Acute aseptic meningitis temporally associated with trimethoprim and sulfamethoxazole: Systematic review

Sulphonamides and trimethoprim, although generally well-tolerated, have been temporally associated with aseptic meningitis. To address its presentation and outcome, a literature search was performed. We retained articles reporting patients with features of acute aseptic meningitis following intake of trimethoprim, sulfamethoxazole or sulfisoxazole. A cerebrospinal fluid investigation in ≥1 episode was a prerequisite for inclusion. Sixty articles reporting on 74 patients experiencing a total of 155 episodes were retained. Forty-five (61%) patients had one or more recurrences. Median age at first episode was 43 (interquartile range [IQR] 23–61) years. Symptoms presented within 48 (IQR 6–168) hours of intake at the first episode and within 1.3 (IQR 1–5) hours at recurrences (p <.0001). Cerebrospinal fluid analysis revealed a predominantly neutrophilic (82%, IQR 65%–94%) pleocytosis (180, IQR 38–507 106 cells/L), without low glucose or high proteins. Recovery took place within 2 (IQR 1–3) days after stopping the suspected agent. All but one patient completely recovered.