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D A Eschenbach

Publications and source records attributed to D A Eschenbach.

At least 19 recordsLinked to original sources

A review of premature birth and subclinical infection.

Premature birth causes high rates of neonatal morbidity and mortality. There are multiple causes of preterm birth. This article reviews the evidence linking subclinical infection and premature birth. Although maternal genital tract colonization with specific organisms has been inconsistently associated with preterm birth and/or premature rupture of membranes, some infections have been consistently associated with preterm delivery. The association of histologic chorioamnionitis with prematurity is a consistent finding, but the mechanisms require further study. The relationship between histologic chorioamnionitis infection and the chorioamnionitis of prematurity requires additional research. A varying number of patients in "idiopathic" preterm labor have positive amniotic fluid cultures (0% to 30%), but it is not clear whether infection preceded labor or occurred as a result of labor. Evidence of subclinical infection as a cause of preterm labor is raised by finding elevated maternal serum C-reactive protein and abnormal amniotic fluid organic acid levels in some patients in preterm labor. Biochemical mechanisms for preterm labor in the setting of infection are suggested by both in vitro and in vivo studies of prostaglandins and their metabolites, endotoxin and cytokines. Some, but by no means all, antibiotic trials conducted to date have reported decreases in prematurity. These results support the hypothesis that premature birth results in part from infection caused by genital tract bacteria. In the next few years, research efforts must be prioritized to determine the role of infection and the appropriate prevention of this cause of prematurity.

Anti-Bacterial Agents

The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor.

To evaluate the relationships between gestational age, neonatal outcome, and amniotic fluid (AF) bacteria, we obtained AF from women with intact membranes in idiopathic preterm labor. Positive cultures were obtained from 20 (19%) of 105 women. The frequency of positive cultures was inversely related to gestational age: 23-26 weeks, nine of 20; 27-30 weeks, four of 24; and 31-34 weeks, seven of 61 (chi2 for trend, P less than .001). Fusobacterium nucleatum, Bacteroides ureolyticus, and Ureaplasma urealyticum were the most common isolates. Facultative and anaerobic bacteria were more commonly isolated from women at less than 30 weeks' gestation, and Ureaplasma urealyticum was commonly isolated at greater than 30 weeks' gestation. Forty percent of the patients identified as having positive AF facultative and anaerobic cultures by the research laboratory had negative cultures in the clinical laboratory. Clinical characteristics and maternal white blood cell count and differential did not differ between women with and without positive cultures. Elevated C-reactive protein levels and a positive AF Gram stain were the two most sensitive and specific methods to predict positive AF cultures. Women with positive cultures delivered a median of 1.0 day after enrollment, compared with 28.5 days for women with negative cultures. The median gestational age at delivery for women with positive cultures was 27.5 weeks, and the median birth weight was 866 g. Positive AF cultures were associated with respiratory distress syndrome, bronchopulmonary dysplasia, and neonatal death. If occult AF infection among women in preterm labor is a treatable cause of preterm birth, then treatment could markedly reduce both perinatal morbidity and mortality.

Amniotic Fluid

The relationship of hydrogen peroxide-producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women.

Lactobacilli provide an important microbial defense against genital colonization by pathogens. The role of hydrogen peroxide (H2O2) in the control of genital microflora was explored in a cross-sectional study of 275 women in the second trimester of pregnancy. Vaginal cultures were obtained for detection of H2O2-positive and H2O2-negative lactobacilli and other members of the genital microflora. Compared with women with H2O2-negative lactobacilli, women colonized by H2O2-positive lactobacilli were less likely to have bacterial vaginosis, symptomatic candidiasis, and vaginal colonization by Gardnerella vaginalis, Bacteroides, Peptostreptococcus, Mycoplasma hominis, Ureaplasma urealyticum, and viridans streptococci (P less than or equal to .05 for each comparison). In addition to the above organisms, women without vaginal lactobacilli were more likely than those women with H2O2-positive lactobacilli to have Chlamydia trachomatis, and less likely to be colonized by Enterococcus or coagulase-negative staphylococci (P less than .05 for each comparison). Vaginal colonization by group B streptococci or Escherichia coli was not related to the presence of H2O2-positive lactobacilli. These data suggest that the presence of H2O2-positive lactobacilli in the vagina is inversely correlated with infection by some genital pathogens in pregnant women.

Bacteria

Pelvic inflammatory disease. Key treatment issues and options.

