Genetic relationship, antibiotic resistance pattern and virulence factors of Klebsiella pneunoniae strains isolated from meningitis patients

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Published Jun 29, 2023
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Vol. 2 No. 02 (2023): June

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Mohammad Hussain Rustampoor
Reza Beigverdi
Najibullah Shafaq

Abstract

‌Backgroud: Meningitis due to Klebsiella pneunoniae is increasingly reported from several Asian countries.  Microbiological characteristic of K. pneumoniae strains causing meningitis is not yet explored in Iran. The aim of this study was to demonstrate antibiotic resistance pattern and virulence factors, as well as the genetic relationship of K. pneumoniae strains isolated from meningitis patients.
Materials and Mehtods: Eight K. pneumoniae isolates were collected from hospitalized patients at Imam Khomeini hospital, Tehran-Iran from 14 May 2018 to 15 Mar 2020. The antibiotic resistance pattern was determined by disc diffusion method.  Antibiotic resistance genes and virulence-associated genes were traced by Polymerase Chain Reaction. Repetitive Extragenic Palindromic Polymerase Chain Reaction was used for evaluation of the genetic relationships among isolates.
Findings: Six out of eight isolates were resistant to almost all the 15 antibiotics tested. These six isolates harbored triple antibiotic resistance genes: blaOXA-48, blaSHV, and aac (6’)-Ib. Five of these isolates co-harbored aac (3)-IIa gene. Besides, blaTEM and blaCTXM-1 were detected in five and three isolates respectively. blaNDM-1 was identified in one isolate. All isolates harbored acrAB, ompK36, and tolC resistance genes. None of the isolates were related to K1 or K2 capsular serotypes. The most commonly detected virulence genes were entB (100%), mrkD (100%), ybtS (62.5%) and kfu (25%). rep-PCR fingerprinting discriminated seven isolates into three clusters.
Conclusion: Simulations presence of the genes coding for Extended Spectrum Beta Lactamases, Carbapenemases, and Aminoglycoside Modifying Enzymes narrows therapeutic alternatives and imposes a heavy load on the public health system. Antibiotic susceptibility test is recommended however, Carbapenems can still be considered as first-line medications for preliminary empirical treatment of K. pneumoniae meningitis before obtaining susceptibility test results. Low genetic diversity suggests the circulation of certain K. pneumoniae clones in hospital which highlights the establishing of effective infection observation and prevention program.

Keywords

Klebsiella pneumoniae

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How to Cite
Rustampoor, M. H., Beigverdi, R., & Shafaq, N. (2023). Genetic relationship, antibiotic resistance pattern and virulence factors of Klebsiella pneunoniae strains isolated from meningitis patients. NUIJB, 2(02), 106–117. Retrieved from https://nuijb.nu.edu.af/index.php/nuijb/article/view/55

