Evaluation of Co-production of Colistin Resistance and ESBL Genes among Gram-negative Clinical Isolates from Usmanu Danfodiyo University Teaching Hospital Sokoto, Nigeria
DOI:
https://doi.org/10.47430/ujmr.2491.015Keywords:
Colistin resistance, ESBL genes, Co-occurrence resistance, Gram-negative isolatesAbstract
Study’s Excerpt/Novelty
- This study presents a comprehensive evaluation of colistin-resistant and extended-spectrum beta-lactamase (ESBL) gene co-production among Gram-negative clinical isolates from Usmanu Danfodiyo University Teaching Hospital in Sokoto.
- Notably, 13.9% of the isolates exhibited phenotypic co-production of colistin resistance and ESBL, with a significant presence of blaCTX-M and CTX-M 8 genes among ESBL producers, although no colistin resistance genes (mcr-1 and mcr-2) were detected via PCR.
- These findings highlight the necessity for integrated molecular and phenotypic investigations to fully elucidate resistance mechanisms in Gram-negative bacteria and emphasised the need for further research to uncover alternative pathways contributing to observed resistance phenotypes.
Full Abstract
The emergence of antimicrobial resistance (AMR) is a major threat to global health. Its effects include high mortality and morbidity rates, treatment failure, and increased treatment costs. This study aimed to evaluate the co-production of colistin-resistant and extended-spectrum beta-lactamase (ESBL) genes among Gram-negative clinical isolates from Usmanu Danfodiyo University Teaching Hospital in Sokoto. Gram-negative bacteria were isolated from clinical specimens, including urine, feces, and wound aspirates. The Double-Disk Synergy Test and the Colistin Agar Test, respectively, were used to phenotypically validate the existence of colistin resistance and ESBL. Polymerase chain reaction (PCR) was used for molecular characterization. Primers were used to target genes linked to colistin resistance (mcr-1 and mcr-2) and ESBL genes (blaCTX-M, CTX-M 1, CTX-M 2, and CTX-M 8). The findings indicated that 13.9% of the isolates displayed co-production of Colistin and ESBL, and of these isolates, 60% had blaCTX-M genes, and 20% had CTX-M 8 linked to ESBL production. However, the presence of colistin resistance genes was not detected by PCR. Therefore, molecular analysis did not confirm the existence of the colistin resistance genes (mcr-1 and mcr-2) in these isolates. Consequently, the findings showed no molecular co-production of the ESBL and colistin resistance genes. This work emphasizes how crucial it is to look into molecular and phenotypic traits to completely comprehend how colistin resistance and ESBL genes coexist in Gram-negative isolates. More research is required to investigate other mechanisms behind the resistance phenotypes identified.
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References
Abbas, G., Khan, I., Mohsin, M., Sajjad-ur-Rahman, Younas, T., & Ali, S. (2019). High rates of CTX-M group-1 extended-spectrum Beta-lactamases producing Escherichia coli from pets and their owners in Faisalabad, Pakistan. Infection and Drug Resistance, 571–578. https://doi.org/10.2147/IDR.S189884
Adeluola AO, Oyedeji KS, Mendie UE, Johnson JR, Porter JR. (2018). Detection, inhibition and molecular analysis of multidrug resistant aerobic gram-negative clinical isolates from a tertiary hospital in Nigeria. Afr J Biomed Res., 21(1):15–21. https://www.ajol.info/index.php/ajbr/article/view/165960
Anyanwu, M., Okpala, C., Chah, K., & Shoyinka, V. (2021). Prevalence and traits of mobile colistin resistance gene harbouring isolates from different ecosystems in africa. Biomed Research International, 2021, 1-20. https://doi.org/10.1155/2021/6630379.
