Penny Clark

Risk factors for neonatal sepsis.

Objective To determine the associations between maternal characteristics, intrapartum events, and neonatal sepsis by multivariate analysis. Methods We enrolled 823 women from a high-risk population and analyzed maternal and neonatal demographic and outcome variables with univariate analysis and multivariate logistic modeling. Results Two-hundred sixteen women (26%) were colonized with group B streptococci, 82 (10%) developed chorioamnionitis, and 141 (17%) delivered prematurely. Cultureproven neonatal sepsis or meningitis was found in 15 of 833 (1.8%) neonates, and 101 of the remaining 818 (12.3%) infants were suspected to have sepsis or pneumonia. Multivariate analysis of risk factors for proven neonatal sepsis demonstrated a statistically significant association with decreasing gestational age, duration of internal monitoring for more than 12 hours (odds ratio [OR] 7.2, 95% confidence interval [CI] 1.6–32.2), maternal group B streptococcal infection (OR 4.2, 95% CI 1.4–13.1), chorioamnionitis (OR 4.4, 95% CI 1.2–16.1), and endometritis (OR 6.4, 95% CI 1.2–34.2). Conclusion Through the use of multivariate modeling, we determined that chorioamnionitis or endometritis, preterm delivery, group B streptococcal colonization, and a prolonged duration of internal monitoring are independent risk factors for neonatal sepsis. We postulate that the presence of a foreign body that traverses the birth canal may facilitate ascending peripartal infection.

Antibiotic susceptibility profiles for group B streptococci isolated from neonates, 1995-1998

Antibiotic susceptibility profiles were analyzed for 119 invasive and 227 colonizing strains of group B streptococci isolated from neonates at 6 US academic centers. All strains were susceptible to penicillin, vancomycin, chloramphenicol, and cefotaxime. The rate of resistance to erythromycin was 20.2% and to clindamycin was 6.9%. Resistance to erythromycin increased in 1997. Type V strains were more resistant to erythromycin than were type Ia (P=.003) and type Ib (P=.004) strains and were more resistant to clindamycin than were type Ia (P<.001), type Ib (P=.01), and type III (P=.001) strains. Resistance rates varied with geographic region: in California, there were high rates of resistance to erythromycin and clindamycin (32% and 12%, respectively), and low rates in Florida (8.5% and 2.1%, respectively). Penicillin continues to be the drug of choice for treatment of group B streptococcus infection. For women who are penicillin intolerant, however, the selection of an alternative antibiotic should be guided by contemporary resistance patterns observed in that region.

Level of Maternal IgG Anti-Group B Streptococcus Type III Antibody Correlated with Protection of Neonates against Early-Onset Disease Caused by This Pathogen

The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients (neonates with EOD caused by GBS type III) and 143 matched control subjects (neonates colonized by GBS type III who did not develop EOD) of > or = 34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had > or = 10 microg/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of < 2 microg/mL. A vaccine that induces IgG anti-GBS type III levels of > or = 10 microg/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen.

Level of Maternal Antibody Required to Protect Neonates against Early-Onset Disease Caused by Group B Streptococcus Type Ia: A Multicenter, Seroepidemiology Study

Because of the difficulty of conducting efficacy trials of vaccines against group B streptococcus (GBS), the licensure of these vaccines may have to rely on studies that measure vaccine-induced antibody levels that correlate with protection. This study estimates the level of maternal antibody required to protect neonates against early-onset disease (EOD) caused by GBS type Ia. Levels of maternal serum IgG GBS Ia antibodies, measured by ELISAs in 45 case patients (neonates with EOD caused by GBS Ia) and in 319 control subjects (neonates colonized by GBS Ia but without EOD) born at > or =34 weeks gestation were compared. The probability of developing EOD declined with increasing maternal levels of IgG GBS Ia antibody (P = .03). Neonates whose mothers had levels of IgG GBS Ia antibody > or =5 microg/mL had an 88% lower risk (95% confidence interval, 7%-98%) of developing type-specific EOD, compared with those whose mothers had levels < 0.5 microg/mL. A vaccine that induces IgG GBS Ia antibody levels > or =5 microg/mL in mothers can be predicted to confer a high degree of type-specific immunity to EOD to their infants.

