Can The Systemic Immune-Inflammation Index (SII) and Charlson Comorbidity Index (CCI) be used to predict mortality in patients with necrotizing fasciitis?

PURPOSE: This study aimed to determine the impact of mortality and morbidity indices on the diagnosis and prognosis of patients suffering from necrotizing fasciitis. METHODS: A retrospective analysis was performed on 41 patients (26 females, 15 males) with necrotizing fasciitis (NF). The SII (Systemic Immune-Inflammation Index) was computed using the formula SII = (P × N)/L, where P, N, and L measure the counts of peripheral platelets, neutrophils, and lymphocytes, respectively. This study evaluated the clinicopathological characteristics and follow-up information to assess the comparative effectiveness of SII, CCI (Charlson Comorbidity Index), and LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) scores as mortality and morbidity indices for patients with NF. RESULTS: The optimal cut-off for SII was determined to be 455. The SII value in the group with mortality was significantly higher compared to the group without mortality (p < 0.05). The CCI value in the group with mortality was significantly higher than the group without mortality (p < 0.05). The SII and CCI values were found to be effective in distinguishing between patients who suffered mortality and those who did not. CONCLUSION: SII is a powerful tool for predicting mortality in patients with necrotizing fasciitis (NF). The SII index provides a novel, easily accessible, and inexpensive indicator for monitoring the progress and predicting the survival of patients with NF.

The characteristics of oro-cervical necrotizing fasciitis-Comparison with severe cellulitis of oro-cervical region and necrotizing fasciitis of other body regions.

BACKGROUND: Necrotizing fasciitis (NF) is an acute and life-threatening soft-tissue infection however rarely seen in oro-cervical region. Therefore, the details of oro-cervical NF (OCNF) are not well known. The purpose of this study was to investigate the characteristics of OCNF by comparing it with severe cellulitis of oro-cervical region (OCSC) or NF of other body regions (e.g., limb, perineum, and trunk) (BNF), respectively. MATERIALS AND METHODS: At first, various risk factors for OCNF in oro-cervical severe infection (OCSI; composed of OCNF and OCSC), including neutrophil-to-lymphocyte ratio (NLR) and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score, were investigated by univariate and multivariate analyses. Next, the differences between OCNF and BNF, including inflammatory markers and mortality, were investigated. RESULTS: In the present study, 14 out of 231 OCSI patients had OCNF. Multivariate analyses of OCSI patients showed that NLR ≥15.3 and LRINEC score ≥6 points were significantly related to OCNF. During the same period, 17 patients had BNF. The OCNF group had significantly higher inflammatory markers than the BNF group when diagnosis, but significantly lower clinical stages at the time and mortality as outcomes. CONCLUSION: We found that compared to BNF, OCNF can be detected at lower clinical stage by using indexes, such as NLR and LRINEC score, besides clinical findings, which may help contributing to patient's relief.

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.

Periocular necrotizing soft tissue infection in Greater Copenhagen.

PURPOSE: Necrotizing soft tissue infection, also known as necrotizing fasciitis (NF), is a fast-spreading life-threatening infection that most commonly affects the lower limbs, groin, or abdomen. Periocular necrotizing fasciitis (PNF) is rare. Limited data exist on PNF immune cell subset; hence, this study aims to determine the representation of immune cell subsets in patients diagnosed with PNF using immunohistochemical stainings. METHODS: All patients diagnosed with PNF at Copenhagen University Hospital from 2008 to 2018 were included. Their electronic medical records and pathology reports were assessed, and available tissue specimens were reviewed and stained with monoclonal antibodies for CD1a+ Langerhans' cells, CD3+ T lymphocytes, CD15+ granulocytes, CD44+ lymphohematopoietic cells, CD68+ histiocytes, CD79α+ B lymphocytes, and FXIIIa+ dendritic macrophages and Langerhans' cells. The number of positive cells was counted, and an average score was calculated. The location of immune cells and bacteria was assessed. RESULTS: The specimens were characterized by acute inflammation and necrosis of the fascia, while striated muscle involvement was less frequent. Haemolytic group A streptococci and Staphylococcus aureus were identified and mainly located in the deep dermis and subcutis in close relation to the fascia. Only few areas harboured both bacteria and inflammatory cells. Granulocytes, histiocytes and CD44+ lymphohematopoietic cells were demonstrated to be abundant in all patients, while B and T lymphocytes, dendritic macrophages and Langerhans' cells were less frequent. CONCLUSION: The immune cell subsets found in this study of PNF were consistent with those identified in the literature on NF in other anatomical locations. This study concludes that immune cells are abundant and exhibit a typical pattern in PNF.

