Antimicrobial Stewardship and Dose Adjustment of Restricted Antimicrobial Drugs in Hospital Setting.

Antimicrobial consumption is increasing. In order to maximize the effectiveness of antimicrobial stewardship and provide safe and optimal use of restricted antimicrobial drugs, renal dosing should be evaluated. The aim of this study was to determine the prevalence of restricted antimicrobial drugs that required dose adjustment according to renal function. A retrospective, consecutive study was conducted at University Hospital Dubrava. This study analyzed requests for restricted antimicrobial drugs (n = 2890) during a 3-month period. Requests for antimicrobial agents were evaluated by the antimicrobial therapy management team (A-team). This study included 412 restricted antimicrobial drug requests requiring dose adjustment, of which 39.1% did not have an adjusted dose. Meropenem, Ciprofloxacin, Piperacillin/Tazobactam, Vancomycin, Colistin and the antimycotic Fluconazole were the most frequent restricted antimicrobial drugs that required dose adjustment according to impaired renal function. The results of this research highlight the importance of the A-team in the optimization of restricted antimicrobial therapy. Non-adjusted doses of restricted antimicrobial drugs increase the possibility of adverse drug reactions and therefore jeopardize pharmacotherapy outcomes and patient safety.

The screening and evaluation of potential clinically significant HIV drug combinations against the SARS-CoV-2 virus.

Spike glycoprotein is essential for the reproduction of the SARS-CoV-2 virus, and its inhibition using already approved antiviral drugs may open new avenues for treatment of patients with the COVID-19 disease. Because of that we analyzed the inhibition of SARS-CoV-2 spike glycoprotein with FDA-approved antiviral drugs and their double and triple combinations. We used the VINI in silico model of cancer to perform this virtual drug screening, showing HIV drugs to be the most effective. Besides, the combination of cobicistat-abacavir-rilpivirine HIV drugs demonstrated the highest in silico efficacy of inhibiting SARS-CoV-2 spike glycoprotein. Therefore, a clinical trial of cobicistat-abacavir-rilpivirine on a limited number of COVID-19 patients in moderately severe and severe condition is warranted.

Topical use of antifibrinolytic agents reduces postoperative bleeding: a double-blind, prospective, randomized study.

OBJECTIVE: Postoperative bleeding is still one of the most common complications of cardiac surgery. Antifibrinolytic agents successfully reduce bleeding, but there are controversies concerning adverse effects after their systemic use. By topical application of antifibrinolytic agents in pericardial cavity, most of these effects are avoided. We compared the effects of topically applied aprotinin, tranexamic acid and placebo on postoperative bleeding and transfusion requirements. METHODS: In this single-center prospective, randomized, double-blind trial, 300 adult cardiac patients were randomized into three groups to receive one million IU of aprotinin (AP group), 2.5g of tranexamic acid (TA group) or placebo (PL group) topically before sternal closure. Groups were comparable with respect to all preoperative and intraoperative variables. Postoperative bleeding, transfusion requirements and hematologic parameters were evaluated. RESULTS: Postoperative bleeding within first 12-h period (AP group 433+/-294 [350; 360]ml, TA group 391+/-255 [350; 305]ml, PL group 613+/-505 [525; 348]ml), as well as cumulative blood loss within 24h (AP group 726+/-432 [640; 525]ml, TA group 633+/-343 [545; 335]ml, PL group 903+/-733 [800; 445]ml), showed statistically significant inter-group differences (both p<0.001). Bleeding rates values were significantly higher in placebo group compared to the groups treated with antifibrinolytic agents (AP and TA groups) concerning both variables. Although TA group showed the lowest values, no statistical differences between TA and AP groups were found. Inter-group difference of blood product requirements was not statistically significant. CONCLUSIONS: Topical use of either tranexamic acid or aprotinin efficiently reduces postoperative bleeding. TA seems to be at least as potent as aprotinin, but potentially safer and with better cost-effectiveness ratio.

Supplementation with antioxidants in the treatment of Graves' disease; the effect on glutathione peroxidase activity and concentration of selenium.

BACKGROUND: The effect of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) was monitored on the speed of attaining euthyroidism in a group of patients with Graves' disease, treated with methimazole. METHODS: The activity of glutathione peroxidase in whole blood and the concentrations of selenium, pituitary and thyroid hormones in serum were measured, prior to commencement of therapy and after 30 and 60 days. RESULTS Patients who received supplementation with antioxidants in addition to therapy with methimazole (Group A, n=29) attained euthyroidism faster than the patients treated with only methimazole (Group B, n=28). The concentration of selenium in the serum of patients in Group A increased significantly during treatment (p<0.001), while there was no statistically significant change in the patients in Group B. The concentration of selenium in the serum between the groups differed statistically significantly 30 days (p<0.05) and 60 days (p<0.01) after the commencement of therapy. Activity of glutathione peroxidase in whole blood increased during treatment in both groups of patients. However, a statistically more significant increase occurred in Group A compared to Group B, 30 days after the commencement of therapy (p<0.01). CONCLUSION: The results of the study clearly indicate that supplementation with antioxidants in the treatment of Graves' disease is justified, particularly those containing selenium.

Antioxidant supplementation and serum lipids in patients with Graves' disease: effect on LDL-cholesterol.

The effect of supplementation with a fixed combination of antioxidants (beta-carotene, selenium, vitamins C and E) on serum lipids was monitored in patients with newly detected Graves' disease. Measurements were made prior to the commencement of therapy and after 30 and 60 days. Patients were randomized into two groups. Test group comprised patients who received antioxidant supplementation in addition to methimazole, while patients treated with methimazole only were in the control group. The concentration of total and HDL-cholesterol increased significantly in test and control groups (p < 0.05) but these groups did not differ significantly. Concentration of LDL-cholesterol increased significantly in the test group only (p < 0.005) and was significantly different from the control group 60 days after the commencement of therapy (p < 0.005). Significant increase in the LDL-cholesterol concentration in the test group requires further investigations.