RESUMEN
Inactivation of Bacillales and Clostridiales spores is of interest, since some cause food spoilage and human diseases. A recent publication (mSphere 3: e00597-1, 2018) reported that glycerol monolaurate (GML) in a non-aqueous gel (GMLg) effectively killed spores of Bacillus subtilis, Bacillus cereus and Clostridioides difficile, and Bacillus anthracis spores to a lesser extent. We now show that (i) the B. subtilis spores prepared as in the prior work were impure; (ii) if spore viability was measured by diluting spores 1/10 in GMLg, serially diluting incubations 10-fold and spotting aliquots on recovery plates, there was no colony formation from the 1/10 to 1/1000 dilutions due to GMLg carryover, although thorough ethanol washes of incubated spores eliminated this problem and (iii) GMLg did not kill highly purified spores of B. subtilis, B. cereus, Bacillus megaterium and C. difficile in 3-20 h in the conditions used in the recent publication. GMLg also gave no killing of crude B. subtilis spores prepared as in the recent publication in 5 h but gave ~1·5 log killing at 24 h. Thus, GMLg does not appear to be an effective sporicide, although the gel likely inhibits spore germination and could kill spores somewhat upon long incubations. SIGNIFICANCE AND IMPACT OF THE STUDY: Given potential deleterious effects of spores of Bacillales and Clostridiales, there is an ongoing interest in new ways of spore killing. A recent paper (mSphere 3: e00597-1, 2018) reported that glycerol monolaurate (GML) in a non-aqueous gel (GMLg) effectively killed spores of many species. We now find that (i) the Bacillus subtilis spores prepared as in the previous report were impure and (ii) GMLg gave no killing of purified spores of Bacillales and Clostridiales species in ≤5 h under the published conditions. Thus, GMLg is not an effective sporicide, though may prevent spore germination or kill germinated spores.
Asunto(s)
Antibacterianos/farmacología , Bacillales/efectos de los fármacos , Clostridiales/efectos de los fármacos , Lauratos/farmacología , Monoglicéridos/farmacología , Esporas Bacterianas/efectos de los fármacos , Esporas Bacterianas/crecimiento & desarrollo , Bacillales/crecimiento & desarrollo , Bacillus cereus/efectos de los fármacos , Bacillus megaterium/efectos de los fármacos , Bacillus subtilis/efectos de los fármacos , Clostridiales/crecimiento & desarrollo , Clostridioides difficile/efectos de los fármacos , Microbiología de Alimentos , Geles/farmacologíaRESUMEN
Streptococcus pyogenes strains producing pyrogenic exotoxin A (scarlet fever toxin) have recently caused episodes of streptococcal toxic-shock-like syndrome (TSLS). We exploited knowledge of genetic diversity and relationships among exotoxin A-producing patient strains provided by multilocus enzyme electrophoresis to select strains for comparative sequencing of toxin genes. Our analysis identified four alleles of speA in natural populations, one of which (speA1) occurs in many distinct clonal lineages and is probably old. Two other alleles (speA2 and speA3), characterized solely by single amino acid substitutions, were each identified in single clones that together have caused the majority of TSLS episodes. It is unlikely that these alleles have had a long association with S. pyogenes clones. A fourth allele (speA4) also is present in a single phylogenetic lineage and is 9% divergent from the other three toxin alleles. An absence of synonomous (silent) nucleotide changes in speA2 and speA3 is unusual and suggests that the allelic variation is not selectively neutral, which implies that the toxins are not functionally equivalent. These results may be important in helping to understand the recent increase in frequency and severity of disease caused by S. pyogenes.
