ANTIBIOTICS: CURE AND RISK FACTOR FOR CLOSTRIDIOIDES DIFFICILE INFECTION

Authors

  • Kiril Mihajlov Institute of Microbiology and Parasitology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Elena Trajkovska Dokic Institute of Microbiology and Parasitology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Liljana Labachevska Gjatovska Institute of Microbiology and Parasitology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Marko Kostovski Institute of Microbiology and Parasitology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Radomir Jovchevski Institute of Microbiology and Parasitology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Danica Kovacheva-Trpkovska Institute of Microbiology and Parasitology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Ivana Ignjatovikj Mihajlova University Clinic for Children’s Diseases, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia

Keywords:

Clostridioides difficile infection, C. difficile, antimicrobial susceptibility

Abstract

Introduction: The major risk factor for acquiring an infection with Clostridioides difficile (CDI) is a long-term antibiotic treatment. Contrarily, the treatment of severe CDI cases involves application of antibiotics like vancomycin or metronidazole. Our aim was to investigate the percentage of resistance to eight antibiotics (vancomycin, metronidazole, tetracycline, clindamycin, erythromycin, imipenem, ciprofloxacin and moxifloxacin) among Clostridioides difficile isolates, indirectly evaluating the risks of acquiring CDI and the risks of therapeutic failure.

Materials and methods: Eighty isolates of Clostridioides difficile, collected from fecal samples from as many patients during a four-year period, were subject to PCR ribotyping and to antibiotic susceptibility testing by using the E test.

Results: Ribotyping of the 80 isolates of C. difficile showed that they belonged to 20 different ribotypes. The most common one was 001/072, with 40% of the isolates.  All 80 of C. difficile isolates in this study showed a good sensitivity towards vancomycin and metronidazole. Resistance percentages towards tetracycline, clindamycin, erythromycin, imipenem, ciprofloxacin and moxifloxacin were 1.25%, 49%, 55%, 57%, 100% and 45%, respectively. The highest antimicrobial resistance percentages were detected in isolates taken from patients hospitalized in surgical clinics and in isolates belonging to the dominant ribotype 001/072 and hypervirulent ribotypes 017 and 027.

Conclusions: Vancomycin and metronidazole should remain the first option therapy for CDI. Therapy with clindamycin, erythromycin, imipenem, ciprofloxacin and moxifloxacin could be a risk factor for CDI. Excessive use of a particular antibiotic plays a major role in selecting and multiplying resistant clones of Clostridioides difficile strains.

References

Bacci S, St-Martin G, Olesen B, Bruun B, Olsen KE, Nielsen EM, et al. Outbreak of Clostridium difficile 027 in North Zealand, Denmark, 2008-2009. Euro Surveill 2009; 14(16): 19183.

Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med 2006; 145(10): 758-764. doi: 10.7326/0003-4819-145-10-200611210-00008.

Trajkovska-Dokic E, Mihajlov K, Popovska K, Mircevska G, Kartalov A, & Kuzmanovska B. The role of probiotic "Diastop probio” in prevention of Clostridium difficile colonization and infection in hospitalized patients. Archives of Public Health 2018; 10(1): 12-18.

Kyne L. Clostridium difficile--beyond antibiotics. N Engl J Med 2010; 362(3): 264-265. doi: 10.1056/NEJMe0910055.

Wong SS, Woo PC, Luk WK, Yuen KY. Susceptibility testing of Clostridium difficile against metronidazole and vancomycin by disk diffusion and Etest. Diagn Microbiol Infect Dis 1999; 34(1): 1-6. doi: 10.1016/s0732-8893(98)00139-4.

Mihajlov K, Grdanoska T, Trajkovska Dokic E. Distribution of Clostridioides difficile ribotypes isolated from patients in North Macedonia - Update. Academic Medical Journal 2023; 3: 32-40. https://www.doi.org/10.53582/AMJ2332032m.

Spigaglia P. Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection. Ther Adv Infect Dis 2016; 3(1): 23-42. doi: 10.1177/2049936115622891.

Freeman J, Vernon J, Morris K, Nicholson S, Todhunter S, Longshaw C, et al. Pan-European Longitudinal Surveillance of Antibiotic Resistance among Prevalent Clostridium difficile Ribotypes' Study Group. Pan-European longitudinal surveillance of antibiotic resistance among prevalent Clostridium difficile ribotypes. Clin Microbiol Infect 2015; 21(3): 248.e9-248.e16. doi: 10.1016/j.cmi.2014.09.017.

Adler A, Miller-Roll T, Bradenstein R, Block C, Mendelson B, Parizade M, et al. A national survey of the molecular epidemiology of Clostridium difficile in Israel: the dissemination of the ribotype 027 strain with reduced susceptibility to vancomycin and metronidazole. Diagn Microbiol Infect Dis 2015; 83: 21-24. doi: 10.1016/j.diagmicrobio.2015.05.015.

Snydman DR, McDermott LA, Jacobus NV, Thorpe C, Stone S, Jenkins SG, et al. U.S.-Based National Sentinel Surveillance Study for the Epidemiology of Clostridium difficile-Associated Diarrheal Isolates and Their Susceptibility to Fidaxomicin. Antimicrob Agents Chemother 2015; 59(10): 6437-6443. doi: 10.1128/AAC.00845-15.

Peng Z, Jin D, Kim HB, Stratton CW, Wu B, Tang YW, et al. Update on Antimicrobial Resistance in Clostridium difficile: Resistance Mechanisms and Antimicrobial Susceptibility Testing. J Clin Microbiol 2017; 55(7): 1998-2008. doi: 10.1128/JCM.02250-16.

Bartlett JG, Onderdonk AB, Cisneros RL, Kasper DL. Clindamycin-associated colitis due to a toxin-producing species of Clostridium in hamsters. J Infect Dis 1977; 136(5): 701-705. doi: 10.1093/infdis/136.5.701.

McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005; 353(23): 2433-2441. doi: 10.1056/NEJMoa051590.

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Published

2024-04-22

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Original Articles