Fatal non-traumatic gas gangrene caused by Clostridium perfringens type A in a Siberian Husky dog.

An 8-y-old, castrated male Siberian Husky dog was admitted to an emergency clinic with acute collapse and severe swelling of both forelimbs, ventral thorax, and axillary region. The clinical assessment, with laboratory tests and radiologic investigation, confirmed severe subcutaneous emphysema and multi-organ failure. The animal died while receiving emergency treatment. On postmortem examination, Clostridium perfringens was isolated from the subcutaneous fluid and the effusion from the thoracic and abdominal cavities. Relevant histopathology findings included subcutaneous emphysema and multi-organ perivascular and intravascular, intralesional myriad 0.5-3-µm gram-positive rod bacteria, with no associated inflammation. Whole-genome sequencing and phylogenetic analysis identified C. perfringens type A. Virulence genes detected included cpa (alpha toxin), cadA (v-toxin), colA (collagenase A), nagH (hyaluronidase), nanH, nanI, nanJ (sialidases), and pfoa (perfringolysin). These virulence genes have previously been reported to act synergistically with alpha toxin in C. perfringens-mediated gas gangrene.

Essential oil combinations against Clostridium perfringens and Clostridium septicum - the causative agents of gas gangrene.

AIMS: The inhibitory and bactericidal effect of a wide range of essential oils, and their selected combinations against two pathogens (Clostridium perfringens and Clostridium septicum), the causative pathogens of gas gangrenous infections were investigated. Fractional inhibitory indices were also calculated to determine the interactions. METHODS AND RESULTS: The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays were used to determine the efficacy of the essential oils. Santalum austrocaledonicum demonstrated the highest activity inhibiting both Clostridial pathogens at the lowest concentration of 0·02 mg ml-1 . Santalum austrocaledonicum combined with Cymbopogon martinii had the strongest inhibition against C. perfringens (MIC 0·02 mg ml-1 ) and C. septicum (MIC 0·01 mg ml-1 ). Selected combinations demonstrated synergy (ΣFIC ≤ 0·50) in combination against both pathogens tested. Antagonism was also observed in many combinations. CONCLUSIONS: Selected essential oils, when studied either individually or in combination, have high inhibitory and bactericidal effects against both Clostridial strains. Nine combinations have proven to be synergistic with 23 combinations additive; 96 indifferent and 77 having an antagonistic effect against the pathogenic strains. Some combinations demonstrated extreme antagonism and as such, careful consideration needs to be given to essential oil selection against these pathogens. SIGNIFICANT IMPACT OF THE STUDY: Very few essential oils have been antimicrobially screened (MIC and MBC) against Clostridial strains and furthermore, the efficacies in combination are not known.

Gas Where It Shouldn't Be! Imaging Spectrum of Emphysematous Infections in the Abdomen and Pelvis.

OBJECTIVE. The purpose of this article is to review the spectrum, etiopathogenesis, clinical presentation, imaging features, differential diagnoses, and management of emphysematous infections of the abdomen and pelvis. CONCLUSION. Emphysematous infections are associated with high morbidity and mortality and thus need urgent medical and surgical interventions. CT is the most sensitive modality to detect gas; CT provides definitive diagnosis in most cases and can depict the extent of involvement.

Gas gangrene-associated gliding motility is regulated by the Clostridium perfringens CpAL/VirSR system.

Clostridium perfringens strains cause a wide variety of human and animal disease, including gas gangrene or myonecrosis. Production of toxins required for myonecrosis, PFO and CPA, is regulated by the C. perfringens Agr-like (CpAL) system via the VirSR two-component system. Myonecrosis begins at the site of infection from where bacteria migrate deep into the host tissue likely using a previously described gliding motility phenotype. We therefore assessed whether gliding motility was under the control of the CpAL/VirSR regulon. The migration rate of myonecrosis-causing C. perfringens strain 13 (S13) was investigated during a 96 h period, including an adaptation phase with bacterial migration (∼1.4 mm/day) followed by a gliding phase allowing bacteria faster migration (∼8.6 mm/day). Gliding required both an intact CpAL system, and signaling through VirSR. Mutants lacking ΔagrB, or ΔvirR, were impaired for onward gliding while a complemented strain S13ΔagrB/pTS1303 had the gliding phenotype restored. Gene expression studies revealed upregulated transcription of pili genes (pilA1, pilA2 and pilT) whose encoded proteins were previously found to be required for gliding motility and CpAL/VirSR-regulated pfoA and cpa toxin genes. Compared to S13, transcription of cpa and pfoA significantly decreased in S13ΔagrB, or S13ΔvirR, strains but not that of pili genes. Further experiments demonstrated that mutants S13ΔpfoA and S13Δcpa migrated at the same rate as S13 wt. We demonstrated that CpAL/VirSR regulates C. perfringens gliding motility and that gliding bacteria have an increased transcription of toxin genes involved in myonecrosis.

