Bifidobacterium animalis subsp. lactis 420 mitigates the pathological impact of myocardial infarction in the mouse.

There is a growing appreciation that our microbial environment in the gut plays a critical role in the maintenance of health and the pathogenesis of disease. Probiotic, beneficial gut microbes, administration can directly attenuate cardiac injury and post-myocardial infarction (MI) remodelling, yet the mechanisms of cardioprotection are unknown. We hypothesised that administration of Bifidobacterium animalis subsp. lactis 420 (B420), a probiotic with known anti-inflammatory properties, to mice will mitigate the pathological impact of MI, and that anti-inflammatory T regulatory (Treg) immune cells are necessary to impart protection against MI as a result of B420 administration. Wild-type male mice were administered B420, saline or Lactobacillus salivarius 33 (Ls-33) by gavage daily for 14 or 35 days, and underwent ischemia/reperfusion (I/R). Pretreatment with B420 for 10 or 28 days attenuated cardiac injury from I/R and reduced levels of inflammatory markers. Depletion of Treg cells by administration of anti-CD25 monoclonal antibodies eliminated B420-mediated cardio-protection. Further cytokine analysis revealed a shift from a pro-inflammatory to an anti-inflammatory environment in the probiotic treated post-MI hearts compared to controls. To summarise, B420 administration mitigates the pathological impact of MI. Next, we show that Treg immune cells are necessary to mediate B420-mediated protection against MI. Finally, we identify putative cellular, epigenetic and/or post-translational mechanisms of B420-mediated protection against MI.

Maternal ABO blood group type B: a risk factor in the developement of neonatal group B streptococcal disease.

In a prospective study of maternal genital colonization with group B streptococci (GBS) at the time of delivery, epidemiological data, including blood type (ABO group), were recorded for the 1,062 patients studied. Blood type B was found in a statistically significant higher proportion of patients colonized with GBS (28%) compared with the total population (16.4%) (P less than .005, X2 = 8.43). Women with blood type B were twice as likely to be colonized as those with types O or A. Hypotheses to explain this observation include the possibilities that GBS possess a B-like antigen, rendering parturients who lack anti-B antibody at increased risk for GBS colonization, or that GBS possess a receptor site for B surface antigens. One may speculate that a mutation toward an affinity for the human ABO blood group type B accounts for the advent of the group B Streptococcus as a significant perinatal pathogen.

Vertical transmission of Ureaplasma urealyticum in full term infants.

Ureaplasma urealyticum is a common inhabitant of the urogenital tract of pregnant women. Although colonization of newborn infants with U. urealyticum has been documented previously, the actual rate of vertical transmission has not been determined. Cervical cultures for U. urealyticum were performed on 1315 pregnant women on admission to the labor suite. A positive culture was found in 810 (62%). Eye, nasopharyngeal and/or throat, vaginal and rectal cultures were obtained in the first 5 days of life from 132 full term infants born to mothers colonized with U. urealyticum. Fifty-nine infants (45%) had at least one culture site positive for U. urealyticum (eye, 4%; nasopharynx 24%; throat, 16%; vagina, 53%; and rectum, 9%). None of the infants had evidence of disease caused by U. urealyticum during the nursery stay. Vertical transmission was not affected by the method of delivery. However, among the vaginally delivered infants, rupture of membranes greater than 1 hour correlated with an increased rate of vertical transmission of U. urealyticum (52%) compared with rupture of membranes less than or equal to 1 hour (22%) (P less than 0.05). Because vertical transmission of U. urealyticum occurs frequently, caution must be exercised when attributing disease to U. urealyticum based solely on positive cultures of mucosal surfaces.

Vertical transmission of Ureaplasma urealyticum from mothers to preterm infants.

Ureaplasma urealyticum is a common component of the vaginal flora during pregnancy. Although colonization of low birth weight infants with U. urealyticum occurs frequently, the actual rate of vertical transmission of U. urealyticum in preterm infants has not been determined. Sixty-five preterm infants (less than 37 weeks of gestation) born to mothers colonized with U. urealyticum had eye, throat, vagina and rectum cultured for U. urealyticum at 1, 3 and 7 days of age and weekly thereafter for the first month of life while the infants remained in the hospital. Thirty-eight infants (58%) had at least one culture site positive for U. urealyticum (eye, 8%; throat, 37%, vagina, 54%; and rectum, 18%). Vertical transmission was not affected by method of delivery or duration of rupture of amniotic membranes. The rate of vertical transmission of U. urealyticum was higher among infants with birth weight less than 1,000 g (89%) than among those with birth weight of 1,000 g or greater (54%) (P = 0.07). Chronic lung disease developed in 9 of the 65 (14%) infants; 8 were colonized with U. urealyticum. The high rate of ureaplasmal colonization and chronic lung disease in infants less than 1,000 g makes these infants a suitable target population for a clinical treatment trial to determine whether eradication of U. urealyticum would decrease the incidence of chronic lung disease.