A Rare Presentation of Escherichia coli Necrotizing Fasciitis in Renal Transplantation.

Necrotizing fasciitis is a devastating, rapidly pro-gressive soft tissue infection. We present an unusual case of Escherichia coli necrotizing fasciitis following renal transplant. The patient was a 50-year-old woman previously on long-term hemodialysis who presented with left thigh erythema adjacent to the site of a central venous catheter 5 days after renal transplant. The classical features of necrotizing fasciitis were initially absent, and, despite aggressive resuscitation and debridement, she did not survive. Monomicrobial E. coli necrotizing fasciitis is rare, especially in this cohort of patients. Immunosuppression is a known risk factor for infection, and patients may present atypically. Shock and erythema may be the only clues to infection. Necrotizing fasciitis must be considered in acutely unwell renal transplant recipients so that immediate and life-saving surgical debridement can be delivered.

Yokenella regensburgei necrotizing fasciitis in an immunocompromised host.

We report a case of necrotizing skin infection caused by Yokenella regensburgei in an immunosuppressed patient with orthotopic liver transplantation. Initial bacterial culture identification was suggestive of Hafnia alvei. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed identification of Y. regensburgei. Necrotizing fasciitis is potentially fatal and requires aggressive management, including early diagnosis, appropriate antibiotic selection, and operative debridement.

Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells' Type 1 Interferon Response.

Group A Streptococcus causes severe invasive infections, including necrotizing fasciitis. The expression of an array of virulence factors targeting specific host immune functions impedes successful bacterial clearance. The virulence factor streptococcal DNase Sda1 was previously shown to interfere with the entrapment of bacteria through neutrophil extracellular traps and TLR9 signaling. In this study, we showed that plasmacytoid dendritic cells are recruited to the infected tissue during group A streptococcal necrotizing fasciitis. We found that the streptococcal DNase Sda1 impairs plasmacytoid dendritic cell recruitment by reducing IFN-1 levels at the site of infection. We found that streptococcal DNase Sda1 interferes with stabilization of the DNA by the host molecule HMGB1 protein, which may account for decreased IFN-1 levels at the site of infection.

Atypical Presentation of Escherichia coli Monomicrobial Necrotizing Fasciitis in a Renal Transplant Patient: A Case Report.

Skin and soft tissue infections (SSTIs) are one of most frequent infectious causes for referral to the emergency department and one of the most frequent infectious causes of hospital admissions. Escherichia coli, the most commonly occurring gram-negative pathogen involved in these infections, contributes to about 7% of all SSTIs cases where gram-positive organisms reign dominant. Patients are more susceptible to these gram-negative SSTIs if they are neutropenic, have hematologic malignancies, have undergone solid organ or hematopoietic transplantation, or have cirrhotic liver disease. Due to their immunocompromised state, the prognosis is very poor and not well understood. We report a case of an atypical presentation of an E coli monomicrobial necrotizing fasciitis in a renal transplant patient. Our findings support improved mortality with rapid aggressive interventions, such as amputation, in immunocompromised patients.

Immunoregulation of Neutrophil Extracellular Trap Formation by Endothelial-Derived p33 (gC1q Receptor).

