Clinical Usefulness of Klebsiella Pneumoniae Carbapenemase-Producing K. Pneumoniae Genotyping: The Experience of a Single-Center Epidemic

Marianna Rossi, Liliane Chatenoud, Egidio Franco Viganò, Anna Maria Peri, Laura Alagna, Simone Bramati, Monica Manenti, Monica Raggi, Annalisa Cavallero, Luca Bisi, Sebastiano Leone, Guglielmo Marco Migliorino, Alessandra Bandera, Andrea Gori

Abstract


Background: During the last decade, the spread of Klebsiella pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) has increased dramatically worldwide. In this scenario, growing interest has been addressed to genotyping of KPC-Kp strains, which emerged as an important tool for a better understanding of the epidemiological and clinical characteristics of the outbreaks.

Methods: We performed a retrospective cohort study on patients infected with KPC-Kp during a 28-month outbreak period (January 2010–April 2012) at San Gerardo Hospital (Monza, Italy), investigating KPC-Kp genotypes by means of repetitive element sequence-based polymerase chain reaction (Rep-PCR).

Results: We enrolled 97 patients infected with KPC-Kp. Rep-PCR analysis identified 5 distinct clone types, with different distribution over time. During the first 12 months of the outbreak period, only 1 clone was detected (clone A, in 47 patients), while the 4 other clones were identified over the remaining 16 months (clones C, E, and F/L in 23, 24, and 3 patients respectively). Mechanical ventilation was less frequent in patients infected with clones C/E/F/L (OR=0.14; 95% CI: 0.05-0.37) compared to clone A, and the Charlson comorbidity index (CI) was more likely to have a score >5 in patients infected with clones C/E/F/L (OR=7.21; 95% CI: 2.24-23.14) compared to clone A.

Overall mortality was higher in patients infected with clones C/E/F/L (13/20 patients, 65%) compared to those infected with clone A (7/20, 35%). Mortality in patients infected with clones C/E/F/L remained significantly higher even after adjusting for the potential confounding effect of comorbidities (ie, CI), with a hazard ratio (HR) of 4.65 (95% CI: 1.83-11.89).

Keywords


KPC-Kp; carbapenemases; Enterobacteriaceae; genotyping profiles; drug-resistant

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References


1. Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL, Cormican M, Cornaglia G, Garau J, Gniadkowski M, Hayden MK, Kumarasamy K, Livermore DM, Maya JJ, Nordmann P, Patel JB, Paterson DL, Pitout J, Villegas MV, Wang H, Woodford N, Quinn JP. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2013;13(9):785-96. PubMed PMID: 23969216. Pubmed Central PMCID: 4673667. doi: 10.1016/S1473-3099(13)70190-7

2. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, Alberti S, Bush K, Tenover FC. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother. 2001;45(4):1151-61. PubMed PMID: 11257029. Pubmed Central PMCID: 90438. doi:

3. Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis. 2009;9(4):228-36. PubMed PMID: 19324295. doi:

4. Schwaber MJ, Carmeli Y. Carbapenem-resistant Enterobacteriaceae: a potential threat. JAMA. 2008;300(24):2911-3. PubMed PMID: 19109119. doi: 10.1001/jama.2008.896

5. Cornaglia G, Giamarellou H, Rossolini GM. Metallo-beta-lactamases: a last frontier for beta-lactams? Lancet Infect Dis. 2011;11(5):381-93. PubMed PMID: 21530894. doi: 10.1016/S1473-3099(11)70056-1

6. Canton R, Akova M, Carmeli Y, Giske CG, Glupczynski Y, Gniadkowski M, Livermore DM, Miriagou V, Naas T, Rossolini GM, Samuelsen O, Seifert H, Woodford N, Nordmann P, European Network on C. Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe. Clin Microbiol Infect. 2012;18(5):413-31. PubMed PMID: 22507109. doi: 10.1111/j.1469-0691.2012.03821.x

7. Gasink LB, Edelstein PH, Lautenbach E, Synnestvedt M, Fishman NO. Risk factors and clinical impact of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Infect Control Hosp Epidemiol. 2009;30(12):1180-5. PubMed PMID: 19860564. Pubmed Central PMCID: 2893218. doi: 10.1086/648451

8. Shields RK, Potoski BA, Haidar G, Hao B, Doi Y, Chen L, Press EG, Kreiswirth BN, Clancy CJ, Nguyen MH. Clinical Outcomes, Drug Toxicity, and Emergence of Ceftazidime-Avibactam Resistance Among Patients Treated for Carbapenem-Resistant Enterobacteriaceae Infections. Clin Infect Dis. 2016;63(12):1615-8. PubMed PMID: 27624958. Pubmed Central PMCID: 5146720. 10.1093/cid/ciw636

9. Zarkotou O, Pournaras S, Tselioti P, Dragoumanos V, Pitiriga V, Ranellou K, Prekates A, Themeli-Digalaki K, Tsakris A. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin Microbiol Infect. 2011;17(12):1798-803. PubMed PMID: 21595793. doi: 10.1111/j.1469-0691.2011.03514.x

10. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother. 2012 Apr;56(4):2108-13. doi: 10.1128/AAC.06268-11

