Amphotericin B (AmB) is the first-line agent for the treatment of life-threatening invasive fungal infections. The aim of this study was to monitor AmB in critically ill Saudi patients in ICU after i.v. administration of 0.68 ± 0.1 mg/kg/day Fungizone®. A selective, sensitive and precise UPLC MS/MS method was developed to measure AmB concentrations in these patients. Seven ICU patients with creatinine clearance (ClCr) >40 mL/min were included. AmB levels were analyzed using a Waters Aquity UPLC MS/MS system, a BEH Shield RP18 column and detection via electrospray ionization source with positive ionization mode. The precision and accuracy of the developed UPLC method in the concentration range of 200-4000 ng/mL show no significant difference among inter- and-intra-day analysis (p > 0.05). Linearity was observed over the investigated range with correlation coefficient, r > 0.995 (n = 6/day). The pharmacokinetics of AmB in these patients, at steady state, showed a high terminal half-life of 124.6 ± 73.4 h, with a highest concentration of 513.9 ± 281.1 ng/mL, a lowest concentration 316.4 ± 129.0 ng/mL and a mean clearance 91.1 ± 39.2 mL/h/kg. The pharmacokinetics of AmB in critically ill Saudi patients in ICU was studied using a fully validated assay. A weak correlation (r = -0.22) of AmB Cl with ClCr was obtained, which suggests the need for further investigation in a larger population.
Background:
The clinical spectrum of COVID-19 is variable and ranges from asymptomatic, mildly symptomatic, moderately severe and severe disease. A small proportion might develop severe disease and may have cytokine storm. One of the therapeutic options to treat such cases is Tocilizumab (TCZ). In this study, we present cases of severe COVID-19 treated with TCZ and glucocorticoids and discuss the treatment responses.
Methods:
This is a retrospective observational study of severe COVID-19 cases treated with TCZ and glucocorticoids. The case series examined the characteristics and outcome of those patients.
Results:
This study included 40 Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) confirmed patients who received TCZ and glucocorticoids. The mean age of the included patients was 57.55 (±Standard deviation 12.86) years. There were 34 (85%) males, 19 (47.5%) were obese (BMI >30), 13 (32.5%) over weight, and five (12.5%) normal weight. The mean days from positive SARS-CoV-2 polymerase chain reaction (PCR) test to admission was 1.641 (±3.2) days. Of the patients, 18 (45%) had diabetes mellitus, 14 (35%) had hypertension. The mean days from hospital admission to ICU was 1.8 (±2.6), 20 (50%) required mechanical ventilation, 39 (97.5%) had received prone position, seven (17.5%) had renal replacement therapy, 13 (32.5%) required inotropes, four (10%) had plasmapheresis, one (2.5%) had intravenous immunoglobulin, all patients received steroid therapy, and the majority 31 (77.5%) did not receive any anti-viral therapy. Of all the patients, six (15%) died, 28 (70%) were discharged and six (15%) were still in hospital.
Conclusion:
The overall mortality rate was lower than those cited in meta-analysis. As our understanding of the COVID-19 continues, the approach and therapeutics are also evolving.
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