The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: (1) How should HAE-1/2 be defined and classified?, (2) How should HAE-1/2 be diagnosed?, (3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, (4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and (5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures?

Reduced virulence of group A streptococcal Tn916 mutants that do not produce streptolysin S.

Streptolysin S (SLS) is a potent cytolytic toxin produced by nearly all group A streptococci (GAS). SLS-deficient Tn916 insertional mutants were generated from two clinical isolates of GAS, MGAS166s and T18Ps (M serotypes 1 and 18, respectively), by transposon mutagenesis using Tn916 donor strain Enterococcus faecalis CG110. Representative nonhemolytic transconjugants SBNH5 and SB30-2 each harbored a single Tn916 insertion in identical loci. The insertion in SBNH5 was located in the promoter region of an open reading frame, designated sagA, rendering it transcriptionally inactive. Protease, streptolysin O, and DNase activities and the production of M protein remained the same in the nonhemolytic mutants and the wild-type strains, as did the growth rates and exoprotein profiles. Transconjugants were evaluated in an established murine model by injecting the organisms subcutaneously and monitoring the mice for alterations in weight and the development of necrotic lesions. Animals infected with SBNH5, compared to those infected with MGAS166s, gained weight during the first 24 h (+1.15 versus -1.16 g; P < 0.05) and had fewer necrotic lesions (0 versus 7; P = 0.0007). Animals infected with SB30-2, compared to those infected with T18Ps, also gained weight within the first 24 h (+0.54 versus -0.66 g; P < 0.05) and produced fewer necrotic lesions (1 versus 8; P = 0.001). Revertants of the mutants in which Tn916 had been excised regained the hemolytic phenotype and the virulence profile of the wild-type strains. This study demonstrates that SLS-deficient mutants of GAS, belonging to different M serotypes and containing identical Tn916 mutations, are markedly less virulent than their isogenic parents.

Streptococcal toxic shock syndrome in dogs.

OBJECTIVE: To determine the clinical, pathologic, and bacteriologic findings in dogs that developed severe invasive infections with group G streptococci (GGS) over a 6-month period in southern Ontario. DESIGN: Prospective case series. ANIMALS: 7 dogs n southern Ontario with severe streptococcal infection during a 6-month period. PROCEDURE: Using pulsed-field gel electrophoresis, molecular typing of streptococcal isolates was performed. Isolates were examined for the M protein gene emm1.0, pyrogenic exotoxin genes speA, speB, speF, hyaluronic acid synthase genes hasA, hasB, and for C5a peptidase gene scpA by use of DNA probes or polymerase chain reaction. RESULTS: 3 dogs with streptococcal shock without necrotizing fasciitis died or were euthanatized within 48 hours of admission, whereas 4 dogs with streptococcal shock and necrotizing fasciitis survived following surgical debridement, supportive medical treatment, and treatment with antibiotics. Of the 6 Lancefield group G streptococcal isolates available for characterization, 5 were Streptococcus canis and 1 had characteristics of group G streptococcal strains of human origin. Results of molecular typing indicated that isolates were unrelated to each other. Examination of the canine isolates for putative virulence genes found in human group A streptococci resulted in identification of the emm1.0 gene only in 1 of the isolates. The canine isolates otherwise lacked virulence genes associated with human group A streptococcal toxic shock infections. CLINICAL-IMPLICATIONS: The development of severe invasive infection in dogs resulting from GGS indicates that a virulent form of GGS has developed in southern Ontario.

Enterococcis: pathogens of the 90s.

The genus Enterococcus consists of at least 12 species, two of which account for over 95% of the clinically important strains, E faecalis (85%-90%) and E faecium (5%-10%). Despite their ubiquity and frequent isolation, they have not been thought to cause serious disease because they lack common virulence factors. Now, however, enterococci are regarded as true pathogens and are the second leading cause of nosocomial infections. This change results from their increasing antimicrobial resistance and the extensive use of antimicrobial drugs (for example-cephalosporins) that are not active against them. Serious infections should usually be treated with a beta-lactam and an aminoglycoside, but glycopeptides have been increasingly used during the last decade. Two novel resistance patterns of particular concern recently are high level aminoglycoside resistance (HLAR) and vancomycin resistance. The prevalence of HLAR is between 15% and 55%, and glycopeptide resistance has become widespread in various geographical areas. This poses a serious problem, as such resistance may spread to other Gram-positive organisms and is often associated with resistance to other antimicrobial drugs. This may theoretically result in groups of organisms for which there will be no effective antimicrobial treatment.