Severe Soft Tissue Infections Research Articles

Is overweight a predictor for a more severe course of disease in cases of necrotizing fasciitis?

Necrotizing fasciitis is a rare but severe soft tissue infection, and its diagnosis is difficult and often delayed. Immediate treatment comprising extensive debridement, highly dosed broad-spectrum antibiotic therapy and intensive care is necessary to prevent fatal outcomes. Considering the global rise in overweight patients and the known negative effects of obesity on the immune system, the aim of this study was to analyze whether overweight results in a more severe course of necrotizing fasciitis, worse outcomes and an increased mortality rate among overweight patients compared than in normal weight patients. The present study involved a retrospective analysis of 29 patients who were treated for necrotizing fasciitis in our level one trauma center during the eight-year period between 2013 and 2020. Based on their BMIs, the patients were assigned to either the overweight group (BMI > 25) or the normal weight group. In the study population, being overweight appeared to be a predictor for a more severe course of necrotizing fasciitis. Overweight patients suffered from sepsis significantly more often than normal weight patients (13 vs. 5; p = 0.027). Furthermore, they were dependent on invasive ventilation (26.6 ± 33.8 vs. 5.9 ± 11.9 days; p = 0.046) as well as catecholamine support (18.4 ± 23.7 vs. 3.6 ± 5.7 days; p = 0.039) for significantly longer. Necrotizing fasciitis remains a challenging and potentially fatal disease. Within the patient collective, the severity of the disease and treatment effort were increased among overweight patients.

Invasive group A Streptococcus infection (Streptococcus pyogenes): Current situation in Spain.

Group A ß-hemolytic Streptococcus (S. pyogenes), also known as GAS, is a Gram-positive bacterium. It can be easily identified in the microbiology laboratory by its ability to hemolyse blood in culture media. This bacterium is highly virulent due to its production of enzymes and toxins, and its ability to cause immunologically mediated diseases such as rheumatic fever and post-streptococcal glomerulonephritis. GAS is the primary cause of bacterial pharyngotonsillitis, although it is typically a benign and non-invasive disease. However, it also has the potential to cause severe skin and soft tissue infections, necrotising fasciitis, bacteraemia and endocarditis, pneumonia and empyema, and streptococcal toxic shock syndrome, without any age or predisposition limits. The term invasive GAS disease (iGAS) is used to refer to this group of conditions. In more developed countries, iGAS disease has declined thanks to improved hygiene and the availability of antibiotics. For example, rheumatic fever has practically disappeared in countries such as Spain. However, recent data suggests a potential increase in some iGAS diseases, although the accuracy of this data is not consistent. Because of this, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has posed several questions about invasive GAS infection, especially its current situation in Spain. The committee has enlisted the help of several experts in the field to answer these questions. The following lines contain the answers that we have collaboratively produced, aiming to assist not only the members of ICOMEM but also anyone interested in this topic.

Clinical Presentation and Treatment Outcomes of Necrotizing Fasciitis: A Prospective Comparative Study of Children and Adults in Sokoto

Abstract Background: Necrotizing fasciitis (NF) is a severe soft tissue infection typified by swiftly spreading necrosis of the fascia and subcutaneous fat with successive necrosis of the skin which affects all age groups. Objective: To compare the clinical presentation and treatment outcome of NF between children and adults. Materials and Methods: A prospective descriptive study of all patients presenting with NF to the (Usmanu Danfodiyo Univrersity Teaching Hospital, Sokoto), from September 2018 to August 2019. Participants were stratified into adults and children for comparison during data analysis. Results: A total of 32 patients were analyzed, 24 (75.0%) were adults. The age range was 2 weeks to 75 years with a median age of 35 years. Necrotic skin patches and skin erythema were the most common cutaneous findings. The lower limb was the most commonly affected region in adults (58.3%), whereas the head and neck and abdominal wall were equally commonly involved in children (37.5%). Children had more multiple isolates than adults, 87.5% compared to 62.5%, respectively, and it was significant (P value 0.04). Escherichia coli and Klebsiella species were both significantly commoner in isolates of children than adults (P value 0.01 and 0.04, respectively). The method of wound coverage was significantly different (P value 0.003) as fewer children required skin grafting. The mortality rate was 6.25%, the two deaths occurred in adults. Conclusion: NF is commoner in adults in our region. The predilection sites of the disease in the two groups differ and healing by secondary intention was more possible in children.

