• KHALID MUBARAK BINDAYNA Department of Microbiology, Immunology and Infectious Diseases, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
  • RONNI MOL JOJI Department of Microbiology, Immunology and Infectious Diseases, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
  • HICHAM EZZAT Department of Microbiology, Immunology and Infectious Diseases, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
  • HAITHAM ALI JAHRAMI Rehabilitation Services, Ministry of Health, Manama, Kingdom of Bahrain.


Objective: The objective of the study was to look on the prevalence of six AMR genes (CTX-M, TEM, SHV, NDM-1, OXA-48, and VIM genes) in the province of the Arabian Gulf. We performed a systematic review and meta-analysis of the published studies from the Arabian Gulf countries and analyzed the antimicrobial resistance (AMR) genes pattern present in Klebsiella pneumoniae.

Methods: The present study used the Meta-analysis Of Observational Studies in Epidemiology as a guideline for reporting findings. An electronic search was conducted in online databases such as PubMed/MEDLINE, EMBASE, Scopus, Google Scholar, Science Direct, and Web of Science from January 2014 to June 2020 following the inclusion and exclusion criteria. Articles published were included in the study resistance pattern among 2036 isolates were analyzed. These isolates conferred the AMR genes including OXA-48 (n=500), CTX-M (n= 1796), SHV (n=1637), TEM (n=1492), NDM-1 (n=500), and VIM (n=302).

Results: Of 160 initially searched studies, 28 entries met the inclusion criteria and were subjected to meta-analysis. Critical appraisal of studies or quality assessment revealed a mean quality score was 4.2, with an SD of 1.6. The analysis revealed predominant AMR genes wereOXA-48 followed by CTX-M, SHV, TEM, NDM-1, and VIM in the Arabian Gulf region.

Conclusion: The Arabian Gulf countries share a high prevalence of OXA-48, CTX-M followed by SHV, TEM, NDM-1, and VIM genes. Antimicrobial-resistant in K. pneumoniae is a threat to public health and this needs strong surveillance to curb this threat.

Keywords: Antimicrobial resistance genes, Arabian Gulf region, Klebsiella pneumoniae, Meta-analysis, Systematic review


1. Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: Epidemiology, taxonomy, typing methods, and pathogenicity factors.Clin Microbiol Rev 1998;11:589-603.
2. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014;370:1198-208.
3. Piruozi AF, Farahani A, Forouzandeh Z, Ahmadi I, Abdizadeh R, Kalantar M, et al. Investigating the frequency of Klebsiella infection and drug resistance among inpatients and outpatients referring to Amir Al-Momenin Hospital, Gerash, Iran. Gene Cell Tissue 2019;6:e93161.
4. Munita JM, Arias CA. Mechanisms of antibiotic resistance. Microbiol Spectrum 2016;4:1128.
5. Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013. Atlanta: Centers for Disease Control and Prevention; 2014.
6. Effah CY, Sun T, Liu S, Wu Y. Klebsiella pneumoniae: An increasing threat to public health. Ann Clin Microbiol Antimicrob 2020;19:1.
7. Sarojamma V, Ramakrishna V. Prevalence of ESBL-producing Klebsiella pneumoniae isolates in tertiary care hospital. ISRN Microbiol 2011;2011:318348.
8. Daehre K, Projahn M, Friese A, Semmler T, Guenther S, Roesler UH. ESBL-producing Klebsiella pneumoniae in the broiler production chain and the first description of ST3128. Front Microbiol 2018;9:2302.
9. Al-Tawfiq JA, Stephens G, Memish ZA. Inappropriate antimicrobial use and potential solutions: A Middle Eastern perspective. Expert Rev Antiinfect Ther 2010;8:765-74.
10. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 2000;283:2008-12.
11. Sánchez-Romero I, Asensio Á, Oteo J, Muñoz-Algarra M, Isidoro B, Vindel A, et al. Nosocomial outbreak of VIM-1-producing Klebsiella pneumoniae isolates of multilocus sequence Type 15: Molecular basis, clinical risk factors, and outcome. Antimicrob Agents Chemother 2012;56:420-7.
12. Al-Zahrani IA, Alsiri BA. The emergence of carbapenem-resistant Klebsiella pneumoniae isolates producing OXA-48 and NDM in the Southern (Asir) Province, Saudi Arabia. Saudi Med J 2018;39:23-30.
