Comparison of ceftriaxone with standard therapy for bacterial meningitis. Ceftriaxone alone compared to ampicillin and chloramphenicol in the treatment of bacterial meningitis. Ceftazidime vs. standard therapy for pediatric meningitis: therapeutic, pharmacologic and epidemiologic observations. Prospective comparative trial of ceftriaxone vs. conventional therapy for treatment of bacterial meningitis in children. Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study. Comparison of the efficacy and safety of ceftriaxone to ampicillin/chloramphenicol in the treatment of childhood meningitis. Ceftriaxone versus penicillin G in the short-term treatment of meningococcal meningitis in adults. Comparison of ceftriaxone and traditional therapy of bacterial meningitis. Ceftriaxone versus ampicillin and chloramphenicol for treatment of bacterial meningitis in children. Cefotaxime versus penicillin-chloramphenicol in purulent meningitis: a controlled single-blind clinical trial. A prospective randomized comparison of cefotaxime vs ampicillin and chloramphenicol for bacterial meningitis in children. Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis. Ceftriaxone compared with a combination of ampicillin and chloramphenicol in the treatment of bacterial meningitis in adults. Intravenous chloramphenicol plus penicillin versus intramuscular ceftriaxone for the treatment of pyogenic meningitis in Nepalese children. Cefotaxime vs. conventional therapy for the treatment of bacterial meningitis of infants and children.
nan One hundred patients (71 males and 29 females) with bacterial meningitis were randomly assigned into two therapeutic regimens. Patients in group I were intravenously given ceftriaxone (CRO: Rocephin) to adults and intramuscularly to children once daily in a dose of 100 mg/kg/day. Patients in group II received ampicillin 160 mg/kg/day and chloramphenicol (AMCL) 100 mg/kg/day (i.v. to adults and i.m. to children) every 6 h. No significant difference was observed between the two therapeutic regimens with regard to mortality, time taken to become afebrile, fully alert and sequelae. Seven patients in the CRO group died compared to 10 in the AMCL group. The mean number of days taken to become afebrile were 3.4 and 3.5, and to become fully alert 3.9 and 3.5 for groups I and II, respectively. CRO administered in a single daily dose appears to be as effective as a combination of ampicillin and chloramphenicol given every 6 h in the treatment of acute bacterial meningitis. However, the once daily dose is more appropriate for use especially in areas where nursing care is limited. One hundred patients ages 1 month to 15 years received either ceftazidime (CZ) at a dose of 150 mg/kg/day divided every 8 hours or conventional treatment with chloramphenicol and ampicillin (CA). Seventy-eight had isolates recovered from the cerebrospinal fluid: 40 (51%) were Haemophilus influenzae (all ampicillin-susceptible); 16 (21%) were Streptococcus pneumoniae; 14 (18%) were Neisseria meningitidis; 3 (4%) were salmonellae; 1 (2%) was Pseudomonas; and 1 (2%) was Group B Streptococcus. Six patients with negative cerebrospinal fluid culture had positive latex agglutination (two H. influenzae, three N. meningitidis, one S. pneumoniae). Sixty-one patients had positive blood cultures. CZ inhibited 100% of H. influenzae at 0.78 micrograms/ml, S. pneumoniae at 0.39, N. meningitidis at 0.04 and salmonellae at 0.39 micrograms/ml. The mean peak serum concentration of CZ was 36.4 micrograms/ml with a mean cerebrospinal fluid level of 7.4 micrograms/ml. If one eliminates from the statistics those patients who died less than or equal to 24 hours after admission, five (10%) of 49 patients treated with CZ died, one (2%) improved and 43 (88%) were cured. Overall 29 patients died, 12 receiving CZ (20%) and 8 receiving CA (21%). There were no significant CZ-related toxicities. Gross neurologic sequelae were noted in 5% of 38 CZ patients and 4% of 28 CA patients. CZ compared favorably to CA for treatment of meningitis. Fifty children with bacterial meningitis were prospectively evaluated in a randomized comparative trial of twice daily ceftriaxone with conventional ampicillin and chloramphenicol therapy. The groups were comparable in age, sex, days of illness before admission, severity of illness at admission, etiology and admission cerebrospinal fluid (CSF) parameters and bacterial