# Pediatric Coccidioidal Meningitis: A Systematic Review and Proportional Synthesis of Cases Reported in the Fluconazole Era (2000–2025)

## TL;DR

This study reviews pediatric coccidioidal meningitis cases from 2000 to 2025, finding that high serum CF titers predict poor outcomes and emphasizing the need for better pediatric guidelines.

## Contribution

The study provides the first systematic synthesis of pediatric coccidioidal meningitis cases in the fluconazole era, identifying risk factors and outcomes specific to children.

## Key findings

- High serum CF titers (≥1:16) are independently associated with adverse outcomes in pediatric CM.
- Lifelong azole therapy is linked to improved survival in pediatric CM patients.
- Hydrocephalus occurs in 37.5% of pediatric CM cases, highlighting its severity.

## Abstract

Coccidioidal meningitis (CM) is a rare but life-threatening complication of disseminated coccidioidomycosis, occurring in ~16% of cases, particularly among children in endemic regions such as the southwestern US and northern Mexico. Without timely diagnosis and antifungal therapy, pediatric CM is almost universally fatal within the first year. Hydrocephalus develops in up to 50% of cases. In 2000, Galgiani et al. established fluconazole as first-line therapy for CM. Subsequent guidelines refined management but did not specifically address pediatric patients (>1 month–≤19 years). No studies in the fluconazole era have systematically evaluated risk factors for complications in this population. We therefore conducted a systematic review and proportional synthesis of pediatric CM cases, focusing on CNS complications and outcomes. PubMed/MEDLINE, Embase (Ovid), and Web of Science were systematically searched (2000–2025). PROSPERO registration ID (1130290). Inclusion criteria encompassed epidemiological studies, case series, and case reports that described at least one pediatric case of CM or CNS involvement, confirmed by diagnostic methods. Cases in adults, neonates (<1 month), congenital infections, teratogenicity studies, reviews, or incomplete reports were excluded. Only cases with complete individual data (n = 48) were included. Methodological rigor was ensured using JBI Critical Appraisal Tools. Of 1089 studies, 31 met the inclusion criteria, representing 3874 pediatric cases. CM/CNS involvement was confirmed in 165 cases (4.25%; 95% CI: 3.6–4.9%), with hydrocephalus in 62 (37.5%). Among 48 case reports with complete data, fluconazole was first-line therapy in 65%. Serum CF titers ≥ 1:16 were associated with hydrocephalus plus stroke (p = 0.027) and independently predicted adverse outcomes (relapse/death; OR = 4.5, p = 0.037), whereas lifelong azole therapy was associated with improved outcomes (overall survival mean, 82 vs. 32 months; p = 0.002). Pediatric CM remains highly lethal, with hydrocephalus a frequent and severe complication. High serum CF titers (≥1:16) predict poor outcomes, emphasizing the urgent need for standardized, pediatric-specific diagnosis and management guidelines.