Prospective derivation and validation of a NECROtizing Soft tissue InfectionS (NECROSIS) score: An EAST multicenter trial.

Although several risk indices have been developed to aid in the diagnosis of NSTIs, these instruments suffer from varying levels of reproducibility and failure to incorporate key clinical variables in model development. The objective of this study was to derive and validate a clinical risk index score - NECROSIS - for identifying NSTIs in emergency general surgery (EGS) patients being evaluated for severe skin and soft tissue infections. We performed a prospective study across 16 sites in the US of adult EGS patients with suspected NSTIs over a 30-month period. Variables analyzed included demographics, admission vitals and labs, physical exam, radiographic, and operative findings. The main outcome measure was the presence of NSTI diagnosed clinically at the time of surgery. Multivariate analysis was performed to identify independent predictors for the presence of NSTI using the Hosmer-Lemeshow test and the Akaike information criteria. Of 362 patients, 297 (82%) were diagnosed with a NSTI. Overall mortality was 12.3%. Multivariate analysis identified 3 independent predictors for NSTI: systolic blood pressure ≤ 120 mmHg, violaceous skin, and WBC ≥15 (x103/uL). Multivariate modelling demonstrated Hosmer-Lemeshow goodness of fit (p = 0.9) with a c-statistic for the prediction curve of 0.75. Test characteristics of the NECROSIS score were similar between the derivation and validation cohorts. NECROSIS is a simple and potentially useful clinical index score for identifying at-risk EGS patients with NSTIs. Future validation studies are warranted. Diagnostic Tests or Criteria, Level III.

Characterisation of PVL-Positive Staphylococcus argenteus from the United Arab Emirates.

Staphylococcus argenteus is a recently described staphylococcal species that is related to Staphylococcus aureus but lacks the staphyloxanthin operon. It is able to acquire both resistance markers such as the SCCmec elements and mobile genetic elements carrying virulence-associated genes from S. aureus. This includes those encoding the Panton-Valentine leukocidin (PVL), which is associated mainly with severe and/or recurrent staphylococcal skin and soft tissue infections. Here, we describe the genome sequences of two PVL-positive, mecA-negative S. argenteus sequence type (ST) 2250 isolates from the United Arab Emirates in detail. The isolates were found in a dental clinic in the United Arab Emirates (UAE). Both were sequenced using Oxford Nanopore Technology (ONT). This demonstrated the presence of temperate bacteriophages in the staphylococcal genomes, including a PVL prophage. It was essentially identical to the published sequence of phiSa2wa_st78 (GenBank NC_055048), a PVL phage from an Australian S. aureus clonal complex (CC) 88 isolate. Besides the PVL prophage, one isolate carried another prophage and the second isolate carried two additional prophages, whereby the region between these two prophages was inverted. This "flipped" region comprised about 1,083,000 bp, or more than a third of the strain's genome, and it included the PVL prophage. Prophages were induced by Mitomycin C treatment and subjected to transmission electron microscopy (TEM). This yielded, in accordance to the sequencing results, one or, respectively, two distinct populations of icosahedral phages. It also showed prolate phages which presumptively might be identified as the PVL phage. This observation highlights the significance bacteriophages have as agents of horizontal gene transfer as well as the need for monitoring emerging staphylococcal strains, especially in cosmopolitan settings such as the UAE.

Severe skin and soft tissue infection in cohort patients admitted in a teaching hospital in Belgium: identification of risk factors for surgery