Asunto(s)
Alelos , Proteínas Bacterianas/genética , Exotoxinas/genética , Genes Bacterianos , Proteínas de la Membrana , Streptococcus pyogenes/genética , Secuencia de Bases , Genotipo , Relación Estructura-ActividadRESUMEN
The three-dimensional structure of an unglycosylated T cell antigen receptor (TCR) beta chain has recently been determined to 1.7 A resolution. To investigate whether this soluble beta chain (murine V beta 8.2J beta 2.1C beta 1) retains superantigen (SAG)-binding activity, we measured its affinity for various bacterial SAGs in the absence of MHC class II molecules. Dissociation constants (KDs) were determined using two independent techniques: surface plasmon resonance detection and sedimentation equilibrium. Specific binding was demonstrated to staphylococcal enterotoxins (SEs) B, C1, C2, and C3 and to streptococcal pyrogenic exotoxin A (SPEA), consistent with the known proliferative effects of these SAGs on T cells expressing V beta 8.2. In contrast, SEA, which does not stimulate V beta 8.2-bearing cells, does not bind the recombinant beta chain. Binding of the beta chain to SAGs was characterized by extremely fast dissociation rates (> 0.1 s-1), similar to those reported for certain leukocyte adhesion molecules. Whereas the beta chain bound SEC1, 2, and 3 with KDs of 0.9-2.5 microM, the corresponding value for SEB was approximately 140 microM. The much weaker binding to SEB than to SEC1, 2, or 3 was surprising, especially since SEB was found to actually be 3- to 10-fold more effective, on a molar basis, than the other toxins in stimulating the parental T cell hybridoma. We interpret these results in terms of the ability of SEC to activate T cells independently of MHC, in contrast to SEB. We have also measured SE binding to the glycosylated form of the beta chain and found that carbohydrate apparently does not contribute to recognition, even though the N-linked glycosylation sites at V beta 8.2 residues Asn24 and Asn74 are at or near the putative SAG-binding site. This result, along with the structural basis for the V beta specificity of SEs, are discussed in relation to the crystal structure of the unglycosylated beta chain.
Asunto(s)
Enterotoxinas/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Superantígenos/metabolismo , Enterotoxinas/metabolismo , Glicosilación , Humanos , Cinética , Activación de Linfocitos , Modelos Moleculares , Unión Proteica , Conformación Proteica , Proteínas Recombinantes , Solubilidad , Staphylococcus aureus/inmunología , Relación Estructura-Actividad , UltracentrifugaciónRESUMEN
T lymphocyte infiltration is a prominent feature of the skin inflammation associated with infections by toxin (superantigen)-secreting Staphylococcus aureus or Streptococcus bacteria. The cutaneous lymphocyte-associated antigen (CLA) has been hypothesized to be a homing receptor (HR) involved in selective migration of memory/effector T cells to the skin. Since the expression of this putative skin-selective HR is known to be under strict microenvironmental control, we sought to determine the effect of staphylococcal and streptococcal toxins on T cell expression of CLA. After in vitro stimulation of peripheral blood mononuclear cells with staphylococcal enterotoxin B, toxic shock syndrome toxin-1, and streptococcal pyrogenic exotoxins A and C, there was a significant increase in the numbers of CLA+ T cell blasts (p < 0.01), but not blasts bearing the mucosa-associated adhesion molecule alpha e beta 7-integrin, compared with T cells stimulated with phytohemaglutinin (PHA) or anti-CD3. Bacterial toxins were also found to specifically induce interleukin (IL) 12 production. More importantly, induction of toxin-induced CLA expression was blocked by anti-IL-12, and the addition of IL-12 to PHA-stimulated T cells induced CLA, but not alpha e beta 7-integrin, expression. These data suggest that bacterial toxins induce the expansion of skin-homing CLA+ T cells in an IL-12-dependent manner, and thus may contribute to the development of skin rashes in superantigen-mediated diseases.
