Nuo Xu

and 10 more

Caspofungin is an echinocandin antifungal commonly used as the first-line therapy for invasive candidiasis, salvage therapy for invasive aspergillosis. Pharmacokinetic variabilities and suboptimal exposure have been reported for caspofungin, increasing the risk of insufficient efficacy. We aimed to consolidate information from population pharmacokinetic studies, compare model performance, identify significant covariates affecting caspofungin’s PKs, evaluate probability of target attainment in different studies and assemble pharmacokinetic/pharmacodynamic target to address existing knowledge gaps that may warrant further investigation in future. We performed a systematic search strategy to review the PPK studies of caspofungin. Four databases were searched. We extracted information for the comparison of models, evaluation of the impact of covariates on clearance and apparent volume and the calculation of probability of target attainment under specific minimum inhibitory concentration. Thirteen studies were included. The simulation results showed that under labeled dose, pediatrics exhibited notably higher exposure than adults. Body size was the most identified covariate that affected both clearance and volume of distribution. For C. albicans and C. parapsilosis, none of the populations achieved a PTA of ≥ 90%. In contrast, for C. glabrata, 70% of the adult patients reached a PTA of ≥ 90%, while all pediatric patients achieved the same PTA level. At the recommended dosage, adults showed lower exposure to caspofungin compared to pediatrics. It is crucial to consider body size, liver function and serum albumin when determining caspofungin dosage regimens. Furthermore, further research is required to comprehensively understand the pharmacokinetics of caspofungin in pediatrics.

Mei Zeng

and 13 more

Objectives: To understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai. Study designs: This study included local COVID-19 cases<18 years in Shanghai referred to the exclusively designated hospital by the end of March 2022 since emergence of Omicron epidemic. Clinical data, epidemiological exposure and COVID-19 vaccination status were collected. Relative risks (RR) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease. Results: A total of 376 pediatric cases of COVID-19 (median age:6.0±4.2 years) were referred to the designated hospital during the period of March 7-31, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children ≥3 years eligible for COVID-19 vaccination, 110 (40.4%) received 2-dose vaccines and 16 (4.0%) received 1-dose vaccine. The median interval between 2-dose vaccination and infection was 3.5 (IQR: 3, 4.5) months (16 days-7 months). Two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35%(RR 0.65, 95% CI: 0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81). Two hundred and sixteen (83.4%) symptomatic cases had fever (mean duration:1.7±1.0.8 days), 104 (40.2%) had cough, 16.4% had transient leukopenia; 307 (81.6%) had an epidemiological exposure in household (69.1%) , school (21.8%) and residential area (8.8%). Conclusion: The surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer some protection against symptomatic infection and febrile dise