This prospective study was designed to identify the role of postnatal penicillin prophylaxis in the prevention of neonatal group B streptococcus (GBS) infection. We studied 10 998 infants. Of these, 5389 were in the penicillin prophylaxis group (PP) and 5609 infants did not receive penicillin prophylaxis (NPP). Infants were allocated to treatment by month of birth, alternating 3‐mo blocks or 2‐mo blocks to the two groups after the first block was randomly assigned. The use of PP reduced the incidence of clinical sepsis (1.7% PP versus 2.5% NPP, p<0.01), GBS infection (0.4% PP versus 0.9% NPP, p < 0.001) and deaths from sepsis (0.1% PP versus 0.3% NPP, p < 0.05). We conclude that the routine use of postnatal penicillin prophylaxis appears to be effective in reducing the incidence of clinical sepsis and death from sepsis in neonates. □Antimicrobial prophylaxis, group B streptococcus, neonatal sepsis
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