Asunto(s)
Interleucina-12/biosíntesis , Glicoproteínas de Membrana/inmunología , Receptores Mensajeros de Linfocitos/inmunología , Piel/inmunología , Superantígenos/inmunología , Linfocitos T/inmunología , Antígenos Bacterianos/inmunología , Antígenos de Diferenciación de Linfocitos T , Antígenos de Neoplasias , Células Cultivadas , Humanos , Staphylococcus aureus/inmunología , Streptococcus/inmunologíaRESUMEN
The three-dimensional structure of the complex between a T cell receptor (TCR) beta chain (mouse Vbeta8.2Jbeta2.1Cbeta1) and the superantigen (SAG) staphylococcal enterotoxin C3 (SEC3) has been recently determined to 3.5 resolution. To evaluate the actual contribution of individual SAG residues to stabilizing the beta-SEC3 complex, as well as to investigate the relationship between the affinity of SAGs for TCR and MHC and their ability to activate T cells, we measured the binding of a set of SEC3 and staphylococcal enterotoxin B (SEB) mutants to soluble recombinant TCR beta chain and to the human MHC class II molecule HLA-DR1. Affinities were determined by sedimentation equilibrium and/or surface plasmon detection, while mitogenic potency was assessed using T cells from rearrangement-deficient TCR transgenic mice. We show that there is a clear and simple relationship between the affinity of SAGs for the TCR and their biological activity: the tighter the binding of a particular mutant of SEC3 or SEB to the TCR beta chain, the greater its ability to stimulate T cells. We also find that there is an interplay between TCR-SAG and SAG-MHC interactions in determining mitogenic potency, such that a small increase in the affinity of a SAG for MHC can overcome a large decrease in the SAG's affinity for the TCR. Finally, we observe that those SEC3 residues that make the greatest energetic contribution to stabilizing the beta-SEC3 complex ("hot spot" residues) are strictly conserved among enterotoxins reactive with mouse Vbeta8.2, thereby providing a basis for understanding why SAGs having other residues at these positions show different Vbeta-binding specificities.
Asunto(s)
Enterotoxinas/metabolismo , Antígeno HLA-DR1/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Superantígenos/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión , Activación de Linfocitos , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Mutación , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. OBJECTIVES: To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. METHODS: This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2-49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. RESULTS: An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. CONCLUSIONS: In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.
Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Fármacos Dermatológicos/administración & dosificación , Inmunosupresores/administración & dosificación , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Tacrolimus/análogos & derivados , Administración Cutánea , Adolescente , Adulto , Niño , Preescolar , Dermatitis Atópica/microbiología , Método Doble Ciego , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vehículos Farmacéuticos/administración & dosificación , Infecciones Cutáneas Estafilocócicas/inmunología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/inmunología , Superantígenos/inmunología , Tacrolimus/administración & dosificación , Adulto JovenRESUMEN
Streptococcal and staphylococcal superantigens (SAg's) have been implicated in the pathogenesis of inflammatory skin diseases, but the mechanisms by which these toxins act are unknown. The present study assessed the ability of nanogram quantities of topically applied purified toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin type B, and streptococcal pyrogenic enterotoxin types A and C to induce inflammatory reactions in clinically uninvolved skin of normal controls and subjects with psoriasis, atopic dermatitis, and lichen planus. These SAg's triggered a significantly greater inflammatory skin response in psoriatics than in normal control subjects or in subjects with atopic dermatitis or lichen planus. Surprisingly, skin biopsies did not exhibit the T-cell receptor Vbeta stimulatory properties predicted for SAg-induced skin reactions. By 6 hours after patch testing with SAg's, TNF-alpha mRNA had increased in the epidermis (but not the dermis) in biopsies from psoriatics, compared with controls. Immunohistochemical studies revealed significantly higher HLA-DR expression in keratinocytes from psoriatics than from controls. However, a mutant TSST-1 protein that fails to bind HLA-DR did not elicit an inflammatory skin reaction. These results indicate that keratinocyte expression of HLA-DR enhances inflammatory skin responses to SAg's. They may also account for previous studies failing to demonstrate selective expansion of T-cell receptor Vbetas in psoriatics colonized with SAg-producing Staphylococcus aureus, and they identify a novel T cell-independent mechanism by which SAg's contribute to the pathogenesis of inflammatory skin diseases.
