Efficacy of Sofosbuvir plus Ledipasvir in Egyptian patients with COVID-19 compared to standard treatment: a randomized controlled trial.

COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to the hepatitis C virus (HCV) in the replication process. Sofosbuvir/ledipasvir is an approved drug to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection. This is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group that received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings. 250 patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p<0.001). Kaplan-Meir plot showed a considerably higher cure over time in the S.L. group (Log-rank test, p=0.032). There were no deaths in the S.L. group, but there were six deaths (4.8%) in the OCH group (RR=0.08, p=0.013). Seven patients (5.6%) in the S.L. group and six patients (4.8%) in the OCH group were admitted to the intensive care unit (ICU) (RR=1.17, P=0.776). There were no significant differences between treatment groups regarding total leukocyte and neutrophils count, lymph, and urea. Sofosbuvir/ledipasvir is suggestive of being effective in treating patients with moderate COVID-19 infection. Further studies are needed to compare Sofosbuvir/ledipasvir with new treatment protocols.

Prospective, comparative clinical study between high-dose colistin monotherapy and colistin-meropenem combination therapy for treatment of hospital-acquired pneumonia and ventilator-associated pneumonia caused by multidrug-resistant Klebsiella pneumoniae.

OBJECTIVES: In clinical practice, colistin is used as combination therapy to improve its antibacterial activity, despite the consequent increase in toxicity. This prospective, comparative study evaluated the effectiveness and adverse effects of using colistin alone at a loading dose of 9 million international units (MIU) followed by 3 MIU every 8h (q8h) versus colistin+meropenem 1g q8h in treating multidrug-resistant (MDR) Klebsiella pneumoniae-induced hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). The primary outcome measure was in-hospital mortality. The secondary measure was the occurrence of colistin toxicity. METHODS: A total of 60 patients were divided into two groups (30 patients each); the first group received intravenous colistin at a mean daily dose of 8.304 MIU and the second group received colistin 8.58 MIU combined with meropenem (mean daily dose of 2.88g for 15 days). RESULTS: The colistin-meropenem combination group showed a significant decrease in mortality versus colistin alone [16.7% (5/30) vs. 43.3% (13/30); P=0.047]. The improved clinical response mediated by combination therapy was not associated with any significant nephrotoxicity, hepatotoxicity or neurotoxicity. Moreover, the 42 surviving patients showed normal procalcitonin values associated with a decrease in SOFA score, whilst 12 of them showed significantly elevated C-reactive protein (CRP) (P=0.0002). CONCLUSIONS: This study revealed the superiority of colistin-meropenem combination therapy over colistin monotherapy in the treatment of MDR K. pneumoniae-induced HAP or VAP and highlights the advantage of procalcitonin over CRP as a marker for eradication of sepsis and suspension of therapy.