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Background Necrotizing fasciitis (NF) is a life-threatening and acute progressive soft tissue infection and needs early surgical intervention, that is, debridement or amputation. Surgical strategy or prognosis is influenced by the speed of progression and patients’ general condition, which can be calculated by the Charlson Comorbidity Index (CCI). The purpose of this study was to investigate the association between the CCI scores and prognosis of patients with NF of the upper/lower extremities. Methods In the retrospective cohort study, we analyzed patients with NF of the upper/lower extremities who were determined to undergo surgery by orthopedic surgeons at four tertiary hospitals between August 2003 and April 2016. We divided the patients into two groups, Group L (low CCI scores of 0–2) and Group H (high CCI scores of ≥3). The primary event of this study was defined as death or amputation. Mortality cases were included when amputation was informed with documented certification but patients died while waiting for surgery. We compared the patients’ background, laboratory data on admission, the laboratory risk indicator for necrotizing fasciitis (LRINEC) score, and primary outcome between the two groups. Results Of the 56 patients, 28 patients were classified into Group L and the other 28 patients into Group H. The data in this study showed that patients in Group H had lower white blood cell counts and hemoglobin and higher creatinine than Group L, but there was no difference in LRINEC scores between the two groups. Streptococcus pyogenes was the most common infectious agent in Group L (54%) but not in Group H (11%). Poorer outcome was observed in Group H compared with Group L (4 mortality and 16 amputation vs. no mortality and 9 amputation, P = 0.007). Conclusions Laboratory data and causative microorganisms were different between high CCI and low CCI patients with NF. High CCI scores were associated with limb amputation or death caused by NF of the upper/lower extremities; whereas, low CCI scores were more likely associated with S. pyogenes monoinfection.

This review and meta-analysis aims to assess the prognostic value of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score for detecting necrotizing fasciitis in the extremities. The LRINEC score has been validated in multiple studies as a clinical tool for differentiating necrotizing fasciitis from non-necrotizing infections however many studies do not specify the location of infection. As the prevalence of diabetes and diabetic foot infections continues to rise, the utility of LRINEC scores in these populations becomes of increased importance. Four databases were reviewed for citations between January 2010 and December 2020. English, full text articles reporting the diagnostic effects of LRINEC were utilized in the systematic review portion of this paper. Further inclusion of 2 × 2 tables and discussion specific to the extremities were applied for citations implemented in the meta-analysis. Of the 111 results, 12 citations (n = 932) were included in this review. The diagnostic sensitivity of the LRINEC score ranged from 36% to 77% while specificity ranged from 72% to 93%. Cumulative odds ratio for LRINEC ≥6 among the 4 studies assessing extremity necrotizing fasciitis was 4.3 with p value of

Background The UK has one of the highest rates of recreational drug use and consequent deaths in Europe. Scotland is the “Drug deaths capital of Europe.” Intravenous drug use can result in limb- and life-threatening pathology. This study aimed to characterise limb-related admissions associated with intravenous drug use, outcomes and healthcare expenditure. Methods Retrospective data collection between December 2011 and August 2018. Patients were identified through discharge codes. Admission details were extracted from electronic records and a database compiled. Statistical analyses were performed using Statistical Package for the Social Science, P Results There were 558 admissions for 330 patients (1–9 admissions/patient), mean age 37 years (+/-7.6 SD) and 196 (59.2%; 319 admissions, 57.2%) were male. Three hundred forty-eight (62.4%) admissions were to surgical specialties, predominantly Vascular Surgery (247). Including onward referrals, Vascular ultimately managed 54.8% of admissions. Patients presented with multiple pathologies: 249 groin abscesses; 38 other abscesses; 74 pseudoaneurysms; 102 necrotising soft tissue infections (NSTI); 85 cellulitis; 138 deep venous thrombosis (DVTs); 28 infected DVTs and 70 other diagnoses. Two hundred and seventy-seven admissions (220 patients) required operations, with 361 procedures performed (1–7 operations/admission). There were 24 major limb amputations and 74 arterial ligations. Eleven amputations were due to NSTI and 13 followed ligation (17.6% of ligations). During follow-up 50 (15.2%) patients died, of which 6 (12%) had amputations (OR 3.2, 95% CI 1.04–9.61, P = 0.043). Cumulative cost of acute care was £4,783,241. Conclusions Limb-related sequalae of intravenous drug use represents a substantial surgical workload, especially for Vascular. These are complex, high-risk patients with poor outcomes and high healthcare costs.

Necrotizing soft tissue infections of the upper extremity threaten life and limb. Their presentation is often difficult to recognize and multiple factors contribute to the varied presentation, speed of spread, and morbidity of the disease process. The only treatment to be definitively shown to improve outcomes is prompt surgical treatment. It should be expected to perform multiple debridements as well as reconstructive procedures once the infection and necrosis has been arrested. The use of a multidisciplinary team is mandatory to optimize care for these patients. Despite advances in knowledge and treatment, these infections still have high mortality and morbidity.

Necrotizing soft-tissue infections are a rare complication following hip arthroplasty procedures. These rapidly spreading infections have a high mortality rate and must be diagnosed and treated in an expeditious manner. This article discusses the epidemiology, classification, diagnosis, and treatment of these conditions and describes 2 related case reports.

As the at-risk population expands and new antifungal resistance patterns develop, it is critical to understand and recognize cutaneous manifestations of old and emerging fungal diseases. PURPOSE OF REVIEW The aim of this review is to provide an overview of the most frequent and emerging deep cutaneous fungal infections following either primary inoculation or secondary spread after haematogenous seeding in disseminated infections in different geographical areas. RECENT FINDINGS Fungal skin and soft tissue infections (SSTIs) encompass a variety of pathological conditions based on the site of the infection, route of acquisition of the pathogen, epidemiological setting and the virulence of the fungus in relation to the host. The approach to a patient suspected of having a fungal SSTI is complex and usually poses a major diagnostic challenge. The treatment approach should include attempts at immune reconstitution, targeted antifungal therapy and/or aggressive surgical debridement. SUMMARY Fungal SSTIs can be an important cause of morbidity and mortality in both immunocompromised and immunocompetent patients and are being reported with increasing frequency worldwide.

