Necrotizing Soft Tissue Infections Patients Research Articles

Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes

BackgroundStreptococcus pyogenes (group A streptococcus, GAS) causes a variety of diseases ranging from mild superficial infections of the throat and skin to severe invasive infections, such as necrotizing soft tissue infections (NSTIs). Tissue passage of GAS often results in mutations within the genes encoding for control of virulence (Cov)R/S two component system leading to a hyper-virulent phenotype. Dendritic cells (DCs) are innate immune sentinels specialized in antigen uptake and subsequent T cell priming. This study aimed to analyze cytokine release by DCs and other cells of monocytic origin in response to wild-type and natural covR/S mutant infections.MethodsHuman primary monocyte-derived (mo)DCs were used. DC maturation and release of pro-inflammatory cytokines in response to infections with wild-type and covR/S mutants were assessed via flow cytometry. Global proteome changes were assessed via mass spectrometry. As a proof-of-principle, cytokine release by human primary monocytes and macrophages was determined.ResultsIn vitro infections of moDCs and other monocytic cells with natural GAS covR/S mutants resulted in reduced secretion of IL-8 and IL-18 as compared to wild-type infections. In contrast, moDC maturation remained unaffected. Inhibition of caspase-8 restored secretion of both molecules. Knock-out of streptolysin O in GAS strain with unaffected CovR/S even further elevated the IL-18 secretion by moDCs. Of 67 fully sequenced NSTI GAS isolates, 28 harbored mutations resulting in dysfunctional CovR/S. However, analyses of plasma IL-8 and IL-18 levels did not correlate with presence or absence of such mutations.ConclusionsOur data demonstrate that strains, which harbor covR/S mutations, interfere with IL-18 and IL-8 responses in monocytic cells by utilizing the caspase-8 axis. Future experiments aim to identify the underlying mechanism and consequences for NSTI patients.

No role for standard imaging workup of patients with clinically evident necrotizing soft tissue infections: a national retrospective multicenter cohort study

PurposeTo assess the diagnostic contribution of different imaging studies to diagnose necrotizing soft tissue infections (NSTIs) and the time to surgery in relation to imaging with the hypothesis that imaging studies may lead to significant delays without being able to sufficiently dismiss or confirm the diagnosis since a NSTI is a surgical diagnosis.MethodsA retrospective multicenter cohort study of all NSTI patients between 2010 and 2020 was conducted. The primary outcome was the number of cases in which imaging contributed to or led to change in treatment. The secondary outcomes were time to treatment determined by the time from presentation to surgery and patient outcomes (amputation, intensive care unit (ICU) admission, length of ICU stay, hospital stay, and mortality).ResultsA total of 181 eligible NSTI patients were included. The overall mortality was 21% (n = 38). Ninety-eight patients (53%) received imaging in the diagnostic workup. In patients with a clinical suspicion of a NSTI, 81% (n = 85) went directly to the operating room and 19% (n = 20) underwent imaging before surgery; imaging was contributing in only 15% (n = 3) by ruling out or determining underlying causes. In patients without a clinical suspicion of a NSTI, the diagnosis of NSTI was considered in 35% and only after imaging was obtained.ConclusionIn patients with clinically evident NSTIs, there is no role for standard imaging workup unless it is used to examine underlying diseases (e.g., diverticulitis, pancreatitis). In atypical presenting NSTIs, CT or MRI scans provided the most useful information. To prevent unnecessary imaging and radiation and not delay treatment, the decision to perform imaging studies in patients with a clinical suspicion of a NSTI must be made extremely careful.

