What Is the Role for Metronidazole in the Treatment of Clostridium difficile Infection? Results From a National Cohort Study of Veterans With Initial Mild Disease

Appaneal, Haley J; Caffrey, Aisling R.; LaPlante, Kerry L.

doi:10.1093/cid/ciy1077

Cited by 23 publications

(16 citation statements)

References 40 publications

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“…CDI is not restricted to this type, however, as infections caused by RT001, RT002, RT014/020, and RT078 are frequently reported in both Europe and the United States 7,8 . Metronidazole is used for the treatment of mild-to-moderate infections and vancomycin for severe infections, though vancomycin is increasingly indicated as a general first-line treatment [9][10][11][12][13][14][15][16] . Fidaxomicin has recently also been approved for CDI treatment, but its use is limited by high costs 12 .…”

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confidence: 99%

Plasmid-mediated metronidazole resistance in Clostridioides difficile

et al. 2020

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Metronidazole was until recently used as a first-line treatment for potentially life-threatening Clostridioides difficile (CD) infection. Although cases of metronidazole resistance have been documented, no clear mechanism for metronidazole resistance or a role for plasmids in antimicrobial resistance has been described for CD. Here, we report genome sequences of seven susceptible and sixteen resistant CD isolates from human and animal sources, including isolates from a patient with recurrent CD infection by a PCR ribotype (RT) 020 strain, which developed resistance to metronidazole over the course of treatment (minimal inhibitory concentration [MIC] = 8 mg L −1). Metronidazole resistance correlates with the presence of a 7-kb plasmid, pCD-METRO. pCD-METRO is present in toxigenic and non-toxigenic resistant (n = 23), but not susceptible (n = 563), isolates from multiple countries. Introduction of a pCD-METRO-derived vector into a susceptible strain increases the MIC 25-fold. Our finding of plasmid-mediated resistance can impact diagnostics and treatment of CD infections.

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confidence: 99%

Plasmid-mediated metronidazole resistance in Clostridioides difficile

et al. 2020

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“…3,12,14 One recent study examined patients under 65 and found no significant differences between the use of vancomycin and metronidazole in milder cases. 13 After factoring in patient mortality, our study demonstrated no differences mortality among surviving patients between outpatients and inpatients. 3,6,11 This again raises the question of metronidazole prescriptions in the clinic setting, as these findings are not consistent with the 2017 CDI guidelines.…”

Section: Discussionmentioning

confidence: 60%

“…For those clinic-based providers who opt to use metronidazole, this raises issues due to possibility of missing potential cases of severe CDI and treatment appropriateness. 3,4,6,[11][12][13] In this sample, physicians in the control group (hospital patient) were more likely to adhere to the 2010 CDI guidelines. (Table 2) However, this difference was likely accounted for mostly by a significant number of clinic-based physicians prescribing oral vancomycin instead of metronida-zole, which is now consistent with first-line therapy according to the 2017 IDSA Guidelines.…”

Section: Discussionmentioning

confidence: 95%

The Face of Clostriodes Difficile Infections in the Outpatient Setting

Wang

Faheem

Mangio

et al. 2020

Spartan Medical Research Journal

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BACKGROUND BACKGROUND It has long been well-established that Clostridiodes difficile infections (CDI) can cause severe morbidity and mortality. However, most of the literature to date has focused on hospital-diagnosed infections with less emphasis on clinic-based CDI cases. Guidelines from the 2010 IDSA/SHEA for CDI advocate for metronidazole as first-line therapy for mild to moderate CDI cases. However, the 2017 guidelines recommend oral vancomycin or fidaxomicin as first-line therapy due to their superior efficacy. Objective: The purpose of this study was to compare Clostriodes difficile infections in convenience samples of clinic vs. hospital patients. METHODS METHODS In 2019, a retrospective, case-controlled study was performed by the first six authors between 2015-2017 (i.e., prior to the 2017 IDSA/SHEA CDI guidelines) to compare ambulatory and hospital CDI treatment prescriptions. Analytic data included frequency of White blood cells (WBC) and creatinine collection, frequency of severe CDI cases, compliance with the 2010 guidelines, CDI recurrence, and mortality. RESULTS RESULTS An eligible subgroup of N = 92 hospital patients at Spectrum Health Lakeland were more likely to have WBC (98.4% vs 32.6%, p<0.001) and creatinine (97.8 vs. 39.4, P < 0.001) drawn than 184 patients receiving clinic-based care. Hospital sampled patients were more likely to have severe CDI (46.7% vs 6.7%, p < 0.001). Mortality was less common in hospital patients (1.1% vs. 7.6%, p = 0.017) and the recurrence rates were similar. (21.2% inpatient vs. 28.3% outpatient, (p = 0.224). CONCLUSIONS CONCLUSIONS Based on these results, assessment of CDI severity remains limited in the ambulatory population due to the lack of severity markers. It is unclear if this is due to lack of available laboratory resources or difference in clinical presentation. Of those sample patients who have available markers of severity, patients receiving clinic-based diagnoses were less likely assessed to have severe CDI.