Objectives: To assess the clinical and epidemiological characteristics of hospitalized cancer patients with skin and soft-tissue infections (SSTIs). Methods: An observational retrospective study was conducted between March 2016 and December 2020 at the Oncology Department of King Saudi Medical City, Riyadh, Saudi Arabia. Patients with complicated and uncomplicated SSTIs were included. Results: A total of 204 cancer patients with SSTIs were evaluated. The incidence of SSTIs was 1.67% (204/12,203). Breast cancer (39%) was the most common solid tumor in all patients with SSTIs. Exit site infection (n=84, 41.2%) was the most common SSTI in cancer patients, followed by wound infection (n=72, 35.3%), and cellulitis (n=44, 21.5%). The majority of patients received appropriate antimicrobial therapy (n=150, 73.5%). Conclusion: This study has shown a modest incidence of SSTIs in hospitalized cancer patients, with many of the patients received appropriate antimicrobial therapy.

Purpose of review Skin and soft tissue infections (SSTIs) are a leading cause of morbidity, emergency department visits and hospitalization. In recent years, the spread of carbapenem-resistant gram-negative bacteria (GNB) is also increasing in SSTIs. However, the armamentarium of available drugs is recently expanding as well. In this review, we reported the most recent data and about management and treatment of SSTIs caused by GNB, mainly for the treatment of carbapenem-resistant Enterobacterales (CRE), Pseudomonas spp and Acinetobacter spp. Recent findings The increasing incidence of carbapenem-resistant GNB is challenging for management and treatment, considering the high rate of inappropriate empiric and targeted antimicrobial treatments. The role of new antibiotics, mainly licensed for the treatment of other infections, is an object of continuous debate. As a matter of fact, no specific clinical trials on SSTIs have been performed for new drugs; however, recent data about the use in real life of new compounds in clinical practice are available. Summary Some recently approved drugs are actually considered the backbone of targeted therapy in patients with severe infections caused by susceptible carbapenem-resistant GNB strains. Prompt diagnosis of cSSTIs is crucial and, when necessary, surgical debridement for source control of infection is the milestone of the treatment. The physicians should be confident to identify patients at high risk for multidrug-resistant pathogens to minimize inappropriate empiric therapy.

Purpose of review Staphylococcus aureus is a pathogen incriminated in skin and soft tissue infections (SSTIs), with methicillin-resistant S. aureus (MRSA) becoming the predominant cause and representing a significant burden to the healthcare system. The last updated Infectious Diseases Society of America (IDSA) guidelines concerning MRSA infections and SSTIs management were published in 2011 and 2014, respectively. The UK updated guidelines for MRSA infection treatment were published in 2021. Older treatment options may be associated with toxicity and require frequent dosing. There is a paucity of recent reviews on the armamentarium of new agents for MRSA SSTIs treatment. Recent findings Since 2005, several new antibiotics received a fast-track approval by the Food and Drug Administration (FDA) for SSTI treatment. These drugs include delafloxacin, omadacycline, tedizolid, ceftaroline, dalbavancin, oritavancin and telavancin. In this manuscript, we will review the data that led to these new drugs approval and discuss their advantages and disadvantages in MRSA SSTIs management. Summary MRSA is a major cause of SSTIs. Several novel therapies covering MRSA were FDA-approved for SSTIs. However, the current IDSA guidelines for MRSA infection and SSTIs as well as the recently published UK guidelines on MRSA treatment only consider these drugs as alternative choices or do not mention them at all.

Background Pressure ulcers are the most common complications in bedridden patients or those with spinal cord injuries. Marjolin's ulcer refers to a malignant transformation arising from burn scars or chronic nonhealing wounds—such as pressure ulcers—over many years. Squamous cell carcinoma is the major histopathologic type of Marjolin's ulcer, and the gold standard for diagnosis is tissue biopsy. Medical professionals may have difficulty distinguishing pressure ulcers from Marjolin's ulcer, especially when the latter presents with invasive infections. Thus, malignant transformations arising from pressure ulcers are frequently overlooked. Herein, we describe a case of squamous cell carcinoma arising from pressure ulcers on the left ischium, which was initially identified as a necrotizing soft tissue infection. Case report A 59-year-old paraplegic patient presented with stage 3 left ischial pressure ulcer, which involves full-thickness skin loss and extends into deep subcutaneous tissue, and arrived at our hospital with suspected sepsis. Upon physical examination, the patient presented with fever and shivering. Initial examination and imaging findings revealed the presence of necrotizing soft tissue infections. Three weeks later, rapid increase in granulation in the deep part of the ulcer was observed. Samples from multiples ulcer sites were collected for tissue biopsy. Finally, histological examination revealed well-differentiated squamous cell carcinoma. The patient received radiation therapy and chemotherapy and died 11 months after the diagnosis. Conclusion Malignant transformations arising from pressure ulcers may closely resemble pressure ulcer infections. In these cases, tissue biopsies should be performed during primary care for the infection to exclude malignant transformations.

Bacterial skin and soft tissue infections are among the most common bacterial infections and constitute a major burden for patients and healthcare systems. Care is complicated by the variety of potential pathogens, some with resistance to previously effective antimicrobial agents, the wide spectrum of clinical presentations and the risk of progression to life-threatening forms. More-efficient care pathways are needed that can reduce hospital admissions and length of stay, while maintaining a high quality of care and adhering to antimicrobial stewardship principles. Several agents approved recently for treating acute bacterial skin and skin structure infections have characteristics that meet these requirements. We address the clinical and pharmacological characteristics of the fourth-generation fluoroquinolone delafloxacin, and the long-acting lipoglycopeptide agents dalbavancin and oritavancin.

Patients with severe acute respiratory syndrome coronavirus 2 infection may have bacterial co-infections, including pneumonia and bacteremia. Bordetella hinzii infections are rare, may be associated with exposure to poultry, and have been reported mostly among immunocompromised patients. We describe B. hinzii pneumonia and bacteremia in a severe acute respiratory syndrome coronavirus 2 patient.

