Septicum Infection Research Articles

Clostridium septicum manifests a bile salt germinant response mediated by Clostridioides difficile csp gene orthologs

Clostridium septicum infections are highly predictive of certain malignancies in human patients. To initiate infections, C. septicum spores must first germinate and regain vegetative growth. Yet, what triggers the germination of C. septicum spores is still unknown. Here, we observe that C. septicum germinates in response to specific bile salts. Putative bile salt recognition genes are identified in C. septicum based on their similarity in sequence and organization to bile salt-responsive csp genes in Clostridioides difficile. Inactivating two of these csp orthologs (cspC-82 and cspC-1718) results in mutant spores that no longer germinate in the presence of their respective cognate bile salts. Additionally, inactivating the putative cspBA or sleC genes in C. septicum abrogates the germination response to all bile salt germinants, suggesting that both act at a convergent point downstream of cspC-82 and cspC-1718. Molecular dynamics simulations show that both CspC-82 and CspC-1718 bear a strong structural congruence with C. difficile’s CspC. The existence of functional bile salt germination sensors in C. septicum may be relevant to the association between infection and malignancy.

Clostridium Septicum: Cause of Gas Gangrene in the Upper Extremity Leading to Proximal Trans-Humeral Amputation, A Review of Clostridium septicum

Introduction: Gas gangrene is a rare, often lethal infection of soft tissue that is commonly associated with the Clostridial species due to penetrating injuries. Case reports of spontaneous atraumatic gas gangrene due to the Clostridium septicum species are exceedingly rare. Atraumatic C. septicum is notably related to bowel pathologies, immunodeficiencies, and individuals with vascular insufficiency. The rapid progression of Clostridium myonecrosis contributes to its high mortality rates. Case Report: The authors report a case of a 71-year-old right-hand-dominant female who developed fulminant atraumatic left forearm pain and swelling. The patient was indicated for emergent irrigation and debridement (I&D) of the left upper extremity. She was later found to have C. septicum bacteremia and required multiple I&Ds including the left side of the neck and chest wall. Repeat post-operative examinations revealed no motor function or sensation distal to the elbow and she was subsequently indicated for a proximal trans-humeral amputation. Conclusion: Although she had a prolonged hospital stay, she progressed well and was eventually discharged to a rehabilitation facility. This case report highlights the importance of early recognition of Clostridial myonecrosis as well as the need for emergent surgical intervention for the patient’s survival. Keywords: Trans-humeral amputation, gas gangrene, Clostridium septicum infection.

60-year-old male with rapidly progressive pneumocephalus caused by Clostridium septicum in the setting of an occult colonic adenocarcinoma

BackgroundDisseminated Clostridium septicum infection is an uncommon complication associated with malignancies, particular colonic adenocarcinoma. The organism appears to preferentially colonize large masses in rare individuals and subsequently seed the blood via mucosal ulceration. This has rarely been reported to lead to central nervous system infection and, in several cases, rapidly progressive pneumocephalus. In the few cases reported, this was a universally fatal condition. The current case adds to the reports of this extremely rare complication and provides a unique and complete clinicopathologic characterization with autopsy examination, microscopy, and molecular testing.Case PresentationA 60-year-old man with no known past medical history was discovered having seizure-like activity and stroke-like symptoms. Blood cultures turned positive after six hours. Imaging revealed a large, irregular cecal mass as well as 1.4 cm collection of air in the left parietal lobe that progressed to over 7 cm within 8 h. By the following morning, the patient had lost all neurologic reflexes and died. Post-mortem examination revealed brain tissue with multiple grossly evident cystic spaces and intraparenchymal hemorrhage, while microscopic exam showed diffuse hypoxic-ischemic injury and gram-positive rods. Clostridium septicum was identified on blood cultures and was confirmed in paraffin embedded tissue from the brain by 16 S ribosomal sequencing and from the colon by C. septicum specific PCR.ConclusionsC. septicum is an anaerobic, gram-positive rod that can become invasive and is strongly associated with gastrointestinal pathology including colonic adenocarcinomas. Central nervous system infection with rapidly progressive pneumocephalus is a rarely reported and universally fatal complication of disseminated C. septicum infection.