Risk model for predicting mortality in patients with necrotizing soft tissue infections in the intensive care unit

BackgroundThe goal of this study is to look into the factors that lead to death in patients with necrotizing soft tissue infections（NSTIs） in the intensive care unit and create a mortality risk model. MethodsThe clinical data of 106 patients with necrotizing soft tissue infections admitted to intensive care unit(ICU) of the First Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2021 were retrospectively analyzed. Univariate analysis and multivariate analysis were performed to evaluate the risk factors impacting patient mortality. The regression coefficient in binary logistic regression analysis was converted into the item score in the model, and then the model score of each patient was calculated. Finally, an ROC curve was constructed to evaluate the efficiency of the model for predicting mortality. Thirteen patients with NSTIs admitted to ICU between January 2022 and November 2022 were used to validate the model. ResultsThe death group had 44 patients, while the survival group had 62 patients. The overall mortality was 41.5%. Binary logistic regression analysis showed that risk factors for mortality were age≥ 60 years(OR:4.419; 95%CI:1.093–17.862; P = 0.037), creatinine ≥ 132μmol/L(OR:11.166; 95%CI:2.234–55.816; P = 0.003), creatine kinase ≥ 1104 U/L(OR:4.019; 95%CI:1.134–14.250; P = 0.031), prothrombin time ≥ 24.4 s(OR:11.589; 95%CI:2.510–53.506; P = 0.002), and invasive mechanical ventilation (OR:17.404; 95%CI:4.586–66.052; P＜0.000). The AUC of the model for predicting mortality was 0.940 (95% CI:0.894–0.986). When the cut-off value for the model was 4 points, the sensitivity was 95.5% and the specificity was 83.9%. ConclusionThe death risk model in this study for NSTIs patients in the intensive care unit shows high sensitivity and specificity. Patients with a score of ≥ 4 points have a higher risk of mortality.

Levels of small extracellular vesicles in patients treated with hyperbaric oxygenation.

Hyperbaric oxygen (HBO2) therapy involves the inhalation of pure oxygen in a pressure chamber under increased ambient pressure. Recent research indicates that circulating small extracellular vesicles (sEVs) play important roles in human physiology and pathology. Therefore, the objective of this pilot study was to monitor the impact of HBO2 therapy on the levels of circulating sEVs in the serum of patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) or idiopathic sudden sensory neural hearing loss (ISSNHL). Serum-derived sEVs were isolated and quantified in 80 patients before and after HBO2 therapy applied for NSTI, ISSNHL and ABN patients as well as in normal controls who received neither HBO2 therapy nor steroids. We observed a significant increase of circulating sEVs in patients with ISSNHL after HBO2 therapy (p < 0.05), as well as significantly elevated levels of sEVs after HBO2 therapy compared to patients with NSTI (p < 0.05) and ABN (p < 0.01). The increase in the levels of sEVs in ISSNHL may be evidence for both the intended reduction of inflammation as a result of steroid therapy and the inhibitory effect of oxidative stress induced by HBO2 therapy. Thus, sEVs released during HBO2 therapy might play an important biological role in mediating the response to therapy and might be a promising approach to gain further insights into the therapeutic efficacy of HBO2 therapy.

512 Mean Arterial Pressure, Morbidity, and Mortality Associated with Necrotizing Soft Tissue Infection

Abstract Introduction Adequate mean arterial pressure (MAP), or the average pressure in arteries during one cardiac cycle, plays an important role in ensuring adequate blood flow and perfusion in critically ill patients. MAP values of 65 mmHg or greater have been widely regarded as the ideal value for hospitalized patients in the past, especially those suffering from septic shock. Necrotizing soft tissue infections (NSTIs) present a unique challenge due to their rapid progression and high mortality, which creates the need for specific diagnostic and treatment guidelines that differ from those directed toward the care of sepsis secondary to other causes. Further research is still required to better understand the complex interactions between mean arterial pressure and morbidity and mortality among those with necrotizing soft tissue infections. Methods Data was collected from a retrospective cohort study of 50 adult patients hospitalized with an NSTI from 2015-2021. MAP ranges in the first 48 hours of admission were sorted into four categories: under 60 mmHg, 60-69 mmHg, 70-79 mmHg, and above 79 mmHg. We investigated outcomes relating to increased morbidity, including need for repeat debridement, need for dialysis, or development of acute kidney injury. Statistical logistic regressions were fitted to model the outcome as a function of the available pool of predictors: demographic variables, co-morbidities, and hemodynamic variables, such as MAP and use of vasopressors. Results In this small study, we found no significant association between time spent in different MAP groups or vasopressor volumes on the need for repeat debridement for NSTI patients or overall patient morbidity and mortality (p=0.1742). Patients who were significantly more likely to need a repeat debridement included those with previously diagnosed diabetes and hypertension (p=0.0485 and 0.0252, respectively). Conclusions NSTI patients can tolerate mild fluctuations in MAP without these pressures significantly impacting their need for repeat debridement or other sources of morbidity. However, patients who are hypertensive at baseline or diabetic are significantly more likely to require a second surgery, necessitating a more extensive primary debridement. Applicability of Research to Practice Patients hospitalized for NSTI can fluctuate at pressures below the established MAP goal of 65 mmHg without a significant need for pressors. Those with a history of hypertension or diabetes should be followed closely for possible spread of infection after primary surgery.