Background Postoperative dehiscence and surgical site infection after spinal surgery can carry serious morbidity. Multidisciplinary involvement of plastic surgery is essential to minimizing morbidity and achieving definitive closure. However, a standardized approach is lacking. The aim of this study was to identify effective reconstructive interventions for the basis of an evidence-based management protocol. Methods A retrospective review was performed at a single tertiary institution for 45 patients who required 53 reconstruction procedures with plastic surgery for wounds secondary to spinal surgery from 2010 to 2019. Statistical analysis was performed for demographics, comorbidities, and treatment methods. Primary outcomes were postoperative complications, including dehiscence, seroma, and infection. The secondary outcome was time to healing. Results The overall complication rate was 32%, with dehiscence occurring in 17%, seroma in 15% and infection in 11% of cases. Median follow-up was 10 months (interquartile range, 4–23). Use of antibiotic beads did not affect rate of infection occurrence after wound closure (P=0.146). Use of incisional negative pressure wound therapy (iNPWT) was significant for reduced time to healing (P=0.001). Patients treated without iNPWT healed at median of 67.5 days while the patients who received iNPWT healed in 33 days. Demographics and comorbidities between these two groups were similar. Conclusions This data provides groundwork for an evidence-based approach to soft tissue reconstruction and management of dehiscence after spinal surgery. Timely involvement of plastic surgery in high-risk patients and utilization of evidence-based interventions such as iNPWT are essential for improving outcomes in this population.

Introduction Hospitalizations for severe injection-related infections (SIRI), such as endocarditis, osteomyelitis, and skin and soft tissue infections (SSTI) are increasingly common. People who inject drugs (PWID) experiencing SIRIs often receive inadequate substance use disorder (SUD) treatment and lack of access to harm reduction services. This translates into lengthy hospitalizations with high rates of patient-directed discharge, readmissions, and post-hospitalization mortality. The purpose of this study was to describe the development of an integrated “SIRI Team” and its initial barriers and facilitators to success. Materials and methods The Jackson SIRI Team was developed to improve both hospital and patient-level outcomes for individuals hospitalized with SIRIs at Jackson Memorial Hospital, a 1550-bed public hospital in Miami, Florida, United States. The SIRI Team provides integrated infectious disease and SUD treatment across the healthcare system starting from the inpatient setting and continuing for 90-days post-hospital discharge. The team uses a harm reduction approach, provides care coordination, focuses on access to medications for opioid use disorder (MOUD), and utilizes a variety of infection and addiction treatment modalities to suit each individual patient. Results Over the initial 8-months of the SIRI Team, 21 patients were treated with 20 surviving until discharge. Infections included osteomyelitis, endocarditis, bacteraemia/fungemia, SSTIs, and septic arthritis. All patients had OUD and 95% used stimulants. All patients were discharged on MOUD and 95% completed their prescribed antibiotic course. At 90-days post-discharge, 25% had been readmitted and 70% reported taking MOUD. Conclusions A model of integrated infectious disease and SUD care for the treatment of SIRIs has the potential to improve infection and addiction outcomes. Providing attentive, patient-centered care, using a harm reduction approach can facilitate engagement of this marginalized population with the healthcare system.KEY MESSAGESIntegrated infectious disease and addiction treatment is a novel approach to treating severe injection-related infections.Harm reduction should be applied to treating patients with severe injection-related infections with a goal of facilitating antibiotic completion, remission from substance use disorder, and reducing hospital readmissions.

Many dental infections that otherwise could be treated in-office are directly referred to emergency departments (ED) outside of normal business hours. This study sought to determine if odontogenic infections presenting to EDs were less severe on the weekends.This was a retrospective cohort study of the 2014 Nationwide Emergency Department Sample. All patients with the primary diagnosis of an oral soft tissue infection were included in the study sample. The primary study predictor was day of presentation. The study outcome was inpatient admission from the ED. A multivariate regression model was created for ED admission rate to identify independent predictors.A total of 6,560 records were included in the final sample. Overall, 34.8% of encounters occurred on the weekend, and these patients were more likely to have private insurance and reside in higher income locations. The unadjusted ED admission rate (9.4 vs 13.4%, P.01) was lower for patients evaluated on the weekend. The multiple regression model confirmed that weekend presentation was associated with a significantly lower odds of admission (OR = 0.69, P.01).Weekend odontogenic infections were less severe than those presenting on the weekdays. Off-hour dental emergencies remain a potential source of ED waste and should be scrutinized in any reforms seeking to reduce unnecessary emergency room encounters.

Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively (p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable (n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings.

Background: The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) has been proposed as a diagnostic tool for necrotizing soft tissue infection (NSTI). However, its utility remains underreported, particularly in patients with comorbid conditions. The purpose of this study was to identify the test characteristics of LRINEC for patients with various comorbid conditions. Patients and Methods: We conducted a retrospective study including patients with suspected NSTI. Our study patients were then relegated into the subgroups; intravenous drug use (IVDU), end-stage liver disease (ESLD), and diabetes mellitus (DM). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a positive LRINEC score (≥ 6 or 8) were calculated in reference to intra-operative findings or results of the pathologic examination. Area under the curve (AUC) using receiver operating characteristic (ROC) plots were compared between each subgroup and the overall study population using DeLong test. Results: A total of 220 patients were included for the analysis. Overall, the sensitivity was 76%, specificity of 52%, PPV of 32%, and NPV of 88%. The subgroup analysis showed low PPVs in all subgroups. The DM and ESLD groups had a high NPV (90.5% and 88.0%, respectively), whereas NPV in the IVDU group was 70.6%. The AUC and DeLong test for the subgroups were 0.649 (p = 0.902) for ESLD, 0.699 (p = 0.683) for DM, and 0.565 (p = 0.034) for IVDU. Conclusions: The LRINEC can be a useful adjunct to rule out the diagnosis of NSTI with exception of IVDU. In contrast, further diagnostic workup might be still required in those patients with positive LRINEC.

