An open randomized trial of ceftriaxone v penicillin and gentamicin in infant bacterial meningitis in Malawi

Current research

The overall case fatality rate of meningitis in infants <2 months of age in Blantyre Malawi is 49%. Half the cases are caused by Gram-positive and half by Gram-negative bacteria. First line antimicrobial therapy is, according to WHO guidelines, parenteral penicillin and gentamicin. This covers some Gram-positive bacteria (namely Group B streptococci and some Strep pneumoniae), but is not adequate for many Gram-negative infections, in particular non-typhoidal salmonellae that is the second most common cause of meningitis in this age group. Gentamicin may ‘hold’ a NTS’ infection but it is unlikely to eradicate it from the CSF.

Second line antimicrobial therapy is ceftriaxone, which is the WHO recommendation as cefotaxime is not available. It has many advantages. Almost all bacteria cultures in our unit are sensitive to ceftriaxone. Generic ceftriaxone is cheap. It is available and importantly need only be given once daily. Mothers find the vast number of injections required for Pen and Gent (56- 70) abhorrent and may abscond without finishing treatment.

Concerns have been raised about using ceftriaxone in premature infants especially if they are jaundiced or require calcium. We can monitor bilirubin levels and other electrolytes including calcium, provide phototherapy if necessary and have not given calcium to a neonate in the last 15 years.  

We wish to undertake an open randomised trial to compare the outcome of infant meningitis when either penicillin and gentamicin, (our standard first line treatment) or ceftriaxone (our second line drug) are used as first line therapy. We hypothesise that the case fatality rate will be 20% less in the ceftriaxone group (30% v 50%)