Sordellii Infection Research Articles

Requirements for Germination ofClostridium sordelliiSporesIn Vitro

Clostridium sordellii is a spore-forming, obligately anaerobic, Gram-positive bacterium that can cause toxic shock syndrome after gynecological procedures. Although the incidence of C. sordellii infection is low, it is fatal in most cases. Since spore germination is believed to be the first step in the establishment of Bacilli and Clostridia infections, we analyzed the requirements for C. sordellii spore germination in vitro. Our data showed that C. sordellii spores require three structurally different amino acids and bicarbonate for maximum germination. Unlike the case for Bacilli species, d-alanine had no effect on C. sordellii spore germination. C. sordellii spores germinated only in a narrow pH range between 5.7 and 6.5. In contrast, C. sordellii spore germination was significantly less sensitive to temperature changes than that of the Bacilli. The analysis of the kinetics of C. sordellii spore germination showed strong allosteric behavior in the binding of l-phenylalanine and l-alanine but not in that of bicarbonate or l-arginine. By comparing germinant apparent binding affinities to their known in vivo concentrations, we postulated a mechanism for differential C. sordellii spore activation in the female reproductive tract.

Innate immune recognition of, and response to, Clostridium sordellii

Clostridium sordellii, an anaerobic pathogen, has recently been associated with rapidly fatal infections following medically induced abortions and injecting drug use. Patients with C. sordellii infection display few signs of inflammation such as fever, or redness and pain at the site of infection. We hypothesized that this could be due to reduced recognition of the organism by Toll-like receptors (TLRs) of the innate immune system. An ELAM-NF-κB luciferase reporter system in TLR-transfected HEK cells was used to measure TLR-dependent recognition of washed, heat-killed C. sordellii and other pathogenic clostridial species. Results demonstrated that all clostridia were well recognized by TLR2 alone and that responses were greatest when TLR2 was co-expressed with TLR6. Further, isolated human monocytes produced the pro-inflammatory cytokine TNFα and the immunoregulator IL-10 in response to C. sordellii. In addition, C. sordellii-stimulated monocytes produced 30% less TNFα following treatment with an anti-TLR2 blocking antibody. These data demonstrate that innate immune recognition of, and response to, cell-associated components of C. sordellii and other clostridial pathogens are mediated by TLR2 in combination with TLR6. We conclude that the characteristic absence of inflammatory signs and symptoms in C. sordellii infection is not related to inadequate immune detection of the organism, but rather is attributable to a species-specific immune system dysfunction that remains to be elucidated.

A Rare Case of Clostridium sordellii Bacteremia in an Immunocompromised Patient

Clostridium sordellii is a gram-positive, anaerobic sporeforming rod with peritrichous flagella that is rarely associated with disease in humans. In most cases, infections occur after trauma, childbirth and routine gynecological procedures or intravenous drug abuse. C. sordellii produce several exotoxins that lead to progressive edema and shock, and C. sordellii infections have high mortality rates of up to 70%. Since its first report in 1922, only a few cases of bacteremia have been reported. This report describes a case of C. sordellii bacteremia in a patient with rectum carcinoma and liver metastases.

Misoprostol Impairs Female Reproductive Tract Innate Immunity against Clostridium sordellii

Fatal cases of acute shock complicating Clostridium sordellii endometritis following medical abortion with mifepristone (also known as RU-486) used with misoprostol were reported. The pathogenesis of this unexpected complication remains enigmatic. Misoprostol is a pharmacomimetic of PGE(2), an endogenous suppressor of innate immunity. Clinical C. sordellii infections were associated with intravaginal misoprostol administration, suggesting that high misoprostol concentrations within the uterus impair immune responses against C. sordellii. We modeled C. sordellii endometritis in rats to test this hypothesis. The intrauterine but not the intragastric delivery of misoprostol significantly worsened mortality from C. sordellii uterine infection, and impaired bacterial clearance in vivo. Misoprostol also reduced TNF-alpha production within the uterus during infection. The intrauterine injection of misoprostol did not enhance mortality from infection by the vaginal commensal bacterium Lactobacillus crispatus. In vitro, misoprostol suppressed macrophage TNF-alpha and chemokine generation following C. sordellii or peptidoglycan challenge, impaired leukocyte phagocytosis of C. sordellii, and inhibited uterine epithelial cell human beta-defensin expression. These immunosuppressive effects of misoprostol, which were not shared by mifepristone, correlated with the activation of the G(s) protein-coupled E prostanoid (EP) receptors EP2 and EP4 (macrophages) or EP4 alone (uterine epithelial cells). Our data provide a novel explanation for postabortion sepsis leading to death and also suggest that PGE(2), in which production is exaggerated within the reproductive tract during pregnancy, might be an important causal determinant in the pathogenesis of more common infections of the gravid uterus.