Introduction Necrotizing soft tissue infections (NSTIs) carry high morbidity and mortality. While early aggressive surgical debridement is well-accepted treatment for NSTIs, the optimum duration of adjunct antibiotic therapy is unclear. An increasing focus on safety and evidence-based antimicrobial stewardship suggests a value in addressing this knowledge gap. Objective To determine whether shorter antibiotic courses have similar outcomes compared to longer courses in patients with NSTI following adequate source control. Population 142 consecutive patients with surgically managed NSTI were identified on retrospective chart review between December 2014 and December 2018 at two academic medical centers. Results Patients were predominately male (74%) with a median age of 52 and similar baseline characteristics. The median number of debridements to definitive source control was 2 (IQR 1-3) with the short course group undergoing a greater number of debridements control 2.57 ± 1.8 vs 1.9 ± 1.2, ( P = .01). Of 142 patients, 34.5% received a short course and the remaining 65.5% received a longer course of antibiotics. There was no significant difference in the incidence of bacteremia or wound culture positivity between groups. There was also no significant difference in in-hospital mortality, 8% vs 6% ( P = .74), incidence of C. difficile infection, median length of stay, or 30-day readmission. Conclusion Provided adequate surgical debridement, similar outcomes in morbidity and mortality suggest antibiotic courses of 7 days or less are equally safe compared to longer courses.

Significance: Opioid use disorder and transition to injection drug use (IDU) are an urgent, nationwide public health crisis. Wounds and skin and soft tissue infections (SSTIs) are common complications of IDU that disproportionately affect people who inject drugs (PWID) and are a major source of morbidity and mortality for this population. Critical Issues: Injections in a nonsterile environment and reusing or sharing needles facilitates bacterial inoculation, with subsequent risk of serious complications such as sepsis, gangrene, amputation, and death. PWID are susceptible to infections with a wide spectrum of organisms beyond common culprits of SSTI, including Clostridium and Bacillus spp., as well as Candida. Recent Advances: Syringe services programs (SSPs) are cost-effective and successful in reducing harms associated with IDU. SSPs provide new equipment to PWID and aid in discarding used equipment. SSPs aim to reduce the risks of unhygienic injecting practices, which are associated with transmission of infections and blood-borne pathogens. Future Directions: Concurrently run SSPs and wound care clinics are uniquely positioned to facilitate care to PWID. Providing new, sterile equipment as well as early wound care intervention can reduce morbidity and mortality as well as health care expenditures by reducing the number of SSTI and injection-related wounds that require hospital admission. Establishment of wound care clinics as part of an SSP represents an untapped potential to reduce harm.

BACKGROUND Nontuberculous mycobacteria are commonly found pathogens; however, skin and soft tissue infections due to nontuberculous mycobacteria are often associated with surgical procedures, particularly after lipoplasty. Although nontuberculous mycobacteria are resistant to some chemical disinfectants, glutaraldehyde, peracetic acid, povidone iodine, alcohol, and chlorine are still used for the sterilization of medical instruments. This study investigated the efficacy of various disinfectants in a fatty environment with adipose and a bloody environment without adipose. In addition, this study was also used to identify the most effective disinfectant against nontuberculous mycobacteria. METHODS Three nontuberculous mycobacteria (Mycobacterium avium, M. abscessus, and M. fortuitum), pathogens frequently found in skin and soft tissue infections, were used. Seven chemical disinfectants were tested in both fatty and bloody environments. The disinfectants used were considered to have a sterilization effect when the log10 reduction factor exceeded 5. RESULTS Most disinfectants had some sterilizing effects against nontuberculous mycobacteria; however, glutaraldehyde was the most effective against all 3. Chlorhexidine and povidone iodine also displayed sterilizing effects. Of the disinfectants tested, only alkyldiaminoethylglycine hydrochloride showed a diminished effect with statistical significance, specifically against M. fortuitum in a fatty environment, whereas it had effective results in a bloody environment. CONCLUSIONS Glutaraldehyde showed the greatest sterilizing effect on nontuberculous mycobacteria with a log10 reduction factor >5 in both fatty and bloody environments. However, some chemical disinfectants did not show sufficient sterilizing effects in a fatty environment and, therefore, should be used with caution for the sterilization of nontuberculous mycobacteria. LEVEL OF EVIDENCE Level II.

The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot remains unknown.We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for soft-tissue infections of the diabetic foot results in similar rates of clinical remission and adverse events (AE).The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace.This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of "clinical remission at 2-months follow-up".Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm ( P = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; P = 0.71), and remission in the per-protocol population (25/32 vs 18/27; P = 0.32). Overall, 8 soft tissue DFIs in the 10-day arm and 5 cases in the 20-day arm recurred as a new osteomyelitis [8/35 (23%) versus 5/31 (16%); P = 0.53]. Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (intention-to-treat population, hazard ratio 0.6, 95%CI 0.3-1.1; per-protocol population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course.In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way.ClinicalTrials NCT03615807.

Skin and soft tissue infections (SSTIs) are the most common medical complication of injection drug use in the United States, though little work has been done assessing SSTI treatment among people who inject drugs (PWID). We examined past-3-month abscess characteristics, treatment utilization, and barriers to medical treatment among N = 494 community-recruited PWID. We used descriptive statistics to determine the frequencies of self-treatment and medical treatment for their most recent past-3-month abscess as well as barriers to seeking medical treatment. We then used bivariate and multivariate logistic regression to identify factors associated with having an abscess in the past 3 months. Overall, 67% of participating PWID ever had an abscess and 23% had one in the past 3 months. Only 29% got medical treatment for their most recent abscess whereas 79% self-treated. Methods for self-treatment included pressing the pus out (81%), applying a hot compress (79%), and applying hydrogen peroxide (67%). Most (91%) self-treated abscesses healed without further intervention. Barriers to medical treatment included long wait times (56%), being afraid to go (49%), and not wanting to be identified as a PWID (46%). Factors associated independently with having an abscess in the past 3 months were injecting purposely into muscle tissue (adjusted odds ratio [AOR] = 2.64), having difficulty finding a vein (AOR = 2.08), and sharing injection preparation equipment (AOR = 1.74). Our findings emphasize the importance of expanding community-based access to SSTI education and treatment services, particularly at syringe service programs where PWID may be more comfortable seeking resources.

