Necrotising soft tissue infections. / Nekrotiserende bløtdelsinfeksjoner.

Necrotising soft tissue infections can affect the skin, subcutaneous tissue, superficial fascia, deep fascia and musculature. The infections are severe, they spread quickly and can result in extensive tissue loss. Although rare, morbidity and mortality rates are high. Early clinical identification is crucial for the outcome, and rapid infection control through surgery and targeted antibiotic treatment is needed to save lives. Few prospective clinical trials have been conducted for the treatment of this type of infection. Specific challenges include rapid identification of the condition and the uncertain efficacy of the various treatment options. In this clinical review article, we describe clinical characteristics, diagnostics and treatment.

Systemic immune activation profiles in streptococcal necrotizing soft tissue infections: A prospective multicenter study.

OBJECTIVE: Early stages with streptococcal necrotizing soft tissue infections (NSTIs) are often difficult to discern from cellulitis. Increased insight into inflammatory responses in streptococcal disease may guide correct interventions and discovery of novel diagnostic targets. METHODS: Plasma levels of 37 mediators, leucocytes and CRP from 102 patients with ß-hemolytic streptococcal NSTI derived from a prospective Scandinavian multicentre study were compared to those of 23 cases of streptococcal cellulitis. Hierarchical cluster analyses were also performed. RESULTS: Differences in mediator levels between NSTI and cellulitis cases were revealed, in particular for IL-1ß, TNFα and CXCL8 (AUC >0.90). Across streptococcal NSTI etiologies, eight biomarkers separated cases with septic shock from those without, and four mediators predicted a severe outcome. CONCLUSION: Several inflammatory mediators and wider profiles were identified as potential biomarkers of NSTI. Associations of biomarker levels to type of infection and outcomes may be utilized to improve patient care and outcomes.

Clinical Characteristics and Histopathology in Suspected Necrotizing Soft Tissue Infections.

Background: Necrotizing 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. Methods: This 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. Results: Tissue 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). Conclusions: Our 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.

Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections.

BACKGROUNDNecrotizing soft-tissue infections (NSTIs) are rapidly progressing infections frequently complicated by septic shock and associated with high mortality. Early diagnosis is critical for patient outcome, but challenging due to vague initial symptoms. Here, we identified predictive biomarkers for NSTI clinical phenotypes and outcomes using a prospective multicenter NSTI patient cohort.METHODSLuminex multiplex assays were used to assess 36 soluble factors in plasma from NSTI patients with positive microbiological cultures (n = 251 and n = 60 in the discovery and validation cohorts, respectively). Control groups for comparative analyses included surgical controls (n = 20), non-NSTI controls (i.e., suspected NSTI with no necrosis detected upon exploratory surgery, n = 20), and sepsis patients (n = 24).RESULTSThrombomodulin was identified as a unique biomarker for detection of NSTI (AUC, 0.95). A distinct profile discriminating mono- (type II) versus polymicrobial (type I) NSTI types was identified based on differential expression of IL-2, IL-10, IL-22, CXCL10, Fas-ligand, and MMP9 (AUC >0.7). While each NSTI type displayed a distinct array of biomarkers predicting septic shock, granulocyte CSF (G-CSF), S100A8, and IL-6 were shared by both types (AUC >0.78). Finally, differential connectivity analysis revealed distinctive networks associated with specific clinical phenotypes.CONCLUSIONSThis study identifies predictive biomarkers for NSTI clinical phenotypes of potential value for diagnostic, prognostic, and therapeutic approaches in NSTIs.TRIAL REGISTRATIONClinicalTrials.gov NCT01790698.FUNDINGCenter for Innovative Medicine (CIMED); Region Stockholm; Swedish Research Council; European Union; Vinnova; Innovation Fund Denmark; Research Council of Norway; Netherlands Organisation for Health Research and Development; DLR Federal Ministry of Education and Research; and Swedish Children's Cancer Foundation.

Risk Factors and Predictors of Mortality in Streptococcal Necrotizing Soft-tissue Infections: A Multicenter Prospective Study.

BACKGROUND: Necrotizing soft-tissue infections (NSTI) are life-threatening conditions often caused by ß-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.

Beta-Hemolytic Streptococci and Necrotizing Soft Tissue Infections.

ß-hemolytic streptococci are major causes of necrotizing soft tissue infections (NSTIs), Streptococcus pyogenes (group A streptococcus; GAS) in particular. NSTIs caused by Streptococcus dysgalactiae (SD) have also been reported. In the INFECT cohort of 409 NSTIs patients, more than a third of the cases were caused by GAS (31%) or SD (7%). Risk factors of streptococcal NSTIs compared to streptococcal cellulitis have previously been largely unknown. The INFECT study confirmed blunt trauma as an important risk factor. In addition, absence of pre-existing skin lesions and a lower BMI were associated with NSTIs. The study also confirmed that septic shock is more frequent in GAS cases than in other types of NSTIs. Septic shock was also among several predictors of mortality. The role of intravenous immunoglobulin (IVIG) in streptococcal NSTIs has been unclear. In the INFECT cohort, IVIG treatment was associated with increased survival. As in other studies, a significant microbial diversity was observed, but with predominance of a few emm types. Overall, the INFECT study gives a comprehensive and contemporary picture of the clinical characteristics and the microbes involved in streptococcal NSTIs. The reported severity of disease underscores the need for new efforts aimed at identifying novel diagnostic measures and improved treatment.

