Group B Beta-hemolytic Streptococcus Research Articles

Microbiological characteristics of perianal streptococcal dermatitis: a retrospective study of 105 patients in a 10-year period.

Beta-hemolytic streptococci (BHS) are the most common causative agents of perianal streptococcal dermatitis (PSD). This study evaluates the distribution of BHS isolates in perianal bacterial cultures. We retrospectively reviewed microbiological results for perianal BHS that were isolated in our laboratory between 2006 and 2015. We identified a total of 105 BHS isolates from rectal swabs and swabs of clinically intact perianal skin. The majority of BHS were of group A (GABHS) (73/105; 69.5%), followed by group B BHS (GBBHS) (27/105; 25.7%), and non-group A or B BHS (5/105; 4.8%). The distribution of GABHS was age-specific, with the majority of GABHS obtained from young children. All BHS isolates were susceptible to penicillin. GABHS were universally susceptible to clindamycin, whereas 1.4% were resistant to erythromycin. GBBHS were resistant to erythromycin and clindamycin in 14.8% and 7.4% of cases. In addition, we wanted to emphasize the importance of correct diagnosis of PSD. Hence, we provide a review of protocols that can decrease the time to diagnosis and treatment of PSD, reduce patients' discomfort, and prevent unnecessary diagnostic procedures.

Prevalence of Group B Beta Hemolytic Streptococcus in Teenagers

Group B Beta hemolytic streptococcus (GBBS) is a Gram positive bacteria known to cause significant morbidity and mortality in newborns. In 2010, there were more than 1,200 cases of neonatal sepsis with 30% mortality in infants delivered prior to 33 weeks gestation. Risk factors for early onset GBBS neonatal sepsis include teenage pregnancy and low maternal levels of GBS specific anticapsular antibody.

Visual Diagnosis: Sepsis, Respiratory Distress, and a Persistent Right Lung Opacification in a Newborn

1. Himalee Sabnis, MD* 2. Beena G. Sood, MD, MS* 3. Mark Zilberman, MD* 4. Cristie Becker, MD† 1. *Carman and Ann Adams Department of Pediatrics 2. †Department of Pediatric Radiology, Wayne State University, Children's Hospital of Michigan, Detroit, Mich A 20-year-old primigravida woman delivers a term female infant weighing 3,112 g via caesarean section under spinal anesthesia. The mother's antenatal test results are unremarkable, including a negative group B beta-hemolytic Streptococcus (GBS) screen at 33 to 34 weeks’ gestation. Apgar scores are 8 and 9 at 1 and 5 minutes, respectively. Physical examination results are normal. Four hours after delivery, the infant develops tachypnea, grunting, and “blue” lower extremities. Supplemental oxygen is provided, blood and urine cultures are performed, and empiric treatment with intravenous ampicillin and cefotaxime is initiated. A chest radiograph reveals a normal cardiac silhouette with bilateral perihilar “streaking” of the lungs. Complete blood count reveals leukopenia, with an absolute neutrophil count of 200 cells/mm3 and thrombocytopenia. At 12 hours of age, the blood culture is positive for gram-positive cocci, later identified as GBS. A lumbar puncture yields xanthochromic cerebrospinal fluid (CSF) that contains 9 red blood cells and 52 white blood cells, of which 97% are mononuclear. CSF glucose concentration is 50 mg/dL (2.8 mmol/L) (blood glucose, 93 mg/dL [5.2 mmol/L]) and protein concentration 191 mg/dL. GBS antigen is detected in both the CSF and urine. At 18 hours of age, the infant becomes mottled in appearance, develops severe respiratory acidosis, and requires assisted ventilation. A chest radiograph at this time reveals patchy infiltrates consistent with pneumonia. Fluid resuscitation and alkali therapy are initiated for hypotension and metabolic acidosis, respectively. At 20 hours of age, the baby is transferred to a level III neonatal intensive care unit for management. On admission to the intensive care nursery, physical examination reveals an intubated infant who has a hyperdynamic precordium and good air entry in both lungs. Admission chest radiograph shows …

