Prevalence of blaCTX-M and blaTEM genes in Enterobacter cloacae isolated from urine samples in Iraqi patients
Abstract:
clinically relevant uropathogen and an increasing cause of opportunistic infections is Enterobacter cloacae, primarily driven by worldwide distribution of extended-spectrum β-lactamase--encoding genes. Among those, blaCTX-M and blaTEM are predominant genes responsible for the resistance towards β-lactam antibiotics and hence restricting treatment choices. The present work was designed to analyse the occurrence of blaCTX-M and blaTEM genes in E. cloacae isolated from urine samples of Iraqi patients, as well as assess their correlation with antimicrobial resistance profile. This condition-specific, cross-sectional study was performed at Al-Sadr Medical City Hospital, in Najaf in Iraq from summer season 2024 to early winter 2025. Eighty-four patients with a suspicion of UTI were included in this study. Midstream urine specimens were cultured and E. cloacae isolates were identified by routine microbiological and biochemical tests. Susceptibility to ceftriaxone, ciprofloxacin, gentamicin, imipenem and meropenem testing was determined by the Kirby–Bauer disc diffusion method according to CLSI guidelines. blaCTX-M and blaTEM genes were identified by traditional PCR. The relationship between gene carriage and antibiotic resistance was evaluated by statistical analysis. Ceftriaxone (75.0%) had the highest resistance rate, followed by ciprofloxacin (54.8%), and gentamicin (48.8%), while meropenem (16.7%) and imipenem (14.3%) were less resistive agents. Molecular investigation determined the prevalence of blaCTX-M and blaTEM genes in 69.0% and 52.4% of isolates, respectively. The presence of blaCTX-M and resistance ceftriaxone, ciprofloxacin and gentamicin (p < 0.001) were highly significantly associated between them while resistant to ceftriaxone and ciprofloxacin had a significant association with blaTEM (p < 0.05). The presence of either gene did not show a statistically significant relationship with carbapenem resistance. The high rates of blaCTX-M and blaTEM genes among urinary E. cloacae isolates drawn attention to the emerging problem of ESBL-mediated resistance in Iraq. The high prevalence of ESBL gene carriage and resistance to the commonly used antibiotics calls for ongoing molecular surveillance, judicious antibiotic use, and implementation of efficient infection control measures to curb the spread of resistant E. cloacae strains.
KeyWords:
blaVIM and blaNDM, Enterobacter cloacae, UTIs, ESBLs
References:
- Araújo, M. R. B., Sant'Anna, L. O., Santos, N. N. C. D., Seabra, L. F., & Santos, L. S. D. (2023). Monitoring fluoroquinolone resistance among ESBL-positive and ESBL-negative Escherichia coli strains isolated from urinary tract infections: An alert for empirical treatment. Revista da Sociedade Brasileira de Medicina Tropical, 56, e0513. https://doi.org/10.1590/0037-8682-0513-2022
- Cantón, R., & Coque, T. M. (2006). The CTX-M beta-lactamase pandemic. Current opinion in microbiology, 9(5), 466–475. https://doi.org/10.1016/j.mib.2006.08.011
- Cantón, R., González-Alba, J. M., & Galán, J. C. (2012). CTX-M Enzymes: Origin and Diffusion. Frontiers in microbiology, 3, 110. https://doi.org/10.3389/fmicb.2012.00110
- Carattoli A. (2013). Plasmids and the spread of resistance. International journal of medical microbiology : IJMM, 303(6-7), 298–304. https://doi.org/10.1016/j.ijmm.2013.02.001
- Castanheira, M., Simner, P. J., & Bradford, P. A. (2021). Extended-spectrum β-lactamases: an update on their characteristics, epidemiology and detection. JAC-antimicrobial resistance, 3(3), dlab092. https://doi.org/10.1093/jacamr/dlab092
- Cave, R., Cole, J., & Mkrtchyan, H. V. (2021). Surveillance and prevalence of antimicrobial resistant bacteria from public settings within urban built environments: Challenges and opportunities for hygiene and infection control. Environment international, 157, 106836. https://doi.org/10.1016/j.envint.2021.106836
- Cheesbrough, M. (2006) District Laboratory Practice in Tropical Countries. Part 2, 2nd Edition, Cambridge University Press Publication, South Africa, 1-434.