CLOSTRIDIUM SEPTICUM FASCIITIS IN A PATIENT WITH OCCULT COLON MALIGNANCY: A CASE REPORT AND LITERATURE REVIEW

Introduction and aim. Gas gangrene is usually related to a trauma and can involve different districts of the body. It is a life-threatening condition, and its consequences lead to functional and aesthetical deficit. Atraumatic gas gangrene is a rare event, sometimes related to a Clostridium septicum (C. septicum) bacteremia. Aim of this article is to discuss existing literature about relation between colon adenocarcinoma and Clostridia infections, integrating with a case-report. Patients and methods. A 54-year-old obese female patient developed an atraumatic gas gangrene of the posterior trunk, started from a C. septicum bacteremia. Gas gangrene involved skin, soft tissues and muscles of the back. A multidisciplinary clinical and surgical management involved anesthesiologists, general and plastic surgeons. During hospitalization, an occult colon adenocarcinoma was diagnosed and recognized as the bacteremia trigger, and it was successfully addressed. The gangrene was properly treated with seriate surgical debridement and final soft tissue coverage. After a long hospital stay, the patient was discharged in stable clinical conditions. Results and conclusions. C. septicum gas gangrene remains one of the most fearful infections. An early diagnosis and a prompt antibiotic and surgical treatment, with life supportive care, are mandatory to avoid the necrotizing fasciitis spreading and the death of the patient. However, due to the rarity and variability of this condition, there is no standardized protocol for its treatment. Since a strong relation between C. septicum infection and colon malignancy is reported in literature, in cases of C. septicum bacteremia it should be mandatory to investigate gastrointestinal tract to exclude colon malignancy.

IFx-Hu2.0 phase I first in human study for unresectable melanoma for an intralesional “in-situ vaccine” approach.

e21542 Background: Many melanoma patients do not respond to anti-PD1 therapy due to lack of antigen specific responses. IFx-Hu2.0 (plasmid DNA encoding the streptococcal membrane protein, Emm55, contained within a cationic polymer) primes innate and antigen dependent responses in murine/equine melanoma models to produce an environment needed for checkpoint inhibitor efficacy. We describe the first in human study utilizing IFx-Hu2.0 in unresectable melanoma - NCT03655756. Methods: Melanoma patients (unresectable stage III/IV) had cutaneous lesions injected with IFx-Hu2.0 to test safety and feasibility. Patients were refractory to standard of care (anti-PD1, BRAF/MEK) or did not wish these treatments. 1-3 lesions (> 3 mm – 0.1 mg/0.2 mL) were injected, pre/post treatment biopsies obtained, and the primary endpoint of 5/6 patients without dose limiting toxicity (DLT) was assessed at 28 days. Retreatment was permitted. ≥2 lesions were needed: one for injection and uninjected lesion for biopsy. Tissue samples were analyzed for mRNA profiles, antigen responses (PEPperPRINT assay), and multiplex immunofluorescence (markers: CD3, CD8, FOXP3, PD1, PDL1, SOX10, DAPI). Results: The primary endpoint was met in 6 evaluable patients out of 7 enrolled. Observed toxicities included: G1-2 Injection site reactions - 5/7; G1 Bleeding - 1/7; G1-2 Pain - 2/7, G1 Lymphopenia - 1/7, G1 Pruritis - 1/7; with no ≥ G3 toxicities related to study drug observed. One G5 toxicity (Clostridium septicum infection 20 days post injection) was deemed unlikely related to study drug. 5/6 patients received 1 cycle prior to post-protocol immune-based therapy. One treatment naïve patient retreated once with IFx-Hu2.0 required no additional therapy > 9 months. Available paired tissue and plasma sampling revealed increased T cell infiltration into treated lesions, increase in IgM and IgG epitope recognition to melanoma associated antigens in the plasma (detected by PEPperPRINT assay), an increase in mRNA associated with innate immune responses in the injected lesion (CXCL13, LAG3, CXCL11, CXCL10, ICOS) and an adaptive immune response (IL-12, HLA-DRB5, WNT4, CD3D, Arg I) in uninjected lesions associated with downregulation of known melanoma antigens. Of 4 anti-PD1 refractory patients, three patients had clinical benefit to post-protocol retreatment with anti-PD1 based therapy (Stable Disease (SD) lasting > 2 years followed by surgical resection, Partial Response (PR) lasting > 9 months, PR subsequently surgical resected and rendered no evidence of disease). Conclusions: In this pilot study, intralesional IFx-Hu2.0 demonstrated a favorable safety profile. These data support encouraging immunological correlative responses and further study of IFx-Hu2.0 as a priming agent to enhance or restore sensitivity to immune checkpoint inhibitor therapy in melanoma. Clinical trial information: NCT03655756.

