Phenotypic and Genotypic Investigation of the Resistance of Pathogenic Bacteroides fragilis Group Bacteria to Carbapenems

Year 2024, Volume: 14 Issue: 4, 901 - 905

Aleyna Özkar , Sevim Alpsoy , Nurver Ülger

https://doi.org/10.33808/clinexphealthsci.1495596

Abstract

Objective: Bacteroides fragilis, predominantly found in the intestinal microbiota, is one of the most frequently encountered anaerobic pathogens and exhibits resistance to many antimicrobials. The carbapenem-resistant B. fragilis (CR-BF) isolates have been reported in several countries recently with increasing global attention. The high frequency of CR-BF in our hospitalized patients has become an important problem.
For this reason, B. fragilis isolated in our hospital need to be closely monitored for carbapenem resistance. Therefore, we aimed to determine carbapenem resistance in B. fragilis isolated from clinical samples and the presence of the cfiA gene, which encodes for carbapenemase.
Methods: B. fragilis strains isolated from various clinical samples collected between January 2018 and December 2022 were included in the study. Identification of the isolates was performed using MALDI-TOF MS. The susceptibility testing for meropenem and imipenem was determined by the agar dilution method. The cfiA gene was detected by PCR.
Results: A total 89 B. fragilis strains were studied, mostly from intra-abdominal abscesses (31%) and blood cultures (27%). Susceptibility rates for meropenem and imipenem were 85.4% and 89%, respectively. Notably, 12 out of 13 cfiA gene-positive isolates were resistant, suggesting this gene as a marker for carbapenem resistance. However, resistance in one cfiA-negative isolates implies alternative resistance mechanisms.
Conclusion: Routine anaerobic culture, determination of antibiotic susceptibility profiles of isolates, and close monitoring are crucial for managing infections. Regular antimicrobial susceptibility testing helps predict the risk of developing carbapenem resistance, assists clinicians in selecting appropriate antibiotics for empirical therapy, and improves treatment success rates.

Keywords

Bacteroides fragilis, carbapenem, cfiA gene

Ethical Statement

Ethics Committee approved the study protocol (E-15342631-730.03.02-385946)

Supporting Institution

Major financial support for this study was provided by a research grant from Marmara University, the Scientific Research Projects Coordination Unit, (BAP, Project No. TYL-2023-10991).

