Necrotizing Skin Infections Research Articles

Treating necrotizing skin and soft-tissue infections.

Treating necrotizing skin and soft-tissue infections.

Profiling Mycobacterium ulcerans: sporulation, survival strategy and response to environmental factors.

Mycobacterium ulcerans is the causative agent of Buruli ulcer - a necrotizing skin infection. As an environmental pathogen, it has developed stress response mechanisms for survival. Similar to endospore formation in M. marinum, it is likely that M. ulcerans employs sporulation mechanisms for its survival and transmission. In this review, we modeled possible transmission routes and patterns of M. ulcerans from the environment to its host. We provided insights into the evolution of M. ulcerans and its genomic profiles. We discuss reservoirs of M. ulcerans as an environmental pathogen and its environmental survival. We comprehensively discuss sporulation as a possible stress response mechanism and modelled endospore formation in M. ulcerans. At last, we highlighted sporulationassociated markers, which upon expression trigger endospore formation.

Rational Use of Ceftriaxone in Necrotizing Fasciitis and Mortality Associated with Bloodstream Infection and Hemorrhagic Bullous Lesions.

Necrotizing fasciitis (NF) is an uncommon life-threatening necrotizing skin and soft tissue infection. The formation of hemorrhagic bullae is a special skin sign of NF. The purposes of this study were to investigate the incidence of hemorrhagic bullae formation and bacteremia associated with different organisms, to appraise the appropriate use of ceftriaxone, and to compare the clinical and laboratory risk indicators of NF patients with Gram-positive and Gram-negative infections on the initial examination. Methods: From March 2018 to December 2020, there were seventy-four NF patients with positive monomicrobial bacterial cultures enrolled based on surgical confirmation, and were categorized into two groups: the Gram-positive group and the Gram-negative group. Ceftriaxone susceptibility tests were carried out using the standard disk diffusion technique. Data, such as demographics, clinical outcomes, microbiological results, presentations of hemorrhagic bullae, and laboratory findings, were compared among these two groups. Results: The Gram-negative group included 52 patients, of whom 6 patients died, resulting in a mortality rate of 11.5%. The Gram-positive group included 22 patients and none died. Patients with bacteremia, hemorrhagic bullae, shock, fever, higher segmented forms and banded forms, and lower platelet counts constituted higher proportions in the Gram-negative group than in the Gram-positive group. The multivariate analysis identified six variables for the differentiation of Gram-negative and Gram-positive NF: the presentation of bacteremia, hemorrhagic bullae, shock at first consultation, fever with body temperature > 38.5 °C, band forms > 0%, and segmented forms ≦ 74%. A total of 66 isolates (89.2%) was susceptible to ceftriaxone. Conclusions: Gram-negative NF patients were significantly associated with hemorrhagic bullae presentation, blood stream infection, and mortality. Physicians should be alert to NF patients with the appearance of bacteremia, shock, fever, higher WBC banded and segmented forms, and lower platelet counts at the emergency department, with patients revealed to more likely have Gram-negative infections. Ceftriaxone with/without other appropriate antibiotics under the supervision of infectious doctors appeared to be clinically effective for the treatment of NF and blood stream infections.

Integrated Management Strategies (Diagnosis, Treatment, and Wound Care Management) for Improved Clinical Outcomes of Buruli Ulcer in Ghana: A Retrospective Case Report in the Ga West Municipal Hospital, Amasaman

Buruli ulcer is a necrotizing skin infection caused by Mycobacterium ulcerans. BU lesions may start with characteristic painlessness but most often, the typical presentations of the disease are characterized by large ulcers with undermined edges. If left untreated, BU lesions may result in extensive ulceration that can cover 15% of the body. Even though public sensitization and education have resulted in sufficient and improved knowledge about the etiology of the disease in Ghana, patients still report to health facilities with advanced forms of the disease.