The Leukemoid Reaction inClostridium sordelliiInfection: Neuraminidase Induction of Promyelocytic Cell Proliferation

Life-threatening Clostridium sordellii infections have recently been reported in women undergoing therapeutic abortion, during natural childbirth, and in injection drug users. Shock, diffuse capillary leak, and a leukemoid reaction (LR) are cardinal features of these infections. The magnitude of the LR is highly correlated with mortality. We have isolated a 42-kDa extractable protein from C. sordellii culture supernatant that stimulates proliferation of promyelocytic HL-60 cells in vitro. Using mass spectrometry, we have identified this protein as the C. sordellii neuraminidase, NanS. Recombinant NanS (rNanS) dose dependently stimulated HL-60 cell proliferation. Increased proliferation was observed when HL-60 cells were cocultured with both rNanS and granulocyte-macrophage colony stimulating factor. In addition, NanS also modified vascular cell adhesion molecule 1, which orchestrates the release of mature and immature granulocytes from bone marrow stromal cells. Thus, neuraminidase likely plays an important role in the characteristic LR in C. sordellii infection.

Clostridium sordellii Infection: Epidemiology, Clinical Findings, and Current Perspectives on Diagnosis and Treatment

Clostridium sordellii infections pose difficult clinical challenges and are usually fatal. Most commonly, these infections occur after trauma, childbirth, and routine gynecological procedures, but they have recently been associated with medically induced abortions and injection drug use. We report 2 fatal cases, one of which was associated with minor trauma, and the other of which was associated with normal childbirth, and we summarize the clinical features of 43 additional cases of reported C. sordellii infection. Of these 45 cases, 8 (18%) were associated with normal childbirth, 5 (11%) were associated with medically induced abortion, and 2 (0.4%) were associated with spontaneous abortion. The case-fatality rate was 100% in these groups. Ten (22%) of the C. sordellii infections occurred in injection drug users, and 50% of these patients died. Other cases of C. sordellii infection (in 19 patients [43%]) occurred after trauma or surgery, mostly in healthy persons, and 53% these patients died. Overall, the mortality rate was 69% (31 of 45 patients). Eighty-five percent of all patients with fatal cases died within 2-6 days of initial infection, and nearly 80% of fatal cases developed leukemoid reactions. Rapid diagnostic tests and improved treatments are needed to reduced the morbidity and mortality associated with this devastating infection.

Clostridium sordellii Infection in Medical Abortion

A newly described, rare, lethal entity that affects previously healthy young people and has no known prevention or treatment constitutes a true public health nightmare. It also excites public attention and demands for action. The review of Clostridium sordellii infections by Aldape et al. [1] in this issue of Clinical Infectious Diseases tells the beginning of an infectious disease story to which epidemiology and clinical medicine have not yet written an ending. The organism C. sordellii is an uncommon human pathogen, although it has been more thoroughly described in veterinary medicine. Recently, several dozen cases of human infection have been reported. The number of cases in the literature has accumulated more rapidly in recent years, suggesting that this condition, like other rare diseases, is more likely to be identified when knowledge of the syndrome is more widely disseminated. Perhaps the most dramatic of the cases

Candida sepsis originating from bulbar abscess of the penis

We describe a patient with a very unusual penile abscess. Antibiotic treatment for Clostridium sordellii and Candida albicans infection and drainage of pus was curative. We propose that the penile abscess may have been an unusual manifestation of a rectal fistula.

