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Sample records for clostridium sordellii infection

  1. Foot infection by Clostridium sordellii: case report and review of 15 cases in France.

    PubMed

    Bouvet, Philippe; Sautereau, Jean; Le Coustumier, Alain; Mory, Francine; Bouchier, Christiane; Popoff, Michel-R

    2015-04-01

    We report a case of foot infection by Clostridium sordellii and review 15 human infections registered at a Reference Center in France during the period 1998 to 2011. All strains were found nontoxigenic, lacking the lethal toxin gene coding for TcsL. Like Clostridium septicum, several C. sordellii infections were associated with intestinal neoplasms. PMID:25609723

  2. Foot Infection by Clostridium sordellii: Case Report and Review of 15 Cases in France

    PubMed Central

    Sautereau, Jean; Le Coustumier, Alain; Mory, Francine; Bouchier, Christiane; Popoff, Michel-R.

    2015-01-01

    We report a case of foot infection by Clostridium sordellii and review 15 human infections registered at a Reference Center in France during the period 1998 to 2011. All strains were found nontoxigenic, lacking the lethal toxin gene coding for TcsL. Like Clostridium septicum, several C. sordellii infections were associated with intestinal neoplasms. PMID:25609723

  3. Identification and Characterization of Clostridium sordellii Toxin Gene Regulator

    PubMed Central

    Sirigi Reddy, Apoorva Reddy; Girinathan, Brintha Parasumanna; Zapotocny, Ryan

    2013-01-01

    Toxigenic Clostridium sordellii causes uncommon but highly lethal infections in humans and animals. Recently, an increased incidence of C. sordellii infections has been reported in women undergoing obstetric interventions. Pathogenic strains of C. sordellii produce numerous virulence factors, including sordellilysin, phospholipase, neuraminidase, and two large clostridial glucosylating toxins, TcsL and TcsH. Recent studies have demonstrated that TcsL toxin is an essential virulence factor for the pathogenicity of C. sordellii. In this study, we identified and characterized TcsR as the toxin gene (tcsL) regulator in C. sordellii. High-throughput sequencing of two C. sordellii strains revealed that tcsR lies within a genomic region that encodes TcsL, TcsH, and TcsE, a putative holin. By using ClosTron technology, we inactivated the tcsR gene in strain ATCC 9714. Toxin production and tcsL transcription were decreased in the tcsR mutant strain. However, the complemented tcsR mutant produced large amounts of toxins, similar to the parental strain. Expression of the Clostridium difficile toxin gene regulator tcdR also restored toxin production to the C. sordellii tcsR mutant, showing that these sigma factors are functionally interchangeable. PMID:23873908

  4. A fatal postpartum Clostridium sordellii associated toxic shock syndrome.

    PubMed Central

    Bitti, A; Mastrantonio, P; Spigaglia, P; Urru, G; Spano, A I; Moretti, G; Cherchi, G B

    1997-01-01

    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 deaths have been associated with C sordellii infection causing a rapidly lethal toxin mediated syndrome. This is the first reported case of postpartum death in a 29 year old woman, in which a toxigenic C sordellii was isolated from the patient's blood antemortem during the fatal toxic shock, strongly indicating its role in this rare syndrome. PMID:9155682

  5. Clostridium sordellii in a brown bear (Ursus arctos) from Spain.

    PubMed

    Balseiro, Ana; Oleaga, Álvaro; Polledo, Laura; Aduriz, Gorka; Atxaerandio, Raquel; Kortabarria, Nekane; Marín, Juan F García

    2013-10-01

    Clostridium sordellii is found in the environment and occasionally in animal (including human) intestines and may cause myonecrosis and large outbreaks of enterotoxemia. A few cases of fatal clostridial infection in bears (Ursus spp.) have been described worldwide but none attributed to C. sordellii. We describe a fatal case of septicemia caused by C. sordellii in an illegally trapped brown bear (Ursus arctos). At necropsy, acute gangrenous myositis was the primary lesion. Serohemorrhagic edema was observed in the abdominal cavity, thorax, pericardium, and skeletal muscle, mostly affecting femoral, humeral, and scapular muscles. Hemorrhage was observed in the heart, skeletal muscles, stomach, and intestine. Liver, spleen, and kidney appeared with loss of consistency, hemorrhages, and edema. Microscopically, primary lesions were in skeletal muscle, stomach, and small intestine, with gram-positive, clostridial-like bacilli. Biochemical and molecular tests identified C. sordellii in cultures from liver, muscle, and intestine. Sequences showed a homology of >99% with the 16S rRNA gene sequence of C. sordellii. The severity of effects of the C. sordellii infection reveal the importance of this pathogen as a wildlife health risk with conservation concerns, as well as the need to consider possible infection with this pathogen in management actions involving immobilization, stress, or severe muscular activity of wild brown bears. PMID:24502739

  6. Clostridium novyi, sordellii, and tetani: mechanisms of disease.

    PubMed

    Aronoff, David M

    2013-12-01

    Clostridia represent a diverse group of spore-forming gram positive anaerobes that include several pathogenic species. In general, diseases caused by clostridia are a result of intoxication of the infected host. Thus, clostridial toxins have been targeted for diagnostic, therapeutic, and preventive strategies against infection. Studying the mechanisms of action of clostridial toxins has not only shed light on the pathogenesis of infection but has provided important new insights into cell biology and immunology. A primary purpose of this manuscript is to provide a succinct review on the mechanisms of disease caused by intoxication by the pathogens Clostridium tetani, Clostridium novyi, and Clostridium sordellii. PMID:24036420

  7. Non-lethal Clostridium sordellii bacteraemia in an immunocompromised patient with pleomorphic sarcoma.

    PubMed

    Bonnecaze, Alex K; Stephens, Sarah Ellen Elza; Miller, Peter John

    2016-01-01

    Clostridium sordellii is a spore-forming anaerobic Gram-positive rod that has rarely been reported to cause disease in humans. Resultant mortality from infection is estimated at nearly 70% and is most often correlated with gynaecological procedures, intravenous drug abuse or trauma. C. sordellii infection often presents similarly to toxic shock syndrome (TSS); notable features of infection include refractory hypotension, haemoconcentration and marked leucocytosis. Although clinically similar to TSS, a notable difference is C. sordellii infections rarely involve fever. The organism's major toxins include haemorrhagic (TcsH) and lethal factor (TcsL), which function to disrupt cytoskeletal integrity. Current literature suggests treating C. sordelli infection with a broad-spectrum penicillin, metronidazole and clindamycin. We present a case of C. sordellii bacteraemia and septic shock in an immunocompromised patient who was recently diagnosed with pleomorphic gluteal sarcoma. Despite presenting in critical condition, the patient improved after aggressive hemodynamic resuscitation, source control and intravenous antibiotic therapy. PMID:27489063

  8. Misoprostol Impairs Female Reproductive Tract Innate Immunity against Clostridium sordellii1

    PubMed Central

    Aronoff, David M.; Hao, Yibai; Chung, Jooho; Coleman, Nicole; Lewis, Casey; Peres, Camila M.; Serezani, Carlos H.; Chen, Gwo-Hsiao; Flamand, Nicolas; Brock, Thomas G.; Peters-Golden, Marc

    2009-01-01

    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 PGE2, 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-α 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-α and chemokine generation following C. sordellii or peptidoglycan challenge, impaired leukocyte phagocytosis of C. sordellii, and inhibited uterine epithelial cell human β-defensin expression. These immunosuppressive effects of misoprostol, which were not shared by mifepristone, correlated with the activation of the Gs 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 PGE2, 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. PMID:18523288

  9. Clostridium sordellii as a Cause of Fatal Septic Shock in a Child with Hemolytic Uremic Syndrome.

    PubMed

    Beyers, Rebekah; Baldwin, Michael; Dalabih, Sevilay; Dalabih, Abdallah

    2014-01-01

    Clostridium sordellii is a toxin producing ubiquitous gram-positive anaerobe, mainly associated with trauma, soft tissue skin infections, and gynecologic infection. We report a unique case of a new strain of Clostridium sordellii (not present in the Center for Disease Control (CDC) database) infection induced toxic shock syndrome in a previously healthy two-year-old male with colitis-related hemolytic uremic syndrome (HUS). The patient presented with dehydration, vomiting, and bloody diarrhea. He was transferred to the pediatric critical care unit (PICU) for initiation of peritoneal dialysis (PD). Due to increased edema and intolerance of PD, he was transitioned to hemodialysis through a femoral vascular catheter. He subsequently developed severe septic shock with persistent leukocytosis and hypotension, resulting in subsequent death. Stool culture confirmed Shiga toxin producing Escherichia coli 0157:H7. A blood culture was positively identified for Clostridium sordellii. Clostridium sordelli is rarely reported in children; to our knowledge this is the first case described in a pediatric patient with HUS. PMID:24891968

  10. Rapid, Simultaneous Detection of Clostridium sordellii and Clostridium perfringens in Archived Tissues by a Novel PCR-Based Microsphere Assay: Diagnostic Implications for Pregnancy-Associated Toxic Shock Syndrome Cases

    PubMed Central

    Bhatnagar, Julu; DeLeon-Carnes, Marlene; Kellar, Kathryn L.; Bandyopadhyay, Kakali; Antoniadou, Zoi-Anna; Shieh, Wun-Ju; Paddock, Christopher D.; Zaki, Sherif R.

    2012-01-01

    Clostridium sordellii and Clostridium perfringens are infrequent human pathogens; however, the case-fatality rates for the infections are very high, particularly in obstetric C. sordellii infections (>90%). Deaths from Clostridium sordellii and Clostridium perfringens toxic shock (CTS) are sudden, and diagnosis is often challenging. Formalin-fixed, paraffin-embedded (FFPE) tissues usually are the only specimens available for sudden fatal cases, and immunohistochemistry (IHC) for Clostridia is generally performed but it cannot identify species. A clear need exists for a rapid, species-specific diagnostic assay for FFPE tissues. We developed a duplex PCR-based microsphere assay for simultaneous detection of C. sordellii and C. perfringens and evaluated DNA extracted from 42 Clostridium isolates and FFPE tissues of 28 patients with toxic shock/endometritis (20 CTS, 8 non-CTS, as confirmed by PCR and sequencing). The microsphere assay correctly identified C. sordellii and C. perfringens in all known isolates and in all CTS patients (10 C. sordellii, 8 C. perfringens, 2 both) and showed 100% concordance with PCR and sequencing results. The microsphere assay is a rapid, specific, and cost-effective method for the diagnosis of CTS and offers the advantage of simultaneous testing for C. sordellii and C. perfringens in FFPE tissues using a limited amount of DNA. PMID:22536012

  11. A novel murine model of Clostridium sordellii myonecrosis: Insights into the pathogenesis of disease.

    PubMed

    Aldape, Michael J; Bayer, Clifford R; Bryant, Amy E; Stevens, Dennis L

    2016-04-01

    Clostridium sordellii infections have been reported in women following natural childbirth and spontaneous or medically-induced abortion, injection drug users and patients with trauma. Death is rapid and mortality ranges from 70 to 100%. Clinical features include an extreme leukemoid reaction, the absence of fever, and only minimal pain or erythema at the infected site. In the current study, we developed a murine model of C. sordellii soft tissue infection to elucidate the pathogenic mechanisms. Mice received 0.5, 1.0 or 2.0 × 10(6) CFU C. sordellii (ATCC 9714 type strain) in the right thigh muscle. All doses caused fatal infection characterized by intense swelling of the infected limb but no erythema or visible perfusion deficits. Survival rates and time to death were inoculum dose-dependent. Mice developed a granulocytic leukocytosis with left shift, the onset of which directly correlated with disease severity. Histopathology of infected tissue showed widespread edema, moderate muscle damage and minimal neutrophil infiltration. Circulating levels of granulocyte colony-stimulating factor (G-CSF), soluble tumor necrosis factor receptor I (sTNF-RI) and interlukin-6 (IL-6) were significantly increased in infected animals, while TNF-α, and IL-1β levels were only mildly elevated, suggesting these host factors likely mediate the leukocytosis and innate immune dysfunction characteristic of this infection. Thus, this model mimics many of the salient features of this infection in humans and has allowed us to identify novel targets for intervention. PMID:26805011

  12. Clostridium sordellii Lethal-Toxin Autoprocessing and Membrane Localization Activities Drive GTPase Glucosylation Profiles in Endothelial Cells

    PubMed Central

    Craven, Ryan

    2015-01-01

    ABSTRACT Clostridium sordellii infections cause gangrene and edema in humans and gastrointestinal infections in livestock. One of the principle virulence factors is TcsL, a large protein toxin which glucosylates host GTPases to cause cytopathic and cytotoxic effects. TcsL has two enzymatic domains, an N-terminal glucosyltransferase domain (GTD) and an autoprocessing domain responsible for release of the GTD within the cell. The GTD can then use its N-terminal membrane localization domain (MLD) for orientation on membranes and modification of GTPases. This study describes the use of conditionally immortalized murine pulmonary microvascular endothelial cells as a model for the study of TcsL functional activities. Point mutations that disrupt the glucosyltransferase, autoprocessing, or membrane localization activities were introduced into a recombinant version of TcsL, and the activities of these mutants were compared to those of wild-type toxin. We observed that all mutants are defective or impaired in cytotoxicity but differ in their modification of Rac1 and Ras. The data suggest a model where differences in GTPase localization dictate cellular responses to intoxication and highlight the importance of autoprocessing in the function of TcsL. IMPORTANCE Clostridium sordellii is a bacterium that can infect humans and cause serious disease and death. The principle virulence factor associated with clinical symptoms is a large protein toxin known as lethal toxin. The mechanism of lethal-toxin intoxication is assumed to be similar to that of the homologous toxins from C. difficile, but very few studies have been done in the context of endothelial cells, a relevant target in C. sordellii infections. This study was designed to test the role of the lethal-toxin enzymatic activities and membrane localization in endothelial cell toxicity and host substrate modification. PMID:27303685

  13. The Sialidase NanS Enhances Non-TcsL Mediated Cytotoxicity of Clostridium sordellii.

    PubMed

    Awad, Milena M; Singleton, Julie; Lyras, Dena

    2016-01-01

    The clostridia produce an arsenal of toxins to facilitate their survival within the host environment. TcsL is one of two major toxins produced by Clostridium sordellii, a human and animal pathogen, and is essential for disease pathogenesis of this bacterium. C. sordellii produces many other toxins, but the role that they play in disease is not known, although previous work has suggested that the sialidase enzyme NanS may be involved in the characteristic leukemoid reaction that occurs during severe disease. In this study we investigated the role of NanS in C. sordellii disease pathogenesis. We constructed a nanS mutant and showed that NanS is the only sialidase produced from C. sordellii strain ATCC9714 since sialidase activity could not be detected from the nanS mutant. Complementation with the wild-type gene restored sialidase production to the nanS mutant strain. Cytotoxicity assays using sialidase-enriched culture supernatants applied to gut (Caco2), vaginal (VK2), and cervical cell lines (End1/E6E7 and Ect1/E6E7) showed that NanS was not cytotoxic to these cells. However, the cytotoxic capacity of a toxin-enriched supernatant to the vaginal and cervical cell lines was substantially enhanced in the presence of NanS. TcsL was not the mediator of the observed cytotoxicity since supernatants harvested from a TcsL-deficient strain displayed similar cytotoxicity levels to TcsL-containing supernatants. This study suggests that NanS works synergistically with an unknown toxin or toxins to exacerbate C. sordellii-mediated tissue damage in the host. PMID:27322322

  14. The Sialidase NanS Enhances Non-TcsL Mediated Cytotoxicity of Clostridium sordellii

    PubMed Central

    Awad, Milena M.; Singleton, Julie; Lyras, Dena

    2016-01-01

    The clostridia produce an arsenal of toxins to facilitate their survival within the host environment. TcsL is one of two major toxins produced by Clostridium sordellii, a human and animal pathogen, and is essential for disease pathogenesis of this bacterium. C. sordellii produces many other toxins, but the role that they play in disease is not known, although previous work has suggested that the sialidase enzyme NanS may be involved in the characteristic leukemoid reaction that occurs during severe disease. In this study we investigated the role of NanS in C. sordellii disease pathogenesis. We constructed a nanS mutant and showed that NanS is the only sialidase produced from C. sordellii strain ATCC9714 since sialidase activity could not be detected from the nanS mutant. Complementation with the wild-type gene restored sialidase production to the nanS mutant strain. Cytotoxicity assays using sialidase-enriched culture supernatants applied to gut (Caco2), vaginal (VK2), and cervical cell lines (End1/E6E7 and Ect1/E6E7) showed that NanS was not cytotoxic to these cells. However, the cytotoxic capacity of a toxin-enriched supernatant to the vaginal and cervical cell lines was substantially enhanced in the presence of NanS. TcsL was not the mediator of the observed cytotoxicity since supernatants harvested from a TcsL-deficient strain displayed similar cytotoxicity levels to TcsL-containing supernatants. This study suggests that NanS works synergistically with an unknown toxin or toxins to exacerbate C. sordellii-mediated tissue damage in the host. PMID:27322322

  15. Clostridium Sordellii as an Uncommon Cause of Fatal Toxic Shock Syndrome in a Postpartum 33-Year-Old Asian Woman, and the Need for Antepartum Screening for This Clostridia Species in the General Female Population.

