[Wounds after necrotizing soft tissue infections: the treatment options]. / Wonden na een necrotiserende wekedeleninfectie.

Necrotizing soft tissue infection (NSTI) is a life-threatening illness that can seriously harm a person. Over the last years the incidence of NSTI has increased. A rapid and thorough debridement is crucial to let patients survive. After this debridement, patients will often end up with large skin defects. A burn center is specialized in treating skin defects. Patients with large skin defects after the acute phase of NSTI can be referred to this for a multidisciplinary approach. In this article we describe the surgical treatment of the complex wounds of three referred patients with NSTI in our burn center.

Dihydrothiazolo ring-fused 2-pyridone antimicrobial compounds treat Streptococcus pyogenes skin and soft tissue infection.

We have developed GmPcides from a peptidomimetic dihydrothiazolo ring-fused 2-pyridone scaffold that has antimicrobial activities against a broad spectrum of Gram-positive pathogens. Here, we examine the treatment efficacy of GmPcides using skin and soft tissue infection (SSTI) and biofilm formation models by Streptococcus pyogenes. Screening our compound library for minimal inhibitory (MIC) and minimal bactericidal (MBC) concentrations identified GmPcide PS757 as highly active against S. pyogenes. Treatment of S. pyogenes biofilm with PS757 revealed robust efficacy against all phases of biofilm formation by preventing initial biofilm development, ceasing biofilm maturation and eradicating mature biofilm. In a murine model of S. pyogenes SSTI, subcutaneous delivery of PS757 resulted in reduced levels of tissue damage, decreased bacterial burdens, and accelerated rates of wound healing, which were associated with down-regulation of key virulence factors, including M protein and the SpeB cysteine protease. These data demonstrate that GmPcides show considerable promise for treating S. pyogenes infections.

Pathogenomic profile and clonal diversity of potential zoonotic MRSA-CC7-ST789-t091-SCCmecV from human skin and soft tissue infections.

The whole genome sequence (WGS) of prevalent MRSA strains harboring mecA gene obtained from skin and soft tissue infections (SSTIs) in Nigerian hospitals were profiled for pathogenomic structure and evaluated for clonal diversity. The two MRSA strains identified among 66 isolated multi-drug resistant S. aureus from a collection of 256 clinical samples were phenotyped for antibiotic resistance and genotyped for mecA, SCCmec, and spa types. The mecA positive MRSA was analysed using whole-genome sequencing for resistomes, virulomes, phylogenomic profiles and clonal diversity. The identified MRSA-CC7-ST789-t091-SCCmecV strains from a female child (aged 1 year) with severe otorrhea and an adult male (aged 23) with purulent wound abscess showed high-level resistance to streptomycin, vancomycin, kanamycin, sulfamethoxazole and ciprofloxacin. Both strains harbored abundant resistomes, inherent plasmids, chromosomal replicons and typical seven housekeeping genes (arc3, aroE4, glpF1, gmk4, pta4, tpi6, yqiL3). The most abundant putative virulomes were pathogenesis-associated proteins (included hemolysin gamma, leucocidins, proteases, staphylococcal superantigen/enterotoxin-like genes (Set/Ssl), capsule- and biofilm-associated genes, and hyaluronate lyase). Comparative phylogenomic analysis revealed the relatedness of the two clonal strains with prevalent MRSA-CC7 pathotypes observed in Italy (2013 and 2014), Denmark (2014), Thailand (2015 and 2016), USA (2018), and Nigeria (2016 and 2020); and share high genetic similarities with livestock strains from cow milk and cattle. Identified MRSA-CC7-ST789-t091-SCCmecV pathotypes implicated in SSTIs from Nigeria harboring repertoires of antibiotic resistance and virulence genes, and genetic relatedness with livestock strains; show the possibility of gene transfer between animal and human. Adequate hospital MRSA infection control and geno-epidemiological surveillance for animal and human transfer is required.

[Necrotizing soft tissue infections]. / Nekrotisierende Weichgewebsinfektionen.

Necrotizing soft tissue infections are a heterogeneous group of severe infections of the skin, connective tissue and muscles in which necrotic destruction of the tissue occurs at the site of infection. Various bacteria are known as "typical" triggering pathogens and the infection can occur on the entire surface of the body. Necrotizing soft tissue infections are always a time-sensitive emergency associated with high mortality. Many affected patients are critically ill and require treatment in an intensive care unit. The rapid and radical surgical treatment is an essential part of management and in addition an adequate and timely antimicrobial treatment is of great importance. The health consequences for surviving patients are often severe, as extensive soft tissue damage leads to functional impairments. In many cases extensive plastic surgery follow-up is necessary. Therefore, necrotizing soft tissue infections are "complicated" in every phase of the disease and require interprofessional treatment. This review article provides a current overview of various aspects of the diagnostics, treatment and aftercare of necrotizing soft tissue infections.

