Dexamethasone treatment for bacterial meningitis

In the pre-antibiotic era more than 9096 of children with bacterial meningitis died from their disease. The introduction of antibiotics and intensive care reduced mortality to approximately 5%, but significant morbidity remained. A prospective study of 50 children who recovered from Haemophilus influenzae type b meningitis reported that 28% had significant physical or intellectual disabilities 3 years after their illness.¹ The failure of new and more powerful antibiotics to improve the outcome of meningitis meant that other treatment modalities needed to be evaluated.     

Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin.

BACKGROUND: Trovafloxacin is a new fluoroquinolone that exhibits good penetration into the central nervous system and excellent antimicrobial activity against common meningeal pathogens, including beta-lactam-resistant pneumococci. PURPOSE AND DESIGN: A multicenter, randomized clinical trial was conducted in children with bacterial meningitis to compare the safety and efficacy of trovafloxacin with that of ceftriaxone with or without vancomycin therapy. RESULTS: A total of 311 patients, ages 3 months to 12 years, were enrolled, of whom 203 were fully evaluable, 108 treated with trovafloxacin and 95 with the conventional regimen. Both groups were comparable with regard to baseline characteristics: age; cerebrospinal fluid findings; use of dexamethasone; history of seizures; and etiologic agents. No significant differences between trovafloxacin and the comparator, respectively, were detected in any of the following outcome measures: clinical success at 5 to 7 weeks after treatment (79% vs. 81%); deaths (2% vs. 3%); seizures after enrollment (22% vs. 21%); and severe sequelae (14% vs. 14%). Only 4 of 284 children developed joint abnormalities up to 6 months after treatment, 1 (0.9%) child received trovafloxacin and 3 (3.1%) received the comparator regimen. None of the evaluable patients experienced significant abnormalities of liver function during treatment. One nonevaluable patient who received trovafloxacin for 5 days and ceftriaxone for 11 days was readmitted to the hospital with hepatitis of unknown etiology 1 day after discharge. The episode resolved with liver function tests returning to normal within 2 months. CONCLUSIONS: We conclude that trovafloxacin is an effective antibiotic for treatment of pediatric bacterial meningitis. These favorable results support further evaluation of fluoroquinolone therapy for children with meningitis or other serious bacterial infections.     

Seven days vs. 10 days ceftriaxone therapy in bacterial meningitis

Ceftriaxone is recommended in children with acute bacterial meningitis (ABM) for 10 days. However, the drug is expensive, and shorter duration of therapy, if equally effective, would cut costs of therapy and hospitalization. The aim of this study was to compare the outcome of 7 days vs. 10 days' ceftriaxone therapy in children with ABM. Seventy-three children aged 3 months to 12 years with ABM, consecutively admitted to hospital were enrolled. Ceftriaxone was given for 7 days to all. Randomization to group I (7 days) and group II (10 days) therapy was done on the seventh day. At the end of 7 days' therapy in group I and 10 days in group II, children were evaluated using a clinical scoring system. Children with a score of more than 10 were labelled as 'treatment failures' and were continued on ceftriaxone. If a score was less than 10, the antibiotic was stopped. Complications were appropriately evaluated and managed. All children were followed-up 1 month after discharge: neurodevelopmental assessment, Denver Development Screening Tests, IQ and hearing assessment were done. After excluding four patients, there were 35 children in group I and 34 in group II. The two groups were comparable with respect to age, sex, nutritional status, presenting clinical features, and CSF parameters. Organism identification was possible in 38 per cent of children: (Streptococcus pneumoniae, 21 per cent; Haemophilus influenzae, 13 per cent; meningococcus, 4 per cent). Treatment failure rate was comparable in both groups (9 in group I and 8 in group II) as was the sequelae at discharge and at 1 month (9 in group I, 15 in group II,p > 0.1). Status epilepticus and focal deficits at presentation were significantly associated with treatment failures and sequelae in both the groups (p < 0.05). Length of hospital stay was shorter in group I (10.8 +/- 6.0 days) as compared with group II (14.4 +/- 7.2 days,p < 0.05) and frequency of nosocomial infection was significantly more in group II (p < 0.05). It was concluded that clinical outcome of patients treated with 7 days' ceftriaxone therapy is similar to that of 10 days' therapy, and is associated with lesser nosocomial infection and earlier hospital discharge. Seven days ceftriaxone therapy may be recommended for uncomplicated ABM in children in developing countries.     

