Accurate and quick predictor of necrotizing soft tissue infection: Usefulness of the LRINEC score and NSTI assessment score.

OBJECTIVE: The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is a diagnostic tool for necrotizing soft tissue infection (NSTI), which is validated and is considered to have high diagnostic value. However, some experts criticize LRINEC score for consisting of laboratory test results only. METHODS: In this single-center retrospective study, we created a new scoring system (NSTI assessment score; NAS), which also incorporated vital signs as another diagnostic tool for NSTI using cases from our hospital and also evaluated diagnostic accuracy of LRINEC score. We identified NSTI predictors by comparing 24 NSTI patients and 80 non NSTI patients using uni- and multivariate logistic regression analysis, and created NAS based on odds ratio of variables which are statistically significant in the multivariate model. RESULTS: We identified mean arterial pressure, C-reactive protein, hemoglobin, serum creatinine, and glucose as a predictor for NSTI. The maximum value of NAS was 11 points with the cut-off value of 6. Sensitivity, specificity, positive predictive value, and negative predictive value of the NAS for diagnosis of NSTI were 87.5%, 91.3%, 75.0%, and 96.1%, respectively. Area under the receiver operating characteristic curve was 0.926 (0.851-1.00) for the NAS and 0.903 (0.833-0.973) for the LRINEC score, and they were not statistically different (p = 0.167). CONCLUSION: The NAS has high diagnostic accuracy in predicting NSTI, and is comparable with the LRINEC score. The NAS needs to be validated in other cohorts in the future.

Influence of hyperbaric oxygen therapy on thrombus formation ability in humans.

Background: Hyperbaric oxygen (HBO2) therapy was introduced nearly 300 years ago. However, its effect on thrombus formation is unclear. This may be because platelet and coagulation functions are unstable, yielding variable results; hence, accurate measurement is difficult. Our study aimed to analyze changes in thrombus formation before and after HBO2 therapy by using a total thrombus formation analysis system (TTAS). Methods: Six patients were prescribed HBO2 therapy for skin and soft tissue ulcers, and necrotic fasciitis. Blood samples were collected immediately before and after treatment. Then samples were put into a reservoir that connected to AR-chip to assess changes in the thrombus formation ability of both platelets and coagulation factors. We examined the differences in the thrombus formation ability using T-TAS. Time until the onset of white thrombus formation (T10) and complete occlusion of the capillary (T80) were analyzed by a two-way repeated measure analysis of variance (ANOVA). Results: The duration to pressure increase of samples after HBO2 therapy was longer than the duration before HBO2 therapy (p<0.05). This suggests decreased clot adhesiveness to the inner surface of the simulated blood vessel and reduced clot formation ability. Conclusions: The results for T10 and T80 suggest that HBO2 therapy reduced thrombus formation ability in the enrolled patients. We believe that T-TAS is a promising method to predict the efficacy of HBO2 therapy.

Red cell distribution width is an independent predictor of mortality in necrotizing fasciitis.

INTRODUCTION: Necrotizing fasciitis (NF) is a rapidly progressing and potentially lethal infectious disease of the soft tissue. An elevated red blood cell distribution width (RDW) is associated with increased risk of death in patients with heart disease and infectious disease. We retrospectively assessed the association of elevated RDW with in-hospital mortality due to NF. METHODS: All patients had diagnoses of NF and were admitted to the emergency department of a single institution in Taiwan over a 4-year period. Demographics, comorbidities, clinical presentations, and laboratory parameters were retrospectively reviewed. Red blood cell distribution width was categorized as elevated (>14.5%) or not elevated. Multivariate regression analysis was used to identify risk factors associated with mortality. RESULTS: A total of 98 patients were enrolled, and the mortality rate was 23%. Univariate analysis indicated that advanced age, initial hypotension, low hemoglobin level, and elevated RDW (69.6% vs 20%, OR = 9.14, P < .001) were significantly associated with mortality. Multivariate analysis indicated that RDW was a significant and independent predictor of mortality in enrolled patients. CONCLUSIONS: Elevated RDW is a significant and independent predictor of in-hospital mortality for patients with NF.

