What?

Why?

Bacterial meningitis is an important cause of morbidity and mortality in children in developing countries with case-fatality rates ranging from 11- 40% and a large number of survivors being left with severe neurological sequelae. However, early identification and prompt treatment with appropriate antibiotics can minimize this. Unfortunately, the continuous spread of antimicrobial resistance in developing nations is impeding their ability to treat and contain infections like meningitis with traditional therapies like penicillin plus chloramphenicol.

The WHO recommends that ceftriaxone be used as a first-line therapy for childhood meningitis in areas with significant penicillin resistance. But the optimal duration of therapy for bacterial meningitis is uncertain and recommendations have varied. There are several limitations and factors to consider to determine an optimal therapy: high cost of antibiotic therapy, especially third generation Cephalosporins in developing countries (the price of Ceftriaxone is 3 to 4 times higher than the equivalent regimen of injectable penicillin plus Chloramphenicol); difficulty of hospitalization and maintenance of intravenous infusions over a 10-day; limited number of tertiary care beds and resources available in developing countries; higher cost of longer hospitalizations; risk of nosocomial infections due to increased hospitalization; and indirect costs to the family for hospitalization in shape of lost income, transportation and food expenses.

How?

We compared 5 vs. 10 days (Standard) of ceftriaxone therapy for bacterial meningitis in a prospective, double-blind, placebo-controlled, randomized study. Children 2 month to 5 years 11 months of age with suspected bacterial meningitis were hospitalized in various centres in developing countries. All children received 5 days of injectable ceftriaxone initially and were randomized on day 5 to either receive five days (days 6-10) of additional ceftriaxone or placebo. Outcome variables were studied, including bacteriological failure or relapse, mortality, hearing loss and other neurological sequelae determined at days 10, 40, 190 days after hospital admission. Definitions of treatment failure have varied in clinical trials of meningitis. The most objective definition of failure is bacteriological relapse during treatment or shortly after completion of therapy. Clinical evidence of failure has often been based on persistent fever or other clinical signs in the absence of objective evidence of bacteriologic failure. Fever often persists for 5 or more days due to the inflammatory response, although treatment with third generation Cephalosporins results in sterilization of the CSF within 48 hours in almost all patients.

Upon admission, lumbar punctures (LP) were done on children clinically suspected of having meningitis, and full history and details recorded. If meningitis was suspected after LP, blood samples were taken and treatment was started with ceftriaxone. After 48hrs, after starting treatment, a second LP was done. If the 2nd sample was still bacteriologically positive, the child was excluded from random assignment. Children alive on day 5, clinically stable and/or improving were considered for inclusion. Detailed methods in the publication below.

What we found

In this multi-center study, 2000 children were recruited in total on day 0, 1820 of whom had confirmed bacterial meningitis. By day 5, 1551 were alive, and 1027 of them were assigned to treatment groups. Overall, the study findings showed that in children in this age group with acute bacterial meningitis caused by the 3 major pathogens, there was no difference between the short and long term antibiotic treatment when the clinical conditions were stable or improving by day 5. Detailed results in the publication below.