References

  1. Aksöz, E. D. C. A. N. (2015). Klebsiella pneumoniae: characteristics of carbapenem resistance and virulence factors. ABP, Vol. 62 No 4, 867–874
  2. Al Bshabshe, A., Al-Hakami, A., Alshehri, B., Al-Shahrani, K. A., Alshehri, A. A., Al Shahrani, M. B., Hamid, M. E. (2020). Rising Klebsiella pneumoniae Infections and Its Expanding Drug Resistance in the Intensive Care Unit of a Tertiary Healthcare Hospital, Saudi Arabia. Cureus, 12(8), e10060. doi:10.7759/cureus.10060
  3. Choi, M., Hegerle, N., Nkeze, J., Sen, S., Jamindar, S., Nasrin, S., Tennant, S. M. (2020). The Diversity of Lipopolysaccharide (O) and Capsular Polysaccharide (K) Antigens of Invasive Klebsiella pneumoniae in a Multi-Country Collection. Front Microbiol, 11, 1249. doi:10.3389/fmicb.2020.01249
  4. Clinical and Laboratory Standard Institute. (2019). Wayne: CLSI document M-100.
  5. Compain, F., Babosan, A., Brisse, S., Genel, N., Audo, J., Ailloud, F., Decré, D. (2014). Multiplex PCR for detection of seven virulence factors and K1/K2 capsular serotypes of Klebsiella pneumoniae. J Clin Microbiol, 52(12), 4377-4380. doi:10.1128/JCM.02316-14
  6. El Fertas-Aissani, R., Messai, Y., Alouache, S., & Bakour, R. (2013). Virulence profiles and antibiotic susceptibility patterns of Klebsiella pneumoniae strains isolated from different clinical specimens. Pathol Biol (Paris), 61(5), 209-216. doi:10.1016/j.patbio.2012.10.004
  7. El-Badawy, M. F., Tawakol, W. M., El-Far, S. W., Maghrabi, I. A., Al-Ghamdi, S. A., Mansy, M. S., Shohayeb, M. M. (2017). Molecular Identification of Aminoglycoside-Modifying Enzymes and Plasmid-Mediated Quinolone Resistance Genes among Klebsiella pneumoniae Clinical Isolates Recovered from Egyptian Patients. Int J Microbiol, 2017, 8050432. doi:10.1155/2017/8050432
  8. Ellis, J., Luintel, A., Chandna, A., & Heyderman, R. S. (2019). Community-acquired acute bacterial meningitis in adults: a clinical update. Br Med Bull, 131(1), 57-70. doi:10.1093/bmb/ldz023
  9. Falagas, M. E., & Kopterides, P. (2007). Old antibiotics for infections in critically ill patients. Current Opinion in Critical Care, 13(5), 592-597. doi:10.1097/MCC.0b013e32827851d7
  10. Fernández-Martínez, M., Ruiz Del Castillo, B., Lecea-Cuello, M. J., Rodríguez-Baño, J., Pascual, Á., & Martínez-Martínez, L. (2018). Prevalence of Aminoglycoside-Modifying Enzymes in Escherichia coli and Klebsiella pneumoniae Producing Extended Spectrum β-Lactamases Collected in Two Multicenter Studies in Spain. Microb Drug Resist, 24(4), 367-376. doi:10.1089/mdr.2017.0102
  11. Forge, A., & Schacht, J. (2000). Aminoglycoside antibiotics. Audiol Neurootol, 5(1), 3-22.
  12. Galani, I., Nafplioti, K., Adamou, P., Karaiskos, I., Giamarellou, H., & Souli, M. (2019). Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance. BMC Infect Dis, 19(1), 167. doi:10.1186/s12879-019-3801-1
  13. GelarehNasiri, A., TaghiNaserpourFarivar,Peyman Hosseini. (2018). Molecular epidemiology of aminoglycoside resistance in clinical isolates of Klebsiella pneumoniae collected from Qazvin and Tehran provinces, Iran. Infection, Genetics and Evolution.
  14. Granov, D., Dedeić-Ljubović, A., & Salimović-Bešić, I. (2020). Characterization of Carbapenemase-Producing Klebsiella pneumoniae in Clinical Center University of Sarajevo, Bosnia and Herzegovina. Microb Drug Resist, 26(9), 1038-1045. doi:10.1089/mdr.2019.0188
