Molecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft tissue infections.
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ABSTRACT:
SUBMITTER: Thanert R
PROVIDER: S-EPMC6710258 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Necrotizing fasciitis caused by group A streptococcus (GAS) is a life-threatening, rapidly progressing infection. At present, biofilm is not recognized as a potential problem in GAS necrotizing soft tissue infections (NSTI), as it is typically linked to chronic infections or associated with foreign devices. Here, we present a case of a previously healthy male presenting with NSTI caused by GAS. The infection persisted over 24 days, and the surgeon documented the presence of a "thick layer biofilm" in the fascia. Subsequent analysis of NSTI patient tissue biopsies prospectively included in a multicenter study revealed multiple areas of biofilm in 32% of the patients studied. Biopsies associated with biofilm formation were characterized by massive bacterial load, a pronounced inflammatory response, and clinical signs of more severe tissue involvement. In vitro infections of a human skin tissue model with GAS NSTI isolates also revealed multilayered fibrous biofilm structures, which were found to be under the control of the global Nra gene regulator. The finding of GAS biofilm formation in NSTIs emphasizes the urgent need for biofilm to be considered as a potential complicating microbiological feature of GAS NSTI and, consequently, emphasizes reconsideration of antibiotic treatment protocols.
| S-EPMC5033946 | biostudies-literature
Project description:Host genetic variations play an important role in several pathogenic diseases, and we have previously provided strong evidences that these genetic variations contribute significantly to differences in susceptibility and clinical outcomes of invasive Group A Streptococcus (GAS) infections, including sepsis and necrotizing soft tissue infections (NSTIs). Our initial studies with conventional mouse strains revealed that host genetic variations and sex differences play an important role in orchestrating the severity, susceptibility and outcomes of NSTIs. To understand the complex genetic architecture of NSTIs, we utilized an unbiased, forward systems genetics approach in an advanced recombinant inbred (ARI) panel of mouse strains (BXD). Through this approach, we uncovered interactions between host genetics, and other non-genetic cofactors including sex, age and body weight in determining susceptibility to NSTIs. We mapped three NSTIs-associated phenotypic traits (i.e., survival, percent weight change, and lesion size) to underlying host genetic variations by using the WebQTL tool, and identified four NSTIs-associated quantitative genetic loci (QTL) for survival on mouse chromosome (Chr) 2, for weight change on Chr 7, and for lesion size on Chr 6 and 18 respectively. These QTL harbor several polymorphic genes. Identification of multiple QTL highlighted the complexity of the host-pathogen interactions involved in NSTI pathogenesis. We then analyzed and rank-ordered host candidate genes in these QTL by using the QTLminer tool and then developed a list of 375 candidate genes on the basis of annotation data and biological relevance to NSTIs. Further differential expression analyses revealed 125 genes to be significantly differentially regulated in susceptible strains compared to their uninfected controls. Several of these genes are involved in innate immunity, inflammatory response, cell growth, development and proliferation, and apoptosis. Additional network analyses using ingenuity pathway analysis (IPA) of these 125 genes revealed interleukin-1 beta network as key network involved in modulating the differential susceptibility to GAS NSTIs.
| S-EPMC4939974 | biostudies-literature
Project description:BackgroundNecrotizing soft-tissue infections (NSTI) are life-threatening conditions often caused by ?-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.MethodsFrom 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.ResultsThe 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.ConclusionsStreptococcal 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.
| S-EPMC7840107 | biostudies-literature
Project description: Not available
| S-EPMC6494525 | biostudies-literature
Project description:Necrotizing soft-tissue infections (NSTIs) have multiple causes, risk factors, anatomical locations, and pathogenic mechanisms. In patients with NSTI, circulating metabolites may serve as substrate having impact on bacterial adaptation at the site of infection. Metabolic signatures associated with NSTI may reveal potential be useful as diagnostic and prognostic markers, as well as novel targets for therapy. This study used untargeted metabolomics analyses of plasma from NSTI patients (n=34) and healthy (non-infected) controls (n=24) to identify the metabolic signatures and connectivity patterns among metabolites associated with NSTI.
2019-10-28 | ST001270 | MetabolomicsWorkbench
Project description:Necrotizing soft tissue infections (NSTIs) are aggressive infections associated with significant morbidity, including amputation and organ failure, and high mortality. The rapid progression and significant risk of morbidity and mortality associated with NSTIs makes quick diagnosis and treatment critical. The objective of this study was to determine the presentation of patients diagnosed with NSTIs and their in-hospital outcomes.This was a retrospective review of adult (>17 years) patients with a discharge diagnosis of necrotizing fasciitis at London Health Sciences Centre (annual census 125,000) over a 5-year period (April 2008-March 2013).Sixty patients with confirmed NSTI were included in this study. Common comorbidities at presentation included immunocompromise (58.3%), diabetes mellitus (41.7%), vascular disease (45.0%), and obesity (24.6%). Initial presentations included swelling (91.7%), erythema (86.7%), bullae (28.3%), petechiae (8.3%), and bruising (45.0%). Fifty (83.3%) underwent surgery, with a median (interquartile range) time from initial emergency department presentation to surgery of 15.5 hours (7.8, 74.9). In-hospital mortality among those who had surgical intervention was 14.0%, compared to 60.0% for patients who did not have surgery (Δ46.0%; 95% CI: 14.8% to 70.2%).Diabetes mellitus, immune-compromise, vascular disease, and obesity are common comorbidities of NSTIs. Survival is higher among patients who receive surgical treatment. Patients presenting with this clinical picture warrant a high degree of suspicion.