Pathophysiology of Mifepristone-Induced Septic Shock Due toClostridium sordellii

To explain the role of mifepristone in medical abortions that results in fulminant and lethal septic shock due to Clostridium sordellii. MEDLINE, PubMed, and Google Scholar databases were searched (1984-March 2005). Key search terms were mifepristone, RU38486, RU486, Mifeprex, medical abortion, septic shock, innate immune system, cytokines, and Clostridium sordellii. All articles identified from the data sources were evaluated and all information deemed relevant was included for the information related to the development of the understanding of the pathophysiology of mifepristone-induced septic shock due to C. sordellii. The mechanisms of action of mifepristone were incorporated into the pathophysiology of septic shock due to C. sordellii. Mifepristone, by blocking both progesterone and glucocorticoid receptors, interferes with the controlled release and functioning of cortisol and cytokines. Failure of physiologically controlled cortisol and cytokine responses results in an impaired innate immune system that results in disintegration of the body's defense system necessary to prevent the endometrial spread of C. sordellii infection. The abnormal cortisol and cytokine responses due to mifepristone coupled to the release of potent exotoxins and an endotoxin from C. sordellii are the major contributors to the rapid development of lethal septic shock. Theoretically, it appears that the mechanisms of mifepristone action favor the development of infection that leads to septic shock and intensifies the actions of multiple inflammatory cytokines, resulting in fulminant, lethal septic shock.

A Fatal Case of Clostridium sordellii Septic Shock Syndrome Associated With Medical Abortion

Clostridia bacteria are infrequent human pathogens. In the obstetric and gynecologic literature, Clostridium sordellii infections have been very rarely reported. This is a case of infection following medical termination of early pregnancy with mifepristone and misoprostol. A 27-year-old woman presented for termination of pregnancy at 5.5 weeks from her last menstrual period. She received mifepristone 200 mg orally followed by 800 microg vaginal misoprostol. Three days after administration of misoprostol, she complained of dizziness, pelvic pain, and bleeding. The next day, she experienced worsening of symptoms and was hospitalized. She developed pulmonary edema, ascites, and heart failure. Despite supportive measures, antibiotics, and hysterectomy, she died 3 days later. The post mortem examinations indicated that death was caused by shock secondary to C sordellii infection. The frequency of infection following medical abortion is low. The rapid and fatal course of this infection is similar to other obstetric and gynecologic cases reported in the literature. Although providers should remain vigilant to the possibility of infection following medical abortion, the overall proven safety of medical abortion remains the same.

Outbreak of necrotizing fasciitis due to Clostridium sordellii among black-tar heroin users.

In California, black tar heroin (BTH) use among injection drug users (IDUs) has resulted in an increased number of cases of wound botulism due to Clostridium botulinum, tetanus due to Clostridium tetani, and necrotizing soft-tissue infections due to a variety of clostridia. From December 1999 to April 2000, nine IDUs in Ventura County, California, developed necrotizing fasciitis; 4 died. Cultures of wound specimens from 6 case patients yielded Clostridium sordellii. Some of the patients appeared to have the toxic shock syndrome previously reported to be characteristic of toxin-mediated C. sordellii infection, which is characterized by hypotension, marked leukocytosis, and hemoconcentration. The suspected source of this outbreak was contaminated BTH that was injected subcutaneously or intramuscularly ("skin popped"). This outbreak of C. sordellii infection serves as another example of how BTH can potentially serve as a vehicle for transmitting severe and often deadly clostridial infections, and reinforces the need to educate IDUs and clinicians about the risks associated with skin popping of BTH.

Postpartum Clostridium sordellii infection associated with fatal toxic shock syndrome

Clostridium bacteria are anaerobic Gram positive spore-form-ing bacilli, known to cause distinct clinical syndromes such as botulism, tetanus, pseudomembranous colitis and myonecrosis. The natural habitats of Clostridium species are soil, water and the gastrointestinal tract of animals and humans. In 5-10% of all women, Clostridium species are also found to be normal inhabitants in the microbial flora of the female genital tract. In case of a non-sexually transmitted genital tract infection, Clostridium species are isolated in 4-20%, and clostridium welchii seems to be the most common isolate. Clostridium sordellii is rarely encountered in clinical specimens (1% of Clostridium species), but it has been described as a human pathogen with fatal potential. Two toxins, a lethal and a hemorrhagic (that antigenically and pathophysiologically appear similar to Clostridium difficile toxins B and A, respectively) are responsible for this potential. Reviewing the obstetric literature, only six cases of postpartum endometritis caused by C. sordellii, are described - all being fatal. In addition, one lethal case of spontaneous endometritis resulting from C. sordellii is reported. The clinical aspects of these cases include: - sudden onset with influenza-like symptoms in previously healthy women - progressive refractory hypotension - local and spreading tissue edema - absence of fever Laboratory findings include: - marked leukocytosis - elevated hematocrit. This paper reports the seventh fatal postpartum C. sorlellii associated toxic shock syndrome - the first recognized in Scandinavia.

