CPE) pose a significant global health threat.

Objective:

To conduct a systematic review of health outcomes and long-term sequelae attributable to CPE infection.

Methods:

We followed PRISMA reporting guidelines and published our review protocol on PROSPERO (CRD42018097357). We searched Medline, Embase, CINAHL and the Cochrane Library. We included primary studies with a carbapenem-susceptible control group in high-income countries, published in English. Quality appraisal was completed using Joanna Briggs Institute checklists. We qualitatively summarized frequently reported outcomes and conducted a meta-analysis.

Results:

Our systematic review identified 8,671 studies; 17 met the eligibility criteria for inclusion. All studies reported health outcomes; none reported health-related quality-of-life. Most studies were from Europe (65%), were conducted in teaching or university-affiliated hospitals (76%), and used case-control designs (53%). Mortality was the most commonly reported consequence of CPE-infections; in-hospital mortality was most often reported (62%). Our meta-analysis (n = 5 studies) estimated an absolute risk difference (ARD) for in-hospital bloodstream infection mortality of 0.25 (95% confidence interval [CI], 0.17–0.32). Duration of antibiotic therapy (range, 4–29.7 vs 1–23.6 days) and length of hospital stay (range, 21–87 vs 15–43 days) were relatively higher for CPE-infected patients than for patients infected with carbapenem-susceptible pathogens. Most studies (82%) met >80% of their respective quality appraisal criteria.

Conclusions:

The risk of in-hospital mortality due to CPE bloodstream infection is considerably greater than carbapenem-susceptible bloodstream infection (ARD, 0.25; 95% CI, 0.17–0.32). Health outcome studies associated with CPE infection are focused on short-term (eg, in-hospital) outcomes; long-term sequelae and quality-of-life are not well studied.

Trial Registration:

PROSPERO (CRD42018097357).

Type
Original Article
Information
Infection Control & Hospital Epidemiology , Volume 41 , Issue 1 , January 2020 , pp. 37 - 43
Copyright
© 2019 by The Society for Healthcare Epidemiology of America. All rights reserved. 

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Footnotes

a

Authors of equal contribution.