  15. Grundmann, H., Glasner, C., Albiger, B., Aanensen, D. M., Tomlinson, C. T., Andrasević, A. T., Monnet, D. L. (2017). Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study. Lancet Infect Dis, 17(2), 153-163. doi:10.1016/s1473-3099(16)30257-2
  16. Hou, X. H., Song, X. Y., Ma, X. B., Zhang, S. Y., & Zhang, J. Q. (2015). Molecular characterization of multidrug-resistant Klebsiella pneumoniae isolates. Braz J Microbiol, 46(3), 759-768.
  17. Khan, F. Y., Abukhattab, M., AbuKamar, M., & Anand, D. (2014). Adult Klebsiella pneumoniae meningitis in Qatar: clinical pattern of ten cases. Asian Pac J Trop Biomed, 4(8), 669-672.
  18. Kiaei, S., Moradi, M., Hosseini-Nave, H., Ziasistani, M., & Kalantar-Neyestanaki, D. (2019). Endemic dissemination of different sequence types of carbapenem-resistant Klebsiella pneumoniae strains harboring bla (NDM) and 16S rRNA methylase genes in Kerman hospitals, Iran, from 2015 to 2017. Infect Drug Resist, 12, 45-54. doi:10.2147/idr.s186994
  19. Krause, K. M., Serio, A. W., Kane, T. R., & Connolly, L. E. (2016). Aminoglycosides: An Overview. Cold Spring Harb Perspect Med, 6(6). doi:10.1101/cshperspect.a027029
  20. Ku, Y. H., Chuang, Y. C., Chen, C. C., Lee, M. F., Yang, Y. C., Tang, H. J., & Yu, W. L. (2017). Klebsiella pneumoniae Isolates from Meningitis: Epidemiology, Virulence and Antibiotic Resistance. Sci Rep, 7(1), 6634. doi:10.1038/s41598-017-06878-6
  21. Li, B., Zhao, Y., Liu, C., Chen, Z., & Zhou, D. (2014). Molecular pathogenesis of Klebsiella pneumoniae. Future Microbiol, 9(9), 1071-1081. doi:10.2217/fmb.14.48
  22. Lu, C. H., Huang, C. R., Chang, W. N., Chang, C. J., Cheng, B. C., Lee, P. Y., Chang, H. W. (2002). Community-acquired bacterial meningitis in adults: the epidemiology, timing of appropriate antimicrobial therapy, and prognostic factors. Clin Neurol Neurosurg, 104(4), 352-358.
  23. Mahsa Harir ForoushM.Sc., L. S. P. D. M. M. D. (2018). Prevalence of Genes Encoding Aminoglycoside Modifying Enzymes in Clinical Isolates of Klebsiella Pneumoniae in the Hospitals of Borujerd I J M L, 5(1), 35-41.
  24. Moghadampour, M., Rezaei, A., & Faghri, J. (2018). The emergence of blaOXA-48 and blaNDM among ESBL-producing Klebsiella pneumoniae in clinical isolates of a tertiary hospital in Iran. Acta Microbiol Immunol Hung, 65(3), 335-344. doi:10.1556/030.65.2018.034
  25. Mohammad Mehdi Feizabadi, S. D., Nafiseh Raji, Araz Majnooni, Marzieh Aligholi, Fereshteh Shahcheraghi, Mahmood Parvin, and Davud Yadegarinia. (2010). Distribution of blaTEM, blaSHV, blaCTX-M Genes Among Clinical Isolates of Klebsiella pneumoniae at Labbafinejad Hospital, Tehran, Iran. MICROBIAL DRUG RESISTANCE, Volume 16, Number 1.
  26. Mokhtari, H., Eslami, G., Zandi, H., Dehghan-Banadkouki, A., & Vakili, M. (2018). Evaluating the Frequency of aac(6')-IIa, ant(2″)-I, intl1, and intl2 Genes in Aminoglycosides Resistant Klebsiella pneumoniae Isolates Obtained from Hospitalized Patients in Yazd, Iran. Avicenna J Med Biotechnol, 10(2), 115-119.
  27. Nielsen, J. B., Skov, M. N., Jørgensen, R. L., Heltberg, O., Hansen, D. S., & Schønning, K. (2011). Identification of CTX-M15-, SHV-28-producing Klebsiella pneumoniae ST15 as an epidemic clone in the Copenhagen area using a semi-automated Rep-PCR typing assay. Eur J Clin Microbiol Infect Dis, 30(6), 773-778. doi:10.1007/s10096-011-1153-x
