Clinical Analysis of Intravenous and Oral Sequential Treatment With Voriconazole for Candida Central Nervous System Infection in Six Premature Infants

Abstract

Objective: The aim of the study was to observe the clinical efficacy and safety of intravenous and oral sequential treatment with voriconazole for Candida central nervous system (CNS) infection in premature infants.Methods: The study included retrospective analysis of the clinical data of six premature infants with Candida CNS infection admitted to the neonatology department in Shanghai Children’s Hospital between November 2016 and November 2019. By reviewing the characteristics of voriconazole based on the literature, it showed that infants without gastrointestinal dysfunction could be effectively treated by intravenous and oral sequential therapy with voriconazole (both 7 mg/kg/dose, every 12 h). Clinical manifestations, the time required for the cerebrospinal fluid (CSF), blood culture, nonspecific infection markers such as platelets and C-reactive protein (CRP) to turn normal, and drug-related side effects were observed and recorded in the process of treatment. All data were statistically analyzed by T test and Mann–Whitney U test.Results: A total of six premature infants were diagnosed with Candida CNS infection, two cases were diagnosed by a positive CSF culture and four cases were clinically diagnosed. Blood culture was positive for Candida in five cases. Among the 6 patients, 4 cases were Candida albicans and 2 cases were Candida parapsilosis. All the six cases were cured. After 3–5 days of treatment, symptoms such as lethargy, apnea, and feeding intolerance were improved and disappeared; a repeated blood culture turned negative in 3–7 days; CSF returned to normal in 15 ± 9 days on an average. Brain abscess, meningeal inflammation, and other infectious lesions were cleared on cranial magnetic resonance imaging (MRI) after treatment. The average total course of voriconazole was 61 ± 29 days, and the average oral treatment was 28 ± 15 days. No Candida recurrence was found during the treatment, and no drug-related side effects such as skin rash, liver and kidney function impairment, or visual abnormalities were found. The white blood cells, CSF glucose/plasma glucose ratio, and protein in CSF were significantly improved after the treatment (p < 0.05). No statistically significant difference was identified in the liver and kidney function indexes (p > 0.05).Conclusion: Voriconazole is a relatively safe and effective alternative treatment for Candida CNS infection in preterm infants. No severe drug-related side effects were detected.