Diagnosis and treatment of bacterial meningitis

This review focuses on recent advances of topical interest regarding the diagnosis and treatment of common causes of bacterial meningitis occurring in children beyond the neonatal period. Tuberculous meningitis is beyond the scope of this review.     

Randomized trial of four vs. seven days of ceftriaxone treatment for bacterial meningitis in children with rapid initial recovery

BACKGROUND: Seven days or more of antimicrobial treatment is the standard for bacterial meningitis, although third generation cephalosporins are usually able to sterilize cerebrospinal fluid within 24 h. The limited experience from shorter regimens in children is encouraging, and we hypothesized that in rapidly recovering patients older than 3 months of age it would pose no risk for adverse outcome. METHODS: Strict clinical and laboratory criteria were used to define rapid initial recovery, in which case ceftriaxone therapy was either stopped after 4 days (4 injections) in children born on even dates (N = 53) or continued for 7 days in patients born on odd dates (N = 47). Outcomes were compared on Day 7 of hospitalization and at 1 to 3 months after discharge. RESULTS: On Day 7 no differences (P > 0.05 for each criteria) were observed between the 4-day and the 7-day groups regarding fever, clinical signs or serum C-reactive protein concentration. At the follow-up visit 1 to 3 months after discharge the 4-day group had fewer sequelae than the 7-day group (0% vs. 5% neurologic sequelae, P = 0.39 and 3% vs. 9% hearing loss, P = 0.49, respectively). One child in the 4-day group who had fully recovered was subsequently readmitted 53 days after the first hospitalization with recurrent Haemophilus influenzae meningitis. CONCLUSIONS: Four days of ceftriaxone therapy proved to be a safe alternative in patients with rapid initial recovery from bacterial meningitis. A 4-day course of treatment is particularly beneficial for countries with limited resources.     

Once daily ceftriaxone for meningococcemia and meningococcal meningitis

Twenty children with meningococcal disease (15 with meningococcal meningitis and 5 with meningococcemia without meningitis) were treated with ceftriaxone, 80 to 100 mg/kg/day for 4 days. An additional 22 patients with meningococcal disease (13 with meningitis, 9 with meningococcemia without meningitis) were treated with penicillin G. On the basis of the Damrosch-Stiehm scoring system, 19 patients were classified in the poor prognostic group and were treated with antishock therapy. Clinical recovery time and normalization of CSF were compared in two groups. When the complications were compared, necrotic skin lesions were more frequently seen in the penicillin G group than in those who received ceftriaxone. Ceftriaxone is an effective and safe drug and offers the advantage of once daily administration for treatment of meningococcal disease in pediatric patients.     

Diagnosis and treatment of bacterial meningitis.

This review focuses on recent advances of topical interest regarding the diagnosis and treatment of common causes of bacterial meningitis occurring in children beyond the neonatal period. Tuberculous meningitis is beyond the scope of this review.     

Dexamethasone treatment for bacterial meningitis in children and adults

Four hundred twenty-nine patients with bacterial meningitis were assigned on a nonselective alternating basis into one of two therapeutic regimens. Patients in Group I received dexamethasone in addition to standard antibacterial chemotherapy of ampicillin and chloramphenicol whereas those in Group II received antibacterial chemotherapy alone. Dexamethasone was given intramuscularly (8 mg to children younger than 12 years and 12 mg to adults every 12 hours for 3 days). Both treatment groups were comparable with regard to age, sex, duration of symptoms and state of consciousness at the time of hospitalization. A significant reduction in the case fatality rate (P less than 0.01) was observed in patients with pneumococcal meningitis receiving dexamethasone; only 7 of 52 patients died compared with 22 of 54 patients not receiving dexamethasone. A reduction in the overall neurologic sequelae (hearing impairment and paresis) was observed in patients receiving dexamethasone. This reduction was significant only in patients with Streptococcus pneumoniae meningitis; none of the 45 surviving patients receiving steroids had hearing loss whereas 4 of 32 patients not receiving dexamethasone had severe hearing loss (P less than 0.05). No significant difference was observed between the two groups with regard to time for patients to become afebrile or to regain consciousness or in the mean admission and 24- to 36-hour cerebrospinal fluid leukocyte count, glucose or protein content.     