  28. Paczosa, M. K., & Mecsas, J. (2016). Klebsiella pneumoniae: Going on the Offense with a Strong Defense. Microbiol Mol Biol Rev, 80(3), 629-661. doi:10.1128/mmbr.00078-15
  29. Paterson, D. L., & Bonomo, R. A. (2005). Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev, 18(4), 657-686. doi:10.1128/cmr.18.4.657-686.2005
  30. Queenan, A. M., & Bush, K. (2007). Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev, 20(3), 440-458, table of contents. doi:10.1128/cmr.00001-07
  31. Ragheb, S. M., Tawfick, M. M., El-Kholy, A. A., & Abdulall, A. K. (2020). Phenotypic and Genotypic Features of Klebsiella pneumoniae Harboring Carbapenemases in Egypt: OXA-48-Like Carbapenemases as an Investigated Model. Antibiotics (Basel), 9(12). doi:10.3390/antibiotics9120852
  32. Rastegar, S., Moradi, M., Kalantar-Neyestanaki, D., Ali Golabi, D., & Hosseini-Nave, H. (2019). Virulence Factors, Capsular Serotypes and Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae and Classical Klebsiella pneumoniae in Southeast Iran. Infect Chemother.
  33. Scheld, W. M., Koedel, U., Nathan, B., & Pfister, H. W. (2002). Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury. J Infect Dis, 186 Suppl 2, S225-233. doi:10.1086/344939
  34. Shi, W., Li, K., Ji, Y., Jiang, Q., Wang, Y., Shi, M., & Mi, Z. (2013). Carbapenem and cefoxitin resistance of Klebsiella pneumoniae strains associated with porin OmpK36 loss and DHA-1 β-lactamase production. Braz J Microbiol, 44(2), 435-442. doi:10.1590/s1517-83822013000200015
  35. Shoja, S., Ansari, M., Faridi, F., Azad, M., Davoodian, P., Javadpour, S., Karmostaji, A. (2018). Identification of Carbapenem-Resistant Klebsiella pneumoniae with Emphasis on New Delhi Metallo-Beta-Lactamase-1 (blaNDM-1) in Bandar Abbas, South of Iran. Microb Drug Resist, 24(4), 447-454.
  36. Tang, L. M., & Chen, S. T. (1994). Klebsiella pneumoniae meningitis: prognostic factors. Scand J Infect Dis, 26(1), 95-102. doi:10.3109/00365549409008596
  37. Tang, L. M., Chen, S. T., Hsu, W. C., & Chen, C. M. (1997). Klebsiella meningitis in Taiwan: an overview. Epidemiol Infect, 119(2), 135-142. doi:10.1017/s0950268897007930
  38. Wasfi, R., Elkhatib, W. F., & Ashour, H. M. (2016). Molecular typing and virulence analysis of multidrug resistant Klebsiella pneumoniae clinical isolates recovered from Egyptian hospitals. Scientific Reports, 6, 38929-38929. doi:10.1038/srep38929
  39. Wong, Y. P., Chua, K. H., & Thong, K. L. (2014). One-step species-specific high resolution melting analysis for nosocomial bacteria detection. J Microbiol Methods, 107, 133-137.
  40. Xu, M., Fu, Y., Fang, Y., Xu, H., Kong, H., Liu, Y., Li, L. (2019). High prevalence of KPC-2-producing hypervirulent Klebsiella pneumoniae causing meningitis in Eastern China. Infect Drug Resist, 12, 641-653.
  41. Zeinab Jafari, A. A. H., Mehri Haeili, Jalil Kardan-Yamchi, Sirous Jafari, Fereshteh Jabalameli, Alipasha Meysamie, Alireza Abdollahi, and Mohammad Mehdi Feizabadi. (2018). Molecular Epidemiology and Drug Resistance Pattern of Carbapenem-Resistant Klebsiella pneumoniae Isolates from Iran. MICROBIAL DRUG RESISTANCE, Volume 00, Number 00.