Ecthyma Gangrenosum about a Case at the Centre Hospitalier Roi Baudoin de Guédiawaye in Senegal

Background and Aim: Ecthyma gangrenosum (EG) is a rare necrotic skin infection caused by Pseudomonas aeruginosa occurring on healthy skin mainly, but not exclusively, in immunocompromised patients. We report the case of EG of unusual presentation in a 12-month-old infant. Case Presentation: This was a 12-month-old male infant who was referred from a peripheral structure for the treatment of facial swelling associated with fever. In his antenatal and intra nasal history, there was a notion of hospitalization for 15 days for early neonatal infection and a delay in psychomotor development. The admission examination showed the fair general condition, hyperthermia at 39°C, tachycardia at 136 beats/minute, and polypnea at 48 cycles/minute. The weight-for-height index with a z-score of 3DS was also found. The dermatological examination at the entrance found an extensive brownish inflammatory tense infiltrated plaque taking the mandibular, submental, retro-auricular occipital regions rapidly evolving towards necrosis, a significant swelling predominant on the upper right eyelid preventing the opening of the associated eyes to mouth ulceration. Biological abnormalities were predominantly neutrophilic leukocytosis, elevated CRP, and elevated muscle enzymes. Microbiological examination of skin samples had isolated Pseudomonas aeruginosa. He had received antibiotic therapy, and a necrosectomy under general anesthesia. The evolution was favorable and he was discharged from the hospital on D26 of hospitalization. Conclusion: This observation is rare due to its location, its early onset, and non-neutropenic background.

1361. Actinotignum schaalii an Under-recognized Cause of Infections: A Case Series in Calgary from 2012 - 2020

Abstract Background Actinotignum schaalii is a gram-positive rod that is a fastidious commensal of the urogenital tract. Infections with A. schaalii are underdiagnosed previously because phenotypic methods fail to identify it. Both MALDI-TOF mass spectrometry and 16S rRNA sequencing allow definitive identification of this opportunistic emerging pathogen. A. schaalii is an infrequent but important cause of UTIs in the elderly, particularly with urological abnormalities. The spectrum of invasive disease caused by A. schaalii is not well characterized; however, it has been isolated in severe infections including necrotizing skin and soft tissue infections, bacteremia, osteomyelitis, and endocarditis. We used a population-based approach to characterize and describe the clinical and microbiological features of invasive A. schaalii infections in our region. Methods All adult and pediatric cases enrolled had microbiological isolates of Actinotignum schaalii recovered from blood cultures, sterile fluids and tissue cultures from Jan 2012 to Dec 2020 by APL, a regional centralized microbiology laboratory serving the Calgary Zone in Alberta, Canada. Clinical data were retrieved and linked from administrative health databases, chart review and the laboratory information system. Standard descriptive statistics were used. Results We identified 84 unique A. schaalii infections, 35 were from bloodstream, 32 soft tissue, 7 post-operative infections. Median age and Charslon comorbidity score was higher in BSI. 54.3% of patient with BSI had a genitourinary pathology, with 51.4% caused by a complicated urinary infection, while soft and skin tissue infections caused 65.3% of non-BSI. Using EUCAST MIC cut-offs, 48% and 100% of the isolates were resistant to clindamycin and metronidazole, respectively. In contrast, all specimens were susceptible to penicillin. Hospitalization and 90-days mortality were higher in the BSI group. Conclusion A. schaalii is an anaerobic opportunistic pathogen that can cause life-threatening invasive infections, particularly in older adults with underlying genitourinary pathology. BSI were associated with higher rates of hospitalization and mortality. In contrast, patients with A. schaalii isolated from cutaneous sources were younger and had better clinical outcomes. Disclosures All Authors: No reported disclosures

Lumbar Skin Lesion in a Term Infant.

Lumbar Skin Lesion in a Term Infant.

An Ulcerating Perineal Rash in an 8-month-old Girl.

An Ulcerating Perineal Rash in an 8-month-old Girl.

A large epidemic of a necrotic skin infection in the Democratic Republic of São Tomé and Principe: an epidemiological study

IntroductionIn 2016–18, the Democratic Republic of São Tomé and Príncipe suffered a necrotic skin infection epidemic. MethodsA surveillance system was established after increased hospitalisations for this infection. Microbiology results were available for samples analysed in December 2016 and March 2017 using whole genome sequencing and metagenomics. Negative binomial regression was used to study the association of weather conditions with monthly case counts in a time-series analysis. ResultsFrom October 2016 to October 2018, the epidemic cumulative attack rate was 1.5%. The first peak lasted 5 months, accounting for one-third of total cases. We could not conclusively identify the aetiological agent(s) due to the country's lack of microbiology capacity. Increased relative humidity was associated with increased monthly cases (incidence rate ratio (IRR) 1.05, 95% CI 1.02–1.09), and higher precipitation in the previous month with a higher number of cases in the following month (months with 0–49 mm rainfall compared with months with 50–149 mm and ≥150 mm: IRR 1.44, 95 % CI 1.13–1.78 and 1.50, 95% CI 1.12–1.99, respectively). DiscussionThis epidemic was favoured by increased relative humidity and precipitation, potentially contributing to community-based transmission of ubiquitous bacterial strains superinfecting skin wounds. FundingWorld Health Organization Regional Office for Africa, Ministry of Health