Background Necrotizing soft tissue infections (NSTIs) are associated with significant mortality if not promptly diagnosed and surgically treated. Aim This study aims to compare patients with severe skin and soft tissue infection treated with or without a surgical intervention and to identify risk factors that can predict the need for early surgery. Methods Demographics, clinical, laboratory, Risk Indicator for Necrotizing Fasciitis (LRINEC) and imaging results were retrospectively collected. Results There were 91 non-NSTI (group 1), 26 NSTI who were operated (group 2) and eight suspected NSTI who were not operated (group 3). In the multivariate analysis, skin necrosis, tachycardia, CRP value and hyperglycemia were predictive for surgery. A performance analysis revealed AUC of 0.65 (95%CI: 0.52–0.78) as to the LRINEC score for the use of surgery. The AUC for a predictive model associating four variables (heart rate, skin necrosis, CRP and glycemia at admission) was 0.71 (95%CI: 0.59–0.84). In terms of outcome, the median length of stay (LOS) was statistically higher in group 2 vs. group 1 (seven days (5–15) vs. 34 days (20–42), p < .001) and in group 2 vs. group 3 (34 days (20–42) vs. 14 days (11–19), p = .005). The overall in-hospital mortality at 30 days was 3.2% and did not statistically differ between the three groups. Conclusions Although the LRINEC score performed well in predicting surgery, the AUC of a model combining four predictive variables (glycemia, skin necrosis, CRP and heart rate) was superior. Further research is needed to validate this model.

Validating the laboratory risk indicator for necrotizing fasciitis (LRINEC) score: a prospective cohort study in a resource limited setting.

Necrotising fasciitis is a rare and fulminant soft tissue infection. Prompt surgical debridement of the involved soft tissues and necrotic fascia is its definitive treatment, with any delay associated with increased mortality. The LRINEC score is a scoring system initially designed to aid in early diagnosis of necrotising fasciitis to facilitate early surgical intervention. This score utilizes common biochemical tests to produce a score of 0-13, stratifying patients into risk categories. A prospective cohort study was designed including all patients presenting with severe soft tissue infection from June 2011 to January 2014. Exclusion criteria included: less than 15 years or above 90 years, antibiotics within 48 h of presentation or prior debridement of their soft tissue infection. All patients underwent routine blood investigations, required for calculation of the LRINEC score. The positive predictive value of the LRINEC score was 95.42%, whilst the negative predictive value was 81.16%. There was a statistically significant correlation between white cell count, serum creatinine, blood glucose level and positive histopathology. The mortality rate for patients with histopathologically-confirmed necrotising fasciitis was 10%. The LRINEC score is a clinical adjunct to risk stratify patients presenting to the emergency department with soft tissue infections. It utilizes common blood tests commonly to calculate a score, which risk stratifies patients. The use of this scoring system can facilitate better allocation of resources and aids in the decision to transfer patients in rural or regional settings, which are often complicated by being a resource limited environment.

Haemolysin Ahh1 secreted from Aeromonas dhakensis activates the NLRP3 inflammasome in macrophages and mediates severe soft tissue infection

Severe soft tissue infections caused by Aeromonas dhakensis, such as necrotizing fasciitis or cellulitis, are prevalent in southern Taiwan and around the world. However, the mechanism by which A. dhakensis causes tissue damage remains unclear. Here, we found that the haemolysin Ahh1, which is the major virulence factor of A. dhakensis, causes cellular damage and activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome signalling pathway. Deletion of ahh1 significantly downregulated caspase-1, the proinflammatory cytokine interleukin 1β (IL-1β) and gasdermin D (GSDMD) and further decreased the damage caused by A. dhakensis in THP-1 cells. In addition, we found that knockdown of the NLRP3 inflammasome confers resistance to A. dhakensis infection in both THP-1 NLRP3-/- cells and C57BL/6 NLRP3-/- mice. In addition, we demonstrated that severe soft-tissue infections treated with antibiotics combined with a neutralizing antibody targeting IL-1β significantly increased the survival rate and alleviated the degree of tissue damage in model mice compared control mice. These findings show that antibiotics combined with therapies targeting IL-1β are potential strategies to treat severe tissue infections caused by toxin-producing bacteria.

Dilute Povidone-Iodine Solution Soaking Is Ineffective in Improving Outcomes of Necrotizing Fasciitis Caused by Diabetic Foot.

