High prevalence of OXA-48-like and NDM carbapenemases among carbapenem resistant Klebsiella pneumoniae of clinical origin from Iran
Abstract
Background and Objectives: Klebsiella pneumoniae is increasingly developing resistance to last-resort antibiotics such as carbapenems. This study aimed to investigate the dissemination of common carbapenemase encoding genes among 48 clinical isolates of carbapenem-resistant Klebsiella pneumoniae (CRKP).
Materials and Methods: Antimicrobial susceptibility testing was performed by broth dilution and disc diffusion methods. The phenotypic evaluation of carbapenemase production was performed by using Modified Carbapenem Inactivation Method. Presence of carbapenemase encoding genes blaKPC, blaNDM, blaOXA-48-like, blaIMP, and blaVIM was screened by PCR.
Results: Overall, carbapenemases were produced in all CRKP isolates. The blaOXA-48-like and blaNDM were the most prevalent genes detected among all and 66.6% (n=32) of CRKP isolates respectively. The blaVIM was detected in only one isolate co-harboring NDM and OXA-48-like carbapenemases. The blaKPC and blaIMP genes were not identified in any of the isolates. While tigecycline was the most active agent against CRKP isolates with low resistance rate (4.1%), high rate of resistance was observed to colistin (66.6%), amikacin (79%) and most of other tested antimicrobials.
Conclusion: Our results revealed predominant prevalence of OXA-48-like and NDM carbapenemases among CRKP clinical isolates. High rate of resistance to last-resort agents such as colistin among CRKP isolates is a source of great concern.
2. Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: past, present, and future. Antimicrob Agents Chemother 2011; 55: 4943-4960.
3. Band VI, Satola SW, Burd EM, Farley MM, Jacob JT, Weiss DS. Carbapenem-resistant Klebsiella pneumoniae exhibiting clinically undetected colistin heteroresistance leads to treatment failure in a murine model of infection. mBio 2018; 9(2): e02448-17.
4. Sheu C-C, Chang Y-T, Lin S-Y, Chen Y-H, Hsueh P-R. Infections caused by carbapenem-resistant Enterobacteriaceae: an update on therapeutic options. Front Microbiol 2019; 10: 80.
5. Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev 2017; 41: 252-275.
6. Castanheira M, Deshpande LM, Mendes RE, Doyle TB, Sader HS. Prevalence of carbapenemase genes among carbapenem-nonsusceptible Enterobacterales collected in US hospitals in a five-year period and activity of ceftazidime/avibactam and comparator agents. JAC Antimicrob Resist 2022; 4: dlac098.
7. Protonotariou E, Meletis G, Pilalas D, Mantzana P, Tychala A, Kotzamanidis C, et al. Polyclonal endemicity of carbapenemase-producing Klebsiella pneumoniae in ICUs of a Greek tertiary care hospital. Antibiotics (Basel) 2022; 11: 149.
8. Bonura C, Giuffrè M, Aleo A, Fasciana T, Di Bernardo F, Stampone T, et al. An update of the evolving epidemic of bla KPC carrying Klebsiella pneumoniae in Sicily, Italy, 2014: emergence of multiple non-ST258 clones. PLoS One 2015; 10(7): e0132936.
9. Albiger B, Glasner C, Struelens MJ, Grundmann H, Monnet DL. Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill 2015; 20: 10.2807/1560-7917.ES.2015.20.45.30062.
10. Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother 2012; 67: 1597-1606.
11. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, et al. Characterization of a new metallo-β-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.
12. Khan AU, Maryam L, Zarrilli R. Structure, genetics and worldwide spread of New Delhi metallo-β-lactamase (NDM): a threat to public health. BMC Microbiol 2017; 17: 101.
13. Procop GW, Church DL, Hall GS, Janda WM. Koneman's color atlas and textbook of diagnostic microbiology: Jones & Bartlett Publishers; 2020.
14. Weinstein MP. Performance standards for antimicrobial susceptibility testing: Clinical and Laboratory Standards Institute; 2021.
15. Haeili M, Barmudeh S, Omrani M, Zeinalzadeh N, Kafil HS, Batignani V, et al. Whole-genome sequence analysis of clinically isolated carbapenem resistant Escherichia coli from Iran. BMC Microbiol 2023; 23: 49.
16. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 2011; 70: 119-123.
17. Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis 2011; 53: 60-67.
