Cytokine response to group B streptococcus infection in mice

This study was undertaken to better understand the complex relationship between specific and non-specific host defence mechanisms and group B streptococci (GBS). A comprehensive kinetics analysis of cytokine mRNA expression was performed, by Northern blot assay, in peritoneal exudate cells (PEC) and spleen cells (SC) recovered from CD-1 mice at various times during the course of an intraperitoneal infection with a lethal dose (5 x 10(3) microorganisms/mouse) of type Ia GBS, reference strain 090 (GBS-Ia). Analysis of cytokines involved in the development of a specific TH response shows that GBS-Ia in PEC induce only a weak increase of IL-2 mRNA expression and in SC a cytokine pattern characterized by IL-2, IFN-gamma and IL-12 in the absence of IL-4, IL-5 and IL-10. This selected cytokine pattern could provide appropriate conditions for the development of a TH1 response. Analysis of inflammatory cytokines, which are usually induced early during an in vivo infection, shows that there is a significant expression of mRNA specific for IL-1beta, TNFalpha and IL-6, both in PEC and SC only at 24 h which persists at a high level until 36 h. This delayed cytokine induction, accompanied by the contemporary activation of splenic phagocytic cells, occurs only when the number of GBS-Ia is extremely high. In fact, at 24 h GBS-Ia have heavily colonized all organs. In vitro infection of thioglycollate-elicited peritoneal macrophages confirms that the ability of GBS-Ia to induce a strong inflammatory cytokine response depends strictly on the number of infecting microorganisms. Indeed, macrophages respond to GBS-Ia with a very rapid induction of IL-1beta and TNFalpha mRNA when infected at a ratio of 1:10, but not at 100:1. Two major observations emerged from this study: (1) GBS-Ia, by inducing a cytokine pattern which seems to favour development of a TH1 response, could evade antibody production essential for resistance to GBS; and (2) inflammatory cytokine response is induced when a heavy microbial invasion of the host has already occurred. These novel features of GBS-Ia could contribute to the development and progression of lethal infection in mice.     

Antibiotic susceptibility profile of group B streptococcus acquired vertically

OBJECTIVE: To determine the contemporary antibiotic susceptibility profile of vertically acquired group B streptococcal isolates. METHODS: Susceptibility to ampicillin, penicillin G, erythromycin, clindamycin, cefazolin, and gentamicin was assessed by two methods, minimal inhibitory concentration and disc diffusion. RESULTS: The susceptibility profiles of 119 colonizing and eight invasive strains of group B streptococcus isolated from January 1996 to September 1997 at two hospitals in Birmingham, Alabama-University of Alabama at Birmingham and Cooper Green-were studied. Minimal inhibitory concentration determinations indicated that all colonizing strains were susceptible or moderately susceptible to ampicillin and penicillin G. Resistance was noted by at least one strain to each of the other antibiotics; all were resistant to gentamicin, whereas 27 (21%) were resistant to erythromycin, five (4%) to clindamycin, and one (1%) to cefazolin. All of the eight invasive strains were susceptible or moderately susceptible to ampicillin, penicillin G, clindamycin, and cefazolin; one (13%) was resistant to erythromycin, and all were resistant to gentamicin. Disc diffusion results generally were concordant with minimal inhibitory concentration results, although by disc diffusion fewer isolates were classified as susceptible, and more as moderately susceptible, to ampicillin and penicillin G than by minimal inhibitory concentration. CONCLUSION: Universal susceptibility of group B streptococcus to members of the penicillin family supports the continued use of penicillin G or ampicillin for early onset neonatal group B streptococcal disease prevention. For patients allergic to beta-lactam agents, clindamycin (4% resistance) may be a better alternative than erythromycin (21% resistance).     

