Pyogenic streptococci cause significant morbidity and mortality, and the incidence of invasive group C and G streptococcal disease appears to be increasing. In this retrospective study we describe the epidemiological characteristics of invasive group A, C and G, along with non-invasive group C and G streptococcal infections in Western Norway from 1999 to 2013. A total of 512 invasive streptococcal infections were identified, of these 297 (58%) were group A (GAS), 24 (5%) group C (GCS) and 188 (37%) group G streptococci (GGS). In the non-invasive group, 4935 GCS and GGS-infections were identified. GCS and GGS were treated as one group (GCGS) for statistical purposes. All microbial categories displayed increasing incidence with age, seasonal variation and a male predominance. The incidence of invasive GCGS infections increased significantly from 1.4/100,000 inhabitants in 1999 to 6.3/100,000 in 2013 (p <0.001). Conversely, the annual rates of invasive GAS infection exhibited marked fluctuations, ranging from 2.7/100,000 (2000) to 8.3/100,000 (1999), but no significant temporal trends were observed. The incidence of non-invasive GCGS infections decreased significantly during the study period (p <0.001). The most frequently encountered emm-types among the 209 iGAS-isolates analysed were emm1 (24%), emm3 (14%) and emm28 (14%); whereas stG643 (19%), stG485 (15%) and stG6 (13%) were most prevalent among the 122 iGCGS-isolates available for typing. The increasing burden of invasive β-haemolytic streptococcal disease in our community calls for sustained attentiveness to the clinical and molecular aspects of GAS, GCS and GGS infections.

This prospective study of cellulitis identified β-hemolytic streptococci as the dominating cause in all investigated subgroups. Group C/G streptococci were more frequently detected than group A streptococci. No single clinical feature substantially increased the probability of confirmed streptococcal etiology.

Background Necrotizing soft-tissue infections (NSTI) are life-threatening conditions often caused by β-hemolytic streptococci, group A Streptococcus (GAS) in particular. Optimal treatment is contentious. The INFECT cohort includes the largest set of prospectively enrolled streptococcal NSTI cases to date. Methods From the INFECT cohort of 409 adults admitted with NSTI to 5 clinical centers in Scandinavia, patients culture-positive for GAS or Streptococcus dysgalactiae (SD) were selected. Risk factors were identified by comparison with a cohort of nonnecrotizing streptococcal cellulitis. The impact of baseline factors and treatment on 90-day mortality was explored using Lasso regression. Whole-genome sequencing of bacterial isolates was used for emm typing and virulence gene profiling. Results The 126 GAS NSTI cases and 27 cases caused by SD constituted 31% and 7% of the whole NSTI cohort, respectively. When comparing to nonnecrotizing streptococcal cellulitis, streptococcal NSTI was associated to blunt trauma, absence of preexisting skin lesions, and a lower body mass index. Septic shock was significantly more frequent in GAS (65%) compared to SD (41%) and polymicrobial, nonstreptococcal NSTI (46%). Age, male sex, septic shock, and no administration of intravenous immunoglobulin (IVIG) were among factors associated with 90-day mortality. Predominant emm types were emm1, emm3, and emm28 in GAS and stG62647 in SD. Conclusions Streptococcal NSTI was associated with several risk factors, including blunt trauma. Septic shock was more frequent in NSTI caused by GAS than in cases due to SD. Factors associated with mortality in GAS NSTI included age, septic shock, and no administration of IVIG.

Background Streptococcus equi subsp. zooepidemicus is a beta-hemolytic group C streptococcus mainly causing infections in domesticated animals. Here we describe the first case of zoonotic necrotizing myositis caused by this bacterium.Case presentationThe patient was a 73-year-old, previously healthy farmer with two asymptomatic Shetland ponies in his stable. After close contact with the ponies while feeding them, he rapidly developed erythema of his left thigh and sepsis with multiple organ failure. The clinical course was severe and complicated, requiring repetitive surgical excision of necrotic muscle, treatment with vasopressors, mechanical ventilation and continuous venovenous hemofiltration, along with adjunctive hyperbaric oxygen therapy. The patient was discharged from hospital at day 30, without obvious sequelae.The streptococcal isolate was identified as Streptococcus equi by MALDI-ToF MS, and was later assigned subspecies identification as S. equi subsp. zooepidemicus. Multilocus sequence typing identified the strain as a novel sequence type (ST 364), closely related to types previously identified in horses and cattle. A focused proteomic analysis revealed that the ST 364 expressed putative virulence factors similar to that of Streptococcus pyogenes, including homologues of the M protein, streptodornases, interleukin 8-protease and proteins involved in the biosynthesis of streptolysin S.ConclusionThis case illustrates the zoonotic potential of S. equi subsp. zooepidemicus and the importance of early clinical recognition, rapid and radical surgical therapy, appropriate antibiotics and adequate supportive measures when necrotizing soft tissue infection is suspected. The expression of Streptococcus pyogenes-like putative virulence determinants in ST 364 might partially explain the fulminant clinical picture.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2262-7) contains supplementary material, which is available to authorized users.

In this prospective study of cellulitis, several nonpharmacological factors were associated with lack of early response. Such early nonresponse was rarely related to inappropriate therapy but strongly predictive of early treatment escalation, suggesting that broadening antibiotic treatment often may be premature.

