The interrelationship of complement-activation fragments and angiogenesis-related factors in early pregnancy and their association with pre-eclampsia.

OBJECTIVE: To determine the interrelationships during early pregnancy of complement-activation fragments Bb, C3a and sC5b-9, and angiogenesis-related factors placental growth factor (PiGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and their associations with pre-eclampsia. DESIGN: Prospective cohort study. SETTING: Denver complement study (June 2005-June 2008). POPULATION: A total of 668 pregnant women with singleton gestations, recruited between 10 and 15 weeks of gestation. METHODS: Using univariable and multivariable logistic regression analysis, concentrations of complement-activation fragments and angiogenesis-related factors were compared between 10 and 15 weeks of gestation in women who subsequently did or did not develop pre-eclampsia. Interrelationships between these variables were tested using the non-parametric Spearman rank correlation coefficient. MAIN OUTCOME MEASURE: Pre-eclampsia. The association of complement-activation fragments and angiogenesis-related factors with obesity was also examined. RESULTS: The mean (+/-SD) levels of complement Bb in early pregnancy among women who did and did not develop pre-eclampsia were 0.84 (+/-0.26) microg/ml and 0.69 (+/-0.2) microg/ml, respectively (P = 0.001). Concentrations of PiGF were significantly (P = 0.01) lower (31 +/- 12 pg/ml) in early pregnancy in the pre-eclamptic group of women, as compared with the normotensive group (39 +/- 32 pg/ml). The adjusted odds ratio (AOR) of Bb and PiGF were 2.1 (CI = 1.4-3.1, P < 0.0003) and 0.2 (CI = 0.07-0.7, P = 0.01), respectively. There was no significant difference in the levels of C3a, sC5b-9, sFlt-1 and sEng in early pregnancy among women who developed pre-eclampsia, compared with women who remained normotensive during pregnancy. Higher levels of Bb (P = 0.0001) and C3a (P = 0.03), and lower levels of sFlt-1 (P = 0.0002) and sEng (P = 0.0001) were found among women with obesity, compared with non-obese controls. No meaningful relationships were found between the complement-activation fragments and the angiogenesis-related factors. CONCLUSIONS: In this cohort during early pregnancy, increased concentrations of complement-activation factor Bb and lower concentrations of PiGF were associated with the development of pre-eclampsia later in pregnancy.

Impact of infectious diseases on women's health: 1776-2026.

In this commentary, the author reviews the impact of infectious diseases on women's health, beginning with the late 18th century when clinically recognized infections took the heaviest toll on women. The review continues through the 19th and 20th centuries when public health measures and the advent of antibiotic agents led to apparent control of infection, and ends with a forecast for the next 25 years. Foreboding considerations for the future include spread of human immune deficiency virus infection and other sexually transmitted diseases and the development of new infections, antibiotic-resistant bacteria, and the recognition of infection as a cause of many obstetric-gynecologic and chronic disorders. Obstetricians and gynecologists can contribute to the solution of these problems individually and collectively.

A randomized controlled trial of interleukin-1 receptor antagonist in a rabbit model of ascending infection in pregnancy.

OBJECTIVE: To determine whether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amniotic fluid concentrations of tumor necrosis factor alpha (TNF-alpha) and prostaglandins or clinical or microbiological outcomes in a model of ascending bacterial infection in pregnancy. METHODS: Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation of the cervices with 10(6) - 10(7) cfu Escherichia coli. Animals were randomly assigned in a blinded manner to a 5-h intravenous infusion of human IL1-ra (10 mg/kg) or placebo beginning 1-2 h after inoculation. Blood was drawn from the does for assay of serum IL1-ra concentration before inoculation, at mid-infusion, after the infusion ended and at necropsy. At necropsy, temperature and cultures were taken, and aspirated amniotic fluid was pooled for assays of TNF-aalpha, prostaglandin E2 (PGE2) and ILI-ra. RESULTS: Serum IL1-ra concentrations rose to a mean of 2 microg/ml at mid-infusion and fell markedly after the infusion to concentrations barely detectable at necropsy. Between the two groups, there were no significant differences in the rates of fever or positive cultures or in amniotic fluid concentrations of PGE2 or TNF-alpha. One unique finding was the demonstration that administration of human IL1-ra to the does resulted in measurable concentrations of human IL1-ra in the amniotic fluid. CONCLUSIONS: Treatment with an intravenous infusion of human IL1-ra after cervical inoculation with E. coli did not affect clinical or microbiological outcomes or amniotic fluid concentrations of TNF-alpha or PGE2. This experiment providesthefirstdemonstration of passage of human IL1-ra from the maternal bloodstream to the amniotic fluid.