Clostridium septicum α-toxin activates the NLRP3 inflammasome by engaging GPI-anchored proteins.

Clostridium species are a group of Gram-positive bacteria that cause diseases in humans, such as food poisoning, botulism, and tetanus. Here, we analyzed 10 different Clostridium species and identified that Clostridium septicum, a pathogen that causes sepsis and gas gangrene, activates the mammalian cytosolic inflammasome complex in mice and humans. Mechanistically, we demonstrate that α-toxin secreted by C. septicum binds to glycosylphosphatidylinositol (GPI)-anchored proteins on the host plasma membrane, oligomerizing and forming a membrane pore that is permissive to efflux of magnesium and potassium ions. Efflux of these cytosolic ions triggers the activation of the innate immune sensor NLRP3, inducing activation of caspase-1 and gasdermin D, secretion of the proinflammatory cytokines interleukin-1β and interleukin-18, pyroptosis, and plasma membrane rupture via ninjurin-1. Furthermore, α-toxin of C. septicum induces rapid inflammasome-mediated lethality in mice and pharmacological inhibition of the NLRP3 inflammasome using MCC950 prevents C. septicum-induced lethality. Overall, our results reveal that cytosolic innate sensing of α-toxin is central to the recognition of C. septicum infection and that therapeutic blockade of the inflammasome pathway may prevent sepsis and death caused by toxin-producing pathogens.

Emphysematous Abdominal Aortic Aneurysm by Clostridium septicum with Synchronous Colon Cancer

Introduction: Clostridium septicum (C. septicum) aortitis is a rare condition frequently associated with colon adenocarcinoma and carries a poor prognosis. Case Report: We report the case of an 80-year-old man who was waiting for an elective endovascular repair of an abdominal aortic aneurysm (AAA) with a diameter of 5.8 × 5.4 cm. He underwent a colonoscopy because of a thickening of the colon wall in the preoperatory CT. One week after that, he presented at the emergency with a 48-hour duration of fever and abdominal pain. Abdominal CT imaging revealed an increased aneurysm size to 6.1 × 6.6 cm including gas within the aorta. Treatment consisted of antibiotics, urgent axillar to femoro-femoral bypass, excision and ligation of the infrarenal aorta and right hemicolectomy with end-ileostomy. Aortic cultures were positive for C. septicum. The postoperative was complicated by renal failure and the patient died. Conclusion: C. septicum-infected aortic aneurysm is a rare entity that is strongly associated with colon cancer. The presence of gas within the aorta or emphysematous aortitis is the most common sign of C. septicum infection. Broad-spectrum antibiotics should be initiated and emergency surgical management with excision of the infected aneurysm and grafting is required.

A sudden cardiac death caused by Clostridium septicum infection in left lower limb: Case report and literature review

A sudden cardiac death caused by Clostridium septicum infection in left lower limb: Case report and literature review

First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas Gangrene.

