Secondary prophylaxis for Clostridioides difficile infection for patients on non-C. difficile antibiotics: a retrospective cohort study.

OBJECTIVES: Recurrent Clostridioides difficile infection (CDI) poses healthcare challenges and morbidity. Preventing recurrence with prophylactic oral CDI antibiotics lack consensus. METHODS: We used data from the largest healthcare provider in Israel to identify all adults aged 18 years or older diagnosed with a first episode of CDI (Index CDI) between February 2018 and December 2022 and subsequently received a non-CDI antibiotic within 2-8 weeks. Patients who received a concurrent prophylactic CDI antibiotic constituted the CDI prophylaxis group. Multivariable Cox proportional hazard regression models were used to examine the association of secondary CDI prophylaxis with CDI recurrence according to the severity of the index CDI (primary objective) and with 4- and 8-week all-cause mortality (secondary objective). RESULTS: A total of 434 eligible patients were included. Among them, 327 did not receive CDI antibiotic prophylaxis, while 107 did. CDI antibiotic prophylaxis was associated with a significant risk reduction of CDI recurrence with an adjusted HR of 0.51 (95% CI, 0.27-0.97). The magnitude of the association was modified by the severity of the index CDI episode (P for interaction 0.0182). Specifically, the HR for recurrence was 0.163 (95% CI 0.045-0.593) for non-severe CDI, and 1.242 (95% CI 0.524-2.946) for severe CDI. No significant association was found between CDI antibiotic prophylaxis and 4-8 weeks mortality. CONCLUSION: Secondary prophylaxis with CDI antibiotics appears to be associated with a reduced risk of recurrence in patients with previous non-severe CDI episode. Further studies are needed to confirm this finding.

Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients.

BACKGROUND: Paxlovid was granted an Emergency Use Authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19), based on the interim analysis of the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real-world data to evaluate the effectiveness of Paxlovid. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first-ever positive test for severe acute respiratory syndrome coronavirus 2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28-day hazard ratio (HR) for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable. RESULTS: Overall, 180 351 eligible patients were included; of these, only 4737 (2.6%) were treated with Paxlovid, and 135 482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HRs of 0.54 (95% confidence interval [CI], .39-.75) and 0.20 (95% CI, .17-.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction P < .05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status. CONCLUSIONS: This study suggests that in the era of Omicron and in real-life settings, Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.

Effectiveness of Molnupiravir in High-Risk Patients: A Propensity Score Matched Analysis.

BACKGROUND: Molnupiravir was granted emergency use authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). In this study, we used population-based real-world data to evaluate the effectiveness of molnupiravir. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults with first-ever positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) performed in the community during January-February 2022, who were at high risk for severe COVID-19, and had no contraindications for molnupiravir use. Patients were included regardless of SARS-CoV-2 vaccination status. A total of 2661 patients who received molnupiravir were propensity score matched with 2661 patients who have not received molnupiravir (control group). Patients were followed through 10 March 2022 for up to 28 days for the first occurrence of the composite severe COVID-19 or COVID-19-specific mortality. RESULTS: The composite outcome occurred in 50 patients in the molnupiravir group and 60 patients in the control group. Molnupiravir was associated with a nonsignificant reduced risk of the composite outcome: hazard ratio, 0.83 (95% confidence interval, .57-1.21). However, subgroup analyses showed that molnupiravir was associated with a significant decrease in the risk of the composite outcome in older patients 0.54 (0.34-0.86), in females 0.41 (0.22-0.77), and in patients with inadequate COVID-19 vaccination 0.45 (0.25-0.82). The results were similar when each component of the composite outcome was examined separately. CONCLUSIONS: This study suggests that in the era of Omicron and in real-life setting, molnupiravir might be effective in reducing the risk of severe COVID-19 and COVID-19-related mortality, particularly in specific subgroups.