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.

[Life-threatening intrauterine infection with Clostridium perfringens].

In this case report, a 40-year-old woman with a history of a uterine leiomyoma presented with abdominal pain and fever. Initially, her symptoms were associated with a bleeding from an ovarian cyst seen on a CT scan of the abdomen showing free intraperitoneal fluid surrounding the internal genitals. Meanwhile, her blood cultures came out positive for Clostridium perfringens, and her condition deteriorated despite intravenous antibiotics. A new CT scan revealed intrauterine gas development. A laparotomy was performed with removal of the internal genitals, and the patient improved on continuous antibiotics.

Mycotic aneurysm caused by Clostridium septicum in a patient with colorectal cancer.

A mycotic aneurysm caused by a Clostridium septicum is a rare infection and has a strong association with colorectal cancer. If left untreated, the mortality rate of the first 24 h is high. This case report discusses the optimal treatment of emergency surgery combined with antibiotic treatment to improve survival. We present a fatal case of a 71-year-old male with abscedation of a caecal carcinoma who shortly after developed a mycotic aneurysm of the infrarenal aorta as a result of a C. septicum infection.

Opioid analgesics stop the development of clostridial gas gangrene.

Gas gangrene is a potentially fatal disease that is primarily caused by the ubiquitous, anaerobic bacteria Clostridium perfringens and Clostridium septicum. Treatment is limited to antibiotic therapy, debridement of the infected tissue, and, in severe cases, amputation. The need for new treatment approaches is compelling. Opioid-based analgesics such as buprenorphine and morphine also have immunomodulatory properties, usually leading to faster disease progression. However, here we show that mice pretreated with buprenorphine and morphine do not die from clostridial myonecrosis. Treatment with buprenorphine after the onset of infection also arrested disease development. Protection against myonecrotic disease was specific to C. perfringens-mediated myonecrosis; buprenorphine did not protect against disease caused by C. septicum infection even though infections due to both species are very similar. These data provide the first evidence of a protective role for opioids during infection and suggest that new therapeutic strategies may be possible for the treatment of C. perfringens-mediated myonecrosis.

Clostridium septicum gas gangrene in the orbit: a case report.

Our report presents a case of Clostridium septicum gas gangrene in an unusual, orbital localization. The predisposing factors are typical: colon tumour and lymphatic malignancy. Most probably bacteria from the intestinal flora entered the bloodstream through the compromised intestinal wall and settled in the orbit resulting in the development of an abscess containing gas. At the site of the gas gangrene, an indolent B cell lymphoma was present. After surgery and antibiotic treatment, the patient healed from the C. septicum infection; but subsequently died as a consequence of the tumour.

[New insight from basic research of Clostridium perfringens alpha-toxin].

Clostridium perfringens causes gas gangrene with inflammatory myopathies and infrequently septicemia associated with massive intravascular hemolysis. The microorganism is known to produce a variety of toxins and enzymes that are responsible for severe myonecrotic lesions. Notably, alpha-toxin, which possesses hemolytic, necrotic and lethal activities, and phospholipase C and sphingomyelinase activities, is an important agent for the diseases. The cytokine storm induced by alpha-toxin, mainly the release of TNF-alpha, plays an important role in the death and massive hemolysis. The toxin-induced release of TNF-alpha from neutrophils and macrophages is dependent on the activation of ERK1/2 signal transduction via TrkA receptor. In addition, 14- and 15-membered macrolides specifically block the toxin-induced events through the activation of neutrophils and macrophages.

Reactive oxygen species and the MEK/ERK pathway are involved in the toxicity of clostridium perfringens α-toxin, a prototype bacterial phospholipase C.

Clostridium perfringens, the most broadly distributed pathogen in nature, produces a prototype phospholipase C, also called α-toxin, which plays a key role in the pathogenesis of gas gangrene. α-Toxin causes plasma membrane disruption at high concentrations, but the role of intracellular mediators in its toxicity at low concentrations is unknown. This work demonstrates that α-toxin causes oxidative stress and activates the MEK/ERK pathway in cultured cells and furthermore provides compelling evidence that O(2)(-.), hydrogen peroxide, and the OH(.) radical are involved in its cytotoxic and myotoxic effects. The data show that antioxidants and MEK1 inhibitors reduce the cytotoxic and myotoxic effects of α-toxin and demonstrate that edaravone, a clinically used hydroxyl radical trap, reduces the myonecrosis and the mortality caused by an experimental infection with C. perfringens in a murine model of gas gangrene. This knowledge provides new insights for the development of novel therapies to reduce tissue damage during clostridial myonecrosis.

Co-infection with Toxoplasma gondii and Clostridium perfringens in a postpartum woman with uterine gas gangrene: a case report.

Toxoplasmosis is a protozoan infection caused by Toxoplasma gondii. We report a case of Toxoplasma gondii and Clostridium perfringens co-infection complicating uterine gas gangrene following a term pregnancy. The histological examination of the necrotic uterine tissues and uterine swab cultures obtained at laparotomy revealed T. gondii and C. perfringens, respectively. Treatment was administered with bactericidal activity against both pathogens and the patient had an uneventful post-operative recovery. Although there have been some cases that have documented an association between toxoplasmosis and non-uterine C. perfringens infection, such a relationship has not been established. It is of interest to determine if the presence of both organisms can explain the severe myonecrosis that occurs in some cases of uterine gas gangrene.

Clostridium septicum myonecrosis presenting as an acute painful foot.