Necrotizing fasciitis: an urgent diagnosis.

Necrotizing fasciitis (NF) is a rare, life-threatening soft-tissue infection and a medical and surgical emergency, with increasing incidence in the last few years. It is characterized by a rapidly spreading, progressive necrosis of the deep fascia and subcutaneous tissue. Necrotizing fasciitis is often underestimated because of the lack of specific clinical findings in the initial stages of the disease. Many adjuncts such as laboratory findings, bedside tests--e.g., the "finger test" or biopsy--and imaging tests have been described as being helpful in the early recognition of the disease. Imaging is very useful to confirm the diagnosis, but also to assess the extent of the disorder, the potential surgical planning, and the detection of underlying etiologies. The presence of gas within the necrotized fasciae is characteristic, but may be lacking. The main finding is thickening of the deep fasciae due to fluid accumulation and reactive hyperemia, best seen on magnetic resonance imaging.

Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense.

Phylogenetically conserved serine protease cascades play an important role in invertebrate and vertebrate immunity. The mammalian coagulation system can be traced back some 400 million years and shares homology with ancestral serine proteinase cascades that are involved in, for example, Toll receptor signaling in insects and release of antimicrobial peptides during hemolymph clotting. In the present study, we show that the induction of coagulation by bacteria leads to immobilization and killing of Streptococcus pyogenes bacteria inside the clot. The entrapment is mediated via cross-linking of bacteria to fibrin fibers by the action of coagulation factor XIII (fXIII), an evolutionarily conserved transglutaminase. In a streptococcal skin infection model, fXIII(-/-) mice developed severe signs of pathologic inflammation at the local site of infection, and fXIII treatment of wild-type animals dampened bacterial dissemination during early infection. Bacterial killing and cross-linking to fibrin networks was also detected in tissue biopsies from patients with streptococcal necrotizing fasciitis, supporting the concept that coagulation is part of the early innate immune system.

The microbiological profile and presence of bloodstream infection influence mortality rates in necrotizing fasciitis.

INTRODUCTION: Necrotizing fasciitis (NF) is a life threatening infectious disease with a high mortality rate. We carried out a microbiological characterization of the causative pathogens. We investigated the correlation of mortality in NF with bloodstream infection and with the presence of co-morbidities. METHODS: In this retrospective study, we analyzed 323 patients who presented with necrotizing fasciitis at two different institutions. Bloodstream infection (BSI) was defined as a positive blood culture result. The patients were categorized as survivors and non-survivors. Eleven clinically important variables which were statistically significant by univariate analysis were selected for multivariate regression analysis and a stepwise logistic regression model was developed to determine the association between BSI and mortality. RESULTS: Univariate logistic regression analysis showed that patients with hypotension, heart disease, liver disease, presence of Vibrio spp. in wound cultures, presence of fungus in wound cultures, and presence of Streptococcus group A, Aeromonas spp. or Vibrio spp. in blood cultures, had a significantly higher risk of in-hospital mortality. Our multivariate logistic regression analysis showed a higher risk of mortality in patients with pre-existing conditions like hypotension, heart disease, and liver disease. Multivariate logistic regression analysis also showed that presence of Vibrio spp in wound cultures, and presence of Streptococcus Group A in blood cultures were associated with a high risk of mortality while debridement > = 3 was associated with improved survival. CONCLUSIONS: Mortality in patients with necrotizing fasciitis was significantly associated with the presence of Vibrio in wound cultures and Streptococcus group A in blood cultures.

Evaluation of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score for detecting necrotizing soft tissue infections in patients with diabetes and lower extremity infection.

