D Harvey

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.

Infantile meningitis in England and Wales: a two year study.

A two year prospective study identified 1922 cases of meningitis in children under 1 year of age. A further 201 cases were identified from other sources. The annual incidence of meningitis during the first year of life was 1.6/1000; during the first 28 days of life it was 0.32/1000, and among postneonatal infants it was 1.22/1000. The male:female ratio was 1.4:1. The overall case fatality rate was 19.8% for neonates and 5.4% for postneonatal infants. Two thirds of deaths identified in the study, 50% of all deaths, were not attributed to meningitis by the Office of Population Censuses and Surveys. Group B beta haemolytic streptococci (28%), Escherichia coli (18%), and Listeria monocytogenes (5%) were most frequently isolated from neonates and Neisseria meningitidis (31%), Haemophilus influenzae (30%), and Streptococcus pneumoniae (10%) from postneonatal infants. At 2-6 months of age N meningitidis meningitis was most common, and at 7-12 months H influenzae predominated. Meningitis caused by group B beta haemolytic streptococci occurred up to 6 months of age and had a consistent mortality of 25%. Neonatal meningitis due to Gram negative enteric rods had a mortality of 32%. Low birth weight was a significant predisposing factor for both neonates and postneonatal infants. In both groups mortality was significantly higher among children admitted in coma. There was no seasonal variation in incidence in either group. Neonates were treated with either group. Neonates were treated with either chloramphenicol (50%) or gentamicin (48%) usually in combination with a penicillin; 40% received a third generation cephalosporin. Of the 1472 postneonatal infants treated 84% received chloramphenicol with a penicillin and 10% received a third generation cephalosporin. Relapse occurred in 49 patients and three died. Eighteen babies coned as a result of raised intracranial pressure, including four neonates, and four died. Mortality among the 133 (7%) children who received steroids was significantly higher than in the rest of the study group.

Neonatal meningitis in England and Wales: sequelae at 5 years of age

This study determined the prevalence of serious sequelae among a national cohort of 5-year old children, born in England and Wales in 1996–7, who had had neonatal meningitis. The results were compared with those from two matched control groups. In addition the results from this study were compared with those from a previous 5-year follow-up of children who had had neonatal meningitis in 1985–7. Follow-up questionnaires requesting information about the children’s health and development were sent to the general practitioners (GPs) and parents of the index children and controls. Information was collected on 166 of 232 (72%) children who had had meningitis as neonates, 109 general practice controls and 191 hospital controls. At 5 years, 39/166 (23%) index children had a serious disability compared to 2% of GP controls and 7% of hospital controls. There was a 16-fold increase in risk of serious disability compared to GP-matched controls and a 4-fold increase in risk compared to hospital controls. The isolation of bacteria from the CSF was the best single predictor of serious long-term disability. Although there was a 70% fall in acute phase mortality between 1985 (22%) and 1996 (6.6%), the overall incidence of serious disability remained alarmingly high, 25.5% in 1985 compared to 23.5% in 1996. In the present study, however, fewer children had cerebral palsy or seizure disorders. Conclusion:Despite the dramatic improvement in acute phase survival following neonatal meningitis, the prevalence of serious sequelae remains alarmingly high.

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.

Effect of meningitis in infancy on school-leaving examination results

Objectives: To determine whether having had meningitis in infancy adversely affects academic achievement at age 16. Methods: A case–control study in England and Wales of 461 teenagers who had bacterial meningitis in infancy and 289 GP matched controls recruited when the index cases were aged 5. Outcome measures: Comparison between index cases and controls of the type of school attended; the number of GCSE examinations attempted; the number of examinations passed (grades A*–C) and achievement in five key subjects. Assessment of examination results according to the age at which meningitis occurred. The effect of meningitis-associated disability on GCSE results. Results: 36/461 (7.8%) index cases compared with none of the controls were in special schools. Significantly more index cases (117/461 (25.4%)) than controls (19/289 (6.6%)) did not pass any GCSE examinations. Significantly more index cases (184/385 (47.8%)) than controls (59/232 (25.4%)) attending comprehensive schools failed to achieve the national educational standard of five passes at grade C. Pupils attending comprehensive schools who did not have meningitis-associated disability also passed significantly fewer GCSE examinations than the controls. The age at which meningitis had occurred was not associated with subsequent academic achievement. Conclusions: After meningitis in infancy a quarter of survivors failed to pass any GCSE examinations; nearly half of those attending state schools did not attain the national educational standard. “Healthy” survivors of bacterial meningitis in infancy pass significantly fewer GCSE examinations than the controls. All cases of bacterial meningitis in infancy should have a full postinfection assessment and continuing supervision.