Wound soaking is a physical debridement method that helps reduce bacterial colonization and consequently promotes wound healing. Although soaking in povidone-iodine solution was ineffective in reducing bacterial colonization in acute trauma wounds, there is still a lack of evidence supporting the efficacy of this method in treating severe soft tissue infection. This study aimed to explore the effects of wound soaking in 1% dilute povidone-iodine solution on necrotizing fasciitis caused by diabetic foot ulcers. We retrospectively reviewed and finally included 153 patients who were admitted because of diabetic foot ulcers after undergoing fasciotomy for necrotizing infection from January 2018 to December 2021. Results showed no statistical difference in the outcomes between patients in the soaking and nonsoaking groups. End-stage renal disease (P = 0.029) and high serum C-reactive protein level (P = 0.007) were the only independent factors for below-knee amputation in the univariate and multivariate logistic regression analyses. Therefore, soaking diabetic wounds with severe infection in 1% dilute povidone-iodine solution may not reduce the hospital length of stay, risk of below-knee amputation, and readmission rate.

Comparison of Adjuvant Clindamycin vs Linezolid for Severe Invasive Group A Streptococcus Skin and Soft Tissue Infections.

Linezolid may be an option for severe group A Streptococcus (GAS) infections based on its potent in vitro activity and antitoxin effects, but clinical data supporting its use over clindamycin are limited. This study evaluated treatment outcomes in patients with severe GAS skin and soft tissue infections who received either linezolid or clindamycin. This retrospective single-center cohort study examined patients with GAS isolated from blood and/or tissue cultures with invasive soft tissue infection or necrotizing fasciitis who underwent surgical debridement and received linezolid or clindamycin for at least 48 hours. The primary outcome was percentage change in Sequential Organ Failure Assessment (SOFA) score from baseline through 72 hours of hospitalization. After adjustment for time to first surgical intervention among patients with a baseline SOFA score >0 (n = 23 per group), there was no difference in reduction of SOFA score over the first 72 hours in patients receiving clindamycin vs linezolid. In the entire cohort (n = 26, clindamycin; n = 29, linezolid), there was no difference in inpatient mortality (2% vs 1%) or any secondary outcomes, including duration of vasopressor therapy, intensive care unit length of stay, and antibiotic-associated adverse drug events. There was no difference in reduction of critical illness as measured by SOFA score between baseline and 72 hours among patients treated with clindamycin vs linezolid. Given its more favorable side effect profile, linezolid may be a viable option for the treatment of serious GAS infections and should be further studied.

Staphylococcus aureus Adaptation to the Skin in Health and Persistent/Recurrent Infections.

Staphylococcus aureus is a microorganism with an incredible capability to adapt to different niches within the human body. Approximately between 20 and 30% of the population is permanently but asymptomatically colonized with S. aureus in the nose, and another 30% may carry S. aureus intermittently. It has been established that nasal colonization is a risk factor for infection in other body sites, including mild to severe skin and soft tissue infections. The skin has distinct features that make it a hostile niche for many bacteria, therefore acting as a strong barrier against invading microorganisms. Healthy skin is desiccated; it has a low pH at the surface; the upper layer is constantly shed to remove attached bacteria; and several host antimicrobial peptides are produced. However, S. aureus is able to overcome these defenses and colonize this microenvironment. Moreover, this bacterium can very efficiently adapt to the stressors present in the skin under pathological conditions, as it occurs in patients with atopic dermatitis or suffering chronic wounds associated with diabetes. The focus of this manuscript is to revise the current knowledge concerning how S. aureus adapts to such diverse skin conditions causing persistent and recurrent infections.

Aeromonas sobria cellulitis with septic shock: rare but potentially lethal in chronic liver disease

Aeromonas, a common bacterial resident of freshwater is known to cause gastrointestinal illness in humans. Contaminated water and aquatic foods are the usual sources. Gastrointestinal disease is usually mild in normal individuals and responds to common antibiotics. However, extra-intestinal infections by Aeromonas species have been increasingly reported. Severe skin and soft tissue infection followed by septic shock may be seen in immunocompromised individuals. Bacteremia can also occur secondary to invasive gastroenteritis in persons with impaired immunity. Patients with decompensated chronic liver disease have been noted to be at especially high risk for fatal infection due to this pathogen. It can cause early bacteremia and rapid death without surgical debridement. We report a case of fatal Aeromonas cellulitis with septic shock in a patient with known advanced alcoholic liver disease. It started following minor skin injury and subsequent exposure to pond water. The patient presented late with septic shock and succumbed to his illness.

