Treatment of severe pertussis: a study of the safety and pharmacology of intravenous pertussis immunoglobulin

Background. Pertussis in infants is often severe, resulting in complication s and prolonged hospitalization. Treatment is limited to supportive care. A ntibiotics do not significantly alter the course of the disease. Therapies directed at pertussis toxin, a major virulence factor of Bordetella pertuss is, might be beneficial. This study examines the safety and pharmacology of intravenous pertussis immunoglobulin (P-IGIV), which has high levels of pe rtussis toxin antibodies. Methods. P-IGIV was prepared as a 4% IgG solution from the pooled plasma fr om donors immunized with inactivated pertussis toroid. The IgG pertussis to xin antibody concentration of 733 mu g/ml is >7-fold higher than contained in conventional intravenous immunoglobulin products. Children with presumpt ive pertussis were allocated to one of three treatment doses of P-IGIV, Results. Twenty-six of 30 enrolled children had confirmed pertussis. There were no adverse events associated with P-IGIV except one patient who had tr ansient hypotension that responded to an infusion rate decrease. P-IGIV dos es of 1500, 750 and 250 mg/kg achieved greater than or equal to 4-fold, gre ater than or equal to 3-fold and >2-fold rises in peak geometric mean titer s of pertussis toxin IgG antibodies, respectively. P-IGIV exhibited a half- life of 38.4 days and a volume of distribution of 87.8 ml/kg. All three tre atment groups showed declines in lymphocytosis (P < 0.05) and paroxysmal co ughing by the third day after P-IGIV infusion compared with preinfusion val ues. Conclusion. P-IGIV is safe and achieves high pertussis toxin antibody titer s in infants. This study provides data for a prospective, controlled trial of P-IGIV.