AIMS: The aim of this pilot study was to assess the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), a scoring system for Necrotizing Soft Tissue Infections, to diagnose Necrotizing Soft Tissue Infections of the lower extremity in patients with diabetes. METHODS: Sixty-nine patients with lower extremity infections were prospectively enrolled. The Laboratory Risk Indicator for Necrotizing Fasciitis was calculated and logistic regression was performed for each laboratory value. RESULTS: The Laboratory Risk Indicator for Necrotizing Fasciitis was associated with Necrotizing Soft Tissue Infection diagnosis in patients with diabetes (p = 0.01). Sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 69%, 16.6%, and 100% respectively. Elevated C-reactive protein (OR 1.01, p = 0.02, 95% CI [1.002-1.23]) and white blood cell count (OR 1.34, p < 0.01, 95% CI [1.1-1.7]) were associated with Necrotizing Soft Tissue Infection. CONCLUSIONS: The Laboratory Risk Indicator for Necrotizing Fasciitis was useful as a negative predictor of Necrotizing Soft Tissue Infection while C- reactive protein and white blood cell count may have value as individual predictors. We recommend high clinical suspicion of Necrotizing Soft Tissue Infections in diabetics as laboratory evaluation may be non-specific.

International normalised ratio as an independent predictor of mortality in limb necrotising fasciitis with sepsis.

INTRODUCTION: Necrotising fasciitis with sepsis is a life threatening disease. The aim of this study was to analyse the association between international normalised ratio (INR) and mortality in sepsis patients with necrotising fasciitis. METHODS: A retrospective review was undertaken of 106 patients suffering from necrotising fasciitis with sepsis between November 2007 and December 2016. Data on comorbidities, clinical manifestations, laboratory findings, causative microbiological organisms, APACHE II (Acute Physiology and Chronic Health Evaluation II) score and outcomes were extracted. Logistic regression was carried out to examine the factors affecting mortality. RESULTS: Forty patients (37.7%) died. There was no significant difference in the white blood count (WBC) for the survivor and non-survivor groups. Non-survivors had a lower mean oxygenation index (OI) (288.7mmHg vs 329.4mmHg, p=0.032) and platelet count (PC) (139.5 vs 214.8 x 109/l, p=0.028), and a higher mean INR (1.9 vs 1.3, p=0.000), activated partial thromboplastin time (APTT) (54.6 vs 44.2 seconds, p=0.005) and serum creatinine (2.3mg/dl vs 1.4mg/dl, p=0.007). Mortality in patients with INR >1.5 was significantly higher than in those with INR <1.5 when all risk factors (WBC, PC, OI, INR, APTT, creatinine) were considered (odds ratio: 4.414, 95% confidence interval: 1.263-15.428, p=0.020). Even after adjusting for age, sex, bacteraemia, diabetes and hepatic disorders, the data still exhibited elevated mortality for patients with INR >1.5 (odds ratio: 5.600, 95% confidence interval: 1.415-22.166, p=0.014). CONCLUSIONS: INR is a significant independent predictor of mortality in sepsis patients diagnosed with necrotising fasciitis.

[Prognostic value of the LRINEC score (Laboratory Risk Indicator for Necrotizing Fasciitis) in soft tissue infections: a prospective study at Clermont-Ferrand University hospital]. / Valeur pronostique du score Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) dans les dermohypodermites infectieuses : étude prospective au CHU de Clermont-Ferrand.

BACKGROUND: The LRINEC score was developed in a retrospective study in order to distinguish necrotizing fasciitis from severe soft tissue infections using laboratory data. AIM: To evaluate the prognostic value of the LRINEC score in infectious cellulitis. PATIENTS AND METHODS: A prospective study was performed at the departments of infectious diseases and dermatology of the Clermont-Ferrand University Hospital. The three evaluation criteria were: time from initiation of antibiotics to regression of erythema, duration of fever and occurrence of complications (abscess, surgery, septic shock, necrotizing fasciitis, death, transfer to intensive care). Potential predictive variables were: LRINEC score>6 at admission, comorbidities, local appearance, clinical presentation and soft tissue ultrasound results. RESULTS: Fifty patients were included. The rate of complications was higher for patients with a LRINEC score>6 (54%) than for patients with a score<6 (12%, P=0.008). However, a LRINEC score>6 on admission was not significantly associated with increased duration of erythema or of fever. Prior lymphoedema was associated with a better prognosis. DISCUSSION: The LRINEC score may be a useful tool for the detection of complicated forms of soft tissue infections. Patients with a LRINEC score>6 on admission should be carefully evaluated (hospitalization, surgical assessment, close monitoring).

