Reduced Vancomycin Susceptibility in Clostridioides Difficile Is Associated With Lower Rates of Initial Cure and Sustained Clinical Response

Overview

Journal Clin Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2024 Feb 21

PMID 38382090

Authors

Taryn A Eubank

Chetna Dureja

Kevin W Garey

Julian G Hurdle

Anne J Gonzales-Luna

Affiliations

Soon will be listed here.

Abstract

Background: Epidemiologic studies have shown decreasing vancomycin susceptibility among clinical Clostridioides difficile isolates, but the impact on patient outcomes is unknown. We hypothesized that reduced vancomycin susceptibility would be associated with decreased rates of sustained clinical response (SCR).

Methods: This multicenter cohort study included adults with C. difficile infection (CDI) treated with oral vancomycin between 2016 and 2021. Clostridioides difficile isolates underwent agar dilution vancomycin susceptibility testing, ribotyping, and Sanger sequencing of the vancomycin resistance vanR gene. Reduced susceptibility was defined as vancomycin minimum inhibitory concentration (MIC) >2 μg/mL. The primary outcome was 30-day SCR; secondary outcomes were 14-day initial cure, 30-day recurrence, and 30-day mortality. Exploratory analysis assessed the association between the VanR Thr115Ala polymorphism, susceptibility, and outcomes.

Results: A high proportion (34% [102/300]) of C. difficile isolates exhibited reduced vancomycin susceptibility (range, 0.5-16 μg/mL; MIC50/90 = 2/4 μg/mL). Ribotype 027 accounted for the highest proportion (77.4% [41/53]) of isolates with reduced vancomycin susceptibility. Overall, 83% (249) of patients achieved 30-day SCR. Reduced vancomycin susceptibility was associated with lower rates of 30-day SCR (76% [78/102]) than vancomycin-susceptible strains (86% [171/198]; P = .031). A significantly lower rate of 14-day initial cure was also observed among individuals infected with strains with reduced vancomycin susceptibility (89% vs 96%; P = .04). Reduced susceptibility remained an independent predictor of 30-day SCR in multivariable modeling (odds ratio, 0.52 [95% confidence interval, .28-.97]; P = .04).

Conclusions: Reduced vancomycin susceptibility in C. difficile was associated with decreased odds of 30-day SCR and lower 14-day initial cure rates in the studied patient cohort.

Citing Articles

A quantitative PCR to detect non-toxigenic .

Begum K, Chua H, Alam M, Garey K, Jo J Microbiol Spectr. 2024; 13(1):e0160824.

PMID: 39660903 PMC: 11705841. DOI: 10.1128/spectrum.01608-24.

Reduced Vancomycin Susceptibility in Is Associated With Specific Ribotypes.

Eubank T, Dureja C, Gonzales-Luna A, Hurdle J, Garey K Open Forum Infect Dis. 2024; 11(11):ofae588.

PMID: 39512425 PMC: 11542623. DOI: 10.1093/ofid/ofae588.

Therapeutics involved in managing initial and recurrent infection: An updated literature review.

Nagesh V, Tran H, Elias D, Kianifar Aguilar I, Sethi T, Menon A World J Gastrointest Pharmacol Ther. 2024; 15(5):95467.

PMID: 39281262 PMC: 11401021. DOI: 10.4292/wjgpt.v15.i5.95467.

References

Mikamo H, Tateda K, Yanagihara K, Kusachi S, Takesue Y, Miki T . 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(9):744-752. DOI: 10.1016/j.jiac.2018.05.010. View

Putsathit P, Hong S, George N, Hemphill C, Huntington P, Korman T . Antimicrobial resistance surveillance of Clostridioides difficile in Australia, 2015-18. J Antimicrob Chemother. 2021; 76(7):1815-1821. DOI: 10.1093/jac/dkab099. View

Dureja C, Olaitan A, Hurdle J . Mechanisms and impact of antimicrobial resistance in Clostridioides difficile. Curr Opin Microbiol. 2022; 66:63-72. PMC: 9064893. DOI: 10.1016/j.mib.2022.01.004. View

Gargis A, Karlsson M, Paulick A, Anderson K, Adamczyk M, Vlachos N . Reference Susceptibility Testing and Genomic Surveillance of Clostridioides difficile, United States, 2012-17. Clin Infect Dis. 2022; 76(5):890-896. PMC: 10839785. DOI: 10.1093/cid/ciac817. View

Gonzales-Luna A, Olaitan A, Shen W, Deshpande A, Carlson T, Dotson K . Reduced Susceptibility to Metronidazole Is Associated With Initial Clinical Failure in Infection. Open Forum Infect Dis. 2021; 8(8):ofab365. PMC: 8351808. DOI: 10.1093/ofid/ofab365. View