    PubMed

    Guzzetta, Melissa; Williamson, Alex; Duong, Scott

    2016-08-01

    Clostridium sordellii (C. sordellii) is an anaerobic gram-positive rod most commonly found in the soil and sewage but also as part of the normal flora of the gastrointestinal tract and vagina of a small percentage of healthy individuals. C. sordellii infection is considered to result from childbirth, abortion, and/or gynecological procedures. Although many strains of C. sordellii are nonpathogenic, virulent toxin-producing strains exist. Infection with this organism typically manifests as a patient experiencing septic shock rapidly followed by end-organ failure. Identification of C. sordelli has been successful by traditional culture, mass spectrometry methods, and via molecular methods. Herein, we present a fatal case of C. sordellii infection of a postpartum 33-year-old Asian woman. The organism was isolated by culture and identified using matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) technology. With the advent of rapid detection methods, antepartum screening for the fatal Clostridium species should be implemented in the general female population. PMID:27371657

  16. Metal Ion Activation of Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B.

    PubMed

    Genth, Harald; Schelle, Ilona; Just, Ingo

    2016-01-01

    Lethal Toxin from Clostridium sordellii (TcsL) and Toxin B from Clostridium difficile (TcdB) belong to the family of the "Large clostridial glycosylating toxins." These toxins mono-O-glucosylate low molecular weight GTPases of the Rho and Ras families by exploiting UDP-glucose as a hexose donor. TcsL is casually involved in the toxic shock syndrome and the gas gangrene. TcdB-together with Toxin A (TcdA)-is causative for the pseudomembranous colitis (PMC). Here, we present evidence for the in vitro metal ion activation of the glucosyltransferase and the UDP-glucose hydrolysis activity of TcsL and TcdB. The following rating is found for activation by divalent metal ions: Mn(2+) > Co(2+) > Mg(2+) > Ca(2+), Cu(2+), Zn(2+). TcsL and TcdB thus require divalent metal ions providing an octahedral coordination sphere. The EC50 values for TcsL were estimated at about 28 µM for Mn(2+) and 180 µM for Mg(2+). TcsL and TcdB further require co-stimulation by monovalent K⁺ (not by Na⁺). Finally, prebound divalent metal ions were dispensible for the cytopathic effects of TcsL and TcdB, leading to the conclusion that TcsL and TcdB recruit intracellular metal ions for activation of the glucosyltransferase activity. With regard to the intracellular metal ion concentrations, TcsL and TcdB are most likely activated by K⁺ and Mg(2+) (rather than Mn(2+)) in mammalian target cells. PMID:27089365

  17. Metal Ion Activation of Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B

    PubMed Central

    Genth, Harald; Schelle, Ilona; Just, Ingo

    2016-01-01

    Lethal Toxin from Clostridium sordellii (TcsL) and Toxin B from Clostridium difficile (TcdB) belong to the family of the “Large clostridial glycosylating toxins.” These toxins mono-O-glucosylate low molecular weight GTPases of the Rho and Ras families by exploiting UDP-glucose as a hexose donor. TcsL is casually involved in the toxic shock syndrome and the gas gangrene. TcdB—together with Toxin A (TcdA)—is causative for the pseudomembranous colitis (PMC). Here, we present evidence for the in vitro metal ion activation of the glucosyltransferase and the UDP-glucose hydrolysis activity of TcsL and TcdB. The following rating is found for activation by divalent metal ions: Mn2+ > Co2+ > Mg2+ >> Ca2+, Cu2+, Zn2+. TcsL and TcdB thus require divalent metal ions providing an octahedral coordination sphere. The EC50 values for TcsL were estimated at about 28 µM for Mn2+ and 180 µM for Mg2+. TcsL and TcdB further require co-stimulation by monovalent K+ (not by Na+). Finally, prebound divalent metal ions were dispensible for the cytopathic effects of TcsL and TcdB, leading to the conclusion that TcsL and TcdB recruit intracellular metal ions for activation of the glucosyltransferase activity. With regard to the intracellular metal ion concentrations, TcsL and TcdB are most likely activated by K+ and Mg2+ (rather than Mn2+) in mammalian target cells. PMID:27089365

  18. Rac1 inactivation by lethal toxin from Clostridium sordellii modifies focal adhesions upstream of actin depolymerization.

    PubMed

    Geny, Blandine; Grassart, Alexandre; Manich, Maria; Chicanne, Gaëtan; Payrastre, Bernard; Sauvonnet, Nathalie; Popoff, Michel R

    2010-02-01

    Inactivation of different small GTPases upon their glucosylation by lethal toxin from Clostridium sordellii strain IP82 (LT-82) is already known to lead to cell rounding, adherens junction (AJ) disorganization and actin depolymerization. In the present work, we observed that LT-82 induces a rapid dephosphorylation of paxillin, a protein regulating focal adhesion (FA), independently of inactivation of paxillin kinases such as Src, Fak and Pyk2. Among the small GTPases inactivated by this toxin, including Rac, Ras, Rap and Ral, we identified Rac1, as responsible for paxillin dephosphorylation using cells overexpressing Rac1(V12). Rac1 inactivation by LT-82 modifies interactions between proteins from AJ and FA complexes as shown by pull-down assays. We showed that in Triton X-100-insoluble membrane proteins from these complexes, namely E-cadherin, beta-catenin, p120-catenin and talin, are decreased upon LT-82 intoxication, a treatment that also induces a rapid decrease in cell phosphoinositide content. Therefore, we proposed that Rac inactivation by LT-82 alters phosphoinositide metabolism leading to FA and AJ complex disorganization and actin depolymerization. PMID:19840028

  19. Antibodies against recombinant catalytic domain of lethal toxin of Clostridium sordellii neutralize lethal toxin toxicity in HeLa cells.

    PubMed

    Arya, Preetika; Ponmariappan, S; Singh, Lokendra; Prasad, G B K S

    2013-02-01

    Lethal toxin of Clostridium sordellii (MLD 150 ng/kg) is one of the most potent Clostridial toxins and is responsible for most of the diseases including sudden death syndrome in cattle, sheep and toxic shock syndrome, necrotizing faciitis, neonatal omphalitis and gangrene in humans. Lethal toxin (TcsL) is a single chain protein of about 270 kDa. In the present study, 1.6 kb DNA fragment encoding for the catalytic domain of TcsL was PCR amplified, cloned in pQE30 UA vector and expressed in E. coli SG 13009. The expression of recombinant lethal toxin protein (rTcsL) was optimized and it was purified under native conditions using a single step Ni-NTA affinity chromatography. The purified recombinant protein was used for the production of polyclonal antibodies in mice and rabbit. The raised antibodies reacted specifically with the purified rTcsL and intact native lethal toxin on Western blot. The biological activity of the recombinant protein was tested in HeLa cells where it showed the cytotoxicity. Further, the polyclonal antibodies were used for in-vitro neutralization of purified rTcsL, acid precipitated C. sordellii and C. difficile native toxins in HeLa cells. Mice and rabbit anti-rTcsL sera effectively neutralized the cytotoxicity of rTcsL and C. sordellii native toxin but it did not neutralize the cytotoxicity of C. difficile toxin in HeLa cells. PMID:22894159

  20. Characterization and regulation of the NADP-linked 7 alpha-hydroxysteroid dehydrogenase gene from Clostridium sordellii.

    PubMed Central

    Coleman, J P; Hudson, L L; Adams, M J

    1994-01-01

    A bile acid-inducible NADP-linked 7 alpha-hydroxysteroid dehydrogenase (7 alpha-HSDH) from Clostridium sordellii ATCC 9714 was purified 310-fold by ion-exchange, gel filtration, and dye-ligand affinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the purified enzyme showed one predominant peptide band (30,000 Da). The N-terminal sequence was determined, and the corresponding oligonucleotides were synthesized and used to screen EcoRI and HindIII genomic digests of C. sordellii. Two separate fragments (4,500 bp, EcoRI; 3,200 bp, HindIII) were subsequently cloned by ligation to pUC19 and transformation into Escherichia coli DH5 alpha-MCR. The EcoRI fragment was shown to contain a truncated 7 alpha-HSDH gene, while the HindIII fragment contained the entire coding region. E. coli clones containing the HindIII insert expressed high levels of an NADP-linked 7 alpha-HSDH. Nucleotide sequence analyses suggest that the 7 alpha-HSDH is encoded by a monocistronic transcriptional unit, with DNA sequence elements resembling rho-independent terminators located in both the upstream and downstream flanking regions. The transcriptional start site was located by primer extension analysis. Northern (RNA) blot analysis indicated that induction is mediated at the transcriptional level in response to the presence of bile acid in the growth medium. In addition, growth-phase-dependent expression is observed in uninduced cultures. Analysis of the predicted protein sequence indicates that the enzyme can be classified in the short-chain dehydrogenase group. Images PMID:8050999

  1. Inhibition of small G proteins by clostridium sordellii lethal toxin activates cdc2 and MAP kinase in Xenopus oocytes.

    PubMed

    Rime, H; Talbi, N; Popoff, M R; Suziedelis, K; Jessus, C; Ozon, R

    1998-12-15

    The lethal toxin (LT) from Clostridium sordellii is a glucosyltransferase that modifies and inhibits small G proteins of the Ras family, Ras and Rap, as well as Rac proteins. LT induces cdc2 kinase activation and germinal vesicle breakdown (GVBD) when microinjected into full-grown Xenopus oocytes. Toxin B from Clostridium difficile, that glucosylates and inactivates Rac proteins, does not induce cdc2 activation, indicating that proteins of the Ras family, Ras and/or Rap, negatively regulate cdc2 kinase activation in Xenopus oocyte. In oocyte extracts, LT catalyzes the incorporation of [14C]glucose into a group of proteins of 23 kDa and into one protein of 27 kDa. The 23-kDa proteins are recognized by anti-Rap1 and anti-Rap2 antibodies, whereas the 27-kDa protein is recognized by several anti-Ras antibodies and probably corresponds to K-Ras. Microinjection of LT into oocytes together with UDP-[14C]glucose results in a glucosylation pattern similar to the in vitro glucosylation, indicating that the 23- and 27-kDa proteins are in vivo substrates of LT. In vivo time-course analysis reveals that the 27-kDa protein glucosylation is completed within 2 h, well before cdc2 kinase activation, whereas the 23-kDa proteins are partially glucosylated at GVBD. This observation suggests that the 27-kDa Ras protein could be the in vivo target of LT allowing cdc2 kinase activation. Interestingly, inactivation of Ras proteins does not prevent the phosphorylation of c-Raf1 and the activation of MAP kinase that occurs normally around GVBD. PMID:9882492

  2. Clostridium difficile infection

    PubMed Central

    Viswanathan, VK; Mallozzi, MJ

    2010-01-01

    Clostridium difficile infection (CDI) is the primary cause of antibiotic-associated diarrhea and is a significant nosocomial disease. In the past ten years, variant toxin-producing strains of C. difficile have emerged, that have been associated with severe disease as well as outbreaks worldwide. This review summarizes current information on C. difficile pathogenesis and disease, and highlights interventions used to combat single and recurrent episodes of CDI. PMID:21327030

  3. Clostridium difficile infection.

    PubMed

    Smits, Wiep Klaas; Lyras, Dena; Lacy, D Borden; Wilcox, Mark H; Kuijper, Ed J

    2016-01-01

    Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota. PMID:27158839

  4. Clostridium Difficile Infections

    MedlinePlus

    Clostridium difficile (C. difficile) is a bacterium that causes diarrhea and more serious intestinal conditions such as colitis. Symptoms include Watery ... Nausea Abdominal pain or tenderness You might get C. difficile disease if you have an illness that ...

  5. The Tip of the Four N-Terminal α-Helices of Clostridium sordellii Lethal Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating Small GTPases Glucosylation

    PubMed Central

    Varela Chavez, Carolina; Haustant, Georges Michel; Baron, Bruno; England, Patrick; Chenal, Alexandre; Pauillac, Serge; Blondel, Arnaud; Popoff, Michel-Robert

    2016-01-01

    Clostridium sordellii lethal toxin (TcsL) is a powerful virulence factor responsible for severe toxic shock in man and animals. TcsL belongs to the large clostridial glucosylating toxin (LCGT) family which inactivates small GTPases by glucosylation with uridine-diphosphate (UDP)-glucose as a cofactor. Notably, TcsL modifies Rac and Ras GTPases, leading to drastic alteration of the actin cytoskeleton and cell viability. TcsL enters cells via receptor-mediated endocytosis and delivers the N-terminal glucosylating domain (TcsL-cat) into the cytosol. TcsL-cat was found to preferentially bind to phosphatidylserine (PS)-containing membranes and to increase the glucosylation of Rac anchored to the lipid membrane. We have previously reported that the N-terminal four helical bundle structure (1–93 domain) recognizes a broad range of lipids, but that TcsL-cat specifically binds to PS and phosphatidic acid. Here, we show using mutagenesis that the PS binding site is localized on the tip of the four-helix bundle which is rich in positively-charged amino acids. Residues Y14, V15, F17, and R18 on loop 1, between helices 1 and 2, in coordination with R68 from loop 3, between helices 3 and 4, form a pocket which accommodates L-serine. The functional PS-binding site is required for TcsL-cat binding to the plasma membrane and subsequent cytotoxicity. TcsL-cat binding to PS facilitates a high enzymatic activity towards membrane-anchored Ras by about three orders of magnitude as compared to Ras in solution. The PS-binding site is conserved in LCGTs, which likely retain a common mechanism of binding to the membrane for their full activity towards membrane-bound GTPases. PMID:27023605

  6. Clostridium difficile infections in China.

    PubMed

    Jin, Ke; Wang, Shixia; Huang, Zuhu; Lu, Shan

    2010-11-01

    Clostridium difficile (C. difficile) infection has become one of the major hospital-associated infections in Western countries in the last two decades. However, there is limited information on the status of C. difficile infection in Chinese healthcare settings. Given the large and increasing elderly population and the well-recognized problem of over-prescribing of broad spectrum antibiotics in China, it is critical to understand the epidemiology and potential risk factors that may contribute to C. difficile infection in China. A literature review of available published studies, including those in Chinese language-based journals, was conducted. A review of the currently available literature suggested the presence of C. difficile infections in China, but also suggested that these infections were not particularly endemic. This finding should lead to better designed and greatly expanded studies to provide a more reliable epidemiologically-based conclusion on the actual status of C. difficile infection in China, including the identification of any associated risk factors. Such information is ultimately valuable to develop appropriate strategies to prevent C. difficile infection and the vast negative impact of such infections in China and other developing countries. PMID:23554657

  7. Clostridium difficile infection in Thailand.

    PubMed

    Putsathit, Papanin; Kiratisin, Pattarachai; Ngamwongsatit, Puriya; Riley, Thomas V

    2015-01-01

    Clostridium difficile is the aetiological agent in ca. 20% of cases of antimicrobial-associated diarrhoea in hospitalised adults. Diseases caused by this organism range from mild diarrhoea to occasional fatal pseudomembranous colitis. The epidemiology of C. difficile infection (CDI) has changed notably in the past decade, following epidemics in the early 2000s of PCR ribotype (RT) 027 infection in North America and Europe, where there was an increase in disease severity and mortality. Another major event has been the emergence of RT 078, initially as the predominant ribotype in production animals in the USA and Europe, and then in humans in Europe. Although there have been numerous investigations of the epidemiology of CDI in North America and Europe, limited studies have been undertaken elsewhere, particularly in Asia. Antimicrobial exposure remains the major risk factor for CDI. Given the high prevalence of indiscriminate and inappropriate use of antimicrobials in Asia, it is conceivable that CDI is relatively common among humans and animals. This review describes the level of knowledge in Thailand regarding C. difficile detection methods, prevalence and antimicrobial susceptibility profile, as well as the clinical features of, treatment options for and outcomes of the disease. In addition, antimicrobial usage in livestock in Thailand will be reviewed. A literature search yielded 18 studies mentioning C. difficile in Thailand, a greater number than from any other Asian country. It is possible that the situation in Thailand in relation to CDI may mirror the situation in other developing Asians countries. PMID:25537687

  8. Clostridium difficile infection in patients with inflammatory bowel disease

    PubMed Central

    Biesiada, Grażyna; Perucki, William; Mach, Tomasz

    2014-01-01

    Clostridium difficile is a bacterium widely distributed in the human environment. In the last decade the incidence and severity of Clostridium difficile infection has grown, particularly in Europe and North America, making it one of the more common nosocomial infections. A group particularly susceptible to Clostridium difficile infection are patients with inflammatory bowel disease, especially those with involvement of the colon. This paper presents relevant data on Clostridium difficile infections in inflammatory bowel disease patients, including epidemiology, pathogenesis, diagnosis and treatment. PMID:25097707

  9. Clostridium difficile Infection: A Worldwide Disease

    PubMed Central

    Burke, Kristin E.