A Randomized Controlled Trial of Metronidazole Vaginal Cream in the Treatment of Papanicolaou Smears Showing Atypical Squamous Cells of Undetermined Significance (ASCUS).

OBJECTIVE: To compare topical metronidazole gel vs. placebo to assess resolution to normal in subsequent Pap smears of patients with ASCUS. MATERIALS AND METHODS: Patients with ASCUS pap smears were randomized to metronidazole or placebo. Resolution of ASCUS vs. persistence, or progression, was the endpoint. A subanalysis stratified patients for bacterial vaginosis (BV) to determine if this population responded differently. Discrete variables were compared using chi-square analysis. RESULTS: Forty-nine patients received metronidazole and 52 received placebo. The rate of resolution in the placebo group were 60%, and 67% in the metronidazole group. With BV, the rate of resolution in the placebo group was 67%, and 70% in the metronidazole group. These were not significantly different. CONCLUSIONS: Treatment of ASCUS Pap smears using topical metronidazole did not demonstrate a significant increase in the rate of resolution in subsequent Pap smears in the overall group nor in a subgroup with BV.

The relationship between infections and adverse pregnancy outcomes: an overview.

Preterm birth with its subsequent morbidity and mortality is the leading perinatal problem in the United States. Infants born before the thirty-seventh week of gestation account for approximately 6% to 9% of all births, but 70% of all perinatal deaths and half of all long-term neurologic morbidity. Current approaches focus on symptomatic treatment. Despite widespread use of drugs to arrest preterm labor (tocolytics), there has been no decrease in low birth weight or preterm infants in the last 20 years. It is likely that therapy directed at preventing or treating underlying causes would be more successful. Evidence from many sources links preterm birth to symptomatic infections, for example, of the urinary or respiratory tracts. In the last decade, great interest has been generated to support the hypothesis that subclinical infection is an important cause of preterm labor. Evidence to support this may be categorized as follows: histological chorioamnionitis is increased in preterm births; clinical infection is increased after preterm birth; there is significant association of some lower genital tract organisms and infections with preterm birth or preterm premature rupture of the membranes; there are positive cultures of amniotic fluid or membranes from some patients with preterm labor and preterm birth; there are markers of infections in preterm birth; bacteria or their products induce preterm birth in animal models; and some antibiotic trials have shown a lower rate of preterm birth or have deferred preterm birth. In the last 5 years, additional exciting information has suggested that not only is subclinical infection responsible for preterm birth but also many serious neonatal sequelae including periventricular leukomalacia, cerebral palsy, respiratory distress, and even bronchopulmonary dysplasia and necrotizing enterocolitis. In sum, a large body of clinical and laboratory information suggests that subclinical infection is a major cause of preterm birth, especially those occurring before 30 weeks. This concept holds promise that new approaches can be developed to prevent prematurity.

Histologic inflammation in the maternal and fetal compartments in a rabbit model of acute intra-amniotic infection.