Life-Threatening Streptococcal Soft Tissue Infections in Children with Chickenpox: A Post-COVID-19 Case Series

Abstract Objective Children with chickenpox complicated by soft tissue infections can become critically unwell. We investigated cases that were referred to our center to examine the role of medical and surgical management in their care. Methods Children presenting with severe soft tissue infections (SSTIs) associated with varicella infections to a tertiary children's hospital in London serving the South East of England were identified. A retrospective review of the patients' records was performed. Results Ten patients presented having developed severe fever and localized cellulitis at around day 4 of their varicella infection. Group A Streptococcus (GAS) was identified as the causative organism in 90% of cases. Every patient required surgical intervention in addition to medical therapy to establish control of their soft tissue infection. We report 100% survival, and no patients required further reconstructive surgery. Conclusion SSTIs, often caused by invasive GAS, can severely complicate otherwise innocuous cases of chickenpox. Failure to respond to maximal medical therapy should prompt urgent referral to a specialist center, and early surgical intervention can prevent progression to more serious illness.

Severe and complicated soft tissue infections: a single-centre case series.

To assess the demographic and clinical characteristics, laboratory findings, and economic burden of patients with a diagnosis of complicated skin and soft tissue infection (cSSTI). The demographic and clinical characteristics, laboratory findings, surgical interventions, cost of treatment, and outcome of patients diagnosed with cSSTIs between January 2017 and December 2019 were retrospectively analysed. A total of 24 patients with cSSTIs were included in the study. The median age was 53 (22-85) years, and 14 (58%) were female. The most common comorbidity was diabetes (54%). On admission, 75% of patients presented with sepsis, and 70% had a high-grade Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score. The causative microorganism was isolated from 21 (87%) patients, and the multidrug resistance rate of Gram-negative bacteria was 50%. The median number of debridements was 3 (1-12). In all, 11 patients were followed up in the intensive care unit, and the mortality rate was 29%. The presence of confusion (p=0.025), causative Gram-negative microorganisms (p=0.009), hyponatraemia (p=0.034), the need for intensive care (p=0.001), anti-meticillin-resistant Staphylococcus aureus antibiotics (p=0.023) and the rate of antibiotic changes during treatment (p=0.019) were significantly higher in the non-survival patient group. Hyponatraemia was a significant independent risk factor for mortality (p=0.048). The median cost of per-patient treatment was $9453 USD in the non-surviving and $1536 in the surviving group. It is important to know possible factors and local resistance rates at the beginning of empirical antibacterial and surgical treatment. The presence of hyponatraemia, sepsis and a high LRINEC score can be considered to be the mortality predictors.

Severe soft tissue infection: A complication of mpox in an individual with HIV coinfection requiring vaccinia intravenous immunoglobulin and intravenous tecovirimat.

We highlight a case of a 38-year-old immunocompromised man with untreated human immunodeficiency virusand Hepatitis C who presented with progressive soft tissue infection of the right foot despite appropriate antibiotic therapy. While he was admitted, thepatient disclosed a recent diagnosis of mpox treated with oral tecovirimat. He subsequently developed worsening lesions over his entire body. In addition, a polymerase chain reaction of the wound on the right foot was positive for mpox virus, and the patient improved on treatment with intravenous tecovirimat and vaccinia immunoglobulin.

Ruptured ulcerated and inflammed gout tophi with deep soft tissue infection of left foot – when rheumatology meets surgery: a case report treated with local ozone therapy

Abstract&#x0D; Tophaceouse gout is a rare condition and chronic complication of gout due to storage of derivates of uric acid – crystals of monosodium urate, accompanied by lipids, mucopolisaharides matrix and proteins. Rheumatology meets the surgery in cases of rupture, ulceration and inflammation of tophi with complication with severe soft tissue infection, sepsis, large swelling, destruction of affected joints and periphery neuropathy chronic pain. Spontaneous or traumatic perforation and ulceration of tophi are rare conditions, that’s why there no any rheumatology or surgical guideline for management of that condition. We present a case report of male patient with posttraumatic perforated gout tophus and soft tissue secondary infection of left foot. He was treated with standard surgical debridement and local ozone therapy with stabilized ozonides over wound surface. That article presents a pioneer experience in the treatment of complicated tophaceouse gout with topical administration of ozonated olive oil with vitamin E and shows the effect of that treatment in progress.