Biologic agents may predispose patients to skin and soft tissue infections (SSTIs). Guidelines recommend discontinuing the agent preoperatively; the true risk of infection is unclear.To assess the incidence of SSTIs in patients receiving biologic agents for all clinical indications. A secondary aim was to assess those undergoing surgery to determine postoperative SSTI risk.A retrospective medical record review was conducted at 2 urban tertiary care hospitals. Biologic agent use ranged from June 2013 to June 2018. Data were extracted on biologic agent injections, surgical procedures, and patient characteristics.Hypertension, former smoking, and corticosteroid use were significantly associated with SSTI risk (P .05). There was no increased SSTI risk among biologic agents (P = .49). Biologic therapy with concomitant corticosteroid use increased risk of SSTI (P = .0049). There was no difference in postoperative SSTI risk in patients who stopped biologic therapy before surgery and those who did not.This study is limited by its retrospective design.There was no increased risk of either postoperative or nonperioperative SSTI risk among biologic agents. Concomitant corticosteroid use increased SSTI risk. Current guidelines regarding stopping biologic agents before surgery warrant re-evaluation, because there was no difference in SSTI risk in patients who did so.

Background: Skin and soft tissue infection (SSTI) after hernia surgery is infrequent yet catastrophic and is associated with mesh infection, interventions, and hernia recurrence. Although hernia repair is one of the most common general surgery procedures, uncertainty persists regarding incidence of long-term infections. Our goal is to develop a machine learning regression model that detects the occurrence of long-term hernia-associated SSTI. Patients and Methods: The data set consisted of veterans receiving hernia repair with implanted synthetic mesh during 2008-2015. The outcome of interest was occurrence of SSTI related to the index hernia surgery over a five-year follow-up. A neural network regression was fit on a medical record reviewed sample, then applied to the study population. Results: The study population was 96,435 surgeries, of which 76,886 (79.7%) were inguinal, 11,177 (11.6%) were umbilical, and 8,372 (8.7%) were ventral. In the training set, 40 patients had SSTI probability ≥90%, of whom 38 (95%) had a true SSTI. In 249 patients with SSTI probability 90% and all were true-positives. In 100 patients with probability

Of 100 patients discharged from short-stay units (SSUs) with antibiotics, 47 had a skin and soft-tissue infection, 22 had pneumonia, and 21 had a urinary tract infection. Among all discharge antibiotic prescriptions, 78% involved antibiotic overuse, most commonly excess duration (54 of 100) and guideline discordant selection (44 of 100).

Community-acquired pneumonia (CAP)/community-acquired bacterial pneumonia (CABP) and complicated skin and soft tissue infection (cSSTI)/acute bacterial skin and skin structure infection (ABSSSI) represent major causes of morbidity and mortality in children. β-Lactams are the cornerstone of antibiotic treatment for many serious bacterial infections in children; however, most of these agents have no activity against methicillin-resistant Staphylococcus aureus (MRSA). Ceftaroline fosamil, a β-lactam with broad-spectrum in vitro activity against Gram-positive pathogens (including MRSA and multidrug-resistant Streptococcus pneumoniae) and common Gram-negative organisms, is approved in the European Union and the United States for children with CAP/CABP or cSSTI/ABSSSI. Ceftaroline fosamil has completed a pediatric investigation plan including safety, efficacy, and pharmacokinetic evaluations in patients with ages ranging from birth to 17 years. It has demonstrated similar clinical and microbiological efficacy to best available existing treatments in phase III–IV trials in patients aged ≥ 2 months to < 18 years with CABP or ABSSSI, with a safety profile consistent with the cephalosporin class. It is also approved in the European Union for neonates with CAP or cSSTI, and in the US for neonates with ABSSSI. Ceftaroline fosamil dosing for children (including renal function adjustments) is supported by pharmacokinetic/pharmacodynamic modeling and simulations in appropriate age groups, and includes the option of 5- to 60-min intravenous infusions for standard doses, and a high dose for cSSTI patients with MRSA isolates, with a ceftaroline minimum inhibitory concentration of 2–4 mg/L. Considered together, these data suggest ceftaroline fosamil may be beneficial in the management of CAP/CABP and cSSTI/ABSSSI in children. Supplementary Information The online version contains supplementary material available at 10.1007/s40272-021-00468-w.

Background/Purpose Ceftaroline, with a unique activity against methicillin-resistant Staphylococcus aureus (MRSA), was not launched in Taiwan before 2019. The in vitro susceptibility data of ceftaroline against important Taiwanese pathogens are lacking. Methods The in vitro susceptibility of ceftaroline against important pathogens collected from 2012 through 2018 were extracted from the Antimicrobial Testing Leadership and Surveillance program. Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) to ceftaroline against all isolates. Results During the study period, the in vitro data regarding isolates of S. aureus (n = 2049), Staphylococcus epidermidis (n = 185), Streptococcus pneumoniae (n = 334), Streptococcus pyogenes (n = 170), Haemophilus influenzae (n = 75), Haemophilus parainfluenzae (n = 10) and Klebsiella pneumoniae (n = 680) regardless of hospital sites of collection were analyzed. Among the S. aureus isolates studied, 19.4% showed MICs of 1 mg/L to ceftaroline, and 4.4% showed in vitro susceptible-dose dependent to ceftaroline (all MICs, 2 mg/L). Most of other Gram-positive cocci, all H. influenzae and H. parainfluenzae isolates were susceptible to ceftaroline. By contrast, about one-third (35.9%) of K. pneumoniae isolates, irrespective of infection sources, exhibited non-susceptibility to ceftaroline (MIC range, 0.015–256 mg/L; MIC50 and MIC90 values, 0.12 and 256 mg/L, respectively). Conclusions From the pharmacodynamic perspectives, the ceftaroline dosage of 600 mg as a 2-h intravenous infusion every 8 h is effective against all S. aureus and other Gram-positive isolates regardless of acquisition sites in Taiwan. Before ceftaroline is prescribed in treatment of the patient with Gram-negative infection, a cautious evaluation about patient's healthcare-associated factor is warranted.

