Persistence of penicillin G benzathine in pregnant group B streptococcus carriers

OBJECTIVE: To determine if streptococcicidal levels of penicillin G benzathine can be detected in maternal serum 4 weeks after treatment with 4.8 million units. METHODS: Thirty-seven pregnant women with positive group B streptococcus vaginal or urine cultures were each given 4.8 million units of penicillin G benzathine. Maternal blood samples were collected after injection and at delivery. Serum penicillin levels were measured by high-pressure liquid chromatography. Follow-up cultures were done when possible. RESULTS: None of the patients had serum penicillin levels below 0.20 microgram/mL 30 days after treatment. Cord blood levels were approximately 50% lower than maternal levels. In all but three subjects, cord blood levels exceeded 0.06 microgram/mL, the minimal inhibitory concentration for group B streptococcus. The three exceptions were patients who delivered more than 100 days after treatment. Group B streptococcus cultures were negative at the time of delivery in 72% of cases. None of the patients with positive cultures were moderately or heavily colonized. CONCLUSION: In pregnant women, penicillin G benzathine levels are high enough to inhibit the growth of group B streptococcus for more than 4 weeks after injection with 4.8 million units. Further studies are needed to evaluate whether this regimen can prevent neonatal colonization and invasive group B streptococcus disease.     

Opportunities for prevention of perinatal group B streptococcal disease: a multistate surveillance analysis. The Neonatal Group B Streptococcal Disease Study Group

OBJECTIVE: To evaluate the potential impact of ACOG and Centers for Disease Control and Prevention (CDC) consensus strategies for the prevention of perinatal group B streptococcal disease. METHODS: We evaluated cases of early-onset group B streptococcal disease identified by active surveillance during 1995, in four areas in North America with an aggregate 186,000 births per year. We reviewed the hospital records of mothers and infants and any prenatal records available on site. Cases were determined to be preventable based on whether group B streptococcal screening could have been performed prenatally, sensitivity of screening, presence of obstetric complications, and opportunity to administer antibiotics. RESULTS: We reviewed records for 245 of 246 infants with early-onset group B streptococcal disease in the surveillance areas. Most of the 53 case-mothers who delivered preterm and 192 who delivered full-term had had at least one prenatal visit (83% and 99%, respectively). Few case-mothers had prenatal group B streptococcal screening cultures, although compliance was high for other prenatal screening tests. Fifty-four percent of case-mothers had a recognized obstetric risk factor for group B streptococcal disease: labor or rupture of membranes at less than 37 weeks, rupture of membranes for 18 hours on longer, or temperature 38C or greater. The estimated preventable portion of early-onset group B streptococcal cases was 78% for the screening-based approach (range 74% to 82% by area), compared with 41% for the risk-based approach (range 39% to 53% by area). CONCLUSION: Comprehensive implementation of either of the recommended prevention strategies could potentially prevent a substantial proportion of early-onset group B streptococcal disease.     

Risk of preterm delivery in pregnant women with group B streptococcal urinary infections or urinary antibodies to group B streptococcal and E. coli antigens

OBJECTIVE: To establish whether there is an association between preterm delivery and either group B streptococcal urinary infection or the presence of urinary antibodies to group B streptococcal or E. coli antigens. DESIGN: A prospective study with urine culture and antibody measurement performed at the first antenatal visit and at 28 weeks gestation. SETTING: Ninewells Hospital, Dundee. SUBJECTS: Two thousand and forty-three women registering consecutively at an antenatal clinic. MAIN OUTCOME MEASURE: Delivery at less than 37 weeks gestation. RESULTS: No increase in preterm delivery was observed in women with positive urine cultures for group B streptococci either at booking or at 28 weeks, even when confirmed by positive repeat cultures. Preterm delivery was more common in women with elevated urinary antibodies to E. coli antigens at booking (relative risk 1.81, 95% CI 1.22-2.68, P = 0.005) and at 28 weeks (relative risk 2.36, 95% CI 1.60-3.48, P < 0.0001) and to group B streptococcal antigens at 28 weeks (relative risk 2.24, 95% CI 1.46-3.43, P = 0.0003). CONCLUSIONS: These data do not support previous reports that positive urine cultures for group B streptococci are associated with an increased risk of preterm delivery. Our report of an association between elevated levels of urinary antibodies and preterm delivery is a new finding consistent with the possibility that a local inflammatory response to uro-genital infection may be important in stimulating the onset of preterm labour. The results suggest that screening for urinary antibodies at 28 weeks gestation might help to identify a group of women at increased risk of prematurity.     