Asunto(s)
Dermatitis por Contacto , Epidermis/inmunología , Antígenos HLA-DR/inmunología , Psoriasis/inmunología , Superantígenos/inmunología , Toxinas Biológicas/inmunología , Adulto , Animales , Estudios de Casos y Controles , Dermatitis Atópica/inmunología , Epidermis/anatomía & histología , Exotoxinas/inmunología , Antígenos HLA-DR/metabolismo , Humanos , Hibridación in Situ , Leucocitos Mononucleares/inmunología , Liquen Plano/inmunología , Ratones , Persona de Mediana Edad , Pruebas del Parche , Psoriasis/patología , Staphylococcus/inmunología , Streptococcus/inmunología , Linfocitos T/inmunología , Linfocitos T/patología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The streptococcal pyrogenic toxins A, B, and C (SPEA, SPEB, and SPEC) are responsible for the fever, rash, and other toxicities associated with scarlet fever and streptococcal toxic shock syndrome. This role, together with the ubiquity of diseases caused by Streptococcus pyogenes, have prompted structural analyses of SPEA by several groups. Papageorgiou et al. (1999) have recently reported the structure of SPEA crystallized in the absence of zinc. Zinc has been shown to be important in the ability of some staphylococcal and streptococcal toxins to stimulate proliferation of CD4+ T-cells. Since cadmium is more electron dense than zinc and typically binds interchangeably, we grew crystals in the presence of 10 mM CdCl2. Crystals have been obtained in three space groups, and the structure in the P2(1)2(1)2(1) crystal form has been refined to 1.9 A resolution. The structural analysis revealed an identical tetramer as well as a novel tetrahedral cluster of cadmium in all three crystal forms on a disulfide loop encompassing residues 87-98. No cadmium was bound at the site homologous to the zinc site in staphylococcal enterotoxins C (SECs) despite the high structural homology between SPEA and SECs. Subsequent soaking of crystals grown in the presence of cadmium in 10 mM ZnCl2 showed that zinc binds in this site (indicating it can discriminate between zinc and cadmium ions) using the three ligands (Asp77, His106, and His110) homologous to the SECs plus a fourth ligand (Glu33).
Asunto(s)
Proteínas Bacterianas , Exotoxinas/química , Proteínas de la Membrana , Metales/química , Modelos Moleculares , Conformación ProteicaRESUMEN
The structure of toxic shock syndrome toxin-1 (TSST-1), the causative agent in toxic shock syndrome, has been determined in three crystal forms. The three structural models have been refined to R-factors of 0.154, 0.150, and 0.198 at resolutions of 2.05 A, 2.90 A, and 2.75 A, respectively. One crystal form of TSST-1 contains a zinc ion bound between two symmetry-related molecules. Although not required for biological activity, zinc dramatically potentiates the mitogenicity of TSST-1 at very low concentrations. In addition, the structure of the tetramutant TSST-1H [T69I, Y80W, E132K, I140T], which is nonmitogenic and does not amplify endotoxin shock, has been determined and refined in a fourth crystal form (R-factor = 0.173 to 1.9 A resolution).
