Cefuroxime plasma and CSF levels in children with meningitis.

Cefuroxime (25 mg/kg) given intravenously every four hours to 7 children with bacterial meningitis resulted in satisfactory therapeutic blood and CSF levels. All children made a full recovery and side effects were absent.     

Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial

In a multicenter randomized trial, 107 children with bacterial meningitis were initially given either cefuroxime or ampicillin plus chloramphenicol. Patients were alternately assigned to 7- or 10-day courses of the designated antimicrobial regimen. CSF isolates included Haemophilus influenzae type b (89, of which 25% were beta-lactamase positive), Streptococcus pneumoniae, and Neisseria meningitidis. Although mean CSF bactericidal titers against Haemophilus isolates were 1:6 in each treatment group, H. influenzae was cultured from CSF in four of 39 patients receiving cefuroxime, 24 to 48 hours after initiation of therapy, compared with none of 40 patients given ampicillin plus chloramphenicol (P = 0.11). Clinical cure rates were similar (95%); one death occurred in each group. One child given cefuroxime had persistent meningitis after 5 days of therapy, and mastoiditis with secondary bacteremia developed in one on day 10. Three patients had relapse or reinfection. One patient who received cefuroxime for 10 days had a relapse of epiglottitis 17 days later, and of the patients given ampicillin plus chloramphenicol, one had a relapse of meningitis 1 week after 7 days of therapy, and bacteremia developed in one 42 days after completion of 10 days of therapy. No increase in either in-hospital complications or relapses occurred with a 7-day treatment course. Proof of the equivalence of the antibiotic regimens and the efficacy of 7-day courses of treatment, as well as the consequences of delayed CSF sterilization, will require additional investigation.     

Changes in bacterial meningitis.

In 1964, one of us (WHG) undertook a retrospective study of bacterial meningitis in childhood in the north east of Scotland during the period 1946-61. We have recently carried out a similar review of cases occurring during 1971-86, to compare the incidence, mortality, and bacteriological patterns. During the earlier period 285 cases occurred, a total incidence of 16.9/100,000 children per year. In the later period 274 children were affected, an annual incidence of 17.8/100,000. The overall mortality rate fell dramatically from 11.9% to 1.8%, the latter figure comparing favourably with recent published studies from Scandinavia and the United States. There was a change in the bacteriological profile in the second period with a significant rise in cases due to Haemophilus influenzae at all ages. A fall in cases of meningococcal meningitis was significant in infants under 1 year of age only. Possible reasons for the change in the bacteriological pattern are discussed.     

Persistent pleocytosis in bacterial meningitis.

Persistent pleocytosis of greater than 60 white blood cells/mm3 was commonly seen in children adequately treated for bacterial meningitis. It occurred in 13 of 21 (62%) children with Hemophilus influenzae meningitis and in 2 of 9 (22%) with pneumococcal meningitis. Pleocytosis alone cannot be used as an indication of prolonging therapy; significance of persistent pleocytosis is not known.     

Cephalosporins in childhood bacterial meningitis.

Bacterial meningitis remains one of the most common life threatening infections of childhood. There exists a conventional therapy for this disease. However, with the increasing incidence of Haemophilus strains resistant to ampicillin and chloramphenicol and Streptococcus pneumonia strains relatively resistant to penicillin, alteration of current therapeutic regimens for meningitis may become necessary. Cephalosporins were considered as alternatives to the conventional therapy for the treatment of bacterial meningitis during the past decade. However, there are still some discrepancies on the use of these against some organisms despite the advent of the cephalosporins. Thus, a review article analyzing quite a number of reliable clinical trials related to cephalosporins for the treatment of bacterial meningitis during the past decade to date is introduced.     

Epidemiology of bacterial meningitis.

This 10 year retrospective study of all causes of bacterial meningitis for children resident in Nottingham District Health Authority area reports an annual incidence rate per 100,000 children aged 0-16 years of 16.0 (95% confidence interval 14.0 to 18.1). There was a steady increase in incidence from 9.6/100,000 in 1980 to 24.3/100,000 in 1989. This was mainly due to an increase in the incidence of meningococcal infections in the age group 1 month to 5 years. Incidence rates varied with age being: 37.2/100,000 (25.9 to 53.5) for 0-28 days of age, 115.5/100,000 (93.9 to 141.9) for 1-11 months of age, 28.5/100,000 (23.1 to 35.3) for 12-59 months of age, and 2.8/100,000 (1.9 to 4.1) for 5-16 years of age. Overall annual mortality incidence per 100,000 was 1.8 (1.2 to 2.8). For the different age groups this was: 10.1 (4.8 to 21.1) for 0-28 days, 11.5 (6.0 to 22.2) for 1-11 months, 1.0 (0.3 to 3.1) for 12-59 months, and 0.4 (0.1 to 1.2) for 5-16 years of age. There were interactions between the type of meningitis and the year of the infection on the mortality rate. Mortality decreased in those with infections caused by bacteria other than Neisseria meningitidis and Haemophilus influenzae.     