13. AlTamimi M, AlSalamah A, AlKhulaifi M, AlAjlan H. Comparison of phenotypic and PCR methods for detection of carbapenemases production by Enterobacteriaceae. Saudi J Biol Sci 2017;24:155-61.
14. Shibl A, Al-Agamy M, 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:e1130-3.
15. Sonnevend A, Ghazawi AA, Hashmey R, Jamal W, Rotimi VO, Shibl AM, et al. Characterization of carbapenem-resistant Enterobacteriaceae with high rate of autochthonous transmission in the Arabian Peninsula. PLoS One 2015;10:e0131372.
16. Jamal W, Rotimi VO, Albert MJ, Khodakhast F, Nordmann P, Poirel L. High prevalence of VIM-4 and NDM-1 metallo-beta-lactamase among carbapenem-resistant Enterobacteriaceae. J Med Microbiol 2013;62:1239-44.
17. Eltai NO, Al Thani AA, Al-Ansari K, Deshmukh AS, Wehedy E, Al- Hadidi SH, et al. Molecular characterization of extended spectrum beta-lactamases Enterobacteriaceae causing lower urinary tract infection among pediatric population. Antimicrob Resist Infect Control 2018;7:90.
18. Elhassan MM, Hemeg HA, Ahmed AA. Dissemination of CTX-M extended-spectrum ?-lactamases (ESBLs) among Escherichia coli and Klebsiella pneumoniae in Al-Madenah Al-Monawwarah Region, Saudi Arabia. Int J Clin Exp Med 2016;9:11051-7.
19. Al-Qahtani AA, Al-Agamy MH, Ali MS, Al-Ahdal MN, Aljohi MA, Shibl AM. Characterization of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae from Riyadh, Saudi Arabia. J Chemother 2014;26:139-45.
20. Alsultan AA, Amin TT. ESBL-producing E. coli and K. pneumoniae in Al-Ahsa, Saudi Arabia: Antibiotic susceptibility and prevalence of blaSHV and blaTEM. J Infect Dev Ctries 2013;7:1016-9.
21. Ahmed MA, Acharya A, Elmi AA, Hamid JM, Ahmed AM, Chandra P, et al. Antimicrobial susceptibility and molecular epidemiology of extended-spectrum betalactamase-producing Enterobacteriaceae from intensive care units at Hamad Medical Corporation, Qatar. Antimicrob Resist Infect Control 2016;5:4.
22. Alfaresi M, Sing GK, Senok A. First report of blaCTX-M-28 in Enterobacteriaceae isolates in the United Arab Emirates. J Pathog 2018;2018:1304793.
23. Alzahrania AK, Abbadia SH, Hassan MM, Gaberc A, Abdel- Moneima AS. Antibiotic resistance profile and random amplification typing of ?-lactamase-producing Enterobacteriaceae from the local area of Al-Taif and nearby cities in Saudi Arabia. Asian Biomed 2016;10:219-28.
24. Hassan MI, Alzahrani AJ, Obeid OE, Khamis AH, Diab A. Detection of extended spectrum beta-lactamases-producing isolates and effect of AmpC overlapping. J Infect Dev Ctries 2013;7:618-29.
25. Leangapichart T, Dia NM, Olaitan AO, Gautret P, Brouqui P, Rolain JM. Acquisition of extended-spectrum beta-lactamases by Escherichia coli and Klebsiella pneumoniae in gut microbiota of pilgrims during the Hajj Pilgrimage of 2013. Antimicrob Agents Chemother 2016;60:3222-6.
26. Soliman MS, Wahid JB, Refaat KM. Phenotyping and molecular characterization of extended-spectrum beta-lactamases among clinical isolates of gram-negative bacilli in arar tertiary care Hospital, Saudi Arabia. J Commun Dis 2018;50:22-7.
27. Somily AM, Arshad MZ, Garaween GA, Senok AC. Phenotypic and genotypic characterization of extended-spectrum b-lactamases producing Escherichia coli and Klebsiella pneumoniae in a tertiary care hospital in Riyadh, Saudi Arabia. Ann Saudi Med 2015;35:435-9.
