Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-25T08:58:15.514Z Has data issue: false hasContentIssue false
  • English
  • Français

Carbapenem Resistance, Initial Antibiotic Therapy, and Mortality in Klebsiella pneumoniae Bacteremia: A Systematic Review and Meta-Analysis

Published online by Cambridge University Press:  27 September 2017

Philipp P. Kohler ,
Cheryl Volling ,
Karen Green ,
Elizabeth M. Uleryk ,
Prakesh S. Shah  and
Allison McGeer
Philipp P. Kohler*
Affiliation:
Mount Sinai Hospital, Toronto, Ontario, Canada University of Toronto, Institute of Health Policy, Management and Evaluation, Toronto, Ontario, Canada Clinic for Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
Cheryl Volling
Affiliation:
Mount Sinai Hospital, Toronto, Ontario, Canada
Karen Green
Affiliation:
Mount Sinai Hospital, Toronto, Ontario, Canada
Elizabeth M. Uleryk
Affiliation:
Mount Sinai Hospital, Toronto, Ontario, Canada E.M. Uleryk Consulting, Mississauga, Ontario, Canada
Prakesh S. Shah
Affiliation:
Mount Sinai Hospital, Toronto, Ontario, Canada University of Toronto, Institute of Health Policy, Management and Evaluation, Toronto, Ontario, Canada
Allison McGeer
Affiliation:
Mount Sinai Hospital, Toronto, Ontario, Canada University of Toronto, Institute of Health Policy, Management and Evaluation, Toronto, Ontario, Canada
*
Address correspondence to Philipp Kohler, MD, MSc, Clinic for Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland ([email protected]).
Get access Rights & Permissions [Opens in a new window]

Abstract

BACKGROUND

Mortality associated with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) is higher than mortality due to carbapenem-sensitive pathogens.

OBJECTIVE

To examine the association between mortality from bacteremia caused by carbapenem-resistant (CRKP) and carbapenem-sensitive Klebsiella pneumoniae (CSKP) and to assess the impact of appropriate initial antibiotic therapy (IAT) on mortality.

DESIGN

Systematic review and meta-analysis

METHODS

We searched MEDLINE, EMBASE, CINAHL, and Wiley Cochrane databases through August 31, 2016, for observational studies reporting mortality among adult patients with CRKP and CSKP bacteremia. Search terms were related to Klebsiella, carbapenem-resistance, and infection. Studies including fewer than 10 patients per group were excluded. A random-effects model and meta-regression were used to assess the relationship between carbapenem-resistance, appropriateness of IAT, and mortality.

RESULTS

Mortality was higher in patients who had CRKP bacteremia than in patients with CSKP bacteremia (15 studies; 1,019 CRKP and 1,148 CSKP patients; unadjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.8–2.6; I2=0). Mortality was lower in patients with appropriate IAT than in those without appropriate IAT (7 studies; 658 patients; unadjusted OR, 0.5; 95% CI, 0.3–0.8; I2=36%). CRKP patients (11 studies; 1,326 patients; 8-year period) were consistently less likely to receive appropriate IAT (unadjusted OR, 0.5; 95% CI, 0.3–0.7; I2=43%). Our meta-regression analysis identified a significant association between the difference in appropriate IAT and mortality (OR per 10% difference in IAT, 1.3; 95% CI, 1.0–1.6).

CONCLUSIONS

Appropriateness of IAT is an important contributor to the observed difference in mortality between patients with CRKP bacteremia and patients with CSKP bacteremia.

Infect Control Hosp Epidemiol 2017;38:1319–1328

Type
Original Articles
Information
Infection Control & Hospital Epidemiology , Volume 38 , Issue 11 , November 2017 , pp. 1319 - 1328
Copyright
© 2017 by The Society for Healthcare Epidemiology of America. All rights reserved 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

PREVIOUS PRESENTATION. An oral presentation of this work was given at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) on April 23, 2017, in Vienna, Austria.

a

Authors with equal contribution.

