Antibiotic resistance profile and detection of extended-spectrum β-lactamase producing bacteria in patients with breast Cancer
DOI:
https://doi.org/10.31530/cjnst.2025.1.1.4Keywords:
Bacterial isolation, Molecular identification, Extended-spectrum beta-lactamase, Antibiotic resistance, Breast cancerAbstract
Abstract
Background: Breast cancer patients face increased risk for bacterial infections due to immunocompromised status and treatment-related factors. The human gut microbiota has emerged as a critical modulator of breast cancer development through multiple interconnected pathways, with significant compositional differences in gut microbial communities between breast cancer patients and healthy individuals. The evolution of antimicrobial resistance has become crucial in cancer care, especially regarding bacteria that produce extended-spectrum β-lactamases (ESBLs).
Aims: This study aimed to characterize bacterial isolates from stool samples of breast cancer patients using 16S rRNA gene sequencing and evaluate antimicrobial resistance patterns and extended-spectrum β-lactamase (ESBL) production
Methodology: Fifty bacterial isolates were collected from stool specimens of breast cancer patients at Nanakali Hospital, Erbil, Kurdistan region-Iraq, from September to December 2024. Bacterial identification was employed by conventional biochemical methods followed by 16S rRNA gene sequencing. Antimicrobial susceptibility testing used disc diffusion against 12 antibiotics based on CLSI guidelines. ESBL production was detected through phenotypic screening and multiplex PCR targeting blaTEM, blaSHV, and blaCTX-M genes.
Results: Escherichia coli was most prevalent (42%), followed by Salmonella enterica (14%), Enterobacter cloacae (10%) and Klebsiella pneumoniae (10%). General susceptibility was observed against carbapenems and netilmicin, while complete resistance was observed against ticarcillin-clavulanic acid and tigecycline across all the isolates. ESBL production was detected in 56% of the isolates, with K. pneumoniae showing highest rates (75%). All the ESBL isolates harbored ≥1 ESBL gene; blaTEM was the predominant single genotype, and blaTEM + blaCTX-M was the most common combination, particularly in E. coli (47.61%).
Conclusion: High antimicrobial resistance burden exists among bacterial isolates from breast cancer patients, with notable ESBL prevalence and concerning resistance patterns. The universal presence of ESBL genes in all isolates provides important clinical management insights. While carbapenem susceptibility remains intact, high resistance rates to common antibiotics underscore the need for comprehensive antimicrobial stewardship in oncology settings.
References
[1] Deng X, Yang L, et al. Bibliometric analysis of global research trends between gut microbiota and breast can-cer: from 2013 to 2023. Frontiers in Microbiology. 2024;15:1393422. DOI: https://doi.org/10.3389/fmicb.2024.1393422
[2] Bawaneh A, Wilson P, et al. Intestinal microbiota in-fluence doxorubicin responsiveness in triple-negative breast cancer. Cancers. 2022;14(19):4849. DOI: https://doi.org/10.3390/cancers14194849
[3] Liu K, Jia Q, et al. Current and future research on the association between gut microbiota and breast cancer. Frontiers in Microbiology. 2023;14:1272275. DOI: https://doi.org/10.3389/fmicb.2023.1272275
[4] Sui Y, Wu J, et al. The role of gut microbial β-glucuronidase in estrogen reactivation and breast can-cer. Frontiers in Cell and Developmental Biology. 2021;9:631552. DOI: https://doi.org/10.3389/fcell.2021.631552
[5] Vernaci G, Savarino E, et al. Characterization of gut microbiome composition in patients with triple-negative breast cancer treated with neoadjuvant chem-otherapy. The Oncologist. 2023;28(9):e703-e711. DOI: https://doi.org/10.1093/oncolo/oyad060
[6] Arnone AA, Ansley D, et al. Gut microbiota interact with breast cancer therapeutics to modulate efficacy. EMBO Molecular Medicine. 2025;17(2):219-234. DOI: https://doi.org/10.1038/s44321-024-00185-0
[7] Bush K, Bradford PA. Epidemiology of β-lactamase-producing pathogens. Clinical Microbiology Reviews. 2020;33(2):10.1128/cmr.00047-00019. DOI: https://doi.org/10.1128/CMR.00047-19
[8] Gajic I, Kabic J, et al. Antimicrobial susceptibility test-ing: a comprehensive review of currently used meth-ods. Antibiotics. 2022;11(4):427. DOI: https://doi.org/10.3390/antibiotics11040427
[9] Butler I, Turner A, et al. Standardization of 16S rRNA gene sequencing using nanopore long read sequencing technology for clinical diagnosis of culture negative in-fections. Frontiers in Cellular and Infection Microbiol-ogy. 2025;15:1517208. DOI: https://doi.org/10.3389/fcimb.2025.1517208
[10] Janes, M. E., Halpin, A. L., Beganovic, M., Stratton, C. W., & Burnham, C. A. D. (2023). Direct 16S/18S rRNA gene PCR followed by Sanger sequencing as a clinical diagnostic tool for detection of bacterial and fungal infections: a systematic review and meta-analysis. Journal of Clinical Microbiology, 61(8), e00338-23. DOI: https://doi.org/10.1128/jcm.00338-23
[11] Matsuo, Y., Komiya, S., Yasumizu, Y., Yasuoka, Y., Mizushima, K., Takagi, T., Naito, Y., Mizuno, S., Chinda, D., Tsuji, H., Takahashi, S., Hattori, M., & Shinohara, M. (2021). Full-length 16S rRNA gene am-plicon analysis of human gut microbiota using Min-ION™ nanopore sequencing confers species-level reso-lution. BMC Microbiology, 21(1), 35. DOI: https://doi.org/10.1186/s12866-021-02094-5
[12] Clinical and Laboratory Standards Institute. (2011). Performance standards for antimicrobial susceptibility testing; twenty-first informational supplement. CLSI document M100-S21. Wayne, PA: Clinical and Labora-tory Standards Institute.
