Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
RESEARCH ARTICLE   (Open Access)

Antibiotic Resistance and Inflammatory Response in Urology Infections Caused by E. coli: A Molecular and Clinical Investigation

Amani Alhejely 1*

+ Author Affiliations

Journal of Angiotherapy 8(7) 1-9 https://doi.org/10.25163/angiotherapy.879789

Submitted: 04 June 2024  Revised: 15 July 2024  Published: 20 July 2024 

Abstract

Background: Urinary tract infections (UTIs) are a common condition resulting from bacterial invasion of the urinary system, which includes the kidneys, ureters, bladder, and urethra. These infections are particularly prevalent among females due to anatomical differences and hormonal factors. UTIs can range from uncomplicated cases, where there are no structural abnormalities, to more severe infections that may ascend to the kidneys, causing pyelonephritis. Methods: This study aimed to isolate and diagnose Escherichia coli (E. coli) bacteria in patients with UTIs, identify specific virulence genes, and assess the bacteria's resistance to various antibiotics. A total of 100 clinical samples were collected from patients with UTIs at the General Hospital of Homadiyah and Ahmed Maher from October 2021 to December 2022. Bacterial identification was performed using biochemical tests and polymerase chain reaction (PCR) techniques, while antibiotic sensitivity was assessed using the Kirby-Bauer disk diffusion method. Additionally, inflammatory markers (TNF-α, IL-6, and IL-8) were measured using ELISA. Results: E. coli was isolated in 56% of the samples, with the highest prevalence in patients aged 31-40 years. The antibiotic sensitivity test revealed varying levels of resistance, with the highest sensitivity observed to third-generation cephalosporins, particularly ceftriaxone (32.2% resistance). PCR analysis identified the presence of several virulence genes, including the Hly gene in 96.6% of isolates and the iha gene in 10% of isolates. Elevated levels of inflammatory markers were observed in patients with UTIs, indicating a strong immune response to bacterial infection. Conclusion: E. coli is a significant pathogen in UTIs, exhibiting considerable antibiotic resistance, particularly to first-generation cephalosporins. The presence of specific virulence genes correlates with the severity of infection. These findings underscore the need for targeted antibiotic therapy and the development of strategies to manage antibiotic resistance in UTIs.

Keywords: Urology infections, E. coli, Antibiotic resistance, Inflammatory markers, PCR diagnostics

References

Abdullah, A. M., Abdullah, R. M., & Salman, S. L. (2009). Use of chromogenic agar in detection of urinary tract pathogens and antimicrobial susceptibility. Journal of the Faculty of Medicine Baghdad, 51(1), 39-42. https://doi.org/10.32007/jfacmedbagdad.5111168

Abu Daia, J. M., Al-Aaly, M. A., & De Castro, R. (2000). Urinary tract infection in childhood. Saudi Medical Journal, 21(7), 711-714. https://pubmed.ncbi.nlm.nih.gov/11423881/

Agace, W. W., Hedges, S. R., Ceska, M., & Svanborg, C. (1993). IL-8 and the neutrophil response to mucosal gram-negative infection. Journal of Clinical Investigation, 92(3), 780-785. https://doi.org/10.1172/JCI116635

Akbar, D. H., Ahmed, M. M., & Algamdi, A. A. (2003). Cardiovascular risk factors in Saudi Arabian and non-Saudi Arabian diabetic patients in Saudi Arabia. Eastern Mediterranean Health Journal, 9(5-6), 884-892. https://pubmed.ncbi.nlm.nih.gov/16450518/

AL-Bero, B. R., Agrawal, K. C., & Agnihotri, V. (2000). Transferable drug resistance in Escherichia coli isolated from women with chronic UTI. Indian Journal of Medical Research, 71(1), 83–91.