A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis

The optimal number of blood cultures needed to document sepsis in an ill neonate has undergone little critical evaluation. Multiple site cultures may improve pathogen detection if intermittent bacteremia occurs, or if a low density of bacteria is present in the blood. We hypothesized, however, that bacterial clearance is slower and bacteremia more continuous in septic neonates, so that a single site blood culture should be sufficient to accurately document true septicemia. To determine the need for multiple site blood cultures in the evaluation of neonates for sepsis. Clinical data were prospectively collected for 216 neonates who had 269 pairs of blood cultures taken from two different peripheral sites for the evaluation of possible sepsis. A minimum of 1 ml of blood was obtained from the two peripheral sites within 15-30 min of each other. Based on prior retrospective data, we determined that 203 infants would need to have two site blood cultures to demonstrate a significant improvement in pathogen detection at an alpha of 0.05 and a beta of 0.20 (80%) power. A total of 186 culture pairs were taken for evaluation of early-onset sepsis in 186 neonates, while 83 pairs were drawn for evaluation of late-onset sepsis in 43 neonates. In all, 21 neonates from the late-onset group were evaluated more than once, and 12 neonates were evaluated for both early- and late-onset sepsis. In all, 20 (9.2%) of 216 neonates had 22 episodes of culture-proven sepsis at a median age of 18 days. All neonates with positive cultures had the same organism with a similar sensitivity pattern obtained from the two different peripheral sites. The other 196 study neonates had negative blood cultures from both sites. The single episode of early-onset sepsis was caused by Listeria monocytogenes, while all remaining episodes were late-onset with the following organisms: Staphylococcus epidermidis (7), methicillin-resistant Staphylococcus aureus (MRSA) (3), combined MRSA and Candida albicans (2), Candida albicans alone (2), late-onset Group B beta-hemolytic Streptococcus (GBS) (2), Klebsiella pneumoniae (2), Enterococcus fecalis (1), Escherichia coli (1), and Serratia marcescens (1). Since no infant grew organisms from only one of the two sites, the data indicate that the diagnosis of sepsis would have been made correctly in all infants with a single site culture. Two site blood cultures for the initial evaluation of neonatal sepsis do not have a better yield in pathogen detection. Sepsis in neonates can be detected with no loss of accuracy with a single site blood culture with blood volume of>or=1 ml.

Historical perspectives

In the preantibiotic era, the group A beta-hemolytic Streptococcus was much more likely to be associated with serious bacterial infection of women and infants than was group B beta-hemolytic Streptococcus (GBS). Soon after the introduction of penicillin and other antibiotics, the most likely organisms to be cultured from neonates who had sepsis were gram-negative bacilli, most notably Escherichia coli. When penicillin-resistant staphylococci emerged, Staphylococcus aureus became prominent. By 1958, a review of neonatal sepsis (septicemia) indicated that GBS could be a devastating organism. (1) Between 1933 and 1943, two cases of neonatal sepsis due to GBS (also called S agalactiae ) were reported, and four more were seen between 1943 and 1947. Of the six infants, four had meningitis and two had pneumonia; all died. (1) Over the next few years, the importance of GBS in perinatal infection began to emerge. First documented as an important organism in the perinatal period (for both women and infants) by Hood and associates in 1961, (2) early-onset meningitis caused by GBS was reported in 1962, (3) and the role of GBS in neonatal infection was emphasized by Eickhoff and colleagues in 1964. (4) During the next decade, the ascendancy of GBS continued, to the extent that by 1973, McCracken (5) considered it to be “the new challenge” and a year later, with a colleague, described a wide spectrum of disease resulting from GBS infection. (6) The emergence of GBS infection was not limited to the United States; it appeared to be widespread throughout Europe. In the early 1970s, there were reports of infection in the language of the country from Bulgaria, France, Germany, Hungary, and the United Kingdom. (7) At about this time, the idea of “early-”and “late-”onset infections was proposed (8) and was well established by the end of the decade. …

Vaginal chlorhexidine during labour to prevent early-onset neonatal group B streptococcal infection.