Clostridial Gas Gangrene - A Rare but Deadly Infection: Case series and Comparison to Other Necrotizing Soft Tissue Infections.

OBJECTIVE: Clostridial gas gangrene (GG) or clostridial myonecrosis is a very rare but life-threatening necrotizing soft tissue infection (NSTI) caused by anaerobic, spore-forming, and gas-producing clostridium subspecies. It is the most rapidly spreading and lethal infection in humans, also affecting muscle tissue. The high mortality, of up to 100%, in clostridial GG is mediated by potent bacterial exotoxins. Necrotizing fasciitis (NF) is an important differential diagnosis, most often caused by group A streptococci, primarily not affecting musculature but the subcutaneous tissue and fascia. In the early stages of the infection, it is difficult to distinguish between GG and NF. Therefore, we compare both infection types, identify relevant differences in initial clinical presentation and later course, and present the results of our patients in a retrospective review. METHODS: Patients diagnosed with GG from 2008 to 2018 in our level one trauma center were identified. Their charts were reviewed retrospectively and data analyzed in terms of demographic information, microbiological and histological results, therapeutic course, outcome, and mortality rates. The laboratory risk indicator for NF (LRINEC) score was applied on the first blood work acquired. Results were compared to those of a second group diagnosed with NF. RESULTS: Five patients with GG and nine patients with NF were included in the present study. Patients with GG had a mortality rate of 80% compared to 0% in patients with NF. In eight patients with NF, affected limbs could be salvaged; one NF underwent amputation. LRINEC did not show significant differences between the groups; however, C-reactive protein was significantly increased (P = 0.009) and hemoglobin (Hb) was significantly decreased (P = 0.02) in patients with GG. Interleukin-6 and procalcitonin levels did not show significant difference. Patients with GG were older (70.2 vs 50 years). Of the isolated bacteria, 86% were sensitive to the initial calculated antibiotic treatment with ampicillin-sulbactam or imipenem plus metronidazole plus clindamycin. CONCLUSION: Both GG and NF need full-scale surgical, antibiotic, and intensive care treatment, especially within the first days. Among patients with NSTI, those with clostridial GG have a significantly increased mortality risk due to early septic shock caused by clostridial toxins. In the initial stages, clinical differences are hardly detectable. Immediate surgical debridement is the key to successful therapy for NSTI and needs to be performed as early as possible. However, patients should be treated in a center with an experienced interdisciplinary intensive care team based on a predetermined treatment plan.

The Agr-Like Quorum-Sensing System Is Important for Clostridium perfringens Type A Strain ATCC 3624 To Cause Gas Gangrene in a Mouse Model.

