Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease. I. Epidemiologic rationale.

Between 1973 and 1981, 61 cases of neonatal group B streptococcal early-onset disease occurred among 32,384 infants born at Michael Reese Hospital and Medical Center, Chicago. Forty-one (67%) of the 61 affected infants were bacteremic at birth, implying intrapartum acquisition of infection. No significant deviations from the overall attack rate of 1.9 per 1,000 live births were associated with maternal demographic factors, but increased attack rates were associated with birth weights of less than or equal to 2.5 kg (7.9 per 1,000), rupture of amniotic membranes greater than 18 hr before birth (7.6 per 1,000), and intrapartum fever (6.5 per 1,000). Forty-five (74%) of the 61 affected infants and 15 (94%) of the 16 with fatal outcome had one or more of these three perinatal risk factors. Based on an intrapartum vaginal carriage rate of 16.7% among parturients with perinatal risk factors, an attack rate of 45.5 per 1,000 was estimated for infants born to colonized "high-risk" parturients, a subgroup comprising approximately 3% of our obstetric population. These findings provide a compelling epidemiologic rationale for trials of selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease.

Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease. II. Predictive value of prenatal cultures.

To determine the value of prenatal cultures in defining maternal colonization status at delivery, 5,586 pregnant women were screened at prenatal visits for vaginal and rectal carriage of group B streptococci (GBS). GBS were isolated from 1,272 (22.8%). At delivery, semiquantitative cultures were obtained from 393 prenatal carriers, of whom 264 (67.2%) retained carriage at delivery. Seventeen (8.5%) of 200 women with negative prenatal cultures acquired carriage. The predictive value of a positive prenatal culture was highest (72.5%) in women with prenatal vaginal and rectal colonization and lowest (59.7%) in women with only rectal colonization. The predictive value varied inversely with the interval between prenatal sampling and delivery. In mothers with prenatal carriage, density of colonization at parturition was not predicted by the sites of prenatal colonization. Density of colonization, however, strongly influenced rates of vertical transmission to neonates and rates of heavy infant colonization. Ten infants born to prenatally cultured mothers developed group B streptococcal early-onset disease; the mothers of eight (80%) of the 10 had prenatal colonization with the homologous GBS serotype.

Selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease. III. Interruption of mother-to-infant transmission.

The effect of intrapartum ampicillin treatment on vertical transmission of group B streptococci (GBS) was examined in 575 prenatally colonized parturient women and their 580 newborn infants. Eighty women (43 receiving ampicillin) with premature labor and/or prolonged rupture of amniotic membranes were randomized. The other 495 were stratified into groups of 358 (31 receiving ampicillin) with no perinatal risk factors; 119 (28 receiving ampicillin) with premature labor and/or prolonged membrane rupture; and 23 (18 receiving ampicillin) with intrapartum fever. Ampicillin virtually eliminated vertical transmission in the treatment group with no risk factors and in both treatment groups with premature labor and/or prolonged membrane rupture. GBS colonization of neonates was detected only in women with intrapartum fever or brief (less than 1 hr) duration of treatment prior to delivery. Ampicillin treatment was associated with a highly significant reduction in maternal postpartum vaginal colonization by GBS. There were six group B streptococcal early-onset infections in infants of untreated subjects and no cases in treated subjects.

Rapid identification of material colonization with group B streptococci by use of fluorescent antibody.