colony counts. The pathogens were Haemophilus influenzae type b (34 beta-lactamase-negative, 8 beta-lactamase-positive); Streptococcus pneumoniae (4); Neisseria meningitidis (3); and Streptococcus agalactiae (1). Initial CSF colony counts ranged from 2.5 X 10(2) to 1 X 10(10) colony-forming units/ml. In 44 children a lumbar puncture was repeated 10.5 to 18 hours after starting treatment; 16 of 24 (67%) ceftriaxone patients and 12 of 20 (60%) conventional therapy patients had sterile cultures. The reduction in the CSF bacterial colony counts (6.3 log10 colony-forming units/ml) was similar in both groups. Ceftriaxone CSF levels ranged from 1.0 to 8.0 micrograms/ml, representing a mean CSF penetration of 11.3% (range, 3.0 to 24.5%) of the simultaneous serum concentration. The median ceftriaxone bactericidal titer in CSF was 1:1024 compared with 1:4 achieved with conventional therapy. There were no significant differences in clinical responses or in frequency of complications, except for diarrhea which occurred in 59% of the ceftriaxone group and in 22% of the other (P less than 0.01). Despite one H. influenzae type b relapse occurring in the ceftriaxone group, ceftriaxone appears to be safe and as effective as conventional therapy for bacterial meningitis in children older than 2 months of age. In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis.
                In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses.
                Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported.
                Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis. Ceftriaxone is a new cephalosporin with a broad spectrum of antibacterial activity and unique serum and CSF pharmacokinetics. The drug was compared in a randomized fashion with ampicillin and chloramphenicol in the treatment of 19 children with Haemophilus influenzae type b meningitis. Ceftriaxone was also administered non-randomly to six other patients including three children with Gram-negative meningitis. Among the children with H. influenzae meningitis, no deaths were noted and the outcomes of the study and the control groups were similar. Ninety per cent of the isolates of H. influenzae were inhibited by 0.0625, 1 and 1 mg/l of ceftriaxone, ampicillin and chloramphenicol respectively. One child with pneumococcal meningitis and two children with meningococcal meningitis recovered rapidly and without incident during ceftriaxone therapy. Three children with Gram-negative meningitis caused by multiply-drug resistant organisms were bacteriologically cured within five days of the onset of therapy. Persistent pleocytosis and neurological disabilities were noted in two at the conclusion of therapy. Ceftriaxone, as a single agent, was comparable in efficacy with traditional antimicrobial therapy usually employed in childhood meningitis. Short-term treatment with ceftriaxone 2 g once daily for two days (group 1) was compared to treatment with a standard regimen of penicillin G (group 2) for six days in adults with meningococcal meningitis. Thirty-six patients were allocated in a randomized fashion to a treatment group: 16 to group 1 and 20 to group 2. The clinical and microbiological results were comparable in the two treatment groups. In both groups cultures of cerebrospinal fluid were sterile after 24 hours. One patient in each group died. In group 1 one case of fulminant meningococcemia and one case of brain abscess required further antibiotic treatment. It is concluded that short-term treatment with ceftriaxone is feasible but patients with severe forms of meningitis would not be eligible for treatment with this regimen, and careful follow-up of the patients receiving ceftriaxone is necessary. Forty-five children (aged 1 day to 15 years) with bacterial meningitis were randomized to receive either traditional therapy (ampicillin and chloramphenicol or gentamicin, pending sensitivity) or ceftriaxone (100 mg/kg per day in two doses for a minimum of 10 days). The etiological agents involved were similar for the two groups and included Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae, and group B streptococcus. Repeat spinal taps were carried out 24 to 48 h after admission. Organisms were seen on the Gram stain of one patient treated with ceftriaxone, but five patients in the traditional therapy group had organisms present on Gram stain of uncentrifuged spinal fluid or positive