Different types of bullae of limbs with necrotizing fasciitis predict different outcome: a prospective study

Study objectiveNecrotizing fasciitis (NF) is an uncommon life-threatening necrotizing skin and soft tissue infection. Bullae are special skin manifestations of NF. This study was conducted to analyze the differences between different types of bullae of limbs with NF for providing the information to emergency treatment.MethodsFrom April 2015 to August 2018, patients were initially enrolled based on surgical confirmation of limbs with NF. According to the presence of different bullae types, patients were divided into no bullae group (Group N), serous-filled bullae group (Group S), and hemorrhagic bullae group (Group H). Data such as demographics, clinical outcomes, microbiological results, presenting symptoms/signs, and laboratory findings were compared among these groups.ResultsIn total, 187 patients were collected, with 111 (59.4%) patients in Group N, 35 (18.7%) in Group S, and 41 (21.9%) in Group H. Group H had the highest incidence of amputation, required intensive care unit care, and most patients infected with Vibrio species. In Group N, more patients were infected with Staphylococcus spp. than Group H. In Group S, more patients were infected with β-hemolytic Streptococcus than Group H. Patients with bacteremia, shock, skin necrosis, anemia, and longer prothrombin time constituted higher proportions in Group H and S than in Group N.ConclusionsIn southern Taiwan, patients with NF accompanied by hemorrhagic bullae appear to have more bacteremia, Vibrio infection, septic shock, and risk for amputation. If the physicians at the emergency department can detect for the early signs of NF as soon as possible, and more patient’s life and limbs may be saved.

440: Glycemic Control in Patients With a Necrotizing Skin and Soft Tissue Infection

1Vanderbilt University Medical Center, Brentwood, TN 2Vanderbilt University Medical Center, Nashville, TN

Predictors for gram-negative monomicrobial necrotizing fasciitis in southern Taiwan

BackgroundNecrotizing fasciitis (NF) is a rare and life-threatening necrotizing skin and soft-tissue infection. Infectious pathogens of NF must be detected early and treated rapidly to prevent loss of limb or a fatal outcome. This study aimed to detect more reliable predictors between gram-negative and gram-positive monomicrobial NF of limbs.MethodsA total of 100 patients with limb monomicrobial NF were diagnosed prospectively from April 2015 to July 2018. These monomicrobial NF pathogens can be divided into gram-negative and gram-positive groups according to the result of Gram staining and final bacterial reports. Data such as demographics, seawater or seafood contact history, infectious location, comorbidities, presenting signs and symptoms, and laboratory findings were recorded and compared.ResultsA total of 55 patients were infected with gram-negative organisms and 45 patients with gram-positive organisms. Among the 55 cases of monomicrobial gram-negative NF, 48 (87.3%) were caused mainly by Vibrio spp. (38, 69.1%) and Aeromonas spp. (10, 18.2%). A higher incidence of chronic kidney disease, cerebrovascular accident, tachypnea, and septic shock; a higher rate of band forms of leukocytes of more than 3%, serum lactate of more than 20 mg/dL, and C-reactive protein level of less than 150 mg/dL; prolonged prothrombin time; and a lower fibrinogen level were observed in patients with gram-negative infection. In a multivariate analysis, a higher incidence of seawater or seafood contact history (odds ratio [OR]: 66.301; 95% confidence interval [CI]: 7.467–588.702), a higher rate of hyperlactatemia (OR: 7.904; 95% CI: 1.231–50.744), and a low fibrinogen level (OR: 1.013; 95% CI: 1.004–1.023) indicated gram-negative infection.ConclusionsIn southern Taiwan, NF of limbs mainly affected the lower limbs, exhibited monomicrobial infection, and was predominated by gram-negative bacteria. Gram-negative monomicrobial NF of limbs often occurred in individuals with the more seawater or seafood contact history, hyperlactatemia, and low fibrinogen levels.

Functional and Proteomic Analysis of Streptococcus pyogenes Virulence Upon Loss of Its Native Cas9 Nuclease.

