Dataset Information

Microbiological Characterization and Clinical Outcomes After Extended-Pulsed Fidaxomicin Treatment for Clostridioides difficile Infection in the EXTEND Study.

ABSTRACT: Background:Clostridioides (Clostridium) difficile infection (CDI) is diagnosed using clinical signs and symptoms plus positive laboratory tests. Recurrence of CDI after treatment is common, and coinfection with other enteric pathogens may influence clinical outcomes. Methods:We aimed to assess rates of C difficile positivity, by enzyme-linked immunosorbent assay (ELISA) toxin A/B and BioFire FilmArray, and the effect of enteric coinfection on clinical outcomes, using samples from the EXTEND study of extended-pulsed fidaxomicin (EPFX) versus standard vancomycin. Results:All 356 randomized and treated patients tested positive for C difficile toxin A/B by local tests; a majority (225 of 356, 63.2%) also tested positive by both ELISA and BioFire. Most stool samples taken at screening tested positive for C difficile only using BioFire (EPFX: 112 of 165, 69.7%; vancomycin: 118 of 162, 72.8%). Of the 5 patients who failed treatment and had stool samples available, all (1) had tested negative for C difficile by BioFire at screening and (2) were negative by ELISA at time of treatment failure. When analyzed by BioFire results at screening, rates of sustained clinical cure at 30 days after end of treatment were numerically higher with EPFX than with vancomycin for almost all patients, except for those who tested negative for C difficile but positive for another pathogen. However, these outcome differences by presence of coinfection did not reach statistical significance. Whole-genome sequencing analysis determined that 20 of 26 paired samples from patients with recurrence were reinfections with the same C difficile strain. Conclusions:Testing for presence of copathogens in clinical trials of antibiotics could help to explain clinical failures.

SUBMITTER: Wilcox MH

PROVIDER: S-EPMC6834086 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Microbiological Characterization and Clinical Outcomes After Extended-Pulsed Fidaxomicin Treatment for <i>Clostridioides difficile</i> Infection in the EXTEND Study.

Wilcox Mark H MH Cornely Oliver A OA Guery Benoit B Longshaw Chris C Georgopali Areti A Karas Andreas A Kazeem Gbenga G Palacios-Fabrega Jose Alejandro JA Vehreschild Maria J G T MJGT

Open forum infectious diseases 20191106 11

<h4>Background</h4><i>Clostridioides</i> (<i>Clostridium</i>) <i>difficile</i> infection (CDI) is diagnosed using clinical signs and symptoms plus positive laboratory tests. Recurrence of CDI after treatment is common, and coinfection with other enteric pathogens may influence clinical outcomes.<h4>Methods</h4>We aimed to assess rates of <i>C difficile</i> positivity, by enzyme-linked immunosorbent assay (ELISA) toxin A/B and BioFire FilmArray, and the effect of enteric coinfection on clinical o ...[more]

PMID: 31723569

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Project description:ObjectivesTreatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study evaluated the cost-effectiveness of fidaxomicin and bezlotoxumab for initial CDI compared with standard therapy with oral vancomycin.MethodsA Markov model with eight health states was built based on transition probabilities, costs and health utilities derived from literature to evaluate the cost-effectiveness of standard fidaxomicin, bezlotoxumab plus vancomycin, and extended-pulsed fidaxomicin versus standard oral vancomycin over a lifetime horizon from the US societal perspective.ResultsFor overall CDI treatment, oral vancomycin had a cost of $39 178 and was associated with a gain of 11.64 quality-adjusted life-years (QALYs). Extended-pulsed fidaxomicin had a higher QALY gain of 11.65 at a lower cost of $37 613, and therefore was dominant over vancomycin. Standard fidaxomicin had a QALY gain of 11.94 versus vancomycin at an incremental cost of $495 per QALY. Bezlotoxumab plus vancomycin led to a QALY gain of 11.77 at an incremental cost of $17 746 per QALY. At the willingness-to-pay (WTP) threshold of $150 000 per QALY, extended-pulsed fidaxomicin, bezlotoxumab plus vancomycin and standard fidaxomicin were more cost-effective compared with vancomycin alone, yielding incremental net monetary benefits of $3248, $17 011 and $44 308, respectively. One-way sensitivity analysis suggested that the probabilities of sustained cure from the initial episode were the most sensitive inputs, and results were overall not particularly sensitive to any drug costs.ConclusionsBased on a WTP threshold of $150 000, standard fidaxomicin was estimated to be the most cost-effective treatment. Standard-of-care vancomycin was dominated by extended-pulsed fidaxomicin for treating an episode of CDI and preventing further recurrence, and the addition of bezlotoxumab to vancomycin was dominated by standard fidaxomicin.

Dataset Information

Microbiological Characterization and Clinical Outcomes After Extended-Pulsed Fidaxomicin Treatment for Clostridioides difficile Infection in the EXTEND Study.

Publications

Microbiological Characterization and Clinical Outcomes After Extended-Pulsed Fidaxomicin Treatment for <i>Clostridioides difficile</i> Infection in the EXTEND Study.

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