Prognostic factors for intraoperative detection of necrotizing fasciitis in severe soft tissue infections.

Necrotizing fasciitis (NF) is a rare but lethal soft-tissue infection. There is still a paucity of information regarding the diagnostic tools and therapeutic strategies for the treatment of this devastating disease. This study aims to identify important perioperative parameters related to necrotizing fasciitis and to assess their relevance in terms of identifying NF. We retrospectively analyzed patients who underwent surgical exploration for suspected necrotizing fasciitis at a tertiary referral center, to explore the clinical features and factors related to the presence of necrotizing fasciitis and mortality. Between 2010 and 2017, 88 patients underwent surgical exploration for suspected NF. The infection occurred in the lower extremities in 48 patients, in the thoracocervical region in 18 patients, and the perineum and abdomen in 22 patients. Histological evidence of NF was present in 59 of 88 patients. NF was associated with a longer hospital stay and ICU stay (p = 0.05 and 0.019 respectively) compared to patients without NF. ROC analysis showed that only macroscopic fascial appearance could discriminate patients with histological evidence of NF. Moreover, multivariate logistic regression revealed, that liver failure (p = 0.019), sepsis (p = 0.011), positive Gram stain (p = 0.032), and macroscopic fascial appearance (p <0.001) were independent prognostic parameters for histological evidence of NF. Intraoperative tissue evaluation by an experienced surgeon is the most important diagnostic tool in identifying necrotizing fasciitis. An intraoperative Gram stain is an independent prognostic tool and therefore its use can be recommended especially in case of clinical uncertainty.

A successful process of treatment with necrotizing fasciitis of upper extremities in patients with diabetes mellitus: a case report.

This case report presents on a patient with diabetes mellitus rapidly developed a NF of the upper extremities following a minor trauma in the palmar of greater thenar. In the initial stages of her hospital admission, severe hand soft tissue infection, and systemic toxicity is the most prominent clinical manifestation. During her hospitalization, efficacious multidisciplinary treatment was carried out to avoid severe consequences. The objective of this case report is to present a successful individual strategy in a complex case to standardize the treatment process. Accurate and standardized management can improve the prognosis of patients affected from upper extremities NF of diabetic avoiding and severe complications and saving lives.

Impaired mTOR Signaling Causes Immune Suppression in Diabetes

Abstract It is estimated that over 11% of the U.S. population has diabetes and that 38% of the adult population is pre-diabetic. Diabetes carries increased risk and severity of many infections, which has been attributed to defects in the innate immune system. Despite the high impact of diabetes on infection, the underlying mechanisms of immune dysfunction in the diabetic host have yet to be fully elucidated. We have recently shown that innate immune cells in a diabetic host environment cannot undergo respiratory burst of reactive oxygen species and nitric oxide in response to infection with Staphylococcus aureus, the most common pathogen associated with frequently severe and invasive skin and soft tissue infection (SSTI) in patients with diabetes. The inhibition of respiratory burst was due to defects in the activation-dependent expression of the glucose transporter GLUT1, which is required for respiratory burst in neutrophils and macrophages. We therefore sought to further elucidate the specific mechanisms by which phagocytes in a diabetic environment are impaired in their ability to control S. aureusSSTI. We observed that mTOR signaling is impaired in a diabetic mouse model of S. aureusSSTI, which is upstream of both respiratory burst and GLUT-1 expression. Inhibition of mTOR signaling with rapamycin phenocopies the higher bacterial burden during diabetic infection, as well as the inhibition of respiratory burst and GLUT-1 expression. We further observed that mTOR activity upon macrophage activation is impaired in the absence of insulin and growth factor signaling. These findings begin to elucidate a role for mTOR signaling in the mechanism of immune suppression caused by diabetes.

Cryptococcal Necrotizing Fasciitis in a Patient With Sarcoidosis

Abstract Necrotizing fasciitis, a severe soft tissue infection that rapidly destroys the fascial layer through necrosis and inflammation, is often caused by Streptococcus pyogenes, gram-negative bacteria, Clostridium, and, rarely, fungal organisms. We present a case of necrotizing fasciitis caused by Cryptococcus neoformans in a patient with sarcoidosis on oral prednisone therapy.