Persistence of penicillin G benzathine in pregnant group B streptococcus carriers

OBJECTIVE: To determine if streptococcicidal levels of penicillin G benzathine can be detected in maternal serum 4 weeks after treatment with 4.8 million units. METHODS: Thirty-seven pregnant women with positive group B streptococcus vaginal or urine cultures were each given 4.8 million units of penicillin G benzathine. Maternal blood samples were collected after injection and at delivery. Serum penicillin levels were measured by high-pressure liquid chromatography. Follow-up cultures were done when possible. RESULTS: None of the patients had serum penicillin levels below 0.20 microgram/mL 30 days after treatment. Cord blood levels were approximately 50% lower than maternal levels. In all but three subjects, cord blood levels exceeded 0.06 microgram/mL, the minimal inhibitory concentration for group B streptococcus. The three exceptions were patients who delivered more than 100 days after treatment. Group B streptococcus cultures were negative at the time of delivery in 72% of cases. None of the patients with positive cultures were moderately or heavily colonized. CONCLUSION: In pregnant women, penicillin G benzathine levels are high enough to inhibit the growth of group B streptococcus for more than 4 weeks after injection with 4.8 million units. Further studies are needed to evaluate whether this regimen can prevent neonatal colonization and invasive group B streptococcus disease.     

Management of neonates born to mothers with group B streptococcus colonization

Approximately 20% of pregnant women harbor group B streptococcus (GBS) in the lower genital tract at the time of delivery. Intrapartum chemoprophylaxis of mothers with GBS colonization who have risk factors for neonatal GBS at delivery improves the outcome of the neonates. The recommendations for treating newborn infants of mothers who receive intrapartum chemoprophylaxis for GBS colonization and the recommendations for those who do not remain empiric, because clinical studies to support such recommendations are not available. An algorithm for treatment of neonates born to mothers with GBS colonization that is based on available data and empiric recommendations is presented. These guidelines are intended to guide medical practice and not to replace clinical judgment.     

Biochemical mediators of meningeal inflammatory response to group B streptococcus in the newborn piglet model

The meningeal inflammatory response to a heat-killed mutant unencapsulated strain of type III group B Streptococcus (GBS) was studied in a newborn piglet model. GBS (10(9) colony-forming unit equivalents) or saline (control) was inoculated intraventricularly. Serial cerebrospinal fluid measurements were done at baseline and over the course of the next 24 h for cytochemical changes and production of tumor necrosis factor (TNF) and prostaglandins. In separate experiments, we defined the time course of early changes during the first 6 h and dose response relationship over a range of inocula 10(6) to 10(9) colony-forming unit equivalents. The intraventricular inoculation of the heat-killed unencapsulated GBS induced marked leukocytosis and increased protein by 6 h. These changes were preceded by a several hundredfold increase in TNF (maximum at 2 h) and prostaglandins (maximum at 2-4 h). The early and sharp rise in TNF suggests its pivotal role in initiating the inflammatory cascade. The magnitude of the inflammatory response increased with increasing bacterial dose over the range studied. To study the effect of encapsulation of GBS in the induction of meningeal inflammation, we compared the response to the unencapsulated mutant strain with that to the encapsulated parent strain. The encapsulated strain produced much smaller inflammatory changes, and only with high doses of bacteria. The GBS cell wall appeared to be the primary bacterial product triggering inflammation. Intraventricular injection of the heat-killed unencapsulated GBS with exposed cell wall can serve as a valid model for studying neonatal meningitis.     

A simple, quantitative, reproducible avidin-biotin ELISA for the evaluation of group B streptococcus type-specific antibodies in humans

Type-specific antibodies to the capsular polysaccharides (CP) of group B Streptococcus (GBS) are protective. Historically, the radioactive antigen-binding assay (RABA) has been used to determine GBS antibody levels. This method measures total immunoglobulin and employs the use of radioactive materials. We have developed an avidin-biotin ELISA that is less hazardous and is able to measure GBS Ia, Ib, II or III CP specific IgG. To avoid inconsistent binding to the plate, the CPs from GBS Ia, Ib, II and III were derivatized using adipic acid dihydrazide (ADH) and subsequently biotinylated without altering their antigenic epitopes and bound to avidin coated plates. Plasma from three different human subjects immunized with a tetravalent CP vaccine were used to prepare IgG references for Ia, II and III, respectively, thus rendering the assay quantitative for those types. The assay is able to detect nanograms per milliliter of GBS Ia, Ib, II or III specific antibody. This method is reproducible, sensitive and correlates with RABA by 76%.     

