Frequency of Carbapenemase Producing Klebsiella pneumoniae in Makkah, Saudi Arabia

Objective: Carbapenemase producing Klebsiella pneumoniae is emerging as an important pathogen worldwide which has alarming clinical threat with serious effects on patients’ outcome. The aim of our study is to determine prevalence of carbapenemase producing K. pneumoniae and its antibiotic susceptibility pattern in tertiary care hospitals. Methods: A prospective study was performed on 260 clinical isolates of K. pneumoniae collected from five different hospitals of Makkah, Saudi Arabia from January to July 2015. All clinical isolates were confirmed as K. pneumoniae using Vitek 2 system. These isolates were then screened for potential carbapenemase producers by determining reduced susceptibility to carbapenems using representative antibiotic disks of third generation cephalosporins and carbapenems in the disk diffusion test following guidelines of Clinical and Laboratory Standards Institute. Minimum inhibitory concentration of isolates found positive in screening test were determined for cephalosporins, carbapenems, aminoglycosides and tigecycline and colistin using Vitek-2 system. Modified Hodge test was performed to detect carbapenemase production on the isolates suspected for carbapenemase production. Results: Out of 260 K. pneumoniae isolates, 31 (11.9%) have shown 100% resistance to all cephalosporins. Of 31 K. pneumoniae isolates, 15 (48.4%) were found positive for carbapenemase. All carbapenem resistant isolates were sensitive to colistin and tigecycline. However, these isolates have shown resistance to amikacin (41.9%) and gentamicin (51.6%), respectively. Conclusion: This is the first report from Makkah reporting carbapenamse producing K.pneumoniae. Of 12% potential carbapenemase producing K.pneumoniae, 48.4% were found positive for carbapenemase production. Molecular characterization of these strains will help to determine the type of carbapenemase prevalent in this area. J Microbiol Infect Dis 2016;6(3): 121-127  