Comparison of NNA agar culture and selective broth culture for detection of group B streptococcal colonization in women

In 1996, the Centers for Disease Control and Prevention recommended the use of a selective broth culture for the improved detection of genital tract or anorectal carriage of group B streptococci (GBS) in pregnant women. In order to verify this recommendation in our laboratory, we compared the sensitivity of Todd-Hewitt medium with gentamicin and nalidixic acid (SBM) with our current method of direct plating on blood agar medium containing neomycin and nalidixic acid (NNA). Five hundred consecutive cervicovaginal and anorectal specimens submitted for GBS culture were included in the study. Swabs were plated onto NNA and the swabs were immersed in SBM, followed by overnight incubation at 35 degrees C. On the following day, the NNA plates were examined for colonies typical of GBS and the organisms were identified by the CAMP test or by latex agglutination. SBM cultures were subcultured onto blood agar and CNA agar plates, and the plates were reincubated for 24 h. Negative specimens from either medium were incubated for an additional 24 h and were examined again before finalization of the results. GBS were recovered from 78 specimens by both methods; from SBM only for 17 specimens (sensitivity, 86%) and from NNA only for 16 specimens (sensitivity, 85%). A moderate to heavy growth of Enterococcus faecalis was observed on plates containing NNA-positive, SBM-negative specimens. Competitive growth studies suggested that E. faecalis suppressed the growth potential of GBS in SBM. Our study suggests that direct plating on NNA, as a single method, is equivalent in sensitivity to SBM for the recovery of GBS, and the results are often available 24 h sooner. However, it appears that both direct plating and selective broth amplification techniques are required for the maximum level of identification of colonization with GBS in pregnant women.     

Colonization with group B streptococci in neonates and premature infants from selected neonatal departments

Group B streptococci are considered an important etiological agent of sepsis and meningitis in neonates and, particularly, in premature infants. There is a close correlation between colonization with these bacteria and the frequency of symptomatic infection. It is estimated that symptomatic infections occur in 1.0% of colonised neonates. The purpose of this work was to investigate the frequency of neonate colonization with group B streptococci for determination of the risk of symptomatic infection.     

neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group

PURPOSE: It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS: A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION: neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.     

Change in susceptibility of group B streptococci to penicillin G from 1968 through 1975

This report describes a study of 212 isolates of group B streptococci from sore throats over an 8-year period. A small but increasing percentage showed increased resistance to penicillin G when tested in an in vitro system.     

Incidence, technique of isolation, and treatment of group B streptococci in obstetric patients

A prospective study was performed to determine the incidence of group B streptococci cultured from the cervix in a series of obstetric clinic patients at St. Margaret's Hospital. Cultures were taken during each trimester and planted to both a blood agar plate and a selective broth medium. Of a total of 812 cultures, 18 were positive, an over-all incidence of 2.2 per cent. During the first, second, and third trimesters, 2.2 per cent, 2.5 per cent, and 1.9 per cent of cultures were positive, respectively. Women with positive cultures were treated with a 10 day course of oral penicillin or a suitable alternative; four of 16 had persistent positive cultures at the end of the first treatment period, three of these four responded to a second course of antibiotics, and the remaining patient responded after a third treatment course. The total number of positive cultures by selective broth was 24, compared to nine in blood agar, indicating a 2.7-fold increase in pickup by the selective broth.     

Nasal immunization with group B streptococci can induce high levels of specific IgA antibodies in cervicovaginal secretions of mice

We have studied the cervicovaginal antibody responses in mice, by ELISA, following mucosal immunizations with group B streptococci (GBS) serotype III/R4. Immunizations were carried out either: (1) rectally with GBS alone; (2) rectally with GBS plus cholera toxin (CT); (3) nasally with GBS alone; (4) nasally with GBS+CT; or (5) nasally under general anesthesia with GBS+CT. Nasal immunizations with GBS alone led to at least tenfold higher levels of specific IgA-antibodies to GBS in cervicovaginal secretions than with any other immunization. These mucosal antibody levels were higher than after rectal immunizations, and 2-17 times higher than the corresponding IgA antibody levels in sera. Markedly lower cervicovaginal antibody levels were found in mice which had received GBS together with CT as a mucosal adjuvant than in mice immunized by the same routes with GBS alone. Our observations indicate that a nasal vaccine consisting of GBS might induce sufficient antibody levels to protect against genital colonization of these bacteria.     