OBJECTIVE: This study was undertaken to determine the course of acute inflammation in the maternal and fetal compartments during experimentally induced ascending intra-amniotic infection. STUDY DESIGN: Forty pregnant rabbits at 70% gestation were inoculated endocervically with 10(5) colony-forming units of Escherichia coli. Does were killed at 0, 4, 8, 16, 24, and 30 hours after inoculation. At necropsy, blood, peritoneal fluid, amniotic fluid, and uterine tissue were cultured. Fetal brain, lung, heart, gut, and kidney were collected for histologic examination. Necrosis, infiltrates, congestion, and edema were each assessed semiquantitatively, and mean composite histologic-inflammation scores were compared with analysis of variance. Inflammation, mitotic activity, and apoptosis were evaluated in the fetal brain, and groups were compared with analysis of variance. RESULTS: Twenty-six animals were evaluated after 14 were excluded (lack of fever or positive culture results). A significant increase in histologic inflammation score was seen in the uterus (P<.001), placenta(P = .011), and fetal lung (P = .001) but not in other fetal tissues. These changes were seen earlier in the uterus and placenta and later in the fetal lung. Mitotic activity in the fetal brain decreased significantly by 8 hours after cervical inoculation. There was no inflammation in the fetal brain, and apoptosis in the fetal brain did not increase with time. CONCLUSIONS: Histologic inflammation occurs early in both the uterus and the placenta and later in the fetal lung in the rabbit model of acute intra-amniotic infection. This contrasts with the previously reported chronic model of intra-amniotic infection in the rabbit.

Acute intrauterine infection results in an imbalance between pro- and anti-inflammatory cytokines in the pregnant rabbit.

PROBLEM: Intrauterine infection results in an increase in cytokines. This study compared the time courses for the pro- and anti-inflammatory cytokine responses in 33 pregnant rabbits at 70% gestation. Pro-inflammatory markers were activated nuclear factor-kappa B (NF-kappaB) in placenta and tumor necrosis factor-alpha (TNF-alpha) in amniotic fluid. These were compared to the anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), in placenta and uterus. METHOD OF STUDY: Does were endoscopically inoculated with Escherichia coli through their cervices and sacrificed at six intervals between 0 and 30 hr post-inoculation. RESULTS: Activated NF-kappaB, determined by electromobility gel shift assay, increased significantly 16 hr after bacterial inoculation (P < or = 0.05). This was directly mirrored by TNF-alpha concentrations, determined by bioassay, in the amniotic fluid. However, IL-1ra levels, determined by enzyme-linked immunosorbent assay, did not increase in response to infection. CONCLUSIONS: Intrauterine infection results in an imbalance between pro- and anti-inflammatory cytokines that may potentiate infection-induced preterm delivery.

A randomized trial of conjugated group B streptococcal type Ia vaccine in a rabbit model of ascending infection.

OBJECTIVE: Maternal vaccination may become a central strategy in the prevention of early-onset group B Streptococcal sepsis. Unlike earlier group B streptococcal polysaccharide vaccines that were poorly immunogenic, newer vaccines conjugated to tetanus toxoid have been developed and have improved immunogenicity. We sought to evaluate a conjugated vaccine using our rabbit model of ascending infection. STUDY DESIGN: Rabbit does were randomized to receive either conjugated group B streptococcal type Ia (Ia-tetanus toxoid) or conjugated group B streptococcal type III (III-tetanus toxoid) vaccine. Does were vaccinated 7 days before conception and 7 and 21 days after conception. On days 28 to 30 of a 30-day gestation, does were inoculated intracervically with 10(6) colony-forming units of type Ia group B Streptococcus. Labor was induced if does were undelivered after 72 hours. Does were observed up to 7 days after inoculation. Offspring were observed up to 4 days. We obtained maternal cultures from the uterus, peritoneum, and blood and offspring cultures from the mouth, anus, and blood. Antibody levels were also determined. RESULTS: Offspring survival was significantly improved in the group receiving Ia-tetanus toxoid (P =.047). Outcomes such as maternal sepsis and severe illness, although not reaching statistical significance, showed a trend toward improved outcomes in the Ia-tetanus toxoid group. CONCLUSIONS: This is the first study to evaluate the conjugated group B streptococcal vaccine by using any model of ascending infection. The Ia-tetanus toxoid vaccine led to improved survival and was immunogenic but fell short of its expected efficacy in preventing ascending group B streptococcal disease under these experimental conditions.