    2014-01-01

    Clostridium difficile, an anaerobic toxigenic bacterium, causes a severe infectious colitis that leads to significant morbidity and mortality worldwide. Both enhanced bacterial toxins and diminished host immune response contribute to symptomatic disease. C. difficile has been a well-established pathogen in North America and Europe for decades, but is just emerging in Asia. This article reviews the epidemiology, microbiology, pathophysiology, and clinical management of C. difficile. Prompt recognition of C. difficile is necessary to implement appropriate infection control practices. PMID:24516694

  10. Blastocystis sp. Infection Mimicking Clostridium Difficile Colitis

    PubMed Central

    Gil, Gaby S.; Chaudhari, Shobhana; Shady, Ahmed; Caballes, Ana; Hong, Joe

    2016-01-01

    We report an unusual case of severe diarrhea related to Blastocystis sp. infection in a patient with end stage renal disease on hemodialysis. The patient was admitted due to profuse diarrhea associated with fever and leukocytosis. Pertinent stool work-up such as leukocytes in stool, stool culture, clostridium difficile toxin B PCR, and serology for hepatitis A, hepatitis B, and hepatitis C and cytomegalovirus screening were all negative. Ova and parasite stool examination revealed Blastocystis sp. The patient was given intravenous metronidazole with clinical improvement by day three and total resolution of symptoms by day ten. PMID:27247810

  11. Novel Risk Factors for Recurrent Clostridium difficile Infection in Children

    PubMed Central

    Nicholson, Maribeth R.; Thomsen, Isaac P.; Slaughter, James C.; Creech, C. Buddy; Edwards, Kathryn M.

    2014-01-01

    Objectives Clostridium difficile, a common cause of antibiotic-associated diarrhea, has been reported to recur in high rates in adults. The rates and risk factors for recurrent Clostridium difficile infection (rCDI) in children have not been well established. Methods We conducted a retrospective cohort study of 186 pediatric patients seen at a tertiary care referral center over a 5-year period diagnosed with a primary infection with Clostridium difficile. Children with recurrent disease, defined as return of symptoms of Clostridium difficile infection and positive testing ≤60 days after the completion of therapy, were compared to children who did not experience an episode of recurrence. Results Of the 186 pediatric patients included in this study, 41 (22%) experienced recurrent Clostridium difficile infection. On univariable analysis, factors significantly associated with recurrent Clostridium difficile infection included malignancy, recent hospitalization, recent surgery, antibiotic use, number of antibiotic exposures by class, acid blocker use, immunosuppressant use, and hospital acquired disease. On multivariable analysis, malignancy (OR=3.39, 95% CI=1.52–7.85), recent surgery (OR=2.40, 95% CI=1.05–5.52), and the number of antibiotic exposures by class (OR=1.33, 95% CI=1.01–1.75) were significantly associated with recurrent disease in children. Conclusions The rate of recurrent Clostridium difficile infection in children was 22%. Recurrence was significantly associated with the risk factors of malignancy, recent surgery, and the number of antibiotic exposures by class. PMID:25199038

  12. [New aspects on Clostridium difficile infection].

    PubMed

    von Müller, Lutz

    2016-08-01

    Clostridium difficile infection (CDI) is a frequent and complex disease which is influenced by the repertoire of bacterial virulence factors, by host immunity and by the intestinal microbiome. These complex interaction opens a number of options which may be used for treatment in the future. One example for new treatment options is fecal microbiota transplantation (FMT). Driven by C. difficile related research activities the knowledge of protective microorganism is increasing and it may be assumed that bacteriotherapy by next-generation probiotics may be used very soon also for other diseases. Very often, CDI reflects to the clinician that antibiotic therapy is associated with side effects. Therefore, C. difficile is the guilty conscience which helps to implement targeted and restrictive antibiotic use in the daily practice. PMID:27509341

  13. Flooding and Clostridium difficile infection: a case-crossover analysis

    EPA Science Inventory

    Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospttalized and/or receiving antibiotics; however, community­ associated infections affecting otherwise healthy individuals have become more ...

  14. Clostridium perfringens infection after transarterial chemoembolization for large hepatocellular carcinoma

    PubMed Central

    Li, Jing-Huan; Yao, Rong-Rong; Shen, Hu-Jia; Zhang, Lan; Xie, Xiao-Ying; Chen, Rong-Xin; Wang, Yan-Hong; Ren, Zheng-Gang

    2015-01-01

    We report an unusual case of Clostridium perfringens liver abscess formation after transcatheter arterial chemoembolization (TACE) for large hepatocellular carcinoma. Severe deterioration in liver and renal function accompanied with hemocytolysis was found on the 2nd day after TACE. Blood culture found Clostridium perfringens and abdominal computed tomography revealed a gas-containing abscess in the liver. Following antibiotics administration and support care, the infection was controlled and the liver and renal function turned normal. The 2nd TACE procedure was performed 1.5 mo later and no recurrent Clostridium perfringens infection was found. PMID:25892893

  15. Clostridium perfringens infection after transarterial chemoembolization for large hepatocellular carcinoma.

    PubMed

    Li, Jing-Huan; Yao, Rong-Rong; Shen, Hu-Jia; Zhang, Lan; Xie, Xiao-Ying; Chen, Rong-Xin; Wang, Yan-Hong; Ren, Zheng-Gang

    2015-04-14

    We report an unusual case of Clostridium perfringens liver abscess formation after transcatheter arterial chemoembolization (TACE) for large hepatocellular carcinoma. Severe deterioration in liver and renal function accompanied with hemocytolysis was found on the 2(nd) day after TACE. Blood culture found Clostridium perfringens and abdominal computed tomography revealed a gas-containing abscess in the liver. Following antibiotics administration and support care, the infection was controlled and the liver and renal function turned normal. The 2(nd) TACE procedure was performed 1.5 mo later and no recurrent Clostridium perfringens infection was found. PMID:25892893

  16. Laboratory Diagnosis of Clostridium difficile Infection

    PubMed Central

    Tenover, Fred C.; Baron, Ellen Jo; Peterson, Lance R.; Persing, David H.

    2011-01-01

    The laboratory diagnosis of Clostridium difficile infection (CDI) continues to be challenging. Recent guidelines from professional societies in the United States note that enzyme immunoassays for toxins A and B do not have adequate sensitivity to be used alone for detecting CDI, yet the optimal method for diagnosing this infection remains unclear. Nucleic acid amplification tests (NAATs) that target chromosomal toxin genes (usually the toxin B gene, tcdB) show high sensitivity and specificity, provide rapid results, and are amenable to both batch and on-demand testing, but these tests were not universally recommended for routine use in the recent guidelines. Rather, two-step algorithms that use glutamate dehydrogenase (GDH) assays to screen for C. difficile in stool specimens, followed by either direct cytotoxin testing or culture to identify toxin-producing C. difficile isolates, were recommended in one guideline and either GDH algorithms or NAATs were recommended in another guideline. Unfortunately, neither culture nor direct cytotoxin testing is widely available. In addition, this two-step approach requires 48 to 92 hours to complete, which may delay the initiation of therapy and critical infection control measures. Recent studies also show the sensitivity of several GDH assays to be <90%. This review considers the role of NAATs for diagnosing CDI and explores their potential advantages over two-step algorithms, including shorter time to results, while providing comparable, if not superior, accuracy. PMID:21854871

  17. The Changing Epidemiology of Clostridium difficile Infections

    PubMed Central

    Freeman, J.; Bauer, M. P.; Baines, S. D.; Corver, J.; Fawley, W. N.; Goorhuis, B.; Kuijper, E. J.; Wilcox, M. H.

    2010-01-01

    Summary: The epidemiology of Clostridium difficile infection (CDI) has changed dramatically during this millennium. Infection rates have increased markedly in most countries with detailed surveillance data. There have been clear changes in the clinical presentation, response to treatment, and outcome of CDI. These changes have been driven to a major degree by the emergence and epidemic spread of a novel strain, known as PCR ribotype 027 (sometimes referred to as BI/NAP1/027). We review the evidence for the changing epidemiology, clinical virulence and outcome of treatment of CDI, and the similarities and differences between data from various countries and continents. Community-acquired CDI has also emerged, although the evidence for this as a distinct new entity is less clear. There are new data on the etiology of and potential risk factors for CDI; controversial issues include specific antimicrobial agents, gastric acid suppressants, potential animal and food sources of C. difficile, and the effect of the use of alcohol-based hand hygiene agents. PMID:20610822

  18. Current status of Clostridium difficile infection epidemiology.

    PubMed

    Lessa, Fernanda C; Gould, Carolyn V; McDonald, L Clifford

    2012-08-01

    The dramatic changes in the epidemiology of Clostridium difficile infection (CDI) during recent years, with increases in incidence and severity of disease in several countries, have made CDI a global public health challenge. Increases in CDI incidence have been largely attributed to the emergence of a previously rare and more virulent strain, BI/NAP1/027. Increased toxin production and high-level resistance to fluoroquinolones have made this strain a very successful pathogen in healthcare settings. In addition, populations previously thought to be at low risk are now being identified as having severe CDI. Recent genetic analysis suggests that C. difficile has a highly fluid genome with multiple mechanisms to modify its content and functionality, which can make C. difficile adaptable to environmental changes and potentially lead to the emergence of more virulent strains. In the face of these changes in the epidemiology and microbiology of CDI, surveillance systems are necessary to monitor trends and inform public health actions. PMID:22752867

  19. [Epidemiology of Clostridium difficile infection in Spain].

    PubMed

    Asensio, Angel; Monge, Diana

    2012-06-01

    There has been increasing interest in Clostridium difficile infection (CDI) due its association with healthcare and its impact on morbidity and mortality in the elderly. During the last few years there has been a growing increase in the number of published studies on the incidence, changes on the clinical presentation and on the epidemiology, with the description of new risk factors. The frequency of CDI in Spain is not sufficiently characterised. The available data indicates that incidence is within the range of that of surrounding countries but increasing. Furthermore, the high and growing use of broad spectrum antibiotics, both in our hospitals and in the community setting, are factors that favour the increase of the disease. The hyper-virulent ribotype 027 has not spread in our hospitals. We need to know with enhanced validity and accuracy the incidence of CDI, both community and healthcare-associated, the information on outbreaks, the incidence on certain population groups, the characterisation of circulating ribotypes and the impact of the disease in terms of mortality and health costs. We need to implement programs for the improvement of antibiotic therapy in the hospital, as well as in the community. Furthermore, the knowledge and the performance of standard precautions need to be improved, particularly hand hygiene, and the specific measures to limit the transmission of C. difficile among the healthcare institutions. PMID:22136747

  20. Clostridium difficile associated infection, diarrhea and colitis

    PubMed Central

    Hookman, Perry; Barkin, Jamie S

    2009-01-01

    A new, hypervirulent strain of Clostridium difficile, called NAP1/BI/027, has been implicated in C. difficile outbreaks associated with increased morbidity and mortality since the early 2000s. The epidemic strain is resistant to fluoroquinolones in vitro, which was infrequent prior to 2001. The name of this strain reflects its characteristics, demonstrated by different typing methods: pulsed-field gel electrophoresis (NAP1), restriction endonuclease analysis (BI) and polymerase chain reaction (027). In 2004 and 2005, the US Centers for Disease Control and Prevention (CDC) emphasized that the risk of C. difficile-associated diarrhea (CDAD) is increased, not only by the usual factors, including antibiotic exposure, but also gastrointestinal surgery/manipulation, prolonged length of stay in a healthcare setting, serious underlying illness, immune-compromising conditions, and aging. Patients on proton pump inhibitors (PPIs) have an elevated risk, as do peripartum women and heart transplant recipients. Before 2002, toxic megacolon in C. difficile-associated colitis (CDAC), was rare, but its incidence has increased dramatically. Up to two-thirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors. Fulminant colitis is reported more frequently during outbreaks of C. difficile infection in patients with inflammatory bowel disease (IBD). C. difficile infection with IBD carries a higher mortality than without underlying IBD. This article reviews the latest information on C. difficile infection, including presentation, vulnerable hosts and choice of antibiotics, alternative therapies, and probiotics and immunotherapy. We review contact precautions for patients with known or suspected C. difficile-associated disease. Healthcare institutions require accurate and rapid diagnosis for early detection of possible outbreaks, to initiate

  1. Colonic Immunopathogenesis of Clostridium difficile Infections

    PubMed Central

    Turnwald, Bradley P.; Koo, Hoonmo L.; Garey, Kevin W.; Jiang, Zhi-Dong; Aitken, Samuel L.; DuPont, Herbert L.

    2014-01-01

    There are major gaps in our understanding of the immunopathogenesis of Clostridium difficile infections (CDIs). In this study, 36 different biomarkers were examined in the stools of CDI and non-CDI patients using the Proteome Profiler human cytokine array assay and quantitative enzyme-linked immunosorbent assay. Diarrheal stools from patients with CDI (CDI-positive diarrheal stools) showed higher relative amounts of the following inflammatory markers than the diarrheal stools from CDI-negative patients (CDI-negative diarrheal stools): C5a, CD40L, granulocyte colony-stimulating factor, I-309, interleukin-13 (IL-13), IL-16, IL-27, monocyte chemoattractant protein 1, tumor necrosis factor alpha, and IL-8. IL-8 and IL-23 were present in a larger number of CDI-positive diarrheal stools than CDI-negative diarrheal stools. Th1 and Th2 cytokines were not significantly different between the CDI-positive and CDI-negative diarrheal stools. Lactoferrin and calprotectin concentrations were also higher in the CDI-positive diarrheal stools. Our results demonstrate that CDI elicits a proinflammatory host response, and we report for the first time that IL-23 is a major marker in CDI-positive diarrheal stools. IL-23 may explain the lack of a robust immunological response exhibited by a proportion of CDI patients and may relate to recurrence; the IL-23 levels induced during CDI in these patients may be inadequate to sustain the cellular immunity conferred by this cytokine in promoting the induction and proliferation of effector memory T cells. PMID:24477852

  2. Clostridium difficile strains from community-associated infections.

    PubMed

    Limbago, Brandi M; Long, Cherie M; Thompson, Angela D; Killgore, George E; Hannett, George E; Havill, Nancy L; Mickelson, Stephanie; Lathrop, Sarah; Jones, Timothy F; Park, Mahin M; Harriman, Kathleen H; Gould, L Hannah; McDonald, L Clifford; Angulo, Frederick J

    2009-09-01

    Clostridium difficile isolates from presumed community-associated infections (n = 92) were characterized by toxinotyping, pulsed-field gel electrophoresis, tcdC and cdtB PCR, and antimicrobial susceptibility. Nine toxinotypes (TOX) and 31 PFGE patterns were identified. TOX 0 (48, 52%), TOX III (18, 20%), and TOX V (9, 10%) were the most common; three isolates were nontoxigenic. PMID:19571021

  3. Clostridium difficile Infection: Epidemiology, Pathogenesis, Risk Factors, and Therapeutic Options

    PubMed Central

    Seyedjavadi, Sima Sadat; Goudarzi, Hossein; Mehdizadeh Aghdam, Elnaz; Nazeri, Saeed

    2014-01-01

    The incidence and mortality rate of Clostridium difficile infection have increased remarkably in both hospital and community settings during the last two decades. The growth of infection may be caused by multiple factors including inappropriate antibiotic usage, poor standards of environmental cleanliness, changes in infection control practices, large outbreaks of C. difficile infection in hospitals, alteration of circulating strains of C. difficile, and spread of hypervirulent strains. Detection of high-risk populations could be helpful for prompt diagnosis and consequent treatment of patients suffering from C. difficile infection. Metronidazole and oral vancomycin are recommended antibiotics for the treatment of initial infection. Current treatments for C. difficile infection consist of supportive care, discontinuing the unnecessary antibiotic, and specific antimicrobial therapy. Moreover, novel approaches include fidaxomicin therapy, monoclonal antibodies, and fecal microbiota transplantation mediated therapy. Fecal microbiota transplantation has shown relevant efficacy to overcome C. difficile infection and reduce its recurrence. PMID:24991448

  4. Models for the study of Clostridium difficile infection

    PubMed Central

    Best, Emma L.; Freeman, Jane; Wilcox, Mark H.

    2012-01-01

    Models of Clostridium difficile infection (C. difficile) have been used extensively for Clostridium difficile (C. difficile) research. The hamster model of C. difficile infection has been most extensively employed for the study of C. difficile and this has been used in many different areas of research, including the induction of C. difficile, the testing of new treatments, population dynamics and characterization of virulence. Investigations using in vitro models for C. difficile introduced the concept of colonization resistance, evaluated the role of antibiotics in C. difficile development, explored population dynamics and have been useful in the evaluation of C. difficile treatments. Experiments using models have major advantages over clinical studies and have been indispensible in furthering C. difficile research. It is important for future study programs to carefully consider the approach to use and therefore be better placed to inform the design and interpretation of clinical studies. PMID:22555466

  5. Community-Acquired Clostridium Difficile Infection: Awareness and Clinical Implications

    PubMed Central

    Juneau, Cheryl; Mendias, Elnora (Nonie) P.; Wagal, Nihas; Loeffelholz, Michael; Savidge, Tor; Croisant, Sharon; Dann, Sara

    2013-01-01

    The epidemiology of Clostridium difficile infection (CDI) is changing. CDI, usually depicted as a nosocomial infection in the elderly, is now occurring in community-dwelling persons who are younger and otherwise dissimilar. A more virulent isolate (North American Pulsed Field type 1 (NAP1) associated with increased morbidity and mortality, has been identified. In 2005, similar strains were associated with severe disease in community-dwelling patients at a rate of 7.6/100,000. Screening patients with potential CDI symptoms and implementing preventative measures, including judicious use of antibiotics, can reduce disease burden. PMID:23814528

  6. Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.

