The impact of COVID-19 on antimicrobial prescription and drug resistance in fungi and bacteria.

Secondary infections are one of the complications in COVID-19 patients. We aimed to analyze the antimicrobial prescriptions and their influence on drug resistance in fungi and bacteria isolated from severely ill COVID-19 patients. Seventy-nine severely ill COVID-19 hospitalized patients with secondary bacterial or fungal infections were included. We analyzed the prescribed antimicrobial regimen for these patients and the resistance profiles of bacterial and fungal isolates. In addition, the association between drug resistance and patients' outcome was analyzed using correlation tests. The most prescribed antibacterial were ceftriaxone (90.7% of patients), vancomycin (86.0%), polymyxin B (74.4%), azithromycin (69.8%), and meropenem (67.4%). Micafungin and fluconazole were used by 22.2 and 11.1% of patients, respectively. Multidrug-resistant (MDR) infections were a common complication in severely ill COVID-19 patients in our cohort since resistant bacteria strains were isolated from 76.7% of the patients. Oxacillin resistance was observed in most Gram-positive bacteria, whereas carbapenem and cephalosporin resistance was detected in most Gram-negative strains. Azole resistance was identified among C. glabrata and C. tropicalis isolates. Patients who used more antimicrobials stayed hospitalized longer than the others. The patient's age and the number of antibacterial agents used were associated with the resistance phenotype. The susceptibility profile of isolates obtained from severely ill COVID-19 patients highlighted the importance of taking microbial resistance into account when managing these patients. The continuous surveillance of resistant/MDR infection and the rational use of antimicrobials are of utmost importance, especially for long-term hospitalized patients with COVID-19.

Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain. Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days. Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed. Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia. Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.