Frequency of toxin genes and antibiotic resistance pattern of Clostridioides difficile isolates in diarrheal samples among hospitalized patients in Hamadan, Iran
Gastroenterology and Hepatology from Bed to Bench,
Vol. 14 No. 2 (2021),
8 Esfand 2021
,
Page 165-173
https://doi.org/10.22037/ghfbb.v14i2.2197
Abstract
Aim: This study was designed to investigate the prevalence of Clostridioides difficile, its toxin-producing genes, and antibiotic resistance patterns in diarrheal samples from hospitalized patients in Hamadan, Iran.
Background: Today, concerns over Clostridioides difficile infection (CDI) have significantly increased due to reduced susceptibility to antibiotics used for CDI treatment. Toxins produced by C. difficile strains are associated with disease severity and outcome.
Methods: In this cross-sectional study, a total of 130 diarrheal samples of patients admitted to different wards of three hospitals in Hamadan from November 2018 to September 2019 were collected. C. difficile isolates were identified by culture on CCFA and PCR (Polymerase chain reaction). The presence of toxin-encoding genes (tcdA and tcdB) and binary toxin genes (cdtA and cdtB) was analyzed by PCR. Resistance of the isolates to metronidazole, vancomycin and clindamycin antibiotics was determined using agar dilution method.
Results: Out of 130 diarrheal samples from hospitalized patients, 16 (12.3%) C. difficile isolates were obtained. PCR results were positive for two toxin-producing genes, tcdA and tcdB, in all (100%) C. difficile isolates, and the binary toxin genes cdtA and cdtB were detected in 6 (37.5%) and 8 (50%) isolates, respectively. The results of antibiotic susceptibility testing showed resistance to metronidazole, vancomycin, and clindamycin in 3 (18.7%), 3 (18.7%), and 2 (12.5%) isolates, respectively, and all isolates were resistant to rifampicin.
Conclusion: The results of this study showed toxigenic C. difficile with tcdA+/tcdB+ profile is a major cause of nosocomial diarrhea in Hamadan, and clinical laboratories should routinely perform C. difficile diagnostic testing on diarrheal specimens of hospitalized patients. Resistance to conventional antibiotic therapy against C. difficile should be considered as a warning to prevent irrational administration of antibiotics.
Keywords: Clostridioides difficile, TcdA, TcdB, Binary toxin, Antibiotic resistance.
(Please cite as: Shokoohizadeh L, Alvandi F, Yadegar A, Azimirad M, Hashemi SH, Alikhani MY. Frequency of toxin genes and antibiotic resistance pattern of Clostridioides difficile isolates in diarrheal samples among hospitalized patients in Hamadan, Iran. Gastroenterol Hepatol Bed Bench 2021;14(2):165-173).
- Clostridioides difficile, tcdA, tcdB, Binary toxin, Antibiotic resistance
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References
Riggs MM, Sethi AK, Zabarsky TF, Eckstein EC, Jump RL, Donskey CJ. Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin infect Dis 2007;45:992-8.
Rodriguez-Palacios A, Borgmann S, Kline TR, LeJeune JT. Clostridium difficile in foods and animals: history and measures to reduce exposure. Anim Health Res Rev 2013;14:11.
Azimirad M, Noukabadi FN, Lahmi F, Yadegar A. Prevalence of binary-toxin genes (cdtA and cdtB) among clinical strains of Clostridium difficile isolated from diarrheal patients in Iran. Gastroenterol Hepatol Bed Bench 2018;11:59-65.
Tokimatsu I, Shigemura K, Osawa K, Kinugawa S, Kitagawa K, Nakanishi N, et al. Molecular epidemiologic study of Clostridium difficile infections in university hospitals: Results of a nationwide study in Japan. J Infect Chemother 2018;24:641-7.
Heidari H, Ebrahim-Saraie HS, Amanati A, Motamedifar M, Hadi N, Bazargani A. Toxin profiles and antimicrobial resistance patterns among toxigenic clinical isolates of Clostridioides (Clostridium) difficile. Iran J Basic Med Sci 2019;22:813-9.