The public health impact of Streptococcus pyogenes (group A Streptococcus, GAS) as a top 10 cause of infection-related mortality in humans contrasts with its benefit to biotechnology as the main natural source of Cas9 nuclease, the key component of the revolutionary CRISPR-Cas9 gene editing platform. Despite widespread knowledge acquired in the last decade on the molecular mechanisms by which GAS Cas9 achieves precise DNA targeting, the functions of Cas9 in the biology and pathogenesis of its native organism remain unknown. In this study, we generated an isogenic serotype M1 GAS mutant deficient in Cas9 protein and compared its behavior and phenotypes to the wild-type parent strain. Absence of Cas9 was linked to reduced GAS epithelial cell adherence, reduced growth in human whole blood ex vivo, and attenuation of virulence in a murine necrotizing skin infection model. Virulence defects of the GAS Δcas9 strain were explored through quantitative proteomic analysis, revealing a significant reduction in the abundance of key GAS virulence determinants. Similarly, deletion of cas9 affected the expression of several known virulence regulatory proteins, indicating that Cas9 impacts the global architecture of GAS gene regulation.

Laboratory confirmation of Buruli ulcer cases in Ghana, 2008-2016.

BackgroundBuruli ulcer (BU), a necrotizing skin infection caused by Mycobacterium ulcerans is the third most important mycobacterial disease globally after tuberculosis and leprosy in immune competent individuals. This study reports on the retrospective analyses of microbiologically confirmed Buruli ulcer (BU) cases in seventy-five health facilities in Ghana.Method/Principal findingsPathological samples were collected from BU lesions and transported either through courier services or by car directly to the laboratory. Samples were processed and analysed by IS2404 PCR, culture and Ziehl-Neelsen staining for detection of acid-fast bacilli. From 2008 to 2016, we analysed by PCR, 2,287 samples of 2,203 cases from seventy-five health facilities in seven regions of Ghana (Ashanti, Brong Ahafo, Central, Eastern, Greater Accra, Northern and Volta). The mean annual positivity rate was 46.2% and ranged between 14.6% and 76.2%. The yearly positivity rates from 2008 to 2016 were 52.3%, 76.2%, 56.7%, 53.8%, 41.2%, 41.5%, 22.9%, 28.5% and 14.6% respectively. Of the 1,020 confirmed cases, the ratio of female to male was 518 and 502 respectively. Patients who were 15 years of age and below accounted for 39.8% of all cases. The median age was 20 years (IQR = 10–43). Ulcerative lesions were 69.2%, nodule (9.6%), plaque (2.9%), oedema (2.5%), osteomyelitis (1.1%), ulcer/oedema (9.5%) and ulcer/plaque (5.2%). Lesions frequently occurred on the lower limbs (57%) followed by the upper limbs (38%), the neck and head (3%) and the least found on the abdomen (2%).Conclusions/SignificanceOur findings show a decline in microbiological confirmed rates over the years and therefore call for intensive education on case recognition to prevent over-diagnosis as BU cases decline.

Necrotizing fasciitis caused by Apophysomyces variabilis in an immunocompetent patient

Mucormycosis caused by Apophysomyces variabilis is rarely reported in humans. A case of A. variabilis infection in an immunocompetent men after friction burns in a car accident is described. The infection presented as a rapidly progressive necrotizing infection of the skin and soft tissue, which required extensive surgical debridement and total colonic defunctioning colostomy associated with prolonged antifungal therapy. A. variabilis infection should be considered as a differential diagnosis of rapidly progressive necrotizing skin and soft tissue infections in immunocompetent individuals.

Worsening Necrotic Skin Infection: What Lurks Below.

Worsening Necrotic Skin Infection: What Lurks Below.