Oral quinolone in the treatment of experimental polymicrobial puerperal infection in rabbits.

OBJECTIVE: To evaluate the efficacy of oral levofloxacin in the treatment of experimental polymicrobial puerperal infection in the rabbit. METHODS: Timed pregnant rabbits were anesthetized on day 29 or 30 of a 31-day gestation and 106 colony-forming units each of Escherichia coli, group B streptococcus, and Staphylococcus saccharolyticus were inoculated endoscopically in the cervices. Labor was induced with intramuscular oxytocin 16 hours later if it had not occurred spontaneously. The animals then were observed every 3 hours for fever; when a temperature of 104F was reached, treatment was begun. Animals were assigned randomly in a blinded, placebo-controlled manner to received oral levofloxacin (10 mg/kg/day) or placebo and were treated twice daily for 4-5 days. The animals were killed and necropsy was performed 4-6 hours after the last dose. Specimens for culture were taken from uterine horns, peritoneum, and blood. Levofloxacin concentrations were determined from blood samples at necropsy. Clinical cure of fever, eradication of microbes, and presence of uterine abscesses at necropsy were assessed. RESULTS: Compared with placebo-treated rabbits, levofloxacin-treated animals had a significantly greater number of clinical cures (nine of 11 versus four of 12, P=.027) and significantly more eradication of E coli (ten of 11 versus five of 12, P=.022). Four uterine abscesses were seen in 12 placebo-tested animals, compared with none of 11 levofloxacin-tested animals (P=.093). There was no difference in eradication of group B streptococcus between the two groups. No blood cultures were positive for organisms in any animal. Levofloxacin was detected in all treated animals, but at low levels (less than 1 microg/mL). CONCLUSION: Treatment of experimental puerperal infection with oral levofloxacin in rabbits resulted in significantly more clinical cures and eradication of E coli compared with treatment with placebo.

Epidemiology and outcomes associated with moderate to heavy Candida colonization during pregnancy. Vaginal Infections and Prematurity Study Group.

OBJECTIVE: Our purpose was to determine the risk factors, physical findings, microflora, and pregnancy outcome among pregnant women with moderate to heavy vaginal growth of Candida albicans and other Candida species. STUDY DESIGN: A multicenter cohort of 13,914 women were enrolled between 23 and 26 weeks' gestation. Women completed a questionnaire, underwent a physical examination, and had genital specimens taken for culture. A subset of 1459 women were reexamined during the third trimester. Pregnancy outcomes were recorded at delivery. RESULTS: The prevalence of moderate to heavy Candida colonization at midgestation was 10%. Colonized women, 83% of whom carried C. albicans, were more likely to be black or Hispanic, unmarried, a previous oral contraceptive user, and to manifest clinical signs indicative of Candida carriage. Candida colonization was positively associated with Trichomonas vaginalis, group B streptococci, and aerobic Lactobacillus and was not associated with adverse pregnancy outcome. CONCLUSION: These results suggest that Candida colonization is not associated with low birth weight or preterm delivery.

Assessment of office-based care of sexually transmitted diseases and vaginitis and antibiotic decision-making by obstetrician-gynecologists.