Ureaplasma urealyticum colonization and chronic lung disease in low birth weight infants.

Ureaplasma urealyticum is a common component of the vaginal flora during pregnancy. Transmission of U. urealyticum to the low birth weight infant may contribute to neonatal respiratory disease. We studied prospectively 111 infants with birth weights of 2 kg or less who were consecutively admitted to a neonatal intensive care unit during a 7-month period. The infants had eye, throat, vagina and/or rectum cultured for U. urealyticum on days 1, 3 and 7 and weekly thereafter until the time of discharge. Forty-six infants (41%) had at least one culture site positive for U. urealyticum (eye, 9%; throat, 35%; vagina, 34%; and rectum, 13%). Respiratory distress at birth was not associated with U. urealyticum colonization. However, colonization with U. urealyticum was significantly associated with the development of chronic lung disease. Of the infants colonized with U. urealyticum 30% developed chronic lung disease, whereas 8% of those not colonized developed chronic lung disease (P less than 0.05). Duration of positive pressure ventilation and oxygen therapy could not account for the higher incidence of chronic lung disease in the infants colonized with U. urealyticum. Stepwise logistic regression analysis using the profiles of birth weight, need for intubation and status of colonization with U. urealyticum correctly identified 79% of the infants who developed chronic lung disease. Additional studies serologic techniques are needed to confirm the association of U. urealyticum colonization and chronic lung disease in low birth weight infants.

Evaluation of the Gram stain as a screening tool for maternal carriage of group B beta-hemolytic streptococci. The Vaginal Infections and Prematurity Study Group.

To determine the usefulness of the vaginal Gram stain as a screen for maternal group B streptococcal carriage, we compared the presence of gram-positive cocci on Gram stain with a cervicovaginal culture in 7755 women at 23-26 weeks' gestation and in 1452 women at delivery. Group B streptococci were isolated from 18.4% of women at 23-26 weeks and 14.9% of women at delivery. The sensitivity, specificity, positive predictive value, and negative predictive value of the Gram stain were 28, 69, 17, and 81%, respectively, in mid-gestation and 34, 72, 18, and 86%, respectively, at delivery. The presence of gram-positive cocci on Gram stain was strongly associated with the isolation of Gardnerella vaginalis and with the presence of bacterial vaginosis. We conclude that most gram-positive cocci seen on Gram stain are probably anaerobes or micrococci and that the vaginal Gram stain is neither sensitive nor specific enough to be of use as a tool in the diagnosis of maternal group B streptococcal carriage.

The epidemiology of group B streptococcal colonization in pregnancy. Vaginal Infections and Prematurity Study Group.

Risk factors for cervicovaginal group B streptococcal colonization at 23-26 weeks' gestation were studied in 7742 women participating in the Vaginal Infections and Prematurity study. The prevalence of group B Streptococcus was 18.6%, and was greatest in (predominantly Caribbean) Hispanics from New York City, followed by blacks, whites, and other (predominantly Mexican) Hispanics. Group B Streptococcus was more common among older women and women of lower parity, and less common among women living with their partner compared with those living alone. Current smoking was associated with a decreased risk of colonization, and group B Streptococcus was less common among women with more education. Increased risk was seen only with extreme increases in sexual activity including both frequent intercourse and multiple partners during the previous year. The risk of colonization was greater when there was concurrent colonization with Candida sp, but group B Streptococcus was not associated with carriage of Chlamydia trachomatis, Ureaplasma urealyticum, Trichomonas vaginalis, and Mycoplasma hominis. External genital erythema and scaling, purulent vaginal discharge, and pH greater than 5 were associated with increased colonization. Although these associations can raise the clinical index of suspicion for group B streptococcal colonization in a given patient, the study data did not enable us to select a small group of women with a very high probability of colonization. We conclude that selective screening is not useful in detecting group B streptococcal colonization in pregnancy.

The epidemiology of preterm labor.

There are many factors that are associated with preterm labor and delivery. These include maternal conditions such as medical illness, anemia and uterine malformation. They may be related to past events such as prior obstetric complication, previous preterm labor, cervical surgery or induced abortion. They may be intrinsic to the current pregnancy, such as reproductive tract infection, multifetal gestation, maternal age, short interpregnancy interval or prolonged menstrual conception interval. Maternal behaviors such as smoking and substance abuse can be risk factors for a short gestation. Demographic variables such as race, employment and socioeconomic status can also be associated with preterm labor. This article briefly reviews these subjects.

Hypothyroidism caused by topical povidone-iodine in a newborn with omphalocele.