OBJECTIVE: --To examine available data regarding optimal antimicrobial therapy for pelvic inflammatory disease (PID) and to address selected treatment issues confronting clinicians caring for women with PID. DATA SOURCES: --Studies evaluated to help establish the Centers for Disease Control's 1989 Sexually Transmitted Diseases Treatment Guidelines and other reports published since 1985. A MEDLINE search of English-language literature was conducted using the indexing terms "pelvic inflammatory disease" or "pelvic infections" or "salpingitis" and "treatment". In addition, abstracts and bibliographies of articles and books were reviewed. STUDY SELECTION: --Studies were selected for detailed review if they evaluated the effectiveness of an antimicrobial regimen for treatment of PID. DATA EXTRACTION: --All studies were evaluated to determine the numbers of women treated and the percentage with clinical or microbiologic evidence of cure. DATA SYNTHESIS: --A variety of combination antimicrobial regimens are highly effective in providing clinical and microbiologic evidence of cure; few data are available to assess optimal therapy for prevention of late sequelae. Because PID is polymicrobial in cause, recommended antimicrobial regimens are broad-spectrum in coverage. CONCLUSIONS: --No single agent that provides sufficient coverage is currently available. Several combination regimens appear highly effective clinically even among women with tubo-ovarian abscess formation. Uncertainties regarding the effectiveness of antimicrobial therapy for prevention of late sequelae complicate decisions regarding the choice among regimens and the appropriateness of ambulatory treatment of women with PID. Pending better data, hospitalization should be strongly considered, where feasible, particularly for those women with PID desiring further childbearing. Sex partners of all women with PID should be treated.

Anti-Bacterial Agents

Microbiologic causes and neonatal outcomes associated with chorioamnion infection.

Chorioamnion infection is associated with histologic chorioamnionitis and prematurity, but the specific chorioamnion microorganisms associated with histologic chorioamnionitis, prematurity, and poor neonatal outcome have not been identified. Bacteria were recovered from the chorioamnion cultures of 32% of 112 placentas delivered at less than or equal to 34 weeks' gestation and from 19% of 156 placentas delivered at greater than 34 weeks' gestation (odds ratio 2.1; 95% confidence interval 1.1 to 3.8). Chorioamnion bacteria most highly related to both prematurity and histologic chorioamnionitis were group B Streptococcus and Fusobacterium species. Chorioamnion infection with Peptostreptococcus was significantly related only to preterm delivery, and infection with Escherichia coli, Bacteroides, and Ureaplasma were significantly related to histologic chorioamnionitis. Among preterm infants, isolation of bacteria from the chorioamnion was related to an increased risk of neonatal death (rate ratio 3.8; 95% confidence interval 1.4 to 11.6). Bacterial infection of the chorioamnion is related to preterm birth, histologic chorioamnionitis, and neonatal death.

Adolescent

Antepartum cultures for Ureaplasma urealyticum are not useful in predicting pregnancy outcome. The Vaginal Infections and Prematurity Study Group.

To test the hypothesis that genital colonization with Ureaplasma urealyticum would predict adverse pregnancy outcome, 4934 women from five medical centers were evaluated for vaginal colonization with U. urealyticum between 23 and 26 weeks' gestation and followed up to delivery. U. urealyticum colonization was associated with maternal age, parity, racial-ethnic group, martial status, income, education, smoking, number of sexual partners, and colonization with Trichomonas vaginalis, Mycoplasma hominis, and bacterial vaginosis. After adjustment for medical and sociodemographic factors in a multivariate analysis, there was no difference in the mean birth weight or proportion of low-birth-weight infants delivered by women who carried U. urealyticum and those who did not. U. urealyticum colonization at 23 to 26 weeks was not associated with preterm rupture of membranes, preterm labor, or preterm delivery. A positive vaginal culture for U. urealyticum in midgestation does not predict those women at risk for preterm labor, preterm delivery, preterm premature rupture of membranes, or delivery of a low-birth-weight infant.

Adolescent

A randomized placebo-controlled trial of erythromycin for the treatment of Ureaplasma urealyticum to prevent premature delivery. The Vaginal Infections and Prematurity Study Group.