McDonald LC, Killgore GE, Thompson A, Owens Jr RC, Kazakova SV, Sambol SP, et al. An epidemic, toxin gene–variant strain of Clostridium difficile. N Engl J Med 2005;353:2433-41.
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;55:1998-2008.
Huang H, Weintraub A, Fang H, Nord CE. Antimicrobial resistance in Clostridium difficile. Int J Antimicrob Agents 2009;34:516-22.
Goudarzi M, Navidinia M. Overview Perspective of Bacterial Strategies of Resistance to Biocides and Antibiotics. Arch Clin Infect Dis 2019;14:e65744
Shoaei P, Shojaei H, Khorvash F, Hosseini SM, Ataei B, Tavakoli H, et al. Molecular epidemiology of Clostridium difficile infection in Iranian hospitals. Antimicrob Resist Infect Control 2019;8:1-7.
Azimirad M, Krutova M, Yadegar A, Shahrokh S, Olfatifar M, Aghdaei HA, et al. Clostridioides difficile ribotypes 001 and 126 were predominant in Tehran healthcare settings from 2004 to 2018: A 14-year-long cross-sectional study. Emerg Microbes Infect 2020;9:1432-43.
Azimirad M, Krutova M, Balaii H, Kodori M, Shahrokh S, Azizi O, et al. Coexistence of Clostridioides difficile and Staphylococcus aureus in gut of Iranian outpatients with underlying inflammatory bowel disease. Anaerobe 2020;61:102113.
Cohen SH, Tang YJ, Silva Jr J. Analysis of the pathogenicity locus in Clostridium difficile strains. J Infect Dis 2000;181:659-63.
Terhes G, Urbán E, Sóki J, Hamid KA, Nagy E. Community-acquired Clostridium difficile diarrhea caused by binary toxin, toxin A, and toxin B gene-positive isolates in Hungary. J Clin Microbiol 2004;42:4316-8.
CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 28th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute;2018.
Peng Z, Addisu A, Alrabaa S, Sun X. Antibiotic resistance and toxin production of Clostridium difficile isolates from the hospitalized patients in a large hospital in Florida. Front Microbiol 2017;8:2584.
Bouza E. Consequences of Clostridium difficile infection: understanding the healthcare burden. Clin Microbiol Infect 2012;18:5-12.
Bauer MP, Notermans DW, Van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, et al. Clostridium difficile infection in Europe: a hospital-based survey. Lancet 2011;377:63-73.
Curcio D, Cané A, Fernández FA, Correa J. Clostridium difficile-associated diarrhea in developing countries: A systematic review and meta-analysis. Infect Dis Ther 2019;8:87-103.
Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431-55.
Depestel DD, Aronoff DM. Epidemiology of Clostridium difficile infection. J Pharm Pract 2013;26:464-75.
Forrester JD, Cai LZ, Mbanje C, Rinderknecht TN, Wren SM. Clostridium difficile infection in low‐and middle‐human development index countries: a systematic review. Trop Med Int Health 2017;22:1223-32.
Freeman J, Bauer MP, Baines SD, Corver J, Fawley WN, Goorhuis B, et al. The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev 2010;23:529-49.
Burke KE, Lamont JT. Clostridium difficile infection: a worldwide disease. Gut Liver 2014;8:1-6.
Crobach MJ, Dekkers OM, Wilcox MH, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin Microbiol Infect 2009;15:1053-66.
Planche T, Aghaizu A, Holliman R, Riley P, Poloniecki J, Breathnach A, et al. Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis 2008;8:777-84.
Eastwood K, Else P, Charlett A, Wilcox M. Comparison of nine commercially available Clostridium difficile toxin detection assays, a real-time PCR assay for C. difficile tcdB, and a glutamate dehydrogenase detection assay to cytotoxin testing and cytotoxigenic culture methods. J Clin Microbiol 2009;47:3211-7.
McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018;66:e1-48.
Cheng JW, Xiao M, Kudinha T, Xu ZP, Sun LY, Hou X, et al. The role of glutamate dehydrogenase (GDH) testing assay in the diagnosis of Clostridium difficile infections: a high sensitive screening test and an essential step in the proposed laboratory diagnosis workflow for developing countries like China. PLoS one 2015;10:e0144604.