Contemporary strategies for diagnosis and management of necrotizing soft tissue infections: Α review

The necrotizing soft tissue infection (NSTI) is an uncommon but rapidly progressive destructive disease associated with high mortality. In this study, we review basic knowledge and emphasize contemporary perspectives in diagnosis and treatment of adult NSTI. The mainstays of management of NSTI that can modify outcomes are the awareness for early detection and that all aspects of multidisciplinary treatment should be started promptly and simultaneously. Surgical debridement entails aggressive approach with extensive, and, if required, repeat necrectomies to completely control advancing sepsis in soft tissues. There is general agreement that the principles of damage control surgery should be applied on deranged NSTI patients. Continuous supportive care and scheduled management of residual open wounds are considered as extremely important. It has also been recognized that relative clinical guidelines and recommendations are growing in number and may vary widely in quality. Notably, the compliance of therapists to given guidelines differs among studies, and variations in aspects of clinical practice exist. Many studies comprise small numbers of patients, making evaluation of proposed novel techniques or adjuncts unreliable. Concluding, NSTI diagnosis should be promptly established, surgery should never be delayed so that sepsis remains reversible, and supportive care should be continuous. Novel therapeutics are required to combat this persistently lethal disease, thus, the next research steps should focus on determining if optimization of modifiable predictors would improve outcomes. Stronger well-conducted studies and wider dissemination of developed evidence-based instructions, while ensuring the strict compliance of daily clinicians’ practices, are required to further improve outcomes.

Investigating the Effects of Hyperbaric Oxygen Treatment in Necrotizing Soft Tissue Infection With Transcriptomics and Machine Learning (the HBOmic Study): Protocol for a Prospective Cohort Study With Data Validation.

Necrotizing soft tissue infections (NSTIs) are complex multifactorial diseases characterized by rapid bacterial proliferation and progressive tissue death. Treatment is multidisciplinary, including surgery, broad-spectrum antibiotics, and intensive care; adjunctive treatment with hyperbaric oxygen (HBO2) may also be applied. Recent advances in molecular technology and biological computation have given rise to new approaches to infectious diseases based on identifying target groups defined by activated pathophysiological mechanisms. We aim to capture NSTI disease signatures and mechanisms and responses to treatment in patients that receive the highest standard of care; therefore, we set out to investigate genome-wide transcriptional responses to HBO2 treatment during NSTI in the host and bacteria. The Effects of Hyperbaric Oxygen Treatment Studied with Omics (HBOmic) study is a prospective cohort study including 95 patients admitted for NSTI at the intensive care unit of Copenhagen University Hospital (Rigshospitalet), Denmark, between January 2013 and June 2017. All participants were treated according to a local protocol for management of NSTI, and biological samples were obtained and stored according to a standard operational procedure. In the proposed study, we will generate genome-wide expression profiles of whole-blood samples and samples of infected tissue taken before and after HBO2 treatment administered during the initial acute phase of infection, and we will analyze the profiles with unsupervised hierarchical clustering and machine learning. Differential gene expression will be compared in samples taken before and after HBO2 treatment (N=85), and integration of profiles from blood and tissue samples will be performed. Furthermore, findings will be compared to NSTI patients who did not receive HBO2 treatment (N=10). Transcriptomic data will be integrated with clinical data to investigate associations and predictors. The first participant was enrolled on July 27, 2021, and data analysis is expected to begin during autumn 2022, with publication of results immediately thereafter. The HBOmic study will provide new insights into personalized patient management in NSTIs. ClinicalTrials.gov NCT01790698; https://clinicaltrials.gov/ct2/show/NCT01790698. DERR1-10.2196/39252.