Increasing incidence rates of invasive Streptococcus dysgalactiae subspecies equisimilis (SDSE) infections have been reported worldwide, but the evolutionary mechanisms underlying this development remain elusive. Through prospective surveillance of invasive SDSE infections in western Norway, we observed the emergence of a novel and virulent SDSE genotype, stG62647. This emm-type, rarely encountered as a cause of invasive disease during 1999–2012, emerged in 2013 as the predominant SDSE-genotype. The stG62647-infections were associated with an aggressive clinical course, including the occurrence of streptococcal toxic shock syndrome, necrotizing soft-tissue infections and endocarditis. All the invasive stG62647-isolates were subjected to whole genome sequencing, attempting to explore the genetic events underpinning its epidemicity. Although 10% of the genomes was unique for stG62647-genotype, notably 18 out of 19 isolates contained a disrupted streptococcal invasive locus (sil) due to the insertion of a transposase, IS1548, into the silB-gene. We postulate that the virulence of stG6267-isolates could be partly attributable to the abrogation of the attenuating control normally exerted by this regulon, although experimental verification was not performed. To the best of our knowledge, this is the first study employing large scale whole genome sequencing to illuminate the genetic landscape of epidemic lineages in SDSE.

dWe present a case of infective endocarditis caused by Streptococcus dysgalactiae subsp. dysgalactiae, a major cause of bovine mastitis and previously thought to be an animal-restricted pathogen. The patient reported no direct contact with animals, and the clinical course was severe and complicated. CASE REPORTA 65-year-old male patient was admitted to Haukeland University Hospital in western Norway with radiating pain in his left shoulder, fever, and muscle ache. One month earlier, he had been admitted to a hospital in Spain with similar symptoms but was rapidly discharged with a diagnosis of shoulder tendinitis. He had a family history of sudden cardiac death, and his previous medical history included hypertrophic obstructive cardiomyopathy and a normal coronary angiography 7 years prior to the actual admission.Upon admission, he had a pulse rate of 100/min, a temperature of 39°C, and a respiratory frequency of 24/min, thus fulfilling the criteria of systemic inflammatory response syndrome (SIRS). He was pale, with a blood pressure of 118/59 mm Hg, and a holosystolic murmur was heard at the apex. No local signs of infection were observed over his left shoulder.The initial blood chemistry results were as follows, with normal range values in parentheses: hemoglobin, 8.5 g/dl (13.4 to 17.0 g/dl); C-reactive protein, 277 mg/liter (Ͻ5 mg/liter); leukocytes, 20.8 ϫ 10 9 /liter (3.5 ϫ 10 9 to 11.0 ϫ 10 9 /liter); neutrophils, 18.5 ϫ 10 9 /liter (1.7 ϫ 10 9 to 8.2 ϫ 10 9 /liter); sedimentation rate, 102 mm/h (0 to 20 mm/h); procalcitonin, 12.1 g/liter (Ͻ0.10 g/ liter); and troponin T, 896 ng/liter (Ͻ25 ng/liter). Thrombocytes were within the normal range. The electrocardiogram (ECG) demonstrated ST segment elevation in leads V 1 and V 2 and T inversion in leads V 4 to V 6 , indicative of ischemia.Antibiotic therapy was started on day 1 and included meropenem and vancomycin. A broader initial regimen than that recommended in the Norwegian National Antibiotic Guidelines was chosen since the patient had recently been admitted to a hospital in Spain. The following day, all four blood cultures grew nonhemolytic bacteria on blood agar. Species identification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and showed that the isolate was Streptococcus dysgalactiae. Subsequently, group C carbohydrate specificity was documented using a slide agglutination test (Oxoid, Cambridge, United Kingdom). The antimicrobial susceptibility testing showed that the group C streptococcus (GCS) isolate was fully susceptible to all tested antibiotics, with the following MICs: penicillin G, 0.008 mg/liter; ceftriaxone, Ͻ0.016 mg/liter; clindamycin, 0.25 mg/liter; vancomycin, 0.25 mg/liter; teicoplanin, 0.25 mg/liter; and linezolid, 1 mg/liter.A more thorough anamnestic interview revealed a history of weight loss of 6 kg, bloody stools, increasing pain in the left shoulder, and inaccuracy of vision. On examination, he had no peripheral vascular phenomena indicative of septic emboliz...

Streptococcus dysgalactiae subsp. equisimilis (SDSE) has emerged as an important cause of severe skin and soft tissue infections, but little is known of the pathogenic mechanisms underlying tissue pathology. Patient samples and a collection of invasive and non-invasive group G SDSE strains (n = 69) were analyzed with respect to virulence factor expression and cytotoxic or inflammatory effects on human cells and 3D skin tissue models. SDSE strains efficiently infected the 3D-skin model and severe tissue pathology, inflammatory responses and altered production of host structural framework proteins associated with epithelial barrier integrity were evident already at 8 hours post-infection. Invasive strains were significantly more cytotoxic towards keratinocytes and expressed higher Streptokinase and Streptolysin O (SLO) activities, as compared to non-invasive strains. The opposite was true for Streptolysin S (SLS). Fractionation and proteomic analysis of the cytotoxic fractions implicated SLO as a factor likely contributing to the keratinocyte cytotoxicity and tissue pathology. Analyses of patient tissue biopsies revealed massive bacterial load, high expression of slo, as well as immune cell infiltration and pro-inflammatory markers. Our findings suggest the contribution of SLO to epithelial cytotoxicity and tissue pathology in SDSE tissue infections.