Borren NZ, Ghadermarzi S, Hutfless S, Ananthakrishnan AN. The emergence of Clostridium difficile infection in Asia: A systematic review and meta-analysis of incidence and impact. PloS one 2017;12:e0176797.
Malekzadegan Y, Halaji M, Hasannejad-Bibalan M, Jalalifar S, Fathi J, Ebrahim-Saraie HS. Burden of Clostridium (Clostridioides) difficile Infection among Patients in Western Asia: A Systematic Review and Meta-Analysis. Iran J Public Health 2019;48:1589.
Senok AC, Aldosari KM, Alowaisheq RA, Abid OA, Alsuhaibani KA, Khan MA, et al. Detection of Clostridium difficile antigen and toxin in stool specimens: comparison of the C. difficile Quik Chek Complete enzyme immunoassay and GeneXpert C. difficile polymerase chain reaction assay. Saudi J Gastroenterol 2017;23:259.
Al-Tawfiq JA, Rabaan AA, Bazzi AM, Raza S, Noureen M. Clostridioides (Clostridium) difficile-associated disease: Epidemiology among patients in a general hospital in Saudi Arabia. Am J Infect Control 2020;48:1152-7.
Jamal W, Pauline E, Rotimi V. A prospective study of community-associated Clostridium difficile infection in Kuwait: epidemiology and ribotypes. Anaerob 2015; 35:28-32.
Al-Thani AA, Hamdi WS, Al-Ansari NA, Doiphode SH, Wilson GJ. Erratum: Polymerase chain reaction ribotyping of Clostridium difficile isolates in Qatar: a hospital-based study. BMC Infect Dis 2015;15:173.
Vaishnavi C, Singh M, Mahmood S, Kochhar R. Prevalence and molecular types of Clostridium difficile isolates from faecal specimens of patients in a tertiary care centre. J Med Microbiol 2015;64:1297-304.
Tang C, Cui L, Xu Y, Xie L, Sun P, Liu C, et al. The incidence and drug resistance of Clostridium difficile infection in Mainland China: a systematic review and meta-analysis. Sci Rep 2016;6:37865.
Kwon SS, Gim JL, Kim MS, Kim H, Choi JY, Yong D, et al. Clinical and molecular characteristics of community-acquired Clostridium difficile infections in comparison with those of hospital-acquired C. difficile. Anaerobe 2017;48:42-6.
Goudarzi M, Goudarzi H, Alebouyeh M, Rad MA, Mehr FSS, Zali MR, et al. Antimicrobial susceptibility of Clostridium difficile clinical isolates in Iran. Iran Red Crescent Med J 2013;15:704-11.
Hematyar Y, Pirzadeh T, Moaddab SR, Rezaee MA, Memar MY, Kafil HS. Clostridium difficile in patients with nosocomial diarrhea, Northwest of Iran. Health Promot Perspect 2020;10:148-151.
Gholam-Mostafaei FS, Yadegar A, Aghdaei HA, Azimirad M, Daryani NE, Zali MR. Anti-TNF containing regimens may be associated with increased risk of Clostridioides difficile infection in patients with underlying inflammatory bowel disease. Curr Res Transl Med 2020;68:125-30.
Alimolaei M, Rahimi HR, Ezatkhah M, Bafti MS, Afzali S. Prevalence, characteristics and antimicrobial susceptibility patterns of Clostridioides difficile isolated from hospitals in Iran. J Glob Antimicrob Resist 2019;19:22-7.
Rezazadeh Zarandi E, Mansouri S, Nakhaee N, Sarafzadeh F, Iranmanesh Z, Moradi M. Frequency of antibiotic associated diarrhea caused by Clostridium difficile among hospitalized patients in intensive care unit, Kerman, Iran. Gastroenterol Hepatol Bed Bench 2017;10:229-34.
Krutova M, Nyc O, Matejkova J, Allerberger F, Wilcox MH, Kuijper EJ. Molecular characterisation of Czech Clostridium difficile isolates collected in 2013–2015. Int J Med Microbiol 2016;306:479-85.
