Daphne E. Holt

Neonatal meningitis in England and Wales: 10 years on.

OBJECTIVES To determine the incidence of neonatal meningitis in England and Wales. DESIGN A national postal survey using the British Paediatric Surveillance Unit (BPSU) card scheme supplemented by information from other sources. SETTING England and Wales 1996–1997. SUBJECTS A total of 274 babies less than 28 days of age who were treated for meningitis. RESULTS The incidence of neonatal meningitis in England and Wales has not changed since our previous study in 1985–1987. However, the acute phase mortality has fallen from 19.8% in 1985–1987 to 6.6% in this study. Group B streptococci (42%) and Escherichia coli(16%) remain the most common infecting microorganisms. Eight of 69 (12%) babies with group B streptococci and 4/26 (15%) withE coli died. Antibiotic regimens based on the third generation cephalosporins, notably cefotaxime, were most commonly used (84%). The BPSU scheme identified 72% of cases during the study period. Most cases of viral meningitis were not reported through the BPSU. Less than a third of samples from aseptic meningitis were examined for viruses; 56% of these were positive. CONCLUSIONS Although the incidence of neonatal meningitis remains unchanged, mortality from this infection has fallen significantly. If this improvement is maintained as reflected in the level of sequelae at 5 years of age, then the fear surrounding meningitis during the neonatal period will have been dramatically reduced.

Bacterial Meningitis in the Newborn: A Prospective Study of Mortality and Morbidity

Neonatal bacterial meningitis is a serious disease around the world, with the incidence changing little in the past 30 years. Group B streptococci, Escherichia coli, and Klebsiella pneumoniae are common causative organisms and lumbar puncture remains the definitive method of diagnosis. The mortality rate has declined in industrialized countries over the years, from almost 50% in the 1970s to less than 10% in 1997. However, neurological sequelae are still frequently observed despite major changes in treatment. Preliminary analysis of our own data from a prospective study of cases in the United Kingdom suggests that treatment with third generation cephalosporins is related to a decrease in mortality but not morbidity.

Long term follow up after meningitis in infancy: behaviour of teenagers

Aims: To determine the effects of meningitis in infancy on subsequent teenage behaviour. Methods: A national postal survey of parents and teachers using an established standard behavioural questionnaire. Subjects were 739 of the surviving children from the national incidence study of infantile meningitis in England and Wales carried out between 1985 and 1987, together with a group of 606 matched controls that had been recruited when the index cases were 5 years old. Results: 46% of parents of children who had had meningitis with complications in infancy, compared with 21% of parents of control children rated their children as having behavioural problems. When the children were rated by their teachers, 37% and 23% respectively, were scored as having behavioural problems. There was no significant difference in behaviour between the 103 children who had had meningitis during the first month of life and the 634 who had had postneonatal meningitis. Eight of the index children had been excluded from school compared to none from the control group. Conclusions: The behaviour of teenage children who had meningitis in infancy is worse than that of control children who did not have infantile meningitis when rated by parents and teachers.

Metabolism of Chloramphenicol by Glutathione S-Transferase in Human Fetal and Neonatal Liver

The glutathione S-transferases of human fetal and neonatal liver catalyse the conjugation of glutathione with chloramphenicol at a low but measurable rate. The highest rates were 1.30 nmol/min/mg protein in a preterm neonate of 26 weeks of gestation and 1.11 nmol/min/mg in a fetus of 22 weeks of gestation, while the lowest measurable was 0.1 nmol/min/mg in a fetus of 17 weeks of gestation. The activity did not correlate with gestational age, but appeared dependent on the concentration of glutathione in the reaction mixture. The rate rose by a factor of three, from 0.39 nmol/min/mg protein with no added glutathione to 1.24 nmol/min/mg with 2 mumol/ml added to the reaction mixture. Chloramphenicol-aldehyde was detectable in the reaction mixture when a liver extract was incubated with glutathione but the proposed intermediate, glutathione-chloramphenicol, could not be demonstrated. Differences in activity with chloramphenicol or a model substrate, under varying conditions, indicate that different isoenzymes are concerned with the conjugation of glutathione to the two substrates. These data support the hypothesis that when glucuronide conjugation is depressed by immaturity, chloramphenicol is metabolised via other pathways.

The Presence and Significance of the Pi Class Glutathione S- Transferase Isoenzyme in Cerebrospinal Fluid during the Course of Meningitis in Children

A rise in the concentration of the Pi class isoenzyme of glutathione S- transferase (GST) in the cerebrospinal fluid (CSF) during meningitis may be an early indicator of inflammation and cell damage. Pi class GST concentrations were measured in 48 samples of CSF from 46 children with proven or suspected meningitis using a commercially available immunoassay. Forty-four fetal brain samples were assayed by isoelectric focusing to determine the nature and number of isoenzymes likely to be released. Twenty-four percent of children had measurable amounts of the isoenzyme in their CSF during the initial stages of the disease. One child, for whom CSF samples were taken pre-, mid-, and post-antibiotic treatment, had measurable Pi class GST in the CSF only in the mid-treatment sample, when bacterial lysis and inflammation are likely to be at their peak. Where follow-up data were available, two of three children with measurable Pi class GST in their CSF at the initial stages had recordable disabilities at 5 y of age compared with 4 of 11 of those in whom no Pi class GST was detected. Two proteins analogous to Pi class GST were detected in frozen brain tissue, but only one was active with a known substrate; only the active protein was seen in fresh tissue. We conclude that 1) initial high levels of CSF Pi class GST may be an indicator of the severity of inflammation and thus of prognostic significance and 2) only one Pi class GST occurs in brain tissue.

The placental transfer of cefuroxime at parturition

Maternal and fetal serum concentrations of cefuroxime were determined at birth in 39 women who were given a single intravenous dose of either 750 mg or 1500 mg of cefuroxime before delivery. Mean serum cefuroxime concentrations in maternal venous and umbilical venous blood were dose dependent, being significantly higher after 1500 mg of cefuroxime (55.0 mg/l, 95% CI 33.4-80.9 and 19.5 mg/l, 95% CI 9.5-26.3, respectively) than after 750 mg (14.7 mg/l, 95% CI 10.5-21.1 and 8.8 mg/l 95% CI 5.8-9.4, respectively). Antibiotic concentration in maternal blood correlated with sampling time but a similar relationship was not found in cord blood. Fetal concentrations did not correlate with mode of delivery or initial maternal blood pressure. No relationship could be demonstrated between cefuroxime concentration in maternal or cord blood and maternal weight, maternal weight gain, birthweight of baby or volume of fluid infused prior to epidural anaesthesia. It is concluded that maternal and fetal concentrations likely to be effective for prophylaxis before delivery require a maternal dose of 1500 mg of cefuroxime and are independent of these physiological variables.