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Tedizolid (TZD) is an oxazolidinone anti-methicillin-resistant Staphylococcus aureus (MRSA) drug. Linezolid (LZD), another oxazolidinone, has been shown to have an anti-inflammatory effect. TZD has been shown to exhibit an anti-inflammatory effect in a murine model of hematogenous pulmonary infection. In this study, we further investigated the anti-inflammatory effect of TZDs using a carrageenan-induced rat footpad edema model. TZD was administered at 0, 10, 20, and 40 mg/kg to the carrageenan-induced rat footpad edema model, and the edema rate was measured over time up to 9 h later. The area under the time curve of the edema rate profile (AUC edema0→9) decreased in a TZD dose-dependent manner. In addition, the correlation between AUC edema0→9 and the area under the time curve of free TZD plasma concentration (f AUC blood) obtained from the pharmacokinetic study of TZD in the carrageenan-induced rat footpad edema model was examined. f AUC blood and AUC edema0→9 showed a good negative correlation. These results indicate that TZD suppresses carrageenan-induced footpad edema and that TZD exerts its anti-inflammatory effects in a plasma concentration-dependent manner. [ABSTRACT FROM AUTHOR]

Because exclusive use of echinocandins can induce the drug-resistant strains, appropriate use of azoles and polyenes is still necessary in the treatment of candidemia. In this study, we conducted a meta-analysis of randomized controlled trials regarding the efficacy and safety of azole and polyene antifungals in the treatment of candidemia. MEDLINE and the Cochrane Register of Controlled Trials were used as reference databases, and papers published up to June 10, 2019 were searched. The search results were carefully scrutinized, duplicate references were removed, and the study was ultimately carried out using three reports. Among azole antifungals, fluconazole and voriconazole were extracted, however; only conventional amphotericin B (AMPH-B) was extracted among polyene antifungals. Treatment successes with the use of azoles and AMPH-B were compared, and findings showed that AMPH-B was significantly superior (RR = 0.90, 95% CI 0.82–1.00, p = 0.04). However, there was no significant difference in mortality (RR = 0.87, 95% CI 0.72–1.07, p = 0.19). Analysis of adverse events showed that renal disorders were significantly less common with azoles than with AMPH-B (RR = 0.26, 95% CI 0.10–0.68, p = 0.006). In conclusion, AMPH-B were superior to azoles in terms of efficacy, but had a risk of causing renal disorders. [ABSTRACT FROM AUTHOR]

Echinocandins are frequent use antifungals in the treatment of invasive candidiasis, and it is important to update information on their efficacy and safety for optimal antifungal drug treatment. The aim of this study is to clarify whether echinocandins are superior to non-echinocandins for the treatment of invasive candidiasis. We conducted a meta-analysis of RCTs of echinocandins and non-echinocandins for adult invasive candidiasis. The MEDLINE, Web of Sciences, Cochrane Register of Controlled Trials, and ClinicalTrials.gov databases before June 2019 were used. The risk ratio (RR) and 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel method random-effects model. We identified 14,846 articles and screened, and five studies were included meta-analysis. The treatment success ratio for echinocandins was significantly higher than that for non-echinocandins (RR = 1.14, 95% CI 1.06–1.22, p = 0.0003). In regard to adverse events, there was no significant difference between the two treatment groups. A subgroup analysis showed that the treatment success ratio for echinocandins was significantly higher than that for azoles (RR = 1.20, 1.08–1.34, p = 0.001), whereas no significant differences were observed between echinocandins and polyenes. In safety analysis, the incidence ratio of electrolyte disorder (RR = 0.50, 0.33–0.76, p = 0.001), renal disorder (RR = 0.19, 0.09–0.40, p < 0.0001), and fever (RR = 0.46, 0.23–0.93, p = 0.03) were significantly lower in patients receiving echinocandins than in those receiving polyenes. This meta-analysis based on RCTs was first to show that use of echinocandins was associated with improved clinical success. Echinocandins may be useful as a first-line drug for invasive candidiasis. [ABSTRACT FROM AUTHOR]