Sociodemographic Disparities in the Surgical Management and Outcomes of Necrotizing Soft Tissue Infections: A Nationwide Analysis

INTRODUCTION: Necrotizing soft tissue infections (NSTIs) are surgical emergencies that require an early diagnosis and aggressive surgical debridement. It has been established that disparities can influence surgical care. Our aim was to assess the association of sociodemographic variables in the surgical management and outcomes of NSTIs. METHODS: Using the Nationwide Inpatient Sample (2015 to 2018), we included patients with a primary diagnosis of NSTIs. We collected demographics and clinical characteristics. Outcomes were in-hospital mortality and number of debridements. Multivariable regression models were used to identify sociodemographic factors associated with the outcomes. RESULTS: A weighted total of 119,764 NSTI admissions were identified. The mean age was 55.4 years (SD 14.88), 65% were male, and 60% were white. Overall mortality was 6.8%, and the mean number of debridements per patient was 1.84 (SD 2.32). After adjusted analysis, female sex (odds ratio 1.21, 95% CI 1.09 to 1.35) and Hispanic ethnicity (odds ratio 1.20, 95% CI 1.02 to 1.42) were associated with increased mortality. Black (incidence rate ratio 0.90, 95% CI 0.86 to 0.94) and Hispanic patients (incidence rate ratio 0.91, 95% CI 0.86 to 0.96) along with those with public insurance (incidence rate ratio 0.93, 95% CI 0.89 to 0.96) were associated with a decreased number of debridements. CONCLUSION: This study shows that there are sociodemographic disparities in the care of NSTI patients based on sex, race/ethnicity, and insurance status. Mortality was higher among minority patients, and they underwent a lower number of surgical debridements. Further work is needed to understand the root cause of this problem and to develop appropriate interventions to ensure everyone receives the highest quality of care.

Sarcopenia Is Associated With Increased Mortality in Patients With Necrotizing Soft Tissue Infections.

Necrotizing soft tissue infections (NSTIs) are surgical emergencies associated with high morbidity and mortality. Identifying risk factors for poor outcome is a critical part of preoperative decision-making and counseling. Sarcopenia, the loss of lean muscle mass, has been associated with an increased risk of mortality and can be measured using cross-sectional imaging. Our aim was to determine the impact of sarcopenia on mortality in patients with NSTI. We hypothesized that sarcopenia would be associated with an increased risk of mortality in patients with NSTI. This is a retrospective cohort study of NSTI patients admitted from 1995 to 2015 to two academic institutions. Operative and pathology reports were reviewed to confirm the diagnosis in all cases. Average bilateral psoas muscle cross-sectional area at L4, normalized for height (Total Psoas Index [TPI]), was calculated using computed tomography (CT). Sarcopenia was defined as TPI in the lowest sex-specific quartile. Primary outcome was in-hospital mortality. Multivariate logistic regression was performed to assess the association between sarcopenia and in-hospital mortality. There were 115 patients with preoperative imaging, 61% male and a median age of 57y interquartile range (IQR 46.6-67.0). Overall in-hospital mortality was 12.1%. There was no significant difference in sex, body mass index (BMI), comorbidities and American Society of Anesthesiologists classification (Table1). After multivariate analysis, sarcopenia was independently associated with increased in-hospital mortality (Odds ratio, 3.5; 95% Confidence Interval [CI], 1.05-11.8). Sarcopenia is associated with increased risk of in-hospital mortality in patients with NSTIs. Sarcopenia identifies patients with higher likelihood of poor outcomes, which can possibly help surgeons in counseling their patients and families.