Capsular Polysaccharide Types of Group B Streptococcal Isolates from Neonates with Early-Onset Systemic Infection

The distribution of serotypes of group B streptococci (GBS) isolated from 67 infants with early-onset sepsis are described. Case-infants were assembled from 13 hospitals across the United States from 15 July 1995 to 5 February 1997 through prospective active surveillance. The distribution of GBS serotypes was Ia, 40%; Ib, 9%; II, 6%; III, 27%; V, 15%; and nontypeable, 3%. Type V occurred more frequently in the northeast region (New York and New Jersey) than in other regions (29% vs. 9%, P = .06). Conversely, type III occurred significantly less frequently in the northeast region than other regions (10% vs. 35%, P = .04). GBS types Ia, III, and V accounted for 82% of the isolates. This report supports previous observations about the emergence of GBS type V, but our data caution that conclusions about serotype distributions based on one geographic location or on a small number of patients may not be generally applicable. Continued monitoring seems necessary for the design of a GBS vaccine.

Phylogenetic Lineages of Invasive and Colonizing Strains of Serotype III Group B Streptococci from Neonates: a Multicenter Prospective Study

ABSTRACT This study compares the phylogenetic lineages of invasive serotype III group B streptococci (GBS) to those of colonizing strains in order to determine lineages associated with invasive disease. Isolates from 29 infants with early-onset disease (EOD) and from 196 colonized infants, collected in a prospective, multicenter study, were assigned a sequence type (ST) by multilocus sequence typing. Overall, 54.5% of the isolates were in the ST-19 complex, and 40.4% were in the ST-17 complex. Invasive strains were more likely to be in the ST-17 complex than were colonizing strains (59% versus 38%, P = 0.03). After we adjusted for potential confounders, the ST-17 complex was more likely to be associated with EOD than were other lineages (odds ratio = 2.51, 95% confidence interval = 1.02 to 6.20). These data support the hypothesis that ST-17 complex GBS are more virulent than other serotype III GBS.

Intrapartum antibiotic prophylaxis 1: relative effects of recommended antibiotics on gram-negative pathogens.

OBJECTIVE To assess whether the antibiotic chosen for intrapartum antibiotic prophylaxis affects the subsequent exposure of the neonate to ampicillin‐resistant gram‐negative bacteria. METHODS We performed a randomized clinical trial of ampicillin versus penicillin for intrapartum antibiotic prophylaxis. Genital tract cultures for Enterobacteriaceae were obtained at study entry and 8–36 hours postpartum. Organisms were isolated, identified, and tested for ampicillin susceptibility. RESULTS The ampicillin (n = 175) and penicillin (n = 177) groups, respectively, did not differ in rates of ampicillin‐resistant Escherichia coli at entry (25% versus 22%, P = .57) or postpartum (36% versus 38%, P = .64). Similarly, groups did not differ in rates of ampicillin‐resistant Enterobacteriaceae at entry (38% versus 32%, P = .23) or postpartum (51% versus 55%, P = .46). However, postpartum culture rates of resistant Escherichia coli were higher than entry culture rates for both the ampicillin (36% versus 25%, P = .026) and penicillin (38% versus 22%, P < .001) groups. Postpartum culture rates of resistant Enterobacteriaceae were also higher than entry culture rates for both the ampicillin (51% versus 38%, P < .001) and penicillin (55% versus 32%, P < .001) groups. Results were similar when considering only women who received two or more doses and no additional antibiotics. CONCLUSION Intrapartum antibiotic prophylaxis with either ampicillin or penicillin increases exposure of neonates to ampicillin‐resistant Enterobacteriaceae.