- Dallenne, C., Da Costa, A., Decré, D., Favier, C., & Arlet, G. (2010). Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae. The Journal of antimicrobial chemotherapy, 65(3), 490–495. https://doi.org/10.1093/jac/dkp498
- Esfahanian, F., Mobasherizadeh, S., Baradaran, A., Abbasi Baghbaderani, S., Naimi, A., Nouri, S., & Rostami, S. (2022). Prevalence of antibiotic resistance in Enterobacteriaceae among patients hospitalized in Al-Zahra Hospital, Isfahan, Iran. Journal of Preventive Epidemiology, x(x), e23166. https://doi.org/10.34172/jpe.2022.23166
- Flores-Mireles, A. L., Walker, J. N., Caparon, M., & Hultgren, S. J. (2015). Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nature reviews. Microbiology, 13(5), 269–284. https://doi.org/10.1038/nrmicro3432
- Foxman B. (2014). Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infectious disease clinics of North America, 28(1), 1–13. https://doi.org/10.1016/j.idc.2013.09.003
- Hamad, P. A., & Khadija, K. M. (2019). Prevalence of ESBL genes among Enterobacteriaceae in Iraq. Mediterranean Journal of Hematology and Infectious Diseases, 11(1), e2019041. https://doi.org/10.4084/mjhid.2019.041
- Mazumder, R., Abdullah, A., Ahmed, D., & Hussain, A. (2020). High Prevalence of blaCTX-M-15 Gene among Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolates Causing Extraintestinal Infections in Bangladesh. Antibiotics (Basel, Switzerland), 9(11), 796. https://doi.org/10.3390/antibiotics9110796
- Mezzatesta, M. L., Gona, F., & Stefani, S. (2012). Enterobacter cloacae complex: clinical impact and emerging antibiotic resistance. Future microbiology, 7(7), 887–902. https://doi.org/10.2217/fmb.12.61
- Mohamed, E. S., Khairy, R. M. M., & Abdelrahim, S. S. (2020). Prevalence and molecular characteristics of ESBL and AmpC β -lactamase producing Enterobacteriaceae strains isolated from UTIs in Egypt. Antimicrobial resistance and infection control, 9(1), 198. https://doi.org/10.1186/s13756-020-00856-w
- Mohammed, A. J., Al-Amara, S. S. M., & Al- Hejjaj, M. Y. (2024). Molecular characterization of blaTEM and blaCTX-M ESBLs genes producing Escherichia coli isolates from urinary tract infections (UTIs) in Al-Basrah province, Iraq. South Eastern European Journal of Public Health, 389–396. https://doi.org/10.70135/seejph.vi.1146
- Paterson, D. L., & Bonomo, R. A. (2005). Extended-spectrum β-lactamases: A clinical update. Clinical Microbiology Reviews, 18(4), 657–686. https://doi.org/10.1128/CMR.18.4.657-686.2005
- Pishtiwan, A. H., & Khadija, K. M. (2019). Prevalence of blaTEM, blaSHV, and blaCTX-M Genes among ESBL-Producing Klebsiella pneumoniae and Escherichia coli Isolated from Thalassemia Patients in Erbil, Iraq. Mediterranean journal of hematology and infectious diseases, 11(1), e2019041. https://doi.org/10.4084/MJHID.2019.041
- Poirel, L., Walsh, T. R., Cuvillier, V., & Nordmann, P. (2011). Multiplex PCR for detection of acquired carbapenemase genes. Diagnostic microbiology and infectious disease, 70(1), 119–123. https://doi.org/10.1016/j.diagmicrobio.2010.12.002
- Rawat, D., & Nair, D. (2010). Extended-spectrum β-lactamases in Gram Negative Bacteria. Journal of global infectious diseases, 2(3), 263–274. https://doi.org/10.4103/0974-777X.68531
- Tängdén, T., & Giske, C. G. (2015). Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control. Journal of internal medicine, 277(5), 501–512. https://doi.org/10.1111/joim.12342