Clostridium septicum is a Gram-positive, toxin-producing, and spore-forming bacterium that is recognized, together with C. perfringens, as the most important etiologic agent of progressive gas gangrene. Clostridium septicum infections are almost always fatal in humans and animals. Despite its clinical and agricultural relevance, there is currently limited knowledge of the diversity and genome structure of C. septicum. This study presents the complete genome sequence of C. septicum DSM 7534T type strain as well as the first comparative analysis of five C. septicum genomes. The taxonomy of C. septicum, as revealed by 16S rRNA analysis as well as by genomic wide indices such as protein-based phylogeny, average nucleotide identity, and digital DNA–DNA hybridization indicates a stable clade. The composition and presence of prophages, CRISPR elements and accessory genetic material was variable in the investigated genomes. This is in contrast to the limited genetic variability described for the phylogenetically and phenotypically related species Clostridium chauvoei. The restriction-modification (RM) systems between two C. septicum genomes were heterogeneous for the RM types they encoded. C. septicum has an open pangenome with 2,311 genes representing the core genes and 1,429 accessory genes. The core genome SNP divergence between genome pairs varied up to 4,886 pairwise SNPs. A vast arsenal of potential virulence genes was detected in the genomes studied. Sequence analysis of these genes revealed that sialidase, hemolysin, and collagenase genes are conserved compared to the α-toxin and hyaluronidase genes. In addition, a conserved gene found in all C. septicum genomes was predicted to encode a leucocidin homolog (beta-channel forming cytolysin) similar (71.10% protein identity) to Clostridium chauvoei toxin A (CctA), which is a potent toxin. In conclusion, our results provide first, valuable insights into strain relatedness and genomic plasticity of C. septicum and contribute to our understanding of the virulence mechanisms of this important human and animal pathogen.

An Immunosuppression Hidden Malignancy: Case Report of An Unexpected Clostridium Septicum Infection and Its Fatal Consequence

Gastroenterology Medicine & Research An Immunosuppression Hidden Malignancy: Case Report of An Unexpected Clostridium Septicum Infection and Its Fatal Consequence Grade M1*, Welk E1, Sostmann H1, Hammerstein HV1, McAulay CH3 and Bostelmann R2 1Department of Gastroenterology, Infectious Diseases and General Internal Medicine Christian Hospital Quakenbrück, Germany 2Department of Neurosurgery and Spine Surgery, Christian Hospital Quakenbrück, Germany 3Department of Radiology, St. Marienhospital, Vechta, Germany *Corresponding author:Grade M, Department of Gastroenterology, Infectious Diseases and General Internal Medicine Christian Hospital Quakenbrück, Germany Submission: May 14, 2021;Published: May 21, 2021 DOI: 10.31031/GMR.2021.05.000625 ISSN 2637-7632Volume5 Issue5

Lethal Clostirium Septicum Infection. Proof of a Direct Bacterial Invasion of a Simple Skin Bruise from the Necrosis Zone of the Colon Cancer - A Case Report

Lethal Clostirium Septicum Infection. Proof of a Direct Bacterial Invasion of a Simple Skin Bruise from the Necrosis Zone of the Colon Cancer - A Case Report

1631. Mycobacterium septicum: A 6-year Clinical Experience from a Tertiary Hospital and Reference Laboratory

Background Mycobacterium septicum is a rapidly growing non-tuberculous mycobacterium. It is a ubiquitous organism capable of causing infections in both healthy and immunocompromised individuals. Only a few cases have been reported to date, and standard therapeutic regimens, and optimal treatment duration have not been defined.MethodsWe conducted a retrospective chart review of all patients seen at Mayo Clinic in Rochester, MN from July 2014 to March 2020 from whom Mycobacterium septicum was isolated in culture by our clinical microbiology laboratory.ResultsThere were 12 patients identified with M. septicum infection – 7 males and 5 females. The average age was 67 years, with an age range of 48 to 80 years. Seven of 12 isolates obtained were from sputum samples. Only one patient was on immunosuppressive medication. Three cases were considered clinically significant infections for which directed anti-mycobacterial therapy was instituted. In two of these three cases, co-infection with Mycobacterium avium complex (MAC) was seen. Underlying structural lung disease was present in the two cases of pulmonary infections. Peritoneal dialysis catheter-related peritonitis was seen in the third case. All the isolates were susceptible to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX). The isolates were resistant to clarithromycin and doxycycline.Patient Characteristics, Associated M. septicum Illness, and Therapy Provided Antimicrobial Susceptibility Profiles of the Mycobacterium septicum Isolates, MIC (mcg/mL) and Interpretation Patient Demographics and Specimen Source of Mycobacerium septicum Isolates ConclusionM. septicum is an unusual cause of non-tuberculous mycobacterial infection. The presence of a foreign body may increase the risk of infection. Individuals with underlying structural lung disease are also likely to be at increased risk of developing pulmonary infection. Generalized treatment recommendations are limited by the lack of prospective controlled trials; hence, optimal antibiotic regimen and treatment duration have not been firmly established. Susceptibility testing should be performed to guide treatment selection, but the use of combination therapy with potentially empiric agents like amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and TMP-SMX as demonstrated in this small study, can be considered. A high rate of macrolide resistance was noted in our study.Disclosures All Authors: No reported disclosures

