Evaluation of fosfomycin, furazidin, and gentamicin impact on growth of uropathogenic ESBL-producing Escherichia coli
DOI:
https://doi.org/10.21164/pomjlifesci.1077Słowa kluczowe:
fitness cost, extended-spectrum β-lactamase, urinary tract infection, Escherichia coli, antimicrobialsAbstrakt
Introduction: Urinary tract infections are a prevalent health issue, significantly impacting both patient well-being and healthcare systems. The rise of antibiotic resistance, particularly among Gram– bacilii, complicates treatment protocols. This study assesses the inhibitory effect of 3 antimicrobials – fosfomycin, furazidin, and gentamicin – against both wild-type and extended-spectrum β-lactamase (ESBL)-producing uropathogenic Escherichia coli clinical strains.
Materials and methods: Sixty E. coli isolates (30 ESBL-producing and 30 wild-type) were collected from clinical urine samples. Identification and antimicrobial susceptibility were assessed using MALDI-TOF MS and VITEK 2 systems. Growth inhibition by antibiotics was measured in Mueller-Hinton broth at optical density 600 nm over 24 h. Extended-spectrum β-lactamase genes were identified via polymerase chain reaction targeting blaCTX-M, blaSHV, blaTEM, blaPER, blaVEB and blaGES genes. Statistical analysis was performed using the Friedman test with Dunn’s correction.
Results: Fosfomycin exhibited significant growth inhibition against both wild-type and ESBL-producing E. coli, particularly those harboring blaCTX-M genes. Furazidin and gentamicin were effective against wild-type strains but not against ESBL producers. Statistically significant inhibition for wild-type strains was observed with fosfomycin (p = 0.004), furazidin (p = 0.007), and gentamicin (p = 0.008). For ESBL producers, significant inhibition was noted only with fosfomycin (p < 0.001).
Conclusions: Fosfomycin shows strong efficacy against both wild-type and ESBL-producing E. coli, suggesting its potential as a first-line treatment for urinary tract infections amidst rising antibiotic resistance. Furazidin and gentamicin, while effective against wild-type strains, are less effective against ESBL-producing strains, underscoring the need for targeted antibiotic use. Further research is recommended to validate these findings and optimize clinical treatment guidelines.
Bibliografia
Dubbs SB, Sommerkamp SK. Evaluation and management of urinary tract infection in the emergency department. Emerg Med Clin North Am 2019;37:707-23.
Masajtis-Zagajewska A, Nowicki M. New markers of urinary tract infection. Clin Chim Acta 2017;471:286-91.
Wang Z, Schorr C, Hunter K, Dellinger RP. Contrasting treatment and outcomes of septic shock: Presentation on hospital floors versus emergency department. Chin Med J 2010;123:3550-3.
Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D, et al. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: A propensity-matched analysis. Crit Care Med 2010;38:1773-85.
Lingenfelter E, Drapkin Z, Fritz K, Youngquist S, Madsen T, Fix M. ED pharmacist monitoring of provider antibiotic selection aids appropriate treatment for outpatient UTI. Am J Emerg Med 2016;34:1600-3.
Wagenlehner FM, Vahlensieck W, Bauer HW, Weidner W, Piechota HJ, Naber KG. Prevention of recurrent urinary tract infections. Minerva Urol Nefrol 2013;65(1):9-20.
Justice SS, Hung C, Theriot JA, Fletcher DA, Anderson GG, Footer MJ, et al. Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Proc Natl Acad Sci USA 2004;101(6):1333-8.
Bonkat G, Bartoletti R, Bruyère F, Cai T, Geerlings SE, Köves B, et al. EAU Guidelines on Urological Infections. Arnhem: European Association of Urology Guidelines Office; 2024.
Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev 2005;18(4):657-86.
Cantón R, González-Alba JM, Galán JC. CTX-M enzymes: origin and diffusion. Front Microbiol 2012;3:110.
Castanheira M, Simner PJ, Bradford PA. Extended-spectrum β-lactamases: An update on their characteristics, epidemiology and detection. JAC Antimicrob Resist 2021;3:dlab092.
Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase-producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis 2010;10(1):43-50.
Karageorgopoulos DE, Wang R, Yu XH, Falagas ME. Fosfomycin: evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens. J Antimicrob Chemother 2012;67(3):255-68.
Bielec F, Wenecka M, Brauncajs M, Pastuszak-Lewandoska D. Analysis of cumulative antibiogram reports in search for optimal empirical urinary tract infection treatment at the Central Teaching Hospital of the Medical University of Lodz, Poland: Results of a 3-Year Surveillance. J Clin Med 2023;12:6270.
Kot B, Grużewska A, Szweda P, Wicha J, Parulska U. Antibiotic resistance of uropathogens isolated from patients hospitalized in District Hospital in Central Poland in 2020. Antibiotics 2021;10:447.
Iqbal R, Ikram N, Shoaib M, Asad M, Mehmood RT, Niazi A, et al. Phenotypic confirmatory disc diffusion test (PCDDT), double disc synergy test (DDST), E-test as diagnostic tool for detection of extended spectrum beta lactamase (ESBL) producing Uropathogens. J Appl Biotechnol Bioeng 2017;3:344-9.
Bielec F, Brauncajs M, Pastuszak-Lewandoska D. Nitrofuran derivatives cross-resistance evidence – Uropathogenic Escherichia coli nitrofurantoin and furazidin in vitro susceptibility testing. J Clin Med 2023;12:5166.
ISO 20776-1:2019. Susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices – Part 1: Broth micro-dilution reference method for testing the in vitro activity of antimicrobial agents against rapidly growing aerobic bacteria involved in infectious diseases. Geneva: ISO; 2019.
