Myonecrosis Research Articles

切除不能膵癌に対する化学療法中に Clostridium perfringens感染による肝ガス壊疽を生じ急激な経過で死亡した1例

切除不能膵癌に対する化学療法中に Clostridium perfringens感染による肝ガス壊疽を生じ急激な経過で死亡した1例

Inactivated recombinant Escherichia coli as a candidate vaccine against Clostridium perfringens alpha toxin in sheep

Clostridium perfringens type A is the causative agent of gas gangrene and gastroenteric (“yellow lamb disease”) disease in ruminants, with C. perfringens alpha toxin (CPA) being the main virulence factor in the pathogenesis of these illnesses. In the present study, we have developed recombinant Escherichia coli bacteria expressing rCPA and used it to vaccinate rabbits and sheep. Doses of up to 200 μg of rCPA used for inoculation, induced 13.82 IU.mL−1 of neutralizing antitoxin in rabbits, which is three times higher than that recommended by the USDA (4 IU.mL−1). In sheep, recombinant bacteria induced antitoxin titers of 4 IU.mL−1, 56 days after the first dose. rCPA which was expressed, mainly, in inclusion bodies, was not found to influence the immunogenicity of the vaccine. The recombinant Escherichia coli bacterin, produced simply and safely, is capable of affording protection against diseases caused by C. perfringens CPA. The current findings represent a novel production method for CPA vaccines potentially applicable to veterinary medicine.

Clostridial diseases diagnosed in cattle from the South of Rio Grande do Sul, Brazil. A forty-year survey (1978-2018) and a brief review of the literature

ABSTRACT: Clostridial diseases are important causes of livestock losses in the southern Rio Grande do Sul. Since 1978 annual surveys conducted at the “Laboratório Regional de Diagnóstico” of the “Universidade Federal de Pelotas” (LRD-UFPel) have shown that clostridial diseases represent 10.40% of the bacterial diseases diagnosed in cattle and 1.65% of all diseases diagnosis in cattle over a 40-year period. The purpose of this study is to review the clinical, epidemiological and pathological aspects of the clostridial diseases diagnosed in cattle from January 1978 to December 2018 at the LRD-UFPel in the hopes that it will constitute a useful guide for field veterinary practitioners and interested farmers. We assessed and review the necropsy protocols of 6,736 cattle; these necropsies were performed either by LRD-UFPel faculty or by field veterinary practitioners; 111 outbreaks (1.65%) were diagnosed as clostridial disease, distributed as follows: 35 outbreaks of tetanus, 34 of blackleg, 23 of bacillary hemoglobinuria, 11 of malignant edema (gas gangrene), and eight of botulism. Approximately 904, from a total of 42,480 cattle at risk, died in these outbreaks.

Necrotizing Fasciitis: Low-Dose Radiotherapy as a Potential Adjunct Treatment.

Necrotizing fasciitis (NF) is a rapidly spreading bacterial infection causing extensive tissue necrosis and destruction. Despite appropriate therapy, the disease results in significant morbidity/mortality and substantial treatment costs. Several studies published in the early 1900s demonstrated the effective use of low-dose X-ray radiotherapy (RT) for the treatment of many diverse inflammatory conditions and diseases (eg, gas gangrene, sinus infections, arthritis, tendonitis, and serious inflammatory lung conditions). The mechanism by which therapeutic RT doses produce positive patient outcomes is related at least in part to its capacity to induce tissue-based anti-inflammatory responses. This action is due to the polarization of macrophages to an anti-inflammatory or M2 phenotype via optimized low-dose RT. Low-dose RT has the potential to significantly reduce debilitating surgeries and aggressive treatments required for NF, providing a 3-prong benefit in terms of patient mortality, length of hospitalization stays, and cost of health care (both short term and long term). Low cost and easy availability of low-dose RT makes it a potentially useful option for patients of every age-group. In addition, low-dose RT may be a particularly useful option in countries treating many patients who are unable to afford surgeries, antibiotics, and hyperbaric oxygen.

The Effects of Hyperbaric Oxygen at Different Pressures on Oxidative Stress and Antioxidant Status in Rats.