OBJECTIVE: Survey office-based obstetric-gynecologic practitioners regarding their knowledge of infectious disease care and antibiotic use. METHODS: A survey questionnaire of multiple-choice questions was mailed to Fellows of the American College of Obstetricians and Gynecologists about clinical entities for which recommendations have undergone recent changes or about which there was a lack of consensus in a prior similar survey (Gibbs RS, McGregor JA, Mead PB, et al.: Obstet Gynecol 83:631-636, 1994). RESULTS: Respondents indicated that oral metronidazole was their most frequent choice to treat bacterial vaginosis. Ampicillin (57%) was used more often than penicillin (39%) for intrapartum group B streptococcus prophylaxis. Azithromycin was preferred (61%) over erythromycin-base (38%) for chlamydia treatment during pregnancy. There were several modes of practice that deviated from accepted care: 27% and 29% did not screen for chlamydia and gonorrhea, respectively, in pregnancy; 17% used cultures for Gardnerella vaginalis to diagnose bacterial vaginosis; 25% considered quinolones to be safe in pregnancy; 93% felt metronidazole should never be used in pregnancy; and the majority (66%) would send a patient treated successfully for pelvic cellulitis home with an oral antibiotic. CONCLUSION: Respondents' infectious disease knowledge and practices in obstetrics and gynecology is appropriate in treating sexually transmitted diseases, bacterial vaginosis, and group B streptococcus. Numerous deficiencies still exist in screening for sexually transmitted diseases in pregnancy and diagnosing bacterial vaginosis, as well as in the choice of antibiotics to use or avoid for certain infections.

Use of antibiotics to prevent preterm birth.

Our purpose is to review recent data and provide a clinical opinion on the use of antibiotics to prevent preterm birth or related maternal-neonatal complications. A literature review and a synthesis of opinion are provided. During prenatal care, standard practices should be applied regarding Neisseria gonorrhoeae, Chlamydia trachomatis, and bacteriuria. In addition, screen for and treat bacterial vaginosis in patients at high risk for preterm birth but do not treat Ureaplasma urealyticum or group B streptococci genital colonization. With preterm labor and intact membranes, standard practices should be applied regarding group B streptococci prophylaxis. Do not give antibiotics routinely to prolong pregnancy, but in patients with bacterial vaginosis and Trichomonas vaginalis specific treatment should be given. With preterm premature rupture of membranes, standard practices should be applied regarding group B streptococci prophylaxis, but additional antibiotics should also be given to prolong pregnancies at 24 to 32 weeks' gestation. Reported adverse effects have been few to date. However, increased diligence is needed for resistant organisms. In selected clinical settings antibiotic therapy is now indicated to prolong pregnancy and prevent maternal-neonatal complications associated with preterm birth.

Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group.

BACKGROUND: Several studies have suggested that pregnant women infected with Trichomonas vaginalis may be at increased risk of an adverse outcome. GOAL: To evaluate prospectively the association between T. vaginalis and risk of adverse pregnancy outcome in a large cohort of ethnically diverse women. STUDY DESIGN: At University-affiliated hospitals and antepartum clinics in five United States cities, 13,816 women (5,241 black, 4,226 Hispanic, and 4,349 white women) were enrolled at mid-gestation, tested for T. vaginalis by culture, and followed up until delivery. RESULTS: The prevalence of T. vaginalis infection at enrollment was 12.6%. Race-specific prevalence rates were 22.8% for black, 6.6% for Hispanic, and 6.1% for white women. After multivariate analysis, vaginal infection with T. vaginalis at mid-gestation was significantly associated with low birth weight (odds ratio 1.3; 95% confidence interval 1.1 to 1.5), preterm delivery (odds ratio 1.3; 95% confidence interval 1.1 to 1.4), and preterm delivery of a low birth weight infant (odds ratio 1.4; 95% confidence interval 1.1 to 1.6). The attributable risk of T. vaginalis infection associated with low birth weight weight in blacks was 11% compared with 1.6% in Hispanics and 1.5% in whites. CONCLUSIONS: After considering other recognized risk factors including co-infections, pregnant women infected with T. vaginalis at mid-gestation were statistically significantly more likely to have a low birth weight infant, to deliver preterm, and to have a preterm low birth weight infant. Compared with whites and Hispanics, T. vaginalis infection accounts for a disproportionately larger share of the low birth weight rate in blacks.

Tips of the slongue: the enduring legacy of W.A. Spooner.