Al-Dupot, L. B., Wullt, Z. X., Shen, D., & Svanborg, C. (1998). Cytokine repertoire of epithelial cells lining the human urinary tract. Journal of Urology, 159(6), 2185–2192. https://doi.org/10.1016/S0022-5347(01)63303-2

Al-Hadithi, H. A. (1996). Urinary tract infection in Ramadi city: A bacteriological study. Journal of Al-Anbar University, 1(1), 76–81. https://doi.org/10.37652/juaps.2007.15330

Alkasaby, N. M., Alsayed, M. A., Zaki, M. E., Bakr, A. O., & Rizk, M. A. (2022). Study of enteropathogenic Escherichia coli producing extended spectrum β-lactamase in children with acute gastroenteritis. Egyptian Journal of Medical Microbiology, 31(3), 83-90. https://doi.org/10.21608/EJMM.2022.248898

Bachur, R., & Caputo, G. L. (1995). Bacteremia and meningitis among infants with urinary tract infections. Pediatric Emergency Care, 11(4), 280–284. https://doi.org/10.1097/00006565-199510000-00004

Bert, F., & Lambert, Z. N. (1999). Current microbiological problems: Antibiotic resistance and therapeutic problems raised by E. coli. Press Medical, 28(1), 451. https://pubmed.ncbi.nlm.nih.gov/10093607/

Bhat, R. G., Katy, T. A., & Place, F. C. (2011). Pediatric urinary tract infections. Emergency Medicine Clinics of North America, 29(3), 637–653. https://doi.org/10.1016/j.emc.2011.04.004

Bollgren, I., & Winberg, J. (1999). The periurethral aerobic flora in girls highly susceptible to urinary infections. Acta Paediatrica Scandinavica, 65(1), 81-87. https://doi.org/10.1001/Actaps.1981.033102700090

Bradford, P. A. (2001). Extended-spectrum beta-lactamases in the 21st century: Characterization, epidemiology, and detection of this important resistance threat. Clinical Microbiology Reviews, 14(4), 933-951. https://doi.org/10.1128/CMR.14.4.933-951.2001

Brooks, G. F., Butel, J. S., & Morse, S. A. (2001). Jawetz, Melnick, and Adelberg’s medical microbiology (22nd ed.). Lange Medical Books/McGraw-Hill.

Cabral, J. P. S. (2010). Water microbiology. Bacterial pathogens and water. International Journal of Environmental Research and Public Health, 7(10), 3657–3703. https://doi.org/10.3390/ijerph7103657

Chang, S. L., & Shortliffe, L. D. (2006). Pediatric urinary tract infections. Pediatric Clinics of North America, 53(3), 379–400. https://doi.org/10.1016/j.pcl.2006.02.011

Collee, G. J., Chambers, S. T., Peddie, B., & Mahanty, K. H. (1996). The association between colicinogenicity and pathogenesis among uropathogenic isolates of Escherichia coli. Microbial Pathogenesis, 20(3), 185-190. https://doi.org/10.1006/mpat.1996.0017

Delzell, J. E., Jr., & Lefevre, M. L. (2000). Urinary tract infections during pregnancy. American Family Physician. Retrieved from https://www.aafp.org/pubs/afp/issues/2000/0201/p713.html

Dontas, A. S., Papanayiotou, P., & Marketos, S. (1997). Bacteriuria in old age. Bulletin of the New York Academy of Medicine, 2(1), 305. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805129/pdf/bullnyacadmed00111-0019.pdf

Dzidic, S., Suskovic, J., & Kos, B. (2008). Antibiotic resistance mechanisms in bacteria: Biochemical and genetic aspects. Acta Pharmaceutica, 46(1), 11-21. https://hrcak.srce.hr/file/34842

Engel, D., Dobrindt, U., Tittel, A., Peters, P., Maurer, J., Gütgemann, I., Kaissling, B., Kuziel, W., Jung, S., & Kurts, C. (2006). Tumor necrosis factor alpha- and inducible nitric oxide synthase-producing dendritic cells are rapidly recruited to the bladder in urinary tract infection but are dispensable for bacterial clearance. Infection and Immunity, 74(2). https://doi.org/10.1128/iai.00881-06

Fair, W. R. (1999). Observations on the origin of urinary tract infections. In P. E. Kincaid-Smith & K. F. Ferley (Eds.), Renal infections and renal scarring (pp. 98-123). Mercedes.