Background: The optimal use of oxygen at greater than atmospheric pressures in any operational or therapeutic application (hyperbaric oxygen, HBO2) requires awareness of the fact that the beneficial effects of oxygen coexist with toxic effects depending on the pressure and duration of exposure. In this study, we aimed to investigate the effect of HBO2 therapy on oxidative stress and antioxidant status in commonly used protocol for acute HBO2 indications, such as carbon monoxide intoxication, central retinal artery occlusion, crush injury, gas gangrene, and to compare it with normobaric oxygen (NBO2) in healthy rats. Materials and Methods: Fifty-six male, young adult Wistar albino rats were randomly divided into seven groups and named as Group I through Group VII. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), and erythrocyte glutathione (GSH) levels in control group were compared to the levels in other groups. Results: The increases in MDA levels and the decrease in SOD activities were statistically significant in HBO2 groups at the end of the first 24 h when compared to the control group, and the significant decrease in erythrocyte GSH level was only at 2.4 atmospheres absolute. Conclusions: The present study showed that pressure and frequency of exposure are important factors to consider when investigating HBO2-induced oxidative stress and antioxidant response.

"Frightening" Resistant Clostridial Myonecrosis: A Case Report

Clostridial myonecrosis is a diffuse necrotizing infection of deep soft tissues. It is known for its acute, rapid progression, poor prognosis, and high mortality. We report a case of traumatic clostridial myonecrosis, a 17-year-old, previously healthy female reported to our department with the complaint of pain in her left arm a week after she suffered a fall from her chair on to her left arm. Due to the injury sustained in the incident, under suspicion of a forearm fracture, a cast was applied to her left arm at a local polyclinic. However, after a few days, she reported unbearable pain, which led to the removal of the cast, and that is when diffuse crepitations due to gaseous accumulation were noted in her entire left upper limb. A week later, X-ray studies failed to reveal any fracture or abnormality. The patient was started on broadspectrum antibiotic coverage with intravenous (IV) benzylpenicillin, rifampicin, and clindamycin for a considerable period of time, but there was no improvement in her condition and the infection continued to spread into adjacent soft tissues, requiring intervention with hyperbaric oxygen therapy.

De novo whole transcriptome profiling of Edwardsiella tarda isolated from infected fish (Labeo catla)

Edwardsiella tarda belongs to the genera of Gram negative bacterium mainly associated with edwardsiellosis, the most commonly found infectious fish disease throughout the globe. E. tarda is also a widespread pathogen which cause infections such as cellulitis or gas gangrene and generalized infections in humans. To control the escalating infection of E. trada on various species, it is essential to decoded the mysterious mechanism behind the bacterial infection at transcript level. In this present study, we carry out a de novo E. tarda Whole transcriptome sequencing, isolated from infected fish intestine using SOLiD sequencing platform. RNA-Seq data analysis was performed using various bioinformatics pipelines. Protein-protein interaction study for pathway enrichment and gene ontology study were executed for further investigation. Assembly statistics for E. tarda dataset showed that the number of transcript contigs was 9657 out of which 6749 were GO annotated whereas 1528 were not assigned any GO terms. GO analysis showed that the expressed genes were enhanced with molecular function, cellular component and biological process. A KEGG enrichment study showed that pathway's that are directly linked with immune diseases like Rheumatoid arthritis (0.2%), Tuberculosis (0.3%) Endocytosis (0.6%) was considerably enriched. Protein-protein interaction study showed that most of the expressed proteins were involved in metabolic pathways, flagellar assembly, Propanoate metabolism, Microbial metabolism in diverse environments, Butanoate metabolism and Carbon. The present study provides novel E. tarda transcriptome sequence data, allowing us to identify biologically significant genes and their functional relationship with fish diseases, and will be useful in recognize the reliable therapeutic targets in near feature.

Draft genome sequence of multidrug-resistant β-lactamase-producing Bacillus cereus S66 isolated from China.