Spontaneous clostridial myonecrosis (gas gangrene) is an uncommonly encountered presentation of skin and soft-tissue infections with high morbidity and mortality. The diagnosis has been associated with colorectal carcinoma, hematologic malignancies, and diabetes. We report the case of an 81-year-old man who experienced a sudden onset of left ankle and foot pain in association with nonpalpable purpura and hemorrhagic bulla. The diagnosis was initially suspected on clinical presentation, gas in tissue on plain-film radiography, and Gram staining of aspirated bulla contents. Cultures grew Clostridium septicum, and a large cecum mass was found by computed tomography of the abdomen. A subsequent right hemicolectomy confirmed a well to moderately differentiated mucinous adenocarcinoma. We emphasized that the early recognition of necrotizing skin and soft-tissue infections warrants further evaluation and appropriate management.

Potent inhibition of bacterial neuraminidase activity by pterocarpans isolated from the roots of Lespedeza bicolor.

Bacterial neuraminidase has been highlighted as a key enzyme for pathogenic infection and sepsis. Six pterocarpans displaying significant levels of neuraminidase inhibitory activity were isolated from the root bark of Lespedeza bicolor. The isolated compounds were identified as three new pterocarpans (1-3) together with known compounds erythrabyssin II (4), lespebuergine G4 (5), and 1-methoxyerythrabyssin II (6). The new compounds were characterized as bicolosin A (1), bicolosin B (2), and bicolosin C (3). All compounds inhibited bacterial neuraminidase in a dose-dependent manner with significant inhibition (IC(50)=0.09-3.25 µM). All neuraminidase inhibitors screened were found to exhibit noncompetitive kinetics. The three most potent neuraminidase inhibitors (1, 3 and 6) feature a methoxy substitution on C-1.

[Microbiological diagnosis of gas gangrene caused by Clostridium septicum (a clinical case)].

Microscopy of gram-stained impression smears is used for the rapid diagnosis of microorganisms in the wound. The shin tissues of patient P. with suspected gas gangrene of lower extremity soft tissues were microscopically found to have gram-positive spore-forming bacteria that were morphologically similar to C. bifermentans that were identified as C. septicum on cultural diagnosis. The pathogenic C. septicum strain spores were likely to be formed in the macroorganism upon exposure of the pathogen to a patient's defense factors and to a package of therapeutic measures. Microbiological data should be used only in combination with clinical and instrumental findings and the results of other laboratory studies when the optimal technology is chosen to treat gas infection. By keeping in mind that there may be clostridial gangrene in the patients and the experience of clinicians and bacteriologists may be insufficient in diagnosing this pathology, it is necessary to strengthen the training of physicians in the diagnosis of this pathology.

[Massive intravascular hemolysis secondary to sepsis due to Clostridium perfringens]. / Hemólisis masiva intravascular secundaria a sepsis por Clostridium perfringens.

Massive hemolysis secondary to sepsis caused by Clostridium perfringens is a rare entity but appears fairly often in the literature. In nearly all published reports, the clinical course is rapid and fatal. We describe the case of a 75-year-old woman with diabetes who was admitted with symptoms consistent with acute cholecystitis. Deteriorating hemodynamics and laboratory findings were consistent with intravascular hemolysis, coagulation disorder, and renal failure. Gram-positive bacilli of the Clostridium species were detected in blood along with worsening indicators of hemolysis. In spite of antibiotic and surgical treatment, hemodynamic support and infusion of blood products, the patient continued to decline and died in the postoperative recovery unit 14 hours after admission. Mortality ranges from 70% to 100% in sepsis due to Clostridium perfringens, and risk of death is greater if massive hemolysis is present, as in the case we report. Only a high degree of clinical suspicion leading to early diagnosis and treatment can improve the prognosis. This bacterium should therefore be considered whenever severe sepsis and hemolysis coincide.

Adjunctive use of superoxidized solution in chest wall necrotizing soft tissue infection.

A 39-year-old Indian man presented with necrotizing soft tissue infection of his right forearm and previously undiagnosed diabetes mellitus. The infection progressively worsened to involve his right lateral chest wall despite multiple debridements and systemic antibiotics. His right arm was eventually disarticulated along with wide debridement of the surrounding tissue. Aggressive wound debridement, mechanical scrubbing, and irrigation were then initiated every 8 hours. A superoxidized solution was later introduced as a wound irrigant and dressing agent. The large defect was suitable for split-thickness skin grafting after 16 days of a strict wound management routine with the superoxidized solution.

Fatal myelotoxicity after azathioprine treatment.

Azathioprine and 6-mercaptopurine have been used for many years in the treatment of inflammatory bowel disease. Approximately 0.3% of the population are homozygous for variant alleles associated with extremely low thiopurine S-methyltransferase enzyme activity. We describe the case of a young patient with ulcerative colitis, homozygous for TPMT*3A alleles, who suffered fatal azathioprine-induced myelotoxicity after standard dosing with azathioprine. Screening for decreased activity of TPMT in patients prior to azathioprine treatment is advised to minimize the risk of drug-induced toxicity.

Clindamycin-resistant Clostridium perfringens cellulitis.

Clostridium perfringens is responsible for a number of clinical conditions ranging from relatively mild food poisoning to the potentially life-threatening gas gangrene. Fortunately, C. perfringens has remained relatively susceptible to first line antibiotics in the treatment of soft tissue infection, however, the prevalence of antibiotic resistance is increasing amongst other anaerobic organisms. A case of anaerobic cellulitis caused by a clindamycin-resistant C. perfringens is described here, emphasising the emerging problem of antimicrobial resistance.