Farshad, S., Ranjbar, R., Japoni, A., Hosseini, M., Anvarinejad, M., & Mohammadzadegan, R. (2012). Microbial susceptibility, virulence factors, and plasmid profiles of uropathogenic Escherichia coli strains isolated from children in Jahrom, Iran. Journal of Archives of Iranian Medicine, 15(5), 312-316. https://pubmed.ncbi.nlm.nih.gov/22519382/

Fuda, C., Suvorov, M., Vakulenko, S. B., & Mobashery, S. (2004). The basis for resistance to beta-lactam antibiotics by penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus. Journal of Biological Chemistry, 279(40), 40802-40806. https://doi.org/10.1074/jbc.M403589200

Gunther, N. W., Virginia, L., David, E., & Harry, L. (2001). In vivo dynamics of type 1 fimbriae regulation in uropathogenic Escherichia coli during experimental urinary tract infection. Infection and Immunity, 69(5), 2838-2846. https://doi.org/10.1128/IAI.69.5.2838-2846.2001

Hara, C. M., Brenner, F. M., & Miller, J. M. (2000). Classification, identification, and clinical significance of Proteus, Providencia, and Morganella. Clinical Microbiology Reviews, 13(4), 534-546. https://doi.org/10.1128/cmr.13.4.534-546.2000

Hedström, M., & Gröndal, L. (1999). Urinary tract infection in patients with hip fractures. Journal of Family Practice, 30(5), 341-343. https://doi.org/10.1016/s0020-1383(99)00094-7

Ho, G. Y. F., Xue, X.-N., Burk, R. D., Kaplan, R. C., Cornell, E., & Cushman, M. (2005). Variability of serum levels of tumor necrosis factor-alpha, interleukin 6, and soluble interleukin 6 receptor over 2 years in young women. Cytokine, 30(1), 1-6. https://doi.org/10.1016/j.cyto.2004.08.008

Hooton, T., Steapleton, A., & Roberts, P. (2001). Perineal anatomy and urine-voiding characteristics of young women with and without recurrent urinary tract infections. Clinical Infectious Diseases, 29(1), 1600. https://doi.org/10.1086/313528

Hows, P. F., Jarvis, J. A., & Mitchell, C. K. (2003). Urinary tract infections. Primary Care: Clinics in Office Practice, 30(1), 41-61.

Jacoby, G. A., & Munoz-Price, L. S. (2005). The new beta-lactamases. New England Journal of Medicine, 352(4), 380-391. https://doi.org/10.1056/NEJMra041359

Jawetz, E., Brooks, G. F., Butel, J. S., & Morse, S. A. (1998). Jawetz Melnick and Adelberg’s Medical Microbiology (21st ed.). Appleton and Lange.

Kunin, C. M. (1994). Urinary tract infections in females. Clinical Infectious Diseases, 18(1), 1-12. https://doi.org/10.1093/clinids/18.1.1

Lane, D. R., & Takhar, S. S. (2011). Diagnosis and management of urinary tract infection and pyelonephritis. Emergency Medicine Clinics of North America, 29(3), 539–552. https://doi.org/10.1016/j.emc.2011.04.001

Lee, K., Hong, S. G., Park, Y. J., Lee, H. S., Song, W., Jeong, J., Yong, D., & Chong, Y. (2005). Evaluation of phenotypic screening methods for detecting plasmid-mediated AmpC β-lactamases-producing isolates of Escherichia coli and Klebsiella pneumoniae. Diagnostic Microbiology and Infectious Disease, 53(4), 319-323. https://doi.org/10.1016/j.diagmicrobio.2005.07.004

MacFaddin, J. F. (2000). Biochemical tests for identification of medical bacteria (3rd ed.). Lippincott Williams & Wilkins.