A case of physiologic hypothyroidism caused by the topical application of povidone-iodine (PVPI) in a newborn with an omphalocele is presented. The literature on systemic absorption and effects of PVPI is reviewed. A management strategy is offered.

Epidemiology of group B streptococcal colonization in pregnancy.

These data support the conclusions that: 1) An intrapartum screening program for GBS colonization favorably affects the outcome of GBSD, with mortality decreased to 10%. 2) Four risk factors--ABO blood group B, unregistered status, PROM and premature labor at less than 32 weeks--identify 83% of mothers whose infants develop GBSD. 3) There is no association between internal monitoring and mode of delivery and the vertical transmission of GBS. 4) Duration of membrane rupture does not affect vertical transmission or development of early-onset disease. This differs from previous findings. 5) Lastly, our findings regarding the natural history of asymptomatic infant carriers suggest that these infants play a previously unsuspected role in the epidemiology of GBS in the entire population.

Will current clinical effectiveness initiatives encourage and facilitate practitioners to use evidence-based practice for the benefit of their clients?

1996 saw the implementation of Clinical Effectiveness Initiatives by the NHS Executive and the Royal College of Nursing to promote the use of evidence-based care. This paper examines whether or not nurses will be encouraged and facilitated by these initiatives to provide evidence-based care for their clients. Both initiatives appear to assume that the use of evidence-based care leads to improved client care, but several issues are raised which still need to be resolved before this assumption can be made. The NHS Executive advocates the use of randomized controlled trials as the method of choice for providing evidence of clinical effectiveness. However, this may not necessarily be the best methodology for some areas of nursing practice. The paper concludes that the Royal College of Nursing's Clinical Effectiveness Initiative has great potential to provide the necessary motivation and facilitation, providing other professional issues are resolved.

Antibiotic resistance patterns of group B streptococci in pregnant women.

This study examined the antibiotic resistance patterns of group B streptococci (GBS) isolated from gravid women. A total of 156 vaginal and cervical isolates of GBS were examined for resistance to penicillin, ampicillin, clindamycin, cefoxitin, gentamicin, and erythromicin. No resistance to penicillin or ampicillin was found, nor was penicillinase production demonstrated. A high level of resistance to gentamicin was noted (91%). Of the isolates examined, 9, 9.5, and 15.3% exhibited either resistance or intermediate susceptibility to erythromycin, clindamycin, and cefoxitin, respectively. Thirty strains (19%) exhibited a multiple antibiotic resistance pattern. Given the high penicillin and ampicillin treatment failure rates when attempting to eradicate vaginal GBS colonization and our findings of higher and multiple drug resistance patterns of GBS, the selection of an alternative antibiotic regimen is of considerable clinical importance. We recommend that routine reporting of GBS susceptibilities by clinical laboratories be adopted.

Premature rupture of membranes, preterm delivery, and group B streptococcal colonization of mothers.

In a prospective study of colonization with group B streptococci (GBS) among 6,706 parturients, we found statistically increased incidences of premature rupture of membranes (PROM) and preterm delivery at less than 32 weeks' gestation among women colonized with GBS. PROM occurred in 8.1% of the total population but in 15.3% of the colonized population (p less than 0.005). Preterm delivery at less than 32 weeks' gestation occurred in 1.8% of the total population but among 5.4% of women colonized with GBS (p less than 0.005). The data suggest a causal relationship between GBS colonization and events leading to preterm birth. The possible impact of eradication of colonization with GBS on prematurity is considered.

Ureaplasma urealyticum and chronic lung disease of prematurity: critical appraisal of the literature on causation.

A critical appraisal of four cohort studies examining the relationship between Ureaplasma urealyticum and chronic lung disease (CLD) of prematurity is presented. Three studies were concurrently conducted, but the fourth was conducted 4 years later when surfactant replacement was a widespread practice. Although infants were enrolled in all studies soon after birth before they had developed CLD, there were differences in patients population, the definition of colonization with U. urealyticum, neonatal management, and the definition of CLD of prematurity. Despite the differences, all four studies found an association between colonization and development of CLD of prematurity. A combined estimate of relative risk for the four studies was 1.91 (95% confidence interval, 1.54-2.37). When infants were categorized into groups by birth weight, the association was not observed in infants who weighed > 1,250 g. The association was also not observed in infants who weighed < 750 g, but the risk of CLD of prematurity in the uncolonized control group was already 82%. Because the cohort study design allows for the possibility that one or more additional factors associated with U. urealyticum may be the true cause(s) of CLD of prematurity, there is strong but not definitive evidence that U. urealyticum causes CLD of prematurity.

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.

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.

Outcome of the Vaginal Infections and Prematurity Study: results of a clinical trial of erythromycin among pregnant women colonized with group B streptococci.

