IntroductionTo achieve target concentrations, the application of higher-than-standard doses of amikacin is proposed for the treatment of sepsis due to an increase in volume of distribution and clearance, but little data are available on aminoglycoside administration in critically ill elderly patients.Patients and methodsForty critically ill elderly patients (aged over 65 years) who required amikacin therapy due to severe documented, or suspected gram-negative infections, were randomly assigned to two treatment groups. Group A (20 patients) received 15 mg/kg amikacin and Group B (20 patients) received 25 mg/kg amikacin per day as a single daily dose. All the patients were monitored for renal damage by the daily monitoring of serum creatinine. The amikacin peak (Cmax) and trough (Cmin) serum concentrations were measured on Days 3 and 7 postadministration.ResultsData from 18 patients in Group A and 15 patients in Group B were finally analyzed. On Day 3, the amikacin mean Cmax levels in the standard and high-dose treatment groups were 30.4±11 and 52.3±16.1 µg/mL (P<0.001), and the Cmin levels were 3.2±2.1 and 5.2±2.8 µg/mL, respectively (P=0.035). On Day 7, the Cmax levels in the standard and high-dose groups were 33±7.3 and 60.0±17.6 µg/mL (P=0.001), and the Cmin levels were 3.2±2.9 and 9.3±5.6 µg/mL, respectively (P=0.002). In only six (40%) of the patients in the high-dose groups and none of the patients in the standard-dose group, amikacin Cmax reached the target levels (>64 µg/mL), whereas the amikacin mean Cmin levels in the high-dose group were above the threshold of toxicity (5 µg/mL).ConclusionOur results suggest that the optimum dose of amikacin should be determined for elderly critically ill patients. It seems that higher-than-standard doses of amikacin with more extended intervals might be more appropriate than standard once-daily dosing in the elderly critically ill patients.

Objective. The aim of our study was to assess and validate the effectiveness of early dose adjustment of vancomycin based on first dose monitoring in achieving target recommended goal in critically ill patients. Methods. Twenty critically ill patients with sepsis received loading dose of 25 mg/kg of vancomycin and then were randomly assigned to 2 groups. Group 1 received maximum empirical doses of vancomycin of 15 mg/kg every 8 hrs. In group 2, the doses were individualized based on serum concentrations of vancomycin. First dose nonsteady state sampling was used to calculate pharmacokinetic parameters of the patients within 24 hours. Results. Steady state trough serum concentrations were significantly higher in group 2 in comparison with group 1 (19.4 ± 4.4 mg/L versus 14.4 ± 4.3 mg/L) (P = 0.03). Steady state AUCs were significantly higher in group 2 compared with group 1 (665.9 ± 136.5 mg·hr/L versus 490.7 ± 101.1 mg·hr/L) (P = 0.008). Conclusions. With early individualized dosing regimen, significantly more patients achieved peak and trough steady state concentrations. In the context of pharmacokinetic/pharmacodynamic goal of area under the time concentration curve to minimum inhibitory concentration (AUC/MIC) ≥400 and also to obtain trough serum concentration of vancomycin of ≥15 mg/L, it is necessary to individualize doses of vancomycin in critically ill patients.

Background Coronavirus disease 2019 (COVID-19), a highly contagious viral disease has spread from Wuhan, Hubei Province, China to all over the world from its first recognition on December 2019. To date, only a few neonatal early-onset sepsis by SARS-COV-2 has been reported worldwide. Case presentation In this report, we present two seriously ill neonates who were born from mothers with stablished COVID-19 pneumonia. Laboratory tests showed lymphopenia with high LDH and hypocalcemia right after the birth. They had fever for days without responding to antibiotics and despite ruling out other potential causes. Both patients had positive RTPCR for SARS-COV-2 in the second round of testing but the first assay tested was negative. Hydroxychloroquine was used to treat both patients; the first patient was treated with it over a period of 14 days before showing signs of improvement. The second patient responded to the treatment over a period of 5 days. Conclusion Although based on the available evidences, vertical transmission of COVID-19 is less likely, many aspects of pathogenesis and transmission of this novel virus are still unclear. Therefore we cannot rule out the vertical transmission totally. Further investigations are warranted to determine the exact mechanisms and routes of transmission.

Objective: Based on previous studies in the sepsis population, Vitamin C could prevent injuries when administered in high doses and before the damage is established. This study aimed to evaluate the protective potentials of high-dose Vitamin C in the progression of coronavirus disease 2019 (COVID-19). Methods: A double-blind, placebo-controlled clinical trial was conducted. Patients with moderate-to-severe disease severity based on the World Health Organization definition were enrolled and received 12 g/d Vitamin C (high-dose intravenous Vitamin C [HDIVC]) or placebo for 4 days. Sequential Organ Failure Assessment (SOFA) score as a primary outcome, National Early Warning Score, Ordinal Scale of Clinical Improvement, and cytokine storm biomarkers were recorded on days 0, 3, and 5. Survival was also assessed on day 28 after enrollment. Findings: Seventy-four patients (37 patients in each group) were enrolled from April 5, 2020, to November 19, 2020, and all patients completed follow-up. A lower increase in SOFA score during the first 3 days of treatment (+0.026 vs. +0.204) and a higher decrease in this parameter in the last 2 days (−0.462 vs. −0.036) were observed in the treatment group. However, these differences did not reach a significance level ( P = 0.57 and 0.12, respectively). Other indices of clinical and biological improvement, length of hospitalization, and intensive care unit admission days were the same between the two groups. Treatment did not affect the 28-day mortality. Conclusion: Among patients with moderate-to-severe disease of COVID-19, the use of HDIVC plus standard care resulted in no significant difference in SOFA score or 28-day mortality compared to the standard care alone.

BackgroundSevere COVID-19 is associated with an increased level of blood IL-6. It is suggested that adjusting the IL-6 level or its effects may diminish the inflammation of the airway and alter the course of the disease. MethodsWe performed a controlled, randomized, double-blind clinical trial including severe hospitalized COVID-19 patients in Iran. The patients were randomly distributed by block randomization to take usual care plus IL-6 inhibitor (tocilizumab 8mg/kg, 1 or 2 dosages) or usual care alone (ratio 1:1). The endpoint was defined by the clinical improvement and discharge or death. Main and safety analysis was performed in the overall population. ResultsWe enrolled 40 eligible patients (20 patients in each group) from July 10, till October 10, 2020, in this study. After randomization, one patient in the usual care arm and three patients in the tocilizumab arm refused to participate in the study and were eliminated from the study and overall analysis. The mean age of participants was 59.62 ± 15.80 and 63.52 ± 12.83 years old in Tocilizumab (8 women and 9 men) and standard care (9 women and 10 men) groups respectively (P-value= 0.426). The number of recovered patients did not significantly differ between tocilizumab and usual care groups (70.6% (n=12) vs 78.9% (n=15) respectively) (P-value=0.563). Also, the survival time was not significantly varied between participants in the tocilizumab intervention and usual care group [Log rank test: P=0.973; Hazard ratio: 1.25; 95% C‎‎I: 0.‎249-4.209]. ConclusionThe study results recommended that tocilizumab could not be a beneficial agent for treating severe cases of COVID-19 patients and have not significantly affected patients' clinical improvement.Clinical trial registrationThis trial was registered in the Iranian Registry of Clinical Trials on 9 July 2020 (ID: IRCT20081027001411N4) (https://www.irct.ir/trial/48396).