Mahyar, A., Ayazi, P., Maleki, M. R., Daneshi-Kohan, M. M., Sarokhani, H. R., Hashemi, H. J., & Talebi-Bakhshayesh, M. (2013). Serum levels of interleukin-6 and interleukin-8 as diagnostic markers of acute pyelonephritis in children. Korean Journal of Pediatrics, 56(5), 218-223. https://doi.org/10.3345/kjp.2013.56.5.218

Naylor, G. H. (1998). A 16-month analysis of urinary tract infection in children. Journal of Medical Microbiology, 17(1), 31-36. https://doi.org/10.1099/00222615-17-1-31

Nicolle, L. E. (2009). Urinary tract infection in the elderly. Journal of Antimicrobial Chemotherapy, 33(1), 99. https://doi.org/10.1016/j.cger.2009.04.005

Prat, C., Domínguez, J., Andreo, F., & Hernández, M. (2006). Urinary antigen test for pneumococcal pneumonia. Chest, 130(3), 849-853. https://doi.org/10.1378/chest.130.3.849

Raka, L., Mulliqi-Osmani, G., Berisha, L., et al. (2004). Etiology and susceptibility of urinary tract isolates in Kosova. International Journal of Antimicrobial Agents, 23(1), 2-5. https://doi.org/10.1016/j.ijantimicag.2003.09.009

Riff, F. (1988). Current microbiological problems: Antibiotic resistance and therapeutic problems raised by E. coli. Press Med, 28(1), 451.

Roilides, E., Papachristou, F., Gioulekas, E., Tsaparidou, S., Karatzas, N., Sotiriou, J., & Tsiouris, J. (1999). Increased urine interleukin-6 concentrations correlate with pyelonephritic changes on 99mTc-dimercaptosuccinic acid scans in neonates with urinary tract infections. Journal of Infectious Diseases, 180(3), 904-907. https://doi.org/10.1086/314960

Segreti, J., Levin, S., & Marshal, A. (1996). Bacteriological and clinical applications of a new extended spectrum parenteral cephalosporin. American Journal of Medicine, 100(6), 45-55. https://doi.org/10.1016/s0002-9343(96)00107-6

Stamm, W. E., & Hooton, T. M. (1993). Management of urinary tract infection in adults. New England Journal of Medicine, 329(18), 1328-1334. https://doi.org/10.1056/NEJM199310283291808

Stukus, P. E. (1997). Investigating microbiology. Harcourt Brace and Company. https://doi.org/10.29079/vol13iss1art275

Tada, D. G., Gandhi, P. J., & Patel, K. N. (2012). A study on antibiotic-related resistance in UTI patients: A comparison between community-acquired and hospital-acquired E. coli. National Journal of Community Medicine, 3(2), 255-258. https://njcmindia.com/index.php/file/article/view/1691

Umegaki, H., Yamada, K., Naito, M., Kameyama, T., Iguchi, A., & Nabeshima, T. (1996). Protective effect of interleukin-6 against the death of PC12 cells caused by serum deprivation or by the addition of a calcium ionophore. Biochemical Pharmacology, 52(6), 911–916. https://doi.org/10.1016/0006-2952(96)00422-4

Vernon, S., Foo, C. K., & Coulthard, M. G. (1997). How general practitioners manage children with urinary tract infection: An audit in the former Northern Region. British Journal of General Practice, 47(418), 297-300. https://pubmed.ncbi.nlm.nih.gov/9219406/

Winberg, G. T., Funk, B. R., & Case, C. L. (1998). Microbiology: An introduction (6th ed.). The Benjamin Cummings Publishing Company.

Wullt, B., Bergsten, G., Connell, H., Röllano, P., Gebretsadik, N., Hull, R., & Svanborg, C. (2000). P-fimbriae enhance the early establishment of E. coli in the human urinary tract. Molecular Microbiology, 38(3), 456-464. https://doi.org/10.1046/j.1365-2958.2000.02165.x

Wullt, B., Bergsten, G., Samuelsson, M., & Svanborg, C. (2002). The role of P fimbriae for Escherichia coli establishment and mucosal inflammation in the human urinary tract. International Journal of Antimicrobial Agents, 19(6), 522–538. https://doi.org/10.1016/s0924-8579(02)00103-6

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