Comparison of group B streptococcal hyperimmune globulin and standard intravenously administered immune globulin in neonates.

Standard intravenously administered immune globulin (IVIG) contains varying amounts of group B streptococcus (GBS) antibody. A GBS hyperimmune IVIG was produced by immunizing plasma donors. The GBS type-specific opsonic activity was > or = 90% in the hyperimmune IVIG at a 1280 dilution-1 versus at a 10 dilution-1 in standard IVIG. Suckling rat survival after GBS type-specific infection was 100% when the rats were treated with hyperimmune IVIG versus < or = 20% with standard IVIG. To evaluate the effect of this product on GBS antibody levels and clinical toxic effects, we randomly administered either GBS hyperimmune IVIG, 500, 250, or 100 mg/kg, or standard IVIG, 500 mg/kg, to 20 neonates with suspected sepsis. No adverse effects were observed. Total and subclass serum IgG levels reflected only the dose; serum GBS type-specific IgG and opsonic activity reflected both the product and dose of IVIG administered. Standard IVIG did not significantly increase serum GBS type-specific IgG, whereas hyperimmune IVIG, 500 mg/kg, produced a fourfold rise for > 6 weeks; more variable increases were observed after 250 and 100 mg/kg doses were given. Serum GBS type-specific opsonic activity correlated with serum GBS type-specific IgG levels (R2 = 0.74; p < 0.0001). Further studies of this or similar products will be necessary to determine whether GBS type-specific antibody improves the outcome of GBS-infected neonates.

Intravenous immune globulin therapy for early-onset sepsis in premature neonates.

Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG-treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens.

Perinatal bacterial infection after prolonged rupture of amniotic membranes: an analysis of risk and management.

Chi-square and logistic stepwise multiple regression analysis of perinatal determinants of infant bacterial infection following prolonged rupture of amniotic membranes for 24 hours or more prior to delivery was applied in 33 infected infants and 66 matched control infants from the NINCDS Collaborative Project. In order of statistical significance, the most important variables were placental inflammation (P = 0.002), gestational age less than 34 weeks (P = 0.008), gestational age 34 to 37 weeks (P = 0.013), male sex (P = 0.015), Apgar score less than 6 at 5 minutes (P = 0.023), and clinical amnionitis (maternal fever, fetal tachycardia, or amniotic or gastric fluid leukocytes or bacteria) (P = 0.044). Duration of labor during PROM, race, and maternal age and parity were insignificant. Using these predictive variables, identification of infected infants for either microbial surveillance (superficial and systemic cultures) or microbial surveillance and anticipatory antibiotic therapy (discontinued after 3 days of negative cultures) was highly significant (P = 0.0001). Incorporating these variables and derived coefficients from multivariate analysis, a mathematical model was used for evaluation and prediction of perinatal bacterial infection with a sensitivity of 82% and specificity of 70%. Analysis of 46 infants prior to and 310 infants after implementation of this process at Harbor-UCLA Medical Center indicated significant improvement in the appropriate management of these infants at risk (from 59% to 87% of the population, P less than 0.05). Inappropriate antibiotic therapy decreased from 35% to 10% (P less than 0.05). In the absence of a shift in the median days of hospitalization of non-PROM infants, determination of the grand median days of PROM infant hospital stay showed a decrease (P less than 0.01) after initiation of this evaluation and management scheme.

Epidemiology of the group B streptococcus: maternal and nosocomial sources for infant acquisitions.

Repeated bacteriologic observations were made in 462 newborn infants and correlated with similar data from their mothers to evaluate the relative contributions of the birth canal and the hospital environment to acquisition of group B streptococci in the first few days of life. Fifty-eight percent of infants whose mothers were intrapartum carriers acquired streptococci in comparison with 12% of those whose mothers were noncarriers. Acquisitions from the birth canal were not influenced by the route of delivery or the time between membrane rupture and birth, but could be related to the quantity of streptococci in maternal cultures. Observations in ten cohorts of infants, including serotyping and bacteriophage susceptibility of group B isolates, demonstrated clear-cut streptococcal spread among infants in two cohorts. Infants appeared to harbor larger numbers of streptococci at more body sites following acquisition from the birth canal than after acquisition from the hospital environment.

Epidemiology of group B Streptococcus: longitudinal observations during pregnancy.

A longitudinal, three-year study of the epidemiology of group B Streptococcus was conducted with repeated (four to 11) observations of 382 patients followed through pregnancy, delivery, and the postpartum period. Group B streptococci (2.3% of which were nonhemolytic) were isolated from the birth canal at first visit from 15% of the patients and from 28% with repeated cultures. Overall, group B streptococci were isolated at 12% of culture visits. Streptococcal carriage was significantly less common among patients who were Mexican-American, 20 years old or older, or in a fourth or later pregnancy. Multivariate analysis indicated that each of these three factors had a significant, independent bearing upon carriage of group B streptococci. Of 108 patients harboring these organisms in the birth canal, 36% could be classified as chronic, 20% as transient, and 15% as intermittent carriers. The relationship of infant colonization to the presence of streptococci in the birth canal at delivery and not to previous or subsequent carriage by the mother was consistent with the observation that maternal colonization was often inconstant.

Aerobic and anaerobic bacteriology of acute otitis media in children.

Tympanocentesis and aerobic and anaerobic cultivation of the middle-ear fluid obtained was performed through one or both tympanic membranes of 62 children with acute otitis media. Aerobic bacteria alone, predominantely pneumococcus and Hemophilus influenzae, were isolated from 57% of patients; anaerobic organisms alone, most commonly Propionibacterium acnes and Peptococcus, from 15%. Thirteen percent yielded mixtures of aerobes and anaerobes, and several had multiple aerobic or anaerobic agents. The isolation of only anaerobic bacteria, supported in some patients by gram-stain observations of middle-ear fluid, suggest that these bacteria, especially Petococcus, may occasionally play a direct role in acute otitis media.

Bactericidal capacity of monocytes of newborn infants.

The peripheral leukocytes of newborn infants and of adult volunteers were studied after separation of polymorphonuclear and mononuclear cells. Monocytes were identified and quantitated with the aid of histochemical staining. The in vitro killing capacity of PMN and of monocytes was assayed against Staphylococcus aureus and Escherichia coli. The monocytes of both infants and adults were significantly less active than were their PMN, but the bactericidal capacity did not differ appreciably between newborn and adult cells of either type.