Pathogenic Detection by Metagenomic Next-generation Sequencing in Skin and Soft Tissue Infection.

BACKGROUND/AIM: Skin and soft tissue infections (SSTIs) can be life-threatening, but the conventional bacterial cultures have low sensitivity and are time-consuming. Metagenomic next-generation sequencing (mNGS) is widely used as a diagnostic tool for detecting pathogens from infection sites. However, the use of mNGS for pathogen detection in SSTIs and related research is still relatively limited. PATIENTS AND METHODS: From January 2020 to October 2021, 19 SSTI samples from 16 patients were collected in a single center (Taichung Veterans General Hospital, Taichung, Taiwan). The clinical samples were simultaneously subjected to mNGS and conventional bacterial culture methods to detect pathogens. Clinical characteristics were prospectively collected through electronic chart review. The microbiological findings from conventional bacterial culture and mNGS were analyzed and compared. RESULTS: The mNGS method detected a higher proportion of multiple pathogens in SSTIs compared to conventional bacterial culture methods. Pseudomonas spp. was among the most commonly identified Gram-negative bacilli using mNGS. Additionally, the mNGS method identified several rare pathogens in patients with SSTIs, including Granulicatella adiacens, Bacillus thuringiensis, and Bacteroides fragilis. Antimicrobial resistance genes were detected in 10 samples (52.6%) using the mNGS method, including genes for extended-spectrum beta-lactamase, Ambler class C ß-lactamases, and carbapenemase. CONCLUSION: mNGS not only plays an important role in the detection of pathogens in soft tissue infections, but also informs clinical professionals about the presence of additional microbes that may be important for treatment decisions. Further studies comparing conventional pathogen culture with the mNGS method in SSTIs are required.

Recurrent skin and soft tissue infections (SSTIs) in three family members caused by methicillin-resistant Staphylococcus aureus (MRSA) with Panton-Valentine leukocidin (PVL) exotoxin.

Three family members attended their general practice and emergency department over a 3-month period with recurrent skin and soft tissue infections (SSTIs) such as paronychia, submandibular carbuncle and groin and gluteal abscess requiring surgical drainage. Only when two family members were concurrently admitted with abscesses requiring drainage under general anaesthetic was the definitive diagnosis reached. The wound swabs identified methicillin-resistant Staphylococcus aureus (MRSA) and subsequent identification of the exotoxin Panton-Valentine leukocidin (PVL). Following MRSA decolonisation therapy with mupirocin and octenidine, only one family member has had one recurrence of an SSTI with MRSA isolated from the wound. When patients present with a history of recurrent SSTIs or a family all have had similar presentations, the clinician should consider MRSA with PVL exotoxin infection. Then patients must be referred for confirmation to ensure management is effective for the SSTI and prescribe MRSA decolonisation therapy concurrently to reduce recurrence.

The interplay between diabetes Mellitus and soft tissue infections in general surgical patients.

BACKGROUND: Diabetes mellitus (DM) is a worldwide pandemic affecting 500 million people. It is known to be associated with increased susceptibility to soft tissue infections (STI). Despite being a major public health burden, the literature relating the effects of DM and the presentation, severity and healing of STIs in general surgical patients remain limited. METHOD: We conducted a retrospective review of all patients admitted with STI in a tertiary teaching hospital over a 12-month period. Patient demographics and surgical outcomes were collected and analysed. RESULTS: During the study period, 1059 patients were admitted for STIs (88% required surgery). DM was an independent risk factor for LOS. Diabetic patients presented with higher body-mass index (28 vs. 26), larger abscess size (24 vs. 14 cm2) and had a longer length of stay (4.4 days vs. 2.9 days). They also underwent a higher proportion of wide debridement and application of negative pressure wound therapy (42% vs. 35%). More diabetic patients underwent subsequent re-operation within the same sitting (8 vs. 4). Diabetic patients were two times more likely to present with carbuncles (p = 0.02). CONCLUSION: The incidence of STIs among DM patients represent a significant disease burden, surgeons should consider intensive patient counselling and partnering with primary care providers in order to help reduce the incidence of future STI admissions based upon lifestyle modification and glucose control.

The bacterial profile and antibiotic susceptibility in skin and soft tissue infections at a tertiary care hospital of Quetta, Pakistan.