Inhibition of neutrophil oxidative burst and phagocytosis by meconium

OBJECTIVE Meconium in amniotic fluid has been associated with an increased prevalence of chorioamnionitis. In an effort to delineate the mechanism of this association, we determined the effect of meconium on the neutrophils capacity for phagocytosis and microbial killing by oxidative burst in vitro. STUDY DESIGN Sterile meconium samples were obtained from four fetuses at the time of breech delivery and were then pooled and lyophilized. Neutrophils were purified from whole blood of each of 13 pregnant nonlaboring patients. Phagocytosis and the oxidative burst of neutrophils in the presence and absence of meconium were assessed by single-cell analysis with flow cytometry. Phagocytosis was measured as the mean fluorescence intensity produced after 30 minutes of incubation with fluorescein-labeled Escherichia coli. Oxidative burst was measured as the mean fluorescence intensity resulting from the oxidation of internalized reduced dichlorodihydrofluorescein after 15 minutes of stimulation with phorbol myristate acetate. Oxidative burst was expressed as the neutrophil oxidative index and the net fluorescence intensity. Neutrophil oxidative index was equivalent to the quotient of the mean fluorescence intensity for phorbol myristate acetate-stimulated and unstimulated cells. Net fluorescence intensity was equivalent to the absolute difference between stimulated and unstimulated cells. RESULTS Exposure of neutrophils to light and very light meconium each resulted in significantly lower mean neutrophil oxidative index compared with unexposed controls (3.2 +/- 4.9 and 4.2 +/- 5.9 vs 16.2 +/- 7.5, p = 0.00002 and p = 0.0007, respectively) and significantly lower mean net fluorescence intensity than that of control cells (112 +/- 220 and 188 +/- 294 vs 613 +/- 328, p = 0.0001 and p = 0.005, respectively). Phagocytosis was significantly impaired in the presence of moderate meconium compared with control cells (2239 +/- 393 vs 4645 +/- 2071, p = 0.0001). Light meconium did not significantly affect phagocytosis. CONCLUSION Meconium has significant effects on neutrophil function in vitro. Both light and very light meconium inhibit the oxidative burst. Moderate meconium inhibits phagocytosis.

Intrapartum antibiotic prophylaxis 2: Positive predictive value of antenatal group B streptococci cultures and antibiotic susceptibility of clinical isolates

OBJECTIVE To estimate the probability of positive intrapartum group B streptococcus cultures among women previously identified as carriers of this organism, and to estimate the susceptibility of group B streptococci to six commonly used antibiotics. METHODS We performed a prospective cohort study of women identified as carriers of group B streptococci by current pregnancy genital tract (group 1) or urine cultures (group 2), or a positive culture in a prior pregnancy (group 3). Intrapartum culture specimens were obtained, and isolates were tested for susceptibility to six antibiotics using the agar disk diffusion technique. RESULTS Intrapartum cultures were positive for 68% (62, 73), 61% (49, 72), and 48% (36, 60) of groups 1 (n = 249), 2 (n = 69), and 3 (n = 59), respectively. Cultures were positive in 67% (61, 73) of women in group 1 whose cultures were done 42 days or less before delivery (n = 218). The proportion of isolates (n = 239) susceptible to penicillin, ampicillin, cefazolin, and vancomycin was 100% (98, 100). The proportion susceptible to clindamycin and erythromycin was 91% (87, 94) and 79% (73, 84), respectively. CONCLUSION The positive predictive value of antenatal group B streptococci cultures is lower than was previously reported. Clindamycin and erythromycin are not optimal agents for prophylaxis against early‐onset neonatal group B streptococcal infection in patients who are allergic to penicillin.

Correlation between cervical cytologic results and Gram stain as diagnostic tests for bacterial vaginosis

Abstract Objective: Our purpose was to determine the reliability of the Papanicolaou smear in making the diagnosis of bacterial vaginosis with the vaginal Gram stain used as the diagnostic standard. Study design: We conducted a prospective, blinded, cross-sectional study of 210 consecutive patients referred to the Colposcopy Clinic for evaluation of abnormal cervical cytologic results. Each patient had a standard Papanicolaou smear and Gram stain of vaginal discharge. The sensitivity, specificity, positive predictive value, and negative predictive value of the Papanicolaou smear were determined with the Gram stain used as the standard for diagnosis of bacterial vaginosis. Results: Of the 210 patients, 80 (38.1%) had Gram stains that were positive for bacterial vaginosis and 118 (56.2%) had negative Gram stains. Twelve (5.7%) had intermediate Gram stains that were also considered negative. Of the 80 patients with positive Gram stains, 44 had cervical smears consistent with bacterial vaginosis and 36 had negative smears. Of the 130 patients with negative Gram stains, two had a positive cervical smear. Therefore, compared to the Gram stain, cervical cytologic test results had a sensitivity of 55% and a specificity of 98%. The respective positive predictive and negative predictive values were 96% and 78%. Conclusion: Compared to Gram stain of vaginal secretions, the cervical Papanicolaou smear has fair sensitivity (55%) and excellent positive predictive value (96%) in diagnosing bacterial vaginosis.