Evaluation of voriconazole related adverse events in pediatric patients with hematological malignancies.

BACKGROUND: Despite therapeutic drug monitoring and pharmacogenetic-guided dose selection are recommended for pediatric patients, safety of voriconazole is mostly monitored by clinical assessment. Having comprehensive knowledge of safety profile and distinguishing incidental events from the reactions that are truly related to voriconazole use are crucial for safer and uninterrupted treatment. OBJECTIVES: This study aimed to address adverse reactions during the first month of voriconazole use by systematically evaluating retrospective records of all adverse events. Patients/Methods: It is a single-center, retrospective analysis of patients who received voriconazole from 1 September 2010 to 1 September 2020. Severity of abnormal findings in medical records were systematically graded. Causality between voriconazole and the events was evaluated by Liverpool Causality Assessment Tool (LCAT), Naranjo Algorithm and World Health Organization Causality Assessment System. The events with possible or probable causal relation to voriconazole are classified as adverse reaction. RESULTS: Records of 45 patients included in the study. The overall frequency of adverse reactions was 51.1%. Hepatobiliary laboratory adverse reactions identified in 48.9% of the patients and led to treatment discontinuation in 20.0%. Amylase and lipase elevation (2.2%), ventricular extra systoles (2.2%), hallucination and nightmares (2.2%) were other adverse reactions. CONCLUSIONS: Hepatobiliary abnormalities were the most common adverse reactions and the most common cause of treatment discontinuation. For safer treatment in critically ill patients, the dose should be personalized. To clearly identify the accurate frequency and the causality of all adverse reactions, prospective studies with much larger sample size are needed.

Clinical characteristics and risk factors for 28-day mortality in critically ill patients with COVID-19: a retrospective cohort study

Background: To date, the coronavirus disease 2019 (COVID-19) caused more than 2.6 million deaths all around the world. Risk factors for mortality remain unclear. The primary aim was to determine the independent risk factors for 28-day mortality. Materials and methods: In this retrospective cohort study, critically ill patients (≥ 18 years) who were admitted to the intensive care unit due to COVID-19 were included. Patient characteristics, laboratory data, radiologic findings, treatments, and complications were analyzed in the study. Results: A total of 249 patients (median age 71, 69.1% male) were included in the study. 28-day mortality was 67.9% (n = 169). The median age of deceased patients was 75 (66­81). Of them, 68.6% were male. Cerebrovascular disease, dementia, chronic kidney disease, and malignancy were significantly higher in the deceased group. In the multivariate analysis, sepsis/septic shock (OR, 15.16, 95% CI, 3.96­58.11, p < 0.001), acute kidney injury (OR, 4.73, 95% CI, 1.55­14.46, p = 0.006), acute cardiac injury (OR, 9.76, 95% CI, 1.84­51.83, p = 0.007), and chest CT score higher than 15 (OR, 4.49, 95% CI, 1.51-13.38, p = 0.007) were independent risk factors for 28-day mortality. Conclusion: Early detection of the risk factors and the use of chest CT score might improve the outcomes in patients with COVID-19.

Primary Cutaneous Aspergillosis in Immunocompetent Adults: Three Cases and a Review of the Literature.

Primary cutaneous aspergillosis (PCA) can rarely affect immunocompetent people. There is limited knowledge about the prevalence, diagnosis and management of the disease because there are only case reports or small case series in the literature. For this reason, the diagnosis and treatment of three immunocompetent adult patients diagnosed with PCA were discussed by reviewing the literature. In the current report, in addition to treatment with voriconazole for 8-12 weeks we performed repeated surgical debridement for the treatment of these cases. After two negative tissue cultures, the wounds were either successfully closed primarily or reconstructed using a skin graft. Management of PCA cases will become easier as more reports and further studies of PCA contribute to our shared knowledge. Currently, the most appropriate management approach is to make individualized treatment decisions according to the patients' clinical features and treatment response which includes several surgical debridement as well as antifungal therapy.