The formation of neutrophil extracellular traps (NETs) is a host defence mechanism, known to facilitate the entrapment and growth inhibition of many bacterial pathogens. It has been implicated that the translocation of myeloperoxidase (MPO) from neutrophilic granules to the nucleus is crucial to this process. Under disease conditions, however, excessive NET formation can trigger self-destructive complications by releasing pathologic levels of danger-associated molecular pattern molecules (DAMPs). To counteract such devastating immune reactions, the host has to rely on precautions that help circumvent these deleterious effects. Though the induction of DAMP responses has been intensively studied, the mechanisms that are used by the host to down-regulate them are still not understood. In this study, we show that p33 is an endothelial-derived protein that has the ability to annul NET formation. We found that the expression of human p33 is up-regulated in endothelial cells upon infections with Streptococcus pyogenes bacteria. Using tissue biopsies from a patient with streptococcal necrotising fasciitis, we monitored co-localisation of p33 with MPO. Further in vitro studies revealed that p33 is able to block the formation of DAMP-induced NET formation by inhibiting the enzymatic activity of MPO. Additionally, mice challenged with S. pyogenes bacteria demonstrated diminished MPO activity when treated with p33. Together, our results demonstrate that host-derived p33 has an important immunomodulating function that helps to counterbalance an overwhelming DAMP response.

Effect of underlying immune compromise on the manifestations and outcomes of group A streptococcal bacteremia.

BACKGROUND: Group A streptococcal bloodstream infection is the most common presentation of invasive group A streptococcal disease. We sought to determine the impact of immunosuppression on severity of disease and clinical outcomes. METHODS: This retrospective review of 148 patients with at least one positive blood culture for Streptococcus pyogenes from 1/2003 to 3/2013 compared immunocompromised patients with those with no immunocompromise in regards to development of severe complications and mortality. RESULTS: Twenty-five patients (17%) were immunocompromised; 123 were not. Skin and soft tissue infection occurred in 60% of immunocompromised vs. 38% of non-immunocompromised patients, p = .04. Necrotizing fasciitis and septic shock were significantly more common in immunocompromised patients, p < .0001 and .028, respectively. Mortality at 30 days was 32% in immunocompromised patients vs. 16% in non-immunocompromised patients, p = .05. CONCLUSION: Patients who are immunocompromised are more likely to develop necrotizing fasciitis and septic shock as complications of group A streptococcal bacteremia and have a higher mortality rate than patients who are not immunocompromised.

Biomarkers of necrotising soft tissue infections: aspects of the innate immune response and effects of hyperbaric oxygenation-the protocol of the prospective cohort BIONEC study.

INTRODUCTION: The mortality and amputation rates are still high in patients with necrotising soft tissue infections (NSTIs). It would be ideal to have a set of biomarkers that enables the clinician to identify high-risk patients with NSTI on admission. The objectives of this study are to evaluate inflammatory and vasoactive biomarkers as prognostic markers of severity and mortality in patients with NSTI and to investigate whether hyperbaric oxygen treatment (HBOT) is able to modulate these biomarkers. The overall hypothesis is that plasma biomarkers can be used as prognostic markers of severity and mortality in patients with NSTI and that HBOT reduces the inflammatory response. METHODS AND ANALYSIS: This is a prospective, observational study being conducted in a tertiary referral centre. Biomarkers will be measured in 114 patients who have been operatively diagnosed with NSTI. On admission, baseline blood values will be obtained. Following surgery and HBOT, daily blood samples for measuring regular inflammatory and vasoactive biomarkers (pentraxin-3, interleukin-6 and nitrite) will be acquired. Samples will be analysed using validated ELISA assays, chemiluminescence and Griess reaction. Clinical data will be obtained during admission in the intensive care unit for a maximum of 7 days. The primary analysis will focus on pentraxin-3, interleukin-6 and nitrite as early markers of disease severity in patients with NSTI. ETHICS AND DISSEMINATION: The study has been approved by the Regional Scientific Ethical Committee of Copenhagen (H-2-2014-071) and the Danish Data Protection Agency (J. no. 30-0900 and J. no. 30-1282). Results will be presented at national and international conferences and published in peer-reviewed scientific journals. TRIAL REGISTRATION: NCT02180906.