    PubMed

    Fu, Nancy; Wong, Titus

    2016-06-01

    Clostridium difficile infection (CDI) is now the leading cause of nosocomial infection. There has been an upsurge of CDI in patients with inflammatory bowel disease (IBD). IBD patients with CDI have increased morbidity and mortality. The establishment, proliferation, and recurrence of CDI in IBD patients form a complex interplay of microbial, environmental, and host-susceptibility factors. Different risk factors have been found predisposing IBD patients to CDI. Vancomycin performs better than metronidazole in treating IBD patients with CDI. Fecal microbiota transplantation continues to be a very effective therapy. New therapeutic modalities such as vaccinations and bile salts are currently being investigated. PMID:27137789

  7. Clostridium difficile infection in the twenty-first century.

    PubMed

    Ghose, Chandrabali

    2013-09-01

    Clostridium difficile is a spore-forming gram-positive bacillus, and the leading cause of antibiotic-associated nosocomial diarrhea and colitis in the industrialized world. With the emergence of a hypervirulent strain of C. difficile (BI/NAP1/027), the epidemiology of C. difficile infection has rapidly changed in the last decade. C. difficile infection, once thought to be an easy to treat bacterial infection, has evolved into an epidemic that is associated with a high rate of mortality, causing disease in patients thought to be low-risk. In this review, we discuss the changing face of C .difficile infection and the novel treatment and prevention strategies needed to halt this ever growing epidemic. PMID:26038491

  8. Two Serious Cases of Infection with Clostridium celatum after 40 Years in Hiding?

    PubMed Central

    Hoegh, Silje Vermedal; Holt, Hanne Marie; Justesen, Ulrik Stenz

    2015-01-01

    Clostridium celatum [ce.la'tum. L. adj. celatum hidden] has been known since 1974, when it was isolated from human feces. In 40 years, no association with human infection has been reported. In this work, we present two serious cases of infection with the anaerobic Gram-positive rod Clostridium celatum. PMID:26560535

  9. Pneumatosis intestinalis in a patient with recurrent Clostridium difficile infection

    PubMed Central

    Ha, Duc; Tsai, Chung-Jyi

    2012-01-01

    A 65-year-old man with long-standing diarrhoea, recurrent Clostridium difficile infection (CDI) in the previous 5 months presented to the gastroenterology clinic with recurrent diarrhoea and abdominal cramping. Physical examination was negative for signs of acute abdomen. Stool C difficile PCR was positive. Abdominal imaging demonstrated an extensive pneumatosis intestinalis involving the small bowel and a dilated small bowel loop. He was treated conservatively with oral vancomycin for recurrent CDI with resolution of diarrhoea and abdominal cramping on 1-month follow-up visit. PMID:23112256

  10. New advances in the treatment of Clostridium difficile infection (CDI)

    PubMed Central

    Hedge, Dennis D; Strain, Joe D; Heins, Jodi R; Farver, Debra K

    2008-01-01

    Clostridium difficile infections (CDI) have increased in frequency throughout the world. In addition to an increase in frequency, recent CDI epidemics have been linked to a hypervirulent C. difficile strain resulting in greater severity of disease. Although most mild to moderate cases of CDI continue to respond to metronidazole or vancomycin, refractory and recurrent cases of CDI may require alternative therapies. This review provides a brief overview of CDI and summarizes studies involving alternative antibiotics, toxin binders, probiotics, and immunological therapies that can be considered for treatment of acute and recurrent CDI in severe and refractory situations. PMID:19209277

  11. [New treatment options for infections with Clostridium difficile].

    PubMed

    van Nood, Els; Keller, Josbert J; Kuijper, Ed J; Speelman, Peter

    2013-01-01

    Currently available broad spectrum antibiotics are not sufficiently effective against recurrent Clostridium difficile infections (CDI). Donor faecal microbiota transplantation is a very effective treatment for second and recurrent infection but is time-consuming and requires careful screening of donors. The new narrow spectrum antibiotic fidaxomicin is a good alternative in a first CDI or a first recurrence, but treatment is expensive and there are no data on its effectiveness in a second or later recurrence. Fidaxomicin is less effective against infections caused by the Ribotype 027 strain, a virulent strain that is regularly encountered in the Netherlands. The effectiveness of various other promising narrow spectrum antibiotics is currently being investigated. Medications that support the gut flora or the immune system seem to offer new perspectives. Expectations for the currently available probiotic preparations and toxin binders are not high. PMID:24279951

  12. Flooding and Clostridium difficile Infection: A Case-Crossover Analysis

    PubMed Central

    Lin, Cynthia J.; Wade, Timothy J.; Hilborn, Elizabeth D.

    2015-01-01

    Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospitalized and/or receiving antibiotics; however, community-associated infections affecting otherwise healthy individuals have become more commonly reported. A case-crossover study was used to assess emergency room (ER) and outpatient visits for C. difficile infection following flood events in Massachusetts from 2003 through 2007. Exposure status was based on whether or not a flood occurred prior to the case/control date during the following risk periods: 0–6 days, 7–13 days, 14–20 days, and 21–27 days. Fixed-effects logistic regression was used to estimate the risk of diagnosis with C. difficile infection following a flood. There were 129 flood events and 1575 diagnoses of C. difficile infection. Among working age adults (19–64 years), ER and outpatient visits for C. difficile infection were elevated during the 7–13 days following a flood (Odds Ratio, OR = 1.69; 95% Confidence Interval, CI: 0.84, 3.37). This association was more substantial among males (OR = 3.21; 95% CI: 1.01–10.19). Associations during other risk periods were not observed (p < 0.05). Although we were unable to differentiate community-associated versus nosocomial infections, a potential increase in C. difficile infections should be considered as more flooding is projected due to climate change. PMID:26090609

  13. Flooding and Clostridium difficile Infection: A Case-Crossover Analysis.

    PubMed

    Lin, Cynthia J; Wade, Timothy J; Hilborn, Elizabeth D

    2015-06-01

    Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospitalized and/or receiving antibiotics; however, community-associated infections affecting otherwise healthy individuals have become more commonly reported. A case-crossover study was used to assess emergency room (ER) and outpatient visits for C. difficile infection following flood events in Massachusetts from 2003 through 2007. Exposure status was based on whether or not a flood occurred prior to the case/control date during the following risk periods: 0-6 days, 7-13 days, 14-20 days, and 21-27 days. Fixed-effects logistic regression was used to estimate the risk of diagnosis with C. difficile infection following a flood. There were 129 flood events and 1575 diagnoses of C. difficile infection. Among working age adults (19-64 years), ER and outpatient visits for C. difficile infection were elevated during the 7-13 days following a flood (Odds Ratio, OR = 1.69; 95% Confidence Interval, CI: 0.84, 3.37). This association was more substantial among males (OR = 3.21; 95% CI: 1.01-10.19). Associations during other risk periods were not observed (p < 0.05). Although we were unable to differentiate community-associated versus nosocomial infections, a potential increase in C. difficile infections should be considered as more flooding is projected due to climate change. PMID:26090609

  14. Contributions to the taxonomy and biology of Clostridium difficile.

    PubMed

    Bittner, J; Macovei, A; Lemeni, D; Arboreanu, D; Potorac, E

    1992-01-01

    Clostridium difficile was incriminated by Hughes and Jarvis (1987) as a cause of intestinal infections in USA in the 1980-1984 period in 45 p. 100 of cases, whereas Salmonellae only in 12 p. 100. Four strains of this organism are studied in this paper in comparison with ten strains of C. bifermentans and six of C. sordellii, because the three species share a common antigen and have other common characteristics, as well. However, spores of C. difficile swell the bacteria and those of other bacteria (C. bifermentans and C. sordellii) do not; C. difficile does not produce indole, whereas the other species produce it. We confirmed the selective capacity of the medium of George et al. (1979) using the "alcohol shock" and as selective agents cycloserine D and cefoxitin. C. difficile proved to be most susceptible to metronidazole and rifampin. Whereas the former antibiotic was considered as a cause of post-antibiotic intestinal infections by different authors, the second was not, to our knowledge. The strain 10463 has a considerable toxicity (1000 DLM/ml for the white mouse, and pathogenicity--2000--5000 DCL for the white mouse, as compared to 25 DCL of the other three strains). Using this toxin an antitoxic serum was obtained in horse, with a capacity of neutralizing the action of the toxin up to a dilution of 1 p. 1000. PMID:1304829

  15. Treatment of Clostridium difficile infection in pediatric patients.

    PubMed

    Esposito, Susanna; Umbrello, Giulia; Castellazzi, Luca; Principi, Nicola

    2015-06-01

    Clostridium difficile causes infections that can either remain asymptomatic or manifest as clinical disease. In this report, problems, possible solutions, and future perspectives on the treatment of C. difficile infections (CDIs) in pediatric patients are discussed. CDI, despite increasing as a consequence of the overuse and misuse of antibiotics, remains relatively uncommon in pediatrics mainly because younger children are poorly susceptible to the action of C. difficile toxins. In most such cases, C. difficile disease is mild to moderate and discontinuation of the administered antibiotics in patients receiving these drugs when CDI develops, or administration of metronidazole, is sufficient to solve this problem. In severe or frequently relapsing cases, vancomycin is the drug of choice. Probiotics do not seem to add significant advantages. Other treatment options must be reserved for severe cases and be considered as a salvage treatment, although potential advantages in pediatric patients remain unclear. PMID:25912469

  16. Recurrent Clostridium difficile infections: The importance of the intestinal microbiota

    PubMed Central

    Zanella Terrier, Marie Céline; Simonet, Martine Louis; Bichard, Philippe; Frossard, Jean Louis

    2014-01-01

    Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability. PMID:24966611

  17. Clostridium difficile infection: molecular pathogenesis and novel therapeutics

    PubMed Central

    Rineh, Ardeshir; Kelso, Michael J; Vatansever, Fatma; Tegos, George P; Hamblin, Michael R

    2015-01-01

    The Gram-positive anaerobic bacterium Clostridium difficile produces toxins A and B, which can cause a spectrum of diseases from pseudomembranous colitis to C. difficile-associated diarrhea. A limited number of C. difficile strains also produce a binary toxin that exhibits ADP ribosyltransferase activity. Here, the structure and the mechanism of action of these toxins as well as their role in disease are reviewed. Nosocomial C. difficile infection is often contracted in hospital when patients treated with antibiotics suffer a disturbance in normal gut microflora. C. difficile spores can persist on dry, inanimate surface for months. Metronidazole and oral vancomycin are clinically used for treatment of C. difficile infection but clinical failure and concern about promotion of resistance are motivating the search for novel non-antibiotic therapeutics. Methods for controlling both toxins and spores, replacing gut microflora by probiotics or fecal transplant, and killing bacteria in the anaerobic gut by photodynamic therapy are discussed. PMID:24410618

  18. Fidaxomicin in Clostridium difficile infection: latest evidence and clinical guidance

    PubMed Central

    2014-01-01

    The incidence of Clostridium difficile infection (CDI) has risen 400% in the last decade. It currently ranks as the third most common nosocomial infection. CDI has now crossed over as a community-acquired infection. The major failing of current therapeutic options for the management of CDI is recurrence of disease after the completion of treatment. Fidaxomicin has been proven to be superior to vancomycin in successful sustained clinical response to therapy. Improved outcomes may be due to reduced collateral damage to the gut microflora by fidaxomicin, bactericidal activity, inhibition of Clostridial toxin formation and inhibition of new sporulation. This superiority is maintained in groups previously reported as being at high risk for CDI recurrence including those: with relapsed infection after a single treatment course; on concomitant antibiotic therapy; aged >65 years; with cancer; and with chronic renal insufficiency. Because the acquisition cost of fidaxomicin far exceeds that of metronidazole or vancomycin, in order to rationally utilize this agent, it should be targeted to those populations who are at high risk for relapse and in whom the drug has demonstrated superiority. In this manuscript is reviewed the changing epidemiology of CDI, current treatment options for this infection, proposed benefits of fidaxomicin over currently available antimicrobial options, available analysis of cost effectiveness of the drug, and is given recommendations for judicious use of the drug based upon the available published literature. PMID:24587892

  19. Recurrent Clostridium difficile Infection: From Colonization to Cure

    PubMed Central

    Shields, Kelsey; Araujo-Castillo, Roger V.; Theethira, Thimmaiah G.; Alonso, Carolyn D.; Kelly, Ciaran

    2015-01-01

    Clostridium difficile infection (CDI) is increasingly prevalent, dangerous and challenging to prevent and manage. Despite intense national and international attention the incidence of primary and of recurrent CDI (PCDI and RCDI, respectively) have risen rapidly throughout the past decade. Of major concern is the increase in cases of RCDI resulting in substantial morbidity, morality and economic burden. RCDI management remains challenging as there is no uniformly effective therapy, no firm consensus on optimal treatment, and reliable data regarding RCDI-specific treatment options is scant. Novel therapeutic strategies are critically needed to rapidly, accurately, and effectively identify and treat patients with, or at-risk for, RCDI. In this review we consider the factors implicated in the epidemiology, pathogenesis and clinical presentation of RCDI, evaluate current management options for RCDI and explore novel and emerging therapies. PMID:25930686

  20. Clostridium difficile infection: New insights into therapeutic options.

    PubMed

    Kachrimanidou, Melina; Sarmourli, Theopisti; Skoura, Lemonia; Metallidis, Symeon; Malisiovas, Nikolaos

    2016-09-01

    Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings and represents a major social and economic burden. The major virulence determinants are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), encoded within the pathogenicity locus. Traditional therapies, such as metronidazole and vancomycin, frequently lead to a vicious circle of recurrences due to their action against normal human microbiome. New disease management strategies together with the development of novel therapeutic and containment approaches are needed in order to better control outbreaks and treat patients. This article provides an overview of currently available CDI treatment options and discusses the most promising therapies under development. PMID:25955884

  1. Clostridium difficile infections among Jordanian adult hospitalized patients.

    PubMed

    Nasereddin, Lina M; Bakri, Fares G; Shehabi, Asem A

    2009-12-01

    This prospective study investigated the important epidemiologic aspects of Clostridium difficile infections (CDIs) among Jordanian adult hospitalized patients. A total of 300 stool specimens were investigated using culture and polymerase chain reaction methods for detection of C difficile, its toxins, and fluoroquinolone resistance. C difficile-positive cultures were found in 13.7% of the patients, and 73% of the isolates carried tcdA and/or tcdB toxin genes, and all C difficile isolates were negative for binary toxin. The isolates showed moderate level of resistance to both ciprofloxacin and levofloxacin, whereas metronidazole and vancomycin were highly susceptible. This study indicates the need for early detection of CDIs and prevention of its severe disease in hospitalized patients. PMID:19712999

  2. Recurrent Clostridium difficile infection: From colonization to cure.

    PubMed

    Shields, Kelsey; Araujo-Castillo, Roger V; Theethira, Thimmaiah G; Alonso, Carolyn D; Kelly, Ciaran P

    2015-08-01

    Clostridium difficile infection (CDI) is increasingly prevalent, dangerous and challenging to prevent and manage. Despite intense national and international attention the incidence of primary and of recurrent CDI (PCDI and RCDI, respectively) have risen rapidly throughout the past decade. Of major concern is the increase in cases of RCDI resulting in substantial morbidity, morality and economic burden. RCDI management remains challenging as there is no uniformly effective therapy, no firm consensus on optimal treatment, and reliable data regarding RCDI-specific treatment options is scant. Novel therapeutic strategies are critically needed to rapidly, accurately, and effectively identify and treat patients with, or at-risk for, RCDI. In this review we consider the factors implicated in the epidemiology, pathogenesis and clinical presentation of RCDI, evaluate current management options for RCDI and explore novel and emerging therapies. PMID:25930686

  3. Prevalence of diverticulosis in recurrent Clostridium difficile infection

    PubMed Central

    Lipp, Michael J; Pagovich, Odelya E; Rabin, David; Min, Albert D; Bernstein, Brett B

    2010-01-01

    AIM: To re-evaluate the theory that colonic diverticulosis is associated with relapse of Clostridium difficile associated disease (CDAD) in light of data suggesting increasing rates of CDAD infection and relapse. METHODS: Charts were reviewed for patients with recurrent CDAD who had also had a prior colonoscopy or flexible sigmoidoscopy. An age and gender matched control group was used to compare the prevalence of diverticulosis. RESULTS: Twenty-two patients met the study criteria, and the prevalence of diverticulosis in patients with CDAD relapse was 23% compared to 32% in age and sex matched controls (P = 0.44). A significant proportion of patients with CDAD relapse had co-morbidities associated with immune suppression. CONCLUSION: Diverticulosis does not appear to be associated with CDAD relapse. PMID:20082480

  4. Clostridium difficile infection: management strategies for a difficult disease

    PubMed Central

    Pardi, Darrell S.