Necrotizing Fasciitis Within 72 hours After Presentation with Skin and Skin Structure Infection.

INTRODUCTION: A small percentage of patients with skin infections later develop necrotizing fasciitis (NF). Diagnostic testing is needed to identify patients with skin infections at low risk of NF who could be discharged from the emergency department (ED) after antibiotic initiation. Elevated lactate has been associated with NF; existing estimates of the frequency of NF are based on retrospective reviews, and cases often lack testing for lactate. We present the incidence of patients with skin infections who developed NF and their baseline lactates. METHODS: In four phase-3 trials, 2883 adults with complicated or acute bacterial skin and skin structure infections were randomized to dalbavancin or comparator, with early and late follow-up visits through Day 28. We prospectively collected baseline plasma lactates in one trial to assess an association with NF. RESULTS: NF was diagnosed in 3/2883 patients (0.1%); all three survived. In the study with prospectively collected baseline lactates (n = 622), 15/622 (2.4%) had a lactate ≥4 millimoles per liter (mmol/L), including 3/622 (0.5%) with a lactate ≥7 mmol/L. NF was not seen in patients with a lactate <4 mmol/L; NF was seen in 1/15 (6.7%) with a lactate ≥4 mmol/L, including 1/3 (33.3%) with lactate ≥7 mmol/L. CONCLUSIONS: NF incidence within 72 hours of antibiotic initiation in patients with complicated or acute bacterial skin and skin structure infections was extremely low (0.1%) and occurred in 6.7% with a lactate ≥4 mmol/L. Lactate <4 mmol/L can be used to identify patients at low risk of NF who could be safely discharged from the ED after antibiotic initiation.

Complement Activation Is Associated With Mortality in Patients With Necrotizing Soft-Tissue Infections-A Prospective Observational Study.

Aim: We assessed whether different complement factors and complement activation products were associated with poor outcome in patients with necrotizing soft-tissue infection (NSTI). Methods: We conducted a prospective, observational study in an intensive care unit where treatment of NSTI is centralized at a national level. In 135 NSTI patients and 65 control patients, admission levels of MASP-1, MASP-2, MASP-3, C4, C3, complement activation products C4c, C3bc, and terminal complement complex (TCC) were assessed. Results: The 90-day mortality was 23%. In a Cox regression model adjusted for sex, and SAPS II, a higher than median MASP-1 (HR 0.378, CI 95% [0.164-0.872], p = 0.0226) and C4 (HR 0.162, 95% CI [0.060-0.438], p = 0.0003), C4c/C4 ratio (HR 2.290 95% CI [1.078-4.867], p = 0.0312), C3bc (HR 2.664 95% CI [1.195-5.938], p = 0.0166), and C3bc/C3 ratio (HR 4.041 95% CI [1.673-9.758], p = 0.0019) were associated with 90-day mortality, while MASP-2, C4c, C3, and TCC were not. C4 had the highest ROC-AUC (0.748, [95% CI 0.649-0.847]), which was comparable to the AUC for SOFA score (0.753, [95% CI 0.649-0.857]), and SAPS II (0.862 [95% CI 0.795-0.929]). Conclusion: In adjusted analyses, high admission levels of the C4c/C4 ratio, C3bc, and the C3bc/C3 ratio were significantly associated with a higher risk of death after 90 days while high admission levels of MASP-1 and C4 were associated with lower risk. In this cohort, these variables are better predictors of mortality in NSTI than C-reactive protein and Procalcitonin. C4's ability to predict mortality was comparable to the well-established scoring systems SAPS score II and SOFA on day 1.

Prospective Validation of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score for Necrotizing Fasciitis of the Extremities.