Objectives: To determine the bacterial profile and antibiotic susceptibility in skin and soft tissue infections among patients in a tertiary care setting. METHODS: The cross-sectional cohort study was conducted at the Centre for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan, Quetta, Pakistan, from June 2021 to May 2022, and comprised bacteriainfected skin samples that were collected from the Bolan Medical Complex Hospital, Quetta, and the Sandeman Provincial Hospital, Quetta. The swab samples were immediately cultured, and positive samples were evaluated for biochemical tests, antibiotic susceptibility test and polymerase chain reaction. Data was analysed using SPSS 22. RESULTS: Of the 800 samples, 598(74.7%) tested positive for pathogenic bacteria. Staphylococcus aureus accounted for 316(39.5%) infections, followed by clostridium perfringens 18.96(2.37%), escherichia coli 120(15.12%), pseudomonas aeruginosa 98(12.25%) and klebsiella pneumoniae 44(5.5%). Among all the infected samples, 380(47.5%) belonged to males, 218(27.25%) to patients aged 5-20 years, 448(56%) to the uneducated subjects, and 462(57.87%) to patients having lower socioeconomic status. Pseudomonas aeruginosa showed the highest level of resistance against all antibiotics. Conclusion: Regular surveillance and proper use of antibiotics should be encouraged in hospitals to limit the spread of antibiotic resistance against pathogenic bacteria.

Pelvic Necrosis with Formation of a Pelvic "Cloaca" and Necrotizing Soft Tissue Infection After Radiation for Anal Squamous Cell Carcinoma.

BACKGROUND Anal squamous cell carcinoma (SCC) is a rare cancer commonly treated with the Nigro protocol, which combines chemotherapy and radiation. Patients who received radiation therapy prior to modern advances, such as computer-based tumor targeting, volumetric planning, and intensity-modulated radiation therapy, experience more acute and chronic adverse effects. Though exceedingly rare, radiation necrosis is of particular concern, as it can result in significant morbidity and mortality, including complex pelvic fistula formation and predisposition to potentially life-threatening necrotizing soft-tissue infections. CASE REPORT Here, we present a case of a 66-year-old woman with a prior history of anal SCC stage T3N×M0 who was treated with the Nigro protocol. Her treatment course was complicated by radiation proctitis, necessitating fecal diversion and ureteral strictures, requiring frequent stent exchanges. She presented 18 years after her cancer treatment, with widespread necrosis of her pelvic organs and surrounding soft tissue, resulting in formation of a large pelvic "cloaca", with a superimposed necrotizing soft-tissue infection. She was successfully treated by expedited resuscitation, septic source control, using multiple extensive debridements, and complete urinary diversion, utilizing a multidisciplinary team. CONCLUSIONS This case highlights the importance of monitoring patients for signs of radiation toxicity, particularly in patients who received radiation prior to the latest technological advancements, as they are at increased risk of developing severe, late adverse effects decades after treatment. When these complications are recognized, early and aggressive intervention is required to spare the patient significant morbidity and mortality.

Association between Insurance Status and Outcomes of Hospitalizations for Necrotizing Soft Tissue Infections.

Background: Lack of insurance is associated with poorer outcomes in hospitalized patients. However, few studies have explored this association in hospitalizations for necrotizing soft tissue infections (NSTIs). This study examined the impact of insurance status on the outcome of NSTI admissions. Methods: All adult hospitalizations for necrotizing fasciitis, gas gangrene, and Fournier gangrene between 2016 and 2018 were examined using the Nationwide Inpatient Sample database. Insurance status was categorized as insured (including Medicare, Medicaid, and Private, including Health maintenance organization (HMO) or uninsured (Self-pay). Outcome measures included mortality rates, limb loss, length of hospital stay, prolonged hospital stay, and critical care admissions. Statistical analysis included weighted sample analysis, chi-square tests, multivariate regression analysis, and negative binomial regression modeling. Results: Approximately 29,705 adult hospitalizations for NSTIs were analyzed. Of these, 57.4% (17,065) were due to necrotizing fasciitis, 22% (6,545) to gas gangrene, and 20.5% (6,095) to Fournier gangrene. Approximately 9.7% (2,875) were uninsured, whereas 70% (26,780) had insurance coverage. Among the insured, Medicare covered 39.6% (10,605), Medicaid 29% (7,775), and private insurance 31.4% (8,400). After adjustments, Medicare insurance was associated with greater odds of mortality (adjusted odds ratio [aOR]: 1.81; 95% confidence interval [CI]: 1.33-2.47; p = 0.001). Medicaid insurance was associated with increased odds of amputation (aOR: 1.81; 95% CI: 1.33-2.47; p < 0.001), whereas private insurance was associated with lower odds of amputation (aOR: 0.70; 95% CI: 0.51-0.97; p = 0.030). Medicaid insurance was associated with greater odds of prolonged hospital stay (aOR: 1.34; 95% CI: 1.09-1.64; p < 0.001). No significant association was observed between the lack of insurance or self-pay and the odds of primary or secondary outcomes. Conclusion: Medicare insurance was correlated with greater odds of mortality, whereas Medicaid insurance was associated with increased odds of amputation and longer hospital stay. Uninsured status was not associated with significant differences in NSTI outcomes.