Use of a DNA probe for the rapid detection of group B streptococci in obstetric patients

OBJECTIVE: To determine the accuracy of a DNA probe as a rapid diagnostic test for detecting colonization of the female genital tract by group B streptococci during pregnancy. METHODS: Two rayon-tipped applicators were used to collect secretions from the posterior vaginal wall of 440 pregnant women. One of the applicators was inoculated into selective Todd-Hewitt broth and used as the reference standard for identification of group B streptococci. The other applicator was used for analysis with the DNA probe, preceded by either 2.5 hours of incubation for the initial 75 patients, or 3.5 hours' incubation for the remaining women. Following hybridization with an acridinium-labeled probe, chemiluminescence was measured with a luminometer. RESULTS: The prevalence of positive cultures was 20%. For the initial 75 patients whose cultures were amplified by incubation for 2.5 hours, the DNA probe had a sensitivity of 44%, specificity 94%, positive predictive value 79%, and negative predictive value 77%. For the cultures that were incubated for 3.5 hours, respective values were 71, 90, 61, and 94%. All vaginal specimens that had an average initial cell count of 1.5 x 10(3) cells/mL were accurately detected by the probe after 3.5 hours' growth amplification. False-positive results occurred primarily when the specimens were grossly contaminated with blood (26 of 39). The mean time required to perform the assay, including 3.5 hours of growth amplification, was 4.3 hours. CONCLUSIONS: The DNA probe demonstrated good overall sensitivity and gave no false-negative results when group B streptococci were present in concentrations of 1 x 10(4) cells/mL or greater. Sensitivity improved significantly with 3.5 hours' growth amplification as compared with 2.5 hours (P < .05), reflecting better identification of lightly colonized patients.     

Multistate case-control study of maternal risk factors for neonatal group B streptococcal disease. The Active Surveillance Study Group

Risk factors for early onset disease (EOD) caused by Group B streptococci (GBS) that are the foundation of prevention guidelines were identified in studies conducted in a few hospital centers. We investigated cases of EOD identified through laboratory-based active surveillance during 1991 and 1992 in a multistate population of 17 million. Ninety-nine cases were compared with 253 controls matched for hospital, date of birth and birth weight. Prematurity (< 37 weeks of gestation) was present in 28% of cases; 53% of case mothers had rupture of membranes > 12 hours; and 48% reported intrapartum fever. The incidence of EOD in each surveillance area was higher among blacks. By multivariate analysis, case mothers were more likely than controls to have rupture of membranes before labor onset (adjusted odds ratio 8.7, P < 0.001), intrapartum fever (adjusted odds ratio 11.9, P < 0.001), and history of urinary infection during pregnancy (adjusted odds ratio 4.3, P < 0.05). Young maternal age was also associated with risk of disease. Three-fourths of case mothers had intrapartum fever, < 37 weeks of gestation and/or prolonged rupture of membranes, indicators previously used to select high risk women for intrapartum chemoprophylaxis. Our findings extend data from single hospitals and suggest prenatal screening and selective intrapartum chemoprophylaxis of high-risk mothers could potentially prevent the majority of EOD in the United States.     

Detection of hepatitis B surface antigen in pregnant women attending a public hospital for delivery: implication for vaccination strategy in Bangladesh

Routine antenatal hepatitis B surface antigen (HBsAg) screening and immunization of risk babies is very effective in preventing perinatal transmission of hepatitis B virus (HBV). We studied 1,800 parturients attending a public hospital to assess the rationale for such vaccination in Bangladesh. In one in every 29 deliveries (63 of 1,800 or 3.5%), the mother was found to be HBsAg positive. All were asymptomatic and many (41 of 63 or 65%) without risk factors would remain undetected if HBsAg screening were performed on selected groups. Most of the HBsAg-positive mothers (54 of 63 or 85.7%) were found to be chronic carriers and 30.2% (19 of 63) were also hepatitis B e antigen (HBeAg) positive, indicating high infectivity. Although 23 cord blood were positive for HBsAg or HBeAg, none were positive for IgM antibody to hepatitis B core antigen (IgM anti-HBc), suggesting transplacental transmission of the antigens rather than intrauterine infection. These findings are discussed in relation to the cost-effectiveness of routine prenatal screening and immunization of risk babies compared with universal infant immunization.     

SXT and Taxo A disks for presumptive identification of group A and B streptococci in throat cultures

A bacitracin (0.04 units, BBL)-SXT (trimethoprim, 1.25 mg, plus sulfamethoxazole, 23.75 mg, BBL) susceptibility test was 94% accurate in presumptively identifying streptococci as either group A, B or not group A and B.     