Bacillus cereus is associated with a variety of human diseases such as haematological malignancies, tetanus, gas gangrene, food poisoning and pseudomembranous colitis. Our team found and isolated a strain, named B. cereus S66, from radiation-contaminated soil in Xinjiang Uygur Autonomous Region. In this study, the drug resistance and toxicity of B. cereus S66 was systematically studied and analysed. Genomic DNA of B. cereus S66 was sequenced using an Illumina HiSeq 2000 sequencing system. The generated reads were assembled using SOAPdenovo, and GapCloser was used to fill in the gaps. The draft genome was annotated, and virulence genes and drug resistance genes were identified by comparison with multiclass databases. The genome of B. cereus strain S66 is 5 628 370 bp with a GC content of 34.95% and contains various genes related to toxicity and antimicrobial resistance. The number of toxicity genes identified was 496, some of which are associated with gastrointestinal infection, eye infection and neutrophil-activating protein NapA. Antimicrobial resistance-related genes comprised 3.23% of the total genes and conferred resistance to lincomycin, tetracycline, fosfomycin, aminoglycosides, linezolid, chloramphenicol, rifampicin, macrolides, daunorubicin and mupirocin. Three different β-lactamases were also found in isolate S66. The genome sequence of B. cereus S66 provides a valuable reference to further research on multidrug resistance characteristics and pathogenic system analysis of Bacillus sp. in the clinic.

Deciphering Potential Drug Targets in Clostridium Perfringens through Metabolic Pathway Analysis

Background: In our day-to-day life, we are facing many dreadful diseases caused by many infectious pathogens. These pathogens invade the living organisms (host) and lethally damaging them. These dreadful pathogens were also be used as bioweapons. Among them, Clostridium perfringens is taken for the study. Clostridium perfringens is an anaerobic, rod shaped, gram positive bacteria capable of forming spores. It is prevalent in the environment and in the intestine of humans and other animals. It is the causative agent for a wide range of diseases including food borne diseases, gas gangrene and flesh eating disease called necrotizing fasciitis. C. perfringens is commonly found on raw meat and poultry that espouse to grow in conditions with very little or no oxygen, and under ideal conditions can multiply very rapidly. These conditions are occasionally lethal due to the substantial number of toxins such as alpha toxin, beta toxin, epsilon toxin and iota toxin produced by C. perfringens. It is significantly important to analyze the Drug targets of the pathogen in order to destroy them. Objective: The present work aims in identifying potential drug targets in C. perfringens through metabolic pathway analysis. Method: Primarily, the metabolic pathways of the host and pathogen are compared to identify unique pathways in the bacteria. Among the enzymes that catalyze unique metabolic pathways, the essential ones for the survival of the pathogen are identified. The druggability of the essential enzymes are predicted through identification of its sub cellular localization and other druggable parameters. Results: The comparative metabolic pathway analysis result shows that, among the 98 metabolic pathways of C.perfringens, 25 pathways were unique that they did not have a counterpart with Human. There were 113 enzymes involved in these unique pathways. The NCBI’s protein Blast search against human was done to identify the non-homologous proteins. There were 93 non-homologous proteins. Among the 93 non-homologous proteins, 47 proteins were found to be essential. Based on their sub-cellular localization, 32 proteins were identified as potential drug targets and 15 are probable vaccine candidates. Conclusion: The present work which started with 25 different pathways with more than a hundred different enzymes, resulted in the identification of 32 putative drug targets against C.perfringens infection. All these 32 identified targets did not have any human homolog and are highly essential for the survival of the organism. They were concluded as potential drug targets. Designing of compounds to inhibit these enzymes would be successful for treating the life threatening infections caused by this pathogen.

Abstract A011: First-in-man clinical trial of intratumoral injection of Clostridiumnovyi-NT spores in patients with treatment-refractory advanced solid tumors: Safety, activity, and immune responses