    2014-01-01

    Clostridium difficile was first described as a cause of diarrhea in 1978 and in the last three decades has reached an epidemic state with increasing incidence and severity in both healthcare and community settings. There also has been a rise in severe outcomes from C. difficile infection (CDI). There have been tremendous advancements in the field of CDI with the identification of newer risk factors, recognition of CDI in populations previously thought not at risk and development of better diagnostic modalities. Several treatment options are available for CDI apart from metronidazole and vancomycin, and include new drugs such as fidaxomicin and other options such as fecal microbiota transplantation. This review discusses the epidemiology, risk factors and outcomes from CDI, and focuses primarily on existing and evolving treatment modalities. PMID:24587820

  5. Clostridium Difficile Infection and Takotsubo Cardiomyopathy: Is There a Relation?

    PubMed Central

    Virk, Hafeez Ul Hassan; Inayat, Faisal

    2016-01-01

    Context: Takotsubo cardiomyopathy (TCM) mimics acute coronary syndrome and is accompanied by reversible left ventricular apical ballooning in the absence of angiographically significant coronary artery stenosis. It is a transient condition that typically precedes physical or emotional triggers. Case Report: We describe the case of a 65-year-old woman who presented to our institution with symptomatic Clostridium difficile infection. 24 hours after admission, the patient complained of severe, retrosternal chest pain. Electrocardiogram showed diffuse elevation of ST-segment in the chest leads; however, coronary angiography demonstrated normal coronary arteries. Therein, an echocardiography was performed, which revealed apical ballooning and hypercontractile base with global left ventricular hypokinesis. These features were consistent with TCM. The patient was managed conservatively. Repeat echocardiogram 2 weeks later showed resolution of heart failure. Conclusion: To our research, this is the first report of TCM caused by C. difficile infection. Clinicians involved in the care of patients with C. difficile infection must be aware of this complication and should consider TCM in those who develop atypical chest pain. PMID:27583241

  6. The Systemic Inflammatory Response to Clostridium difficile Infection

    PubMed Central

    Rao, Krishna; Erb-Downward, John R.; Walk, Seth T.; Micic, Dejan; Falkowski, Nicole; Santhosh, Kavitha; Mogle, Jill A.; Ring, Cathrin; Young, Vincent B.; Huffnagle, Gary B.; Aronoff, David M.

    2014-01-01

    Background The systemic inflammatory response to Clostridium difficile infection (CDI) is incompletely defined, particularly for patients with severe disease. Methods Analysis of 315 blood samples from 78 inpatients with CDI (cases), 100 inpatients with diarrhea without CDI (inpatient controls), and 137 asymptomatic outpatient controls without CDI was performed. Serum or plasma was obtained from subjects at the time of CDI testing or shortly thereafter. Severe cases had intensive care unit admission, colectomy, or death due to CDI within 30 days after diagnosis. Thirty different circulating inflammatory mediators were quantified using an antibody-linked bead array. Principal component analysis (PCA), multivariate analysis of variance (MANOVA), and logistic regression were used for analysis. Results Based on MANOVA, cases had a significantly different inflammatory profile from outpatient controls but not from inpatient controls. In logistic regression, only chemokine (C-C motif) ligand 5 (CCL5) levels were associated with cases vs. inpatient controls. Several mediators were associated with cases vs. outpatient controls, especially hepatocyte growth factor, CCL5, and epithelial growth factor (inversely associated). Eight cases were severe and associated with elevations in IL-8, IL-6, and eotaxin. Conclusions A broad systemic inflammatory response occurs during CDI and severe cases appear to differ from non-severe infections. PMID:24643077

  7. Emerging therapies for Clostridium difficile infection – focus on fidaxomicin

    PubMed Central

    Chaparro-Rojas, Fredy; Mullane, Kathleen M

    2013-01-01

    The epidemiology of Clostridium difficile infections (CDI) has evolved during the last decades, with an increase in the reported incidence, severity of cases, and rate of mortality and relapses. These increases have primarily affected some special populations including the elderly, patients requiring concomitant antibiotic therapy, patients with renal failure, and patients with cancer. Until recently, the treatment of CDI was limited to either metronidazole or vancomycin. New therapeutic options have emerged to address the shortcomings of current antibiotic therapy. Fidaxomicin stands out as the first-in-class oral macrocyclic antibiotic with targeted activity against C. difficile and minimal collateral damage on the normal colonic flora. Fidaxomicin has demonstrated performance not inferior to what is considered the “gold standard” available therapy for CDI, vancomycin, in two separate Phase III clinical trials, but with significant advantages, including fewer recurrences and higher rates of sustained clinical cures. Fidaxomicin constitutes an important development in targeted antibiotic therapy for CDI and must be considered as a first-line agent for patients with risk factors known to portend relapse and severe infection. PMID:23843696

  8. Clostridium difficile infection: epidemiology, diagnosis and understanding transmission.

    PubMed

    Martin, Jessica S H; Monaghan, Tanya M; Wilcox, Mark H

    2016-04-01

    Clostridium difficile infection (CDI) continues to affect patients in hospitals and communities worldwide. The spectrum of clinical disease ranges from mild diarrhoea to toxic megacolon, colonic perforation and death. However, this bacterium might also be carried asymptomatically in the gut, potentially leading to 'silent' onward transmission. Modern technologies, such as whole-genome sequencing and multi-locus variable-number tandem-repeat analysis, are helping to track C. difficile transmission across health-care facilities, countries and continents, offering the potential to illuminate previously under-recognized sources of infection. These typing strategies have also demonstrated heterogeneity in terms of CDI incidence and strain types reflecting different stages of epidemic spread. However, comparison of CDI epidemiology, particularly between countries, is challenging due to wide-ranging approaches to sampling and testing. Diagnostic strategies for C. difficile are complicated both by the wide range of bacterial targets and tests available and the need to differentiate between toxin-producing and non-toxigenic strains. Multistep diagnostic algorithms have been recommended to improve sensitivity and specificity. In this Review, we describe the latest advances in the understanding of C. difficile epidemiology, transmission and diagnosis, and discuss the effect of these developments on the clinical management of CDI. PMID:26956066

  9. Immune-based treatment and prevention of Clostridium difficile infection

    PubMed Central

    Zhao, Song; Ghose-Paul, Chandrabali; Zhang, Keshan; Tzipori, Saul; Sun, Xingmin

    2015-01-01

    Clostridium difficile (C. difficile) causes over 500,000 infections per year in the US, with an estimated 15,000 deaths and an estimated cost of $1–3 billion. Moreover, a continual rise in the incidence of severe C. difficile infection (CDI) has been observed worldwide. Currently, standard treatment for CDI is the administration of antibiotics. While effective, these treatments do not prevent and may contribute to a disease recurrence rate of 15–35%. Prevention of recurrence is one of the most challenging aspects in the field. A better knowledge of the molecular mechanisms of the disease, the host immune response and identification of key virulence factors of C. difficilenow permits the development of immune-based therapies. Antibodies specific for C. difficile toxins have been shown to effectively treat CDI and prevent disease relapse in animal models and in humans. Vaccination has been recognized as the most cost-effective treatment/prevention for CDI. This review will summarize CDI transmission, epidemiology, major virulent factors and highlights the rational and the development of immune-based approaches against this remerging threat. PMID:25668664

  10. Clostridium difficile infection: a review of current and emerging therapies

    PubMed Central

    Ofosu, Andrew

    2016-01-01

    Clostridium difficile (C. difficile) infection (CDI) is the most common cause of ­healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value. PMID:27065726

  11. Using a Novel Lysin To Help Control Clostridium difficile Infections

    PubMed Central

    Wang, Qiong; Euler, Chad W.; Delaune, Aurelia

    2015-01-01

    As a consequence of excessive antibiotic therapies in hospitalized patients, Clostridium difficile, a Gram-positive anaerobic spore-forming intestinal pathogen, is the leading cause of hospital-acquired diarrhea and colitis. Drug treatments for these diseases are often complicated by antibiotic-resistant strains and a high frequency of treatment failures and relapse; therefore, novel nonantibiotic approaches may prove to be more effective. In this study, we recombinantly expressed a prophage lysin identified from a C. difficile strain, CD630, which we named PlyCD. PlyCD was found to have lytic activity against specific C. difficile strains. However, the recombinantly expressed catalytic domain of this protein, PlyCD1–174, displayed significantly greater lytic activity (>4-log kill) and a broader lytic spectrum against C. difficile strains while still retaining a high degree of specificity toward C. difficile versus commensal clostridia and other bacterial species. Our data also indicated that noneffective doses of vancomycin and PlyCD1–174 when combined in vitro could be significantly more bactericidal against C. difficile. In an ex vivo treatment model of mouse colon infection, we found that PlyCD1–174 functioned in the presence of intestinal contents, significantly decreasing colonizing C. difficile compared to controls. Together, these data suggest that PlyCD1–174 has potential as a novel therapeutic for clinical application against C. difficile infection, either alone or in combination with other preexisting treatments to improve their efficacy. PMID:26392484

  12. Fecal Microbiota Transplantation for the Treatment of Clostridium difficile Infection

    PubMed Central

    Rao, Krishna; Safdar, Nasia

    2016-01-01

    Clostridium difficile, a major cause of healthcare-associated diarrhea due to perturbation of the normal gastrointestinal microbiome, is responsible for significant morbidity, mortality, and healthcare expenditures. The incidence and severity of C. difficile infection (CDI) is increasing and recurrent disease is common. Recurrent infection can be difficult to manage with conventional antibiotic therapy. Fecal microbiota transplantation (FMT), which involves instillation of stool from a healthy donor into the gastrointestinal tract of the patient, restores the gut microbiome to a healthy state. FMT has emerged as a promising new treatment for CDI. There are limited data on FMT for treatment of primary CDI, but FMT appears safe and effective for recurrent CDI. The safety and efficacy of FMT in patients with severe primary or recurrent CDI has not been established. Patients with inflammatory bowel disease (IBD) who undergo FMT for CDI may be at increased risk of IBD flare and caution should be exercised with use of FMT in that population. The long-term safety of FMT is unknown; thus, rigorously conducted prospective studies are needed. PMID:26344412

  13. Effect of a Clostridium difficile Infection Prevention Initiative in Veterans Affairs Acute Care Facilities.

    PubMed

    Evans, Martin E; Kralovic, Stephen M; Simbartl, Loretta A; Jain, Rajiv; Roselle, Gary A

    2016-06-01

    Rates of clinically confirmed hospital-onset healthcare facility-associated Clostridium difficile infections from July 1, 2012, through March 31, 2015, in 127 acute care Veterans Affairs facilities were evaluated. Quarterly pooled national standardized infection ratios decreased 15% from baseline by the final quarter of the analysis period (P=.01, linear regression). Infect Control Hosp Epidemiol 2016;37:720-722. PMID:26864803

  14. Procalcitonin Levels Associate with Severity of Clostridium difficile Infection

    PubMed Central

    Rao, Krishna; Walk, Seth T.; Micic, Dejan; Chenoweth, Elizabeth; Deng, Lili; Galecki, Andrzej T.; Jain, Ruchika; Trivedi, Itishree; Yu, Marie; Santhosh, Kavitha; Ring, Cathrin; Young, Vincent B.; Huffnagle, Gary B.; Aronoff, David M.

    2013-01-01

    Objective Clostridium difficile infection (CDI) is a major cause of morbidity and biomarkers that predict severity of illness are needed. Procalcitonin (PCT), a serum biomarker with specificity for bacterial infections, has been little studied in CDI. We hypothesized that PCT associated with CDI severity. Design Serum PCT levels were measured for 69 cases of CDI. Chart review was performed to evaluate the presence of severity markers and concurrent acute bacterial infection (CABI). We defined the binary variables clinical score as having fever (T >38°C), acute organ dysfunction (AOD), and/or WBC >15,000 cells/mm3 and expanded score, which included the clinical score plus the following: ICU admission, no response to therapy, colectomy, and/or death. Results In univariate analysis log10 PCT associated with clinical score (OR 3.13, 95% CI 1.69–5.81, P<.001) and expanded score (OR 3.33, 95% CI 1.77–6.23, P<.001). In a multivariable model including the covariates log10 PCT, enzyme immunoassay for toxin A/B, ribotype 027, age, weighted Charlson-Deyo comorbidity index, CABI, and extended care facility residence, log10 PCT associated with clinical score (OR 3.09, 95% CI 1.5–6.35, P = .002) and expanded score (OR 3.06, 95% CI 1.49–6.26, P = .002). PCT >0.2 ng/mL was 81% sensitive/73% specific for a positive clinical score and had a negative predictive value of 90%. Conclusion An elevated PCT level associated with the presence of CDI severity markers and CDI was unlikely to be severe with a serum PCT level below 0.2 ng/mL. The extent to which PCT changes during CDI therapy or predicts recurrent CDI remains to be quantified. PMID:23505476

  15. Survey of Clostridium difficile infection surveillance systems in Europe, 2011.

    PubMed

    Kola, Axel; Wiuff, Camilla; Akerlund, Thomas; van Benthem, Birgit H; Coignard, Bruno; Lyytikäinen, Outi; Weitzel-Kage, Doris; Suetens, Carl; Wilcox, Mark H; Kuijper, Ed J; Gastmeier, Petra

    2016-07-21

    To develop a European surveillance protocol for Clostridium difficile infection (CDI), existing national CDI surveillance systems were assessed in 2011. A web-based electronic form was provided for all national coordinators of the European CDI Surveillance Network (ECDIS-Net). Of 35 national coordinators approached, 33 from 31 European countries replied. Surveillance of CDI was in place in 14 of the 31 countries, comprising 18 different nationwide systems. Three of 14 countries with CDI surveillance used public health notification of cases as the route of reporting, and in another three, reporting was limited to public health notification of cases of severe CDI. The CDI definitions published by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC) were widely used, but there were differing definitions to distinguish between community- and healthcare-associated cases. All CDI surveillance systems except one reported annual national CDI rates (calculated as number of cases per patient-days). Only four surveillance systems regularly integrated microbiological data (typing and susceptibility testing results). Surveillance methods varied considerably between countries, which emphasises the need for a harmonised European protocol to allow consistent monitoring of the CDI epidemiology at European level. The results of this survey were used to develop a harmonised EU-wide hospital-based CDI surveillance protocol. PMID:27469420

  16. Clostridium difficile infection in a French university hospital

    PubMed Central

    Khanafer, Nagham; Oltra, Luc; Hulin, Monique; Dauwalder, Olivier; Vandenesch, Francois; Vanhems, Philippe

    2016-01-01

    Abstract The epidemiology of Clostridium difficile infection (CDI) has changed with an increase in incidence and severity. Prospective surveillance was therefore implemented in a French university hospital to monitor the characteristics of patients at risk and to recognize local trends. Between 2007 and 2014, all hospitalized patients (≥18 years) with CDI were included. During the survey, the mean incidence rate of CDI was 2.9 per 10,000 hospital-days. In all, 590 patients were included. Most of the episodes were healthcare-associated (76.1%). The remaining cases were community-acquired (18.1%) and unknown (5.9%). The comparison with healthcare-associated cases showed that the community-acquired group had a lower rate of antimicrobial exposure (P < 0.001), proton pump inhibitor (P < 0.001), and immunosuppressive drugs (P = 0.02). Over the study period, death occurred in 61 patients (10.3%), with 18 (29.5%) being related to CDI according to the physician in charge of the patient. Active surveillance of CDI is required to obtain an accurate picture of the real dimensions of CDI. PMID:27281101

  17. Fidaxomicin - the new drug for Clostridium difficile infection

    PubMed Central

    Vaishnavi, Chetana

    2015-01-01

    Clostridium difficile is one of the many aetiological agents of antibiotic associated diarrhoea and is implicated in 15-25 per cent of the cases. The organism is also involved in the exacearbation of inflammatory bowel disease and extracolonic manifestations. Due to increase in the incidence of C. difficile infection (CDI), emergence of hypervirulent strains, and increased frequency of recurrence, the clinical management of the disease has become important. The management of CDI is based on disease severity, and current antibiotic treatment options are limited to vancomycin or metronidazole in the developing countries. this review article briefly describes important aspects of CDI, and the new drug, fidaxomicin, for its treatment. Fidaxomicin is particularly active against C. difficile and acts by inhibition of RNA synthesis. Clinical trials done to compare the efficacy and safety of fidaxomicin with that of vancomycin in treating CDI concluded that fidaxomicin was non-inferior to vancomycin for treatment of CDI and that there was a significant reduction in recurrences. The bactericidal properties of fidaxomicin make it an ideal alternative for CDI treatment. However, fidaxomicin use should be considered taking into account the potential benefits of the drug, along with the medical requirements of the patient, the risks of treatment and the high cost of fidaxomicin compared to other treatment regimens. PMID:26112840

  18. The potential for emerging therapeutic options for Clostridium difficile infection

    PubMed Central

    Mathur, Harsh; Rea, Mary C; Cotter, Paul D; Ross, R Paul; Hill, Colin

    2014-01-01

    Clostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibiotic-associated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. Recently, advancements in next generation sequencing technology (NGS) have highlighted the extent of damage to the gut microbiota caused by broad-spectrum antibiotics, often resulting in C. difficile infection (CDI). Currently the treatment of choice for CDI involves the use of metronidazole and vancomycin. However, recurrence and relapse of CDI, even after rounds of metronidazole/vancomycin administration is a problem that must be addressed. The efficacy of alternative antibiotics such as fidaxomicin, rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota transplantation has been assessed and some have yielded positive outcomes against C. difficile. Some bacteriocins have also shown promising effects against C. difficile in recent years. In light of this, the potential for emerging treatment options and efficacy of anti-C. difficile vaccines are discussed in this review. PMID:25564777

  19. Fecal microbiota transplant for Clostridium difficile infection in older adults

    PubMed Central

    Tauxe, William M.; Haydek, John P.; Rebolledo, Paulina A.; Neish, Emma; Newman, Kira L.; Ward, Angela; Dhere, Tanvi; Kraft, Colleen S.