Group B streptococcus bacteremia in nonpregnant adults

The ability of carbonaceous particles (AST-120), originally developed as an enteral adsorbent of uremic toxins, to quench nitric oxide (NO) was tested. NO in solutions prepared by two methods [NO gas bubbling and NO generating system, i.e., decomposition of 1-hydroxy-2-oxo-3-(aminopropyl)-3-isopropyl-1-triazene] were determined by a NO-specific reduction of carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide using an electron paramagnetic resonance spectrometry. NO concentrations were less in samples containing increasing concentrations of AST-120. In a separate study, nitrite concentrations in lipopolysaccharide-treated RAW264 cells were significantly less in incubation medium containing AST-120. Thus, AST-120 may be applicable as an enteral anti-NO agent.     

Soluble antigens from group B streptococci induce cytokine production in human blood cultures

Group B streptococcal antigens stimulated tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-6 production in human blood cultures in a concentration- and time-dependent fashion. The minimal concentrations of type-specific polysaccharides, lipoteichoic acid, and group-specific polysaccharide required to produce these effects were, respectively, 0.01, 1, and 10 microg/ml. Cell separation experiments indicated that monocytes were the cell type mainly responsible for cytokine production. Time course studies indicated that TNF-alpha was released before the other cytokines. TNF-alpha, however, did not appear to directly induce IL-1beta, as shown by blockade experiments with anti-TNF-alpha antibodies. IL-6 levels were moderately but significantly decreased by anti-TNF-alpha. These data indicate that several products from group B streptococci are able to directly stimulate human monocytes to release TNF-alpha, IL-1beta, and IL-6. These findings may be clinically relevant, since proinflammatory cytokines can mediate pathophysiologic changes during sepsis.     

Surfactant protein-A binds group B streptococcus enhancing phagocytosis and clearance from lungs of surfactant protein-A-deficient mice

Surfactant protein-A (SP-A) gene-targeted mice clear group B streptococcus (GBS) from the lungs at a slower rate than wild-type mice. To determine mechanisms by which SP-A enhances pulmonary clearance of GBS, the role of SP-A in binding and phagocytosis of GBS was assessed in SP-A (-/-) mice infected with GBS in the presence and absence of exogenous SP-A. Coadministration of GBS with exogenous SP-A decreased GBS colony counts in lung homogenates of SP-A (-/-) mice. SP-A bound to GBS in a calcium-dependent manner. Although pulmonary infiltration with macrophages was not altered in SP-A (-/-) versus wild-type mice after GBS infection, the number of alveolar macrophages with phagocytosed bacteria was lower in the SP-A (-/-) mice than in the wild-type mice. When SP-A was coadministered with GBS, phagocytosis was significantly increased. Oxygen radical production by alveolar macrophages from SP-A (-/-) mice infected with GBS was decreased compared with wild-type controls and was increased when SP-A (-/-) mice were infected in the presence of exogenous SP-A. Superoxide (SO) radical generation was deficient in macrophages from SP-A (-/-) mice. SP-A plays an important role in GBS clearance in vivo, mediated in part by binding to and enhancing GBS phagocytosis and by increasing SO production by alveolar macrophages.     

SXT and Taxo A disks for presumptive identification of group A and B streptococci in throat cultures

A bacitracin (0.04 units, BBL)-SXT (trimethoprim, 1.25 mg, plus sulfamethoxazole, 23.75 mg, BBL) susceptibility test was 94% accurate in presumptively identifying streptococci as either group A, B or not group A and B.     

Gender understanding and sex role preference in four cultures.