References

REFERENCES

1. Nordmann, P, Naas, T, Poirel, L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2011;17:1791–1798.Google Scholar
2. Nordmann, P, Poirel, L. The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infect 2014;20:821–830.CrossRefGoogle ScholarPubMed
3. Karaiskos, I, Giamarellou, H. Multidrug-resistant and extensively drug-resistant gram-negative pathogens: current and emerging therapeutic approaches. Expert Opin Pharmacother 2014;15:1351–1370.Google Scholar
4. Pitout, JD, Nordmann, P, Poirel, L. Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother 2015;59:5873–5884.Google Scholar
5. Falagas, ME, Tansarli, GS, Karageorgopoulos, DE, Vardakas, KZ. Deaths attributable to carbapenem-resistant Enterobacteriaceae infections. Emerg Infect Dis 2014;20:1170–1175.Google Scholar
6. 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.Google Scholar
7. Wiener-Well, Y, Raveh-Brawer, D, Fraenkel-Wandel, Y, Yinnon, AM, Assous, MV. Mortality due to blaKPC Klebsiella pneumoniae bacteraemia-authors’ response. J Antimicrob Chemother 2016;71:1744.Google Scholar
8. Giacobbe, DR, Tumbarello, M, Del Bono, V, Viscoli, C, Isgri, S. Comment on: Mortality due to blaKPC Klebsiella pneumoniae bacteraemia. J Antimicrob Chemother 2016;71:1743–1744.CrossRefGoogle ScholarPubMed
9. Vardakas, KZ, Rafailidis, PI, Konstantelias, AA, Falagas, ME. Predictors of mortality in patients with infections due to multi-drug resistant gram-negative bacteria: the study, the patient, the bug or the drug? J Infect 2013;66:401–414.Google Scholar
10. Moher, D, Liberati, A, Tetzlaff, J, Altman, DG, Group, P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535.CrossRefGoogle ScholarPubMed
11. Walther-Rasmussen, J, Hoiby, N. Class A carbapenemases. J Antimicrob Chemother 2007;60:470–482.CrossRefGoogle ScholarPubMed
12. Centers for Disease Control and Prevention. Healthcare associated infections, Diseases and Organisms, Carbapenem-resistant Enterobacteriaceae (CRE): Available at: https://www.cdc.gov/hai/organisms/cre/definition.html.Google Scholar
13. DerSimonian, R, Laird, N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188.Google Scholar
14. Higgins, JP, Thompson, SG, Deeks, JJ, Altman, DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.Google Scholar
15. Daikos, GL, Petrikkos, P, Psichogiou, M, et al. Prospective observational study of the impact of VIM-1 metallo-beta-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother 2009;53:1868–1873.Google Scholar
16. 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
17. Girometti, N, Lewis, RE, Giannella, M, et al. Klebsiella pneumoniae bloodstream infection: epidemiology and impact of inappropriate empirical therapy. Medicine (Baltimore) 2014;93:298–309.CrossRefGoogle ScholarPubMed
18. Alicino, C, Giacobbe, DR, Orsi, A, et al. Trends in the annual incidence of carbapenem-resistant Klebsiella pneumoniae bloodstream infections: a 8-year retrospective study in a large teaching hospital in northern Italy. BMC Infect Dis 2015;15:415.CrossRefGoogle Scholar
19. Gomez-Simmonds, A, Greenman, M, Sullivan, SB, et al. Population structure of Klebsiella pneumoniae causing bloodstream infections at a New York City tertiary care hospital: diversification of multidrug-resistant isolates. J Clin Microbiol 2015;53:2060–2067.Google Scholar
20. Trecarichi, EM, Pagano, L, Candoni, A, et al. Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: an Italian multicentre prospective survey. Clinical Microbiology and Infection 2015;21:337–343.Google Scholar
21. Villegas, MV, Pallares, CJ, Escandon-Vargas, K, et al. Characterization and clinical impact of bloodstream infection caused by carbapenemase-producing Enterobacteriaceae in seven Latin American countries. PLoS ONE 2016;11:no pagination.Google Scholar
22. Vardakas, KZ, Matthaiou, DK, Falagas, ME, Antypa, E, Koteli, A, Antoniadou, E. Characteristics, risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in the intensive care unit. J Infect 2015;70:592–599.CrossRefGoogle ScholarPubMed