Identification of Clostridium septicum in Clinical Cases Suspected to Braxy and Malignant Edema by Traditional and Molecular Method and Evaluation of Toxigenic Isolates for Vaccine Production

Clostridium septicum is the causative agent of the acute fetal disease braxy and gas gangrene with major economic losses in the dairy industry. Accurate and rapid detection is great importance in this regard. Vaccination is an effective process for protection against C. septicum infection. It is necessary to identify and evaluate toxigenic Iranian isolates to produce a vaccine. This study aimed to detect Iranian isolates and evaluate toxigenic isolates as candidates for vaccine production. To this end, a total of 17 samples of animals, clinically suspected to braxy and malignant edema, were obtained. All samples were then cultured on media and microbiological and biochemical tests were performed on the colonies. The test results were confirmed by PCR amplification of the alpha-toxin gene. The toxigenic isolates were then evaluated using MLD. The experimental vaccine was produced and evaluated according to the British Pharmacopoeia Standard. According to the results, out of 17 samples, 15 samples were considered C. septicum. All samples were confirmed by PCR amplification. The most toxigenic isolate was used for experimental vaccine production. The result was successful. The Iranian isolate could be, therefore, used for vaccine production although further studies should be conducted in this regard.

Clostridium Septicum Endogenous Endophthalmitis as the Initial Manifestation of Colorectal Carcinoma: Clinical Case Report and Literature Review

ABSTRACT Purpose To describe the presentation and clinical course of a case of endogenous endophthalmitis caused by Clostridium septicum, an anaerobic and gram positive bacteria. Methods Observational report of a clinical case presented in Spain. Clinical case A 61-year-old male patient was referred to our hospital with a diagnosis of endophthalmitis of his left eye since ten days prior to presentation, and a history of poor response to medical treatment. Evisceration was performed, and C. septicum was isolated from a sample of the vitreous humor. Fourteen days after surgery, the patient returned with orbital cellulitis, and exenteration was performed. Forty-two days after initial presentation, colonoscopy revealed an adenocarcinoma of the proximal colon. Surgical resection of the tumor was performed, and clinical recovery was achieved. Conclusions iSystemic C. septicum infection without a traumatic cause has been associated with malignancy, although an initial presentation of endophthalmitis has rarely been reported. In cases of clostridial endogenous endophthalmitis, investigation for colorectal carcinoma is indicated.

Alpha Toxin Purification and Antibody Production Against Local Strain of Clostridium septicum NH2