Cyclic neutropenia with a novel gene mutation presenting with a necrotizing soft tissue infection and severe sepsis: case report.

BACKGROUND: Cyclic neutropenia is a rare disease. We report a 31-month-old girl with congenital cyclic neutropenia with a novel mutation in the ELANE gene who developed an acute necrotizing soft-tissue infection on her left axillary legion. CASE PRESENTATION: A 31-month-old girl was admitted to our pediatric emergency room because of a necrotizing soft tissue infection of the left axillary area. The infection progressed rapidly and resulted in septic shock. Despite a medical treatment and surgical debridement, the sepsis was not controlled, and severe inflammation developed. After applying of negative-pressure wound therapy, her clinical symptoms improved. Finally, she was diagnosed with cyclic neutropenia with a novel genetic mutation. One month after admission, she was discharged with a completely recovered wound and no need for skin grafting. CONCLUSION: Both adequate medical treatment and effective control of the source of infection are critically important to reduce morbidity in such complex cases of necrotizing fasciitis as appeared in an immunocompromised pediatric patient.

Use of negative pressure wound therapy with instillation in the management of cervical necrotizing fasciitis.

BACKGROUND: Cervical necrotizing fasciitis is an aggressive infection that can be rapidly fatal if aggressive therapies are not initiated early. Negative pressure wound therapy has been established as an effective tool in promoting wound healing, but its use in the acutely infected wound has been avoided because it limits frequent irrigations and standard dressing changes. METHODS: We discuss a novel application of negative pressure wound therapy with instillation in an immunocompromised patient with extensive cervical necrotizing fasciitis. RESULTS: The negative pressure wound therapy with instillation provided pain relief by minimizing the frequency of dressing changes, increased the speed of healing, helped to control infection, and facilitated the development of a healthy wound bed sufficient for reconstruction with a split thickness skin graft. CONCLUSION: The role of negative pressure wound therapy with instillation continues to expand and can be used in the management of both acute and chronic wounds in the head and neck.

The innate immune response elicited by Group A Streptococcus is highly variable among clinical isolates and correlates with the emm type.

Group A Streptococcus (GAS) infections remain a significant health care problem due to high morbidity and mortality associated with GAS diseases, along with their increasing worldwide prevalence. Macrophages play a key role in the control and clearance of GAS infections. Moreover, pro-inflammatory cytokines production and GAS persistence and invasion are related. In this study we investigated the correlation between the GAS clinical isolates genotypes, their known clinical history, and their ability to modulate innate immune response. We constituted a collection of 40 independent GAS isolates representative of the emm types currently prevalent in France and responsible for invasive (57.5%) and non-invasive (42.5%) clinical manifestations. We tested phagocytosis and survival in mouse bone marrow-derived macrophages and quantified the pro-inflammatory mediators (IL-6, TNF-α) and type I interferon (INF-ß) production. Invasive emm89 isolates were more phagocytosed than their non-invasive counterparts, and emm89 isolates more than the other isolates. Regarding the survival, differences were observed depending on the isolate emm type, but not between invasive and non-invasive isolates within the same emm type. The level of inflammatory mediators produced was also emm type-dependent and mostly invasiveness status independent. Isolates of the emm1 type were able to induce the highest levels of both pro-inflammatory cytokines, whereas emm89 isolates induced the earliest production of IFN-ß. Finally, even within emm types, there was a variability of the innate immune responses induced, but survival and inflammatory mediator production were not linked.