To identify women colonized with group B streptococci during parturition, we used pooled type-specific fluorescent antibody to examine vaginal swabs enriched by preincubation in selective broth medium. In preliminary experiments, group B streptococcus strain III-Bell was reliably detectable with fluorescent antibody at concentrations of greater than 10(5) colony-forming units per ml, achieved after 6 h of incubation of small inocula (18 to 26 colony-forming units). Of the vaginal swabs from 924 parturient women examined prospectively by both fluorescent antibody and selective bacteriology techniques, group B streptococci were isolated in 154. The sensitivity of the fluorescent antibody technique increased with increasing incubation time and ranged from 49% (3 to 6 h) to 81% (7 to 12 h) to 83% (13 to 18 h) to 93% (greater than 18 h). Colonized mothers identified within 6 h by the fluorescent antibody technique had higher rates of vertical transmission to their newborn infants (61%) than colonized mothers whose fluorescent antibody examinations were negative within this time interval (32%; P = 0.027). However, because of the timing of their admissions, none of the colonized mothers of the four infants who developed early-onset group B streptococcal sepsis were identified with fluorescent antibody until after delivery. Although its sensitivity approaches selective culture methods after 6 h of incubation, fluorescent antibody examination of vaginal swabs does not appear to offer a practical approach to identifying colonized parturient women for intrapartum antibiotic prophylaxis of group B streptococcal infection.

Nosocomial transmission of bacteriophage type 7/11/12 group B streptococci in a special care nursery.

Two premature infants in a special care nursery acquired late-onset group B streptococcal (GBS) sepsis within a 24-hour period. The infecting strains were serotype III organisms with bacteriophage type 7/11/12. Cultures of the mothers of the two affected infants were negative for GBS, implying nosocomial acquisition of infection. Although 32% of nursery personnel had mucosal carriage of GBS, none of the seven isolates of GBS type III was the same bacteriophage type as the two infecting strains. Of the other infants hospitalized in the nursery, five were asymptomatically colonized with GBS. These infants were in bassinets adjacent to the affected infants; all five of their isolates were identical to the two infecting strains. We conclude that infant-to-infant transmission may result in nosocomial late-onset GBS septicemia.

Prevalence of type-specific group B streptococcal antibody in pregnant women.

Immunoglobulin G antibody against the four major serotypes of group B streptococcus was measured by indirect immunofluorescence in the sera of 200 consecutive pregnant women seen in the obstetric screening clinic of an urban teaching hospital. Antibody was detectable in 26% of undiluted sera against serotype Ia, 52% against serotype Ib, 82% against serotype II, and 45% against serotype III. Only 9% had antibody against all four GBS types. When serotype-specific antibody prevalences in 108 women with GBS vaginal colonization were compared with prevalences in noncolonized women, only women colonized with GBS type Ia were more likely to have antibody against Ia than noncolonized women. Antibody prevalences in sera from 54 mothers whose infants developed invasive GBS disease were significantly lower than those in colonized or noncolonized women. Since low titers of IF antibody to GBS III were present in some sera from mothers of infected infants, the data were analyzed based on IF antibody titers associated with passive protection in a chick embryo model of GBS septicemia. None of the sera from mothers of infected infants had antibody levels associated with chick embryo protection. Less than 10% of women had titers associated with chick embryo protection. These data suggest that the majority of pregnant women lack immunity to GBS, regardless of colonization status.

Human immunity to group B streptococci measured by indirect immunofluorescence: correlation with protection in chick embryos.

An indirect immunofluorescence (IF) assay has been developed as a useful semiquantitative method for determination of type-specific IgG antibody in human sera to the five serotypes of group B Streptococcus. Antibody titers measured by IF correlated with passive protection in chick embryos, and antibody titers associated with chick embryo protection were delineated. Except for types Ia and Ic, IF antibody to each of the streptococcal types was completely absorbed by homologous strains, and antibody titers were unchanged by incubation with heterologous bacteria. For types Ia and Ic, IF antibody was absorbed by either the Ia or the Ic strain and by native Ia carbohydrate antigen. Antibody titers measured by IF and chick embryo protection against types Ia and Ic were similar, but were divergent for Ib and Ic, a finding suggesting that antibody is predominantly directed to the major carbohydrate determinants. In addition, 29 of 31 sera that had been tested in chick embryos yielded comparable results in mice against challenge with type Ia group B Streptococcus, a finding further validating the chick embryo assay. Sera from all of 43 mothers of infants infected with group B streptococci had antibody titers by IF that were less than titers associated with protection in chick embryos.