Bezlotoxumab in Patients with a Primary Clostridioides difficile Infection: A Literature Review
Abstract
:1. Introduction
2. Materials and Methods
Search strategy and Article Identification
3. Results
Studies Description
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Evans, C.T.; Safdar, N. Current trends in the epidemiology and outcomes of Clostridium difficile infection. Clin. Inf. Dis. 2015, 60, S66–S71. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guh, A.Y.; Mu, Y.; Winston, L.G.; Johnston, H.; Olson, D.; Farley, M.M.; Wilson, L.E.; Holzbauer, S.M.; Phipps, E.C.; Dumyati, G.K.; et al. Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes. N. Engl. J. Med. 2020, 382, 1320–1330. [Google Scholar] [CrossRef] [PubMed]
- Khanna, S. My Treatment Approach to Clostridioides difficile Infection. Mayo Clin. Proc. 2021, 96, 2192–2204. [Google Scholar] [CrossRef] [PubMed]
- Khanna, S.; Pardi, D.S.; Aronson, S.L.; Kammer, P.P.; Orenstein, R.; St Sauver, J.L.; Harmsen, W.S.; Zinsmeister, A.R. The epidemiology of community-acquired Clostridium difficile infection: A population-based study. Am. J. Gastroenterol. 2012, 107, 89–95. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lessa, F.C. Community-associated Clostridium difficile infection: How real is it? Anaerobe 2013, 24, 121–123. [Google Scholar] [CrossRef]
- Alicino, C.; Giacobbe, D.R.; Durando, P.; Bellina, D.; AM, D.I.B.; Paganino, C.; Del Bono, V.; Viscoli, C.; Icardi, G.; Orsi, A. Increasing incidence of Clostridium difficile infections: Results from a 5-year retrospective study in a large teaching hospital in the Italian region with the oldest population. Epidemiol. Infect. 2016, 144, 2517–2526. [Google Scholar] [CrossRef] [Green Version]
- Finn, E.; Andersson, F.L.; Madin-Warburton, M. Burden of Clostridioides difficile infection (CDI)—A systematic review of the epidemiology of primary and recurrent CDI. BMC Infect. Dis. 2021, 21, 456. [Google Scholar] [CrossRef] [PubMed]
- Fekety, R.; McFarland, L.V.; Surawicz, C.M.; Greenberg, R.N.; Elmer, G.W.; Mulligan, M.E. Recurrent Clostridium difficile diarrhea: Characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin. Infect. Dis. 1997, 24, 324–333. [Google Scholar] [CrossRef] [PubMed]
- Granata, G.; Petrosillo, N.; Adamoli, L.; Bartoletti, M.; Bartoloni, A.; Basile, G.; Bassetti, M.; Bonfanti, P.; Borromeo, R.; Ceccarelli, G.; et al. Prospective Study on Incidence, Risk Factors and Outcome of Recurrent Clostridioides difficile Infections. J. Clin. Med. 2021, 10, 1127. [Google Scholar] [CrossRef] [PubMed]
- McFarland, L.V.; Surawicz, C.M.; Rubin, M.; Fekety, R.; Elmer, G.W.; Greenberg, R.N. Recurrent Clostridium difficile disease: Epidemiology and clinical characteristics. Infect. Control Hosp. Epidemiol. 1999, 20, 43–50. [Google Scholar] [CrossRef] [PubMed]
- Falcone, M.; Tiseo, G.; Iraci, F.; Raponi, G.; Goldoni, P.; Delle Rose, D.; Santino, I.; Carfagna, P.; Murri, R.; Fantoni, M.; et al. Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes. Clin. Microbiol. Infect. 2019, 25, 474–480. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Johnson, S.; Lavergne, V.; Skinner, A.M.; Gonzales-Luna, A.J.; Garey, K.W.; Kelly, C.P.; Wilcox, M.H. 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, 755–757. [Google Scholar] [CrossRef] [PubMed]
- van Prehn, J.; Reigadas, E.; Vogelzang, E.H.; Bouza, E.; Hristea, A.; Guery, B.; Krutova, M.; Noren, T.; Allerberger, F.; Coia, J.E.; et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin. Microbiol. Infect. 2021, 27 (Suppl. 2), S1–S21. [Google Scholar] [CrossRef]
- Wilcox, M.H.; Gerding, D.N.; Poxton, I.R.; Kelly, C.; Nathan, R.; Birch, T.; Cornely, O.A.; Rahav, G.; Bouza, E.; Lee, C.; et al. MODIFY I and MODIFY II Investigators. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N. Engl. J. Med. 2017, 376, 305–317. [Google Scholar] [CrossRef] [PubMed]
- Goldstein, E.J.C.; Citron, D.M.; Gerding, D.N.; Wilcox, M.H.; Gabryelski, L.; Pedley, A.; Zeng, Z.; Dorr, M.B. Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection: 12-Month Observational Data From the Randomized Phase III Trial, MODIFY II. Clin. Infect. Dis. 2020, 71, 1102–1105. [Google Scholar] [CrossRef] [PubMed]
- Gerding, D.N.; Kelly, C.P.; Rahav, G.; Lee, C.; Dubberke, E.R.; Kumar, P.N.; Yacyshyn, B.; Kao, D.; Eves, K.; Ellison, M.C.; et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence. Clin. Infect. Dis. 2018, 67, 649–656. [Google Scholar] [CrossRef] [PubMed]
- Mikamo, H.; Aoyama, N.; Sawata, M.; Fujimoto, G.; Dorr, M.B.; Yoshinari, T. The effect of bezlotoxumab for prevention of recurrent Clostridium difficile infection (CDI) in Japanese patients. J. Infect. Chemother. 2018, 24, 123–129. [Google Scholar] [CrossRef] [Green Version]