Slips of the tongue are common and often amusing phonic errors. Although surely not the first speaker to make such transpositions, W.A. Spooner (1844-1930) was well known for them and was the source of the eponym, "Spoonerism." Several of his noted slips are presented along with a whimsical obstetric presentation.

Intra-amniotic infection and premature rupture of the membranes.

The outcome of fetuses and newborn infants often is linked to maternal complications. IAI and PROM are key risk factors for neonatal sepsis.

Double-Blind Placebo-Controlled Treatment Trial of Chlamydia trachomatis Endocervical Infections in Pregnant Women.

OBJECTIVE: The purpose of this study was to determine if treatment of pregnant women with Chlamydia trachomatis infection would lower the incidence of preterm delivery and/or low birth weight. METHODS: Pregnant women between the 23rd and 29th weeks of gestation were randomized in double-blind fashion to receive either erythromycin 333 mg three times daily or an identical placebo. The trial continued until the end of the 35th week of gestation. RESULTS: When the results were examined without regard to study site, erythromycin had little impact on reducing low birth weight (8% vs. 11%, P = 0.4) or preterm delivery (13% vs. 15%, P = 0.7). At the sites with high persistence of C. trachomatis in the placebo-treated women, low birth weight infants occurred in 9 (8%) of 114 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.04) and delivery <37 weeks occurred in 15 (13%) of 115 erythromycin-treated and 18 (17%) of 105 placebo-treated women (P = 0.4). CONCLUSIONS: The results of this trial suggest that the risk of low birth weight can be decreased by giving erythromycin to some women with C. trachomatis. Due to the high clearance rate of C. trachomatis in the placebo group, these data do not provide unequivocal evidence that erythromycin use in all C. trachomatis-infected women prevents low birth weight.

Randomized, placebo-controlled trial of transplacental antibiotic prophylaxis of neonatal group B streptococcal colonization and bacteremia in rabbits.

OBJECTIVE: We evaluated the effect of maternal administration of ampicillin/sulbactam on colonization and bacteremia in newborn rabbits after intracervical inoculation of mothers with group B streptococci (GBS). METHODS: New Zealand white rabbits on day 30 of a 31-day gestation were inoculated intracervically with 10(4)-10(5) colony forming units (cfu) GBS. Two hours after inoculation mothers received ampicillin/sulbactam (50 mg/kg) or saline (control) intramuscularly as a single dose, in a randomized double-blinded manner. We induced labor 4 h later with intramuscular oxytocin. At delivery, cultures for GBS were taken from neonatal oropharynx. Thereafter, cultures were taken from neonatal oropharynx and anorectum daily and from neonatal heart at death or after 96 h. Sample size analysis showed a need for 17 pups in each group. RESULTS: In the control group, induction failed in one animal that was excluded from analysis. At birth, 0 of 39 pups of treated does had positive oropharyngeal cultures compared to 26 of 27 (96%) pups of saline-treated does (P < 0.0001). Pups treated with antibiotic in utero were also significantly less likely to have positive oropharyngeal cultures at 24, 48, and 72 h after birth compared to controls (24 h, 0% vs. 100%, P < 0.0001; 48 h, 8% vs. 100%, P < 0.0001; 72 h, 16% vs. 100%, P < 0.0001). Treated pups were significantly less likely to have positive anorectal cultures at 24, 48, and 72 h after birth compared to control animals (24 h, 0% vs. 100%, P < 0.0001; 48 h, 0% vs. 95%, P < 0.0001; 72 h, 0% vs. 92%, P < 0.0001). Treated pups were significantly less likely to have positive heart cultures at 72 h after birth compared to controls (11% vs. 92%, P < 0.0002). Cumulative neonatal survival was higher in treated pups compared to controls at 72 and 96 h after birth (72 h, 32% vs. 0%, P = 0.0003; 96 h, 26% vs. 0%, P = 0.015). CONCLUSIONS: Single dose transplacental prophylaxis given 4 h before delivery resulted in decreased neonatal GBS colonization and bacteremia and improved neonatal survival in rabbits.