    2015-01-01

    Background: The objective of this study was to describe the safety of fecal microbiota transplant (FMT) for Clostridium difficile infection (CDI) among older adults. Methods: We performed a case review of all FMT recipients aged 65 or older treated at Emory University Hospital, a tertiary care and referral center for Georgia and surrounding states. Results: CDI resolved in 27 (87%) of 31 respondents, including three individuals who received multiple FMTs. Among four whose CDI was not resolved at follow up, three respondents did well initially before CDI recurred, and one individual never eradicated his CDI despite repeating FMT. During the study, five deaths and eight serious adverse events requiring hospitalization were reported within the study group during the follow-up period. Fecal transplant was not a causative factor in these events. The most common adverse event reported in 4 (13%) of 31 respondents was subjective worsening of arthritis. Conclusion: FMT is a generally safe and effective treatment option for older adults with CDI. PMID:27134658

  20. Fecal Transplantation for the Treatment of Recurrent Clostridium Difficile Infection

    PubMed Central

    Karadsheh, Zeid; Sule, Sachin

    2013-01-01

    Clostridium difficile infection (CDI) is currently a leading cause of antibiotic and health care-related diarrhea. The incidence and the severity of CDI-related diarrhea have increased dramatically in the USA and Europe in the past few decades. The emergence of multidrug-resistant hypervirulent strains of C. difficile has led to an increase in mortality. Fecal microbiota transplantation (FMT) (also known as fecal bacteriotherapy) has been utilized sporadically since the 1950s; and currently, the interest in using FMT has grown again in the past few years for the treatment of CDI and other chronic gastrointestinal diseases. FMT has shown to be effective, cheap, and has very few side effects. It is believed to manipulate and restore the gut microbiota, and therefore enhances the growth of “healthy” bacteria that break the cycle of recurrent CDI. This article focus on the recent case reports on FMT, and general approach to patients undergoing this therapy. Data were obtained through a literature search via PubMed and Google. PMID:23923106

  1. Characteristics of patients with Clostridium difficile infection in Taiwan.

    PubMed

    Lin, Y-C; Huang, Y-T; Lee, T-F; Lee, N-Y; Liao, C-H; Lin, S-Y; Ko, W-C; Hsueh, P-R

    2013-10-01

    The medical records of 84 patients with stool cultures positive for Clostridium difficile during the period August 2007 to June 2009 were retrospectively reviewed. A case of confirmed (toxigenic)C. difficile infection (CDI) was defined by the presence of symptoms (fever, diarrhoea, abdominal discomfort or distension, ileus) and the presence of toxigenic C. difficile. Patients with compatible clinical symptoms and stool cultures positive for non-toxigenic C. difficile isolates were defined as probable (non-toxigenic) CDI cases. Of these 84 patients, 50 (59.5%) were diagnosed as confirmed CDI and 34 (40.5%) as probable CDI. Thirteen (15.5%) of the 84 patients died during their hospital stay. Usage of proton pump inhibitors was a significant independent risk factor for CDI (OR 3.21, P=0.014). Of the 50 isolates associated with confirmed CDI, seven (8.3%) carried binary toxin genes (cdtAB), and six (7.1%) had a deletion in the tcdC gene. The mortality rate in confirmed CDI patients with isolates exhibiting deletion in the tcdC gene (2/6, 33.3%), those with isolates harbouring binary toxin genes (2/7, 28.6%), and those with isolates containing mutations in gyrA (2/7, 28.6%) and gyrB (1/2, 50%) was higher than the overall mortality rate (10/50, 20%) in patients with confirmed CDI. PMID:23218131

  2. Ridinilazole: a novel therapy for Clostridium difficile infection.

    PubMed

    Vickers, Richard J; Tillotson, Glenn; Goldstein, Ellie J C; Citron, Diane M; Garey, Kevin W; Wilcox, Mark H

    2016-08-01

    Clostridium difficile infection (CDI) is the leading cause of infectious healthcare-associated diarrhoea. Recurrent CDI increases disease morbidity and mortality, posing a high burden to patients and a growing economic burden to the healthcare system. Thus, there exists a significant unmet and increasing medical need for new therapies for CDI. This review aims to provide a concise summary of CDI in general and a specific update on ridinilazole (formerly SMT19969), a novel antibacterial currently under development for the treatment of CDI. Owing to its highly targeted spectrum of activity and ability to spare the normal gut microbiota, ridinilazole provides significant advantages over metronidazole and vancomycin, the mainstay antibiotics for CDI. Ridinilazole is bactericidal against C. difficile and exhibits a prolonged post-antibiotic effect. Furthermore, treatment with ridinilazole results in decreased toxin production. A phase 1 trial demonstrated that oral ridinilazole is well tolerated and specifically targets clostridia whilst sparing other faecal bacteria. Phase 2 and 3 trials will hopefully further our understanding of the clinical utility of ridinilazole for the treatment of CDI. PMID:27283730

  3. Fecal Microbiota Transplantation for Clostridium difficile Infection: The Ochsner Experience

    PubMed Central

    Ray, Arnab; Smith, Robert; Breaux, Jacob

    2014-01-01

    Background Clostridium difficile infection (CDI) accounts for 20%-30% of cases of antibiotic-associated diarrhea and is the most commonly recognized cause of infectious diarrhea in healthcare settings. The incidence of CDI is rising, while the effectiveness of antibiotics for treatment decreases with recurrent episodes. The use of fecal microbiota transplantation (FMT) for cure of CDI has been reported since 1958, and the worldwide cure rate is reported to be 93%. We report our experience with FMT for the treatment of CDI. Methods We performed a retrospective chart review of patients undergoing FMT for CDI at Ochsner Clinic Foundation from August 2012 to November 2013. FMT was administered via colonoscopy for patients with recurrent or severe CDI. Stool donors were screened for infections in the majority of cases. Results FMT was performed in 20 CDI patients. The 16 female and 4 male patients ranged in age from 27 to 89 years (mean 62 years). The average duration of illness from diagnosis to treatment was 49.6 weeks, based on available data. Only 3 donors were unscreened for infectious pathogens. Nine donors were related to the recipients by blood; most of the other donors were spouses. The average length of follow-up after FMT was 3 months. No recurrences of CDI after treatment have been documented. Adverse events reported after treatment included abdominal cramping, bloating, flatulence, and nausea that resolved. Conclusion Although the US Food and Drug Administration currently considers FMT an experimental therapy, we demonstrate that FMT is safe, well tolerated, and effective for recurrent and severe CDI. PMID:25598718

  4. Human Clostridium difficile infection: altered mucus production and composition

    PubMed Central

    Engevik, Melinda A.; Yacyshyn, Mary Beth; Engevik, Kristen A.; Wang, Jiang; Darien, Benjamin; Hassett, Daniel J.; Yacyshyn, Bruce R.

    2014-01-01

    The majority of antibiotic-induced diarrhea is caused by Clostridium difficile (C. difficile). Hospitalizations for C. difficile infection (CDI) have tripled in the last decade, emphasizing the need to better understand how the organism colonizes the intestine and maintain infection. The mucus provides an interface for bacterial-host interactions and changes in intestinal mucus have been linked host health. To assess mucus production and composition in healthy and CDI patients, the main mucins MUC1 and MUC2 and mucus oligosaccharides were examined. Compared with healthy subjects, CDI patients demonstrated decreased MUC2 with no changes in surface MUC1. Although MUC1 did not change at the level of the epithelia, MUC1 was the primary constituent of secreted mucus in CDI patients. CDI mucus also exhibited decreased N-acetylgalactosamine (GalNAc), increased N-acetylglucosamine (GlcNAc), and increased terminal galactose residues. Increased galactose in CDI specimens is of particular interest since terminal galactose sugars are known as C. difficile toxin A receptor in animals. In vitro, C. difficile is capable of metabolizing fucose, mannose, galactose, GlcNAc, and GalNAc for growth under healthy stool conditions (low Na+ concentration, pH 6.0). Injection of C. difficile into human intestinal organoids (HIOs) demonstrated that C. difficile alone is sufficient to reduce MUC2 production but is not capable of altering host mucus oligosaccharide composition. We also demonstrate that C. difficile binds preferentially to mucus extracted from CDI patients compared with healthy subjects. Our results provide insight into a mechanism of C. difficile colonization and may provide novel target(s) for the development of alternative therapeutic agents. PMID:25552581

  5. NAP1 Strain Type Predicts Outcomes from Clostridium difficile Infection

    PubMed Central

    See, Isaac; Mu, Yi; Cohen, Jessica; Beldavs, Zintars G.; Winston, Lisa G.; Dumyati, Ghinwa; Holzbauer, Stacy; Dunn, John; Farley, Monica M.; Lyons, Carol; Johnston, Helen; Phipps, Erin; Perlmutter, Rebecca; Anderson, Lydia; Gerding, Dale N.; Lessa, Fernanda C.

    2015-01-01

    Background Studies conflict regarding the importance of the fluoroquinolone-resistant North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) outcome. We describe strain types causing CDI and evaluate their association with patient outcomes. Methods CDI cases were identified from population-based surveillance. Multivariate regression models were used to evaluate the associations of strain type with severe disease (ileus, toxic megacolon, or pseudomembranous colitis within 5 days; or white blood cell count ≥15,000/mm3 within one day of positive test), severe outcome (intensive care unit admission after positive test, colectomy for C. difficile infection, or death within 30 days of positive test), and death within 14 days of positive test. Results Strain typing results were available for 2,057 cases. Severe disease occurred in 363 (17.7%) cases, severe outcome in 100 (4.9%), and death within 14 days in 56 (2.7%). The most common strain types were NAP1 (28.4%), NAP4 (10.2%) and NAP11 (9.1%). In unadjusted analysis, NAP1 was associated with greater odds of severe disease than other strains. After controlling for patient risk factors, healthcare exposure, and antibiotic use, NAP1 was associated with severe disease (adjusted odds ratio [aOR] 1.74, 95% confidence interval [CI], 1.36–2.22), severe outcome (aOR 1.66, 95% CI, 1.09–2.54), and death within 14 days (aOR 2.12, 95% CI, 1.22–3.68). Conclusion NAP1 was the most prevalent strain and a predictor of severe disease, severe outcome, and death. Strategies to reduce NAP1 prevalence, such as antibiotic stewardship to reduce fluoroquinolone use, might reduce CDI morbidity. PMID:24604900

  6. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... death in injected mice. (iii) L+ dose. The smallest quantity of toxin which can be mixed with one unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard... until injections of mice can be made. (vi) Five Swiss white mice, each weighing 16-20 grams, shall...

  7. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... death in injected mice. (iii) L+ dose. The smallest quantity of toxin which can be mixed with one unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard... until injections of mice can be made. (vi) Five Swiss white mice, each weighing 16-20 grams, shall...

  8. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... death in injected mice. (iii) L+ dose. The smallest quantity of toxin which can be mixed with one unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard... until injections of mice can be made. (vi) Five Swiss white mice, each weighing 16-20 grams, shall...

  9. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... death in injected mice. (iii) L+ dose. The smallest quantity of toxin which can be mixed with one unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard... until injections of mice can be made. (vi) Five Swiss white mice, each weighing 16-20 grams, shall...

  10. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... death in injected mice. (iii) L+ dose. The smallest quantity of toxin which can be mixed with one unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard... until injections of mice can be made. (vi) Five Swiss white mice, each weighing 16-20 grams, shall...

  11. Clostridium infection (jisizheng) in yaks in Qinghai, China.

    PubMed

    Changqing, Q; Xueli, Y

    2001-10-01

    Since the mid-1980s, outbreaks of a disease characterized by a sudden onset, acute deaths and extensive haemorrhages in the viscera and digestive tract of yaks have been prevalent in Qilian, Qinghai, China. The disease is known as jisiheng by local people. Virulent Clostridium perfringens type A and Clostridium haemolytica were isolated from yaks that had died of jisizheng. In 1996 and 1997, yaks were immunized with a polyvalent inactivated vaccine against C. perfringens and with an inactivated vaccine against C. haemolyticum, and this prevented the occurrence of jisizheng. PMID:11583378

  12. Depression, antidepressant medications, and risk of Clostridium difficile infection

    PubMed Central

    2013-01-01

    Background An ancillary finding in previous research has suggested that the use of antidepressant medications increases the risk of developing Clostridium difficile infection (CDI). Our objective was to evaluate whether depression or the use of anti-depressants altered the risk of developing CDI, using two distinct datasets and study designs. Methods In Study 1, we conducted a longitudinal investigation of a nationally representative sample of older Americans (n = 16,781), linking data from biennial interviews to physician and emergency department visits, stays in hospital and skilled nursing facilities, home health visits, and other outpatient visits. In Study 2, we completed a clinical investigation of hospitalized adults who were tested for C. difficile (n = 4047), with cases testing positive and controls testing negative. Antidepressant medication use prior to testing was ascertained. Results The population-based rate of CDI in older Americans was 282.9/100,000 person-years (95% confidence interval (CI)) 226.3 to 339.5) for individuals with depression and 197.1/100,000 person-years for those without depression (95% CI 168.0 to 226.1). The odds of CDI were 36% greater in persons with major depression (95% CI 1.06 to 1.74), 35% greater in individuals with depressive disorders (95% CI 1.05 to 1.73), 54% greater in those who were widowed (95% CI 1.21 to 1.95), and 25% lower in adults who did not live alone (95% CI 0.62 to 0.92). Self-reports of feeling sad or having emotional, nervous or psychiatric problems at baseline were also associated with the later development of CDI. Use of certain antidepressant medications during hospitalization was associated with altered risk of CDI. Conclusions Adults with depression and who take specific anti-depressants seem to be more likely to develop CDI. Older adults who are widowed or who live alone are also at greater risk of CDI. PMID:23647647

  13. Outcome of ICU patients with Clostridium difficile infection

    PubMed Central

    2012-01-01

    Introduction As data from Clostridium difficile infection (CDI) in intensive care unit (ICU) are still scarce, our objectives were to assess the morbidity and mortality of ICU-acquired CDI. Methods We compared patients with ICU-acquired CDI (watery or unformed stools occurring ≥ 72 hours after ICU admission with a stool sample positive for C. difficile toxin A or B) with two groups of controls hospitalized at the same time in the same unit. The first control group comprised patients with ICU-acquired diarrhea occurring ≥ 72 hours after ICU admission with a stool sample negative for C. difficile and for toxin A or B. The second group comprised patients without any diarrhea. Results Among 5,260 patients, 512 patients developed one episode of diarrhea. Among them, 69 (13.5%) had a CDI; 10 (14.5%) of them were community-acquired, contrasting with 12 (17.4%) that were hospital-acquired and 47 (68%) that were ICU-acquired. A pseudomembranous colitis was associated in 24/47 (51%) ICU patients. The median delay between diagnosis and metronidazole administration was one day (25th Quartile; 75th Quartile (0; 2) days). The case-fatality rate for patients with ICU-acquired CDI was 10/47 (21.5%), as compared to 112/443 (25.3%) for patients with negative tests. Neither the crude mortality (cause specific hazard ratio; CSHR = 0.70, 95% confidence interval; CI 0.36 to 1.35, P = 0.3) nor the adjusted mortality to confounding variables (CSHR = 0.81, 95% CI 0.4 to 1.64, P = 0.6) were significantly different between CDI patients and diarrheic patients without CDI. Compared to the general ICU population, neither the crude mortality (SHR = 0.64, 95% CI 0.34 to 1.21, P = 0.17), nor the mortality adjusted to confounding variables (CSHR = 0.71, 95% confidence interval (CI) 0.38 to 1.35, P = 0.3), were significantly different between the two groups. The estimated increase in the duration of stay due to CDI was 8.0 days ± 9.3 days, (P = 0.4) in comparison to the diarrheic population

  14. Considering the antimicrobial sensitivity of the intestinal botulism agent Clostridium butyricum when treating concomitant infections.

    PubMed

    Fenicia, Lucia; Ferrini, Anna Maria; Anniballi, Fabrizio; Mannoni, Veruscka; Aureli, Paolo

    2003-01-01

    In Italy, neurotoxigenic Clostridium butyricum has been reported as a new agent of intestinal toxemia botulism, and most of the cases have been associated with enterocolitis. Although infections concomitant with botulism must be treated with antibiotics, this can increase the severity of botulism. We discuss the sensitivity of this agent to certain antibiotics, compared to findings on the sensitivity of C. botulinum. PMID:14758873

  15. State law mandates for reporting of healthcare-associated Clostridium difficile infections in hospitals.

    PubMed

    Reagan, Julie; Herzig, Carolyn T A; Pogorzelska-Maziarz, Monika; Dick, Andrew W; Stone, Patricia W; Divya Srinath, Jd

    2015-03-01

    US state and territorial laws were reviewed to identify Clostridium difficile infection reporting mandates. Twenty states require reporting either under state law or by incorporating federal Centers for Medicare & Medicaid Services' reporting requirements. Although state law mandates are more common, the incorporation of federal reporting requirements has been increasing. PMID:25695178

  16. Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era

    PubMed Central

    Polage, Christopher R.; Gyorke, Clare E.; Kennedy, Michael A.; Leslie, Jhansi L.; Chin, David L.; Wang, Susan; Nguyen, Hien H.; Huang, Bin; Tang, Yi-Wei; Lee, Lenora W.; Kim, Kyoungmi; Taylor, Sandra; Romano, Patrick S.; Panacek, Edward A.; Goodell, Parker B.; Solnick, Jay V.; Cohen, Stuart H.

