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Bowel disorders
Published in Henry J. Woodford, Essential Geriatrics, 2022
Fidaxomicin is an oral macrocyclic antibacterial agent, with a narrow spectrum of action, that is poorly absorbed from the gut. It has a higher financial cost but may be considered for patients with severe disease at high risk of recurrence, such as frail older people.36 Patients with severe disease that does not respond to initial treatment may be considered for oral rifampicin or intravenous immunoglobulin, but evidence of benefit is lacking.36
Clostridioides difficile
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
For a first recurrent infection, vancomycin 125 mg 6-hourly PO for 10 days can be used again or fidaxomicin 200 mg 12-hourly for 10 days. In case of multiple recurrences, use either vancomycin 125 mg 6-hourly PO for 10 days followed by a pulsed regimen (125–500 mg/day every 2–3 days for at least 3 weeks) or followed by tapered regimen (gradually decreasing the dose to 125 mg per day). Alternatively, fidaxomicin 200 mg 12-hourly for 10 days may be used.
Infections in Solid Organ Transplant Recipients Admitted to the Critical Care Unit
Published in Cheston B. Cunha, Burke A. Cunha, Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Almudena Burillo, Patricia Muñoz, Emilio Bouza
Whenever possible, the first step in managing diarrhea and colitis caused by C. difficile is discontinuation of the antibiotic therapy that precipitated the disease. About 15%–25% of patients respond within a few days. Patients with severe disease should be treated with oral vancomycin or fidaxomicin 200 mg, twice daily, for 10 days. Recent reports of severe clinical forms suggest that vancomycin tapering and fidaxomicin may be preferable for especially virulent strains. The reader is referred to the Infectious Diseases Society of America (IDSA) guidelines on this subject [103]. The prescription of probiotics such as Saccharomyces boulardii or Lactobacillus spp. for the prophylaxis of CDAD remains controversial, and we do not recommend this practice in CCU patients, as severe invasive disease by S. boulardii has been described [105].
Clinical management of severe, fulminant, and refractory Clostridioides difficile infection
Published in Expert Review of Anti-infective Therapy, 2020
Fidaxomicin is also recommended for the treatment of severe disease [9]. In a landmark prospective, double-blind, and randomized study, Louie and colleagues compared vancomycin and fidaxomicin [44]. Fidaxomicin at 200 mg BID for 10 days was found to be non-inferior to vancomycin 125 mg QID for 10 days in the treatment of CDI. In the modified intention to treat population, the SCDI subgroup achieved similarly high cures rates with fidaxomicin (82.1%) and vancomycin (88.6%). The rate of recurrence within 30 days, however, was significantly lower with fidaxomicin compared to vancomycin (13.0% vs 26.6%, p = 0.02). A subsequent double-blind, non-inferiority, randomized controlled trial yielded similar results [45]. Upon comparison of fidaxomicin and vancomycin for the treatment of SCDI, there was no significant difference in clinical cure (76.2% vs 70.5%, p = 0.473), however, fidaxomicin decreased the rate of recurrence (8.3% vs 32.6%, p < 0.05). A recent network meta-analysis comparing fidaxomicin to vancomycin plus metronidazole found that fidaxomicin produced similar rates of CDI cure, but it was significantly more effective at preventing recurrent infection [46].
Non-antibiotic therapy for Clostridioides difficile infection: a review
Published in Critical Reviews in Clinical Laboratory Sciences, 2019
In terms of their cure rate and range of application, antibiotics are the first choice in the treatment of almost all bacterial diseases. Compared with the therapeutic effect of other drugs in bacterial- or fungal-induced gastrointestinal infections, antibiotics possess high-quality efficacy and a short treatment period. First-line antibiotics such as metronidazole, vancomycin and fidaxomicin are widely used in the clinical treatment of CDI [28]; these antibiotics have benefited hundreds of millions of people and promise to benefit many times more. Beinortas et al. [46] performed a systematic review and network meta-analysis to compare and rank the efficacy of different treatments for nonmultiple recurrent infections with C. difficile in adults (Figure 2), finding that fidaxomicin and teicoplanin were significantly better than vancomycin in their cure rate of sustained CDI; teicoplanin, ridinilazole, fidaxomicin, surotomycin, and vancomycin were better than metronidazole. Bacitracin was weaker than teicoplanin and fidaxomicin, and tolevamer was weaker than all drugs except for LFF571 and bacitracin. Overall, the frequency of fidaxomicin used in sustained CDI was the highest, followed by vancomycin and metronidazole. Fidaxomicin is an emerging antibiotic that exhibits effective and well-tolerated treatment for severe CDI and for patients with a high recurrence risk [47,48]. These data indicated that the status of metronidazole, vancomycin and fidaxomicin is still entrenched in CDI treatment over a short time.
Ridinilazole for the treatment of Clostridioides difficile infection
Published in Expert Opinion on Investigational Drugs, 2019
Travis J. Carlson, Bradley T. Endres, Eugénie Bassères, Anne J. Gonzales-Luna, Kevin W. Garey
Of interest is the efficacy of CDI antibiotics on ribotype 027 given inconsistent clinical outcomes in the phase III trials of fidaxomicin [28,29]. In pre-clinical trials, fidaxomicin showed potent in vitro activity against non-typed C. difficile strains (n = 207) with all strains being inhibited at a concentration of ≤0.0625 μg/mL [39]. Furthermore, 16 BI strains from a phase II trial of fidaxomicin demonstrated an MIC90 value of 0.125 (0.03 to 0.25) μg/mL [40]. The MIC90 values against 11 ribotype 027 isolates were 0.25 (0.25 to 0.5) and 0.5 (0.5 to 1) μg/mL for ridinilazole and fidaxomicin, respectively [32]. In contrast, ridinilazole was less potent than fidaxomicin against 11 ribotype 027 isolates in a later study with MIC90 values of 0.125 and 0.06 μg/mL, respectively [34]. Strain-specific activity of both of these compounds will need to be carefully assessed in future clinical studies.