Clostridium Septicum Infection Research Articles

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.

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.

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

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。

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.

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.

The Comparative Efficacy of Antibiotics against Experimental Clostridium septicum Infection

The Comparative Efficacy of Antibiotics against Experimental Clostridium septicum Infection

Temsirolimus therapy and small bowel perforation in a pediatric patient with Clostridium septicum bacteremia

Abstract Temsirolimus has been demonstrated to result in significant disease stabilization in children with high-grade glioma, neuroblastoma, and rhabdomyosarcoma. While mucositis has been reported as a common adverse effect of temsirolimus therapy in adult and pediatric patients, bowel perforation is an infrequent and life-threatening side effect of temsirolimus in adults and has not previously been reported in children. We present a child treated with temsirolimus for recurrent metastatic rhabdomyosarcoma who underwent ileocecectomy and small bowel resection for perforation with frank necrosis. His presentation was complicated by Clostridium septicum infection, a rare, frequently fatal, gastrointestinal pathogen associated with malignancy and bowel ischemia.

Fatal Clostridium Septicum Infection in a Patient with a Hematological Malignancy

A 49-year-old woman with acute myeloid transformation of myelodysplastic syndrome was admitted with mild erythema and pain in the right thigh and left forearm. She was doing well and had been discharged the previous day after consolidation chemotherapy. Examination showed only mild erythema and tenderness of the right thigh. She was started on broad-spectrum antibiotics. Discoloration progressed rapidly, and within hours the right femoral and left brachial pulses were not palpable. She was taken to the operating room for a suspicion of embolic arterial occlusion. Surgical incision, however, revealed extensive necrosis of the tissues with the presence of gas. Her relatives did not want her to undergo amputation. The patient developed refractory hypotension and died within 15 hours of presentation. Blood samples later tested positive for Clostridium septicum. This case is presented to create awareness about the subtle presentation and rapid progression of this infection, which can lead to death in less than 24 hours.

Identification of Clostridium septicum in a tubo-ovarian abscess: A rare case and review of the literature

Tubo-ovarian abscess (TOA) is a conglomerated mass of pelvic organs including the tube, the ovary, and the bowel. The most commonly isolated organisms from TOAs are Escherichia coli (E. coli) and Bacteroides species. We reported a case of Clostridium septicum (C. septicum) infection from a ruptured TOA with atypical clinical features. Culture of intra-abdominal free fluid obtained during surgery yielded C. septicum. VITEK II (bioMérieux, France) automated system was used for advanced identification of the bacteria. Parenteral clindamycin in combination with an aminoglycoside was used. The patient was discharged 19 days after the surgery and was clinically asymptomatic 6 months after the surgery. The differential diagnosis of TOA caused by C. septicum can be difficult, due to the lack of the symptoms. Tissues infected with C. septicum can become necrotic. A combination of early, adequate antibiotic therapy and surgery is the key point of the treatment.

A 2‐YEAR‐OLD BOY WITH HEMOLYTIC UREMIC SYNDROME AND PNEUMOCEPHALUS

Clostridium septicum infection following hemolytic uremic syndrome is rare and carries a poor prognosis, especially when the brain is involved. We report a case of a previously healthy 2-year-old boy who presented with two days of anuria and bloody diarrhea. He was admitted to the local children's hospital with a diagnosis of hemolytic uremic syndrome, presumably secondary to E. coli O157. He soon required intubation and was noted to have fixed and dilated pupils. Head CT revealed left frontal subcortical white matter vasogenic edema and scattered pockets of pneumocephalus. The patient expired 14 hours after admission. Antemortem blood cultures grew C. septicum. Gross pathologic examination of the brain revealed a large intraparenchymal cerebral hemorrhage in the left frontal and parietal lobes. There was extensive cystic changes as well. Microscopic examination revealed vacuolization and diffuse colonization with rod-shaped bacteria, but without the expected tissue response. There have been only six previously reported cases of C. septicum infection following hemolytic uremic syndrome, four of which had brain involvement. Mortality rate is high, with the only known survivor among those with brain involvement having a brain abscess rather than diffuse pneumocephalus.

Clostridium septicum infection of hepatic metastases following alcohol injection: a case report

Clostridium septicum infections are generally associated with gastrointestinal or hematologic malignancies. We report the first case of hepatic metastases infection with Clostridium septicum that followed alcohol injection of liver lesion. Clinicians should consider this possibility in patients with underlying malignancy who present with hepatic abscess, as prompt surgical drainage and empiric antibiotics may be life saving.