Background Skin-sparing debridement (SSd) was introduced as an alternative to en bloc debridement (EBd) to decrease morbidity caused by scars in patients surviving Necrotizing soft-tissue infections (NSTI). An overview of potential advantages and disadvantages is needed. The aim of this review was to assess (1) whether SSd is noninferior to EBd regarding general outcomes, that is, mortality, length of stay (LOS), complications, and (2) if SSd does indeed result in decreased skin defects. Methods A systematic literature search was performed according to the PRISMA guidelines. All human studies describing patients treated with SSd were included, when at least of evidence level consecutive case series. Studies describing up to 20 patients were pooled to improve readability and prevent overemphasis of findings from single small studies. Results Ten studies, one cohort study and nine case series, all classified as poor based on Chambers criteria for case series, were included. Compared to patients treated with EBd, patients treated with SSd had no increased mortality rate, LOS or complication rate. SSd-treated patients had a high rate (75%) of total delayed primary closure (DPC) in the pooled case series. Conclusion The current available evidence is of insufficient quality to conclude whether SSd is noninferior to EBd for all assessed outcomes. There are suggestions that SSd may result in a decreased need for skin transplants, which could potentially improve the (health related) quality of life in survivors. Experienced surgical teams could cautiously implement SSd under close monitoring, ideally with uniform outcome registry.

BACKGROUND Necrotizing soft tissue infections (NSTIs) are an acute surgical condition with high morbidity and mortality. Timely identification, resuscitation, and aggressive surgical management have significantly decreased inpatient mortality. However, reduced inpatient mortality has shifted the burden of disease to long-term mortality associated with persistent organ dysfunction. METHODS We performed a combined analysis of NSTI patients from the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections randomized-controlled interventional trial (ATB-202) and comprehensive administrative database (ATB-204) to determine the association of persistent organ dysfunction on inpatient and long-term outcomes. Persistent organ dysfunction was defined as a modified Sequential Organ Failure Assessment (mSOFA) score of 2 or greater at Day 14 (D14) after NSTI diagnosis, and resolution of organ dysfunction defined as mSOFA score of 1 or less. RESULTS The analysis included 506 hospitalized NSTI patients requiring surgical debridement, including 247 from ATB-202, and 259 from ATB-204. In both study cohorts, age and comorbidity burden were higher in the D14 mSOFA ≥2 group. Patients with D14 mSOFA score of 1 or less had significantly lower 90-day mortality than those with mSOFA score of 2 or higher in both ATB-202 (2.4% vs. 21.5%; p < 0.001) and ATB-204 (6% vs. 16%: p = 0.008) studies. In addition, in an adjusted covariate analysis of the combined study data sets D14 mSOFA score of 1 or lesss was an independent predictor of lower 90-day mortality (odds ratio, 0.26; 95% confidence interval, 0.13-0.53; p = 0.001). In both studies, D14 mSOFA score of 1 or less was associated with more favorable discharge status and decreased resource utilization. CONCLUSION For patients with NSTI undergoing surgical management, persistent organ dysfunction at 14 days, strongly predicts higher resource utilization, poor discharge disposition, and higher long-term mortality. Promoting the resolution of acute organ dysfunction after NSTI should be considered as a target for investigational therapies to improve long-term outcomes after NSTI. LEVEL OF EVIDENCE Prognostic/epidemiology study, level III.

Introduction Bacterial and fungal infections, such as skin and soft tissue infections (SSTIs) and infective endocarditis (IE), are increasing among people who use drugs in the United States. Traditional healthcare settings can be inaccessible and unwelcoming to people who use drugs, leading to delays in getting necessary care. The objective of this study was to examine SSTI treatment experiences among people utilizing services from syringe services programs. This study was initiated by people with lived experience of drug use to improve quality of care. Methods We conducted a cross-sectional survey among participants of five syringe services programs in North Carolina from July through September 2020. Surveys collected information on each participant’s history of SSTIs and IE, drug use and healthcare access characteristics, and SSTI treatment experiences. We examined participant characteristics using counts and percentages. We also examined associations between participant characteristics and SSTI history using binomial linear regression models. Results Overall, 46% of participants reported an SSTI in the previous 12 months and 10% reported having IE in the previous 12 months. Those with a doctor they trusted with drug use-related concerns had 27 fewer (95% confidence interval = − 51.8, − 2.1) SSTIs per every 100 participants compared to those without a trusted doctor. Most participants with a SSTI history reported delaying (98%) or not seeking treatment (72%) for their infections. Concerns surrounding judgment or mistreatment by medical staff and self-treating the infection were common reasons for delaying or not seeking care. 13% of participants used antibiotics obtained from sources other than a medical provider to treat their most recent SSTI. Many participants suggested increased access to free antibiotics and on-site clinical care based at syringe service programs to improve treatment for SSTIs. Conclusions Many participants had delayed or not received care for SSTIs due to poor healthcare experiences. However, having a trusted doctor was associated with fewer people with SSTIs. Improved access to non-judgmental healthcare for people who use drugs with SSTIs is needed. Expansion of syringe services program-based SSTI prevention and treatment programs is likely a necessary approach to improve outcomes among those with SSTI and IE.

Objective To explore the features and risk factors of bacterial skin infections (BSIs) in hospitalized patients with bullous pemphigoid (BP). Methods Records were retrospectively reviewed for 110 hospitalized patients with BP admitted to Peking University First Hospital between 2013 and 2019. Bacterial species and drug resistance were assessed, and then the underlying risk factors for BSIs were evaluated. Results Infections were present in 40% (44/110) of the patients. Staphylococcus aureus (72.7%, 32/44) was the most common bacterium, and it was highly resistant to penicillin (81.3%, 26/32), erythromycin (62.5%, 20/32), and clindamycin (56.3%, 18/32), but 100.0% sensitive to vancomycin and tigecycline. Coronary heart disease (P = .02; odds ratio [OR], 12.68), multisystem comorbidities (P = .02; OR, 3.67), hypoalbuminemia (P = .04; OR, 3.70), high levels of anti-BP180 antibodies (>112.4 U/mL; P = .003; OR, 6.43), and season (spring: reference; summer: P = .002; OR, 23.58; autumn: P = .02; OR, 12.19; winter: P = .02; OR, 13.19) were significantly associated with BSIs. Conclusions Hospitalized patients with BP had a high incidence of BSIs, and those patients with underlying risk factors require careful management to prevent and control BSIs.