In-hospital mortality associated with necrotizing soft tissue infection due to Vibrio vulnificus: a matched-pair cohort study

BackgroundIt remains unclear whether Vibrio vulnificus necrotizing soft tissue infection (NSTI) is associated with higher mortality compared with non-Vibrio NSTI. This study’s objective was to compare outcomes including in-hospital mortality and prognosis between patients with V. vulnificus NSTI and those with non-Vibrio NSTI.MethodA retrospective 1:2 matched-pair cohort study of hospitalized patients with NSTI diagnosed by surgical finding was conducted in two tertiary hospitals in southern Taiwan between January 2015 and January 2020. In-hospital outcomes (mortality, length of stay) were compared between patients with and without V. vulnificus infection. We performed multiple imputation using chained equations followed by multivariable regression analyses fitted with generalized estimating equations to account for clustering within matched pairs. All-cause in-hospital mortality and length of stay during hospitalization were compared for NSTI patients with and without V. vulnificus.ResultA total of 135 patients were included, 45 in V. vulnificus NSTI group and 90 in non-Vibrio group. The V. vulnificus NSTI patients had higher mortality and longer hospital stays. Multivariable logistic regression analysis revealed that V. vulnificus NSTI was significantly associated with higher in-hospital mortality compared with non-Vibrio NSTI (adjusted odds ratio = 1.52; 95% confidence interval 1.36–1.70; p < 0.01).ConclusionVibrio vulnificus NSTI was associated with higher in-hospital mortality and longer hospital stay which may increase health care costs, suggesting that preventing V. vulnificus infection is essential.

Consistent Biofilm Formation by Streptococcus pyogenes emm 1 Isolated From Patients With Necrotizing Soft Tissue Infections.

ObjectivesBiofilm formation has been demonstrated in muscle and soft tissue samples from patients with necrotizing soft tissue infection (NSTI) caused by Streptococcus pyogenes, but the clinical importance of this observation is not clear. Although M-protein has been shown to be important for in vitro biofilm formation in S. pyogenes, the evidence for an association between emm type and biofilm forming capacity is conflicting. Here we characterize the biofilm forming capacity in a collection of S. pyogenes isolates causing NSTI, and relate this to emm type of the isolates and clinical characteristics of the patients.MethodsBacterial isolates and clinical data were obtained from NSTI patients enrolled in a multicenter prospective observational study. Biofilm forming capacity was determined using a microtiter plate assay.ResultsAmong 57 cases, the three most frequently encountered emm types were emm1 (n = 22), emm3 (n = 13), and emm28 (n = 7). The distribution of biofilm forming capacity in emm1 was qualitatively (narrow-ranged normal distribution) and quantitatively (21/22 isolates in the intermediate range) different from other emm types (wide ranged, multimodal distribution with 5/35 isolates in the same range as emm1). There were no significant associations between biofilm forming capacity and clinical characteristics of the patients.ConclusionsThe biofilm forming capacity of emm1 isolates was uniform and differed significantly from other emm types. The impact of biofilm formation in NSTI caused by S. pyogenes on clinical outcomes remains uncertain.