Ureaplasma urealyticum has been associated with low birth weight and histologic chorioamnionitis and it is a frequent isolate from the chorioamnion of patients who are delivered prematurely. In prior clinical trials using antibiotics active against U. urealyticum, antibiotic treatment was associated with reduced prematurity and increased mean birth weight. In this multicenter, randomized, double-blind clinical trial, pregnant women with U. urealyticum were treated with 333 mg of erythromycin base or placebo three times daily, starting between 26 and 30 weeks' gestation and continuing through 35 completed weeks of pregnancy. Women with urinary tract infection or Neisseria gonorrhoeae infection were excluded from the trial, and women with Chlamydia trachomatis or group B streptococci were excluded from these analyses. Erythromycin did not eliminate U. urealyticum from the lower genital tract. There were no significant differences between erythromycin- and placebo-treated women in infant birth weight or gestational age at delivery, in frequency of premature rupture of membranes, or in neonatal outcome.

Adult

Combination antimicrobial therapy in the treatment of acute pelvic inflammatory disease.

We compared the clinical and microbiologic efficacy of two broad-spectrum combination antimicrobial regimens in the treatment of 148 patients with acute pelvic inflammatory disease. Patients were randomized to inpatient treatment with either cefoxitin and doxycycline (n = 75) or clindamycin and tobramycin (n = 73). These antibiotics were administered intravenously for at least 4 days, and up to 48 hours beyond defervescence. Patients were discharged on a regimen of oral doxycycline or clindamycin in accordance with the intravenous regimen to complete a total duration of therapy of 2 weeks. Neisseria gonorrhoeae (53%) and Chlamydia trachomatis (31%) were the microorganisms that were isolated most frequently from the genital tract of enrolled patients. At follow-up, N. gonorrhoeae was isolated in two patients, and C. trachomatis was isolated in none. The overall initial favorable response rate to combination antimicrobial therapy was 98.5% (130/132) in patients with uncomplicated pelvic inflammatory disease and 81% (13/16) in patients with pelvic inflammatory disease that was complicated by tuboovarian abscess. A greater than 70% decrease in abdominal tenderness score occurred in 89% of 111 patients within 6 weeks of hospital discharge. There were no significant differences between antibiotic treatment groups in any response categories or in toxicity. During the initial hospitalization, five patients (three with tuboovarian abscess; one with a pyosalpinx, and one with intractable acute and chronic pelvic inflammatory disease) required surgical intervention. These results support the recommendation to use broad-spectrum combination antimicrobial therapy for the treatment of acute pelvic inflammatory disease.

Acute Disease

Vaginal Bacteroides species are associated with an increased rate of preterm delivery among women in preterm labor.

The relationship of high concentrations of vaginal microorganisms with an increased rate of preterm delivery (less than or equal to 34 weeks) among women in preterm labor was evaluated. Quantitative vaginal cultures were obtained from 211 women in preterm labor between gestational ages of 22 and 34 completed weeks. Preterm delivery occurred in 139 (66%). The rate of preterm delivery was determined by Cox proportional hazards models. Women with greater than 10(7) cfu/ml of vaginal fluid of facultative lactobacilli had a 40% decreased rate of preterm delivery (rate ratio [RR] = 0.6, 95% confidence interval (CI) = 0.4-0.9). An increased rate of preterm delivery occurred among women with Bacteroides bivius at concentrations of greater than 10(4) cfu/ml (RR = 2.0, 95% CI = 1.4-2.9) and Bacteroides fragilis (RR = 1.7, 95% CI = 1.0-2.8). Other microorganisms, including Gardernella vaginalis, the genital mycoplasmas, group B streptococci, Escherichia coli, and Peptostreptococcus species, were not associated with an increased rate of preterm delivery for women in preterm labor.

Adolescent

Control of the microbial flora of the vagina by H2O2-generating lactobacilli.

H2O2-generating lactobacilli (LB+) are present in the vagina of most normal women but are absent from most women with bacterial vaginosis (BV). LB+ at high concentration was toxic to Gardnerella vaginalis (the predominant organism in the vagina of women with BV); when the LB+ was lowered to a level where it was ineffective alone, the addition of myeloperoxidase and chloride reinstituted toxicity. Toxicity was inhibited by catalase and was not seen when H2O2-negative lactobacilli were used, implicating H2O2 as the toxic molecule. LB+ could be replaced by H2O2 and chloride by iodide, bromide, or thiocyanate. The optimum pH for inhibition of G. vaginalis was 5.0-6.0 LB+ also was autoinhibitory when combined with myeloperoxidase and chloride. LB+ alone at low concentrations was toxic to Bacteroides bivius through the formation of H2O2. Adequate amounts of peroxidase were found in the vagina of 17 of 21 women. These findings suggest that LB+ may contribute to the control of the vaginal flora, particularly in the presence of peroxidase and a halide.