[13] Yehia, H. M., Al-Madboly, L. A., & El-Sokkary, M. M. (2020). Phenotypic detection of extended-spectrum β-lactamases among Gram-negative pathogens isolated from clinical specimens. Journal of Pure and Applied Microbiology, 14(1), 89–98.
[14] Gundran, R. S., Cardenio, P. A., Villanueva, M. A., Sison, F. B., Benigno, C. C., & Kreausukon, K. (2019). Prevalence and distribution of blaCTX-M, blaSHV, blaTEM genes in extended-spectrum β-lactamase-producing Escherichia coli isolates from livestock and sewage in the Philippines. Veterinary World, 12(1), 141–147. DOI: https://doi.org/10.1186/s12917-019-1975-9
[15] Boyd, D. A., Tyler, S., Christianson, S., McGeer, A., Muller, M. P., Willey, B. M., Bryce, E., Gardam, M., Nordmann, P., Mulvey, M. R. (2004). Complete nucle-otide sequence of a 92-kilobase plasmid harboring the CTX-M-15 extended-spectrum β-lactamase involved in an outbreak in long-term-care facilities in Toronto, Canada. Antimicrobial Agents and Chemotherapy, 48(10), 3758–3764. DOI: https://doi.org/10.1128/AAC.48.10.3758-3764.2004
[16] Paterson, D. L., Hujer, K. M., Hujer, A. M., Yeiser, B., Bonomo, M. D., Rice, L. B., & Bonomo, R. A. (2003). Extended-spectrum β-lactamases in Klebsiella pneu-moniae bloodstream isolates from seven countries: dominance and widespread prevalence of SHV- and CTX-M-type β-lactamases. Antimicrobial Agents and Chemotherapy, 47(11), 3554–3560. DOI: https://doi.org/10.1128/AAC.47.11.3554-3560.2003
[17] Hassan A, Ojo T, et al. Escherichia coli as a global pathogen. Funksec. 2021;3(1):239-260.
[18] Bonten M, Johnson P, et al. Epidemiology of Esche-richia coli bacteremia: a systematic literature review. Clinical Infectious Diseases. 2021;72(7):1211-1219. DOI: https://doi.org/10.1093/cid/ciaa210
[19] Braz VS, Melchior K, et al. Escherichia coli as a multi-faceted pathogenic and versatile bacterium. Frontiers in Cellular and Infection Microbiology. 2020;10:548492. DOI: https://doi.org/10.3389/fcimb.2020.548492
[20] Lamichhane, B., et al. (2024). "Salmonellosis: an over-view of epidemiology, pathogenesis, and innovative approaches to mitigate the antimicrobial resistant in-fections." Antibiotics 13(1): 76. DOI: https://doi.org/10.3390/antibiotics13010076
[21] Creed, P. V., et al. (2023). "Neonatal Meningitis Due to Cronobacter sakazakii." Pediatric Annals 52(11): e430-e433. DOI: https://doi.org/10.3928/19382359-20230906-04
[22] Diallo, O. O., et al. (2020). "Antibiotic resistance sur-veillance systems: A review." Journal of Global Antimi-crobial Resistance 23: 430-438. DOI: https://doi.org/10.1016/j.jgar.2020.10.009
[23] Toussaint KA, Gallagher JC. β-lactam/β-lactamase in-hibitor combinations: from then to now. Annals of Pharmacotherapy. 2015;49(1):86-98. DOI: https://doi.org/10.1177/1060028014556652
[24] Aitken SL, Clancy CJ. IDSA Guidance on the Treat-ment of Antimicrobial Resistant Gram-Negative Infec-tions. 2020.