Abstract Bacteriolytic strategies offer unique advantages to combat a broad range of cancers often refractive to conventional chemotherapies and/or radiotherapies. C. novyi-NT is an attenuated strain of Clostridium novyi, a spore-forming, gram-positive, obligate anaerobe that lacks a lethal alpha- toxin, expressed by the parental strain. When administered intravenously or intratumorally with percutaneous injection, C. novyi-NT colonizes and replicates within the hypoxic region of the tumors, eliciting robust, tumor-confined cell lysis. In this first-in-man phase 1 study, patients with injectable treatment-refractory solid tumors received a single intratumoral injection of C. novyi-NT spores across 6 dose cohorts (spore concentrations of 104, 3x104, 105, 3x105, 106, 3x106) using a 3+3 trial design. The primary endpoints were to assess the safety profile, the dose limiting toxicity, and the maximum tolerated dose of C. novyi-NT. Key secondary endpoints included assessments of the preliminary antitumor activity of the injected tumor, an overall response evaluated by RECIST v. 1.1, and the host immune and inflammatory response to C. novyi-NT. Twenty-four patients were enrolled between November, 2013 and April, 2017. A single intratumoral injection of C. novyi-NT led to germination and resultant tumor lysis of injected tumor masses in 46% of patients across all dosing cohorts. The cohort 5 dose of 106 spores was defined as the maximum tolerated dose. Dose-limiting toxicities were grade 4 sepsis and grade 4 gas gangrene (n=1), all in patients with germination. In the 22 evaluable patients, 21 (95%) had stable disease (SD) as the best response for the injected lesion (tumor shrinkage of > 10% was observed in 21% of patients) and 19 (86%) had overall SD as the best response per RECIST 1.1. C. novyi-NT injection resulted in transient serum cytokine responses consistent with inflammasome activity, activation of innate immunity, tissue remodeling, and angiogenesis. Tumor antigen specific ELISPOT assays pre- and post- treatment documented enhanced secretion of IFNγ and TNFα by circulating T-cells, indicating improved systemic tumor specific T-cell responses. Multiparametric in situ immunostaining of core biopsies suggested improved immune cell infiltration in metastatic lesions. These early signs of improved antitumor activity in patients with advanced solid tumors have encouraged a new trial of C. novyi-NT in combination with immune checkpoint inhibitors. Citation Format: Filip Janku, Mrinal Gounder, Abdul Mohammad Pezeshki, Ravi Murthy, Andrea Wang-Gillam, Dale Shepard, David S. Hong, Sarina A. Piha-Paul, Anjali Raina, Alexey A. Leontovich, Gary DeCrescenzo, Brent L. Kreider, David Tung, Mary Varterasian, Halle H. Zhang, Khashayarsha Khazaie. First-in-man clinical trial of intratumoral injection of Clostridiumnovyi-NT spores in patients with treatment-refractory advanced solid tumors: Safety, activity, and immune responses [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A011.

An unusual presentation of infrarenal aortoiliac occlusion with metastatic gas gangrene

Gas gangrene is a term reserved for fulminant soft tissue infections caused by Clostridium species. The posttraumatic form of gas gangrene is caused by Clostridium perfringens. Nontraumatic, or spontaneous, gas gangrene is even more rare and is usually caused by Clostridium septicum in two-thirds of cases and by C. perfringens in one-third of cases; the underlying malignancy is often present. It also usually affects patients with some degree of underlying immunocompromised or vascular insufficiency. We report a case of a 30-year-old man with no history of prior trauma presented with pain, paresis of both lower limbs, and developed discolouration of both feet clinically diagnosed to be Leriche's syndrome with dry gangrene. Computed tomography angiography showed infrarenal aortoiliac occlusion and rapidly progressive gas gangrene involving even bladder wall and bone marrow, probably caused by Clostridium septicum. Although several case reports discuss the setting of bowel malignancy, our case illustrates acute onset of aortic iliac occlusion resulting in mesenteric infarction, which is the probable source for the infection.

Clostridium perfringens – epidemiological importance and diagnostics

Clostridium perfringens is one of the most widespread anaerobic spore forming bacteria found in the environment. The toxotype A of the species inhabits the gastrointestinal tract of birds and mammals exhibiting pathogenic properties in the immunocompromised host. The virulence determinants of C. perfringens are toxins and extracellular enzymes which cause gas gangrene, enteritis necroticans, food poisoning, and non-food borne gastrointestinal infections in humans. The young animals suffer from enterotoxaemia, dysentery and necrotic enteritis due to the anaerobic spore forming bacilli. This article reviews the epidemiological significance of C. perfringens and its disease diagnostics, taking into account all known to date virulence determinants of the microorganism.