Latex agglutination testing in bacterial meningitis.

The value of the latex agglutination test in meningitis was assessed. This was positive in 60% cases of Streptococcus pneumoniae, 93% of Haemophilus influenzae type b, and 39% of Neisseria meningitidis infections. We cannot support the view that this test was more valuable than Gram staining in partially treated meningitis and cannot recommend its routine use. It may, however, be valuable if Gram staining does not identify an organism or if it suggests meningococcal infection.     

Intussusception associated with bacterial meningitis.

Despite its common association with viral illnesses, intussusception has only rarely been found in the presence of bacterial infections. Two infants are described, both of whom were admitted to hospital with bilious vomiting, drowsiness, and dehydration. Both infants required urgent intravenous volume expansion. Intussusception was confirmed, and reduction was achieved by enema in both cases. Recovery was slow, and one infant developed a seizure. Evidence of meningococcal meningitis was found in both, with septicaemia in one. Neurological outcome is normal to date, and there has been no recurrence of intussusception in either case.     

Cerebrospinal fluid lactic acidosis in bacterial meningitis.

A rapid, microenzymatic method was used to measure cerebrospinal fluid lactate levels in 205 children with suspected bacterial meningitis. Fifty children with normal CSF containing fewer than 0.005 X 10(9)/l WBC, no segmented neutrophils, glucose 3.4 +/- 0.8 mmol/l (61.2 +/- 14.4 mg/100 ml), and a protein of less than 0.30 g/l had CSF lactate levels below 2.0 mmol/l (18 mg/100 ml) (mean and standard deviation 1.3 +/- 0.3 mmol/l (11.8 +/- 2.7 mg/100 ml)). In 31 cases of proved viral meningitis as with 58 cases of clinically diagnosed viral meningitis, levels were below 3.8 mmol/l (34.5 mg/100 ml), being 2.3 +/- 0.6 mmol/l (20.9 +/- 5.4 mg/100 ml), and 2.1 +/- 0.7 mmol/l (19.1 +/- 6.4 mg/100 ml) respectively. Sixty-six cases of bacterial meningitis had CSF lactate levels ranging from 3.9 mmol/l (35.4 mg/100 ml) to greater than 10.0 mmol/l (90.0 mg/100 ml). Longitudinal studies in 7 children with bacterial meningitis showed that cerebrospinal fluid lactate levels differentiated bacterial from viral meningitis up to 4 days after starting treatment with antibiotics. Use of CSF lactate measurement for monitoring the efficacy of treatment is illustrated in a case of bacterial meningitis due to Pseudomonas aeruginosa. The origin of the cerebrospinal fluid lactate acidosis and the role of lactate in the pathophysiological cycle leading to intensification of brain tissue hypoxia and cellular damage is discussed with respect to the short-term prognosis and the long-term neurological sequelae.     

Thrombocytosis and thrombocytopenia in childhood bacterial meningitis.

To assess factors affecting the development of reactive thrombocytosis during bacterial meningitis, thrombocyte counts of 311 children with cerebrospinal fluid culture-positive bacterial meningitis were followed during hospitalization. Thrombocytosis (platelet counts greater than 500 x 10(9)/liter) was seen in 49% of the patients after the first week of treatment. Thrombocyte counts were higher in infants and in patients with long duration of illness before admission. Subdural effusion and cephalosporin therapy were associated with more pronounced thrombocytosis We found no relation between thrombocytosis and neurologic complications, but the patients who died developed thrombocytopenia instead of thrombocytosis. The difference between the thrombocyte curves of the surviving and dying patients might be utilized in predicting the final outcome in the severest cases of bacterial meningitis. We speculate that inflammatory cytokines, especially interleukin 1-beta, induce reactive thrombocytosis in bacterial meningitis.     

Neonatal bacterial meningitis

Despite major improvements in infant intensive care, neonatal meningitis remains a devastating disease. Survivors of bacterial meningitis are at high-risk for life-long neurological handicaps, and despite a reduction in mortality, the morbidity of neonatal meningitis has not changed substantially over the last thirty years. A substantial improvement in outcome is unlikely to result from further refinements in ICU technology or new antibiotics. However, recent advancements in our understanding of the pathogenesis of meningitis and the pathophysiology of brain injury in meningitis may provide the opportunity to interrupt the mechanisms that allow bacteria to enter the central nervous system and initiate the inflammatory response. Strategies aimed at modulating the inflammatory response must be chosen carefully, so as not to disrupt normal host responses needed for the infant to recover from the infectious episode.