Early-onset group B beta-hemolytic streptococcus (GBS) infection accounts for approximately 30% of neonatal infections, has a high mortality rate and is acquired through vertical transmission from colonized mothers. Several trials have demonstrated the efficacy of intrapartum chemoprophylaxis (IPC) for preventing early-onset disease (EOD). Vaginal disinfection with chlorhexidine during labour has been proposed as another strategy for preventing GBS EOD in the preterm and term neonate. Chlorhexidine has been found to have no impact on antibiotic resistance, is inexpensive, and applicable to poorly equipped delivery sites. To determine the effectiveness of vaginal disinfection with chlorhexidine during labour for preventing early-onset GBS infection in preterm and term neonates. We searched the Cochrane Pregnancy and Childbirth trials register (October 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to October 2003), EMBASE (1980 to March 2003), CINAHL (1982 to March 2003) and LILACS (1982 to September 2003). Randomized and quasi-randomized trials comparing vaginal disinfection with chlorhexidine to placebo, or no treatment. We extracted information from the results sections of the included studies. We reported relative risk (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes. We calculated the number needed to treat (NNT) with 95% CIs when a statistically significant RD was found. We used a chi square test (chi2) and the I2 analysis to test for heterogeneity, and applied a fixed or random effects model accordingly. Five studies, including approximately 2190 term and preterm infants, met the inclusion criteria and reported on at least one of the outcomes of interest for this systematic review. When all studies were combined there was a statistically significant (p = 0.005) reduction in colonisation (RR 0.72, 95% CI 0.56 to 0.91); RD -0.16 (95% CI -0.26 to -0.05); NNT 6 (95% CI 4 to 20). There was no statistically significant between-study heterogeneity. There was no statistically significant between-study heterogeneity both for RR (chi(2) = 3.21 [p = 0.2], I(2) = 37.8%) and for RD (chi(2) = 1.66 [p = 0.44], I(2) = 0%). There was no statistically significant reduction in EOD including GBS infection, GBS pneumonia, GBS meningitis or mortality. Vaginal chlorhexidine resulted in a statistically significant reduction in GBS colonisation of neonates, but was not associated with reductions in other outcomes. The review currently does not support the use of vaginal disinfection with chlorhexidine in labour for preventing EOD. Results should be interpreted with caution as the methodological quality of the studies was poor.

Hemodynamic homeostasis during acute hypoxia in septic and nonseptic piglets: differential role of prostaglandins and nitric oxide.

We studied the hemodynamic responses of 29 anesthetized and mechanically ventilated piglets to acute hypoxia [reduction of Pao2 from 130 to 38 mm Hg induced by inhalation of 7% fraction of inspired oxygen (Fio2) for 7.5 min] before and during group B beta-hemolytic streptococci (GBS) sepsis. During hypoxia, nonseptic piglets maintained stable systemic blood pressure [105+/-9 (SD) to 97+/-14 mm Hg] and cardiac output (CO) (667+/-72 to 685+/-113 mL/min). However, during GBS/hypoxia, systemic blood pressure fell from 94+/-17 to 49+/-25 mm Hg, CO fell from 397+/-146 to 223+/-142 mL/min (both p < 0.001 versus pre-GBS), and cardiac arrest often ensued. We tested three hypotheses that might underlie GBS-induced intolerance to systemic hypoxia: 1) GBS-induced reduction of systemic CO/systemic oxygen delivery (QO2) below a critical QO2 beyond which the superimposition of hypoxia becomes intolerable; this mechanism is unlikely as nonseptic piglets with comparable reductions in CO/QO2 (induced by inflation of a left atrial balloon) tolerated hypoxia well; 2) GBS-induced inhibition of nitric oxide (NO) synthesis that is vital to tolerance of hypoxia; this mechanism is unlikely as infusion of the NO substrate L-arginine did not restore tolerance to hypoxia during GBS infusion (as it did after inhibition of NO synthesis during infusion of N-nitro-L-arginine in nonseptic piglets); and 3) GBS-induced production of pathologic prostaglandins that impaired the piglet's capacity to tolerate hypoxia; this mechanism finds support in the observation that inhibition of prostaglandins with the cyclooxygenase inhibitor indomethacin completely restored the ability of septic piglets to tolerate hypoxia. Further evaluation of GBS-induced intolerance to systemic hypoxia may provide insight into the incompletely understood mechanisms by which sepsis induces circulatory collapse in experimental animals and in humans.