Arif A., Ullah I., Ullah O., and Zaman R. (2022). Identification of colistin resistance and its bactericidal activity against uropathogenic gram negative bacteria from Hayatabad Medical Complex Peshawar. Pak J Med Sci. 38(4Part-II): 981–986. https://doi.org/10.12669/pjms.38.4.5221
Aslam, B., Wang, W., Arshad, M.I., Khurshid, M., Muzammil, S., Rasool, M.H., Nisar, M.A., Alvi, R.F., Aslam, M.A., Qamar, M.U., Salamat, M.K.F., and Baloch, Z. (2018). Antibiotic resistance: a rundown of a global crisis. Infection and Drug Resistance, 11: 1645–1658. https://doi.org/10.2147/IDR.S173867
Borowiak, M., Fischer, J., Hammerl, J. A., Hendriksen, R. S., Szabo, I., and Malorny, B. (2017). Identification of a novel transposon-associated phosphoethanolamine transferase gene, mcr-5, conferring colistin resistance in d-tartrate fermenting Salmonella enterica subsp. enterica serovar Paratyphi B. Journal of Antimicrobial Chemotherapy, 72(12), 3317-3324. https://doi.org/10.1093/jac/dkx327
Brolund, A., and Sandegren, L. (2016). Characterization of ESBL disseminating plasmids. Infectious Diseases, 48(1), 18–25. https://doi.org/10.3109/23744235.2015.1062536
Cannatelli A, Giani T, Aiezza N, et al., 2013. An allelic variant of the PmrB sensor kinase responsible for colistin resistance in an Escherichia coli strain of clinical origin. Antimicrob Agents Chemother. 57(10): 4900-4902.
Cao, L., Li, X., Xu, Y., and Shen, J. (2018). Prevalence and molecular characteristics of mcr-1 colistin resistance in Escherichia coli: Isolates of clinical infection from a Chinese University Hospital. Infection and Drug Resistance, 1597–1603. https://doi.org/10.2147/IDR.S166726
Chagas T.P.G., Alves R.M., Vallim D.C., Seki L.M., Campos L.C. and Asensi M.D. (2011). Diversity of genotypes in CTX-M-producing Klebsiella pneumoniae isolated in different hospitals in Brazil. The Brazilian Journal of Infectious Diseases; 15(5): 420-425. https://doi.org/10.1016/S1413-8670(11)70222-7
CLSI - Clinical and Laboratory Standards Institute (2021). Performance Standards for Antimicrobial Susceptibility Testing. 31st ed. CLSI Supplement M100, Wayne, PA., USA.
Dadgostar, P. (2019). Antimicrobial resistance: Implications and costs. Infection and Drug Resistance, 3903–3910. https://doi.org/10.2147/IDR.S234610
Davies, J., and Davies, D. (2010). Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev. 74(3):417–433. https://doi.org/10.1128/MMBR.00016-10
Egwuatu T.O., Ishola O.D. and Oladele O.E. (2021). The distribution of extended-spectrum Beta-lactamase genes in fomites, healthcare workers, and patients from two hospitals in Lagos State, Nigeria. Ife Journal of Science; 23(2): 015-024. https://dx.doi.org/10.4314/ijs.v23i2.2
Fair, R. J. and Tor, Y. (2014). Antibiotics and bacterial resistance in the 21st century. Perspectives in Medicinal Chemistry, 6, PMC-S14459. https://doi.org/10.4137/PMC.S14459
Hassen B., Hammami S., Hassen A., and Abbassi M.S. (2022). Molecular mechanisms and clonal lineages of colistinresistant bacteria across the African continent: a scoping review. Letters in Applied Microbiology; 75: 1390-1422. https://doi.org/10.1111/lam.13818
Kaye, K. S., Pogue, J. M., Tran, T. B., Nation, R. L., and Li, J. (2016). Agents of last resort: Polymyxin resistance. Infectious Disease Clinics, 30(2), 391–414. https://doi.org/10.1016/j.idc.2016.02.005
Kupferschmidt, K. (2016). Resistance fighters. Science, 352(6287): 758–761. https://doi.org/10.1126/science.352.6287.758