Mapping the evidence about the natural history of acute infections commonly seen in primary care and managed with antibiotics: a scoping review.

BACKGROUND: Knowing the natural history of acute infections in primary care, defined as the course of a disease over time in the absence of specific therapy or treatment, can inform clinicians' and patients' expectations about illness recovery, but this evidence is fragmented across the literature. This scoping review aimed to map existing research and research gaps relevant to the natural history of acute infections. METHODS: We searched MEDLINE, Embase and CENTRAL using a 2-phase hierarchical search approach. In Phase A, we focused on identifying systematic reviews synthesising natural history data for eligible infections (acute respiratory, urinary, and skin and soft tissue) and systematic reviews of treatment effectiveness (of RCTs with placebo or no treatment arm, or cohort studies). For infections without existing reviews, in Phase B, we searched for primary studies (placebo-controlled RCTs or cohort studies). Two reviewers independently screened and extracted the data (study characteristics, outcome data - e.g., symptom duration, proportion with resolution at various time points). RESULTS: We identified 40 systematic reviews, reporting on 45 infections, most commonly (90%) respiratory tract infections. Six (15%) of these aimed to synthesise natural history information. Most reviews reported the proportion of participants with symptom resolution at various time point/s, with 58% providing data on mean symptom duration. Recovery data show the spontaneous resolution of some infections in some people. We found no eligible studies for cellulitis, ecthyma, carbuncle, and erysipelas. CONCLUSIONS: Our review has shown that natural history evidence exists for many common acute infections. It can be utilised by clinicians in implementing patient-centred antibiotic stewardship strategies in primary care. Future research should focus on generating natural history evidence for skin and soft tissue infections and urinary tract infections.

When less is more: the art of communicating clinical microbiology results.

The clinical microbiology laboratory is capable of identifying microorganisms in clinical specimens faster and more accurately than ever before. At face value, this should enable patient care providers to make better-informed decisions and target antimicrobial therapies to deliver individualized care. Ironically, more complete and specific reporting of microorganisms isolated from specimens may result in overtreatment based on the presence of a pathogen, even in the absence of clear signs of clinical infection. This conundrum calls into question the role of the laboratory in contributing to care through selective or "exception" reporting whereby some results are selectively withheld when there is a low probability that laboratory findings correlate with the clinical infection. In a recent article published in the Journal of Clinical Microbiology, Bloomfield et al. (J Clin Microbiol 62:e00342-24, 2024, https://doi.org/10.1128/jcm.00342-24) examine the impact and safety of an exception reporting strategy applied to wound swab specimens. Canonical pathogens associated with skin and soft tissue infections including S. aureus and beta-hemolytic streptococci are withheld from the laboratory report if certain patient criteria are met that would put them at low risk of adverse outcomes if untreated, or if treated with guideline-recommended empiric therapy. Their central finding was an approximately 50% reduction in post-laboratory report antibiotic initiation without adverse events or increased 30-day admission rate (indicative of infection-related complications, e.g., disseminated disease). While effectively achieving their goal, the premise of exception reporting and other modified reporting strategies raises questions about the potential risk of underreporting and how to ensure that the message is being interpreted, and acted upon, by care providers as was intended by the laboratory.

Glucose transporter 1 is essential for the resolution of methicillin-resistant S. aureus skin and soft tissue infections.

Skin/soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) pose a major healthcare burden. Distinct inflammatory and resolution phases comprise the host immune response to SSTIs. Resolution is a myeloid PPARγ-dependent anti-inflammatory phase that is essential for the clearance of MRSA. However, the signals activating PPARγ to induce resolution remain unknown. Here, we demonstrate that myeloid glucose transporter 1 (GLUT-1) is essential for the onset of resolution. MRSA-challenged macrophages are unsuccessful in generating an oxidative burst or immune radicals in the absence of GLUT-1 due to a reduction in the cellular NADPH pool. This translates in vivo as a significant reduction in lipid peroxidation products required for the activation of PPARγ in MRSA-infected mice lacking myeloid GLUT-1. Chemical induction of PPARγ during infection circumvents this GLUT-1 requirement and improves resolution. Thus, GLUT-1-dependent oxidative burst is essential for the activation of PPARγ and subsequent resolution of SSTIs.

