Treatment of Childhood Bacterial Meningitis with Ceftriaxone Once Daily: Open, Prospective, Randomized, Comparative Study of Short-Course versus Standard-Length Therapy

Abstract

Fifty-two children were included in this study to evaluate and compare short- versus standard-length ceftriaxone therapy for bacterial meningitis. The duration of the short-course regimens was 4, 6 and 7 days for Neisseria meningitidis, Hemophilus influenzae and Streptococcus pneumoniae, respectively. The standard-length regimens were twice as long. On the basis of a computer-generated randomization list, 26 children were assigned either to the short- or to the standard-treatment regimen. Ceftriaxone was given intravenously once daily in a dose of 60 mg/kg after an initial loading dose of 100 mg/kg. The population characteristics, the severity of disease and the cerebrospinal fluid (CSF) findings were similar in the two study groups at admission. Bacteriological and clinical response were comparable. There were no significant differences in the incidence of neurological complications, prolonged fever (≥10 days), persistent pleocytosis and side effects between the two groups. Hearing loss occurred in 3 patients in the standard-length group and in no patients in the short-course group. Diarrhea was the only side effect and occurred in 14% of the patients. The results of the study indicate that the short-duration regimen was adequate for the treatment of meningitis caused by the three major meningeal pathogens. However, the small number of patients do not justify the adoption of the short-course regimen for all children with meningitis. At present, prolongation of ceftriaxone therapy or discontinuation of the drug under strict clinical observation of the patient should be considered in some cases.

Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study

“…Previous studies have shown similar CFR and recovery rates without sequelae at 72 h to those in our study. 5,13,14,22,23 All deaths reported in our study took place within 30 h of admission, and all occurred in patients who presented with impaired consciousness at admission. Furthermore, two-thirds of the patients who died had been diagnosed with another infection, either alone or associated with meningococcal meningitis.…”

“…Other studies testing short-course treatment (2-4 days) of ceftriaxone or chloramphenicol with longer follow-up periods than ours also failed to identify individuals with relapsed disease. [11][12][13][14][22][23][24] This scarcity of data could be explained by the fact that CSF is sterile 24-48 h after one injection of ceftriaxone or chloramphenicol. 11,[15][16][17][18]25 In both of our treatment groups, the CFR was lower than those reported from epidemiological surveillance or prospective studies undertaken during meningitis epidemics.…”

“…Several studies have shown the efficacy of a daily dose of ceftriaxone for 4 days in the treatment of bacterial meningitis. [11][12][13][14] Short-course protocols could also be effective because of the pharmacological properties of ceftriaxone that include a long half-life in blood (8 h) and in cerebrospinal fluid (CSF; 14 h), as well as residual amounts in CSF above the minimal inhibitory concentration of most of the organisms 24-48 h after injection. 11,[15][16][17][18] Short-course protocols have been tested in two randomised trials.…”

Guidelines for the management of acute meningitis in children and adults in South Africa

“…No randomised trials exist in adults to support reduced duration. In children, there are a number of studies, including two smaller studies, [41][42] a meta-analysis 43 and a large multicentre, randomised, placebo-controlled trial, 44 that suggest that short-course therapy of 4-7 days is sufficient for acute bacterial meningitis. The latter study compared five vs. 10 days treatment with ceftriaxone for meningitis due Table IV.…”

Use of ceftriaxone during epidemics in patients with suspected meningococcal meningitis

“…Although 7 days of therapy with ceftriaxone has been recommended for the treatment of meningococcal meningitis, several studies have demonstrated the efficacy of a single daily dose of ceftriaxone for 4 days [8], and several small studies have shown efficacy of 2-day courses of therapy [9,10]. Given the limitation of administration of multiple days of antimicrobial therapy of bacterial meningitis in the developing world, short-course therapy offers important advantages in ensuring that patients receive efficacious therapy.…”