OBJECTIVES: The Laboratory Risk Indicator for Necrotizing Fasciitis score was developed as a clinical decision tool for distinguishing necrotizing fasciitis from other soft tissue infections. We prospectively evaluated the performance of the Laboratory Risk Indicator for Necrotizing Fasciitis score for the diagnosis of patients with necrotizing fasciitis in the extremities. METHODS: We conducted a prospective and observational cohort study of emergency department patients with necrotizing fasciitis or severe cellulitis in the extremities between April 2015 and December 2016. The Laboratory Risk Indicator for Necrotizing Fasciitis score was calculated for every enrolled patient. The sensitivity, specificity, positive predictive value, and negative predictive value of cut-off scores of 6 and 8 were evaluated. The accuracy of the Laboratory Risk Indicator for Necrotizing Fasciitis score was expressed as the area under the receiver operating characteristic curve. RESULTS: A total of 106 patients with necrotizing fasciitis and 825 patients with cellulitis were included. With an Laboratory Risk Indicator for Necrotizing Fasciitis cut-off score ≥6, the sensitivity was 43% (95% confidence interval 34% to 53%), specificity was 83% (95% confidence interval 80% to 86%), positive predictive value was 25% (95% confidence interval 20% to 30%), and negative predictive value was 92% (95% confidence interval 91% to 93%); with an Laboratory Risk Indicator for Necrotizing Fasciitis cut-off score ≥8, the sensitivity was 27% (95% confidence interval 19% to 37%), specificity was 93% (95% confidence interval 91% to 94%), positive predictive value was 33% (95% confidence interval 25% to 42%), and negative predictive value was 91% (95% confidence interval 90% to 92%). The area under the receiver operating characteristic curve for accuracy of the Laboratory Risk Indicator for Necrotizing Fasciitis score was 0.696 (95% CI 0.640 to 0.751). CONCLUSION: The Laboratory Risk Indicator for Necrotizing Fasciitis score may not be an accurate tool for necrotizing fasciitis risk stratification and differentiation between severe cellulitis and necrotizing fasciitis in the emergency department setting based on our study.

Necrotizing Soft Tissue Infections: A Focused Review of Pathophysiology, Diagnosis, Operative Management, Antimicrobial Therapy, and Pediatrics.

Background: Necrotizing fasciitis is a major health problem throughout the world. The purpose of this review is to assist providers with the care of these patients through a better understanding of the pathophysiology and management options. Methods: This is a collaborative review of the literature between members of the Surgical Infection Society of North America and World Society of Emergency Surgery. Results: Necrotizing fasciitis continues to be difficult to manage with the mainstay being early diagnosis and surgical intervention. Recognition of at-risk populations assists with the initiation of treatment, thereby impacting outcomes. Conclusions: Although there are some additional treatment strategies available, surgical debridement and antimicrobial therapy are central to the successful eradication of the disease process.

Usefulness of a risk scale based on procalcitonin for early discrimination between necrotising fasciitis and cellulitis of the extremities. / Utilidad de una escala de riesgo basada en la procalcitonina sérica para la discriminación temprana entre fascitis necrosante y celulitis de las extremidades.

BACKGROUND AND OBJECTIVE: To assess the usefulness of a risk scale based on serum procalcitonin (PCT) compared to the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) scale in the early discrimination between necrotising fasciitis (NF) and cellulitis of the extremities. MATERIALS AND METHODS: Retrospective study of consecutive patients with confirmed diagnosis of NF in one limb (n=11). This study group was compared with 23 consecutive patients with a diagnosis of severe limbs cellulitis during the same period. The clinical data and laboratory parameters were analysed, the main variable was the serum level of PCT upon admission. The capacity for NF diagnosis of the two methods, PCT level and LRINEC scale score, were evaluated by ROC curve and determined by the calculation of the area under the curve (AUC). RESULTS: The AUC was significantly higher with PCT measurement, both as a continuous variable and when the risk was categorised. The cut-off point for the PCT level with the highest AUC under the curve was from 0.87ng/ml (sensitivity 90.9%, specificity 82.6%), whereas it was a score of 5 on the LRINEC scale (sensitivity 72.7%, specificity 82.6%). CONCLUSION: PCT measurement was a more effective method than the LRINEC score for early discrimination between NF and cellulitis of the extremities. A low level of PCT, associated with the patient's clinical status and physical examination is especially useful to rule out an early diagnosis of NF.