Sudden death due to gas gangrene caused by Clostridium septicum in goats

BackgroundEven though gas gangrene caused by Clostridium septicum in goats is mentioned in the classical textbooks, we have not managed to find any case description in the literature.Case presentationClinical signs resembling gas gangrene such as subcutaneous bloating, edema and crepitation were detected at various body parts of nine pregnant animals at the ages of 2–3 years on a hair goat farm (n = 170) located in Bingol province, Eastern Turkey. Five of these suspected animals with severe clinical symptoms died within 2 days. Various samples such as internal organs, edematous skin and edema fluid collected from dead and live animals were analyzed for the presence of clostridial agents by histopathological and microbiological methods. As a result of macroscopic and microscopic examination, lesions of gas gangrene were detected. The suspected isolates were identified and confirmed as C. septicum by bacteriological and molecular methods.ConclusionThe present study was the first to report identification of C. septicum as primary agent in the gas gangrene of goats.

1032. A Case Series of Clostridium septicum Aortitis

Background Clostridium septicum is an anaerobic, motile, spore forming, toxin-producing Gram-positive bacillus (GPB) that has been associated with colon and hematologic malignancies. Despite the low incidence of infection, it is a virulent organism leading to rapidly progressive gas gangrene. Only 51 cases of C. septicum related aortic aneurysms have been reported. 100% mortality is reported in patients without surgical intervention vs. 79% undergoing surgery. The primary aim of this study was to determine the incidence and clinical outcomes of patients treated at our institution with C. septicum aortitis.MethodsIn this IRB-approved retrospective case series, we reviewed our microbiology laboratory’s blood and tissue cultures from January 2005 to 2018 to identify cases of C. septicum infection. All patients >18 years of age who had positive cultures were reviewed to provide radiographic or histopathologic correlation.ResultsAmong 50 patients with C. septicum in blood and tissue cultures, seven patients were identified with aortitis. Underlying malignancy was found in four cases and included colon cancer (three cases) and prostate cancer (one case). The most common location for infection was the infrarenal aorta (four cases). Previous vascular surgery had been performed in three cases. Five of the seven patients underwent surgical repair with pathology revealing GPB in three patients and acute inflammation in the other two patients. C. septicum grew in tissue cultures from these patients. Four of the seven patients (all of whom underwent surgery) had positive blood cultures. The two patients that did not undergo surgery died which is consistent with the 100% mortality described in the literature. All patients were treated with β-lactam therapy. The median duration among the five who completed treatment was 7.5 weeks. Among the five patients who underwent surgery, two are alive (one at 1 year and another at 5 months postoperatively), two died within the first year after surgery, and one patient was lost to follow-up.ConclusionA small percentage of patients with C. septicum aortitis survived over 1 year. Earlier recognition and emergent surgery with appropriate antimicrobial therapy are needed to improve the outcome of patients diagnosed with this rare infection.Disclosures S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant.

Protective role of the vulture facial skin and gut microbiomes aid adaptation to scavenging

BackgroundVultures have adapted the remarkable ability to feed on carcasses that may contain microorganisms that would be pathogenic to most other animals. The holobiont concept suggests that the genetic basis of such adaptation may not only lie within their genomes, but additionally in their associated microbes. To explore this, we generated shotgun DNA sequencing datasets of the facial skin and large intestine microbiomes of the black vulture (Coragyps atratus) and the turkey vulture (Cathartes aura). We characterized the functional potential and taxonomic diversity of their microbiomes, the potential pathogenic challenges confronted by vultures, and the microbial taxa and genes that could play a protective role on the facial skin and in the gut.ResultsWe found microbial taxa and genes involved in diseases, such as dermatitis and pneumonia (more abundant on the facial skin), and gas gangrene and food poisoning (more abundant in the gut). Interestingly, we found taxa and functions with potential for playing beneficial roles, such as antilisterial bacteria in the gut, and genes for the production of antiparasitics and insecticides on the facial skin. Based on the identified phages, we suggest that phages aid in the control and possibly elimination, as in phage therapy, of microbes reported as pathogenic to a variety of species. Interestingly, we identified Adineta vaga in the gut, an invertebrate that feeds on dead bacteria and protozoans, suggesting a defensive predatory mechanism. Finally, we suggest a colonization resistance role through biofilm formation played by Fusobacteria and Clostridia in the gut.ConclusionsOur results highlight the importance of complementing genomic analyses with metagenomics in order to obtain a clearer understanding of the host-microbial alliance and show the importance of microbiome-mediated health protection for adaptation to extreme diets, such as scavenging.