Clostridium perfringens type A is involved in gas gangrene in humans and animals. Following a traumatic injury, rapid bacterial proliferation and exotoxin production result in severe myonecrosis. C. perfringens alpha toxin (CPA) and perfringolysin (PFO) are the main virulence factors responsible for the disease. Recent in vitro studies have identified an Agr-like quorum-sensing (QS) system in C. perfringens that regulates the production of both toxins. The system is composed of an AgrB membrane transporter and an AgrD peptide that interacts with a two-component regulatory system in response to fluctuations in the cell population density. In addition, a synthetic peptide named 6-R has been shown to interfere with this signaling mechanism, affecting the function of the Agr-like QS system in vitro In the present study, C. perfringens type A strain ATCC 3624 and an isogenic agrB-null mutant were tested in a mouse model of gas gangrene. When mice were intramuscularly challenged with 106 CFU of wild-type ATCC 3624, severe myonecrosis and leukocyte aggregation occurred by 4 h. Similar numbers of an agrB-null mutant strain produced significantly less severe changes in the skeletal muscle of challenged mice. Complementation of the mutant to regain agrB expression restored virulence to wild-type levels. The burdens of all three C. perfringens strains in infected muscle were similar. In addition, animals injected intramuscularly with wild-type ATCC 3624 coincubated with the 6-R peptide developed less severe microscopic changes. This study provides the first in vivo evidence that the Agr-like QS system is important for C. perfringens type A-mediated gas gangrene.IMPORTANCEClostridium perfringens type A strains produce toxins that are responsible for clostridial myonecrosis, also known as gas gangrene. Toxin production is regulated by an Agr-like quorum-sensing (QS) system that responds to changes in cell population density. In this study, we investigated the importance of this QS system in a mouse model of gas gangrene. Mice challenged with a C. perfringens strain with a nonfunctional regulatory system developed less severe changes in the injected skeletal muscle compared to animals receiving the wild-type strain. In addition, a synthetic peptide was able to decrease the effects of the QS in this disease model. These studies provide new understanding of the pathogenesis of gas gangrene and identified a potential therapeutic target to prevent the disease.

A case report of iatrogenic gas gangrene post colonoscopy successfully treated with conservative management- is surgery always necessary?

BACKGROUND: Colonoscopy is a routine procedure in diagnosis and treatment of colonic disease. While generally regarded as a safe procedure, potentially fatal complications can occur. Gas gangrene is one such complication, with very high mortality. There are few cases of gas gangrene occurring after colonoscopy, making it one of the rarer complications of this procedure. There have been no previously reported cases of a patient surviving such an infection and the optimal treatment strategy is contentious. This report describes a case of intramural gas gangrene of the colon, treated conservatively with antibiotic therapy in which the patient survived with full recovery. CASE PRESENTATION: A 71-year-old, previously healthy male presented 6 h post apparently uncomplicated colonoscopic polypectomy with rigors, nausea, vomiting and right upper quadrant pain. At presentation he was febrile at 40.1 °C but hemodynamically stable. Abdominal computed tomography revealed substantial colonic thickening and several focal intramural gas bubbles (pneumatosis intestinalis) surrounding the polypectomy site. Within 24 h post procedure he became hypotensive and was admitted to ICU in frank septic shock requiring inotropes, and with demonstrable septic myocardial depression. Bloods showed multi-organ derangement with leukocytosis, lactic acidosis, haemolytic anaemia and hyperbilirubinemia. A diagnosis of presumed Clostridial gas gangrene was made, and treatment was initiated with benzylpenicillin, clindamycin, metronidazole and vancomycin. After 4 days in ICU he was stepped down, and discharged after a further 10 days with no surgical or endoscopic interventions. At three-month review he reported being back to full health. CONCLUSIONS: This case demonstrates that gas gangrene infection is a possible complication of colonoscopic polypectomy. This is a cause of rapid deterioration in post-colonoscopy patients and has been misdiagnosed as colonic perforation in previously reported cases of retroperitoneal gas gangrene. Such misdiagnosis delays antibiotic therapy, which likely plays a role in the high mortality of this condition. Early diagnosis and initiation of antibiotic therapy with benzylpenicillin and clindamycin as seen in this case is essential for patient survival. While surgery is typically performed, non-operative management of pneumatosis intestinalis, and potentially gas gangrene is becoming more common and was utilized effectively in this patient.

Postmortem computed tomography of gas gangrene with aortic gas in a dialysis patient.

Recently, postmortem imaging is sometimes used as an alternative to conventional autopsy. However, there are few case reports of postmortem imaging of dialysis patients. Here, we report a fatal case of gas gangrene involving a 76-year-old man who underwent dialysis. He died suddenly before a diagnosis could be established. Immediately after his death, postmortem computed tomography (PMCT) revealed gas accumulation in his right upper extremity and ascending aorta. Gas gangrene progresses rapidly and may sometimes result in sudden death before it is diagnosed. In this case, PMCT findings were useful to diagnose gas gangrene. Intravascular gas is a common finding on PMCT and is generally caused by cardiopulmonary resuscitation and decomposition. However, the detection of gas in the ascending aorta by PMCT was not described previously. Moreover, Gram stain and culture of the exudate showed anaerobic Gram-positive bacilli which suggested that the gas generation in the blood was caused by Clostridia species. To the best our knowledge, this is the first report of a dialysis patient whose cause of death was determined as gas gangrene using PMCT.