HMGB1 in severe soft tissue infections caused by Streptococcus pyogenes.

Extracellular High Mobility Group Box 1 (HMGB1) has been associated with acute and chronic inflammatory conditions. However, little is known about HMGB1 in necrotizing bacterial infections. We hypothesized that the local HMGB1 response is excessive in severe soft tissue infections (STIs), which are characterized by necrosis and hyperinflammation. To explore this, tissue biopsies were collected from patients with varying severity of Streptococcus pyogenes skin and STIs, including erysipelas, cellulitis, and necrotizing fasciitis. Tissue sections were immunostained for HMGB1, S. pyogenes, and inflammatory cell infiltrates and results quantified by acquired computerized image analysis (ACIA). HMGB1 expression increased in parallel to disease severity and was significantly higher in necrotizing fasciitis than in erysipelas (p = 0.0023). Confocal microscopy of sections co-stained for HMGB1 and cell markers revealed both extracellular and cytoplasmic HMGB1, the latter of which was found predominantly in macrophages. To further verify macrophages as main source of activation triggered HMGB1 release, human macrophages were infected with clinical S. pyogenes isolates. The results demonstrated infection triggered release of HMGB1. Dual staining's visualized HMGB1 in areas close to, but not overlapping, with neutrophils, indicating a potential chemotactic role. In vitro transmigration experiments showed a chemotactic effect of HMGB1 on neutrophils. The data furthermore provided in vivo support that HGMB1 may form immunostimulatory complexes with IL-1ß. Taken together, the findings provide the first in vivo evidence that HMGB1 is abundant at the local site of severe bacterial STIs and its levels correlated to severity of infections; hence, indicating its potential value as a biomarker for tissue pathology.

Immunocompromised status in patients with necrotizing soft-tissue infection.

IMPORTANCE: There is a scarcity of research on immunocompromised patients with necrotizing soft-tissue infection (NSTI). OBJECTIVE: To evaluate the effect of immunocompromised status in patients with NSTI. DESIGN AND SETTING: Single-institution retrospective cohort study at a tertiary academic teaching hospital affiliated with a major cancer center. PARTICIPANTS: Patients with NSTI. EXPOSURE: Treatment at Brigham and Women's Hospital and Dana-Farber Cancer Institute between November 25, 1995, and April 25, 2011. MAIN OUTCOME AND MEASURE: Necrotizing soft-tissue infection-associated in-hospital mortality. RESULTS: Two hundred one patients were diagnosed as having NSTI. Forty-six were immunocompromised (as defined by corticosteroid use, active malignancy, receipt of chemotherapy or radiation therapy, diagnosis of human immunodeficiency virus or AIDS, or prior solid organ or bone marrow transplantation with receipt of chronic immunosuppression). At presentation, immunocompromised patients had lower systolic blood pressure (105 vs 112 mm Hg, P = .02), glucose level (124 vs 134 mg/dL, P = .03), and white blood cell count (6600/µL vs 17 200/µL, P < .001) compared with immunocompetent patients. Immunocompromised patients were less likely to have been transferred from another institution (26.1% vs 52.9%, P = .001), admitted to a surgical service (45.7% vs 83.2%, P < .001), or undergone surgical debridement on admission (4.3% vs 61.3%, P = .001). Time to diagnosis and time to first surgical procedure were delayed in immunocompromised patients (P < .001 and P = .001, respectively). Immunocompromised patients had higher NSTI-associated in-hospital mortality (39.1% vs 19.4%, P = .01). CONCLUSIONS: AND RELEVANCE Immunocompromised status in patients with NSTI in this study is associated with delays in diagnosis and surgical treatment and with higher NSTI-associated in-hospital mortality. At presentation, immunocompromised patients may fail to exhibit typical clinical and laboratory signs of NSTI. Physicians caring for similar patient populations should maintain a heightened level of suspicion for NSTI and consider early surgical evaluation and treatment.