| S-EPMC5546773 | biostudies-other
Project description:Necrotizing soft tissue infections (NSTI) have been recognized for millennia and continue to impose considerable burden on both patient and society in terms of morbidity, death, and the allocation of resources. With improvements in the delivery of critical care, outcomes have improved, although disease-specific therapies are lacking. The basic principles of early diagnosis, of prompt and broad antimicrobial therapy, and of aggressive debridement have remained unchanged. Clearly novel and new therapeutics are needed to combat this persistently lethal disease. This review emphasizes the pillars of NSTI management and then summarizes the contemporary evidence supporting the incorporation of novel adjuncts to the pharmacologic and operative foundations of managing this disease.
| S-EPMC5393412 | biostudies-literature
Project description:BackgroundNecrotizing soft tissue infections (NSTIs) are severe diseases with high morbidity and mortality. The diagnosis is challenging. Several guidelines recommend tissue biopsies as an adjunct diagnostic in routine management, but neither biopsy sampling nor classification is standardized or validated. We studied the quality of tissue biopsy examination as part of routine diagnostics in NSTIs.MethodsThis was a retrospective cohort study of adult patients undergoing surgery due to suspected NSTIs in which tissue biopsy was taken as part of routine management. Clinical data were reviewed. The biopsies were evaluated according to a proposed histopathologic classification system and independently assessed by 2 pathologists. Interrater reliability and diagnostic accuracy were determined.ResultsTissue biopsies from 75 patients were examined, 55 NSTIs and 20 non-NSTIs cases. The cohorts were similar in clinical characteristics. Interrater reliability for histopathologic staging was moderate (0.53) and fair (0.37) for diagnosis. The sensitivity of histologic diagnosis was 75% and the specificity 80%. The positive predictive value was 91% and the negative predictive value 53%. Necrotizing Infection Clinical Composite Endpoint (NICCE) success was associated with a more severe histological stage, achieved by 42% and 71% of the cases in stage 1 and 2, respectively (P = .046).ConclusionsOur findings suggest that tissue biopsies have low clinical accuracy. The interrater reliability among experienced pathologists is only fair to moderate. A histopathologically more severe stage was associated with favorable outcome. These findings discourage the use of histopathologic evaluation as part of contemporary management of patients with suspected NSTI.
| S-EPMC9648561 | biostudies-literature
Project description:BackgroundThis study analyzed and described factors related to necrotizing or non-necrotizing soft tissue infections (SSTIs) in a hospitalized patient population in Northeastern South America.Materials and methodsThis retrospective study included patients hospitalized with SSTIs between January 2011 and December 2016. The main factors related to necrotizing SSTIs (NSTIs) or non-necrotizing SSTIs were analyzed together or separately.ResultsOf 344 SSTI patients (161 [46.8%] non-necrotizing, 183 [53.2%] necrotizing), NSTI patients had a higher incidence of heart disease (P = 0.0081) and peripheral arterial disease (PAD; p < 0.001), more antibiotic use, and longer hospital stay (P < 0.001). NSTI was associated with a 9.58, 33.28, 2.34, and 2.27 times higher risk of PAD (confidence interval [CI] 3.69-24.87), amputation (7.97-139), complications (1.45-3.79), and death (1.2-4.26), respectively, than non-necrotizing SSTI. The risk factors associated with amputation were PAD (P < 0.001) and poor glycemic control during hospitalization (P = 0.0011). Factors associated with higher mortality were heart disease (P < 0.001), smoking (P = 0.0135), PAD (P = 0.001), chronic renal failure (P = 0.0039), poor glycemic control (P = 0.0005), and evolution to limb irreversibility (P < 0.001).ConclusionPatients with NSTI have greater illness severity, with a greater association with PAD and amputation. Patients with poor glycemic control more frequently underwent amputation and died.
| S-EPMC7498730 | biostudies-literature
Project description:BackgroundWe conducted this study to evaluate the characteristics of the infectious fluid in soft tissue infection and investigate the utility of the biochemical tests and Gram stain smear of the infectious fluid in distinguishing necrotizing soft tissue infection (NSTI) from cellulitis.MethodsThis retrospective cohort study was conducted in a tertiary care hospital in Taiwan. From April 2019 to October 2020, patients who were clinically suspected of NSTI with infectious fluid accumulation along the deep fascia and received successful ultrasound-guided aspiration were enrolled. Based on the final discharge diagnosis, the patients were divided into NSTI group, which was supported by the surgical pathology report, or cellulitis group. The t test method and Fisher's exact test were used to compare the difference between two groups. The receiver-operator characteristic (ROC) curves and area under the ROC curve (AUC) were used to evaluate the discriminating ability.ResultsTotal twenty-five patients were enrolled, with 13 patients in NSTI group and 12 patients in cellulitis group. The statistical analysis showed lactate in fluid (AUC = 0.937) and LDH in fluid (AUC = 0.929) had outstanding discrimination. The optimal cut-off value of fluid in lactate was 69.6 mg/dL with corresponding sensitivity of 100% and specificity of 76.9%. The optimal cut-off value of fluid in LDH was 566 U/L with corresponding sensitivity of 83.3% and a specificity of 92.3%. In addition, albumin in fluid (AUC = 0.821), TP in fluid (AUC = 0.878) and pH in fluid (AUC = 0.858) also had excellent diagnostic accuracy for NSTI. The Gram stain smear revealed 50% bacteria present in NSTI group and all the following infectious fluid culture showed bacteria growth.ConclusionsThe analysis of infectious fluid along the deep fascia might provide high diagnostic accuracy to differentiate NSTI from cellulitis.
| S-EPMC8742947 | biostudies-literature