Asunto(s)
Toxinas Bacterianas/química , Enterotoxinas/química , Superantígenos/química , Toxinas Bacterianas/genética , Toxinas Bacterianas/inmunología , Cristalografía por Rayos X , Enterotoxinas/genética , Enterotoxinas/inmunología , Mitógenos/química , Mitógenos/genética , Mitógenos/inmunología , Modelos Moleculares , Mutación , Conformación Proteica , Staphylococcus aureus , Superantígenos/genética , Superantígenos/inmunología , Zinc/inmunologíaRESUMEN
Microbial agents are known to play a significant role in aggravating allergic diseases. Recently described viral and bacterial superantigens represent one important strategy by which infectious agents can stimulate the immune response. In previous work, we reported that the staphylococcal toxin toxic shock toxin-1 (TSST-1), a prototypic superantigen, induces in vitro total IgE synthesis after cross-linking T and B cells. This study was carried out to establish a potential link between superantigens and the enhanced IgE response to specific allergens in allergic patients. Peripheral blood mononuclear cells from atopic patients were isolated during and outside the pollen allergen season and stimulated with TSST-1, a prototypic superantigen. Total IgE and interferon-gamma production were measured in supernatants of these cultures. Outside the pollen season, TSST-1 significantly increased total IgE production only in the presence of exogenous interleukin-4, whereas during the pollen season IgE production was significantly enhanced without the need of exogenous interleukin-4. This increase in the absence of exogenous interleukin-4 was associated with significantly lower interferon-gamma production by peripheral blood mononuclear cells stimulated by TSST-1 during the pollen season. Moreover, TSST-1 stimulation of peripheral blood mononuclear cells from inhalant allergic patients was followed by an increased production of allergen-specific IgE that was restricted to the allergen to which the patient was allergic and recently exposed. In addition, TSST-1 induced on B cells the expression of B7.2, a molecule that has recently been demonstrated to enhance T helper 2 responses and to be involved in IgE regulation. This study, by demonstrating that superantigens can augment allergen-specific IgE synthesis and B7.2 expression, provides a mechanism by which microbial superantigens may modulate allergic responses.
Asunto(s)
Alérgenos/inmunología , Toxinas Bacterianas , Dermatitis Atópica/inmunología , Enterotoxinas/farmacología , Inmunoglobulina E/metabolismo , Antígenos CD/efectos de los fármacos , Linfocitos B/química , Antígeno B7-1/efectos de los fármacos , Antígeno B7-2 , Dermatitis Atópica/sangre , Enterotoxinas/fisiología , Humanos , Interferón gamma/biosíntesis , Glicoproteínas de Membrana/efectos de los fármacos , Proteínas de la Membrana/química , Staphylococcus aureus , Superantígenos/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Clinical features and microbiologic data on all cases of serious (hospitalized) Group A streptococcal infections in children managed at our institution between 1985 and 1988 are presented. All 6 cases were caused by toxin-producing strains. Four of 6 were toxin A-producing strains whereas none of 58 community-acquired (Group A streptococcal) pharyngeal isolates in the same period was a toxin A producer. A review of the literature on the incidence of toxin A-producing strains provides information suggesting a resurgence of such strains in the late 1980s after a relative disappearance of toxin B production in isolates from these patients was also significantly greater than in the isolates acquired from the community in uncomplicated pharyngitis. These findings suggest a role for exotoxin in severe manifestations of Group A streptococcal disease in children.
Asunto(s)
Exotoxinas/biosíntesis , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes/aislamiento & purificación , Adolescente , Celulitis (Flemón)/etiología , Niño , Preescolar , Coagulación Intravascular Diseminada/etiología , Femenino , Gangrena/etiología , Humanos , Lactante , Recién Nacido , Masculino , Minnesota/epidemiología , Prevalencia , Sepsis/microbiología , Infecciones Estreptocócicas/epidemiologíaRESUMEN
There is little information available on invasive group B Streptococcus (GBS) infection in pediatric patients older than 3 months of age. Review of infection control records at LeBonheur Children's Medical Center from January 1, 1986, to June 30, 1993, identified 143 patients with a positive GBS culture from normally sterile body fluid. Medical records of 18 (13%) patients > 3 months old with their first GBS infection were reviewed. Age range was 15 weeks to 18 years (median age, 13 months). Ten were black and 11 were girls. Five infants had a history of premature birth and 2 infants were infected with human immunodeficiency virus. The serotype distribution of 12 available GBS isolates was 4 type III, 2 each type V and Ia and 1 each type Ia/c, Ib/c, II and II/c. Bacteremia without a focus (9 patients) was the most common clinical manifestation. All 4 type III isolates were associated with bacteremia. One infant with human immunodeficiency virus infection had sepsis and bullous desquamation; a toxin-producing type V strain was isolated from her blood. Two adolescents with ventriculoperitoneal shunts had meningitis, including one whose cerebrospinal fluid also grew a type V strain. Other clinical manifestations were septic arthritis, endocarditis (Ia, II/c), central venous catheter (Ia/c) and ventriculostomy infections.