Transplacental Transfer of Cefuroxime in Uncomplicated Pregnancies and Those Complicated by Hydrops or Changes in Amniotic-Fluid Volume

The transplacental transfer of cefuroxime was determined at antenatal fetal blood sampling in a cross sectional study of 78 patients between 15-35 weeks gestation, 8-138 minutes after a maternal intravenous dose of 750 mg. Mean serum cefuroxime concentration, measured by high performance liquid chromatography, was 7.4 (95% confidence interval (CI) 6.8 to 8.1) mg/l in control fetuses; concentrations in hydropic fetuses were similar (6.2 mg/l, CI 4.7 to 7.7) but in fetuses with oligohydramnios they were significantly lower, (4.9 mg/l, CI 3.6 to 6.2). Antibiotic concentration did not correlate with gestational age and remained unchanged by transfusion of packed red cells. We conclude that (i) fetal serum concentrations of cefuroxime obtained after a maternal dose of 750 mg are only adequate for prophylaxis against organisms with a minimum inhibitory concentration of < 4 mg/l and (ii) transplacental passage of cefuroxime is significantly reduced in the presence of oligohydramnios.

C-reactive protein response in utero

SummaryC-reactive protein concentration was determined by enzyme immunoassay in fetal serum (gestational ages 15–38 weeks) from a group of 91 patients undergoing fetoscopy. Matched amniotic fluid or maternal serum samples were obtained from the majority of these patients. C-reactive protein levels were also determined in 90 cord serum samples (gestational ages 29–42 weeks) from uneventful deliveries, forceps deliveries, caesarean sections and vaginal deliveries where maternal pyrexia was recorded.C-reactive protein concentration ranged from > 10–200 μg/1 in 91 per cent of fetal and cord serum samples. The protein is present in fetal serum as early as 15 weeks of gestational age. In fetuses > 20 weeks, 50 per cent had serum levels < 10 μg/1 and 36 per cent had serum levels < 200 μg/1. Throughout pregnancy the fetus can produce an apparently independent C-reactive protein response following intra-uterine stimulation. Raised fetal levels are associated with both raised amniotic fluid and raised maternal seru...

68 Treatment of Neonatal Sepsis |[ndash]| A Multicentre, International Study

1316 neonates with clinical signs of sepsis were randomised to receive ceftazidime (CAZ) or gentamicin plus ampicillin (GENT + AMP) in standard doses between Feb 88 and Nov 89. Those centres with a high incidence of Listeria or enterococcal infection added AMP to the CAZ arm. Some centres substituted tobramycin or amikacin for CENT dependant on resistance patterns. 176 (13.4%) had bacteriological proven infection and 489 (37.2%) had strong clinical evidence including an abnormal WBC band count ≥2 or CRP ≥20mg/L. The remaining 651 (49.4%) neonates with weak evidence of infection were analysed for safety. Comparisons of the demographic and baseline data were similar. Cure rates for the bacteriological and clinical populations were 119/146 (82%) for CAZ, 169/184 (92%) for CAZ + AMP and 278/335 (83%) for GENT + AMP (or alternative aminoglycosides). The major pathogens isolated from CSF and blood were Group B streptococci, S. epidermidis and S. aureus and those from urine were E. coli. Drug related adverse events were low for both treatment regimens with only one patient (GENT) requiring to be withdrawn. 8 patients receiving CAZ or CAZ + AMP and 7 patients receiving GENT + AMP died of their infection (23 and 27 neonates respectively died due to their underlying disease). Neonatal sepsis can be efficaciously treated with CAZ, a safe bd alternative to GENT + AMP.