Racial and Socioeconomic Disparities in Necrotizing Soft-Tissue Infection

Background: Necrotizing soft-tissue infection (NSTI) is a medical emergency. We investigated the impact of racial, socioeconomic disparities, and comorbidities on mortality, complications, length of stay, and charges in patients with NSTI. Methods: Data were acquired from the National Inpatient Sample from Q4 2015 to 2017. ICD-10, Clinical Modification codes were utilized to identify relevant cases. Logistic regression was used to assess socioeconomic, racial, and health risk factors for adverse outcomes in NSTI patients. Results: Of 16,071,053 cases identified during the study period, 15,078 (0.094%) NSTI cases were recognized. Black patients had increased odds of amputation (OR 1.40 95% CI 1.24–1.58, p < 0.001), prolonged hospital stay (OR 1.40 95% CI 1.24–1.58, p < 0.001), excessive charges (OR 1.22 95% CI 1.03–1.43, p = 0.019), and adverse discharge disposition (OR 1.32 95% CI 1.19–1.46, p < 0.001) compared to white patients. Hispanic patients had increased odds of mortality (OR 1.30 95% CI 1.05–1.60, p = 0.014) and amputation (OR 1.21 95% CI 1.04–1.42, p = 0.016) compared to white patients. Medicare patients had increased odds of mortality (OR 1.35 95% CI 1.09–1.67, p = 0.006), Medicaid patients had increased odd of amputation (OR 1.33 95% CI 1.17–1.51, p < 0.001) and prolonged LOS (OR 1.33 95% CI 1.17–1.51, p < 0.001). Patients in the lower income quartiles had decreased odds of amputation compared to the highest income quartile, including the 26th to 50th income quartile (OR 0.84 95% CI 0.73–0.98, p = 0.022) and 51st to 75th income quartile (OR 0.84 95% CI 0.73–0.98, p = 0.022). Conclusions: Racial and socioeconomic disparities exist for patients being treated for NSTIs.

The impact of operative time on the outcomes of necrotizing soft tissue infections: a multicenter cohort study

BackgroundThe primary aim of this study was to identify if there is an association between the operative time of the initial debridement for necrotizing soft tissue infections (NSTIs) and the mortality corrected for disease severity.MethodsA retrospective multicenter study was conducted of all patients with NSTIs undergoing surgical debridement. The primary outcome was the 30-day mortality. The secondary outcomes were days until death, length of intensive care unit (ICU) stay, length of hospital stay, number of surgeries within first 30 days, amputations and days until definitive wound closure.ResultsA total of 160 patients underwent surgery for NSTIs and were eligible for inclusion. Twenty-two patients (14%) died within 30 days and 21 patients (13%) underwent an amputation. The median operative time of the initial debridement was 59 min (IQR 35–90). In a multivariable analyses, corrected for sepsis just prior to the initial surgery, estimated total body surface (TBSA) area affected and the American Society for Anesthesiologists (ASA) classification, a prolonged operative time (per 20 min) was associated with a prolonged ICU (β 1.43, 95% CI 0.46–2.40; p = 0.004) and hospital stay (β 3.25, 95% CI 0.23–6.27; p = 0.035), but not with 30-day mortality. Operative times were significantly prolonged in case of NSTIs of the trunk (p = 0.044), in case of greater estimated TBSA affected (p = 0.006) or if frozen sections and/or Gram stains were assessed intra-operatively (p < 0.001).ConclusionsProlonged initial surgery did not result in a higher mortality rate, possible because of a short duration of surgery in most studied patients. However, a prolonged operative time was associated with a prolonged ICU and hospital stay, regardless of the estimated TBSA affected, presence of sepsis prior to surgery and the ASA classification. As such, keeping operative times as limited as possible might be beneficial for NSTI patients.

Association between adjunct clindamycin and in-hospital mortality in patients with necrotizing soft tissue infection due to group A Streptococcus: a nationwide cohort study.

Necrotizing soft tissue infection (NSTI) due to group A Streptococcus (GAS) is a severe life-threatening microbial infection. The administration of adjunct clindamycin has been recommended in the treatment of NSTIs due to GAS. However, robust evidence regarding the clinical benefits of adjunct clindamycin in NSTI patients remains controversial. We aimed to investigate the association between early administration of adjunct clindamycin and in-hospital mortality in patients with NSTI attributed to GAS. The present study was a nationwide retrospective cohort study, using the Japanese Diagnosis Procedure Combination inpatient database focusing on the period between 2010 and 2018. Data was extracted on patients diagnosed with NSTI due to GAS. We compared patients who were administered clindamycin on the day of admission (clindamycin group) with those who were not (control group). A propensity score overlap weighting method was adopted to adjust the unbalanced backgrounds. The primary endpoint was in-hospital mortality and survival at 90days after admission. We identified 404 eligible patients during the study period. After adjustment, patients in the clindamycin group were not significantly associated with reduced in-hospital mortality (19.2% vs. 17.5%; odds ratio, 1.11; 95% confidence interval, 0.59-2.09; p = 0.74) or improved survival at 90days after admission (hazard ratio, 0.92; 95% confidence interval, 0.51-1.68; p = 0.80). In this retrospective study, early adjunct clindamycin does not appear to improve survival. Therefore, the present study questions the benefits of clindamycin as an adjunct to broad spectrum antibiotics in patients with NSTI due to GAS.