Administered a scale of gender understanding and a measure of sex-role preference to 48 3–9 yr olds from each of 4 traditional communities in Belize, Kenya, Nepal, and American Samoa. As in US research, stage-type response patterns were achieved on the gender scale by a large proportion of the Ss. There was also an orderly age progression in attainment of gender stages. Same-sex role choices were positively related to gender stages and to years of schooling. The effect of culture on age of gender stage attainment was significant, largely because Kenyan Ss achieved stage levels at later ages. This difference was most pronounced at the earliest level, that involving classification skills. Attainment of the later stages, involving the ability to maintain gender identity in the face of hypothetical transformations, was little affected by culture, and thus seemed to be under the control of developmental factors. Overall, the findings reflect the strong contribution of cognitive development to the growth of gender understanding. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Streptococcus group B and pregnancy: the therapeutic role of topical intravaginal clindamycin

OBJECTIVE: To evaluate the clinical and therapeutic efficacy of 2% clindamycin vaginal cream in pregnant women heavily colonized with group B streptococci (GBS). STUDY DESIGN: A prospective, clinical trial in which carriers of group B streptococci were randomized to receive topical intravaginal clindamycin or oral amoxicillin. PATIENTS: We randomized 105 pregnant women: 55 received 2% clindamycin vaginal cream (100 mg/day for 7 days) and 50 oral amoxicillin (2 g/day for 7 days). INTERVENTIONS: Patients were treated during pregnancy, none of them received intrapartum chemoprophylaxis. On the other hand, all the neonates, within 24 hours from delivery, were studied from the microbiological point of view, carrying out auricolar, nasal, oropharyngeal and umbilical cultures. RELIEFS: The eradication of the microorganism was evaluated by performing a vaginal culture after 6 weeks from the beginning of antibiotic therapy. RESULTS: The eradication rate of the microorganism was significantly higher in women treated with topical clindamycin compared with the group receiving oral amoxicillin (71% versus 36%; p < 0.05). The neonatal outcome was similar in the two groups in terms of gestational age at delivery and mean birthweight. None of the neonates was admitted to the neonatal intensive care unit and no cases of neonatal sepsis were recorded. CONCLUSIONS: From our experience we can conclude that, during pregnancy, a treatment with topical intravaginal clindamycin may be useful in the eradication of GBS.     

Antagonists for group I mGluRs attenuate excitotoxic neuronal death in cortical cultures

Activation of ion channel-linked glutamate receptors, especially N-methyl-D-aspartate (NMDA) receptors, mediates the excitotoxic effects of glutamate upon central neurons. We examined the hypothesis that activation of group I metabotropic glutamate receptors (mGluRs) would increase NMDA receptor-mediated cortical neuronal death. Addition of the selective group I mGluR agonists, dihydroxyphenylglycine (DHPG) or trans-azetidine-2,4-dicarboxylic acid (t-ADA) potentiated NMDA-induced neuronal death, and application of the group I mGluR-selective antagonist, aminoindan-1,5-dicarboxylic acid (AIDA), as well as the non-selective antagonists methyl-4-carboxyphenylglycine (MCPG) or 4-carboxyphenylglycine (4CPG) reduced NMDA- and kainate-induced neuronal death in murine cortical cultures. The pro-excitotoxic effect of group I mGluR activation may be mediated largely by enhancement of glutamate release, as DHPG potentiated high potassium-stimulated glutamate release, and the protective effects of both AIDA and MCPG were abolished when NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptors were blocked immediately after toxic NMDA receptor overstimulation. The present data support the possibility that antagonizing group I mGluRs may be a useful strategy for attenuating excitotoxic neuronal death in certain disease states.     