Gas gangrene in mammals: a review.

Gas gangrene is a necrotizing infection of subcutaneous tissue and muscle that affects mainly ruminants and horses, but also other domestic and wild mammals. Clostridium chauvoei, C. septicum, C. novyi type A, C. perfringens type A, and C. sordellii are the etiologic agents of this disease, acting singly or in combination. Although a presumptive diagnosis of gas gangrene can be established based on clinical history, clinical signs, and gross and microscopic changes, identification of the clostridia involved is required for confirmatory diagnosis. Gross and microscopic lesions are, however, highly suggestive of the disease. Although the disease has a worldwide distribution and can cause significant economic losses, the literature is limited mostly to case reports. Thus, we have reviewed the current knowledge of gas gangrene in mammals.

The EngCP endo α-N-acetylgalactosaminidase is a virulence factor involved in Clostridium perfringens gas gangrene infections.

Clostridium perfringens is the causative agent of human clostridial myonecrosis; the major toxins involved in this disease are α-toxin and perfringolysin O. The RevSR two-component regulatory system has been shown to be involved in regulating virulence in a mouse myonecrosis model. Previous microarray and RNAseq analysis of a revR mutant implied that factors other than the major toxins may play a role in virulence. The RNAseq data showed that the expression of the gene encoding the EngCP endo α-N-acetylgalactosaminidase (CPE0693) was significantly down-regulated in a revR mutant. Enzymes from this family have been identified in several Gram-positive pathogens and have been postulated to contribute to their virulence. In this study, we constructed an engCP mutant of C. perfringens and showed that it was significantly less virulent than its wild-type parent strain. Virulence was restored by complementation in trans with the wild-type engCP gene. We also demonstrated that purified EngCP was able to hydrolyse α-dystroglycan derived from C2C12 mouse myotubes. However, EngCP had little effect on membrane permeability in mice, suggesting that EngCP may play a role other than the disruption of the structural integrity of myofibres. Glycan array analysis indicated that EngCP could recognise structures containing the monosaccharide N-acetlygalactosamine at 4C, but could recognise structures terminating in galactose, glucose and N-acetylglucosamine under conditions where EngCP was enzymatically active. In conclusion, we have obtained evidence that EngCP is required for virulence in C. perfringens and, although classical exotoxins are important for disease, we have now shown that an O-glycosidase also plays an important role in the disease process.

Clostridium sordellii-associated gas gangrene in 8 horses, 1998-2019.

Gas gangrene occurs in several animal species and is caused by one or more clostridial species. In horses, the disease is most often caused by Clostridium perfringens type A. Although Clostridium sordellii has been associated with gas gangrene in ruminants and humans, cases of the disease associated with this microorganism have not been described in horses, to our knowledge. We report herein 8 cases of gas gangrene caused by C. sordellii in horses. These cases were characterized by myonecrosis and cellulitis, associated with systemic changes suggestive of toxic shock. The diagnosis was confirmed by gross and microscopic changes combined with anaerobic culture, fluorescent antibody test, immunohistochemistry, and/or PCR. The predisposing factor in these cases was an injection or a traumatic skin injury. C. sordellii should be considered as a possible etiologic agent in cases of gas gangrene in horses.

The antibiotic susceptibility pattern of gas gangrene-forming Clostridium spp. clinical isolates from South-Eastern Hungary.