Effects of Treatment with Pentoxifylline on the Cardiovascular Manifestations of Group B Streptococcal Sepsis in the Piglet1

Pentoxifylline (PTXF) is a methylxanthine derivative which modifies leukocyte function and inhibits tumor necrosis factor (TNF)-alpha release. As TNF-alpha is considered a proximal mediator in the cascade leading to septic shock, we evaluated the ability of PTXF to attenuate the cardiovascular manifestations of sepsis secondary to an infusion of group B beta-hemolytic streptococci (GBS). Fifteen anesthetized, mechanically ventilated piglets (weight, 2815 +/- 552 g) were randomly assigned to a treatment group which received a continuous infusion of PTXF (5 mg/kg/h) beginning 30 min after GBS (7.5 x 10(8) colony-forming units/kg/min) administration was started or to a control group which received GBS plus saline as placebo. Comparison of the hemodynamic measurements and arterial blood gases over the first 120 min of bacterial infusion for treatment and control groups revealed the following statistically significant differences (120-min values presented): cardiac output was significantly higher in the PTXF group (0.159 +/- 0.035 versus 0.09 +/- 0.026 L/kg/min; p < 0.05) as was stroke volume (0.54 +/- 0.11 versus 0.27 +/- 0.126 mL/kg/beat; p < 0.01). Pulmonary and systemic vascular resistances remained lower in the PTXF-treated animals (167 +/- 45 versus 233 +/- 69 mm Hg/L/kg/min; p < 0.03) and (427 +/- 162 versus 828 +/- 426 mm Hg/L/kg/min; p < 0.03, respectively). Median survival time was significantly longer in the PTXF group (180 versus 120 min; p < 0.05). In an additional group of animals, PTXF administration before GBS infusion revealed no attenuation in the rise of TNF-alpha, accompanying sepsis. These data demonstrate that treatment with PTXF may ameliorate some of the deleterious hemodynamic manifestations of GBS sepsis and result in improved survival in a young animal model without significantly modifying plasma TNF-alpha levels.

Telegammatherapy of advanced malignant neoplasms of the maxillary sinus. A 3-year follow-up of therapeutic results and failures

Early-onset neonatal group B beta-hemolytic streptococcus (GBS) infection exhibits pathophysiologic characteristics of a toxic shock syndrome, in which a cascade of inflammatory mediators are involved. Thromboxane A2 (TXA2) is thought to play an important role as a mediator of the pulmonary response to GBS toxin, because high lung lymph concentrations of a TXA2 metabolite have been observed after GBS toxin injections in sheep. The aim of this study was to evaluate the effects of a selective antagonist of the TXA2-prostaglandin endoperoxide receptor (SQ 29,548). Six unanesthetized young lambs, each serving as its own control, were given SQ 29,548 or vehicle control followed by GBS toxin challenge. Hemodynamic and lung function (lung mechanics, lung volume, ventilation) responses were followed for 5 h. When compared with the control studies, treatment with SQ 29,548 significantly altered the response to GBS toxin. SQ 29,548 reduced the increase in pulmonary and systemic vascular resistance, improved cardiac output and stroke volume, improved dynamic lung compliance but not airway resistance, and improved oxygenation. The attenuating effect of SQ 29,548 was most pronounced during the first phase of toxin response (15-90 min after toxin infusion), but significant treatment effects were also seen during the second phase (120-300 min after toxin infusion). This study demonstrates that TXA2 is an important mediator of the response to GBS toxin and is responsible for hemodynamic and lung function changes. Thromboxane receptor blockade may offer a potential therapeutic approach to infants with severe early-onset GBS sepsis.