Moghaddam MN, Beidokhti MH, Jamehdar SA, Ghahraman M. Genetic properties of blaCTX-M and blaPER β-lactamase genes in clinical isolates of Enterobacteriaceae by polymerase chain reaction. Iran J Basic Med Sci 2014;17:378-83.
Ejaz H. Dissemination of SHV, TEM and CTX-M genotypes in Pseudomonas aeruginosa: A pre-eminent reason for therapeutic failure in pediatrics. Ann Clin Lab Sci 2020;50:797-805.
Amirkamali S, Naserpour-Farivar T, Azarhoosh K, Peymani A. Distribution of the blaOXA, blaVEB-1, and blaGES-1 genes and resistance patterns of ESBL-producing Pseudomonas aeruginosa isolated from hospitals in Tehran and Qazvin, Iran. Rev Soc Bras Med Trop 2017;50:315-20.
Woodford N, Fagan EJ, Ellington MJ. Multiplex PCR for rapid detection of genes encoding CTX-M extended-spectrum β-lactamases. J Antimicrob Chemother 2006;57:154-5.
Elso CM, Roberts LJ, Smyth GK, Thomson RJ, Baldwin TM, Foote SJ, et al. Leishmaniasis host response loci (lmr13) modify disease severity through a Th1/Th2-independent pathway. Genes Immun 2004;5:93-100.
Baldwin T, Sakthianandeswaren A, Curtis J, Kumar B, Smyth GK, Foote S, et al. Wound healing response is a major contributor to the severity of cutaneous leishmaniasis in the ear model of infection. Parasite Immunol 2007;29:501-13.
Oteo J, Cercenado E, Fernández-Romero S, Saéz D, Padilla B, Zamora E, et al. Extended-spectrum-β-lactamase-producing Escherichia coli as a cause of pediatric infections: Report of a neonatal intensive care unit outbreak due to a CTX-M-14-producing strain. Antimicrob Agents Chemother 2012;56:54-8.
Melzer M, Petersen I. Mortality following bacteraemic infection caused by extended spectrum beta-lactamase (ESBL) producing E. coli compared to non-ESBL producing E. coli. J Infect 2007;55:254-9.
Higuchi H, Nakamura T, Mashino J, Imada T, Morimoto T. Prediction of ESBL-producing E. coli for suspected urinary tract infection. Urologia 2023;90:151-6.
Tüzün T, Sayın Kutlu S, Kutlu M, Kaleli İ. Risk factors for community-
-onset urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli. Turk J Med Sci 2019;49:1206-11.
Mwakyoma AA, Kidenya BR, Minja CA, Mushi MF, Sandeman A, Sabiti W, et al. Allele distribution and phenotypic resistance to ciprofloxacin and gentamicin among extended-spectrum β-lactamase-producing Escherichia coli isolated from the urine, stool, animals, and environments of patients with presumptive urinary tract infection in Tanzania. Front Antibiot 2023;2:1164016.
Sastry S, Doi Y. Fosfomycin: Mechanisms and the increasing prevalence of resistance. Cold Spring Harb Perspect Med 2016;6(1):a025262.
Dos Santos C, Dos Santos LS, Franco OL. Fosfomycin and nitrofurantoin: classic antibiotics and perspectives. J Antibiot (Tokyo) 2021;74:547-58.
Falagas ME, Athanasaki F, Voulgaris GL, Triarides NA, Vardakas KZ. Resistance to fosfomycin: Mechanisms, Frequency and Clinical Consequences. Int J Antimicrob Agents 2019;53:22-8.
Bahy R, Abu El-Wafa W, Abouwarda A. Molecular Mechanisms of Fosfomycin Resistance in MDR Escherichia coli Isolates from Urinary Tract Infections. Egypt J Med Microbiol 2023;32:25-9.
Galindo-Méndez M, Navarrete-Salazar H, Baltazar-Jiménez F, Muñoz de la Paz E, Sánchez-Mawcinitt MF, Gómez-Pardo A, et al. Emergence of Fosfo-mycin Resistance by Plasmid-Mediated fos Genes in Uropathogenic ESBL--Producing E. coli Isolates in Mexico. Antibiotics (Basel) 2022;11:1383.
Garallah ET, Al-Jubori SS. Surveillance of murA and the plasmid-mediated fosfomycin resistance fosA gene in uropathogenic E. coli isolates from UTI patients. Gene Rep 2020;21:100872.
Nasrollahian S, Graham JP, Halaji M. A review of the mechanisms that confer antibiotic resistance in pathotypes of E. coli. Front Cell Infect Microbiol 2024;14:1387497.
Bush K, Bradford PA. Epidemiology of β-Lactamase-Producing Pathogens. Clin Microbiol Rev 2020;33:e00047-19.
Livermore DM, Canton R, Gniadkowski M, Nordmann P, Rossolini GM, Arlet G, et al. CTX-M: changing the face of ESBLs in Europe. J Antimicrob Chemother 2007;59(2):165-74.
Pobrania
Opublikowane
Numer
Dział
Licencja
Prawa autorskie (c) 2026 Filip Bielec
Praca jest udostępniana na licencji Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 Unported License.
Autor pozostaje właścicielem praw autorskich i praw pokrewnych – udziela jedynie nieodpłatnej licencji na udostępnianie pracy zgodnie z licencją Creative Commons Uznanie autorstwa – Użycie niekomercyjne – Bez utworów zależnych 3.0 PL (CC BY-NC-ND 3.0 PL).