References

• Wexler HM. Bacteroides: The good, the bad, and the nitty-gritty. Clin Microbiol Rev. 2007;20(4):593-621. DOI:10.1128/CMR.00008-07
• Nagy E, Boyanova L, Justesen US; ESCMID Study Group of Anaerobic Infections. How to isolate, identify and determine antimicrobial susceptibility of anaerobic bacteria in routine laboratories. Clin Microbiol Infect. 2018;24(11):1139-1148. DOI: 10.1016/j.cmi.2018.02.008.
• Reissier S, Penven M, Guérin F, Cattoir V. Recent trends in antimicrobial resistance among anaerobic clinical isolates. Microorganisms 2023;11(6):1474. DOI: 10.3390/microorganisms11061474.
• Yekani M, Rezaee MA, Beheshtirouy S, Baghi HB, Bazmani A, Farzinazar A, Memar MY, Sóki J. Carbapenem resistance in Bacteroides fragilis: A review of molecular mechanisms. Anaerobe 2022;76:102606. DOI:10.1016/j.anaerobe.2022.102606.
• Podglajen I, Breuil J, Bordon F, Gutmann L, Collatz E. A silent carbapenemase gene in strains of Bacteroides fragilis can be expressed after a one-step mutation. FEMS Microbiol Lett. 1992;70(1):21-29. DOI: 10.1016/03781097(92)90557-5.
• Sóki J, Eitel Z, Urbán E, Nagy E; ESCMID Study Group on Anaerobic Infections. Molecular analysis of the carbapenem and metronidazole resistance mechanisms of Bacteroides strains reported in a Europe-wide antibiotic resistance survey. Int J Antimicrob Agents 2013;41(2):122-125. DOI:10.1016/j.ijantimicag.2012.10.001.
• Eitel Z, Sóki J, Urbán E, Nagy E; ESCMID Study Group on Anaerobic Infection. The prevalence of antibiotic resistance genes in Bacteroides fragilis group strains isolated in different European countries. Anaerobe. 2013;21:43-49. DOI: 10.1016/j.anaerobe.2013.03.001.
• Gao Q, Wu S, Xu T, Zhao X, Huang H, Hu F. Emergence of carbapenem resistance in Bacteroides fragilis in China. Int J Antimicrob Agents. 2019;53(6):859-863. DOI: 10.1016/j.ijantimicag.2019.02.017.
• Toprak Ülger N, Aral C, İlki A, Özer A, Söyletir G. Marmara Üniversitesi Hastanesinde izole edilen ilk imipeneme dirençli Bacteroides fragilis kökeninin fenotipik ve genotipik özelliklerinin araştırılması. (Investigation of phenotypic and genotypic properties of first imipenem resistant bacteroides fragilis isolated from Marmara University Hospital) FLORA 2009;14(4):175-181.(Turkish)
• Ülger Toprak N, Celik C, Cakici O, Söyletir G. Antimicrobial susceptibilities of Bacteroides fragilis and Bacteroides thetaiotaomicron strains isolated from clinical specimens and human intestinal microbiota. Anaerobe 2004;10(5):255-259. DOI:10.1016/j.anaerobe.2004.05.005
• Toprak NU, Uzunkaya OD, Sóki J, Soyletir G. Susceptibility profiles and resistance genes for carbapenems (cfiA) and metronidazole (nim) among Bacteroides species in a Turkish University Hospital. Anaerobe 2012;18(1):169-171. DOI: 10.1016/j.anaerobe.2011.10.004.
• CLSI. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria, Approved Standards-7th Edition, M11-A7, Clinical and Laboratory Standards Institute, Pennsylvania, ABD, 2007.
• EUCAST. European Committee on Antimicrobial Susceptibility Testing, Clinical breakpoints (13.1).2023. http:// www.eucast.org/clinical_breakpoints/
• Kierzkowska M, Majewska A, Karłowicz K, Pituch H. Phenotypic and genotypic identification of carbapenem resistance in Bacteroides fragilis clinical strains. Med Microbiol Immunol. 2023; 212(3):231-240. DOI: 10.1007/s00430-023-00765-w.
• Doğan M, Baysal B. Ceşitli klinik örneklerden izole edilen anaerop bakterilerin tanimlanmasi ve antibiyotik duyarlılıklarının belirlenmesi [Identification of anaerobic bacteria isolated from various clinical specimens and determination of antibiotic susceptibilities]. Mikrobiyol Bul. 2010;44(2):211-219.(Turkish)
• Demir C, Keşli R. Çeşitli klinik örneklerden izole edilen gram-negatif anaerop basillerin tiplendirilmesi ve antibiyotik direnç profillerinin E-test yöntemi ile belirlenmesi. Mikrobiyol Bul. 2018;52(1):72-79. DOI:10.5578/mb.66175 (Turkish)
• Demirci M, Gemicioglu B, Saribas S, Taner Z, Mamal-Torun M, Karatoka B, Aşık-Çağlı L, Güven Ö, Demiryaş S, Kocazeybek BS, Bahar-Tokman H. A retrospective analysis of anaerobic bacteria isolated in 236 cases of pleural empyema and their prevalence of antimicrobial resistance in Turkey. Clin Lab. 2018;64(7):1269-1277. DOI:10.7754/Clin.Lab.2018.180317
• Ulger Toprak N, Akgul O, Bilgin H, Ozaydin AN, Altinkanat Gelmez G, Sayin E, Sili U, Korten V, Soyletir G. Frequency and associated factors for carbapenem-non-susceptible Bacteroides fragilis group bacteria colonization in hospitalized patients: Case control study in a university hospital in Turkey. Indian J Med Microbiol. 2021;39(4):518-522. DOI: 10.1016/j.ijmmb.2021.03.018.