Clinical outcomes in people with diabetes-related foot infections: Analysis from a limb preservation service infection database.

BACKGROUND: Diabetes-related foot infections are common and represent a significant clinical challenge. There are scant data about outcomes from large cohorts. The purpose of this study was to report clinical outcomes from a large cohort of people with diabetes-related foot infections. METHODS: A tertiary referral hospital limb preservation service database was established in 2018, and all new episodes of foot infections were captured prospectively using an electronic database (REDCap). People with foot infections between January 2018 and May 2023, for whom complete data were available on infection episodes, were included. Infection outcomes were compared between skin and soft tissue infections (SST-DFI) and osteomyelitis (OM) using chi-square tests. RESULTS: Data extraction identified 647 complete DFI episodes in 397 patients. The data set was divided into two cohorts identifying each infection episode and its severity as either SST-DFI (N = 326, 50%) or OM (N = 321, 50%). Most infection presentations were classified as being moderate (PEDIS 3 = 327, 51%), with 36% mild (PEDIS 2 = 239) and 13% severe (PEDIS 4 = 81). Infection resolution occurred in 69% (n = 449) of episodes with failure in 31% (n = 198). Infection failures were more common with OM than SST-DFI (OM = 140, 71% vs. SST-DFI = 58, 29%, p < 0.00001). In patients with SST-DFI a greater number of infection failures were observed in the presence of peripheral arterial disease (PAD) compared to the patients without PAD (failure occurred in 30% (31/103) of episodes with PAD and 12% (27/223) of episodes without PAD; p < 0.001). In contrast, the number of observed infection failures in OM episodes were similar in patients with and without PAD (failure occurred in 45% (57/128) of episodes with PAD and 55% (83/193) of episodes without PAD; p = 0.78). CONCLUSIONS: This study provides important epidemiological data on the risk of poor outcomes for DFI and factors associated with poor outcomes in an Australian setting. It highlights the association of PAD and treatment failure, reinforcing the need for early intervention to improve PAD in patients with DFI. Future randomised trials should assess the benefits of revascularisation and surgery in people with DFI and particularly those with OM where outcomes are worse.

Temporal trends of skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus in Gabon.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of mortality due to bacterial antimicrobial resistance. While S. aureus is common in skin and soft tissue infections (SSTI) in Africa, data on MRSA rates are scarce and reports vary widely across the continent (5%-80%). In this study, we describe the proportion of MRSA causing SSTI in Lambaréné, Gabon, over an 11-year period. METHODS: We retrospectively analyzed data from 953 bacterial specimens collected from inpatients and outpatients with SSTI at the Albert Schweitzer Hospital, Lambaréné, Gabon, between 2009 and 2019. We determined temporal changes in the prevalence of MRSA and identified risk factors for SSTI with MRSA. RESULTS: 68% of all specimens with bacterial growth yielded S. aureus (n = 499/731), of which 7% (36/497) with antimicrobial susceptibility testing were identified as MRSA. Age above 18 years, admission to the surgical ward, and deep-seated infections were significantly associated with MRSA as the causative agent. After an initial decline from 7% in 2009, there was a marked increase in the proportion of MRSA among all S. aureus from SSTI from 3 to 20% between 2012 and 2019. The resistance rate to erythromycin was significantly higher in MRSA than in methicillin-susceptible S. aureus (73% vs. 10%), and clindamycin resistance was detected exclusively in MRSA isolates (8%). CONCLUSION: The increasing proportion of MRSA causing SSTI over the 11-year period contrasts with many European countries where MRSA is on decline. Continuous surveillance of MRSA lineages in the hospital and community along with antibiotic stewardship programs could address the increasing trend of MRSA.

Exploring therapeutic options for mild diabetic-related foot infections: a comparative in vitro study of cefditoren versus amoxicillin/clavulanic acid.

Skin and soft tissue infections (SSTIs), and particularly diabetic-related foot infections (DFI), present diagnostic and therapeutic complexities, often leading to severe complications. This study aims to evaluate the in vitro efficacy of cefditoren and amoxicillin/clavulanic acid against typical DFI pathogens. Clinical samples from 40 patients with mild SSTIs were analyzed, revealing a predominance of Staphylococcus spp. and Streptococcus spp. species. Cefditoren exhibited activity against 90% of isolates, with superior potency over amoxicillin/clavulanic acid. These findings underscore the utility of cefditoren in empirical treatment of DFI, although a larger sample size would be desirable for further validation.