BACKGROUND: Clostridium septicum has played a significant role as a causative agent of many acute fetal diseases in man and animals. Alpha- toxin is the main factor in the pathogenesis of C. septicum with hemolytic, necrotic and lethal activities. OBJECTIVES: The study was designed to evaluate alpha-toxin purification and antibody production rate against a local strain of C. septicum NH2 which could be applied in diagnosing kits, potency test of the vaccines, and other related applications. METHODS: Local strain of C. septicum NH2 was cultured in liver broth. Alpha-toxin in supernatant purified by three steps: the first step was done by 25% and 60% of ammoniums sulfate precipitation and continued by DEAE-Sephadex ion exchange chromatography, and finally finished in gel filtration on Sephadex G-50. Alpha-toxin was assayed in all steps and purification procedures were analyzed by SDS-PAGE. After immunization of rabbits with alpha- toxin and serum collection, immunoglobulin was separated by three purifying steps: ammoniums sulfate, ion exchange chromatography, and gel filtration. Serum purification process was evaluated by electrophoresis, double immunodiffusion (DID), single radial immunodiffusion (SRID), western blot, and SDS-PAGE. RESUTLS: SDS-PAGE results showed the alpha-toxin and anti-alpha-toxin were purified partially. Double immunodiffusion and single radial immunodiffusion methods detected the specific antibody. Heavy and light chains of anti-alpha-toxin separated by 2ME in electrophoresis reacted with 48 kDa alpha-toxin during the western blot without any reaction to other proteins in nitrocellulose paper. CONCLUSIONS: The present study showed a modified protocol for C. septicum alpha-toxin and anti-alpha-toxin production. The purification method is more economical and faster than previously reported procedures, and anti-alpha-toxin production is an advantage in detection of C. septicum infection

乳がんに対するドセタキセル投与後の好中球減少性腸炎からClostridium septicumによる腸管壊死を発症した1症例(A fatal case of bowel necrosis due to Clostridium septicum infection following neutropenic enterocolitis associated with docetaxel–based chemotherapy for breast cancer)

要旨好中球減少性腸炎（neutropenic enterocolitis: NE）は，化学療法に伴う好中球減少時に注意しなければならない重篤な合併症である。今回我々は，乳がんに対してドセタキセルによる化学療法施行中にNEを発症し，Clostridium septicum（C. septicum）による急激かつ広範な腸管壊死を来し，救命できなかった症例を経験した。化学療法施行後に好中球減少を伴った発熱と腹部症状を訴えた患者を診察した時は，常にNE発症を鑑別診断の一つとして考慮した治療介入が必要であり，迅速な起炎菌の検索および想定と造影CTなどの画像診断による腸管虚血の評価がその後の救命のために必須である。また，C. septicumはNE発症時の菌血症の原因菌としてしばしば認めることがあり，急激な臓器虚血から多臓器不全を生じるため周知が必要である。

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.

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.

Clostridium septicum arthroplasty infection: beware of occult aortitis and malignancy.

The Clostridia species are responsible for life-threatening conditions such as tetanus, botulism and gas gangrene. Clostridium septicum is a rare cause of clinical infection, accounting for less than 1% of blood culture samples that test positive for Clostridia. However, C. septicum bacteraemia is associated with greater than 60% mortality and in over 80% of cases is associated with an underlying malignancy. We present a review of the literature and the first case of an acute arthroplasty infection and concurrent infective aortitis caused by this organism in the absence of an identified underlying malignancy. Early diagnosis and multi-disciplinary input resulted in the patient surviving a rare and potentially fatal infective aortitis and septic arthritis. This case demonstrates the importance of early systemic investigation to exclude occult infective aortitis in C. septicum infection. The key role of multi-disciplinary input into the management of this often fatal infection is also discussed along with the requirement to exclude occult gastrointestinal and haematological malignancy.

Atraumatic Clostridial Myonecrosis in an Immunocompromised Host

BackgroundNecrotizing fasciitis is usually associated with a surgical or traumatic wound. Clostridial myonecrosis is an uncommon but deadly infection that can develop in the absence of a wound and is often associated with occult gastrointestinal cancer or immunocompromise, or both. Case ReportWe report a case of catastrophic atraumatic Clostridium septicum infection in an immunocompromised host. Why Should an Emergency Physician Be Aware of This?Emergency physicians most commonly associate necrotizing fasciitis with superinfection of an open wound. This case reminds physicians that patients with acquired neutropenia can present with spontaneous gas gangrene due to C. septicum. Providers should consider this diagnosis in immunocompromised patients who present with acute onset of severe atraumatic limb pain.