Objective To evaluate whether favipiravir reduces the time to viral clearance as documented by negative SARS-CoV-2 RT-PCR in mild COVID-19 cases compared to placebo. Methods In this randomized, double-blinded, multicenter, and placebo-controlled trial, adults with PCR confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day one followed by 800 mg twice daily (n=112) or a matching placebo (n=119), for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, ICU admissions, adverse events, and 28-day mortality. Results 231 patients were randomized and began the study (median age, 37 [interquartile range: 32-44] years; 155 [67%] men), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board (DSMB) recommended stopping enrollment because of futility at the interim analysis. The median time to viral clearance was 10 (IQR: 6-12) days in the favipiravir group and 8 (IQR: 6-12) days in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571 to 1.326; p-value =0.51). The median time to clinical recovery was 7 days (IQR: 4-11) in the favipiravir group and 7 days (IQR: 5-10) in the placebo group. There was no difference between the two groups on the secondary outcome of hospital admission. There were no drug-related severe adverse events. Conclusion In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment. Clinical Trial Registration ClinicalTrials.gov identifier ( NCT04464408 ): https://clinicaltrials.gov/ct2/show/NCT04464408 .

Introduction: Multidrug-resistant Pseudomonas aeruginosa isolates have multiple resistance mechanisms, and there are insufficient therapeutic options to target them. Ceftolozane-tazobactam is a novel antipseudomonal agent that contains a combination of an oxyimino-aminothiazolyl cephalosporin (ceftolozane) and a β-lactamase inhibitor (tazobactam). Methods: A single-center retrospective observational study between January 2017 and December 2018 for patients who had been diagnosed with carbapenem-resistant P aeruginosa infections and treated with ceftolozane-tazobactam for more than 72 hours. We assessed clinical success based on microbiological clearance as well as the clinical resolution of signs and symptoms of infection. Results: A total of 19 patients fit the inclusion criteria, with a median age was 57 years, and 53% were female. The types of infections were nosocomial pneumonia, acute bacterial skin, and skin structure infections; complicated intra-abdominal infections; and central line–associated bloodstream infections. All of the isolates were resistant to both meropenem and imipenem. The duration of therapy was variable (average of 14 days). At day 14 of starting ceftolozane-tazobactam, 18 of 19 patients had a resolution of signs and symptoms of the infection. Only 14 of 19 patients (74%) had proven microbiological eradication observed at the end of therapy. During therapy, there was no adverse event secondary to ceftolozane-tazobactam, and no Clostridium difficile infection was identified. The 30-day mortality rate was 21% (4/19). Conclusions: Multidrug-resistant P aeruginosa infection is associated with high mortality, which would potentially be improved using a new antibiotic such as ceftolozane-tazobactam. Studies are required to explain the role of combination therapy, define adequate dosing, and identify the proper duration of treatment.