___

  • 1. Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009; 9: 228-236.
  • 2. World Health Organization. Antimicrobial resistance: global report on surveillance. Geneva: WHO Press 2014: 17-19.
  • 3. Bush K, Jacoby GA. Updated Functional Classification of β-lactamases. Antimicrob Agents Chemother 2010; 54: 969- 976.
  • 4. Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2011; 17:1791-1798.
  • 5. Yigit H, Queenan AM, Anderson GJ, et al. Novel carbapenemhydrolyzing beta-lactamases, KPC-1, from a carbapenem resistant strains of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001; 45:1151-1161.
  • 6. Mammina C, Palma DM, Bonura C, et al. Outbreak of infection with Klebsiella pneumoniae sequence type 258 producing Klebsiella pneumoniae carbapenemase 3 in an intensive care unit in Italy. J Clin Microbiol 2010; 48:1506-1507.
  • 7. Pesesky MW, Hussain T, Wallace M, et al. KPC and NDM-1 Genes in Related Enterobacteriaceae Strains and Plasmids from Pakistan and the United States. Emerg Infect Dis 2015; 21:1034-1037.
  • 8. 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.
  • 9. Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-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; 253:5046–54.
  • 10. Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 2010; 10:597-602.
  • 11. Nordmann P, Poirel L, Walsh TR. The emerging NDM carbapenemases. Trends Microbiol 2011; 19:588-595.
  • 12. Dortet L, Poirel L, Nordmann P. Worldwide dissemination of the NDM-type carbapenemases in gram-negative bacteria. Bio Med Res Int 2014; 1-12.
  • 13. Dortet L, Poirel L, Al Yaqoubi F, Nordmann P. NDM-1, OXA- 48 and OXA-181 carbapenemase-producing Enterobacteriaceae in Sultanate of Oman. Clin Microbiol Infect 2012; 18: E144–E148.
  • 14. El-Herte RI, Araj GF, Matar GM, et al. Detection of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae producing NDM-1 in Lebanon (case report). J Infect Dev Ctries 2012; 6:457-61.
  • 15. Al-Agamy MH, Shibl AM, Elkhizzi NA, Meunier D, Turton JF, Livermore DM. (2013) Persistence of Klebsiella pneumoniae clones with OXA-48 or NDM carbapenemases causing bacteraemias in a Riyadh hospital. Diagn Microbiol Infect Dis 76: 214-216.
  • 16. Shibl AM, Al-Agamy MH, Memish Z, Senok A, Khader SA, Assiri A. The emergence of OXA-48- and NDM-1-positive Klebsiella pneumoniae in Riyadh, Saudi Arabia. Int J Infect Dis 2013; 17:e1130-e1133.
  • 17. Zowawi HM, Sartor AL, Balkhy HH, et al. Molecular characterization of carbapenemase producing Escherichia coli and Klebsiella pneumoniae in the countries of the Gulf Cooperation Council: dominance of OXA-48 and NDM producers. Antimicrob Agents Chemother 2014; 58:3085-3090.
  • 18. Clinical and Laboratory Standard Institute. Performance standards for antimicrobial susceptibility testing; Twentysecond informational supplement. 2013; M100-S23: 33(1). Clinical Laboratory Standards Institute, Wayne, PA. USA
  • 19. Capone A, Giannella M, Fortini D, et al. High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality. Clin Microbiol Infect 2013; 19:E23-E30.
  • 20. Paterson DL, Hujer KM, Hujer AM, et al. Extended spectrum beta-lactamases in K. pneumoniae blood stream isolates from seven countries: dominance and widespread prevalence of SHV- and CTX-M-type beta-lactamases. Antimicrob Agents Chemother 2003; 47:3554-60.
  • 21. Sader HS and Sentry Participants Group (Sentry antimicrobial surveillance program report: Latin American and Brazilian results for 1997 through 2001. Braz J Infect Dis 2004; 8:25-79.
  • 22. Ahmad S, Al-Juaid NF, Alenzi FQ, Mattar EH, Bakheet Oel-S. Prevalence, antibiotic susceptibility pattern and production of extended-spectrum beta-lactamases amongst clinical isolates of Klebsiella pneumoniae at Armed Forces Hospital in Saudi Arabia. J Coll Physicians Surg Pak 2009; 19:264-265.
  • 23. Toroglu S, Keskin D. Antimicrobial resistance and sensitivity among isolates of Klebsiella pneumoniae from hospital patients in Turkey. Int J Agri Biol. 2011; 13: 941–46.
  • 24. Zagorianou A, Silanou E, Losfidis E, et al. Microbiological and molecular characterization of carbapenemase producing Klebsiella pneumoniae endemic in a tertiary Greek hospital during 2004-2010. www.eurosurveillance.org 2012; 1-7.
  • 25. Balkhy HH, El-Saed A, Al Johani SM, et al. The epidemiology of the first described carbapenem-resistant Klebsiella pneumoniae outbreak in a tertiary care hospital in Saudi Arabia: how far do we go? Eur J Clin Microbiol Infect Dis. 2012; 31:1901-1909.
  • 26. Rasheed JK, Kitchel B, Zhu W, et al. New Delhi metallo-β- lactamase-producing Enterobacteriaceae, United States. Emerg Infect Dis 2013; 19:870-78.
  • 27. Rozales FP, Ribeiro VB, Magagnin CM, et al. Emergence of NDM-1-producing Enterobacteriaceae in Porto Alegre, Brazil. Int J Infect Dis 2014; 25:79-81.
  • 28. Wang X, Chen G, Wu X, et al. Increased prevalence of carbapenem resistant Enterobacteriaceae in hospital setting due to cross-species transmission of the blaNDM-1 element and clonal spread of progenitor resistant strains. Front Microbiol 2015; 6:595.
  • 29. Kanj SS and Kanafani ZA. Current concepts in antimicrobial therapy against resistant gram-negative organisms: Extended-Spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug resistant Pseudomonas aeruginosa. Mayo Clinic Proceedings 2011; 86:250-59.
  • 30. Endimiani A, Perez F, Bajaksouzian S, et al. Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced susceptibility. J Clin Microbiol 2010; 48:4417-4425.