28. Sonnevend A, Ghazawi A, Hashmey R, Haidermota A, Girgis S, Alfaresi M, et al. Multihospital occurrence of pan-resistant Klebsiella pneumoniae sequence Type 147 with an ISEcp1-directed blaOXA-181 insertion in the mgrB gene in the United Arab Emirates. Antimicrob Agents Chemother 2017;61:e00418-17.
29. Uz Zaman T, Aldrees M, Al Johani SM, Alrodayyan M, Aldughashem FA, Balkhy HH. Multi-drug carbapenem-resistant Klebsiella pneumoniae infection carrying the OXA-48 gene and showing variations in outer membrane protein 36 causing an outbreak in a tertiary care hospital in Riyadh, Saudi Arabia. Int J Infect Dis 2014;28:186-92.
30. Al Sheikh YA, Marie MA, John J, Krishnappa LG, Dabwab KH. Prevalence of 16S rRNA methylase genes among beta-lactamase-producing Enterobacteriaceae clinical isolates in Saudi Arabia. Libyan J Med 2014;9:24432.
31. Jamal WY, Albert MJ, Rotimi VO. High prevalence of New Delhi metallo-beta-lactamase-1 (NDM-1) producers among carbapenem-resistant Enterobacteriaceae in Kuwait. PLoS One 2016;11:e0152638.
32. Al-Agamy MH, Shibl AM, Elkhizzi NA, Meunier D, Turton JF, Livermore DM. Persistence of Klebsiella pneumoniae clones with OXA-48 or NDM carbapenemases causing bacteraemias in a Riyadh hospital. Diagn Microbiol Infect Dis 2013;76:214-6.
33. Zowawi HM, Sartor AL, Balkhy HH, Walsh TR, Al Johani SM, Al Jindan RY, 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;58:3085-90.
34. Alotaibi FE, Bukhari EE, Al-Mohizea MM, Hafiz T, Essa EB, Al Tokhais YI. Emergence of carbapenem-resistant Enterobacteriaceae isolated from patients in a university hospital in Saudi Arabia. Epidemiology, clinical profiles and outcomes. J Infect Public Health 2017;10:667-73.
35. Al-Agamy MH, Aljallal A, Radwan HH, Shibl AM. Characterization of carbapenemases, ESBLs, and plasmid-mediated quinolone determinants in carbapenem-insensitive Escherichia coli and Klebsiella pneumoniae in Riyadh hospitals. J Infect Public Health 2018;11:64-8.
36. Ahn C, Butt AA, Rivera JI, Yaqoob M, Hag S, Khalil A, et al. OXA- 48-producing Enterobacteriaceae causing bacteremia, United Arab Emirates. Int J Infect Dis 2015;30:36-7.
37. Shahid M. Prevalence of CTX M extended-spectrum beta-lactamases in clinical gram-negative bacteria. Bahrain Med Bull 2014;36:228-31.
38. Hassan H AB. Molecular characterization of extended-spectrum beta-lactamase producing Enterobacteriaceae in a Saudi Arabian tertiary hospital. J Infect Dev Ctries 2014;8:282-8.
39. Bhaskar BH, Mulki SS, Joshi S, Adhikary R, Venkatesh BM. Molecular characterization of extended spectrum beta-lactamase and carbapenemase producing Klebsiella pneumoniae from a tertiary care hospital. Indian J Crit Care Med 2019;23:61-6.
40. Oteo J, Hernandez JM, Espasa M, Fleites A, Saez D, Bautista V, et al. Emergence of OXA-48-producing Klebsiella pneumoniae and the novel carbapenemases OXA-244 and OXA-245 in Spain. J Antimicrob Chemother 2013;68:317-21.
41. Guo L, An J, Ma Y, Ye L, Luo Y, Tao C, et al. Nosocomial outbreak of OXA-48-producing Klebsiella pneumoniae in a Chinese hospital: Clonal transmission of ST147 and ST383. PLoS One 2016;11:e0160754.
42. Shankar C, Mathur P, Venkatesan M, Pragasam AK, Anandan S, Khurana S, et al. Rapidly disseminating blaOXA-232 carrying Klebsiella pneumoniae belonging to ST231 in India: Multiple and varied mobile genetic elements. BMC Microbiol 2019;19:137.
43. Iraz M, Duzgun AO, Sandalli C, Doymaz MZ, Akkoyunlu Y, Saral A, et al. Distribution of beta-lactamase genes among carbapenem-resistant Klebsiella pneumoniae strains isolated from patients in Turkey. Ann Lab Med 2015;35:595-601.