Deletion of repeats in the alpha C protein enhances the pathogenicity of group B streptococci in immune mice

The alpha C protein is a protective surface-associated antigen of group B streptococci (GBS). The prototype alpha C protein of GBS (strain A909) contains nine identical tandem repeats, each comprising 82 amino acids, flanked by N- and C-terminal domains. Clinical isolates of GBS show variable numbers of repeats with a normal distribution and a median of 9 to 10 repeats. Here, we show that escape mutants of GBS expressing one-repeat alpha C protein were 100-fold more pathogenic than GBS expressing wild-type nine-repeat alpha C protein in neonatal mice whose dams were immunized with antiserum elicited to nine-repeat alpha C protein (50% lethal doses of 1.6 x 10(3) and 1.8 x 10(5), respectively; P = 0.0073). There was no difference in pathogenicity in nonimmune mice. Enzyme-linked immunosorbent assay inhibition showed that nine-repeat but not one-repeat alpha C protein is readily available for antibody binding on the surface of intact GBS. Immune electron microscopy studies with antibodies to the capsular polysaccharide (CPS) and to the alpha C protein demonstrated localization of the nine-repeat alpha C protein and the CPS at similar distances from the cell wall. The one-repeat alpha C protein was visualized poorly and only in close proximity to the cell wall, thus suggesting that antibody binding to the protein was hindered by CPS or other cell surface components. We concluded that deletion in the repeat region of the alpha C protein enhanced the pathogenicity of GBS in immune mice by (i) loss of a protective (conformational) epitope(s) and (ii) loss of antibody binding to the alpha C protein due to a decrease in antigen size relative to cell wall components and/or CPS.     

Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group

OBJECTIVE: To determine the factors associated with appendicular bone mass in older women. DESIGN: Cross-sectional analysis of baseline data collected for a multicenter, prospective study of osteoporotic fractures. SETTING: Four clinical centers in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela valley, Pennsylvania. PATIENTS: A total of 9704 ambulatory, nonblack women, ages 65 years or older, recruited from population-based listings. MEASUREMENTS: Demographic and historical information and anthropometric measurements were obtained from a baseline questionnaire, interview, and examination. Single-photon absorptiometry scans were obtained at three sites: the distal radius, midradius, and calcaneus. Multivariate associations with bone mass were first examined in a randomly selected half of the cohort (training group) and were then tested on the other half of the cohort (validation group). RESULTS: In order of decreasing strength of association, estrogen use, non-insulin-dependent diabetes, thiazide use, increased weight, greater muscle strength, later age at menopause, and greater height were independently associated with higher bone mass. Gastric surgery, age, history of maternal fracture, smoking, and caffeine intake were associated with lower bone mass (all P < 0.05). For example, we found that 2 or more years of estrogen use was associated with a 7.2% increase in distal radius bone mass, whereas gastrectomy was associated with an 8.2% decrease in bone mass. The associations between bone mass and dietary calcium intake and rheumatoid arthritis were inconsistent. Alcohol use, physical activity, use of calcium supplements, pregnancy, breast-feeding, parental nationality, and hair color were among the many variables not associated with bone mass. Multivariate models accounted for 20% to 35% of the total variance of bone mass. CONCLUSIONS: A large number of factors influence the bone mass of elderly women; however, age, weight, muscle strength, and estrogen use are the most important factors.     

Decreased capacity for type-specific-antigen synthesis accounts for high prevalence of nontypeable strains of group B streptococci in Mexico

The low incidence of group B streptococcal (GBS) invasive neonatal disease in Mexico has been attributed to the low prevalence of serotype III strains, a major serotype in developed countries. In addition, nontypeable strains account for 12% of the isolates in Mexico and < 1% of the isolates in the United States. In this study, 57 GBS isolates (28 nontypeable by the Lancefield procedure) from carrier and infected neonates and women from Mexico were also examined for the presence of type-specific antigen by an enzymatic procedure using N-acetylmuramidase digestion of the cell wall to release soluble type-specific antigen. Of the 28 nontypeable strains from Mexico, 23 were typeable by the enzyme extraction procedure, with serotype III being the predominant serotype in invasive disease. These results suggest that nontypeable isolates of GBS should be further examined by the enzymatic extraction procedure to determine the presence of type-specific antigen. Furthermore, these limited results suggest that serotype III is likely a major serotype in invasive disease also in Mexico.