[25] Gupta N, Limbago B, et al. Carbapenem-resistant En-terobacteriaceae: epidemiology and prevention. Clinical Infectious Diseases. 2011;53(1):60-67. DOI: https://doi.org/10.1093/cid/cir202
[26] Yaghoubi, S., et al. (2022). "Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review." Europe-an Journal of Clinical Microbiology & Infectious Dis-eases 41(7): 1003-1022. DOI: https://doi.org/10.1007/s10096-020-04121-1
[27] Redgrave, L. S., et al. (2014). "Fluoroquinolone re-sistance: mechanisms, impact on bacteria, and role in evolutionary success." Trends in microbiology 22(8): 438-445. DOI: https://doi.org/10.1016/j.tim.2014.04.007
[28] Tchesnokova, V., et al. (2023). "Increase in the com-munity circulation of ciprofloxacin-resistant Escherich-ia coli despite reduction in antibiotic prescriptions." Communications Medicine 3(1): 110. DOI: https://doi.org/10.1038/s43856-023-00337-2
[29] Sintondji, K., Fabiyi, K., Hougbenou, J., Koudokpon, H., Lègba, B., Amoussou, H., Haukka, K., & Dougnon, V. (2023). Prevalence and characterization of ESBL-producing Escherichia coli in healthy preg-nant women and hospital environments in Benin: an approach based on Tricycle. Frontiers in Public Health, 11, 1227000. https://doi.org/10.3389/fpubh.2023.1227000 DOI: https://doi.org/10.3389/fpubh.2023.1227000
[30] Lukac, P. J., et al. (2015). "Extended-spectrum β-lactamase–producing Enterobacteriaceae in children: old foe, emerging threat." Clinical Infectious Diseases 60(9): 1389-1397. DOI: https://doi.org/10.1093/cid/civ020
[31] Sarojamma, V. and V. Ramakrishna (2011). "Preva-lence of ESBL‐producing Klebsiella pneumoniae iso-lates in tertiary care hospital." International Scholarly Research Notices 2011(1): 318348. DOI: https://doi.org/10.5402/2011/318348
[32] Ahmad, Y. A. and Mustafa, Kh.Kh.(2023). Compara-tive Method between Traditional and Molecular Diag-nosis for Salmonella Species Isolated from different sources in Erbil City-Iraq. Ph.D Dissertation. Sala-haddin University-Erbil.
[33] Lau CL, Neoh H, et al. Prevalence and clinical signifi-cance of the genotypic carriage among ESBL pheno-type-negative Escherichia coli and Klebsiella pneu-moniae clinical isolates in bacteremia: a study in a Ma-laysian tertiary center. Frontiers in Cellular and Infec-tion Microbiology. 2024;14:1429830. DOI: https://doi.org/10.3389/fcimb.2024.1429830
[34] Chaudhary MK, Jadhav S, et al. Molecular detection of plasmid mediated bla TEM, bla CTX− M, and bla SHV genes in Extended Spectrum β-Lactamase (ESBL) Escherichia coli from clinical samples. Annals of Clini-cal Microbiology and Antimicrobials. 2023;22(1):33. DOI: https://doi.org/10.1186/s12941-023-00584-0
[35] Sintondji, K., Fabiyi, K., Hougbenou, J., Koudokpon, H., Lègba, B., Amoussou, H., Haukka, K. and Dougnon, V., 2023. Prevalence and characterization of ESBL-producing Escherichia coli in healthy pregnant women and hospital environments in Benin: an ap-proach based on Tricycle. Frontiers in public health, 11, p.1227000. DOI: https://doi.org/10.3389/fpubh.2023.1227000
[36] Ahmad HP, Mustafa KK. Prevalence of blaTEM, blaSHV, and blaCTX-M Genes among ESBL-Producing Klebsiella pneumoniae and Escherichia coli Isolated from Thalassemia Patients in Erbil, Iraq. Medi-terranean Journal of Hematology and Infectious Diseas-es. 2019;11:e2019041. DOI: https://doi.org/10.4084/mjhid.2019.041
[37] Di Marcantonio L, Ranieri SC, et al. Comprehensive regional study of ESBL Escherichia coli: genomic in-sights into antimicrobial resistance and inter-source dissemination of ESBL genes. Frontiers in Microbiolo-gy. 2025;16:1595652. DOI: https://doi.org/10.3389/fmicb.2025.1595652
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Charmo Journal of Natural Sciences and Technologies
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