Antibiosis

C-reactive protein in normal pregnancy.

Maternal serum C-reactive protein (CRP) has been studied extensively as an adjunct in the diagnosis of subclinical infection among pregnant women with preterm labor or preterm rupture of membranes. However, before the utility of CRP can be studied in pregnancies with these complications, the effects of normal pregnancy and labor on maternal serum CRP levels must be established. We determined CRP levels serially from 22 weeks' gestation until delivery in healthy pregnant women without antepartum complications. Median CRP values for women not in labor ranged from 0.7-0.9 mg/dL, depending on gestational age; 95% of the values were 1.5 mg/dL or lower. No consistent change in CRP levels with gestational age was found among serially sampled women not in labor. The median CRP value for women in labor at term was 1.3 mg/dL, and 32% of values were over 1.5 mg/dL. Median CRP values in normal pregnancies appear to be higher than standardized values for nonpregnant individuals, and CRP values are further elevated in labor. Understanding the physiology and temporal course of the increase in CRP in normal pregnancy and labor may help to clarify the appropriate use of CRP in complicated pregnancies.

Adolescent

Upper genital tract isolates at delivery as predictors of post-cesarean infections among women receiving antibiotic prophylaxis.

The introduction of antibiotic prophylaxis for cesarean delivery has decreased the risk of postpartum endometritis and wound infection, but factors that contribute to prophylaxis failure are not understood. To determine factors that might contribute to postpartum infections following antibiotic prophylaxis, we cultured amniotic fluid, decidua, and chorioamniotic membrane specimens for anaerobic and facultative bacteria and for genital mycoplasmas at cesarean delivery. Women were assessed daily for the development of infections, and if endometritis developed, a protected endometrial culture was obtained. Postpartum endometritis developed in 16 and wound infection in four of 102 women. Infection rates were similar for women receiving cefotetan (N = 50) or cefoxitin (N = 52) for prophylaxis. The isolation of group B streptococcus (P less than .001) or Enterococcus faecalis (P = .03) from the upper genital tract at delivery was significantly associated with postpartum endometritis. Antibiotic-resistant organisms (other than enterococci) were recovered uncommonly at delivery or with postpartum infections. Group B streptococcus was susceptible to the prophylactic agents used, suggesting that virulence factors other than antibiotic resistance are important for the development of postpartum endometritis. Group B streptococcus, E faecalis, and bacteria associated with bacterial vaginosis were recovered from the endometrium at the time of postpartum endometritis.

Bacterial Infections

Microbiological, epidemiological and clinical correlates of vaginal colonisation by Mobiluncus species.

The microbiological and epidemiological correlates of vaginal colonisation by Mobiluncus species were examined among randomly selected women attending a sexually transmitted disease (STD) clinic. Women positive for Trichomonas vaginalis were excluded. Mobiluncus spp. were detected by Gram stained vaginal smear in 21% of 633 STD clinic patients, including 53% of those with and 4% of those without bacterial vaginosis (BV), as diagnosed by clinical criteria. Gardnerella vaginalis and Mycoplasma hominis detected by vaginal culture and Mobiluncus detected by vaginal Gram stain were each independently associated with BV after adjusting by logistic regression for the presence of sexually transmitted disease pathogens, gravidity, parity and number of lifetime sexual partners (p less than 0.001 for each organism). Bacterial vaginosis was negatively correlated with isolation of lactobacilli, yeast and herpes simplex virus. After adjusting for presence or absence of BV, women with Mobiluncus were more likely to harbour G vaginalis (odds ratio 5.6, 95% confidence interval 1.6-19.5), M hominis (OR 3.7, 95% CI 2.0-7.0) and Neisseria gonorrhoeae (OR 2.9, 95% CI 1.4-6.0) and less likely to harbour vaginal yeast (OR 0.4, 95% CI 0.2-1.0); were more likely to be black (OR 2.7, 95% CI 1.5-4.6), and to have been pregnant (OR 1.8, 95% CI 1.1-3.1); but after the adjustment for BV, vaginal colonisation by Mobiluncus was not associated with symptoms of odour, abdominal pain, menstrual irregularities, or with adnexal tenderness. In summary, Mobiluncus, Gardnerella vaginalis and Mycoplasma hominis were independently associated with a clinical diagnosis of bacterial vaginosis, and Mobiluncus was further associated with the presence of BV-associated microorganisms (M hominis and G vaginalis), N gonorrhoeae, black race, and gravidity.