Maternal Administration of Granulocyte Colony-Stimulating Factor Improves Neonatal Rat Survival After a Lethal Group B Streptococcal Infection

Abstract Maternally administered recombinant human granulocyte colony- stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG- CSF augments neonatal defenses against a lethal bacterial challenge.

Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection

Maternally administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG-CSF augments neonatal defenses against a lethal bacterial challenge.

Systemic infection due to group B beta-hemolytic streptococcus in children. A review of 75 outpatient-evaluated cases during 13 years.

We reviewed 75 outpatient cases of systemic infection due to group B beta-hemolytic streptococcus (GBS) evaluated during a 13-year period. Patient ages ranged from five days to eight months; 75% were younger than two months. Early-onset (less than or equal to seven days of age) GBS disease occurred in 10% of the patients, and late-onset GBS disease in 90%. The racial distribution was 60% black, 35% white, and 5% Hispanic. Symptoms included fever, irritability, lethargy, and altered-feeding pattern which lasted less than 24 hours in 88% of patients. On presentation, 33% were afebrile (eight had GBS meningitis); 32% did not appear ill (six had GBS meningitis). Of the total, 40% had GBS meningitis, of these, a greater proportion had either early-onset GBS disease or neutropenia. Infection other than meningitis was identified in 24% of all patients: pneumonia (six cases), cellulitis/adenitis (six cases), osteomyelitis/septic arthritis (five cases), and otitis media (one case). All patients survived. Systemic GBS infection in an outpatient population can involve infants up to eight months old, is more common in blacks than in whites, can be present without fever or compromised appearance, and usually has low mortality.

Hemodynamic effects of heat-killed group B beta-hemolytic streptococcus in newborn lambs: role of leukotriene D4.

Group B beta-hemolytic streptococcus (GBS) infection is an important cause of neonatal pneumonia and sepsis. GBS infection is frequently associated with persistent pulmonary hypertension of the newborn. To better understand the early pulmonary hypertension phase of GBS-induced acute lung injury in a conscious animal, we characterized the pulmonary and systemic hemodynamic response of spontaneously breathing, chronically instrumented newborn lambs to injections of heat-killed type Ib GBS, 0.1-9.0 x 10(9) colony forming units. Heat-killed GBS caused marked dose-dependent increases in mean pulmonary arterial pressure and calculated pulmonary vascular resistance, 190 and 370% at the maximum dose, respectively. Similarly, GBS caused dose-dependent increases in mean systemic arterial pressure and systemic vascular resistance (28.5 and 108% at the maximum dose, respectively) and a decrease in cardiac output (33.5%). Arterial oxygen tension worsened at the higher doses. GBS-induced pulmonary hypertension was decreased by two structurally unrelated, putative leukotriene D4 receptor antagonists. Pretreatment with LY171883 blocked GBS-induced pulmonary hypertension by 95%, and WY48,252 attenuated this effect by 27%. Both drugs completely blocked the hemodynamic effects of exogenous leukotriene D4. For comparison, several lambs received bolus injections of live GBS, either alone or after pretreatment with LY171883. The hemodynamic response to live GBS and attenuation of that response by LY171883 were similar to those caused by similar doses of heat-killed GBS. Thus, bolus injections of heat-killed GBS provide a reproducible model of pulmonary hypertension in conscious newborn lambs. In addition, the sulfidopeptide leukotrienes appear to be important mediators of GBS-induced pulmonary hypertension in newborn lambs.

Group B Streptococcus Infection in Mother and Child

Despite significant advances in obstetric and pediatric health care, group B beta-hemolytic Streptococcus (GBS) remains one of the most prevalent and devastating pathogens in peripartum women and their newborn infants. It may cause urinary tract infection, chorioamnionitis and endometritis, bacteremia, and cesarean wound infection in the peripartum period. Moreover, GBS accounts for nearly 50% of serious neonatal bacterial infections. Approximately three in every 1,000 children born in the United States acquire pneumonia, sepsis, or meningitis from GBS, with combined mortality and morbidity exceeding 50% despite appropriate antibiotic and supportive therapy. Estimates indicate that more than 10,000 infants are affected annually, at a cost of more than $300 million. Neonatal disease is divided into early- and late-onset syndromes: The illness emerging after six days of age differs in terms of GBS serotype, clinical manifestations, and outcome from the disseminated process seen in earlier onset. We describe two infants infected with GBS and discuss risk factors, pathogenesis, diagnosis, therapy, and options for disease prevention in the peripartum woman and her infant.

