Intraventricular antibiotics for bacterial meningitis in neonates.
BACKGROUND
Neonatal meningitis may be caused by bacteria, especially gram-negative bacteria, which are difficult to eradicate from the cerebrospinal fluid (CSF) using safe doses of antibiotics. In theory, intraventricular administration of antibiotics would produce higher antibiotic concentrations in the CSF than intravenous administration alone, and eliminate the bacteria more quickly. However, ventricular taps may cause harm.


OBJECTIVE
To assess the effectiveness and safety of intraventricular antibiotics (with or without intravenous antibiotics) in neonates with meningitis (with or without ventriculitis) as compared to treatment with intravenous antibiotics alone.


METHODS
MEDLINE, EMBASE, The Cochrane Library, Issue 2, 2004, Science Citation Index, and the Oxford Database of Perinatal Trials were searched in June 2004. Pediatric Research (abstracts of proceedings) were searched (1990 - April 2004) as were reference lists of identified trials and personal files. No language restrictions were applied.


METHODS
Selection criteria for study inclusion were: Randomized or quasi-randomized controlled trials in which intraventricular antibiotics with or without intravenous antibiotics were compared with intravenous antibiotics alone in neonates (< 28 days old) with meningitis. One of the following outcomes was required to be reported: mortality during initial hospitalization, neonatal and/or infant mortality, neurodevelopmental outcome, duration of hospitalization, duration of culture positivity of CSF and side effects.


METHODS
All reviewers abstracted information for outcomes reported and one reviewer checked for discrepancies and entered data into RevMan 4.2. Relative risk (RR), risk difference (RD), number needed to treat (NNT) or number needed to harm (NNH), and mean difference (MD), using the fixed effects model are reported with 95% confidence intervals (CI). The fixed effect model was used for meta-analysis.


RESULTS
One study was included in the review. This study assessed the effect of intraventricular gentamicin in a mixed population of neonates (69%) and older infants (31%) with gram negative meningitis and ventriculitis. Mortality was statistically significantly higher in the group that received intraventricular gentamicin in addition to intravenous antibiotics compared to the group receiving intravenous antibiotics alone [RR 3.43 (95% CI, 1.09, 10.74; RD 0.30 (95% CI, 0.08, 0.53); NNH was 3 (95% CI; 2 ,13)]. Duration of CSF culture positivity did not differ significantly (MD -1.20 days (95% CI, -2.67, 0.27).


CONCLUSIONS
In one trial, enrolling infants with gram negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a 3 fold increased RR for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics as tested in this trial should be avoided. Further trials comparing these interventions are not justified in this population.
Shah
S
S
Shared Program in Neonatal-Perinatal Medicine, Division of Neonatology, University of Toronto, 600, University Avenue, Room 775A, Toronto, M5G 1X5, Ontario, Canada. sshahdoc@hotmail.com
Ohlsson
A
A
Shah
V
V
D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D005839:Gentamicins / Q000008:administration & dosage; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D007231:Infant, Newborn; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D016032:Randomized Controlled Trials as Topic
D000900:Anti-Bacterial Agents; D005839:Gentamicins