References

Nordmann, P, Dortet, L, Poirel, L. Carbapenem resistance in Enterobacteriaceae: here is the storm! Trends Mol Med 2012;18:263–272.CrossRefGoogle ScholarPubMed
Tzouvelekis, LS, Markogiannakis, A, Psichogiou, M, Tassios, PT, Daikos, GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin Microbiol Rev 2012;25:682–707.CrossRefGoogle ScholarPubMed
Peleg, AY, Hooper, DC. Hospital-acquired infections due to gram-negative bacteria. N Engl J Med 2010;362:1804–1813.CrossRefGoogle ScholarPubMed
Guh, AY, Limbago, BM, Kallen, AJ. Epidemiology and prevention of carbapenem-resistant Enterobacteriaceae in the United States. Expert Rev Anti Infect Ther 2014;12:565–580.CrossRefGoogle ScholarPubMed
Naas, T, Vandel, L, Sougakoff, W, Livermore, DM, Nordmann, P. Cloning and sequence analysis of the gene for a carbapenem-hydrolyzing class A beta-lactamase, Sme-1, from Serratia marcescens S6. Antimicrob Agents Chemother 1994;38:1262–1270.CrossRefGoogle Scholar
Queenan, AM, Torres-Viera, C, Gold, HS, et al. SME-type carbapenem-hydrolyzing class A-lactamases from geographically diverse Serratia marcescens strains. Antimicrob Agents Chemother 2000;44:3035–3039.CrossRefGoogle Scholar
Watanabe, M, Iyobe, S, Inoue, M, Mitsuhashi, S. Transferable imipenem resistance in Pseudomonas aeruginosa . Antimicrob Agents Chemother 1991;35:147–151.CrossRefGoogle ScholarPubMed
Navarro-San Francisco, C, Mora-Rillo, M, Romero-Gómez, MP, et al. Bacteraemia due to OXA-48-carbapenemase-producing Enterobacteriaceae: a major clinical challenge. Clin Microbiol Infect 2013;19:E72–E79.CrossRefGoogle ScholarPubMed
Roberts, RR, Hota, B, Ahmad, I, et al. Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin Infect Dis 2009;49:1175–1184.CrossRefGoogle Scholar
Mauldin, PD, Salgado, CD, Hansen, IS, Durup, DT, Bosso, JA. Attributable hospital cost and length of stay associated with health care-associated infections caused by antibiotic-resistant gram-negative bacteria. Antimicrob Agents Chemother 2010;54:109–115.CrossRefGoogle ScholarPubMed
Xu, L, Sun, X, Ma, X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae . Ann Clin Microbiol Antimicrob 2017;16:18.CrossRefGoogle ScholarPubMed
Tzouvelekis, LS, Markogiannakis, A, Piperaki, E, Souli, M, Daikos, GL. Treating infections caused by carbapenemase-producing Enterobacteriaceae. Clin Microbiol Infect 2014;20:862–872.CrossRefGoogle ScholarPubMed
Moher, D, Liberati, A, Tetzlaff, J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:1–6.CrossRefGoogle ScholarPubMed
Mackintosh, A, Casañas i Comabella, C, Hadi, M, Gibbons, E, Fitzpatrick, R, Roberts, N, and P-ROMG. PROM group construct and instrument type filters. https://cosmin.nl/wp-content/uploads/prom-search-filter-oxford-2010.pdf. Published 2010. Accessed September 30, 2019.Google Scholar
Strings attached: CADTH’s database search filters. Canadian Agency for Drugs and Technology in Health (CADTH) website. https://www.cadth.ca/resources/finding-evidence/strings-attached-cadths-database-search-filters#health. Published 2016. Accessed February 4, 2019.Google Scholar
Wilczynski, NL, Haynes, RB, Lavis, JN, Ramkissoonsingh, R, Arnold-Oatley, AE, HSR Hedges team. Optimal search strategies for detecting health services research studies in MEDLINE. Can Med Assoc J 2004;171:1179–1185.CrossRefGoogle ScholarPubMed
Yong, D, Toleman, MA, Giske, CG, et al. Characterization of a new metallo-lactamase gene, bla NDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009;53:5046–5054.CrossRefGoogle Scholar
Checklist for cohort studies. The Joanna Briggs Institute website. http://joannabriggs.org/research/critical-appraisal-tools.htmlwww.joannabriggs.org. Published 2017 Accessed October 5, 2018.Google Scholar
Checklist for case control studies. The Joanna Briggs Institute website. http://joannabriggs.org/research/critical-appraisal-tools.htmlwww.joannabriggs.org. Published 2017 Accessed October 5, 2018.Google Scholar
Patel, H, Sander, B, Nelder, MP. Long-term sequelae of West Nile virus-related illness: a systematic review. Lancet Infect Dis 2015;15:951–959.CrossRefGoogle ScholarPubMed
Daikos, GL, Petrikkos, P, Psichogiou, M, et al. Prospective observational study of the impact of VIM-1 metallo-β-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother 2009;53:1868–1873.CrossRefGoogle ScholarPubMed
Falcone, M, Mezzatesta, ML, Perilli, M, et al. Infections with VIM-1 metallo-β-lactamase-producing Enterobacter cloacae and their correlation with clinical outcome. J Clin Microbiol 2009;47:3514–3519.CrossRefGoogle ScholarPubMed