Adult

Evaluation of a rapid enzyme immunoassay test for detection of group B Streptococcus.

The purpose of this study was to determine the reliability of the ICON immunoassay in detecting vaginal group B Streptococcus in pregnant women. Vaginal cultures were obtained at the time of sterile speculum examinations from 300 laboring women. The frequency of vaginal group B streptococcal colonization was 10%. A duplicate vaginal swab was used in the immunoassay, which required less than 10 minutes for completion. The immunoassay could reproducibly detect 3+ to 4+ growth (greater than 10(5) colony-forming units per milliliter of vaginal fluid), which was considered heavy colonization. The overall sensitivity, specificity, positive predictive value, and negative predictive value were 33, 95, 43, and 93%, respectively, compared with culture. For heavy colonization (3+ to 4+ growth), the sensitivity, specificity, positive predictive value, and negative predictive value were 100, 95, 32, and 100%, respectively. The immunoassay is a highly sensitive and specific test for detection of heavy vaginal colonization by group B streptococci in obstetric patients, but cultures are required to detect light group B streptococcal colonization.

Evaluation Studies as Topic

Demographic and behavioral predictors of Trichomonas vaginalis infection among pregnant women. The Vaginal Infections and Prematurity Study Group.

There is little available information on the demographic and behavioral factors associated with Trichomonas vaginalis in pregnant women. Among 13,816 women from six urban clinic centers, the prevalence rate by culture at mid-pregnancy was 12.6%. Women colonized with T vaginalis were significantly more likely to be black, cigarette smokers, unmarried, and less educated (all P less than .01). Several behavioral factors associated with T vaginalis included greater numbers of sexual partners both lifetime and in the last year, 5 years or more of sexual activity, and a history of gonorrhea (all P less than .01). Trichomonas vaginalis-colonized women were less sexually active in the preceding month compared with uncolonized women (P less than .01). Women using either barrier or oral contraception in the 6 months before becoming pregnant were far less likely to be colonized (P less than .01). Other factors such as age, gravidity, income level, age at first coitus, and use of antibiotics, alcohol, or douche during pregnancy were not independently associated with T vaginalis colonization. Because many of the factors predictive of increased risk of colonization have also been shown to be associated with adverse pregnancy outcome, they should be considered in assessing the association of T vaginalis with adverse pregnancy outcome.

Adult

Amoxicillin treatment of bacterial vaginosis during pregnancy.

The purpose of this investigation was to evaluate the efficacy of amoxicillin for treatment of bacterial vaginosis during pregnancy. The diagnosis of bacterial vaginosis was established by clinical examination and microscopic examination of a Gram stain and saline preparation of vaginal secretions. In a double-blind, randomized manner, 108 patients at 15-25 weeks' gestation were assigned to treatment with oral amoxicillin, 500 mg three times daily for 14 days, or placebo. Patients were evaluated 2 weeks after treatment, at 34-36 weeks' gestation, and at delivery. There were no significant differences between the two groups with respect to any clinical or microbiologic measure of treatment outcome. There were also no significant differences in the frequency of obstetric complications. We conclude that amoxicillin is not effective therapy for bacterial vaginosis in pregnant women.

Amoxicillin

Association between vaginal douching and acute pelvic inflammatory disease.

The vaginal douching habits of 100 consecutive municipal hospital patients with verified pelvic inflammatory disease (cases) were compared with those of 762 randomly selected controls (random controls) and 119 women thought to have pelvic inflammatory disease but in whom the diagnosis was not confirmed by laparoscopy and/or endometrial biopsy specimen (internal controls). Because patients had been symptomatic for no more than 3 weeks, current douching was arbitrarily defined as any douching during the previous 2 months. Current douching was more common among those with pelvic inflammatory disease than among random controls or internal controls. Among current douchers, pelvic inflammatory disease was significantly related to frequency of douching. For example, when cases were compared with random controls, those who douched three or more times per month were 3.6 times more likely than those who douched less than once per month to have confirmed pelvic inflammatory disease. A logistic regression model was used to adjust for demographic, behavioral, and other possible confounding variables. Even after adjustments, douching during the previous 2 months remained associated with pelvic inflammatory disease. These data suggest that among these women vaginal douching may be a risk factor for pelvic inflammatory disease.

Acute Disease