A systematic review 1 including 14 observational cohort studies was abstracted in DARE. Five studies (n=1 245) provided data on oral treatment and 12 studies (n=3 357) provided data on parenteral treatment. Oral antibiotic treatment was associated with significantly reduced mortality (5 studies; combined RR 0.17, 95% CI 0.07 to 0.44). Statistical heterogeneity was not significant. For parenteral antibiotics, 8 studies showed a beneficial effect (one significant) and four a harmful effect of treatment. Significant heterogeneity was present among these 12 studies and among the 7 studies that only included patients seen in primary care before admission. In the 5 studies that included data stratified by severity of disease, the proportion of cases classified as severe ranged from 11 to 76%. Statistical heterogeneity was significant (P=0.02). None of the studies showed a statistically significant effect on mortality. The meta-regression indicated that differences in the proportion of cases treated accounted for 100% of the variance between studies of parenteral antibiotics. There was a significant negative association (P=0.04) between the proportion of patients given parenteral antibiotics before admission and mortality after such treatment.
Comment: The quality of evidence is downgraded by imprecise results and by indirectness. Confounding by severity (systematic differences in disease severity between treated and untreated groups) is the most likely explanation for the beneficial effects of oral antibiotics and the harmful effects seen in some studies with parenteral antibiotics. In view of this it is uncertain whether antibiotics given before admission affect mortality. The data are consistent with benefit when a substantial proportion of patients are treated.
A Cochrane review 2 (abstract , review [Abstract]) included one open-label non-inferiority RCT with a total of 510 subjects. The study was conducted in Niger during an epidemic of meningococcal infection. Most patients (55 to 57%) were in the 5 to 14 years age group, with 31% under the age of 5 years. A single dose of intramuscular ceftriaxone was compared to a single dose of intramuscular long acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.2, 95% CI 0.5 to 2.6; N = 503; 308 confirmed meningococcal meningitis; 26 deaths), nor in proportions of survivors who developed neurological sequelae (RR 1.3, 95% CI 0.6 to 2.6; N = 477; 29 with neurological sequelae), or that were classified as clinical failures (RR 0.8, 95% CI 0.3 to 2.2; N = 477, 18 clinical failures). No adverse effects of treatment were seen. Estimated treatment costs were similar. No data were available on disease burden due to sequelae.
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