Flush resuscitation for group A streptococcus toxic shock: a possible role for continuous renal replacement therapy and plasmapheresis

Concentrations of citalopram in medicolegal samples from 92 autopsies and 27 living persons are described. In autopsy cases in which citalopram alone was the cause of death, concentrations ranged from 2.0 to 6.2 mg/kg whole blood. In autopsy cases in which citalopram together with other substances was considered to be the cause of death, the concentrations of citalopram ranged from 0.6 to 5.2 mg/kg whole blood. In autopsy cases toxic concentrations ranged from 0.4 to 0.9 mg/kg whole blood and therapeutic concentrations from 0.03 to 0.6 mg/kg whole blood. In samples from living persons the concentrations of citalopram in whole blood were 0.02 to 0.3 mg/kg.     

Patient preference for and reports of provider behavior: Impact of symmetry on patient outcomes.

Objective: Research has suggested that congruence between patient characteristics and contextual characteristics is a more robust predictor of outcomes than either patient or context characteristics alone. The goal of the present study was to examine the degree of congruence between patient preferences for the clinical encounter and reports of analogous dimensions of provider behavior and the effects of this congruence on patient outcomes. Design: Two hundred eighteen patients with diabetes (predominately Type II) completed measures of preference for and ratings of perceived provider behavior in three domains (1) information sharing, (2) behavioral involvement, and (3) socioemotional support. Main Outcome Measures: Patient satisfaction, self-reported adherence, and a clinical marker of diabetic control (hemoglobin A1c) were the outcomes of interest. Results: Congruence in information sharing and congruence in behavioral involvement were predictive of glycemic control and self-reported adherence, respectively. Congruence in behavioral involvement and congruence in socioemotional support were predictive of greater patient satisfaction. Conclusion: These findings provide further support for the importance of congruence between patient characteristics and contextual characteristics in predicting patient outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vaginal colonization with Group B beta-hemolytic streptococcus as a risk factor for post-cesarean section febrile morbidity

Vaginal colonization of mothers with Group B beta-hemolytic streptococcus (GBS) has been recognized as a risk factor for neonatal morbidity. The relationship of GBS colonization to risks for the mother who undergoes cesarean section has not been defined. In this study, we found that, among patients who underwent cesarean section, the 19% of them who were colonized with GBS had a higher incidence of standard fever (66.6% vs. 30.5%), clinical diagnosis of endomyometritis (61.1% vs. 12.5%), and use of antibiotics (61.1% vs. 26.3%) in relationship to a significantly increased frequency of premature rupture of the membranes (50.0% vs. 14.8%). Reasons for the association between vaginal colonization and increased morbidity are discussed.     

Patient dropout from a couples' group treatment for panic disorder with agoraphobia.

This study examined premature termination from couples' group treatment for panic disorder with agoraphobia. Patients were classified as either treatment noncompleters or treatment completers. Comparisons of pretreatment self-report and clinician-rated measures of anxiety and depression indicated no differences between groups. On communication measures, however, partners of noncompleters rated themselves as less communicative about panic-related issues. Of noncompleters, the majority reported "getting to treatment sessions" as problematic and indicated dissatisfaction with the cognitive-behavioral treatment approach. Results are discussed in terms of these issues and their impact on the treatment of these patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alternative algorithms for prevention of perinatal group B streptococcal infections

The well-known association of hypertension and diabetes mellitus and the lack of suitable animal models to study diabetic hypertension prompted us to transfer 4 chromosomal regions with quantitative trait loci (QTLs) for blood pressure of the spontaneously hypertensive SHR rat onto the genetic background of the diabetes-prone and normotensive BB/OK rat. Four congenic strains developed are named as BB. Sa (Chr.1), BB.Bp2 (Chr.18), BB.1K (Chr.20) and BB.Xs (Chr.X). Because the systolic blood pressure is significantly elevated in all congenics, renal related traits were investigated in serum and urine. Comparing BB/OK and their congenic derivatives, significant differences were found in all serum and in 7 out of 8 urine constituents studied. Most significant differences were found between BB/OK and BB.Bp2 rats. Significant differences were also found between the different congenic strains indicating that each congenic strain has its own phenotype and that each chromosomal region contains most probably further QTLs for some of the traits studied.