Isogenic group B streptococci devoid of capsular polysaccharide or beta-hemolysin: pulmonary hemodynamic and gas exchange effects during bacteremia in piglets.

Group B beta-hemolytic streptococcus (GBS) causes thromboxane (Tx)-associated pulmonary hypertension and hypoxemia in neonatal animals and human infants. The components of GBS that induce these features of sepsis are incompletely characterized. The capsular polysaccharide has been implicated based on the effects of GBS extracts. We used isogenic mutants of a parent GBS strain (COH 31 r/s) devoid of capsular polysaccharide or beta-hemolysin to determine if these components caused the acute features of GBS bacteremia. In neonatal piglets, we observed a similar increase in pulmonary vascular resistance (PVR, mm Hg/L/min) during a 1 h infusion at 5 x 10(8) colony-forming unit/kg/h of COH 31 r/s (n = 5, 11.6 +/- 1.4 to 67.1 +/- 17.9), an isogenic GBS mutant devoid of type III CP (n = 5, 12.5 +/- 1.4 to 56.9 +/- 5.0), and an isogenic GBS mutant devoid of beta-hemolysin (n = 4, 11.0 +/- 1.9 to 51.9 +/- 7.9). All three GBS strains caused increases in blood TxB2 levels, mild arterial hypoxemia, mild reduction in mixed venous PO2, and a 30-40% reduction in cardiac output after a 1 h infusion. The Tx-synthase inhibitor, dazmegrel, completely reversed pulmonary hypertension, and partially reversed arterial hypoxemia and TxB2 levels to baseline values for all GBS strains. In six additional piglets, infusion of polystyrene beads of similar size to GBS at a dose of 5 x 10(8) beads/kg/h caused no changes in gas exchange or blood TxB2 levels, but a mild increase in PVR (13.3 +/- 2.0 to 17.7 +/- 3.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandin E1 Selectively Reduces Group B β-Hemolytic Streptococci–Induced Pulmonary Hypertension in Newborn Piglets

Group B beta-hemolytic streptococci (GBS)-induced pulmonary hypertension was generated in ten newborn piglets. Intravenous infusions of either prostaglandin E1 (PGE1) (n = 5) or placebo (n = 5) were begun after 60 minutes of stable pulmonary hypertension. The effects of these interventions on cardiopulmonary hemodynamics were studied. Pulmonary artery pressure (PAP) increased similarly in both groups during the first 60 minutes of GBS infusion. By two hours after intervention, PAP was significantly lower in the animals given PGE1 (20 +/- 4 vs 32 +/- 5 mm Hg for PGE1 vs placebo). The ratio of pulmonary to systemic vascular resistance followed a pattern analogous to PAP, increasing with the GBS infusion, indicating selective pulmonary vasoconstriction. The pulmonary vascular resistance/systemic vascular resistance ratio decreased after intervention in the group given PGE1 only (0.25 +/- 0.08 vs 0.50 +/- 0.12 for PGE1 vs placebo), indicating selective pulmonary vasodilation. Transient systemic hypotension was noted at one hour after initiation of PGE1 infusion. Prostaglandin E1 infusion selectively improved GBS-induced pulmonary hypertension and hypoxemia in newborn piglets with only transient systemic hypotension.

Selective inhibition of thromboxane synthetase reduces group-B-beta-hemolytic-streptococci-induced pulmonary hypertension in piglets.

13 newborn piglets with group-B-beta-hemolytic-streptococci (GBS)-induced pulmonary hypertension were assigned to receive either placebo (group 1) or Dazmegrel, a thromboxane synthetase inhibitor (group 2). All piglets with pulmonary hypertension had increased thromboxane B2 (TxB2) and 6-keto PGF1 alpha levels. With continued GBS infusion, the placebo group demonstrated a continued elevation of pulmonary artery pressure (PAP) and of TxB2. The Dazmegrel piglets, however, despite continued GBS infusion, demonstrated a selective decrease in PAP associated with a significant decrease in TxB2 levels and stability of systemic pressure and cardiac output. These data demonstrate that thromboxane synthetase inhibition is effective therapeutically in selectively reducing PAP.