Laxminarayan, R., Matsoso, P., Pant, S., Brower, C., Røttingen, J, Klugman, K, Davies, S. (2016). Access to effective antimicrobials: a worldwide challenge. The Lancet, 387(10014): 168-175. https://doi.org/10.1016/S0140-6736(15)00474-2
Li, D., Ge, Y., Wang, N., Shi, Y., Guo, G., Zou, Q., & Liu, Q. (2023). Identification and characterization of a novel major facilitator superfamily efflux pump, sa09310, mediating tetracycline resistance in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 67(4). https://doi.org/10.1128/aac.01696-22
Liakopoulos, A., Mevius, D. J., Olsen, B., and Bonnedahl, J. (2016). The Colistin Resistance Mcr-1 Gene is Going Wild. J. Antimicrob. Chemother. 71(8): 2335–2336. https://doi.org/10.1093/jac/dkw262
Mahmoud AT, Salim MT, Ibrahem RA, Gabr A and Halby HM. (2020). Multiple Drug Resistance Patterns in Various Phylogenetic Groups of Hospital-Acquired Uropathogenic E. coli isolated from Cancer Patients. Antibiotics, 9(3): 108. https://doi.org/10.3390/antibiotics9030108
Mlynarcik, P., and Kolar, M. (2019). Molecular mechanisms of polymyxin resistance and detection of mcr genes. Biomedical Papers of the Medical Faculty of Palacky University in Olomouc, 163(1). https://doi.org/10.5507/bp.2018.070
Moawad, A. A., Hotzel, H., Neubauer, H., Ehricht, R., Monecke, S., Tomaso, H., Hafez, H. M., Roesler, U., and El-Adawy, H. (2018). Antimicrobial resistance in Enterobacteriaceae from healthy broilers in Egypt: Emergence of colistin-resistant and extended-spectrum β- lactamase-producing Escherichia coli. Gut Pathogens, 10, 1–12. https://doi.org/10.1186/s13099-018-0266-5
Mohammed Y., Gadzama GB., Zailani SB. and Aboderin AO. (2016). Characterization of Extended-Spectrum Beta-lactamase from Escherichia coli and Klebsiella Species from North Eastern Nigeria. J Clin Diagn Res.; 10(2): DC07–DC10. https://doi.org/10.7860/JCDR/2016/16330.7254
Ngbede E.O, Poudel A., Kalalah A., Yang Y., Adekanmbi F., Adikwu A.A., Adamu A.M., Mamfe L.M., Daniel S.T., Useh N.M., Kwaga J.K.P., Adah M.I., Kelly P., Butaye P., and Wang C. (2020). Identification of mobile colistin resistance genes (mcr-1.1, mcr-5 and mcr-8.1) in Enterobacteriaceae and Alcaligenes faecalis of human and animal origin, Nigeria. International Journal of Antimicrobial Agents; 56(3): 1-24. https://doi.org/10.1016/j.ijantimicag.2020.106108
Nuhu, T., Bolaji, R. and Olayinka, B. (2015). Prevalence and antimicrobial susceptibility of extended Spectrum Beta-lactamase (ESBL) producing gram-negative uropathogens in Sokoto, Nigeria. Nigerian Journal of Pharmaceutical Research, 11, 59-65.
Nyandwi, E., Veldkamp, A., Amer, S. Karema C. andUmulisa I. (2017). Schistosomiasis mansoni incidence data in Rwanda can improve prevalence assessments, by providing high-resolution hotspot and risk factors identification. BMC Public Health 17 (845): 1-14. https://doi.org/10.1186/s12889-017-4816-4
Olaitan AO, Diene SM, Kempf M, et al., 2014. Worldwide emergence of colistin resistance in Klebsiella pneumoniae from healthy humans and patients in Lao PDR, Thailand, Israel, Nigeria, and France owing to inactivation of the PhoP/PhoQ regulator mgrB: an epidemiological and molecular study. Int J Antimicrob Agents. 44(6):500-507. https://doi.org/10.1016/j.ijantimicag.2014.07.020
Olaitan, A. O., Chabou, S., Okdah, L., Morand, S., and Rolain, J. M. (2016). Dissemination of the mcr-1 colistin resistance gene. The Lancet Infectious Diseases, 16(2), 147-149. https://doi.org/10.1016/S1473-3099(15)00541-1
Olowo-Okere, A. and Yacouba, A. (2020). Molecular mechanisms of colistin resistance in Africa: a systematic review of literature. Germs, 10(4), 367-379.
