Protective efficacy of a modified immune serum globulin in experimental group B streptococcal infection.

In spite of aggressive antimicrobial therapy and extensive support measures, the mortality rate in early-onset group B streptococcal infection continues to be exceedingly high. In previous studies, we have demonstrated that passive immunotherapy with fresh whole blood containing opsonic antibody-improved survival in human neonates with group B disease. Transfusion of whole blood, plasma, or other blood products has a number of drawbacks, however. In the present study, we have evaluated immune serum globulin and a preparation of ISG modified for intravenous use for levels of type-specific antibody, opsonic activity, and protective efficacy against type Ia, II, and III group B streptococci. Type-specific antibody was detected in most of the preparations tested. In general, the level in MISG was less than that in the comparison ISG lot. Opsonic activity was also detected in these preparations against the more antibody-sensitive group B strains but was not present for opsonin resistant strains of type Ia, II, and III. Both ISG and MISG provided protection in neonatal rats infected with group B streptococci; in most cases MISG was more efficacious than the ISG from which it was made. These studies suggest that passive immunotherapy with MISG may be a valuable adjunct to current regimens used in the management of early-onset group B disease. This would be especially so if donors could be selected whose serum or plasma contained high levels of opsonic and protective activity against both antibody-sensitive and antibody-resistant group B strains.

Defective oxidative metabolic responses of neutrophils from stressed neonates.

Oxidative metabolic responses of polymorphonuclear leukocytes were assessed in 24 stressed neonates and 22 well, term infants utilizing particulate and soluble stimuli. Stressed neonatal PMNs demonstrated a depressed CL response to zymosan, whereas O2- production for both normal and stressed PMNs of neonates was significantly elevated compared to that in PMNs from adults. These results were not ascribable to phagocytosis since it was comparable in all groups using radiolabeled bacteria. Stressed neonates' PMN responses to soluble stimuli were significantly elevated when compared with those from well neonate and adult controls. Enhanced responses were most prominent in the most severely stressed infants. Treatment of neonates' PMNs with the antioxidants vitamin E and DHB partially corrected the abnormalities, suggesting peroxidative damage to the PMN membrane had occurred. The oxidative metabolic abnormalities of neonates' PMNs are consistent with either a defect in HMPS activity, a defect in functioning of the later portions of the respiratory burst, or a stimulus-specific abnormality in respiratory burst activity.

Functional analysis of neutrophil granulocytes from healthy, infected, and stressed neonates.

Neutrophil granulocyte function was assessed in 17 well term infants, 14 stressed infants, and eight infants with group B streptococcal infection. Chemiluminescence production elicited by opsonized zymosan or by a wild strain of type III group B streptococci, as well as phagocytosis and killing of streptococci, were measured. Chemiluminescence production by PMNs of term neonates in response to opsonized zymosan or group B streptococci was equal to that of adult controls. In contrast, six of nine stressed or infected neonates had depressed CL responses upon zymosan challenge. When opsonized type III group B streptococci were used to elicit CL, seven of ten stressed or infected infants had markedly depressed responses. Phagocytosis, as determined by a radiolabeled bacterial uptake technique, was normal in the healthy and stressed neonates. Depressed CL production by the PMNs of stressed or infected neonates was associated with impaired intracellular bactericidal activity, however. These studies indicate that stressed or infected neonates have impaired leukocyte metabolic activation that may be associated with depressed bactericidal activity. Such impairment may contribute to the morbidity and mortality observed in serious neonatal infections.