Asunto(s)
Bacteriemia/epidemiología , Infecciones Estreptocócicas/epidemiología , Streptococcus agalactiae/aislamiento & purificación , Adolescente , Distribución por Edad , Edad de Inicio , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/fisiopatología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Estudios Retrospectivos , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/fisiopatologíaRESUMEN
OBJECTIVE: To describe demographic and clinical features of invasive group A streptococcal (GAS) infections in children with varicella in Southern California in early 1994. METHODS: From hospitals of Los Angeles and Orange Counties, children with invasive GAS infections after varicella between January 1 and April 8, 1994, were identified by hospital infection control nurses. Medical records of patients were reviewed, and any available GAS isolate was further tested. RESULTS: Twenty-four cases were identified; 54% were male, 50% were Hispanic and the median age was 3 years (range, 0.5 to 8). Four cases died before hospitalization. The other 20 were hospitalized for a median of 10 days (range, 4 to 50): 14 presented with cellulitis (1 with concomitant epiglottitis), 2 with myositis/necrotizing fasciitis, 2 with pneumonia and 2 with bacteremia without apparent source. Five had evidence of multiorgan involvement including two patients fulfilling criteria of streptococcal toxic shock-like syndrome. Of 19 patients with blood cultures, 10 (53%) had GAS bacteremia. Onset of GAS infection was suggested, as a median, on Day 4 of varicella, with fever, vomiting and localized swelling being commonly reported. The mean maximum temperature on the day of admission was 39.4 degrees C (102.9 degrees F). Four GAS isolates were M1T1 and one was M3T3. Five isolates produced streptococcal pyrogenic exotoxins A and B. CONCLUSIONS: Invasive GAS disease, including streptococcal toxic shock-like syndrome, is a serious complication of varicella. Physicians should be alert for the complication of GAS when fever and localized swelling or signs of cellulitis develop 3 days or more after the onset of varicella. Widespread use of varicella vaccine may decrease invasive GAS infections in this setting.
Asunto(s)
Bacteriemia , Varicela/complicaciones , Choque Séptico , Infecciones Estreptocócicas , Streptococcus pyogenes/aislamiento & purificación , Bacteriemia/complicaciones , Bacteriemia/epidemiología , California/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Choque Séptico/complicaciones , Choque Séptico/epidemiología , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/epidemiología , Tasa de SupervivenciaRESUMEN
BACKGROUND: Outbreaks of nosocomial staphylococcal scalded skin syndrome (SSSS) in infants have been well-described associated with the well baby nursery or delivery room. We describe two cases of SSSS in very low birth weight infants in a neonatal intensive care unit (NICU) and the success of infection control strategies used to prevent an outbreak. METHODS: Staphylococcal scalded skin syndrome was diagnosed in two infants in the NICU: Case I (a 47-day-old, formerly 530-g female); and Case II diagnosed 48 h later (a 41-day old, formerly 706-g female). Multiple infection control measures were implemented: (1) isolation and intravenous antibiotic treatment of cases; (2) placement of exposed infants into a cohort; (3) prophylactic mupirocin treatment of the anterior nares of all infants in the NICU and staff colonized with Staphylococcus aureus; and (4) personnel hand washing with hexachlorophene. Detection of exfoliative toxin A and studies to determine the genetic relatedness of S. aureus strains isolated from patients and staff were performed. RESULTS: In addition to the two SSSS cases, S. aureus was isolated from 2 of 12 (17%) exposed asymptomatic infants, 2 of 20 (10%) ancillary staff, 8 of 30 (27%) nurses and 6 of 24 (25%) physicians. Exfoliative toxin A-producing strains were isolated from both cases and one asymptomatic infant. No toxin was expressed by strains isolated from staff. Pulse field gel electrophoresis demonstrated genetically identical strains of S. aureus from the two SSSS cases and the asymptomatic infant, whereas three staff members harbored strains genetically related to the case strain. Unexpectedly two additional unique clusters of genetically related S. aureus strains were identified from the surveillance cultures. CONCLUSIONS: This report documents the rare occurrence of nosocomial SSSS attributed to transmission in the NICU among extremely low birth weight infants. Multiple infection control strategies were effective in limiting the outbreak. Molecular epidemiology investigation supported a unique S. aureus strain responsible for this event and the presence of bidirectional spread between staff and patients of non-toxin-producing strains.