    2016-01-01

    IMPORTANCE Clostridium difficile is a major cause of health care–associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment. OBJECTIVE To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox−/PCR+) for CDI. DESIGN, SETTING, AND PARTICIPANTS Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015. MAIN OUTCOMES AND MEASURES Patients undergoing C difficile testing were grouped by US Food and Drug Administration–approved toxin and PCR tests as Tox+/PCR+, Tox−/PCR+, or Tox−/PCR−. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days. RESULTS Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox−/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients (P < .001 for all). The median duration of diarrhea was shorter in Tox−/PCR+ patients (2 days; interquartile range, 1-4 days) than in Tox+/PCR+ patients (3 days; interquartile range, 1-6 days) (P = .003) and was

  17. A Review of Management of Clostridium difficile Infection: Primary and Recurrence

    PubMed Central

    Vincent, Yasmeen; Manji, Arif; Gregory-Miller, Kathleen; Lee, Christine

    2015-01-01

    Clostridium difficile infection (CDI) is a potentially fatal illness, especially in the elderly and hospitalized individuals. The recurrence and rates of CDI are increasing. In addition, some cases of CDI are refractory to the currently available antibiotics. The search for improved modalities for the management of primary and recurrent CDI is underway. This review discusses the current antibiotics, fecal microbiota transplantation (FMT) and other options such as immunotherapy and administration of non-toxigenic Clostridium difficile (CD) for the management of both primary and recurrent CDI. PMID:27025632

  18. Complications of Hospital-Onset Healthcare Facility-Associated Clostridium difficile Infections Among Veterans.

    PubMed

    Evans, Martin E; Kralovic, Stephen M; Simbartl, Loretta A; Whitlock, Judith L; Jain, Rajiv; Roselle, Gary A

    2016-06-01

    Complications within 30 days of a clinically confirmed hospital-onset Clostridium difficile infection diagnosis from July 1, 2012, through June 30, 2015, in 127 acute care Veterans Health Administration facilities were evaluated. Pooled rates for attributable intensive care unit admissions, colectomies, and deaths were 2.7%, 0.5%, and 0.4%, respectively. Infect Control Hosp Epidemiol 2016;37:717-719. PMID:26880482

  19. [Recent epidemiology of Clostridium difficile infection in Japan].

    PubMed

    Yamagishi, Yuka; Mikamo, Hiroshige

    2015-12-01

    Clostridium difficile (C. difficile) is a major pathogen for diarrhea in hospitalized patients and because of outbreak of highly virulent strain in EU and US, increased length of hospital stay and increased numbers of severe patients and deaths have become major challenges. In recent years, transmissions through community-acquired or food-borne infections are reported. National surveillance has been already performed overseas. Guidelines for preventing C. difficile infection (CDI) is available, and education activities are promoted for preventing the infection spread. Meanwhile, in Japan, medical hospitals are reporting individual CDI incidence, however, a large-scale research has not been conducted up to the present date and therefore the entire status of CDI including infection of the highly virulent strain has yet to be revealed. This time, we performed a questionnaire-based survey at 2,537 hospitals nationwide between April 15, 2013 and May 31, 2013 to investigate CDI incidence, diagnosis and treatment. Valid responses were obtained from 321 hospitals. Regarding the annual number of CDI patients at all the hospitals, the highest group of hospitals responding "1 to 5 patients a year" was 17.8%, and the second highest group of hospitals responding "no patients a year" was 13.1%. In contrast, there was a group of hospitals with "more than 101 patients a year", which was 3.1%. This indicates that there was the difference in the CDI incidences among hospitals. According to the questionnaire results, a highest group of hospitals responding "0-20%" for CDI patients with serious complication such as toxic megacolon, gastrointestinal perforation, ileus paralytic, bacteremia, sepsis, crohn's disease, and ulcerative colitis was 62.6%, and for CDI patients with recurrence more than one, a group of hospitals answering "0 to 20%" was 56.4%, which was the highest. This suggested that there was only a small number of serious CDI patients and recurrence CDI patients in Japan

  20. Antibiotic therapy and Clostridium difficile infection - primum non nocere - first do no harm.

    PubMed

    Crowther, Grace S; Wilcox, Mark H

    2015-01-01

    Treatment options for Clostridium difficile infection (CDI) remain limited despite this usually nosocomial infection posing an urgent threat to public health. A major paradox of the management of CDI is the use of antimicrobial agents to treat infection, which runs the risk of prolonged gut microbiota perturbation and so recurrence of infection. Here, we explore alternative CDI treatment and prevention options currently available or in development. Notably, strategies that aim to reduce the negative effects of antibiotics on gut microbiota offer the potential to alter current antimicrobial stewardship approaches to preventing CDI. PMID:26396535

  1. Controversies Surrounding Clostridium difficile Infection in Infants and Young Children

    PubMed Central

    Nicholson, Maribeth R.; Thomsen, Isaac P.; Edwards, Kathryn M.

    2014-01-01

    Clostridium difficile is a frequent cause of antibiotic-associated diarrhea in adults and older children. However, as many as 80% of infants can be asymptomatically colonized. The reasons for this have not been well established but are believed to be due to differences in toxin receptors or toxin internalization. Determining which children who test positive for C. difficile warrant treatment is exceedingly difficult, especially in the setting of increased rates of detection and the rising risk of disease in children lacking classic risk factors for C. difficile.

  2. Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection

    NASA Astrophysics Data System (ADS)

    Surawicz, Christina M.

    Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.

  3. Risk Factors and Outcomes for Bloodstream Infections Secondary to Clostridium difficile Infection

    PubMed Central

    Russo, Alessandro; Iraci, Federica; Carfagna, Paolo; Goldoni, Paola; Vullo, Vincenzo; Venditti, Mario

    2015-01-01

    We determined the incidence, risk factors, and outcomes of bloodstream infections (BSI) subsequent to Clostridium difficile infection (CDI). We performed a retrospective study of all patients with definite diagnosis of CDI admitted from January 2014 to December 2014 in two large hospitals in Rome. Two groups of patients were analyzed: those with CDI and subsequent BSI (CDI/BSI+) and those with CDI and no evidence of primary BSI (CDI/BSI−). Data about clinical features, microbiology, treatments, and mortality were obtained. Overall, 393 cases of CDI were included in the final analysis: 72 developed a primary nosocomial BSI, while 321 had CDI without microbiological and clinical evidence of BSI. Etiologic agents of BSI were Candida species (47.3%), Enterobacteriaceae (19.4%), enterococci (13.9%), and mixed infections (19.4%). In multivariate analysis, ribotype 027 status (odds ratio [OR], 6.5), CDI recurrence (OR, 5.5), severe CDI infection (OR, 8.3), and oral vancomycin at >500 mg/day (OR, 3.1) were recognized as factors independently associated with the development of nosocomial BSI. Thirty-day mortality from CDI diagnosis was higher for patients of the CDI/BSI+ group than for the controls (38.9 versus 13.1%; P < 0.001). Among patients of the CDI/BSI+ group, mortality attributable to primary BSI was as high as 57%. Our findings suggest that severe CDI is complicated by the development of nosocomial BSI. Candida species and enteric bacteria appear to be the leading causative pathogens and are associated with poor outcomes. PMID:26482315

  4. Faecal microbiota transplantation for severe Clostridium difficile infection in the intensive care unit.

    PubMed

    Trubiano, Jason A; Gardiner, Bradley; Kwong, Jason C; Ward, Peter; Testro, Adam G; Charles, Patrick G P

    2013-02-01

    We describe a case of faecal microbiota transplantation (FMT) used for severe binary toxin-positive Clostridium difficile infection in an intensive care setting. The patient was admitted to the ICU of a tertiary hospital and failed traditional maximal pharmacological management. Adjunctive therapy with FMT given through gastroscopy resulted in resolution of the C. difficile-related symptoms. Although there is a growing experience with FMT for recurrent C. difficile infection, published evidence in severe disease is very limited. In a landscape of increasingly severe C. difficile infection, adjunctive FMT may be considered a useful early treatment option. PMID:23117471

  5. Administration of probiotic kefir to mice with Clostridium difficile infection exacerbates disease.

    PubMed

    Spinler, Jennifer K; Brown, Aaron; Ross, Caná L; Boonma, Prapaporn; Conner, Margaret E; Savidge, Tor C

    2016-08-01

    Lifeway(®) kefir, a fermented milk product containing 12 probiotic organisms, is reported to show promise as an alternative to fecal microbiota transplantation for recurrent Clostridium difficile infection (CDI). We employed a murine CDI model to study the probiotic protective mechanisms and unexpectedly determined that kefir drastically increased disease severity. Our results emphasize the need for further independent clinical testing of kefir as alternative therapy in recurrent CDI. PMID:27180007

  6. Evaluation of a loop-mediated isothermal amplification assay for diagnosis of Clostridium difficile infections.

    PubMed

    Lalande, Valérie; Barrault, Laurence; Wadel, Sophie; Eckert, Catherine; Petit, Jean-Claude; Barbut, Frédéric

    2011-07-01

    A new assay (illumigene C. difficile; Meridian Bioscience), based on the original loop-mediated isothermal amplification (LAMP) assay, was evaluated with 472 unformed stools from patients suspected of Clostridium difficile infection. Compared to the toxigenic culture, the sensitivity, specificity, and positive and negative predictive values were 91.8, 99.1, 91.8, and 99.1% for the illumigene C. difficile assay and 69.4, 100, 100, and 96.6% for the cytotoxicity assay, respectively. PMID:21525213

  7. Coxofemoral luxation in a border collie as a complication of a Clostridium tetani infection.

    PubMed

    Goldhammer, M A; Chapman, P S; Grierson, J M

    2008-03-01

    A four-month-old male, entire, border collie was presented to the Queen Mother Hospital for Animals with a two day history of muscular spasms and "Risus sardonicus". Tetanus was diagnosed, and the dog was treated with tetanus antitoxin, antibiotics and supportive therapy. Coxofemoral luxation resulted as a complication of the tetanus and was successfully managed by performing a femoral head and neck excision. This is the first report of joint luxation associated with Clostridium tetani infection in a dog. PMID:18005106

  8. WSES guidelines for management of Clostridium difficile infection in surgical patients.

    PubMed

    Sartelli, Massimo; Malangoni, Mark A; Abu-Zidan, Fikri M; Griffiths, Ewen A; Di Bella, Stefano; McFarland, Lynne V; Eltringham, Ian; Shelat, Vishal G; Velmahos, George C; Kelly, Ciarán P; Khanna, Sahil; Abdelsattar, Zaid M; Alrahmani, Layan; Ansaloni, Luca; Augustin, Goran; Bala, Miklosh; Barbut, Frédéric; Ben-Ishay, Offir; Bhangu, Aneel; Biffl, Walter L; Brecher, Stephen M; Camacho-Ortiz, Adrián; Caínzos, Miguel A; Canterbury, Laura A; Catena, Fausto; Chan, Shirley; Cherry-Bukowiec, Jill R; Clanton, Jesse; Coccolini, Federico; Cocuz, Maria Elena; Coimbra, Raul; Cook, Charles H; Cui, Yunfeng; Czepiel, Jacek; Das, Koray; Demetrashvili, Zaza; Di Carlo, Isidoro; Di Saverio, Salomone; Dumitru, Irina Magdalena; Eckert, Catherine; Eckmann, Christian; Eiland, Edward H; Enani, Mushira Abdulaziz; Faro, Mario; Ferrada, Paula; Forrester, Joseph Derek; Fraga, Gustavo P; Frossard, Jean Louis; Galeiras, Rita; Ghnnam, Wagih; Gomes, Carlos Augusto; Gorrepati, Venkata; Ahmed, Mohamed Hassan; Herzog, Torsten; Humphrey, Felicia; Kim, Jae Il; Isik, Arda; Ivatury, Rao; Lee, Yeong Yeh; Juang, Paul; Furuya-Kanamori, Luis; Karamarkovic, Aleksandar; Kim, Peter K; Kluger, Yoram; Ko, Wen Chien; LaBarbera, Francis D; Lee, Jae Gil; Leppaniemi, Ari; Lohsiriwat, Varut; Marwah, Sanjay; Mazuski, John E; Metan, Gokhan; Moore, Ernest E; Moore, Frederick Alan; Nord, Carl Erik; Ordoñez, Carlos A; Júnior, Gerson Alves Pereira; Petrosillo, Nicola; Portela, Francisco; Puri, Basant K; Ray, Arnab; Raza, Mansoor; Rems, Miran; Sakakushev, Boris E; Sganga, Gabriele; Spigaglia, Patrizia; Stewart, David B; Tattevin, Pierre; Timsit, Jean Francois; To, Kathleen B; Tranà, Cristian; Uhl, Waldemar; Urbánek, Libor; van Goor, Harry; Vassallo, Angela; Zahar, Jean Ralph; Caproli, Emanuele; Viale, Pierluigi

    2015-01-01

    In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients. PMID:26300956

  9. Clostridium glycolicum Wound Infections: Case Reports and Review of the Literature▿

    PubMed Central

    Jiang, Wei; Abrar, Sahibzada; Romagnoli, Mark; Carroll, Karen C.

    2009-01-01

    We describe two cases of Clostridium glycolicum wound infections in immunocompetent adults. The bacterium was identified by 16S rRNA gene sequencing. This is the third published report of the recovery of this organism from human clinical material and highlights the importance of the organism as a potential human pathogen. Our report extends the spectrum of the diseases caused by C. glycolicum. PMID:19261780

  10. Clostridium welchii and Bacillus cereus infection and intoxication

    PubMed Central

    Hobbs, Betty C.

    1974-01-01

    Clostridium welchii type A is a common agent of food poisoning when allowed to proliferate to large numbers in cooked foods, usually meat and poultry. The main factors of importance are survival of the spores, frequently found on raw products, through the cooking process, and possible contamination of cooked meats transferred to unclean containers; subsequent germination of spores and rapid multiplication of the vegetative cells during long slow cooling and non-refrigerated storage lead to heavy contamination. The toxin responsible is different from the soluble antigens, and its formation in the intestine is associated with sporulation. Large numbers of Cl. welchii of the same serological types in food and faeces is the main diagnostic factor. Important preventive measures are rapid cooling and cold storage to prevent growth. Bacillus cereus is an aerobic sporulating organism commonly found in cereals. Outbreaks described from Europe have a different aetiology with regard to food vehicles, incubation period and symptoms from those that have been reported recently in the U.K. from fried and boiled rice. The spores survive through cooking procedures and grow out to cells which sporulate readily in the cooked food and which are assumed to produce toxin in the food. Large numbers of B. cereus are found in foods causing illness and, as with Cl. welchii, the main preventive measure is inhibition of growth by quick cooling and cold storage of foods cooked ahead of requirements. A comparative table of the characteristics and clinical symptoms of Cl. welchii and B. cereus is given. PMID:4377580

  11. Diagnosis of Clostridium perfringens intestinal infections in sheep and goats.

    PubMed

    Uzal, Francisco A; Songer, J Glenn

    2008-05-01

    Clostridium perfringens produces enteric diseases, generically called enterotoxemias, in sheep, goats, and other animals. This microorganism can be a normal inhabitant of the intestine of most animal species, including humans, but when the intestinal environment is altered by sudden changes in diet or other factors, C. perfringens proliferates and produces potent toxins that act locally or are absorbed into the general circulation with usually devastating effects on the host. History, clinical signs, and gross postmortem findings are useful tools for establishing a presumptive diagnosis of clostridial enterotoxemia in sheep and goats. Definitive diagnosis requires laboratory confirmation. Isolation of some types of C. perfringens (e.g., B and C) can be of diagnostic value, but other types (e.g., A) are so commonly found in the intestine of normal animals that isolation is meaningless from a diagnostic point of view. The most accepted criterion in establishing a definitive diagnosis of enterotoxemia is detection of C. perfringens toxins in intestinal contents. Also, histopathological examination of brain is very useful for diagnosis of type D disease, as lesions produced by epsilon toxin in the brains of sheep and goats are pathognomonic for type D enterotoxemia. Ancillary tests, such as measuring urine glucose or observing Gram-stained smears of intestinal mucosa, can be used. However, although such tests have a presumptive diagnostic value when positive, they cannot be used to rule out a diagnosis of enterotoxemia when negative. PMID:18460610

  12. Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection

    PubMed Central

    Avila, Meera B.; Avila, Nathaniel P.; Dupont, Andrew W.