The effect of timing of single-dose transplacental ampicillin-sulbactam therapy for prevention of neonatal group B streptococcal colonization and bacteremia in a rabbit model.

OBJECTIVE: Our purpose was to evaluate the effect of maternal administration of ampicillin-sulbactam on group B streptococcal colonization and bacteremia in newborn rabbits. STUDY DESIGN: Before induction of labor, timed pregnant New Zealand White rabbits on day 29 of a 31-day gestation received no therapy or ampicillin-sulbactam 50 mg/kg intramuscularly as a single dose 2 to 8 hours before delivery. Labor was induced with oxytocin. After delivery, the oropharynx of each pup was inoculated with 10(9) cfu of type la group B Streptococcus. Cultures of each pup were taken from the oropharynx and anorectum daily and from the heart at death or after 96 hours. Ampicillin-sulbactam concentrations were determined at delivery in both mothers and pups. RESULTS: Thirteen animals were assigned to no therapy and 14 animals to ampicillin-sulbactam. Untreated pups had 100% oropharyngeal colonization at 24 hours. Pups treated with antibiotic were significantly less likely to have positive oropharyngeal cultures at 24 and 48 hours after birth than did untreated pups (24 hours 47% vs 100%, p < 0.0001; 48 hours 68% vs 91%, p = 0.0006). For anorectal cultures treated pups were significantly less likely to have positive culture results. Heart cultures were also less likely to have positive results for treated animals at 48 and 72 hours than for untreated animals (48 hours 30% vs 96%, p = 0.0001; 72 hours 31% vs 71%, p = 0.03). Treated pups had higher rates of survival at 48 hours (89% vs 62%, p < 0.0001). When neonatal oropharyngeal colonization at 24 hours after birth was compared with length of time from maternal antibiotic injection to delivery, there was a significant polynomial relationship (r = 0.78, p < 0.05). Ampicillin-sulbactam serum concentrations were highest 3 to 5 hours after injection. An inverse relationship existed between the rate of neonatal oropharyngeal colonization with group B streptococci at 24 hours after birth and neonatal ampicillin serum concentrations near birth (r = 0.733). CONCLUSION: Transplacental treatment with a single intramuscular dose of ampicillin-sulbactam significantly decreased neonatal colonization and bacteremia after oral inoculation with type la group B Streptococcus. An effect of ampicillin-sulbactam was evident as early as 2 hours but maximal 3 to 5 hours after injection.

Ascending group B streptococcal genital infection in the rabbit model.

OBJECTIVE: We investigated in a pregnant rabbit model the effects of intravaginal inoculation of type la group B streptococci and antibiotic intervention. STUDY DESIGN: We inoculated 10(4) to 10(6) cfu of type la group B streptococci into the upper vagina hysteroscopically at day 21 to 27 of a 31-day gestation. Initially we studied the natural history in 23 animals and then allocated the next 31 animals to receive either no therapy or ampicillin-sulbactam intramuscularly beginning immediately after inoculation. Outcomes were delivery, fever, positive cultures for group B streptococci, any live fetuses, and maternal death. RESULTS: Without antibiotic treatment upper vaginal inoculation led to frequent complications, namely, fever in 44% (15/34), delivery in 41% (14/34), positive endometrial cultures in 47% (15/32), and positive blood cultures in 26% (7/27). Live fetuses were present in only 53% (18/34). Animals treated with antibiotics were significantly less likely to have fever (p < 0.01), positive endometrial cultures (p < 0.01), or positive blood cultures (p = 0.03) and were more likely to have a live fetus (p = 0.04) than untreated animals were. CONCLUSION: Upper vaginal inoculation with type la group B streptococci in the rabbit led to an ascending infection of the upper genital tract, causing serious adverse outcomes in 40% with bacteremia in 26%. Early antibiotic intervention significantly improved outcomes. The susceptibility of the rabbit to ascending perinatal group B streptococci infection makes it an appealing model for further work pertinent to human disease.