Objectives 1) To measure frequency and yield of blood cultures obtained for observation status adult patients with skin and soft tissue infection (SSTI), 2) describe how often blood cultures were performed according to Infectious Diseases Society of America (IDSA) SSTI guideline indications, 3) identify proportion of patients meeting Center for Medicare Services (CMS) sepsis criteria. Design Retrospective cohort. Setting Tertiary academic center. Patients Consecutive adult observation status patients hospitalized with SSTI between July 2017 and July 2018. Methods We measured the proportion and results of blood cultures obtained among the study cohort and proportion of obtained cultures that satisfied IDSA indications. Results We identified 132 observation status patients with SSTI during the study period; 67 (50.8%) had blood cultures drawn. Only 14 (10.6%) patients met IDSA indications for culture; 51 (38.%) met Center for Medicare Services definition for sepsis. We identified two (3.0%) cases of bacteremia and two (3.0%) cases of skin bacteria contamination. In multivariable analysis, only temperature > 38 °C (OR 3.84, 95%CI 1.09–13.60) and white race (OR 2.71, 95%CI 1.21–6.20) were associated with blood culture obtainment; neither meeting IDSA SSTI guideline indications nor meeting CMS sepsis criteria was associated with culture. Conclusions Among observation status patients with SSTI, over half had blood cultures drawn, though 10% satisfied guideline indications for culture. The proportion of cultures with bacterial growth was low and yielded as many skin contaminants as cases of bacteremia. Our study highlights the need for further quality improvement efforts to reduce unnecessary blood cultures in routine SSTI cases.

Background The limited armamentarium against multidrug-resistant Gram-negative bacilli led to the development of a new generation of β-lactam/β-lactamase inhibitor combinations (BL/BLI). Objectives To evaluate the in vitro activity of ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam against Pseudomonas aeruginosa isolates recovered from patients hospitalized with skin and soft tissue infections (SSTIs) in several countries around the world. Methods A total of 360 P. aeruginosa isolates were consecutively collected from 47 medical centers located in Western Europe, Eastern Europe, the Asia-Pacific region, and Latin America. Susceptibility testing was performed by broth microdilution method at a monitoring laboratory. EUCAST breakpoints were applied. Results Ceftazidime/avibactam (98.3% susceptible), ceftolozane/tazobactam (98.6% susceptible), and imipenem/relebactam (98.3% susceptible) were the most active compounds after colistin (100.0% susceptible) and retained activity against isolates nonsusceptible to piperacillin/tazobactam, meropenem, imipenem, and/or ceftazidime. Meropenem-vaborbactam was active against 94.2% of isolates. Ceftazidime/avibactam was the most active BL/BLI against meropenem-nonsusceptible (92.6% susceptible) and imipenem-resistant (93.8% susceptible) isolates, whereas ceftolozane/tazobactam was the most active BL/BLI against piperacillin/tazobactam-resistant (91.1% susceptible) and ceftazidime-resistant (91.7% susceptible) isolates. Conclusions The recently approved BL/BLIs demonstrated potent activity and broad coverage against contemporary P. aeruginosa isolates from patients with SSTIs.

A model‐informed drug development approach was used to select ceftaroline fosamil high‐dose regimens for pediatric patients with complicated skin and soft‐tissue infections caused by Staphylococcus aureus with a ceftaroline minimum inhibitory concentration (MIC) of 2 or 4 mg/L. Steady‐state ceftaroline concentrations were simulated using a population pharmacokinetics (PK) model for ceftaroline fosamil and ceftaroline including data from 304 pediatric subjects and 944 adults. Probability of target attainment (PTA) for various simulated pediatric high‐dose regimens and renal function categories were calculated based on patients achieving 35% fT>MIC (S. aureus PK/pharmacodynamic target for 2‐log10 bacterial killing). For extrapolation of efficacy, simulated exposures and PTA were compared to adults with normal renal function receiving high‐dose ceftaroline fosamil (600 mg 2‐h infusions every 8 h). For safety, predicted ceftaroline exposures were compared with observed pediatric and adult data. Predicted ceftaroline exposures for the approved pediatric high‐dose regimens (12, 10, or 8 mg/kg by 2‐h infusions every 8 h for patients aged >2 to 99% and ≥81% for MICs of 2 and 4 mg/L, respectively) matched or exceeded the adult predictions. Simulated Cmax,ss values were below the maximum observed data in other indications, including a high‐dose pediatric pneumonia trial, which reported no adverse events related to high exposure.

Background: The Surgical Infection Society (SIS) Guidelines for the treatment of complicated skin and soft tissue infections (SSTIs) were published in October 2009 in Surgical Infections. The purpose of this project was to provide a succinct update on the earlier guidelines based on an additional decade of data. Methods: We reviewed the previous guidelines eliminating bite wounds and diabetic foot infections including their associated references. Relevant articles on the topic of complicated SSTIs from 2008-2020 were reviewed and graded individually. Comparisons were then made between the old and the new graded recommendations with review of the older references by two authors when there was disparity between the grades. Results: The majority of new studies addressed antimicrobial options and duration of therapy particularly in complicated abscesses. There were fewer updated studies on diagnosis and specific operative interventions. Many of the topics addressed in the original guidelines had no new literature to evaluate. Conclusions: Most recommendations remain unchanged from the original guidelines with the exception of increased support for adjuvant antimicrobial therapy after drainage of complex abscess and increased data for the use of alternative antimicrobial agents.