Sbrana, F, Malacarne, P, Bassetti, M, et al. Risk factors for ventilator associated pneumonia due to carbapenemase-producing Klebsiella pneumoniae in mechanically ventilated patients with tracheal and rectal colonization. Minerva Anestesiol 2016;82:635–640.Google ScholarPubMed
Shilo, S, Assous, MV, Lachish, T, et al. Risk factors for bacteriuria with carbapenem-resistant Klebsiella pneumoniae and its impact on mortality: a case-control study. Infection 2013;41:503–509.CrossRefGoogle ScholarPubMed
Tascini, C, Lipsky, BA, Iacopi, E, et al. KPC-producing Klebsiella pneumoniae rectal colonization is a risk factor for mortality in patients with diabetic foot infections. Clin Microbiol Infect 2015;21:e790.e1–790.e3.CrossRefGoogle ScholarPubMed
Torres-Gonzalez, P, Ortiz-Brizuela, E, Cervera-Hernandez, ME, et al. Associated factors and outcomes for OXA-232 carbapenem-resistant Enterobacteriaceae infections in a tertiary care centre in Mexico City: a case–control-control study. Diagn Microbiol Infect Dis 2016;86:243–248.CrossRefGoogle Scholar
Tumbarello, M, Trecarichi, EM, Tumietto, F, et al. Predictive models for identification of hospitalized patients harboring KPC-producing Klebsiella pneumoniae . Antimicrob Agents Chemother 2014;58:3514–3520.CrossRefGoogle ScholarPubMed
Ben-David, D, Kordevani, R, Keller, N, et al. Outcome of carbapenem-resistant Klebsiella pneumoniae bloodstream infections. Clin Microbiol Infect 2012;18:54–60.CrossRefGoogle ScholarPubMed
McLaughlin, MM, Advincula, MR, Malczynski, M, Barajas, G, Qi, C, Scheetz, MH. Quantifying the clinical virulence of Klebsiella pneumoniae-producing carbapenemase Klebsiella pneumoniae with a Galleria mellonella model and a pilot study to translate to patient outcomes. BMC Infect Dis 2014; 14. doi:10.1186/1471-2334-14-31.CrossRefGoogle Scholar
Fraenkel-Wandel, Y, Raveh-Brawer, D, Wiener-Well, Y, Yinnon, AM, Assous, MV. Mortality due to blaKPC Klebsiella pneumoniae bacteraemia. J Antimicrob Chemother 2016;71:1083–1087.CrossRefGoogle ScholarPubMed
Lopez-Gonzalez, L, Candel, F, Vinuela-Prieto, J, et al. Useful independent factors for distinguish infection and colonization in patients with urinary carbapenemase-producing Enterobacteriaceae isolation. Rev Esp Quimioter 2017;30:450–457.Google ScholarPubMed
Lübbert, C, Becker-Rux, D, Rodloff, AC, et al. Colonization of liver transplant recipients with KPC-producing Klebsiella pneumoniae is associated with high infection rates and excess mortality: a case-control analysis. Infection 2014;42:309–316.CrossRefGoogle ScholarPubMed
Mouloudi, E, Protonotariou, E, Zagorianou, A, et al. Bloodstream infections caused by metallo-β-lactamase/Klebsiella pneumoniae carbapenemase–producing K. pneumoniae among intensive care unit patients in Greece: risk factors for infection and impact of type of resistance on outcomes. Infect Control Hosp Epidemiol 2010;31:1250–1256.CrossRefGoogle ScholarPubMed
Mouloudi, E, Massa, E, Papadopoulos, S, et al. Bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae among intensive care unit patients after orthotopic liver transplantation: risk factors for infection and impact of resistance on outcomes. Transplant Proc 2014;46:3216–3218.CrossRefGoogle ScholarPubMed
Papadimitriou-Olivgeris, M, Marangos, M, Fligou, F, et al. KPC-producing Klebsiella pneumoniae enteric colonization acquired during intensive care unit stay: the significance of risk factors for its development and its impact on mortality. Diagn Microbiol Infect Dis 2013;77:169–173.CrossRefGoogle ScholarPubMed
Qureshi, ZA, Paterson, DL, Peleg, AY, et al. Clinical characteristics of bacteraemia caused by extended-spectrum β-lactamase-producing Enterobacteriaceae in the era of CTX-M-type and KPC-type β-lactamases. Clin Microbiol Infect 2012;18:887–893.CrossRefGoogle ScholarPubMed
Sánchez-Romero, I, Asensio, Á, Oteo, J, et al. Nosocomial outbreak of VIM-1–producing Klebsiella pneumoniae isolates of multilocus sequence type 15: molecular basis, clinical risk factors, and outcome. Antimicrob Agents Chemother 2012;56:420–427.CrossRefGoogle ScholarPubMed
Higgins, JPT, Thompson, SG, Deeks, JJ, Altman, DG. Measuring inconsistency in meta-analyses. BMJ Br Med J 2003;327:557–560.CrossRefGoogle ScholarPubMed
Antibiotic resistant threats in the United States. Centers for Disease Control and Prevention website. https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf, 2013. Accessed October 5, 2018.Google Scholar
Vardakas, KZ, Rafailidis, PI, Konstantelias, AA, Falagas, ME. Predictors of mortality in patients with infections due to multidrug-resistant gram-negative bacteria: the study, the patient, the bug or the drug? J Infect 2013;66:401–414.CrossRefGoogle ScholarPubMed
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