Thirty-Day Readmissions in Hospitalized Patients Who Received Bezlotoxumab With Antibacterial Drug Treatment for Clostridium difficile Infection

Prabhu, Vimalanand S.; Cornely, Oliver A.; Golan, Yoav; Dubberke, Erik R.; Heimann, Sebastian; Hanson, Mary E.; Liao, Jane; Pedley, Alison; Dorr, Mary Beth; Marcella, Stephen

doi:10.1093/cid/cix523

Cited by 19 publications

(14 citation statements)

References 30 publications

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“…Bezlotoxumab also reduced the number of CDI-related hospital readmissions in participants with at least 1 risk factor compared with the placebo group (difference, –7.1%). These results are consistent with a previous analysis of bezlotoxumab data demonstrating a reduction in 30-day CDI-associated hospital readmissions in those aged ≥65 years and with severe CDI [ 16 ]. Although the presence of risk factors increased 30- and 90-day mortality rates, the relatively low rates observed in this study vs those observed in observational studies of patients with CDI [ 22 , 23 ] may be in part due to the study entry requirement for participants to survive at least 72 hours, potentially biasing the results to the null when assessing differences in mortality.…”

Section: Discussionsupporting

confidence: 93%

“…Endpoints included proportion of participants who achieved initial clinical cure, where initial clinical cure is defined as no diarrhea for 2 consecutive days after completion of antibiotic therapy administered for ≤16 calendar days; proportion of participants with rCDI, where rCDI is defined as the development of a new episode of diarrhea associated with a positive stool test for toxigenic C. difficile within 12 weeks following study medication infusion assessed in mITT participants who achieved initial clinical cure (clinical cure population); proportion of participants who received a fecal microbiota transplant (FMT), proportion of participants who experienced 30-day all cause and CDI-associated hospital readmissions as defined previously [ 16 ] in mITT participants who were in a healthcare facility at the time of randomization; and proportion of participants who had died at 30 and 60 days after randomization.…”

Section: Methodsmentioning

confidence: 99%

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Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence

Gerding

Kelly

Rahav

et al. 2018

Clinical Infectious Diseases

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161

139

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BackgroundBezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI.MethodsThe analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented.ResultsThe majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI.ConclusionsThe risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit.Clinical Trials RegistrationNCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence

Gerding

Kelly

Rahav

et al. 2018

Clinical Infectious Diseases

Self Cite

161

139

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show abstract

“…In participants who were hospitalized at randomization, the rate of 30-day rehospitalizations associated with CDI was lower in the bezlotoxumab treatment group compared with the placebo group. This is consistent with a similar post hoc analysis of the MODIFY trials, which demonstrated that bezlotoxumab-treated inpatients experienced fewer CDI-associated readmissions during the 30 days after discharge compared with placebo-treated inpatients [ 27 ].…”

Section: Discussionsupporting

confidence: 89%

Analysis of C. difficile infection–related outcomes in European participants in the bezlotoxumab MODIFY I and II trials

