Intraventricular or intrathecal use of polymyxins in patients with Gram-negative meningitis: a systematic review of the available evidence

Several reports have described the use of polymyxins by the intraventricular or intrathecal route for multidrug-resistant Gram-negative meningitis. We reviewed the available clinical evidence regarding intraventricular/intrathecal administration of polymyxins in patients with meningitis, focusing on effectiveness and safety. Relevant studies were identified from PubMed (January 1950 to April 2006) as well as from the references of relevant articles. We identified 31 case reports/series that matched our inclusion criteria. Sixty-four episodes of Gram-negative meningitis (34 in adults) were reviewed. Monotherapy with polymyxins via the intraventricular or intrathecal route was used in 11 episodes and combination of systemic and local polymyxins was used in 25 episodes. In the remaining episodes, various combinations of local polymyxins with systemic and/or local antibiotics were administered. Cure was achieved in 51/64 episodes (80%); in 26/30 episodes (87%) due to Pseudomonas aeruginosa and in 10/11 episodes (91 %) due to Acinetobacter spp. Toxicity related to local administration of polymyxins was noted in 17/60 (28%) patients. The most common toxicity was meningeal irritation (12 cases). Discontinuation of treatment was necessary in four episodes and dose reduction in four episodes; irreversible toxicity was not reported. The limited available evidence suggests that therapy with intraventricular/intrathecal polymyxins alone or in combination with systemic antimicrobial agents is effective against Gram-negative meningitis. Toxicity is not uncommon but it is dose-dependent and reversible. Further studies are needed to evaluate the criteria for initiation of local central nervous system treatment with polymyxins, the optimal dosages and the role of adjuvant systemic or local therapy. (c) 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.