Clostridium septicum sepsis and colorectal cancer - a reminder

BackgroundSpontaneous clostridium septicum infections are rare and are associated with a high mortality. Association of clostridium infection with colorectal malignancies have been previously reported and most cases are described in tumours of the ascending colon. We report our experience of clostridium septicum infection in the presence of tumour perforation in a series of two patients as a reminder of its association with sepsis in the presence of colorectal malignancy.Case PresentationWe isolated clostridium septicum infection in a series of two patients admitted as emergencies. One patient was found to have a perforated caecal tumour intraoperatively whilst the other had a perforated rectal tumour. The clinical outcome and management of each case are reported and underlying reasons for variations in outcome are discussed.ConclusionAlthough uncomman, the possibility of clostridium septicum sepsis should be borne in mind in patients who present with underlying malignancy and have sepsis. The cumulative effect of sepsis and malignant perforation is associated with a high morbidity and mortality. Awareness and early diagnosis of clostridium septicum may improve the prognosis of what is usually regarded as a fatal infection.

Clostridium Septicum Infection Secondary to Immunosuppression by Sulfasalazine in Crohnʼs Disease

Clostridium Septicum Infection Secondary to Immunosuppression by Sulfasalazine in Crohnʼs Disease

Clostridium septicum myonecrosis complicating diarrhea-associated hemolytic uremic syndrome

We report the case of a 19-month-old male child with diarrhea-associated hemolytic uremic syndrome (HUS) who developed swelling of the right arm at the site of a peripherally inserted central venous catheter (PICC), fever, and later, ecchymosis. Wound cultures at the time of surgical debridement grew Clostridium septicum. The child subsequently required amputation of the right arm and prolonged therapy with parenteral penicillin and clindamycin. Clostridium septicum infections in children with HUS have been associated with a high rate of mortality. Along with colon cancer, diarrhea-associated HUS comprises a clinical entity which appears to predispose to atraumatic C. septicum infection, where acidic and anaerobic conditions in the diseased colon favor C. septicum invasion. Though not well recognized among pediatric nephrologists, C. septicum infection constitutes a severe, albeit rare, complication of diarrhea-associated HUS, but one in which a high index of suspicion is warranted as aggressive surgical and antibiotic therapy may be life-saving.

Phenotyping Clostridium septicum Infection: A Surgeon's Infectious Disease

Clostridium septicum infection is associated with malignancy. Whether disease phenotype is affected by malignant status is not known. Surgical treatment is used frequently but its impact on survival has not been examined in a cohort >30 patients. A PubMed search of English language journal articles yielded 320 cases. Full information (infection location, cancer type, operative intervention, and survival) was available for 224 cases + 7 at our institution not previously reported. Seventy-two percent of patients had malignancy or malady of the gastrointestinal (GI) or hematologic (HEME) organ systems. HEME survival was inferior to GI survival (35% versus 55%, P = 0.03). Overall, patients who underwent operation had improved survival (57% versus 26%; P < 0.0001) and this association was maintained within GI and HEME cohorts (P = 0.002 and 0.005, respectively). More GI than HEME patients underwent operation (81% versus 51%, P < 0.001). GI patients were more likely than HEME patients to experience infection of skin and soft tissues (SSTI, P = 0.006). Diabetics were more likely to experience SSTI than nondiabetics (77% versus 45%, P < 0.001). C. septicum infectious phenotype varies with host milieu. The SSTI phenotype is more common in GI and diabetic patients. This recognition may aid in directing the search for occult malignancy, which must be performed given the >70% incidence of concomitant cancer. This infection is more fatal in HEME versus GI patients, perhaps due in part to less HEME group operative intervention. Primary surgical therapy should be considered in GI or HEME patients as operative intervention benefits both groups.

Atraumatische Clostridium-septicum-Infektion bei Granulozytopenie

A fatal Clostridium septicum infection occurred in three patients. Case 1. A 55-year-old man died of septicaemia resulting from granulocytopenia of uncertain aetiology; it was associated with perforation of ileal mucosal ulcers. Autopsy revealed neutropenic enterocolitis and diffuse gas formation, especially in the brain, caused by Clostridium septicum. Case 2. A 18-year-old boy developed a caecal invagination during imipenem-induced granulocytopenia. A fulminant postoperative Clostridium septicum infection ended fatally. At autopsy many ulcers were found at the site of invagination with gas formation involving all organs. Case 3. Myonecrosis of the left arm, caused by Clostridium septicum, developed without external cause in a 12-year-old girl with congenital neutropenia. Despite aggressive surgical intervention she died of toxic shock. Autopsy revealed caecal mucosal ulcers as the portal of entry of Clostridium septicum.

Clostridium septicum Infection Associated with Necrotizing Pancreatitis, Transmural Gastric Necrosis, and Liquefaction of the Spleen.

Spontaneous infection with Clostridium septicum (C. septicum) is rare, but when isolated it is commonly associated with malignancy. We report a case of a 47-year-old man with infected pancreatic necrosis involving greater than 80% of the pancreas, transmural gastric necrosis, and liquefaction necrosis of the spleen. Initial cultures revealed C. septicum infection. He was managed with prompt aggressive surgical debridément, resection, appropriate broad spectrum antibiotics, and early enteral nutrition.