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“…Some guidelines recommend the use of metronidazole for the treatment of CDI ( Abreu et al., 2019 ; Sartelli et al., 2019 ; Xu et al., 2020 ; Baunwall et al., 2021 ; Johnson et al., 2021 ; Kelly et al., 2021 ). Efficacy analysis of one study ( Appaneal et al., 2019 ) show that metronidazole is not different from vancomycin in the risk of all-cause mortality or recurrence of CDI within 30 days, and the cost of metronidazole is lower than that of vancomycin; guidelines do not recommend the use of metronidazole for the treatment of CDI ( Antonelli et al., 2020 ; Lewis et al., 2021 ; Poylin et al., 2021 ). A Cochrane review ( Nelson et al., 2017 ) show that in terms of its cure rate, vancomycin (79%) is more effective than metronidazole (72%; relative risk (RR) 0.90; 95% CI (0.84–0.97)), and metronidazole had potential side effects and a higher recurrence rate.…”

Section: Discussionmentioning

confidence: 99%

Systematic review of guidelines for the diagnosis and treatment of Clostridioides difficile infection

Yang

et al. 2022

Front. Cell. Infect. Microbiol.

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ObjectiveTo systematically assess the current related methodological quality of guidelines for the diagnosis and treatment of Clostridioides difficile infection (CDI), revealing the heterogeneity and reasons for guideline recommendations for the diagnosis and treatment of CDI.MethodsWe searched electronic databases systematically between 2017 and 2021 to find the latest guidelines for the diagnosis and treatment of CDI. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used for quality assessment of the included guidelines. The main recommendations for the diagnosis and treatment of CDI in the guidelines were extracted and evaluated for consistency, and the level of evidence supporting these recommendations was further extracted and analysed.ResultsFourteen guidelines for the diagnosis and treatment of CDI were finally included in this study. There were four guidelines, BSG and HIS, ASCRS, IDSA AND SHEA, and NICE, with an overall score of more than 60%, which is worthy of clinical recommendation. Further analysis of the consistency of the main recommendations for the diagnosis and treatment of CDI in the guidelines showed that the recommendations differed among guidelines. There are no unified classification criteria for the severity of CDI in current studies; some recommendations for the diagnosis and treatment of CDI do not provide evidence to support the recommendations, most recommendations cite low levels of evidence, and there is a lack of high-quality research evidence.ConclusionThe quality of guidelines for the diagnosis and treatment of CDI is uneven. Recommendations on the diagnosis and treatment of CDI have also varied in the guidelines for the past 5 years. Improvements of the aforementioned factors associated with causing heterogeneity would be a rational approach by guideline developers to further update guidelines for the diagnosis and treatment of CDI.

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What Is the Role for Metronidazole in the Treatment of Clostridium difficile Infection? Results From a National Cohort Study of Veterans With Initial Mild Disease

Cited by 23 publications

References 40 publications

Plasmid-mediated metronidazole resistance in Clostridioides difficile

Plasmid-mediated metronidazole resistance in Clostridioides difficile

The Face of Clostriodes Difficile Infections in the Outpatient Setting

Systematic review of guidelines for the diagnosis and treatment of Clostridioides difficile infection

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