Impact of prior antibiotic therapy on severe necrotizing soft-tissue infections in ICU patients: results from a French retrospective and observational study

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.

Antibiotics in Necrotizing Soft Tissue Infections.

Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections characterized by an extensive necrosis of skin and subcutaneous tissues. Initial urgent management of NSTIs relies on broad-spectrum antibiotic therapy, rapid surgical debridement of all infected tissues and, when present, treatment of associated organ failures in the intensive care unit. Antibiotic therapy for NSTI patients faces several challenges and should (1) carry broad-spectrum activity against gram-positive and gram-negative pathogens because of frequent polymicrobial infections, considering extended coverage for multidrug resistance in selected cases. In practice, a broad-spectrum beta-lactam antibiotic (e.g., piperacillin-tazobactam) is the mainstay of empirical therapy; (2) decrease toxin production, typically using a clindamycin combination, mainly in proven or suspected group A streptococcus infections; and (3) achieve the best possible tissue diffusion with regards to impaired regional perfusion, tissue necrosis, and pharmacokinetic and pharmacodynamic alterations. The best duration of antibiotic treatment has not been well established and is generally comprised between 7 and 15 days. This article reviews the currently available knowledge regarding antibiotic use in NSTIs.

Necrotizing Soft Tissue Infections, the Challenge Remains.

Background: Necrotizing Soft Tissue Infections (NSTIs) are uncommon rapidly spreading infection of the soft tissues for which prompt surgical treatment is vital for survival. Currently, even with sufficient awareness and facilities available, ambiguous symptoms frequently result in treatment delay.Objectives: To illustrate the heterogeneity in presentation of NSTIs and the pitfalls entailing from this heterogeneity.Discussion: NSTI symptoms appear on a spectrum with on one side the typical critically ill patient with fast onset and progression of symptoms combined with severe systemic toxicity resulting in severe physical derangement and sepsis. In these cases, the suspicion of a NSTI rises quickly. On the other far side of the spectrum is the less evident type of presentation of the patient with gradual but slow progression of non-specific symptoms over the past couple of days without clear signs of sepsis initially. This side of the spectrum is under represented in current literature and some physicians involved in the care for NSTI patients are still unaware of this heterogeneity in presentation.Conclusion: The presentation of a critically ill patient with evident pain out of proportion, erythema, necrotic skin and bullae is the classical presentation of NSTIs. On the other hand, non-specific symptoms without systemic toxicity at presentation frequently result in a battery of diagnostics tests and imaging before the treatment strategy is determined. This may result in a delay in presentation, delay in diagnosis and delay in definitive treatment. This failure to perform an adequate exploration expeditiously can result in a preventable mortality.

Long-term quality of life in necrotizing soft-tissue infection survivors: a monocentric prospective cohort study