Bouza

Cornely

Ramos‐Martínez

et al. 2020

Eur J Clin Microbiol Infect Dis

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The MODIFY I/II trials demonstrated that bezlotoxumab, a human monoclonal antibody against Clostridioides difficile toxin B, given during antibiotic treatment for Clostridioides difficile infection (CDI) significantly reduced C. difficile recurrence (rCDI) in adults at high risk for rCDI. Efficacy of CDI-directed intervention may depend on ribotype regional epidemiology, and patient characteristics. This post hoc analysis assessed the efficacy of bezlotoxumab in the subgroup of MODIFY I/II trial participants enrolled in Europe. Data from the bezlotoxumab (10 mg/kg single intravenous infusion) and placebo (0.9% saline) groups from MODIFY I/II were compared to assess initial clinical cure (ICC), rCDI, all-cause, and CDI-associated rehospitalizations within 30 days of discharge, and mortality through 12 weeks post-infusion. Of 1554 worldwide participants, 606 were from Europe (bezlotoxumab n = 313, 51%; placebo n = 292; 48%). Baseline characteristics were generally similar across groups, although there were more immunocompromised participants in the bezlotoxumab group (27.2%) compared with placebo (20.1%). Fifty-five percent of participants were female, and 86% were hospitalized at randomization. The rate of ICC was similar between treatment groups. The rate of rCDI in the bezlotoxumab group was lower compared with placebo among European participants overall, and among those with ≥ 1 risk factor for rCDI. Bezlotoxumab reduced 30-day CDI-associated rehospitalizations compared with placebo. These results are consistent with overall results from the MODIFY trials and demonstrate that bezlotoxumab reduces rCDI and CDI-associated rehospitalizations in European patients with CDI. MODIFY I/II (NCT01241552 and NCT01513239)

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“…With the incidence of CDI-associated hospital readmissions rising [ 13 ], it is important to find innovative treatment options to reduce rCDI and rCDI-associated hospital admissions. The results of the current analysis are consistent with a related post hoc analysis of the MODIFY trials in the subgroup of participants who were hospitalized at the time of randomization, demonstrating that bezlotoxumab-treated inpatients experienced fewer CDI-associated readmissions during the 30 days after discharge compared with placebo-treated inpatients [ 21 ].…”

Section: Discussionsupporting

confidence: 85%

Bezlotoxumab Is Associated With a Reduction in Cumulative Inpatient-Days: Analysis of the Hospitalization Data From the MODIFY I and II Clinical Trials

Basu

Prabhu

Dorr

et al. 2018

Open Forum Infectious Diseases

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BackgroundPatients with recurrent Clostridium difficile infection (rCDI) are more likely to have a hospital readmission and spend increased time in inpatient settings compared with patients with primary CDI. MODIFY I and II demonstrated that bezlotoxumab significantly reduced rCDI vs placebo. A post hoc within-trial analysis assessed whether bezlotoxumab was associated with a reduction in cumulative inpatient-days.MethodsData were pooled from the MODIFY trials to estimate the cumulative hospitalized days summed over the 84-day follow-up period. We adjusted inpatient use data from pooled MODIFY I and II for survival and censoring to estimate 84-day cumulative inpatient-days, overall and for subgroups. Treatment effects were obtained using recycled predictions based on trial protocol and rCDI risk, and 95% confidence intervals were obtained using 1000 bootstrap replicates.ResultsMean cumulative inpatient-days were greater in the placebo arm (14.1 days) vs the bezlotoxumab arm (12.1 days) in the overall population. The mean difference between treatment groups was 2.1 days (95% confidence interval, –0.4 to –3.7). This was consistent in participants with risk factors for rCDI: age ≥65 years, compromised immunity, severe CDI, prior CDI, and ribotype 027/078/244 infection. As the number of risk factors increased, bezlotoxumab resulted in greater reductions in the number of inpatient-days compared with placebo (difference: –1.2 days, –2.3 days, –2.5 days, and –3.0 days for 0, 1, 2, and ≥3 risk factors, respectively).ConclusionsBezlotoxumab was associated with a reduction in cumulative inpatient-days, suggesting that treatment with bezlotoxumab may substantially reduce rCDI-associated health care resource use. Trial registrations. MODIFY I (MK-3415A-001, NCT01241552) and II (MK-3415A-002, NCT01513239)

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Thirty-Day Readmissions in Hospitalized Patients Who Received Bezlotoxumab With Antibacterial Drug Treatment for Clostridium difficile Infection

Cited by 19 publications

References 30 publications

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence

Analysis of C. difficile infection–related outcomes in European participants in the bezlotoxumab MODIFY I and II trials

Bezlotoxumab Is Associated With a Reduction in Cumulative Inpatient-Days: Analysis of the Hospitalization Data From the MODIFY I and II Clinical Trials

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