- Prabhu, V.S.; Dubberke, E.R.; Dorr, M.B.; Elbasha, E.; Cossrow, N.; Jiang, Y.; Marcella, S. Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection. Clin. Infect. Dis. 2018, 66, 355–362. [Google Scholar] [CrossRef]
Author | Country | Study Design | Study Aim | Methods | Study Results |
---|---|---|---|---|---|
Wilcox M et al., 2017 [14] | 30 different Countries | Placebo-controlled, double-blind, single-infusion, phase III clinical trial | To evaluate the efficacy and safety of bezlotoxumab (alone and in combination with actoxumab) for the prevention of rCDI | 2655 adult patients with primary or rCDI were randomized 1:1:1 to receive 60 min intravenous infusion of bezlotoxumab (10 mg/kg), actoxumab plus bezlotoxumab (10 mg/kg each) or placebo during the standard of care antibiotic therapy Primary endpoint was the proportion of participants with rCDI during 12 weeks of follow-up in the modified intention-to-treat population | Rate of rCDI was lower with bezlotoxumab than with placebo (MODIFY II: 16% vs. 26%, p < 0.001) The subgroup analysis providing the rCDI rate among primary CDI patients showed that 75/556 (13.5%) patients receiving bezlotoxumab plus standard-of-care treatment had an rCDI, whilst 114/545 (20.9%) patients in the placebo group had rCDI at the twelve weeks follow-up (absolute difference: −7.4) |
Goldstein EJC et al., 2020 [15] | 30 different Countries | Extension of MODIFY II clinical trial | To assess the long-term rates of rCDI and Clostridioides difficile colonization following bezlotoxumab infusion | The study included 293 participants of MODIFY II who provided stool samples at 6, 9 and 12 months. Clostridioides difficile colonization at months 6, 9 and 12 was assessed based on whether a toxigenic Clostridioides difficile strain was isolated in samples | At 12 months, the incidence of rCDI in the bezlotoxumab and placebo groups was 18.8% and 51.5% respectively. Clostridioides difficile colonization rates were 16–24% in the bezlotoxumab group and 19–32% in the placebo groups |
Gerding DN et al., 2018 [16] | 30 different Countries | Sub-analysis of the MODIFY I-II clinical trials | To evaluate the efficacy of bezlotoxumab in reducing rCDI among patients with characteristics associated with increased risk factors for rCDI | Patients treated with bezlotoxumab vs. placebo were stratified by risk factors The efficacy was evaluated as: a) achieving initial clinical cure rate, b) reducing the rate of rCDI and c) reducing the rate of FMT | Bezlotoxumab did not affect initial clinical cure rate; bezlotoxumab reduced the rate of rCDI compared to the low-risk group Among primary CDI patients, 69/424 (16.3%) patients treated with bezlotoxumab versus 106/400 (26.5%) controls had rCDI at 12 weeks (absolute difference: −10.1%) |
Mikamo H et al., 2018 [17] | Japan | Sub-analysis of the MODIFY I-II clinical trial | To evaluate the efficacy of bezlotoxumab and actoxumab in reducing rCDI rate at week 12 | 95 Japanese patients were randomized to bezlotoxumab, actoxumab plus bezlotoxumab or placebo in a 1:1:1 ratio Vancomycin, metronidazole and fidaxomicin were administered as standard-of-care antibiotic treatment | The rCDI rate was lower in the bezlotoxumab group (21%) compared to placebo (46%), p: 0.0197 |
Prabhu VS et al., 2018 [18] | 30 different Countries | Sub-analysis of MODIFY I-II clinical trial | To assess the cost-effectiveness of bezlotoxumab in subgroups of patients at risk of rCDI | The computer simulation followed the cohort over a lifetime, and healthcare services costs were compared to estimate the incremental cost-effectiveness ratios | In the subgroup of patients with no previous CDI episodes in the past six months, the cost-effectiveness model showed that, compared with placebo, bezlotoxumab could reduce rCDI by 10.1% (26.6% versus 16.5%), and the 180-day mortality by 1.1% Bezlotoxumab was associated with a gain in quality-adjusted life-years and was cost-effective |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Granata, G.; Schiavone, F.; Pipitone, G. Bezlotoxumab in Patients with a Primary Clostridioides difficile Infection: A Literature Review. Antibiotics 2022, 11, 1495. https://doi.org/10.3390/antibiotics11111495
Granata G, Schiavone F, Pipitone G. Bezlotoxumab in Patients with a Primary Clostridioides difficile Infection: A Literature Review. Antibiotics. 2022; 11(11):1495. https://doi.org/10.3390/antibiotics11111495
Chicago/Turabian StyleGranata, Guido, Francesco Schiavone, and Giuseppe Pipitone. 2022. "Bezlotoxumab in Patients with a Primary Clostridioides difficile Infection: A Literature Review" Antibiotics 11, no. 11: 1495. https://doi.org/10.3390/antibiotics11111495
APA StyleGranata, G., Schiavone, F., & Pipitone, G. (2022). Bezlotoxumab in Patients with a Primary Clostridioides difficile Infection: A Literature Review. Antibiotics, 11(11), 1495. https://doi.org/10.3390/antibiotics11111495