JUST ANOTHER PINPRICK MADE ME SICK

SESSION TITLE: Critical Care 5 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Fournier’s gangrene is a urological emergency characterized by rapidly progressive fulminant necrotizing infection of the genital, perineal and/or perianal regions.Most case series and observational studies indicate a mortality of 30 to 50 percent without prompt management.It is rare to have gas formation along fascial planes with non-clostridial organisms, however an increasing number of case reports have described a rise in non-clostridial organisms causing gangrene especially in diabetic patients. Emergent surgical debridement followed by aggressive local care and timely initiation of broad spectrum antibiotics remains the backbone of management. CASE PRESENTATION: A 37-year-old man presented with 5-days of worsening left testicular pain, swelling and erythema associated with subjective fevers, chills. He was pricked by a safety-pin in the scrotal area before engaging in sexual activity. He endorses binge drinking over the weekends, but denies tobacco consumption, illicit drug use, any sick contacts or travel outside the country recently. His left scrotum doubled in size with significant surrounding erythema, edema, crepitus and induration, over the course of 24 hours, driving the patient to seek medical attention. Ultrasound of the scrotum revealed extensive soft tissue swelling and gas formation extending to the retroperitoneum via perineum. Imaging revealed extensive gas formation in the perineum, ascending and descending along fascial planes. Subcutaneous emphysema of abdominal wall with mediastinal gas was also noted. Investigation showed WBC count of 22,000 with 12% bands and HIV testing was negative.IV Vancomycin and Ertapenem were administered on presentation followed by emergent debridement of bilateral scrotum, perineum and left inguinal region. Due to the extent of necrosis and gas formation, clindamycin was added for anti-toxin effect. Wound/tissue cultures grew methicillin sensitive staphylococcus aureus, group B streptococcus, group G streptococcus and anaerobic bacteroides. Antibiotics were de-escalated in 48 hours to IV Cefazolin and metronidazole.He has completed his antibiotic course and is currently recovering well. DISCUSSION: Fournier’s gangrene can also be caused due to a synergistic bacterial infection by a combination non-clostridial aerobic and anaerobic organisms. We present a case of traumatic (pinprick induced) rapidly progressive perineal gas gangrene with documented bacterial synergism. It can be hypothesized that the magnitude of gangrene, necrosis and bacterial load was greater because of the bacterial synergism present. CONCLUSIONS: Improved survival can only be achieved by a high index of suspicion leading to prompt diagnosis, early debridement by an experienced surgical team and microbiology guided use of antibiotics. Reference #1: Clinical Features of Non-Clostridial Gas Gangrene and Risk Factors for in-Hospital Mortality. Tokai J Exp Clin Med 40, no. 3 (Sep 20 2015): 124-9. Reference #2: Fatal Morganella morganii bacteremia in a diabetic patient with gas gangrene. Journal of Medical Microbiology(2009), 58: 965-967.Lamerton, A. J. “Fournier's Gangrene: Non-Clostridial Gas Gangrene of the Perineum and Diabetes Mellitus.” J R Soc Med 79, no. 4 (Apr 1986): 212-5. Reference #3: A Case of Fournier's Gangrene. Eplasty 17 (2017): ic25. DISCLOSURES: No relevant relationships by Padmastuti Akella, source=Web Response No relevant relationships by Imola Daniel, source=Web Response No relevant relationships by Himmat Grewal, source=Web Response

Host Defense against Bacterial Infection and Bacterial Toxin-induced Impairment of Innate Immunity

Whereas granulopoiesis during Gram-negative bacterial infection is accelerated through activation of toll-like receptor 4 (TLR4), it has not been elucidated whether Gram-positive bacterial infection can stimulate granulopoiesis. Using the well-known TLR2 agonist peptidoglycan (PGN), it was shown that neutrophils in bone marrow and spleen and plasma granulocyte colony-stimulating factor were increased in mice that had received intraperitoneal administration of PGN. Incorporation of bromodeoxyuridine into bone marrow neutrophils increased in mice administered PGN, demonstrating that PGN promotes granulopoiesis. These results illustrate that bacterial recognition by TLR2 facilitates granulopoiesis during Gram-positive bacterial infection. Thus, granulopoiesis is accelerated to suppress bacterial infection, but some bacteria can still cause severe infections. Clostridium perfringens is a Gram-positive, anaerobic pathogenic bacterium and causes life-threatening gas gangrene in humans. Of the many toxins produced by C. perfringens, α-toxin is known to be a major virulence factor during infection. Recently, it has been revealed that C. perfringens α-toxin impairs the innate immune system by inhibiting neutrophil differentiation, which is crucial for the pathogenesis of C. perfringens. Moreover, the toxin also attenuates erythropoiesis, which would cause severe anemia in clinical settings. The findings provide new insight to understand how hosts strengthen innate immunity to fight pathogenic bacteria and how they evade the hosts' immune systems.