Asunto(s)
Infección Hospitalaria/epidemiología , Enfermedades del Prematuro/epidemiología , Epidemiología Molecular , Síndrome Estafilocócico de la Piel Escaldada/epidemiología , Electroforesis en Gel de Campo Pulsado , Exfoliatinas/análisis , Familia , Femenino , Personal de Salud , Humanos , Recién Nacido , Recien Nacido Prematuro , Control de Infecciones , Transmisión de Enfermedad Infecciosa de Profesional a Paciente , Unidades de Cuidado Intensivo Neonatal , Masculino , Mucosa Nasal/microbiología , Reacción en Cadena de la Polimerasa , Piel/microbiología , Síndrome Estafilocócico de la Piel Escaldada/prevención & control , Síndrome Estafilocócico de la Piel Escaldada/transmisión , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
The challenge to develop antiviral agents effective against DNA viruses such as human papillomavirus (HPV) has been dependent on finding an animal model which mimics the human forms of the disease. We have used an existing model system for the purpose of measuring the effect of antiviral drugs on the inhibition of growth of these lesions. This was based upon domestic rabbits which efficiently grow cutaneous papillomas (warts) when infected with cottontail rabbit papillomavirus (CRPV). One agent which had shown significant success in achieving these goals was ribavirin. Ribavirin was administered intradermally shortly prior to infection at multiple sites with CRPV. Following daily injections of this drug for eight weeks, we have shown a dose-dependent response which had markedly reduced the number of warts, the time of first appearance of warts and reduced the tumor mass as compared to placebo-treated control animals. At the highest dose of ribavirin tested, 30 mg/kg/day, compared to controls, the average reduction in the number of warts was 52%, the average time of first appearance of warts was 49% longer, and the average mass of the warts was reduced by 98%. No detectable antibodies to CRPV were observed in any of the animals. The only side effects which were observed was focal alopecia, and a decrease in body growth upon prolonged treatment, both of which were completely reversible. Pharmacokinetic studies established the metabolism of ribavirin over a 24-h period of time. Ribavirin administered beginning 12 or 30 days post-infection, while not reducing the number of warts, slightly retarded the growth of warts as determined by date of first appearance of warts and mass of warts.