Feuerstadt P, Boules M, Stong L, Dahdal D, Sacks N, Lang K . Clinical complications in patients with primary and recurrent infection: A real-world data analysis. SAGE Open Med. 2021; 9:2050312120986733. PMC: 7812403. DOI: 10.1177/2050312120986733. View

Baghani A, Mesdaghinia A, Kuijper E, Aliramezani A, Talebi M, Douraghi M . High prevalence of Clostridiodes diffiicle PCR ribotypes 001 and 126 in Iran. Sci Rep. 2020; 10(1):4658. PMC: 7070088. DOI: 10.1038/s41598-020-61604-z. View

Odenholt I, Walder M, Wullt M . Pharmacodynamic studies of vancomycin, metronidazole and fusidic acid against Clostridium difficile. Chemotherapy. 2007; 53(4):267-74. DOI: 10.1159/000104471. View

Marchandin H, Anjou C, Poulen G, Freeman J, Wilcox M, Jean-Pierre H . In vivo emergence of a still uncommon resistance to fidaxomicin in the urgent antimicrobial resistance threat Clostridioides difficile. J Antimicrob Chemother. 2023; 78(8):1992-1999. DOI: 10.1093/jac/dkad194. View

10.

Magill S, OLeary E, Janelle S, Thompson D, Dumyati G, Nadle J . Changes in Prevalence of Health Care-Associated Infections in U.S. Hospitals. N Engl J Med. 2018; 379(18):1732-1744. PMC: 7978499. DOI: 10.1056/NEJMoa1801550. View

11.

Cornely O, Crook D, Esposito R, Poirier A, Somero M, Weiss K . Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012; 12(4):281-9. DOI: 10.1016/S1473-3099(11)70374-7. View

12.

Clancy C, Buehrle D, Vu M, Wagener M, Nguyen M . Impact of Revised Infectious Diseases Society of America and Society for Healthcare Epidemiology of America Clinical Practice Guidelines on the Treatment of Clostridium difficile Infections in the United States. Clin Infect Dis. 2020; 72(11):1944-1949. DOI: 10.1093/cid/ciaa484. View

13.

Shen W, Deshpande A, Hevener K, Endres B, Garey K, Palmer K . Constitutive expression of the cryptic vanGCd operon promotes vancomycin resistance in Clostridioides difficile clinical isolates. J Antimicrob Chemother. 2019; 75(4):859-867. PMC: 7069472. DOI: 10.1093/jac/dkz513. View

14.

Snydman D, McDermott L, Thorpe C, Chang J, Wick J, Walk S . Antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from a Phase 2 clinical trial of ridinilazole (SMT19969) and vancomycin. J Antimicrob Chemother. 2018; 73(8):2078-2084. PMC: 6054158. DOI: 10.1093/jac/dky135. View

15.

Tickler I, Goering R, Whitmore J, Lynn A, Persing D, Tenover F . Strain types and antimicrobial resistance patterns of Clostridium difficile isolates from the United States, 2011 to 2013. Antimicrob Agents Chemother. 2014; 58(7):4214-8. PMC: 4068552. DOI: 10.1128/AAC.02775-13. View

16.

Alam M, Anu A, Walk S, Garey K . Investigation of potentially pathogenic Clostridium difficile contamination in household environs. Anaerobe. 2014; 27:31-3. DOI: 10.1016/j.anaerobe.2014.03.002. View

17.

Louie T, Miller M, Mullane K, Weiss K, Lentnek A, Golan Y . Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011; 364(5):422-31. DOI: 10.1056/NEJMoa0910812. View

18.

Johnson S, Lavergne V, Skinner A, Gonzales-Luna A, Garey K, Kelly C . Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021; 73(5):755-757. DOI: 10.1093/cid/ciab718. View

19.

Louie T, Nord C, Talbot G, Wilcox M, Gerding D, Buitrago M . Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection. Antimicrob Agents Chemother. 2015; 59(10):6266-73. PMC: 4576054. DOI: 10.1128/AAC.00504-15. View

20.

Wickramage I, Peng Z, Chakraborty S, Harmanus C, Kuijper E, Alrabaa S . The Mutation 343A>G, Resulting in a Thr115Ala Substitution, Is Associated with an Elevated Minimum Inhibitory Concentration (MIC) of Vancomycin in Clostridioides difficile Clinical Isolates from Florida. Microbiol Spectr. 2023; 11(3):e0377722. PMC: 10269549. DOI: 10.1128/spectrum.03777-22. View