Local complications of adjunct intrathecal antibiotics for nosocomial meningitis associated with gram-negative pathogens: a meta-analysis

Direct delivery of antibiotics to the ventricular system offers an alternative for the management of nosocomial meningitis. However, the available literature frequently results in controversial findings regarding its safety. The present meta-analysis aimed at summarizing the risk of local complications after the administration of intraventricular/intrathecal (IVT/IT) antibiotics for the treatment of ventriculitis/meningitis (VM) associated with gram-negative pathogens. We systematically searched the medical literature from 1964 until July 2018, for clinical studies reporting on complications after the index treatment. The quality of the eligible studies was classified as “high,” “moderated,” and “low” for randomized controlled trials, observational studies, and case series, respectively. The results were summarized as pooled frequencies, estimated by the random- or fixed-effects models, according to the inter-study heterogeneity. The publication bias was visualized in trim-and-fill funnel plots. Τhe analysis included twenty-three primary studies with 229 patients. The overall complication rate was as high as 0.13 (95% CI 0.08; 0.19, I² = 9%); chemical meningitis and seizures represented the majority of the complications, with an occurrence rate of 0.11 (95% CI 0.07; 0.17, I² = 0%) and 0.07 (95% CI 0.04; 0.12; I² = 0%), respectively. The meta-analysis was based on studies of “moderate” and “low” reporting quality, while the publication bias after inspecting of the funnel plots revealed significant asymmetry. The present review denotes the absence of large, high-quality studies in the field. Nevertheless, IVT/IT was associated with moderate morbidity, mainly attributed to chemical meningitis and seizures. Further high-quality studies are still required before this therapeutic modality becomes broadly established.