Erythema migrans after ceftriaxone treatment of aseptic meningitis caused by Borrelia burgdorferi

Erythema migrans is the characteristic exanthem of Lyme disease. The rash initially occurs at the site of inoculation; subsequently satellite lesions can occur. We describe an adolescent girl in whom the rash appeared after the initiation of ceftriaxone therapy for aseptic meningitis. We suggest that the occurrence of rash in this patient was a result of liberated toxin from local bacterial lysis.     

In vitro antibiotic sensitivity pattern of common bacterial isolates from cases of acute bacterial meningitis with special reference to ceftriaxone

Ceftriaxone (RO 13-9904) has only recently been introduced in Benghazi and many parts of the word. We determined itsin vitro antibacterial activity against the primary aetiological agents of childhood meningitis in Benghazi, that included eighteen (23.3%) strains ofH. influenzas, 17 (22.1%) ofStr. pneumoniae and 1 (1.3%) ofN. meningitidis isolated from 77 cases of acute purulent meningitis above the age of neonatal period. All strains ofH. influenzae. Str. pneumoniae andN. meningitidis were sensitive to ceftriaxone and showed wide zones of inhibition by the disc diffusion technique of Kirby-Bauer. Ampicillin and chloramphenicol resistance was observed forH. influenzae (23% and 11% respectively), andStr. pneumoniae (12% and 0% respectively), in addition, 18% of strains ofStr. pneumoniae showed resistance to penicillin. The broad spectrum activity of ceftriaxone has been confirmed for our locality and this finding, together with its exceptionally long half-life, excellent penetration into the C.S.F. and ease of administration (single daily dose) warrants it as the drug of choice in empherical treatment of cases of acute bacterial meningitis in children in Benghazi and in cases where resistance to ampicillin and chloramphenicol are found on subsequent testing.     

Chloramphenicol or ceftriaxone, or both, as treatment for meningitis in developing countries?

AIMS: To determine in children with meningitis whether there is any difference in mortality and neurological sequelae using chloramphenicol as first line treatment, with a change to ceftriaxone if chloramphenicol resistance is shown in vitro, compared to using ceftriaxone as first line treatment, with a change to chloramphenicol if there is no evidence of in vitro resistance. METHODS: An observational study with a retrospective control group nested within a randomised trial of fluid management for bacterial meningitis where clinical care was standardised. Chloramphenicol is standard treatment for bacterial meningitis in Papua New Guinea. In the first 150 cases we used chloramphenicol and only changed treatment to ceftriaxone if chloramphenicol resistance for cerebrospinal fluid isolates was proved. After finding 20% of Haemophilus influenzae were resistant to chloramphenicol, and that most affected children had poor outcomes, we changed to an alternative strategy. In the next 196 cases first line treatment was ceftriaxone and treatment was changed to chloramphenicol if the isolated bacteria were found to be susceptible. RESULTS: When chloramphenicol was used as first line treatment for meningitis followed by ceftriaxone when in vitro resistance was shown, there was invariably a very poor outcome in chloramphenicol resistant disease (71% of children died or had severe neurological complications). Using ceftriaxone as first line treatment was effective in reducing mortality and neurological sequelae from chloramphenicol resistant Haemophilus influenzae type (71% v 9%, relative risk 0.13; 95% CI 0.02 to 0.87; p = 0.013). Changing to chloramphenicol if there was no evidence of in vitro resistance was less than half the cost of empirical use of ceftriaxone for a full course for all children with meningitis. CONCLUSIONS: Using a third generation cephalosporin as first line treatment is effective in dealing with the problem of poor outcomes from meningitis due to Haemophilus influenzae that is resistant to chloramphenicol, and a strategy of changing to chloramphenicol if in vitro susceptibility is shown will reduce the use of expensive third generation cephalosporins without comprising on clinical outcomes. This highlights the urgent need to reduce the costs of third generation cephalosporins, to improve bacteriological services in developing countries, and to introduce effective and affordable vaccines against H influenzae and Streptococcus pneumoniae.     