OBJECTIVE: Our purpose was to determine whether erythromycin treatment of pregnant women colonized with group B streptococci would reduce the occurrence of low birth weight (< 2500 gm) and preterm (< 37 completed weeks) birth. STUDY DESIGN: In a double-blind clinical trial, 938 carriers of group B streptococci were randomized to receive erythromycin base (333 mg three times a day) or matching placebo beginning during the third trimester and before 30 weeks and continuing for 10 weeks or until 35 weeks 6 days of pregnancy. RESULTS: Pregnancy outcomes were available for 97% of randomized women; 14% of subjects withdrew from the trial. Birth weight < 2500 gm occurred in 8.6% of the erythromycin and 6.1% of the placebo recipients (relative risk 1.4, 0.9 to 2.2, p = 0.16). Preterm delivery occurred in 11.4% of women randomized to erythromycin and in 12.3% randomized to placebo (relative risk 0.9, 95% confidence limits 0.6 to 1.3, p = 0.65). Greater benefit of erythromycin in reducing these outcomes was not observed among women reporting the best compliance. CONCLUSIONS: In this study of pregnant women colonized with group B streptococci treatment with erythromycin was not shown to be effective at prolonging gestation or reducing low birth weight. Greater than anticipated complicating factors, including spontaneous clearance of the organism, use of nontrial antibiotics, and density of colonization, may have resulted in population sizes too small to detect a benefit of treatment. Future studies should take these factors into account in determining sample sizes.

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.

Colonization with group B streptococci in pregnancy and adverse outcome. VIP Study Group.

OBJECTIVE: Our purpose was to study the association of cervicovaginal colonization with group B streptococci with pregnancy and neonatal outcome. STUDY DESIGN: A prospective study was conducted at seven medical centers between 1984 and 1989. Genital tract cultures were obtained at 23 to 26 weeks' gestation and at delivery. Prematurity and neonatal sepsis rates were compared between group B streptococci positive and negative women. RESULTS: Group B streptococci was recovered from 2877 (21%) of 13,646 women at enrollment. Heavy colonization was associated with a significant risk of delivering a preterm infant who had a low birth weight (odds ratio = 1.5, 95% confidence interval 1.1 to 1.9). Heavily colonized women given antibiotics effective against group B streptococci had little increased risk of a preterm, low-birth-weight birth. Women with light colonization were at the same risk of adverse outcome as the uncolonized women. Neonatal group B streptococci sepsis occurred in 2.6 of 1000 live births in women with and 1.6 of 1000 live births in women without group B streptococci at 23 to 26 weeks' gestation (p = 0.11). However, sepsis occurred in 16 of 1000 live births to women with and 0.4 of 1000 live births to women without group B streptococci at delivery (p < 0.001). CONCLUSIONS: Heavy group B streptococci colonization of 23 to 26 weeks' gestation was associated with an increased risk of delivering a preterm, low-birth-weight infant. Cervicovaginal colonization with group B streptococci at 23 to 26 weeks' gestation was not a reliable predictor of neonatal group B streptococci sepsis. Colonization at delivery was associated with sepsis.

The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early-onset neonatal group B streptococcal disease.

OBJECTIVE: Our purpose was to evaluate the effectiveness of a risk-based intrapartum antibiotic prophylaxis strategy for the prevention of early-onset neonatal group B streptococcal disease. STUDY DESIGN: Cases and controls were selected from infants born to women with one or more risk factors: preterm labor or rupture of membranes, prolonged rupture of membranes (>18 hours), fever during labor, or previous child with group B streptococcal disease. Cases were matched with controls by birth hospital and gestational age. Data abstracted from medical records were analyzed to estimate the effectiveness of intrapartum antibiotic prophylaxis. RESULTS: We analyzed data from 109 cases and 207 controls. Nineteen (17%) case versus 69 (33%) control mothers received an acceptable regimen of intrapartum antibiotic prophylaxis. In adjusted analyses, the effectiveness of intrapartum antibiotic prophylaxis was 86% (95% confidence interval, 66%-94%). When the first dose of antibiotics was given > or =2 hours before delivery, the effectiveness increased to 89% (95% confidence interval, 70%-96%); when it was given within 2 hours of delivery, the effectiveness was 71% (95% confidence interval, -8%-92%). Effectiveness was lowest in mothers with intrapartum fever (72%, 95% confidence interval, -9%-93%). On the basis of a 70% prevalence of maternal risk factors expected among cases in the absence of intrapartum antibiotic prophylaxis, we estimate that the risk-based strategy could reduce early-onset group B streptococcal disease by 60%. CONCLUSIONS: The risk-based approach to intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease. To achieve the maximum preventive effect, the first dose of antibiotics should be administered at least 2 hours before delivery.