BackgroundCompared to other life-threatening infection survivors, long-term health-related quality of life (QOL) of patients surviving necrotizing soft-tissue infections (NSTI) and its determinants are little known.In this monocentric prospective cohort including NSTI survivors admitted between 2014 and 2017, QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36), the Hospital Anxiety and Depression (HAD), the activity of daily living (ADL), instrumental ADL (IADL) scales and the Impact of Event Scale-Revised (IES-R). The primary outcome measure was the SF-36 physical component summary (PCS). NSTI patients were compared according to intensive care unit (ICU) admission status. ICU survivors were matched on SAPS II with non-NSTI related septic shock survivors.ResultsForty-nine NSTI survivors were phone-interviewed and included in the study. Median PCS was decreased compared to the reference population [− 0.97 (− 2.27; − 0.08) SD]. Previous cardiac disease was the only variable associated with PCS alteration [multivariate regression coefficient: − 8.86 (− 17.64; − 0.07), p = 0.048]. Of NSTI survivors, 15.2% had a HAD-D score ≥ 5 and 61.2% an IES-R score ≥ 33. ICU admission was not associated with lower PCS [35.21 (25.49–46.54) versus (vs) 41.82 (24.12–51.01), p = 0.516], but with higher IES-R score [14 (7.5–34) vs 7 (3–18), p = 0.035] and a higher proportion of HAD-D score ≥ 5 (28.6 vs 4.0%, p = 0.036). Compared to non-NSTI septic shock-matched controls, NSTI patients had similar PCS [33.81 (24.58; − 44.39) vs 44.87 (26.71; − 56.01), p = 0.706] but higher HAD-D [3.5 (1–7) vs 3 (1.5–6), p = 0.048] and IES-R scores [18 (8–35) vs 8 (3–19), p = 0.049].ConclusionsLong-term QOL in NSTI survivors is severely impaired, similarly to that of non-NSTI septic shock patients for physical compartments, but with more frequent depressive and/or post-traumatic stress disorders. Only ICU admission and previous cardiac disease were predictive of QOL impairment.

Pathogenetic and Prognostic Significance of Thrombocytopenia in Patients With Necrotizing Soft Tissue Infections

Necrotizing soft tissue infection (NSTI) is a severe surgical infection which can result in sepsis and septic shock when generalized.The aim of the study was to determine the frequency of thrombocytopenia in patients with generalized NSTI, the factors promoting its development, and its association with septic shock.Materials and Methods. We examined 129 patients with NSTI treated between 09.2015 and 12.2019 at St. George Hospital in St. Petersburg, Russia. Surgical treatment, hematological and biochemical examinations, and bacteriological analysis of blood and wound discharge were performed in each patient. The studied group included 22 patients with systemic inflammatory reaction syndrome, 63 patients with sepsis, and 44 patients with septic shock.Results. We found a decrease in platelet count in NSTI patients with septic shock as early as on the first day of the disease and its further decrease within the next 3 days, with the mean platelet volume (MPV) increasing during the same period and significantly exceeding that in patients with sepsis and systemic inflammatory response syndrome. In NSTI patients with thrombocytopenia on admission, we found a significant correlation between the platelet count and the percentage of segmented neutrophils (r=0.349; P&lt;0.001; n=40). The maximum incidenсe of septic shock was observed in patients infected with Klebsiella pneumoniae (13 out of 19, 65%). These patients had the highest MPV but did not develop thrombocytopenia. Maximum frequency of thrombocytopenia and elevation of MPV and platelet distribution width (PDW) was found in patients with NSTI and underlying chronic viral hepatitis C. However, the relative frequency of septic shock in these patients was not increased.Conclusion. The development of septic shock in NSTI is associated with a specific platelet activation pattern

Factors associated with mortality among patients with necrotizing soft tissue infections: An analysis of 4597 cases using the Diagnosis Procedure Combination Database

ObjectiveThis study aimed to determine the factors associated with mortality among patients with necrotizing soft tissue infection (NSTI) in Japan using inpatient data from the Diagnosis Procedure Combination (DPC) Database. MethodsWe conducted a cross-sectional study using a population retrieved from the Japanese DPC inpatient database of patients who underwent surgical operations from 2014 through 2017. The associations between the covariates and mortality were estimated using multivariate logistic regression models. ResultsIn total, 4597 patients were registered in this study, with an overall mortality rate of 6.9%. Multilevel logistic regression analysis revealed that higher age, lower body mass index (BMI < 18.5 kg/m2), pre-existing cancer diagnosis, sepsis at admission, maintenance dialysis, antithrombin III use, and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotic use were associated with a high mortality rate among NSTI patients. However, sex, underlying diabetes mellitus, ambulance use at admission, intravenous immunoglobulin use, higher hospital case volume, and frequency of operations were not associated with mortality. ConclusionThis study is the first to report the association of lower BMI, antithrombin III use, and anti-MRSA antibiotic use with a higher mortality rate among NSTI patients.