23. Lee, NY, Wu, JJ, Lin, SH, Ko, WC, Tsai, LH, Yan, JJ. Characterization of carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream isolates at a Taiwanese hospital: clinical impacts of lowered breakpoints for carbapenems. Eur J Clin Microbiol Infect Dis 2012;31:1941–1950.Google Scholar
24. Gallagher, JC, Kuriakose, S, Haynes, K, Axelrod, P. Case-case-control study of patients with carbapenem-resistant and third-generation-cephalosporin-resistant Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother 2014;58:5732–5735.Google Scholar
25. Mouloudi, E, Protonotariou, E, Zagorianou, A, et al. Bloodstream infections caused by metallo-beta-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.Google Scholar
26. Liu, SW, Chang, HJ, Chia, JH, Kuo, AJ, Wu, TL, Lee, MH. Outcomes and characteristics of ertapenem-nonsusceptible Klebsiella pneumoniae bacteremia at a university hospital in Northern Taiwan: a matched case-control study. J Microbiol Immunol Infect 2012;45:113–119.Google Scholar
27. Qureshi, ZA, Paterson, DL, Peleg, AY, et al. Clinical characteristics of bacteraemia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae in the era of CTX-M-type and KPC-type beta-lactamases. Clin Microbiol Infect 2012;18:887–893.CrossRefGoogle ScholarPubMed
28. Hussein, K, Raz-Pasteur, A, Finkelstein, R, et al. Impact of carbapenem resistance on the outcome of patients’ hospital-acquired bacteraemia caused by Klebsiella pneumoniae . J Hosp Infect 2013;83:307–313.CrossRefGoogle ScholarPubMed
29. Bartoletti, M, Giannella, M, Caraceni, P, et al. Epidemiology and outcomes of bloodstream infection in patients with cirrhosis. J Hepatol 2014;61:51–58.Google Scholar
30. Paul, M, Shani, V, Muchtar, E, Kariv, G, Robenshtok, E, Leibovici, L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother 2010;54:4851–4863.Google Scholar
31. Tumbarello, M, Viale, P, Viscoli, C, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis 2012;55:943–950.Google Scholar
32. Kang, CI, Kim, SH, Wan, BP, et al. Bloodstream infections caused by antibiotic-resistant gram-negative bacilli: risk factors for mortality and impact of inappropriate initial antimicrobial therapy on outcome. Antimicrob Agents Chemother 2005;49:760–766.Google Scholar
33. Zilberberg, MD, Shorr, AF, Micek, ST, Vazquez-Guillamet, C, Kollef, MH. Multidrug resistance, inappropriate initial antibiotic therapy and mortality in gram-negative severe sepsis and septic shock: a retrospective cohort study. Critical Care 2014;18:596.Google Scholar
34. Schwaber, MJ, Carmeli, Y. Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. J Antimicrob Chemother 2007;60:913–920.Google Scholar
35. 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.Google Scholar
36. Lodise, T, Ye, M, Keyloun, K, Zhao, Q, Gillard, P. Identification of patients at greatest risk for carbapenem resistance in patients with serious hospital-onset infections due to Enterobacteriaceae species. Abstract 1794, IDWeek 2016, New Orleans, LA.Google Scholar
37. Davies, J, Gordon, CL, Tong, SY, Baird, RW, Davis, JS. Impact of results of a rapid Staphylococcus aureus diagnostic test on prescribing of antibiotics for patients with clustered gram-positive cocci in blood cultures. J Clin Microbiol 2012;50:2056–2058.Google Scholar
38. Evans, SR, Hujer, AM, Jiang, H, et al. Rapid molecular diagnostics, antibiotic treatment decisions, and developing approaches to inform empiric therapy: PRIMERS I and II. Clin Infect Dis 2016;62:181–189.CrossRefGoogle ScholarPubMed
39. Tamma, PD, Goodman, KE, Harris, AD, et al. Comparing the outcomes of patients with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae bacteremia. Clin Infect Dis 2017;64:257–264.CrossRefGoogle ScholarPubMed
40. Hombach, M, Bloemberg, GV, Bottger, EC. Effects of clinical breakpoint changes in CLSI guidelines 2010/2011 and EUCAST guidelines 2011 on antibiotic susceptibility test reporting of gram-negative bacilli. J Antimicrob Chemother 2012;67:622–632.Google Scholar
Supplementary material: File

Kohler et al supplementary material

Kohler et al supplementary material 1

Download Kohler et al supplementary material(File)
File 506.8 KB