Comparative efficacy and safety of systemic antifungal agents for candidemia: a systematic review with network meta-analysis and multicriteria acceptability analyses

Aim: Invasive candidiasis is the main fungal infection in patients attending health services and is associated with high mortality rates and prolonged hospital stay. We aimed to comparatively evaluate the efficacy and safety of antifungal agents for treating candidemia. Methods: A systematic review with network meta-analysis (NMA), the surface under the cumulative ranking analysis (SUCRA), and stochastic multicriteria acceptability analyses (SMAA) were performed (PROSPERO-CRD42020149264). Searches were conducted in PubMed and Scopus (Nov-2021). Randomised controlled trials evaluating the effect of oral antifungals (any dose or regimen) on mycological cure, discontinuation rates, and adverse events were included. Results: Overall, 13 trials (n=3,632) were analysed. No significant differences among therapies were found for the efficacy outcomes; however, caspofungin (50-150 mg), rezafungin (200-400mg), and micafungin (100-150 mg) were considered the most promising therapies, leading to higher rates of both clinical and mycological responses (SUCRA overall response over 60%). Fluconazole (400 mg) was rated as the last option for overall response (17%). Rezafungin (200-400mg) and micafungin (100 mg) were associated with lower discontinuation rates (<40%); conventional amphotericin B (0.6-0.7mg/kg) was more likely to be discontinued (OR 0.08 [95% CrI 0.00-0.95] vs. caspofungin 150 mg) and may impair liver function (87%). Conclusion: Echinocandins should be listed as first-line treatments for invasive candidiasis following a priority order of caspofungin and micafungin. Rezafungin, an under-development echinocandin, represents a potential option that should be further investigated. Azoles and liposomal amphotericin B can be used as second-line treatments in cases of fungal resistance or hypersensitivity.info:eu-repo/semantics/publishedVersio

Systematic review with network meta-analysis on the treatments for latent tuberculosis infection in children and adolescents

Background: We aimed to synthesize the evidence on the efficacy and safety of different treatment regimens for latent tuberculosis infection (LTBI) in children and adolescents. Methods: A systematic review with network meta-analysis was performed (CRD142933). Searches were conducted in Pubmed and Scopus (Nov-2021). Randomized controlled trials comparing treatments for LTBI (patients up to 15 years), and reporting data on the incidence of the disease, death, or adverse events were included. Networks using the Bayesian framework were built for each outcome of interest. Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Rank probabilities were calculated via the surface under the cumulative ranking analysis (SUCRA) (Addis-v.1.16.8). GRADE approach was used to rate evidence's certainty. Results: Seven trials (n = 8696 patients) were included. Placebo was significantly associated with a higher incidence of tuberculosis compared to all active therapies. Combinations of isoniazid (15–25 mg/kg/week) plus rifapentine (300–900 mg/week), followed by isoniazid plus rifampicin (10 mg/kg/day) were ranked as best approaches with lower probabilities of disease incidence (10% and 19.5%, respectively in SUCRA) and death (20%). Higher doses of isoniazid monotherapy were significantly associated with more deaths (OR 18.28, 95% ICr [1.02, 48.60] of 4–6 mg/kg/day vs. 10 mg/kg/3x per week). Conclusions: Combined therapies of isoniazid plus rifapentine or rifampicin for short-term periods should be used as the first-line approach for treating LTBI in children and adolescents. The use of long-term isoniazid as monotherapy and at higher doses should be avoided for this population.info:eu-repo/semantics/publishedVersio