[Therapeutic strategies for Escherichia coli neonatal meningitis]

Outcome of early and late onset E. coli neonatal meningitis is poor with 12% (term infant) to 18% (premature infant) mortality rates. Early complications are cerebral abscesses, ventriculitis and ischemo-haemorragic cerebral lesions. Long term sequelae, particularly neurosensorial [14-17%] and neurodevelopmental [10-17%] are frequent. Delayed or unadapted antibiotic treatment is associated with an excess of complications. Main risk factors are hemodynamic failure, apnea, seizures, hypoglycorachia and abnormal EEG. Antibiotics must be started as soon as possible with a third generation cephalosporin (3GC). Cefotaxime is the most largely 3GC used with good tolerance and the most appropriate Pk/PD parameters, frequently in association with ciprofloxacin. Experimentally, neuroprotective drugs were recently proposed to improve prognosis such as inflammatory inhibitors, leakage bacterial components inhibitors, PMN penetration inhibitors in CSF, apoptosis regulators. Clinically protective effect of corticosteroids is discussed. Ciprofloxacin has an intrinsic anti-inflammatory activity and seems interesting to use in addition to conventional antibiotherapy during the first days of treatment. Prevalence of 3GC-resistant E. coli is 5% in the vaginal flora of pregnant women in some hospitals in France; this rate leads to reconsider first line antibiotic treatment and to switch cephalosporin with meropenem in neonates with confirmed gram negative bacilli or 3GC-resistant E. coli meningitis.