18. van Duin D, Cober E, Richter SS, Perez F, Kalayjian RC, Salata RA, et al. Impact of therapy and strain type on outcomes in urinary tract infections caused by carbapenem-resistant Klebsiella pneumoniae. J Antimicrob Chemother 2015; 70: 1203-1211.
19. Messina JA, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, et al. Hospital readmissions in patients with carbapenem-resistant Klebsiella pneumoniae. Infect Control Hosp Epidemiol 2016; 37: 281-288.
20. Abbasi E, Ghaznavi-Rad E. High frequency of NDM-1 and OXA-48 carbapenemase genes among Klebsiella pneumoniae isolates in central Iran. BMC Microbiol 2023; 23: 98.
21. Mokhtari M, Mojtahedi A, Mahdieh N, Jafari A, Arya MJ. High prevalence of blaOXA-48 and blaNDM-producing carbapenem-resistant Klebsiella pneumoniae isolated from clinical samples in shahid rajaei hospital in tehran, Iran. Jundishapur J Microbiol 2022; 15(10): e130804.
22. Boyd SE, Holmes A, Peck R, Livermore DM, Hope W. OXA-48-like β-lactamases: global epidemiology, treatment options, and development pipeline. Antimicrob Agents Chemother 2022; 66(8): e0021622.
23. Stewart A, Harris P, Henderson A, Paterson D. Treatment of infections by OXA-48-producing Enterobacteriaceae. Antimicrob Agents Chemother 2018; 62(11): e01195-18.
24. Castanheira M, Doyle TB, Deshpande LM, Mendes RE, Sader HS. Activity of ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam against carbapenemase-negative carbapenem-resistant Enterobacterales isolates from US hospitals. Int J Antimicrob Agents 2021; 58: 106439.
25. Mairi A, Pantel A, Sotto A, Lavigne J-P, Touati A. OXA-48-like carbapenemases producing Enterobacteriaceae in different niches. Eur J Clin Microbiol Infect Dis 2018; 37: 587-604.
26. Samuelsen Ø, Naseer U, Karah N, Lindemann PC, Kanestrøm A, Leegaard TM, et al. Identification of Enterobacteriaceae isolates with OXA-48 and coproduction of OXA-181 and NDM-1 in Norway. J Antimicrob Chemother 2013; 68: 1682-1685.
27. Khajuria A, Praharaj AK, Kumar M, Grover N. Emergence of Escherichia coli, co-producing NDM-1 and OXA-48 carbapenemases, in urinary isolates, at a tertiary care centre at Central India. J Clin Diagn Res 2014; 8: DC01-4.
28. Dortet L, Cuzon G, Ponties V, Nordmann P. Trends in carbapenemase-producing Enterobacteriaceae, France, 2012 to 2014. Euro Surveill 2017; 22: 30461.
29. Solgi H, Badmasti F, Giske CG, Aghamohammad S, Shahcheraghi F. Molecular epidemiology of NDM-1-and OXA-48-producing Klebsiella pneumoniae in an Iranian hospital: clonal dissemination of ST11 and ST893. J Antimicrob Chemother 2018; 73: 1517-1524.
30. Jafari Z, Harati AA, Haeili M, Kardan-Yamchi J, Jafari S, Jabalameli F, et al. Molecular epidemiology and drug resistance pattern of carbapenem-resistant Klebsiella pneumoniae isolates from Iran. Microb Drug Resist 2019; 25: 336-343.
31. El-Mahallawy HA, El Swify M, Abdul Hak A, Zafer MM. Increasing trends of colistin resistance in patients at high-risk of carbapenem-resistant Enterobacteriaceae. Ann Med 2022; 54: 1-9.
32. Conceição-Neto OC, da Costa BS, Pontes LdS, Silveira MC, Justo-da-Silva LH, de Oliveira Santos IC, et al. Polymyxin resistance in clinical isolates of K. pneumoniae in Brazil: Update on molecular mechanisms, clonal dissemination and relationship with KPC-producing strains. Front Cell Infect Microbiol 2022:12: 898125.
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Issue | Vol 15 No 5 (2023) | |
Section | Original Article(s) | |
DOI | https://doi.org/10.18502/ijm.v15i5.13866 | |
Keywords | ||
Klebsiella pneumoniae; Carbapenem resistance; NDM; OXA-48-like; VIM |
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