44. Rossolini GM, D’Andrea MM, Mugnaioli C. The spread of CTX-M-type extended-spectrum beta-lactamases. Clin Microbiol Infect 2008;14 Suppl 1:33-41.
45. Paterson DL, Hujer KM, Hujer AM, Yeiser B, Bonomo MD, Rice LB, et al. Extended-spectrum beta-lactamases in Klebsiella pneumoniae bloodstream isolates from seven countries: Dominance and widespread prevalence of SHV-and CTX-M-type beta-lactamases. Antimicrob Agents Chemother 2003;47:3554-60.
46. Wang G, Huang T, Surendraiah PK, Wang K, Komal R, Zhuge J, et al. CTX-M beta-lactamase-producing Klebsiella pneumoniae in suburban New York City, New York, USA. Emerg Infect Dis 2013;19:1803-10.
47. Jemima SA, Verghese S. Multiplex PCR for bla(CTX-M) and bla(SHV) in the extended spectrum beta lactamase (ESBL) producing gram-negative isolates. Indian J Med Res 2008;128:313-7.
48. Sekar BS, Arunagiri K, Menaka K, Lalitha P, Aparna V. Detection and Characterization of bla CTX-M Gene by PCR-RFLP Analysis among Third Generation Cephalosporin Resistant Gram Negative Isolates. Proceedings of MICROCON 2006 XXX National Congress of Indian Association of Medical Microbiologists, 2006 October 27-29 OB-17. Nagpur: Government Medical College; 2006. p. 27.
49. Bevan ER, Jones AM, Hawkey PM. Global epidemiology of CTX-M ?-lactamases: Temporal and geographical shifts in genotype. J Antimicrob Chemother 2017;72:2145-55.
50. Ktari S, Arlet G, Mnif B, Gautier V, Mahjoubi F, Ben Jmeaa M, et al. Emergence of multidrug-resistant Klebsiella pneumoniae isolates producing VIM-4 metallo-beta-lactamase, CTX-M-15 extended-spectrum beta-lactamase, and CMY-4 AmpC beta-lactamase in a Tunisian university hospital. Antimicrob Agents Chemother 2006;50:4198-201.
51. Dehshiri M, Khoramrooz SS, Zoladl M, Khosravani SA, Parhizgari N, Motazedian MH, et al. The frequency of Klebsiella pneumonia encoding genes for CTX-M, TEM-1 and SHV-1 extended-spectrum beta lactamases enzymes isolated from urinary tract infection. Ann Clin Microbiol Antimicrob 2018;17:4.
52. Veeraraghavan B, Shankar C, Karunasree S, Kumari S, Ravi R, Ralph R. Carbapenem resistant Klebsiella pneumoniae isolated from bloodstream infection: Indian experience. Pathog Glob Health 2017;111:240-6.
53. Zhang X, Li X, Wang M, Yue H, Li P, Liu Y, et al. Outbreak of NDM- 1-producing Klebsiella pneumoniae causing neonatal infection in a teaching hospital in mainland China. Antimicrob Agents Chemother 2015;59:4349-51.
54. Liu Y, Wan LG, Deng Q, Cao XW, Yu Y, Xu QF. First description of NDM-1-, KPC-2-, VIM-2- and IMP-4-producing Klebsiella pneumoniae strains in a single Chinese teaching hospital. Epidemiol Infect 2015;143:376-84.
55. Falco A, Ramos Y, Franco E, Guzman A, Takiff H. A cluster of KPC- 2 and VIM-2-producing Klebsiella pneumoniae ST833 isolates from the pediatric service of a Venezuelan Hospital. BMC Infect Dis 2016;16:595.
16 Views | 20 Downloads
How to Cite
BINDAYNA, K. M., R. M. JOJI, H. EZZAT, and H. A. JAHRAMI. “GENES CONFERRING ANTIMICROBIAL-RESISTANCE AMONG KLEBSIELLA PNEUMONIAE IN THE ARABIAN GULF COUNTRIES: A SYSTEMATIC REVIEW AND META-ANALYSIS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 14, no. 4, Apr. 2021, pp. 90-99, doi:10.22159/ajpcr.2021.v14i4.40841.
Original Article(s)