A Red Blood Cell Membrane-Camouflaged Nanoparticle Counteracts Streptolysin O-Mediated Virulence Phenotypes of Invasive Group A Streptococcus

Group A Streptococcus (GAS), an important human-specific Gram-positive bacterial pathogen, is associated with a broad spectrum of disease, ranging from mild superficial infections such as pharyngitis and impetigo, to serious invasive infections including necrotizing fasciitis and streptococcal toxic shock syndrome. The GAS pore-forming streptolysin O (SLO) is a well characterized virulence factor produced by nearly all GAS clinical isolates. High level expression of SLO is epidemiologically linked to intercontinental dissemination of hypervirulent clonotypes and poor clinical outcomes. SLO can trigger macrophage and neutrophil cell death and/or the inactivation of immune cell functions, and promotes tissue injury and bacterial survival in animal models of infection. In the present work, we describe how the pharmacological presentation of red blood cell (RBC) derived biomimetic nanoparticles (“nanosponges”) can sequester SLO and block the ability of GAS to damage host cells, thereby preserving innate immune function and increasing bacterial clearance in vitro and in vivo. Nanosponge administration protected human neutrophils, macrophages, and keratinocytes against SLO-mediated cytotoxicity. This therapeutic intervention prevented SLO-induced macrophage apoptosis and increased neutrophil extracellular trap formation, allowing increased GAS killing by the respective phagocytic cell types. In a murine model of GAS necrotizing skin infection, local administration of the biomimetic nanosponges was associated with decreased lesion size and reduced bacterial colony-forming unit recovery. Utilization of a toxin decoy and capture platform that inactivates the secreted SLO before it contacts the host cell membrane, presents a novel virulence factor targeted strategy that could be a powerful adjunctive therapy in severe GAS infections where morbidity and mortality are high despite antibiotic treatment.

Saksenaea erythrospora, an emerging mucoralean fungus causing severe necrotizing skin and soft tissue infections – a study from a tertiary care hospital in north India

Background: Saksenaea erythrospora is an emerging and recently described pathogenic fungus mainly causing invasive cutaneous infections. Globally, very few human cases, caused by S. erythrospora, have been reported. In India, among the genus Saksenaea, S. vasiformis was the only reported pathogenic species, until recently when a case of fungal rhinosinusitis was reported to be caused by S. erythrospora. We observed five human cases of necrotizing skin and soft tissue infections caused by S. erythrospora following traumatic implantation over 1-year study period.Methods: The study was conducted for a year observing the causative role of Saksenaea species in primary cutaneous necrotizing infections. The clinical entities were diagnosed by both microbiological and histopathological examination of the skin biopsies. The final identification of fungal strains was done by comparing internal transcribed spacer (ITS) and D1–D2 domains of the LSU (larger subunit) of the nuclear ribosomal RNA (rRNA) sequences with those of type strains of the different species of Saksenaea.Results: Out of total 23 cases of necrotizing skin and soft tissue infections, 5 were caused by S. erythrospora. Intramuscular injection into the gluteal region was the predisposing factor in four patients, while upper limb involvement, following medicated adhesive tape application, was seen in one patient. All patients were treated with liposomal amphotericin B (LAMB) along with extensive debridement of necrotic tissues. Four patients responded well however one died.Conclusion: Saksenaea erythrospora is an emerging mucoralean fungus isolated in India among patients undergoing inadvertent I/M injections entailing necrotizing fasciitis at the local site.

Ecthyma gangreneux de la paupière compliquant une varicelle

Ecthyma gangrenosum is an acute ulcer necrotic skin infection frequently caused by Pseudomonas aeruginosa. It is characterised by necrotic ulcerations circumscribed by an inflammatory halo. Lesions are normally found in the anal, genital and axillary regions. Ecthyma gangrenosum is most commonly seen in immunodepressed patients (cytotoxic chemotherapy, HIV infection, neutropenia or functional neutrophil deficiency, agammaglobulinemia). It is a rarely described complication in chicken pox. Herein we report the case of a girl aged 2 ½ years presenting in our dermatology department with ecthyma gangrenosum on the right upper eyelid secondary to varicella. The disease course was marked by fibrous scarring of the inner canthus with ptosis of the right upper eyelid. The retractile scarring caused disability. There have been previous reports of the contribution of non-steroidal anti- inflammatory drugs (NSAIDs) to the appearance of necrotic cutaneous super infections during the course of chickenpox. The occurrence of such complications on an eyelid may be harmful not only for the function of the eye but it can also cause extensive aesthetic impairment. Subsequent aesthetic and functional impairment may be improved by corrective surgery.

Genome Sequence of Bacillus pumilus Strain Bonn, Isolated from an Anthrax-Like Necrotic Skin Infection Site of a Child

We report the draft genome sequence of Bacillus pumilus strain Bonn associated with human skin infection. B. pumilus Bonn was isolated from a carbuncle-like necrotic site, resembling cutaneous anthrax, on the back of the hand of a 10-year-old child.