Asunto(s)
Papillomaviridae/efectos de los fármacos , Ribavirina/uso terapéutico , Verrugas/tratamiento farmacológico , Animales , Anticuerpos Antivirales/análisis , Secuencia de Bases , ADN Viral/análisis , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Agar , Ensayo de Inmunoadsorción Enzimática , Inyecciones Intradérmicas , Datos de Secuencia Molecular , Papillomaviridae/inmunología , Papillomaviridae/aislamiento & purificación , Conejos , Análisis de Regresión , Ribavirina/administración & dosificación , Ribavirina/farmacocinética , Verrugas/microbiología , Verrugas/patologíaRESUMEN
BACKGROUND: Laminaria tents used to facilitate surgical abortion are rarely associated with significant infectious morbidity. CASE: A parous woman in midpregnancy had laminaria placed in her cervix followed by a second set after 24 hours. Eight hours later, she presented with dyspnea, hives, fever, tachycardia, and hypotension. Antibiotic treatment was initiated and a dilation and evacuation procedure was performed. Amniotic membrane cultures showed a heavy growth of Staphylococcus aureus with staphylococcal enterotoxin C expression, compatible with toxic shock syndrome. CONCLUSION: Laminaria cervical dilation might be associated with toxic shock syndrome.
Asunto(s)
Laminaria , Choque Séptico/etiología , Infecciones Estafilocócicas/etiología , Aborto Inducido , Femenino , Humanos , Factores de TiempoRESUMEN
Group B streptococcal cells, either viable or heat-killed, contain a substance that induced fever in rabbits with maximal responses occurring four hours after intravenous injection. In contrast, supernatant fluids failed to induce significant fever. Group B streptococcal cells also enhanced host susceptibility to lethal shock by endotoxin as much as 40,000-fold. A graph of log streptococcal cell dose used for pretreatment versus log LD50 endotoxin gave a straight line with a slope of approximately -1. Rabbits that received both streptococcal cells and endotoxin showed initial fever followed by hypothermia, labored breathing, watery diarrhea, evidence of vascular collapse, and finally death. Animals that received streptococcal cells or endotoxin alone showed only fevers and mild diarrhea. A possible theory for the cause of death in the neonate infected with group B streptococci is presented.
Asunto(s)
Endotoxinas/farmacología , Enfermedades del Recién Nacido/etiología , Infecciones Estreptocócicas/etiología , Streptococcus agalactiae/fisiología , Animales , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Endotoxinas/administración & dosificación , Fiebre/etiología , Humanos , Recién Nacido , Dosificación Letal Mediana , Conejos , Choque Séptico/etiologíaRESUMEN
Tampons were tested for effect on growth and production of toxic shock syndrome toxin 1 by Staphylococcus aureus. Under good growth conditions, regular absorbency tampons had little effect on bacterial growth and inhibited toxin production two- to fourfold. In contrast, higher absorbency tampons had three different effects: 1) some tampons had no effect on bacterial growth but inhibited toxin production; 2) many tampons inhibited both growth and toxin production; 3) one tampon inhibited growth but increased exotoxin per cell. These effects were independent of degree of saturation of the tampons and were observed at incubation times of six, 12, and 18 hours. In no instance was the production of toxic shock syndrome toxin 1 per milliliter increased in the presence of tampons when compared with control.
Asunto(s)
Toxinas Bacterianas/biosíntesis , Exotoxinas/biosíntesis , Choque Séptico/microbiología , Staphylococcus aureus/metabolismo , Tampones Quirúrgicos , Absorción , Medios de Cultivo , Femenino , Humanos , Inmunodifusión/métodos , Choque Séptico/etiología , Staphylococcus aureus/crecimiento & desarrollo , Tampones Quirúrgicos/efectos adversos , Factores de TiempoRESUMEN
Recent studies of Staphylococcus aureus isolates from patients with toxic shock syndrome (TSS) have shown the dominance of phage type 29/52 with the capacity to produce pyrogenic exotoxin C and enterotoxin F. They also showed that 29% of the isolates were nontypable and 90% of them had similar toxigenic properties. The existence of unknown and important phages in this disease was postulated. Five new phages were then developed and used for typing three groups of staphylococcal isolates: 236 from patients with TSS, 67 from patients without TSS, and 159 from patients with infected burns. Results showed a high correlation between the lytic action of the new phages and the 29/52 phages, and an additional typing capability in 35% of the previously nontypable TSS isolates, emphasizing further the potential of bacteriophage typing of S aureus in these infections.