https://doi.org/10.18683/germs.2020.1229
Olowo-Okere, A., Ibrahim, Y. K. E. and Olayinka, B. O. (2018). Molecular characterisation of extended-spectrum β-lactamase-producing Gram-negative bacterial isolates from surgical wounds of patients at a hospital in North Central Nigeria. Journal of global antimicrobial Resistance, 14, 85-89. https://doi.org/10.1016/j.jgar.2018.02.002
Olufunke O. A., Aregbesola O.A., and Fashina C.D. (2014). Extended spectrum betalactamase- producing uropathogenic Escherichia coli in pregnant women diagnosed with urinary tract infections in southwestern Nigeria, J. Mol. Bio. Res., 4(1): 34–42. https://doi.org/10.5539/jmbr.v4n1p34
Omoya FO and Ajayi KO. (2016). Synergistic Effect of Combined Antibiotics against Some Selected Multidrug Resistant Human Pathogenic Bacteria Isolated from Poultry Droppings in Akure, Nigeria. Advances in Microbiology, 6(14): 1075-1090. https://doi.org/10.4236/aim.2016.614100.
O'Neill, J. (2014). Antimicrobial resistance: tackling a crisis for the health and wealth of nations, Review on antimicrobial resistance, http://archive.wphna.org/wp-content/uploads/2015/06/2014-UK-paper-on-superbugs-projected-to-2050.pdf
Peculiar-Onyekere O.C., Martina C.A. and Emmanuel A.E. (2019). ESBL Mediated Antimicrobial Nonsusceptibility of Uropathogenic Escherichia coli and Klebsiella pneumoniae Isolates from Pregnant Women in Nnewi, Nigeria. Journal of Advances in Microbiology; 18(2): 1-13. https://doi.org/10.9734/JAMB/2019/v18i230166
Rajivgandhi GN, Alharbi NS, Kadaikunnan S, Khaled JM, Kanisha CC, Ramachandran G, Manoharan N and Alanzi KF. (2021). Identification of carbapenems resistant genes on biofilm forming K. pneumoniae from urinary tract infection. Saudi Journal of Biological Sciences; 28(3): 1750-1756. https://doi.org/10.1016/j.sjbs.2020.12.016
Rozenkiewicz D, Esteve-Palau E, Arenas-Miras M, Grau S, Duran X, Luisa Sorlí L, Montero MM and Horcajada JP. (2021). Clinical and Economic Impact of Community-Onset Urinary Tract Infections Caused by ESBL-Producing Klebsiella pneumoniae Requiring Hospitalization in Spain: An Observational Cohort Study. Antibiotics, 10(585): 1-10. https://doi.org/10.3390/antibiotics10050585
Sharma, J., Sharma, D., Singh, A., and Kumari, S. (2022). Colistin resistance and management of drug resistant infections. Canadian Journal of Infectious Diseases and Medical Microbiology, 2022, 1-10. https://doi.org/10.1155/2022/4315030
Shen, Y., Wu, Z., Wang, Y., Zhang, R., Zhou, H.-W., Wang, S., Lei, L., Li, M., Cai, J., and Tyrrell, J. (2018). Heterogeneous and flexible transmission of mcr-1 in hospital-associated Escherichia coli. MBio, 9(4), 10–1128. https://doi.org/10.1128/mBio.00943-18
Smith, M., et al. (2017). Molecular mechanisms of co-resistance to colistin and carbapenem in Klebsiella pneumoniae: An in-depth analysis of a high-risk clone. Scientific Reports, 7(1), 1-11. https://doi.org/10.1038/s41598-017-05059-9.
