Purpose: Considering the anti-inflammatory effect of atorvastatin and the role of medical comorbidities such as hypertension and coronary artery disease on prognosis of the COVID-19 patients, we aimed to assess the effect of atorvastatin add-on therapy on mortality due to COVID-19. Methods: We conducted a retrospective cohort study, including patients who were hospitalized with confirmed diagnosis of severe COVID-19. Baseline characteristics and related clinical data of patients were recorded. Clinical outcomes consist of in hospital mortality, need for invasive mechanical ventilation and hospital length of stay. COX regression analysis models were used to assess the association of independent factors to outcomes. Results: Atorvastatin was administered for 421 out of 991 patients. The mean age was 61.640±17.003 years. Older age, higher prevalence of hypertension and coronary artery disease reported in patients who received atorvastatin. These patients had shorter hospital length of stay (P=0.001). Based on COX proportional hazard model, in hospital use of atorvastatin was associated to decrease in mortality (HR=0.679, P=0.005) and lower need for invasive mechanical ventilation (HR=0.602, P=0.014). Conclusions: Atorvastatin add-on therapy in patient with severe COVID-19 was associated with lower in hospital mortality and reduced the risk of need for invasive mechanical ventilation which support to continue the prescription of the medication.
Aim: Augmented Renal Clearance (ARC) is a common phenomenon among critically ill patients and create sub-therapeutic concentrations of antibiotics, due to an increase in renal clearance of them. We evaluated the Pharmacokinetic and Pharmacodynamic (PK/PD) properties of recommended doses of meropenem in critically ill patients with ARC. Methods: Adult critically ill patients with confirmed ARC, based on 12-hour Creatinine Clearance (CrCl) (≥130 ml/min/1.73 m2), who received standard doses of meropenem enrolled. Two blood samples were gathered from each participant, at the steady-state time, to determination of peak and trough concentrations. Serum concentrations of meropenem were measured by High-Performance Liquid Chromatography (HPLC) with Ultra-Violet (UV) detector. Results: From eighteen paired samples (peak and trough concentrations) that were obtained from 16 critically ill patients, peak concentrations were significantly lower in group 1 (received meropenem 1g every 8 hours) than group 2 (received meropenem 2g every 8 hours) (mean ±SD, 5.95 ±3.39 µg/mL vs. 11.93± 4.18 µg/mL, respectively, p= 0.005). Trough concentration were sub-threshold (< 2 µg/mL) in 10 patients of group 1 (83.3%) and 3 patients of group 2 (50%). ft > MIC ≥ 50% was achieved in 83.3% of patients in both groups whereas 16.6% of patients of group 1 and 33.3% of patients of group 2 had ft> MIC= 100%. Conclusion: ARC is an essential cause of sub-therapeutic concentrations of meropenem in critically ill patients, and higher than the recommended doses of meropenem administered as an intermittent infusion may be necessary to achieve the PD targets and improve efficacy.