Objectives Emergency department (ED) patients with serious skin and soft tissue infections (SSTIs) are often hospitalized to receive intravenous (IV) antibiotics. Appropriate patients may avoid admission following a single‐dose, long‐acting IV antibiotic. Methods We conducted a preintervention versus postintervention design trial at 11 U.S. EDs comparing hospitalization rates under usual care to those using a clinical pathway that included a single IV dalbavancin dose. We enrolled adults with cellulitis, abscess, or wound infection with an infected area of ≥75 cm2 without other indications for hospitalization. Clinical pathway participants discharged from the ED received a 24‐hour follow‐up telephone call and had a 48‐ to 72‐hour in‐person visit. We hypothesized that, compared to usual care, the clinical pathway would result in a significant reduction in the initial hospitalization rate. Results Of 156 and 153 participants in usual care and clinical pathway periods, median infection areas were 255.0 (interquartile range [IQR] = 150.0 to 500.0) cm2 and 289.0 (IQR = 161.3 to 555.0) cm2, respectively. During their initial care, 60 (38.5%) usual care participants were hospitalized and 27 (17.6%) pathway participants were hospitalized (difference = 20.8 percentage points [PP], 95% confidence interval [CI] = 10.4 to 31.2 PP). Over 44 days, 70 (44.9%) usual care and 44 (28.8%) pathway participants were hospitalized (difference = 16.1 PP, 95% CI = 4.9 to 27.4 PP). Conclusions Implementation of an ED SSTI clinical pathway for patient selection and follow‐up that included use of a single‐dose, long‐acting IV antibiotic was associated with a significant reduction in hospitalization rate for stable patients with moderately severe infections. Registration: NCT02961764.

OBJECTIVES To evaluate whether ultrasound can differentiate between cellulitis and angioedema from insect bites in pediatric patients. METHODS A prospective, pre-post study in an urban pediatric emergency department of patients younger than 21 years with soft tissue swelling from insect bites without abscesses were enrolled. Treating physician's pretest opinions regarding the diagnosis and need for antibiotics were determined. Ultrasound of the affected areas was performed, and effects on management were recorded. Further imaging, medications, and disposition were at the discretion of the enrolling physician. Phone call follow-ups were made within a week of presentation. RESULTS Among 103 patients enrolled with soft tissue swelling secondary to insect bites, ultrasound changed the management in 27 (26%) patients (95% confidence interval [CI], 18-35%). Of the patients who were indeterminate or believed to require antibiotics, ultrasound changed management in 6 (23%) of 26 patients (95% CI, 6%-40%). In those patients who were believed not to require antibiotics, ultrasound changed management in 12 (16%) 77 patients (95% CI, 7%-24%). Patients with diagnosis of local angioedema achieved symptom resolution 1.4 days sooner than patients diagnosed with cellulitis (mean, -1.389; 95% CI, -2.087 to -0.690; P < 0.001). No patient who was initially diagnosed as local angioedema received antibiotics upon patient follow-up. CONCLUSIONS Point-of-care ultrasound changed physician management in 1 of 4 patients in the pediatric emergency department with soft tissue swelling secondary to insect bites. Ultrasound may guide the management in these patients and lead to improved antibiotic stewardship in conjunction with history and physical examination.

Supplemental digital content is available in the text., BACKGROUND During the coronavirus disease 2019 pandemic, New York instituted a statewide stay-at-home mandate to lower viral transmission. While public health guidelines advised continued provision of timely care for patients, disruption of safety-net health care and public fear have been proposed to be related to indirect deaths because of delays in presentation. We hypothesized that admissions for emergency general surgery (EGS) diagnoses would decrease during the pandemic and that mortality for these patients would increase. METHODS A multicenter observational study comparing EGS admissions from January to May 2020 to 2018 and 2019 across 11 NYC hospitals in the largest public health care system in the United States was performed. Emergency general surgery diagnoses were defined using International Classification Diseases, Tenth Revision, codes and grouped into seven common diagnosis categories: appendicitis, cholecystitis, small/large bowel, peptic ulcer disease, groin hernia, ventral hernia, and necrotizing soft tissue infection. Baseline demographics were compared including age, race/ethnicity, and payor status. Outcomes included coronavirus disease (COVID) status and mortality. RESULTS A total of 1,376 patients were admitted for EGS diagnoses from January to May 2020, a decrease compared with both 2018 (1,789) and 2019 (1,668) (p < 0.0001). This drop was most notable after the stay-at-home mandate (March 22, 2020; week 12). From March to May 2020, 3.3%, 19.2%, and 6.0% of EGS admissions were incidentally COVID positive, respectively. Mortality increased in March to May 2020 compared with 2019 (2.2% vs. 0.7%); this difference was statistically significant between April 2020 and April 2019 (4.1% vs. 0.9%, p = 0.045). CONCLUSION Supporting our hypothesis, the coronavirus disease 2019 pandemic and subsequent stay-at-home mandate resulted in decreased EGS admissions between March and May 2020 compared with prior years. During this time, there was also a statistically significant increase in mortality, which peaked at the height of COVID infection rates in our population. LEVEL OF EVIDENCE Epidemiological, level IV.

Introduction: Surgical intervention, broad-spectrum antibiotics and intensive care support are the standard of care in the treatment of necrotising soft-tissue infections (NSTI). Hyperbaric oxygen treatment (HBOT) may be a useful adjunctive treatment and has been used for almost 60 years, but its efficacy remains unknown and has not been systematically appraised. The aim was to systematically review and synthesise the highest level of clinical evidence available to support or refute the use of HBOT in the treatment of NSTI. Methods: The review was prospectively registered (PROSPERO; CRD42020148706). MEDLINE, EMBASE, CENTRAL and CINAHL were searched for eligible studies that reported outcomes in both HBOT treated and non-HBOT treated individuals with NSTI. In-hospital mortality was the primary outcome. Odds ratio (ORs) were pooled using random-effects models. Results: The search identified 486 papers of which 31 were included in the qualitative synthesis and 21 in the meta-analyses. Meta-analysis on 48,744 patients with NSTI (1,237 (2.5%) HBOT versus 47,507 (97.5%) non-HBOT) showed in-hospital mortality was 4,770 of 48,744 patients overall (9.8%) and the pooled OR was 0.44 (95% CI 0.33–0.58) in favour of HBOT. For major amputation the pooled OR was 0.60 (95% CI 0.28–1.28) in favour of HBOT. The dose of oxygen in these studies was incompletely reported. Conclusions: Meta-analysis of the non-random comparative data indicates patients with NSTI treated with HBOT have reduced odds of dying during the sentinel event and may be less likely to require a major amputation. The most effective dose of oxygen remains unclear.