Molecular basis for group B beta-hemolytic streptococcal disease.

Group B beta-hemolytic Streptococcus (GBS) is a major pathogen affecting newborns. We have investigated the molecular mechanism underlying the respiratory distress induced in sheep after intravenous injection of a toxin produced by this organism. The pathophysiological response is characterized by pulmonary hypertension, followed by granulocytopenia and increased pulmonary vascular permeability to protein. 31P NMR studies of GBS toxin and model components before and after reductive alkaline hydrolysis demonstrated that phosphodiester residues are an integral part of the GBS toxin. Reductive alkaline treatment cleaves phosphate esters from secondary and primary alcohols and renders GBS toxin nontoxic in the sheep model and inactive as a mediator of elastase release in vitro from isolated human granulocytes. We propose that the interaction of cellular receptors with mannosyl phosphodiester groups plays an essential role in the pathophysiological response to GBS toxin.

Ultrastructural alterations of term human amnionic epithelium following incubation with group B beta-hemolytic streptococci.

The association between the group B beta-hemolytic streptococcus (GBBHS) and premature labor, premature rupture of the membranes, and chorioamnionitis with intact membranes is well known. However, the mechanisms involved in this association remain unclear. In this study we incubated term chorioamniotic membranes from patients undergoing elective repeat cesarean section in double-armed incubation vessels that isolated the maternal from the fetal surfaces. The GBBHS was placed adjacent to the maternal surface and incubated for 2, 4, 8, 12, and 24 hr. Control membrane specimens from the same patient were incubated under identical conditions for identical time periods but without the presence of GBBHS. Examination of the specimens by transmission electron microscopy revealed progressive nuclear and basement membrane alteration in the study group that was maximal at 12 hr. There was also a progressive decrease in desmosome counts in the study membranes. These in vitro changes support the in vivo association of GBBHS with the aforementioned obstetric complications.

Cardiovascular changes in group B streptococcal sepsis in the piglet: response to indomethacin and relationship to prostacyclin and thromboxane A2.

Seventeen piglets were infected with a continuous intravenous infusion of live group B beta-hemolytic streptococci (GBS). Hemodynamic changes were recorded, and blood samples were drawn for measurement of thromboxane B2 (TxB2) (stable metabolite of thromboxane A2) and 6-keto-PGF1 alpha (stable metabolite of prostacyclin). Control animals (n = 9) received only bacteria, while treatment animals (n = 8) received indomethacin, 3 mg/kg IV, 15 min after the start of the bacterial infusion. Control animals responded to the bacteria within 15 min with marked elevation in mean pulmonary artery pressure (Ppa) from 15 +/- 8 to 39 +/- 6 mm Hg and decline in PaO2 from 80 +/- 11 to 51 +/- 6 mm Hg and cardiac output (CO) from 0.24 +/- 0.07 to 0.13 +/- 0.07 liters/min/kg. Mean arterial blood pressure (AoP) significantly decreased from baseline value of 95 +/- 13 to 51 +/- 32 mm Hg by 180 min. In animals treated with indomethacin, these changes were reversed or significantly attenuated. The hemodynamic changes were associated temporally with elevations in plasma concentrations of TxB2 or 6-keto-PGF1 alpha. In the first 60 min, TxB2 levels in both groups correlated with Ppa (r = 0.72, p less than 0.001) and PaO2 (r = -0.60, p less than 0.001). A strong negative correlation between TxB2 and CO was observed over the first 180 min (r = -0.73, p less than 0.001). There was a statistically significant correlation between AoP and 6-keto-PGF1 alpha concentration between 60 and 180 min (r = -0.54, p less than 0.002). Indomethacin improved the hemodynamic function in this model of GBS sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)