11. Akova M, Daikos GL, Tzouvelekis L, Carmeli Y. Interventional strategies and current clinical experience with carbapenemase-producing Gram-negative bacteria. Clin Microbiol Infect. 2012;18(5):439-48. PubMed PMID: 22507111. doi: 10.1111/j.1469-0691.2012.03823.x

12. Gomez-Simmonds A, Greenman M, Sullivan SB, Tanner JP, Sowash MG, Whittier S, Uhlemann AC. 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(7):2060-7. PubMed PMID: 25878348. Pubmed Central PMCID: 4473223. doi: 10.1128/JCM.03455-14

13. Diago-Navarro E, Chen L, Passet V, Burack S, Ulacia-Hernando A, Kodiyanplakkal RP, Levi MH, Brisse S, Kreiswirth BN, Fries BC. Carbapenem-resistant Klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits. J Infect Dis. 2014;210(5):803-13. PubMed PMID: 24634498. Pubmed Central PMCID: 4432395. doi: 10.1093/infdis/jiu157

14. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 1987;40(5):373-83. PubMed PMID: 3558716.

15. Russell JA. Management of sepsis. N Engl J Med. 2006;355(16):1699-713. PubMed PMID: 17050894. doi: 10.1056/NEJMra043632

16. CDC/NHSN surveillance definitions for specific types of infections. January 2015.

17. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twenty-first informational supplement. CLSI document M100-S21. Wayne, PA: CLSI, 2011.

18. European Committee on Antimicrobial Susceptibility Testing. Available at: http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Disk_test_documents/EUCAST_breakpoints_v1.3_pdf.pdf . Accessed 3 November 2011.

19. Tsakris A, Kristo I, Poulou A, Themeli-Digalaki K, Ikonomidis A, Petropoulou D, Pournaras S, Sofianou D. Evaluation of boronic acid disk tests for differentiating KPC-possessing Klebsiella pneumoniae isolates in the clinical laboratory. J Clin Microbiol. 2009;47(2):362-7. PubMed PMID: 19073868. Pubmed Central PMCID: 2643660. doi: 10.1128/JCM.01922-08

20. Endimiani A, Hujer AM, Perez F, Bethel CR, Hujer KM, Kroeger J, Oethinger M, Paterson DL, Adams MD, Jacobs MR, Diekema DJ, Hall GS, Jenkins SG, Rice LB, Tenover FC, Bonomo RA. Characterization of blaKPC-containing Klebsiella pneumoniae isolates detected in different institutions in the Eastern USA. J Antimicrob Chemother. 2009;63(3):427-37. PubMed PMID: 19155227. Pubmed Central PMCID: 2640158. doi: 10.1093/jac/dkn547

21. Borer A, Saidel-Odes L, Riesenberg K, Eskira S, Peled N, Nativ R, Schlaeffer F, Sherf M. Attributable mortality rate for carbapenem-resistant Klebsiella pneumoniae bacteremia. Infect Control Hosp Epidemiol. 2009;30(10):972-6. PubMed PMID: 19712030. doi: 10.1086/605922

22. Souli M, Galani I, Antoniadou A, Papadomichelakis E, Poulakou G, Panagea T, Vourli S, Zerva L, Armaganidis A, Kanellakopoulou K, Giamarellou H. An outbreak of infection due to beta-lactamase Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae in a Greek university hospital: molecular characterization, epidemiology, and outcomes. Clin Infect Dis. 2010;50(3):364-73. PubMed PMID: 20041768. doi: 10.1086/649865

23. Carmeli Y, Akova M, Cornaglia G, Daikos GL, Garau J, Harbarth S, Rossolini GM, Souli M, Giamarellou H. Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control. Clin Microbiol Infect. 2010;16(2):102-11. PubMed PMID: 20085604. doi: 10.1111/j.1469-0691.2009.03115.x

24. Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, Spanu T, Ambretti S, Ginocchio F, Cristini F, Losito AR, Tedeschi S, Cauda R, Bassetti M. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: Importance of combination therapy. Clin Infect Dis. 2012;55(7):943-50. PubMed PMID: 22752516. doi: 10.1093/cid/cis588

25. Sbrana F, Malacarne P, Viaggi B, Costanzo S, Leonetti P, Leonildi A, Casini B, Tascini C, Menichetti F. Carbapenem-sparing antibiotic regimens for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae in intensive care unit. Clin Infect Dis. 2013;56(5):697-700. PubMed PMID: 23155147. doi: 10.1093/cid/cis969

26. Giske CG, Froding I, Hasan CM, Turlej-Rogacka A, Toleman M, Livermore D, Woodford N, Walsh TR. Diverse sequence types of Klebsiella pneumoniae contribute to the dissemination of blaNDM-1 in India, Sweden, and the United Kingdom. Antimicrob Agents Chemother. 2012;56(5):2735-8. PubMed PMID: 22354295. Pubmed Central PMCID: 3346639. doi: 10.1128/AAC.06142-11

27. Hasan CM, Turlej-Rogacka A, Vatopoulos AC, Giakkoupi P, Maatallah M, Giske CG. Dissemination of blaVIM in Greece at the peak of the epidemic of 2005-2006: clonal expansion of Klebsiella pneumoniae clonal complex 147. Clin Microbiol Infect. 2014;20(1):34-7. PubMed PMID: 23464880. doi: 10.1111/1469-0691.12187


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