Introduction:Clostridium perfringens and other gas gangrene-forming clostridia are commensals of the human gut and vaginal microbiota, but can cause serious or even fatal infections. As there are relatively few published studies on antibiotic susceptibility of these bacteria, we decided to perform a 10-year retrospective study in a South-Eastern Hungarian clinical centre.Methods: A total of 372 gas gangrene-forming Clostridium spp. were isolated from clinically relevant samples and identified with rapid ID 32A (bioMérieux, France) and MALDI-TOF MS (Bruker Daltinics, Germany) methods. Antibiotic susceptibility was determined with E-tests.Results: We identified 313 C. perfringens, 20 C. septicum, 10 C. sordellii, 10 C. sporogenes, 9 C. tertium, 6 C. bifermentans, 4 C. histolyticum isolates. In C. perfringens isolates, the rate of penicillin resistance was 2.6% and the rate of clindamycin resistance 3.8%. Penicillin resistance was found in 6.8% and clindamycin resistance in 8.5% of the non-perfringens Clostridium spp. isolates.Conclusion: The antibiotic susceptibility of C. perfringens isolates was in good agreement with previous publications. The rates of resistance to penicillin and clindamycin were very low. The resistance rates of non-perfringens Clostridium spp. isolates were higher than those of C. perfringens strains, but lower than those published in the literature.

Clostridium septicum-infected aortic aneurysm or graft is a deadly diagnosis.

BACKGROUND: Clostridium septicum is an anaerobic, motile, spore-forming, toxin-producing gram-positive bacillus that can lead to rapidly progressive gas gangrene due to the release of alpha toxin. Aortic aneurysm secondary to C. septicum infection is a rare condition with 60 cases reported in the literature; however, we have recently treated several patients with the condition in our large tertiary care and aortic center. METHODS: Blood and tissue culture results collected between January 2005 and January 2018 and maintained in the microbiology laboratory database at the Cleveland Clinic were reviewed to identify those with C. septicum reported. Each was reviewed to determine radiographic or histopathologic correlation with aortic disease. RESULTS: Seven cases of C. septicum aortitis were reviewed. Underlying malignant disease was found in four cases and a history of remote malignant disease in one case. The most common location for infection was the infrarenal abdominal aorta. Vascular surgery had previously been performed in three of the cases. Five of the seven patients underwent operative repair. All patients were treated with ß-lactam antibiotics. The two patients who did not undergo an operation died, which is consistent with the 100% mortality described in the literature. Of the five patients who underwent an operation, there was only one documented survivor and one was lost to follow-up. CONCLUSIONS: In the largest reported case series, only a small percentage of patients with C. septicum-infected aortic aneurysms survived >1 year. In the patients described, those who did not receive an operation had 100% mortality. Earlier recognition and prompt operation with appropriate antimicrobial therapy are needed to improve the outcome of patients diagnosed with this rare infection.

Gas gangrene as a surgical emergency - own experience.

In this paper the authors would like to present a correct procedure in both surgical and hyperbaric treatment of patients with gas gangrene admitted to a surgical department during ER. Gas gangrene is not very common these days, but when it comes to dealing with gangrenous infection in the emergency it is quite likely to make errors in both diagnostic and therapeutic manners. When there is a gas gangrene in a patient at the emergency time plays crucial role and the proper application of procedures is vital for the patient's survival. 10 cases made the study group here, all of them were patients diagnosed and treated surgically due to gas gangrene. As shown here, It is important to perform a revision of surgical wounds after few hours since primary surgery and to begin hyperbaric treatment as quickly as possible. The findings and suggestions included in this study are supported by own experience of The 2nd Department of General and Gastrointestinal Surgery of Medical University in Bialystok, Poland.

A Rare Case of Myonecrosis with Soft-Tissue Emphysema in a Diabetic Foot Caused by Streptococcus anginosus Isolated in Pure Culture: A Case Study.

Streptococcus anginosus (SAG) is a known human pathogen and member of the Streptococcus milleri group. SAG is a known bacterial cause of soft-tissue abscesses and bacteremia and is an increasingly prevalent pathogen in infections in patients with cystic fibrosis. We describe a rare case of SAG as an infectious agent in a case of nonclostridial myonecrosis with soft-tissue emphysema. This is the only case found in the literature of SAG cultured as a pure isolate in this type of infection and was associated with a prolonged course of treatment in an otherwise healthy patient.

Hepatic gas gangrene caused by Clostridium novyi.

We report the case of a patient with advanced gastric cancer and multiple liver metastases, who presented with bacteremia and hepatic gas gangrene caused by Clostridium novyi (C. novyi). The gas gangrene caused abscesses to form within metastatic lesions. This case highlights the antitumor effects of C. novyi in human.