Advertisement

Retrospective study of the efficacy and safety of metronidazole and vancomycin for Clostridioides difficile infection

      Abstract

      Introduction

      According to the Japanese guidelines for the management of Clostridioides difficile infection (CDI), the first choice is metronidazole (MNZ) for non-severe cases and vancomycin (VCM) for severe cases. However, the appropriateness of this first choice in Japanese patients is unclear. We therefore evaluated the appropriateness of the CDI management guidelines and the incidence of adverse drug reactions.

      Methods

      The electronic chart data at Keio University Hospital between January 2012 and June 2019 were retrospectively reviewed. The response rate, the relapse rate, and the adverse reaction rate of treatment for CDI using MNZ or VCM were investigated according to the disease severity. Factorial analysis associated with the response, relapse, and adverse reaction was also performed.

      Results

      In the 352 patients surveyed, no significant difference was observed in the response rate between MNZ and VCM regardless of the severity of CDI. The presence of cancer was a factor related to the persistence of diarrheal symptoms and older age was a risk factor for relapse. MNZ induced nausea significantly more frequently than VCM, and young age and female sex were risk factors for nausea.

      Conclusion

      As no significant difference was observed in the response rate of CDI between MNZ and VCM, the Japanese CDI management guidelines, which recommend MNZ as the first choice, were demonstrated to be appropriate. Attention to nausea was also suggested to be necessary when administering MNZ to young females.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Infection and Chemotherapy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. The Japanese clinical practice guidelines for management of Clostridioides (Clostridium) difficile infections 2018.
        Jpn J Chemother. 2020; 68: 1-107
        • Cohen S.H.
        • Gerding D.N.
        • Johnson S.
        • Kelly C.P.
        • Loo V.G.
        • McDonald L Clifford
        • 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: 431-455
        • McDonald L.C.
        • Gerding D.N.
        • Johnson S.
        • Bakken J.S.
        • Carroll K.C.
        • Coffin S.E.
        • 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 (48): e1https://doi.org/10.1093/cid/cix1085
        • Fabre V.
        • Dzintars K.
        • Avdic E.
        • Cosgrove S.E.
        Novel assay of immunity: adding more than adding up steroids?.
        Clin Infect Dis. 2018; 67 (8): 1956https://doi.org/10.1093/cid/ciy465
        • Igarashi Y.
        • Tashiro S.
        • Enoki Y.
        • Taguchi K.
        • Matsumoto K.
        • Ohge H.
        • et al.
        Oral vancomycin versus metronidazole for the treatment of Clostridioides difficile infection: meta-analysis of randomized controlled trials.
        J Infect Chemother. 2018; 24: 907-914https://doi.org/10.1016/j.jiac.2018.08.003
        • Physicians F.
        • Pharmacists D.
        • Bailey E.
        • Belliveau P.P.
        • Drew R.H.
        • Freeman C.D.
        • et al.
        ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of clostridium difficile-associated disease.
        Am J Heal Pharm. 1998; 55: 1407-1411https://doi.org/10.1093/ajhp/55.13.1407
        • Zar F.A.
        • Bakkanagari S.R.
        • Moorthi K.M.L.S.T.
        • Davis M.B.
        A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity.
        Clin Infect Dis. 2007; 45: 302-307https://doi.org/10.1086/519265
        • Mikamo H.
        • Tateda K.
        • Yanagihara K.
        • Kusachi S.
        • Takesue Y.
        • Miki T.
        • et al.
        Efficacy and safety of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in a randomized, double-blind, comparative Phase III study in Japan.
        J Infect Chemother. 2018; 24: 744-752https://doi.org/10.1016/j.jiac.2018.05.010
        • Matsumoto K.
        • Kanazawa N.
        • Shigemi A.
        • Ikawa K.
        • Morikawa N.
        • Koriyama T.
        • et al.
        Factors affecting treatment and recurrence of Clostridium difficile infections.
        Biol Pharm Bull. 2014; 37: 1811-1815https://doi.org/10.1248/bpb.b14-00492
        • Yuichi M.
        • Takaaki A.
        • Satoshi O.
        • Masayuki S.
        • Naomi H.
        • Masaki T.
        • et al.
        Appropriate use of metronidazole in patients with positive results for Clostridium difficile: establishment and practice of standard procedures for the infection control team and ward pharmacists.
        J Jpn Soc Hosp Pharm. 2008; 44: 1523-1526
        • Naoya A.
        • Makoto H.
        • Yuki I.
        • Kouichi N.
        • Hiromu F.
        • Youhei M.
        • et al.
        Study on economic effects by standardization of the drug selection of Clostridium dififilcile infection treatment.