Cejas D, Ríos Osorio NR, Quirós R, Sadorin R, Berger MA, Gutkind G, et al. Detection and molecular characterization of Clostridium difficile ST 1 in Buenos Aires, Argentina. Anaerobe 2018;49:14-7.
Luo Y, Zhang W, Cheng JW, Xiao M, Sun GR, Guo CJ, et al. Molecular epidemiology of Clostridium difficile in two tertiary care hospitals in Shandong Province China. Infect Drug Resist 2018;11:489-500.
Sandokji AM, Murshid KR, El-Badry AA, Al-Ali KH, Shalaby SA. Infectious Nosocomial Diarrhea in the Surgical Wards: Role of Parasites and Microbes Imply Stool Analysis. J Taibah Univ Sci 2009;4:73-81.
Putsathit P, Kiratisin P, Ngamwongsatit P, Riley TV. Clostridium difficile infection in Thailand. Int J Antimicrob Agents 2015;45:1-7.
Saha S, Kapoor S, Tariq R, Schuetz AN, Tosh PK, Pardi DS, et al. Increasing antibiotic resistance in Clostridioides difficile: A systematic review and meta-analysis. Anaerobe 2019;58:35-46.
Jin D, Luo Y, Huang C, Cai J, Ye J, Zheng Y, et al. Molecular epidemiology of Clostridium difficile infection in hospitalized patients in eastern China. J Clin Microbiol 2017;55:801.
Tkhawkho L, Nitzan O, Pastukh N, Brodsky D, Jackson K, Peretz A. Antimicrobial susceptibility of Clostridium difficile isolates in Israel. J Glob Antimicrob Resist 2017;10:161-4.
Fraga EG, Nicodemo AC, Sampaio JL. Antimicrobial susceptibility of Brazilian Clostridium difficile strains determined by agar dilution and disk diffusion. Braz J Infect Dis 2016; 20:476-81.
Banawas SS. Clostridium difficile Infections: A Global Overview of Drug Sensitivity and Resistance Mechanisms. Biomed Res Int 2018;2018:8414257.
Sholeh M, Krutova M, Forouzesh M, Mironov S, Sadeghifard N, Molaeipour L, et al. Antimicrobial resistance in Clostridioides (Clostridium) difficile derived from humans: a systematic review and meta-analysis. Antimicrob Resist Infect Control 2020;9:158.
Collins DA, Sohn KM, Wu Y, Ouchi K, Ishii Y, Elliott B, Riley TV, Tateda K, Clostridioides difficile Asia-Pacific Study Group. Clostridioides difficile infection in the Asia-Pacific region. Emerg Microbes Infect 2020;9:42-52.
Martin H, Willey B, Low DE, Staempfli HR, McGeer A, Boerlin P, et al. Characterization of Clostridium difficile strains isolated from patients in Ontario, Canada, from 2004 to 2006. J Clin Microbiol 2008;46:2999-3004.
Spigaglia P. Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection. Ther Adv Infect Dis 2016;3:23-42.
Slimings C, Riley TV. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother 2014;69:881-91.
Baghani A, Mesdaghinia A, Kuijper EJ, Aliramezani A, Talebi M, Douraghi M. High prevalence of Clostridiodes diffiicle PCR ribotypes 001 and 126 in Iran. Sci Rep 2020;10:4658.
Mohammadbeigi M, Safayi Delouyi Z, Mohammadzadeh N, Alaalmohadesin A, Taheri K, Edalati E, et al. Prevalence and antimicrobial susceptibility pattern of toxigenic Clostridium difficilestrains isolated in Iran. Turk J Med Sci 2019;49:384-91.
Jin D, Luo Y, Huang C, Cai J, Ye J, Zheng Y, et al. Molecular Epidemiology of Clostridium difficile Infection in Hospitalized Patients in Eastern China. J Clin Microbiol 2017;55:801-10.
Tilkorn F, Frickmann H, Simon IS, Schwanbeck J, Horn S, Zimmermann O, et al. Antimicrobial Resistance Patterns in Clostridioides difficile Strains Isolated from Neonates in Germany. Antibiotics 2020;9:481.
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. Clin Microbiol Infect 2015;21:248.
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