Antibiotic treatment for bacterial meningitis in children in developing countries

Bacterial meningitis causes 125,000 deaths each year in infants and young children and 96% of these occur in less developed countries where up to 50% of children with this disease die and 25-50% of survivors have neurological sequelae. Although 3rd-generation cephalosporins are optimal empirical therapy for bacterial meningitis, they are unaffordable in many developing countries. The majority of children worldwide are currently treated with cheaper alternatives. This paper reviews the challenges facing clinicians treating bacterial meningitis in developing countries, highlighting the problem of changing patterns of antibiotic resistance. In particular, it details the evidence for the use of chloramphenicol and 3rd-generation cephalosporins.     

Dexamethasone as an adjunctive treatment of bacterial meningitis

This study was conducted on 77 Libyan infants and children aged month to 10 years with acute bacterial meningitis. Upon admission, the patients were divided randomly in two groups. Group I (38 patients) received ceftriaxone plus dexamethasone I.V. Group II (39 patients) received ceftriaxone alone. Both groups were compared for mean changes in CSF sugar, CSF protein and CSF polymorph count at 4th day of treatment. There was a significant difference between the two groups in CSF sugar and protein changes (P < 0.05) but not in CSF polymorph (P > 0.05). Both groups showed prompt clinical response and similar occurrence of acute complications, fatality rate and permanent neurological sequelae. However, group I manifested shorter duration of fever (P < 0.05). Dexamethasone improved the inflammatory reaction in acute bacterial meningitis and shortened the duration of fever but it did not have any significant effect on the fatality and the occurrence of neurological sequelae of this disease.     

Pharmacokinetics of ceftriaxone in neonates and infants with meningitis

The pharmacokinetics of ceftriaxone was studied in the plasma, urine, and cerebrospinal fluid of seven neonates and seven infants with meningitis. In addition, plasma and urine data were obtained in five neonates and one infant receiving ceftriaxone for other serious infections. All neonates younger than 14 days received daily doses of 50 mg/kg ceftriaxone; all other patients but two received 100 mg/kg. The average weight-corrected values for total body clearance (ClT), volume of distribution (Vdss), and biologic half-life (t 1/2) were 0.37 ml/min/kg, 0.45 L/kg, and 16.2 hours in neonates younger than 1 week; 0.77 ml/min/kg, 0.48 L/kg, and 9.2 hours in neonates older than 1 week; and 1.03 ml/min/kg, 0.39 L/kg, and 7.1 hours in older infants, respectively. There was a significant difference in ClT and t 1/2 between the neonates younger and both neonates older than 1 week, and infants. The Vdss was not significantly different among the three age groups. The average renal clearance in neonates younger than 1 week (0.28 ml/min/kg was 70%, in neonates older than 1 week (0.54 ml/min/kg) was 77%, and in older infants (0.49 ml/min/kg) was 47% of ClT, indicating that nonrenal elimination was less developed in neonates. The quantitation of CSF diffusion of ceftriaxone was assessed by comparison of the areas under the CSF and plasma concentration-time curve. The mean ceftriaxone penetration into the CSF in neonates and infants with bacterial meningitis was 17%. On the other hand, penetration in patients with aseptic meningitis amounted to only 4%. Mean ceftriaxone concentrations in the CSF in patients with bacterial meningitis were 2.8 mg/L after 24 hours, exceeding by many times the minimum inhibitory concentration of the common meningitis pathogens at this time.