Necrose Etendue De L’estomac Sur Dilatation Gastrique Chez Un Patient Suivi Pour Tumeur Cerebelleuse

Acute necrosis with a gastric dilatation is very rare. It usually occurs on psychiatric and neurological field. The preoperative diagnosis is difficult, and it is often revealed by radiological exams. With or without surgery, mortality remains high. We report a case of gastric necrosis in a patient with a severe neurological history. The clinical signs were vomiting, without intestinal transit disorders, and poor general condition. The radiological exams revealed gastric gas gangrene in the stomach wall. The surgical management determined the limit of gastric necrosis and gastrectomy was performed.

Comparative efficacy of antibiotics in treating experimental Clostridium septicum infection

Clostridium septicum is a highly pathogenic microbe that causes gas gangrene in humans, and is the principal cause of spontaneous gas gangrene in patients with gastrointestinal maladies, including adenocarcinoma of the colon. Despite modern approaches to manage C. septicum infection, morbidity and mortality remain high (>60%). At present, no objective in-vivo data exist supporting the current antibiotic treatment recommendations for C. septicum infection. Utilizing an established murine model of clostridial myonecrosis, this study investigated the efficacy of standard antibiotics for anaerobic Gram-positive soft tissue infections (penicillin, clindamycin, tetracycline and vancomycin) in treating C. septicum gas gangrene. Following intramuscular challenge with 1 × 106 colony-forming units of C. septicum, antibiotics were administered by intraperitoneal injection every 4 h for a total of four doses. At 30 h, all animals in all treatment groups survived the C. septicum challenge, compared with no survivors in the untreated controls (100% mortality by 10 h). However, by 60 h, mice treated with vancomycin exhibited 40% mortality, with no mortality observed in any other antibiotic treatment group. Microbroth dilution minimum inhibitory concentration analyses for three strains of C. septicum also demonstrated high susceptibility to penicillin, clindamycin and tetracycline, but considerably lower susceptibility to vancomycin. This study suggests that penicillin, clindamycin and tetracycline are suitable alternatives for the treatment of C. septicum infection in humans.

Vacuum-Assisted Closure (VAC) Using Multiple Foam Pieces for Hidden Space Drainage through Less Exposure in Musculoskeletal Infections.

Purulent musculoskeletal infections often require surgical debridement and drainage. However, when the infection is extensive or involving multiple layers of tissues, maintaining drainage of the involved spaces can be difficult, even with the application of vacuum-assisted closure (VAC) therapy. Wide exposure and aggressive debridement is often required for such cases, which in turn may complicate wound coverage. A retrospective review was performed for 16 patients with musculoskeletal infections treated surgically. The diagnosis for the patients consisted of necrotizing fasciitis, large soft tissue abscess, peri-hardware abscess, infected compartment syndrome, emphysematous osteomyelitis, and gas gangrene of diabetic foot. We minimized the incision and resection for debridement and drainage, and instead we placed multiple foam pieces between the tissues involved with VAC, to maintain drainage of the hidden spaces with negative pressure. Infection was successfully controlled in all cases. The mean duration of VAC treatment was 16.1 days (range, 5-36) and the mean number of VAC changes was 5.1 (range, 1-13). Primary wound closure was achieved in 11 cases, while skin grafts were used to cover the remaining five cases, which consisted of necrotizing fasciitis, infected compartment syndrome, and diabetic foot gas gangrene. No complications specifically associated with VAC therapy were observed. VAC using multiple foam pieces for hidden space drainage appears to be effective for infection control. It is helpful for minimizing exposure and resection for drainage and debridement, although subsequent reduction of the necessity or the level of wound coverage should further be investigated.