Treatment of Necrotizing Soft Tissue Infections: Antibiotics.

Necrotizing soft tissue infections (NSTIs) are severe, life-threatening infections, and early therapeutic intervention is essential. Prompt administration of potent antimicrobial agents is pivotal, but inadequate empirical therapy is unfortunately common. Optimization of the antibiotic treatment strategy in NSTIs requires consideration of local epidemiology of causative pathogens and antimicrobial resistance patterns, knowledge on common pathogenetic mechanisms in NSTIs, and adaptations to pharmacokinetic and pharmacodynamic physiological changes in critically ill patients. In the present article we address all these issues, as well as review and compare contemporary guidelines for antimicrobial treatment of NSTIs from around the world.

Microbiological Etiology of Necrotizing Soft Tissue Infections.

Necrotizing soft tissue infections (NSTIs) are severe clinical conditions requiring swift therapeutic intervention, including surgical removal of infected tissue and administration of potent antibiotics. There is wide diversity in the microbial etiologic agents, and tailoring the antibiotic treatment to the offending pathogen is essential. However, the choice of empirical therapy is frequently inadequate, underlining the need for comprehensive and contemporary knowledge on causative pathogens and relevant antimicrobial resistance patterns in NSTIs. Also, studies of the pathogenic mechanisms in different NSTIs are needed, to improve handling of patients through developing patient stratification and tailored therapies. We review the current knowledge on microbial etiology and provide detailed characterizations of the predominant pathogens.

Non-purulent skin and soft tissue infections: predictive power of a severity score and the appropriateness of treatment in a prospective cohort.

Background: Skin and soft tissue infections (SSTIs) are increasing. Frequent over- and under-treatment has been reported, including non-purulent SSTIs where cases demanding surgery or broad-spectrum therapy often are hard to identify. Our aim was to measure the predictive power of a modified severity score and use it to identify areas of improvement in antimicrobial therapy of non-purulent SSTIs.Methods: We prospectively included adult patients admitted to hospital with non-purulent SSTIs. A modified Dundee score at admission was calculated retrospectively, and associations between severity and outcomes were analysed. We evaluated appropriateness of treatment in relation to severity scores, and assessed adverse effects of broad-spectrum therapy.Results: We included 200 cases with cellulitis and 19 cases with necrotising soft tissue infections (NSTIs). Thirty-two per cent were categorised as severity class I, 15% as class II, 28% as class III and 25% as class IV (most severe). In class I, 66 out of 69 cases did not have a complicated course. All but one NSTI case were identified by the class IV criteria. Over-treatment was common and mostly seen in class I. Broad-spectrum antibiotics or clindamycin use was associated with an increased risk of diarrhoea. Prolonged treatment (>14 days) was associated with age, severity and surgery.Conclusions: The modified Dundee score proved valuable in identifying those with the lowest risk of complication and the most severe infections, and could serve as a useful clinical tool in the emergency department. Frequent over-treatment and associated adverse effects were confirmed, underscoring the need for improved risk assessment.

Aetiology and clinical features of facial cellulitis: a prospective study.

BACKGROUND: In the early 20th century, the face was the predominant site of cellulitis. Despite a relative decrease in the incidence of facial cellulitis, it is still common. There are few studies on this condition during the last decades. The aim of this study was to describe contemporary aetiological and clinical characteristics of patients admitted to hospital with non-suppurative facial cellulitis. METHODS: Patients were included prospectively. Clinical details, comorbidities and biochemistry results were recorded. Investigations included cultures of skin swab and blood and tests for streptococcal antibodies during the acute and convalescent stages. RESULTS: Sixty-five patients were included. Serology, cultures and response to penicillin monotherapy identified probable or confirmed ß-haemolytic streptococci (BHS) aetiology in 75% (49/65) of cases. Significant comorbidities were present in 54% (35/65). Fever, chills or rigors before or at admission was noted in 91% (59/65). Patients presented most often with sharply demarcated erythema and raised borders (54/64). Penicillin or penicillinase-resistant penicillin alone or in combination cured 68% (44/65) of the patients. Supplementary clindamycin was used in 28% (18/65), most often only for 1-3 days. Only four patients needed a second course of antibiotics. Clinical failure was more often seen in patients with non-BHS aetiology (p = .037). Few complications were noted; 14.5% (9/62) experienced transient diarrhoea, and only one had confirmed Clostridium difficile infection. No patients developed cerebral venous sinus thrombosis, and there were no fatalities. CONCLUSIONS: Our findings indicate that BHS are the leading cause of facial cellulitis. Most patients exhibit sharply demarcated lesions and systemic symptoms. Narrow-spectrum ß-lactam antibiotics and short hospital stay appear sufficient. Few complications and low recurrence rates were seen.