John de Louvois

Meningitis in infancy in England and Wales: follow up at age 5 years

Abstract Objective: To describe important sequelae occurring among a cohort of children aged 5 years who had had meningitis during the first year of life and who had been identified by a prospective national study of meningitis in infancy in England and Wales between 1985 and 1987. Design: Follow up questionnaires asking about the childrens health and development were sent to general practitioners and parents of the children and to parents of matched controls. The organism that caused the infection and age at infection were also recorded. Setting: England and Wales. Participants: General practitioners and parents of children who had had meningitis before the age of 1 year and of matched controls. Main outcome measures: The prevalence of health and developmental problems and overall disability among children who had had meningitis compared with controls. Results: Altogether, 1584 of 1717 (92.2%) children who had had meningitis and 1391 of 1485 (93.6%) controls were successfully followed up. Among children who survived to age 5 years 247 of 1584 (15.6%) had a disability; there was a 10-fold increase in the risk of severe or moderate disability at 5 years of age among children who had had meningitis (relative risk 10.3, 95% confidence interval 6.7 to 16.0, P<0.001). There was considerable variation in the rates of severe or moderate disability in children infected with different organisms. Conclusion: The long term consequences of having meningitis during the first year of life are significant: 32 of 1717 (1.8%) children died within five years. Not only did almost a fifth of children with meningitis have a permanent, severe or moderately severe disability, but subtle deficits were also more prevalent. What is already known on this topic Meningitis in infancy is associated with important long term consequences There is considerable variation in outcome depending on which organism caused the infection What this study adds This follow up study of 1717 children who had meningitis in infancy found that they had a 10-fold increase in risk of severe or moderate disabilities at age 5 years compared with children in the control group The outcome of having meningitis was associated with the age at infection, and children who had meningitis in the neonatal period were more likely to have health and development problems than those older than 1 month Subtle deficits, such as middle ear disease and visual and behavioural problems, were more prevalent among children who had had meningitis in infancy

The Bacteriology and Chemotherapy of Acute Pyogenic Brain Abscess

Incidence and mortality Pathogenesis Bacteriology Penetration of antibiotics into the brain Antimicrobial treatment of brain abscess Conservative management

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.

ANTIBIOTIC CONCENTRATIONS IN INTRACRANIAL PUS: A STUDY FROM A COLLABORATIVE PROJECT*

The notion of monitoring antibiotic therapy for brain abscess is a relatively unfamiliar one in neurosurgical practice, and there is little information on its value as a guide to therapy. Studies on the penetration of antibiotics into brain tissue are few (Wellman et al., 1953; Ruedy, 1960) and, so far as we are aware, levels of antibiotics in brain abscess cavities have been reported only in one series of six patients (Black et al, 1973). The nature of the blood-brain barrier itself remains a mystery (Eckman et al, 1958) and, although cerebrospinal fluid levels of antibiotics have been measured relative to serum concentration, the gradient between blood and brain tissue has yet to be established for almost all antibiotics. Ancillary to a wider study on the pathogenesis and course of brain abscess, undertaken experimentally and in collaboration with neurosurgeons at nine centres in England and Wales, we have sought to establish reliable methods for the assay of antimicrobial drugs in pus.

13. MENINGITIS DURING THE FIRST YEAR OF LIFE - A TWO YEAR STUDY

During the period September 1985 - August 1987, 653 consultant paediatricians in the UK and Eire cooperated in a prospective study by providing clinical information on cases of meningitis in children under one year of age. Additional information was collected from microbiologists, the CDSC and OPCS. 2498 cases of meningitis were reported; M/F ratio 1.3/1. 484 occurred during the neonatal period of which 360 were bacteriologically proven - 1/3250 live births. Group B streptococci (GBS) (25%) and E. coli (17%) were the commonest isolates. H. influenzae, Str. pneumoniae and N. meningitidis accounted for 13% of cases and L. monocytogenes for 5%. In 48% of neonates treatment was based on chloramphenicol, in 24% on gentamicin and in 14% on cefotaxime. The overall mortality among the newborn was 20% (ranging from 30% with enteric G -ve rods, 5% with listeria to 0% with viruses). Culture negative cases of meningitis had a 3% mortality. Among babies older than 28 days Str pneumoniae (12%), H. influenzae (36%) and N. meningitidis (34%) accounted for 82% of cases and E. coli or GBS for 6%. Mortality among babies over one month of age was 5%. There was a geographical variation in incidence. This is the largest comprehensive study in the British Isles. Information on the long term morbiditty associated with infantile meningitis is now being collected.