        J Jpn Soc Hosp Pharm. 2014; 50: 1461-1464
        • Johnson S.
        • Louie T.J.
        • Gerding D.N.
        • Cornely O.A.
        • Chasan-Taber S.
        • Fitts D.
        • et al.
        Vancomycin, metronidazole, or tolevamer for clostridium difficile infection: results from two multinational, randomized, controlled trials.
        Clin Infect Dis. 2014; 59: 345-354https://doi.org/10.1093/cid/ciu313
        • Kato H.
        • Senoh M.
        • Honda H.
        • Fukuda T.
        • Tagashira Y.
        • Horiuchi H.
        • et al.
        Clostridioides (Clostridium) difficile infection burden in Japan: a multicenter prospective study.
        Anaerobe. 2019; 60: 4-7https://doi.org/10.1016/j.anaerobe.2019.03.007
        • Tickler I.A.
        • Obradovich A.E.
        • Goering R.V.
        • Fang F.C.
        • Tenover F.C.
        Changes in molecular epidemiology and antimicrobial resistance profiles of Clostridioides (Clostridium) difficile strains in the United States between 2011 and 2017.
        Anaerobe. 2019; 60: 102050https://doi.org/10.1016/j.anaerobe.2019.06.003
        • Cornely O.A.
        • Miller M.A.
        • Fantin B.
        • Mullane K.
        • Kean Y.
        • Gorbach S.
        Resolution of Clostridium difficile-associated diarrhea in patients with cancer treated with fidaxomicin or vancomycin.
        J Clin Oncol. 2013; 31: 2493-2499https://doi.org/10.1200/JCO.2012.45.5899
        • Vardakas K.Z.
        • Polyzos K.A.
        • Patouni K.
        • Rafailidis P.I.
        • Samonis G.
        • Falagas M.E.
        Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence.
        Int J Antimicrob Agents. 2012; 40: 1-8https://doi.org/10.1016/j.ijantimicag.2012.01.004
        • Garey K.W.
        • Sethi S.
        • Yadav Y.
        • DuPont H.L.
        Meta-analysis to assess risk factors for recurrent Clostridium difficile infection.
        J Hosp Infect. 2008; 70: 298-304https://doi.org/10.1016/j.jhin.2008.08.012
        • Thongprayoon C.
        • Cheungpasitporn W.
        • Phatharacharukul P.
        • Edmonds P.J.
        • Kaewpoowat Q.
        • Mahaparn P.
        • et al.
        Chronic kidney disease and end stage renal disease are risk factors for poor outcomes of Clostridium difficile infection: a systematic review and meta-analysis.
        Int J Clin Pract. 2015; 69: 998-1006https://doi.org/10.1111/ijcp.12672
        • Kuwata Y.
        • Tanimoto S.
        • Sawabe E.
        • Shima M.
        • Takahashi Y.
        • Ushizawa H.
        • et al.
        Molecular epidemiology and antimicrobial susceptibility of Clostridium difficile isolated from a university teaching hospital in Japan.
        Eur J Clin Microbiol Infect Dis. 2015; 34: 763-772https://doi.org/10.1007/s10096-014-2290-9
        • Sawabe E.
        • Kato H.
        • Osawa K.
        • Chida T.
        • Tojo N.
        • Arakawa Y.
        • et al.
        Molecular analysis of Clostridium difficile at a university teaching hospital in Japan: a shift in the predominant type over a five-year period.
        Eur J Clin Microbiol Infect Dis. 2007; 26: 695-703https://doi.org/10.1007/s10096-007-0355-8
        • Mori N.
        • Yoshizawa S.
        • Saga T.
        • Ishii Y.
        • Murakami H.
        • Iwata M.
        • et al.
        Incorrect diagnosis of Clostridium difficile infection in a university hospital in Japan.
        J Infect Chemother. 2015; 21: 718-722https://doi.org/10.1016/j.jiac.2015.06.009
        • Iwashima Y.
        • Nakamura A.
        • Kato H.
        • Kato H.
        • Wakimoto Y.
        • Wakiyama N.
        • et al.
        A retrospective study of the epidemiology of Clostridium difficile infection at a University Hospital in Japan: genotypic features of the isolates and clinical characteristics of the patients.
        J Infect Chemother. 2010; 16: 329-333https://doi.org/10.1007/s10156-010-0066-4
        • Marsh J.W.
        • Arora R.
        • Schlackman J.L.
        • Shutt K.A.
        • Curry S.R.
        • Harrison L.H.
        Association of relapse of Clostridium difficile disease with BI/NAP1/027.
        J Clin Microbiol. 2012; 50: 4078-4082https://doi.org/10.1128/JCM.02291-12
        • Bauer K.A.
        • Johnston J.E.W.
        • Wenzler E.
        • Goff D.A.
        • Cook C.H.
        • Balada-Llasat J.M.
        • et al.
        Impact of the NAP-1 strain on disease severity, mortality, and recurrence of healthcare-associated Clostridium difficile infection.
        Anaerobe. 2017; 48: 1-6https://doi.org/10.1016/j.anaerobe.2017.06.009
        • Fatima R.
        • Aziz M.
        The hypervirulent strain of Clostridium difficile: NAP1/B1/027 - a brief overview.
        Cureus. 2019; 11: 1-8https://doi.org/10.7759/cureus.3977
        • Warr D.
        Prognostic factors for chemotherapy induced nausea and vomiting.
        Eur J Pharmacol. 2014; 722: 192-196https://doi.org/10.1016/j.ejphar.2013.10.015