Postpartum Clostridium sordellii infection associated with fatal toxic shock syndrome

Postpartum Clostridium sordellii infection associated with fatal toxic shock syndrome

Postpartum Clostridium sordellii infection associated with fatal toxic shock syndrome

Postpartum Clostridium sordellii infection associated with fatal toxic shock syndrome

A fatal postpartum Clostridium sordellii associated toxic shock syndrome.

Clostridium sordellii is an infrequent human pathogen. It has been demonstrated to be occasionally responsible for myonecrosis or gas gangrene. Interestingly, in the obstetric literature, some cases of postpartum maternal...

Clostridium sordellii infection and toxin neutralization

Clostridium sordellii infection and toxin neutralization

Maternal deaths associated with Clostridium sordellii infection

Clostridium sordellii is a common soil and enteric bacterium that is infrequently recovered from the vagina. We describe three women in which C. sordellii caused puerperal infection and a distinctive and lethal toxic shock-like syndrome. Patients were <1 week post partum and each had a single, limited focus of infection including infection associated with a retained vaginal sponge, a cesarean section operative site, and endometritis. Each patient had a distinctive course characterized by sudden onset of clinical shock marked by severe and unrelenting hypotension associated with marked, generalized tissue edema and “third spacing” with increased hematocrit, presence of marked leukemoid reaction with total neutrophil counts of 84,000/mm 3, 66,000/mm 3, and 93,600/mm 3, absence of rash or fever, limited or no myonecrosis, and a rapid and uniformly lethal course. Hypoalbuminemia was also noted. Similar findings were noted in prior isolated reports of C. sordellii-mediated postpartum or surgical infection. Treatment of animals with C. sordellii or closely related C. difficile toxins produces similar findings. We suggest that localized infection with toxin-producing strains of C. sordellii can produce a rapidly lethal toxic shock-like syndrome. Further study and earlier recognition of this syndrome may be life-saving in other patients.

Production od diarrhoea and enteric lesions in calves by the oral inoculation of pure cultures of Clostridium sordellii.

Pure cultures of an isolate of Clostridium sordellii obtained from a case of haemorrhagic enteritis in a two-year-old cow were used to infect calves in three experiments. C sordellii initiated a slight rise in rectal temperature and the passage of soft faeces containing blood and mucus within one to six days of inoculation in six calves in two controlled experiments. C sordellii was isolated from the faeces of all affected animals but only from their large intestines at slaughter. Mild inflammatory changes were seen in the gastrointestinal tract. The pathogenesis of C sordellii infection was studied in experimental calves and culture filtrate was found to produce similar clinical and pathological changes to those produced by whole culture. In these studies the organism was isolated from the anterior parts of the gastrointestinal tract only within four days of inoculation. The histological changes produced consisted of mild congestion and inflammatory change in the jejunal and ileal mucosa and dilatation of the crypts and capillary dilatation in the large intestinal mucosa. The relationship between C sordellii and the changes observed in natural and experimental infections was discussed and compared with that of C difficile infection in man.

N1-BENZOYL-SULPHANILAMIDE IN EXPERIMENTAL GAS GANGRENE

It is shown that in regard to gas gangrene Clostridium the in vitro bacteriostatic action of N1-benzoyl-sulphanilamide is similar to that of sulphathiazole and sulphadiazine. In local treatment of experimental gas gangrene in guinea pigs, N1-benzoyl-sulphanilamide is equal to sulphathiazole in retarding infection with C. welchii, C. novyi, or C. septicum. It is slightly superior to sulphathiazole in retarding C. sordellii infections.