cultures of the spinal fluid (or both). Ceftriaxone entered the cerebrospinal fluid well, and the average cerebrospinal fluid bactericidal activity for ceftriaxone 1 h after a dose was at least 60 times greater than for ampicillin or chloramphenicol. In those patients who received treatment for a long enough period of time to permit evaluation, there was one death in each group, both due to S. pneumoniae. The length of fever and complications were similar for the patients in both groups. Ceftriaxone was well tolerated; diarrhea, seen in 5 of the 22 patients who received the drug, was the most commonly encountered adverse effect. It was mild, and in no case was it necessary to discontinue the drug. Ceftriaxone appears in this preliminary study to be a safe and acceptable single agent for the treatment of bacterial meningitis in children. 78 patients with bacterial meningitis were evaluated in a prospective, randomised study comparing twice-daily ceftriaxone as single-drug therapy with ampicillin and chloramphenicol given every 6 h. The groups were comparable in age, sex, days of illness before admission, and bacterial colony counts in cerebrospinal fluid (CSF). The pathogens were Haemophilus influenzae type b (54 cases), streptococci (9 cases), meningococci (9 cases), and unknown (6 cases). In 40 CSF specimens obtained 4-12 h after initiation of therapy, cultures were negative in 57% of the ceftriaxone patients and in 42% of the others. The mean falls in the CSF bacterial colony counts were 4.7 and 5.0 log10 colony-forming units/ml, respectively. Mean bactericidal activity in CSF was significantly greater in the ceftriaxone than in the conventional treatment group at the beginning and end of therapy. There were no significant differences in clinical responses or in frequency of complications, except for mild diarrhoea, which occurred in 16 ceftriaxone patients and in 8 in the other group (p less than 0.05). In a prospective, controlled, randomized single-blind clinical trial, treatment with cefotaxime (CTX) was compared with that with standard therapy (ST), which consisted of a penicillin-chloramphenicol combination with or without sulphadiazine, in 31 patients (excluding neonates) with proven bacterial meningitis. The two groups of patients were comparable in age, sex, clinical presentation and causative pathogens. The case fatality rate was 12.5% for the CTX group and 20% for the ST group, but this difference was not significant. The times taken for the cerebrospinal fluid (CSF) to become sterile and the temperature to normalize, the mean duration of treatment, complications and adverse effects were similar for the two regimens. Neurological or developmental abnormalities on follow-up were not significantly different for the two groups. It is concluded that CTX is a suitable alternative for treatment of bacterial meningitis in infants and children. Fifty children with bacterial meningitis were prospectively randomized to receive cefotaxime (50 mg/kg/dose every 6 hours) or ampicillin and chloramphenicol in standard doses. Twenty-three patients received cefotaxime and 27 received standard therapy. Bacterial isolates included: Haemophilus influenzae (29), Streptococcus pneumoniae (eight), Neisseria meningitidis (eight), group B streptococci (three), and Salmonella enteritidis (two). Ten (34%) of the H. influenzae isolates were resistant to ampicillin, nine on the basis of beta-lactamase production. All strains were susceptible to cefotaxime. Clinical cure rates for the cefotaxime (100%) and standard therapy (96%) groups were similar; survival without detectable sequelae was similar, at 78% and 77%, respectively. The duration of therapy, 11.1 +/- 2.4 days (range 10 to 21 days) vs 11.9 +/- 3.9 days (range 10 to 21 days), and days to defervescence, 4.7 +/- 2.6 days (range 1 to 14 days) vs 5.6 +/- 2.9 days (range 2 to 17 days), were similar in the cefotaxime and standard therapy groups, respectively. No adverse drug reactions or side effects were noted in either group. Cefotaxime was found to be as safe and effective as standard therapy for the treatment of bacterial meningitis in children. Ceftriaxone, a new third-generation cephalosporin, appears to be promising for the therapy of acute bacterial meningitis. The 90% MBCs of ceftriaxone against 54 recent cerebrospinal fluid isolates of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae were less than or equal to 0.06 to 0.25 micrograms/ml. We examined the efficacy and safety of ceftriaxone therapy of meningitis in Bahia, Brazil. The study was conducted in two phases; in phase A, ceftriaxone was coadministered with ampicillin. The mean cerebrospinal fluid concentrations of ceftriaxone 24 h after an intravenous dose of 80 mg/kg were 4.2 and 2.3 micrograms/ml on days 4 to 6 and 10 to 12 of therapy, respectively. These concentrations were 8- to more than 100-fold greater than the 90% MBCs against the relevant pathogens. In phase B, ceftriaxone (administered once daily at a dose of 80 mg/kg after an initial dose of 100 mg/kg) was compared with conventional dosages of ampicillin and chloramphenicol in a prospective randomized trial of 36 children and adults with meningitis. The groups were comparable based on clinical, laboratory, and etiological parameters. Ceftriaxone given once daily produced results equivalent to those obtained with ampicillin plus chloramphenicol, as judged by cure rate, case fatality ratio, resolution with sequelae, type and severity of sequelae, time to sterility of cerebrospinal fluid, and potentially drug-related adverse effects. The cerebrospinal fluid bactericidal titers obtained 16 to 24 h after ceftriaxone dosing were usually 1:512 to greater than 1:2,048 even late in the treatment course, compared with values of 1:8 to 1:32 in patients receiving ampicillin plus chloramphenicol. Ceftriaxone clearly deserves further evaluation for the therapy of meningitis; the optimal dose, dosing frequency (every 12 h or every 24 h), and duration of therapy remain to be determined. Thirty patients, 25 males and 5 females, aged 16-30 years (mean 21.8 years) with bacterial meningitis were assigned randomly into one of two therapeutic regimens. Patients in Group I received ceftriaxone 100 mg/kg (max 4 g) intravenously (i.v.) once daily. Those in Group II received ampicillin i.v. 160 mg/kg/day plus chloramphenicol i.v. 100 mg/kg/day every 6 h. Of the 15 patients in Group I, N. meningitidis was isolated from 11 patients and S. pneumoniae from 4; and of the 15 patients in Group II, N. meningitidis was isolated from 10 patients and S. pneumoniae from 5. Response to therapy as measured by mortality, time taken for defervescence and for patients to regain full consciousness were comparable in the two groups. One patient in each group died; both died within 24 h of initiation of therapy. The mean no. of days taken to become afebrile were 3.4 and 3.5 and to regain full consciousness were 3.9 and 3.5 for Groups I and II respectively. Ceftriaxone given i.v. appears to be as effective as a combination of ampicillin and chloramphenicol in the treatment of adult patients with meningitis due to N. meningitidis and S. pneumoniae. However, the once-daily schedule of ceftriaxone is more convenient, saving nursing time and expense. nan Eighty-five infants and children were prospectively randomized to receive cefotaxime or ampicillin and chloramphenicol for therapy of bacterial meningitis. The two therapy groups of patients were comparable as to sex, age, clinical status on admission, prior administration of antibiotics and etiology. Three infants (7%) died in each therapy group. Mean number of days of positive cerebrospinal fluid cultures, time to defervescence and duration of treatment and of hospital stay and complications developing during treatment were similar for the two treatment regimens. Median cerebrospinal fluid bactericidal titers against the patients' pathogens in cefotaxime-treated patients (1:64) were larger than those in patients who received conventional therapy (1:8). Mild to moderate motor sequelae were more frequent in those given conventional therapy at the time of discharge only, and not at 4 months or longer of follow-up. We conclude that cefotaxime has similar efficacy when compared with conventional therapy for the management of bacterial meningitis in pediatric patients.
The review shows no clinically important difference between third generation cephalosporins (ceftriaxone or cefotaxime) and conventional antibiotics (ampicillin-chloramphenicol combination, or chloramphenicol alone). Therefore the choice of antibiotic will depend on cost and availability. The antimicrobial resistance pattern against various antibiotics needs to be closely monitored in low- to middle-income countries as well as high-income countries.