Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis.

INTRODUCTION: Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients. METHODS: This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients ≥18 years) admitted April-August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg twice daily loading dose, followed by 800 mg or 600 mg twice daily) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan-Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis. RESULTS: Overall, median time to discharge was 10 days (95%CI = 9-10) in the favipiravir arm versus 15 days (95%CI = 14-16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI = 1.56-2.46). Progression to mechanical ventilation was slower with favipiravir (HRadj = 0.10, 95%CI = 0.04-0.29). There was no significant effect on mortality (HRadj = 1.56, 95%CI = 0.73-3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HRadj = 2.80, 95%CI = 0.99-7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings. CONCLUSION: Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum.

Ten-year review of invasive Candida infections in a tertiary care center in Saudi Arabia.

OBJECTIVES: To review the epidemiology of invasive Candida infections in a single center in Saudi Arabia over a subsequent 10-year period. METHODS: This retrospective study was carried out in a single center in Saudi Arabia over a 10-year period. Records of all patients with invasive Candida infections (ICI) over the period from January 2003 to December 2012 were reviewed. Mann-Whitney U test was used for comparison of Candida albicans (C. albicans) versus non-albicans Candida species, and fluconazole resistance versus fluconazole susceptible in relation to crude mortality at 30 days and 90 days. RESULTS: Eight hundred positive sterile site cultures, associated with 652 ICI were identified. Median age was 52 years and 53% of patients were males. Candida albicans were the most common species (38.7%), followed by Candida tropicalis (18.9%), and Candida glabrata (C. glabrata) (16.3%). The proportion of ICI caused by C. albicans remained stable over time (p=0.07), but C. glabrata increased significantly (p<0.001). The median rate of ICI per 1,000 hospital discharges per year was 1.65, with a significant trend towards higher rates over time (p=0.01). Most isolates were susceptible to fluconazole, voriconazole, and amphotericin B. Only 66.7% of Candida krusei were susceptible to caspofungin. Overall 30-day crude mortality was 40.6%. There was no significant difference in crude mortality in association with C. albicans compared with non-albicans species, nor in association with fluconazole resistance. CONCLUSION: The rate of ICI increased significantly in the proportion of ICI caused by C. glabrata. Most isolates remain susceptible to caspofungin, voriconazole, and amphotericin B. The crude mortality remains high.