Sun, J., Zhang, H., Liu, Y.H., and Feng, Y. (2018). Towards understanding MCR-like colistin resistance. Trends in Microbiology, 26(9), 794–808. https://doi.org/10.1016/j.tim.2018.02.006
Taghizadeh E, Abdollahi E and Nikkhah M. (2018). TP53 hotspot mutations in astrocytoma. Health Biotechnology and Biopharma, 2(1): 38-45. https://doi.org/10.22034/HBB.2018.13
Tanko N., Bolaji R.O., Olayinka A.T., Olayinka B.O. (2020). A systematic review on the prevalence of extended-spectrum beta lactamase-producing Gram-negative bacteria in Nigeria. J Glob Antimicrob Resist; 22: 488-496. https://doi.org/10.1016/j.jgar.2020.04.010.
Udoh, R.H., Tahiru, M., Ansu-Mensah, M., Bawontuo, V., Danquah, F.I., and Kuupiel, D. (2020). Women’s knowledge, attitude, and practice of breast self-examination in sub-Saharan Africa: A scoping review. Archives of Public Health, 78(84): 1-10. https://doi.org/10.1186/s13690-020-00452-9
Ugwu, M., Shariff, M., Nnajide, C., Beri, K., Okezie, U., Ifeanyichukwu, I., and Esimone, C. (2020). Phenotypic and molecular characterization of Beta-lactamases among enterobacterial uropathogens in southeastern nigeria. Canadian Journal of Infectious Diseases and Medical Microbiology, 2020, 1-9. https://doi.org/10.1155/2020/5843904
Van Boeckel, T.P., Gandra, S., Ashok, A., Caudron, Q., Grenfell, B.T., Levin, S.A., Laxminarayan, R. (2014). Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect. Dis., 14(8): 742-750. https://doi.org/10.1016/S1473-3099(14)70780-7
Vounba P., Rhouma M., Arsenault J., Bada Alambédji R., Fravalo P. and Fairbrother J.M. (2019). Prevalence of colistin resistance and mcr-1/mcr-2 genes in extended-spectrum β-lactamase/AmpC-producing Escherichia coli isolated from chickens in Canada, Senegal and Vietnam. J. Glob. Antimicrob. Resist., 19: 222–227. https://doi.org/10.1016/j.jgar.2019.05.002.
WHO (2014). Antimicrobial resistance: Global report on surveillance. WHO press, World Health Organization, Geneva, Switzerland, pp. 1-8.
Woerther, P.L., Burdet, C., Chachaty, E., and Andremont, A. (2013). Trends in human fecal carriage of extended-spectrum Beta-lactamases in the community: Toward the globalization of CTX-M. Clinical Microbiology Reviews, 26(4), 744–758. https://doi.org/10.1128/CMR.00023-13
Xavier, B. B., et al. (2016). Identification of a novel plasmid-mediated colistin resistance gene, mcr-2, in Escherichia coli. Eurosurveillance, 21(27): 30280. https://doi.org/10.2807/1560-7917.ES.2016.21.27.30280
Yamasaki, S., Le, T. D., Vien, M. Q., Van Dang, C., and Yamamoto, Y. (2017). Prevalence of extended-spectrum β-lactamase-producing Escherichia coli and residual antimicrobials in the environment in Vietnam. Animal Health Research Reviews, 18(2): 128–135. https://doi.org/10.1017/S1466252317000160
Zhang, S., Abbas, M., Rehman, M. U., Wang, M., Jia, R., Chen, S., Liu, M., Zhu, D., Zhao, X. and Gao, Q. (2021). Updates on the global dissemination of colistin-resistant Escherichia coli: An emerging threat to public health. Science of The Total Environment, 799, 149280. https://doi.org/10.1016/j.scitotenv.2021.149280
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