    2016-01-01

    Clostridium difficile infection (CDI) has become the most frequently reported health care-associated infection in the United States [1]. As the incidence of CDI rises, so too does the burden it produces on health care and society. In an attempt to decrease the burden of CDI and provide the best outcomes for patients affected by CDI, there have been many recent advancements in the understanding, diagnosis, and management of CDI. In this article, we review the current recommendations regarding CDI testing and treatment strategies. PMID:26918176

  13. Clostridium difficile infection: Early history, diagnosis and molecular strain typing methods.

    PubMed

    Rodriguez, C; Van Broeck, J; Taminiau, B; Delmée, M; Daube, G

    2016-08-01

    Recognised as the leading cause of nosocomial antibiotic-associated diarrhoea, the incidence of Clostridium difficile infection (CDI) remains high despite efforts to improve prevention and reduce the spread of the bacterium in healthcare settings. In the last decade, many studies have focused on the epidemiology and rapid diagnosis of CDI. In addition, different typing methods have been developed for epidemiological studies. This review explores the history of C. difficile and the current scope of the infection. The variety of available laboratory tests for CDI diagnosis and strain typing methods are also examined. PMID:27238460

  14. Implementation of a Clinical Decision Support Alert for the Management of Clostridium difficile Infection

    PubMed Central

    Revolinski, Sara

    2015-01-01

    Clostridium difficile infections are common in hospitalized patients and can result in significant morbidity and mortality. It is imperative to optimize the management of C. difficile infections to help minimize disease complications. Antimicrobial stewardship techniques including guidelines, order sets and other clinical decision support functionalities may be utilized to assist with therapy optimization. We implemented a novel alert within our electronic medical record to direct providers to the C. difficile order set in order to assist with initiating therapy consistent with institutional guideline recommendations. The alert succeeded in significantly increasing order set utilization, but guideline compliance was unchanged. PMID:27025646

  15. Fecal Transplantation using a Nasoenteric Tube during an Initial Episode of Severe Clostridium difficile Infection

    PubMed Central

    Hong, Namki; Kim, Jung Ho; Park, Se Hee; Kim, Sung Bae; Song, In Ji; Ann, Hea Won; Ahn, Jin Young; Kim, Sun Bean; Ku, Nam Su; Lee, Kyungwon; Yong, Dongeun; Kim, June Myung

    2016-01-01

    The incidence of Clostridium difficile infection is increasing worldwide, and its severity and resulting mortality are also on the rise. Metronidazole and oral vancomycin remain the treatments of choice, but there are concerns about treatment failure and the appearance of resistant strains. Furthermore, antibiotic therapy results in recurrence rates of at least 20%. Fecal transplantation may be a feasible treatment option for recurrent C. difficile infection; moreover, it may be an early treatment option for severe C. difficile infection. We report a case of severe C. difficile infection treated with fecal transplantation using a nasoenteric tube during an initial episode. This is the first reported case of fecal transplantation using a nasoenteric tube during an initial episode of C. difficile infection in Korea. PMID:27104013

  16. [Treatment of a severe Clostridium difficile infection with colonic lavages. Report of one case].

    PubMed

    Quezada, Felipe; Castillo, Richard; Villalón, Constanza; Zúñiga, José Miguel; Manterola, Carla; Molina, María Elena; Bellolio, Felipe; Urrejola, Gonzalo

    2015-05-01

    A loop ileostomy with intraoperative anterograde colonic lavage has been described as an alternative to colectomy in the management of cases of Clostridium difficile infection refractory to medical treatment. We report a 69 years old diabetic women admitted with a septic shock. An abdominal CAT scan showed a pan-colitis that seemed to be infectious. A polymerase chain reaction was positive for Clostridium Difficile. Due to the failure to improve after full medical treatment, a derivative loop ileostomy and intra-operatory colonic lavage were performed, leaving a Foley catheter in the proximal colon. In the postoperative period, anterograde colonic instillations of Vancomycin flushes through the catheter were performed every 6 hours. Forty eight hours after surgery, the patient improved. A colonoscopy prior to discharge showed resolution of the pseudomembranous colitis. PMID:26203580

  17. BACTERIOCIN E1073 PRODUCED BY ENTEROCOCCUS FAECIUM LWP1073 IS EFFECTIVE FOR TREATING COMMENSAL CLOSTRIDIUM PERFRINGENS INFECTION IN BROILERS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enterotoxin-producing Clostridium perfringens type A bacteria occupy a significant place in the etiological structure of food-borne infections in humans. One potential approach to minimize infections associated with food-borne pathogens is to control the carriage of C. perfringens in broilers. For ...

  18. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents.

    PubMed

    Van Hise, Nicholas W; Bryant, Alex M; Hennessey, Erin K; Crannage, Andrew J; Khoury, Jad A; Manian, Farrin A

    2016-09-01

    We compared rates of recurrent Clostridium difficile infection in patients receiving or not receiving oral vancomycin prophylaxis with systemic antimicrobial therapy. The incidence of C. difficile infection was significantly lower in patients receiving prophylaxis (4.2% vs 26.6% in those without prophylaxis; odds ratio, 0.12; 95% confidence interval, .04-.4; P < .001). PMID:27318333

  19. Role of obesity and adipose tissue-derived cytokine leptin during Clostridium difficile infection

    PubMed Central

    Madan, Rajat; Petri, William A.

    2015-01-01

    Obesity is among the most pressing health concerns in the world since it is increasingly common even in the developing world, and is clearly associated with increased risk for chronic debilitating diseases and death. Furthermore, obesity can influence the pathogenesis of infectious diseases by affecting the balance of pathogen clearance and pathological inflammation. The mechanisms that result in enhanced inflammation in obese individuals are poorly understood. Clostridium difficile is a major cause of nosocomial infections worldwide. Recent studies have shown that obesity is associated with increased risk of C. difficile infections. In this review, we will discuss our current knowledge of the role of obesity in determining risk of C. difficile infections, and focus on the role of the adipose tissue-derived cytokine leptin in C. difficile infections. PMID:25638400

  20. Role of obesity and adipose tissue-derived cytokine leptin during Clostridium difficile infection.

    PubMed

    Madan, Rajat; Petri, William A

    2015-08-01

    Obesity is among the most pressing health concerns in the world since it is increasingly common even in the developing world, and is clearly associated with increased risk for chronic debilitating diseases and death. Furthermore, obesity can influence the pathogenesis of infectious diseases by affecting the balance of pathogen clearance and pathological inflammation. The mechanisms that result in enhanced inflammation in obese individuals are poorly understood. Clostridium difficile is a major cause of nosocomial infections worldwide. Recent studies have shown that obesity is associated with increased risk of C. difficile infections. In this review, we will discuss our current knowledge of the role of obesity in determining risk of C. difficile infections, and focus on the role of the adipose tissue-derived cytokine leptin in C. difficile infections. PMID:25638400

  1. Evolution of Testing Algorithms at a University Hospital for Detection of Clostridium difficile Infections

    PubMed Central

    Culbreath, Karissa; Ager, Edward; Nemeyer, Ronald J.; Kerr, Alan

    2012-01-01

    We present the evolution of testing algorithms at our institution in which the C. Diff Quik Chek Complete immunochromatographic cartridge assay determines the presence of both glutamate dehydrogenase and Clostridium difficile toxins A and B as a primary screen for C. difficile infection and indeterminate results (glutamate dehydrogenase positive, toxin A and B negative) are confirmed by the GeneXpert C. difficile PCR assay. This two-step algorithm is a cost-effective method for highly sensitive detection of toxigenic C. difficile. PMID:22718938

  2. Microbiome manipulation with faecal microbiome transplantation as a therapeutic strategy in Clostridium difficile infection

    PubMed Central

    Marchesi, J.R.; Thursz, M.R.; Williams, H.R.T.

    2015-01-01

    Faecal microbiome transplantation (FMT) has generated huge recent interest as it presents a potential solution to a significant clinical problem—the increasing incidence of Clostridium difficile infection (CDI). In the short term, however, there remain many practical questions regarding its use, including the optimal selection of donors, material preparation and the mechanics of delivery. In the longer term, enhanced understanding of the mechanisms of action of FMT may potentiate novel therapies, such as targeted manipulation of the microbiome in CDI and beyond. PMID:25193538

  3. Ultrasensitive Detection and Quantification of Toxins for Optimized Diagnosis of Clostridium difficile Infection

    PubMed Central

    2015-01-01

    Recently developed ultrasensitive and quantitative methods for detection of Clostridium difficile toxins provide new tools for diagnosis and, potentially, for management of C. difficile infection (CDI). Compared to methods that detect toxigenic organism, ultrasensitive toxin detection may allow diagnosis of CDI with increased clinical specificity, without sacrificing clinical sensitivity; measurement of toxin levels may also provide information relevant to disease prognosis. This minireview provides an overview of these new toxin detection technologies and considers what these new tools might add to the field. PMID:26659205

  4. An In Vitro Model of the Human Colon: Studies of Intestinal Biofilms and Clostridium difficile Infection.

    PubMed

    Crowther, Grace S; Wilcox, Mark H; Chilton, Caroline H

    2016-01-01

    The in vitro gut model is an invaluable research tool to study indigenous gut microbiota communities, the behavior of pathogenic organisms, and the therapeutic and adverse effect of antimicrobial administration on these communities. The model has been validated against the intestinal contents of sudden death victims to reflect the physicochemical and microbiological conditions of the proximal to distal colon, and has been extensively used to investigate the interplay between gut microbiota populations, antibiotic exposure, and Clostridium difficile infection. More recently the gut model has been adapted to additionally model intestinal biofilm. Here we describe the structure, assembly, and application of the biofilm gut model. PMID:27507345

  5. Clostridium Perfringens Infection in a Febrile Patient with Severe Hemolytic Anemia

    PubMed Central

    Hashiba, Masamitsu; Tomino, Atsutoshi; Takenaka, Nobuyoshi; Hattori, Tomonori; Kano, Hideki; Tsuda, Masanobu; Takeyama, Naoshi

    2016-01-01

    Patient: Male, 82 Final Diagnosis: Clostridium perfringens infection Symptoms: Anemia • fever • shock Medication: — Clinical Procedure: Antimicrobial chemotherapy Specialty: Infectious Diseases Objective: Rare disease Background: Clostridium perfringens (C. perfringens) can cause various infections, including gas gangrene, crepitant cellulitis, and fasciitis. While C. perfringens sepsis is uncommon, it is often rapidly fatal because the alpha toxin of this bacterium induces massive intravascular hemolysis by disrupting red blood cell membranes. Case Report: We present the case of a male patient with diabetes who developed a fatal liver abscess with massive intravascular hemolysis and septic shock caused by toxigenic C. perfringens. The peripheral blood smear showed loss of central pallor, with numerous spherocytes. Multiplex PCR only detected expression of the cpa gene, indicating that the pathogen was C. perfringens type A. Conclusions: C. perfringens infection should be considered in a febrile patient who has severe hemolytic anemia with a very low MCV, hemolyzed blood sample, and negative Coombs test. The characteristic peripheral blood smear findings may facilitate rapid diagnosis. PMID:27049736

  6. Community-acquired Clostridium difficile infection: an increasing public health threat

    PubMed Central

    Gupta, Arjun; Khanna, Sahil

    2014-01-01

    There has been a startling shift in the epidemiology of Clostridium difficile infection over the last decade worldwide, and it is now increasingly recognized as a cause of diarrhea in the community. Classically considered a hospital-acquired infection, it has now emerged in populations previously considered to be low-risk and lacking the traditional risk factors for C. difficile infection, such as increased age, hospitalization, and antibiotic exposure. Recent studies have demonstrated great genetic diversity for C. difficile, pointing toward diverse sources and a fluid genome. Environmental sources like food, water, and animals may play an important role in these infections, apart from the role symptomatic patients and asymptomatic carriers play in spore dispersal. Prospective strain typing using highly discriminatory techniques is a possible way to explore the suspected diverse sources of C. difficile infection in the community. Patients with community-acquired C. difficile infection do not necessarily have a good outcome and clinicians should be aware of factors that predict worse outcomes in order to prevent them. This article summarizes the emerging epidemiology, risk factors, and outcomes for community-acquired C. difficile infection. PMID:24669194

  7. Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection: a prospective pilot trial

    PubMed Central

    Patrick Basu, P.; Dinani, Amreen; Rayapudi, Krishna; Pacana, Tommy; Shah, Niraj James; Hampole, Hemant; Krishnaswamy, N. V.; Mohan, Vinod

    2010-01-01

    Background: Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge. Methods: We evaluated the efficacy of the nonsystemic oral antibiotic rifaximin for the treatment of metronidazole-resistant C. difficile infection. Twenty-five patients with C. difficile infection were enrolled in the study. All had mild-to-moderate C. difficile infection (5–10 bowel movements a day without sepsis) unresponsive to metronidazole (i.e. stools positive for toxins A and B after oral metronidazole 500 mg three times daily [t.i.d.] for 5 days). After discontinuation of metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were followed for 56 days and stool was tested for C. difficile using polymerase chain reaction (PCR) to assess the effect of treatment. A negative PCR test result was interpreted as a favorable response to rifaximin. Results: Sixteen of 22 patients (73%) were eligible for study inclusion and completed rifaximin therapy experienced eradication of infection (stool negative for C. difficile) immediately after rifaximin therapy and 56 days post-treatment. Three patients (12%) discontinued therapy because of abdominal distention. Rifaximin was generally well tolerated. Conclusions: In conclusion, rifaximin may be considered for treatment of mild-to-moderate C. difficile infection that is resistant to metronidazole. Larger randomized trials are needed to confirm these positive findings. PMID:21180604

  8. Therapeutic Success of Rifaximin for Clostridium difficile Infection Refractory to Metronidazole and Vancomycin

    PubMed Central

    Tannous, George; Neff, Guy; Kemmer, Nyingi

    2010-01-01

    We report the case of a 46-year-old white male with confirmed Clostridium difficile infection for >4 weeks after fluoroquinolone therapy. The patient received two courses of metronidazole 500 mg three times daily (t.i.d.) during which time diarrhea resolved; however, symptoms recurred 14–15 days after treatment termination. He received a 2-week course of vancomycin 125 mg four times daily, with symptoms recurring 10 days after treatment conclusion. The patient then received a pulsed tapering schedule of vancomycin with adjunctive Saccharomyces boulardii. Diarrhea recurred 12 days after treatment completion. He received rifaximin 400 mg t.i.d. while hospitalized for diarrhea-associated complications. Symptoms resolved within 24 h. The patient received a 4-week regimen of rifaximin 400 mg orally t.i.d. after discharge. No further episodes of diarrhea were reported within 6 months after treatment termination. The present case supports the potential benefit of rifaximin for the treatment of recurrent Clostridium difficile infection. PMID:21060709

  9. Bacteriotherapy for the treatment of intestinal dysbiosis caused by Clostridium difficile infection.

    PubMed

    Adamu, Blessing O; Lawley, Trevor D

    2013-10-01

    Faecal microbiota transplantation (FMT) has been used for more than five decades to treat a variety of intestinal diseases associated with pathological imbalances within the resident microbiota, termed dysbiosis. FMT has been particularly effective for treating patients with recurrent Clostridium difficile infection who are left with few clinical options other than continued antibiotic therapy. Our increasing knowledge of the structure and function of the human intestinal microbiota and C. difficile pathogenesis has led to the understanding that FMT promotes intestinal ecological restoration and highlights the microbiota as a viable therapeutic target. However, the use of undefined faecal samples creates a barrier for widespread clinical use because of safety and aesthetic issues. An emerging concept of bacteriotherapy, the therapeutic use of a defined mixture of harmless, health-associated bacteria, holds promise for the treatment of patients with severe C. difficile infection, and possibly represents a paradigm shift for the treatment of diseases linked to intestinal dysbiosis. PMID:23866975

  10. [Ulcerous colitis and infection with cytomegalovirus, herpes simplex virus and clostridium difficile].

    PubMed

    Arnold, C; von Sanden, S; Theilacker, C; Blum, H E

    2008-08-01

    The treatment of severe flares of ulcerative colitis is based on systemic corticosteroids, immunomodulators such as cyclosporine and azathioprine and in some cases TNF-alpha-antagonists, respectively. These immunosuppressed patients are susceptible for infectious pathogens. Here we report the case of a patient with a severe flare of ulcerative colitis that was first treated with systemic corticosteroids combined with immunomodulators and subsequent with infliximab. The patient then experienced an infection with Clostridium difficile and cytomegalovirus of the colon and a Herpes simplex esophagitis, respectively. After specific treatment the patient responded well to the immunosuppressive therapy. This case illustrates that infections have to be considered before systemic treatment of an acute flare of ulcerative colitis is instituted especially in the case of disease activation during immunosuppressive treatment. PMID:18759202

  11. Clinical and Laboratory Characteristics of Clostridium difficile Infection in Patients with Discordant Diagnostic Test Results

    PubMed Central

    Kaltsas, Anna; Simon, Matt; Unruh, Larissa H.; Son, Crystal; Wroblewski, Danielle; Musser, Kimberlee A.; Sepkowitz, Kent; Kamboj, Mini

    2012-01-01

    The aim of this study was to compare the clinical and laboratory characteristics of Clostridium difficile infection (CDI) in patients with discordant test results for the cytotoxin assay (CYT) and PCR assays. A retrospective study from May to August 2008 and March to May 2010 was performed. CDI was diagnosed in 128 patients. PCR increased the yield of C. difficile cases by 2-fold compared to that of the CYT assay. Fifty-six cases (44%) were detected by PCR only (CYT negative). Forty-nine percent of patients with non-NAP1 strains were detected by PCR only, compared to 28% of those infected with NAP1 strains (P < 0.05). No significant differences were found in the clinical severity of illness and outcome among patients that tested positive for CDI by both tests (CYT and PCR) compared to those that tested positive by PCR only. PMID:22238444

  12. Clinical update for the diagnosis and treatment of Clostridium difficile infection

    PubMed Central

    IV, Edward C Oldfield; III, Edward C Oldfield; Johnson, David A

    2014-01-01

    Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies. PMID:24729930

  13. An update on antibody-based immunotherapies for Clostridium difficile infection

    PubMed Central

    Hussack, Greg; Tanha, Jamshid

    2016-01-01

    Clostridium difficile continues to be one of the most prevalent hospital-acquired bacterial infections in the developed world, despite the recent introduction of a novel and effective antibiotic agent (fidaxomicin). Alternative approaches under investigation to combat the anaerobic Gram-positive bacteria include fecal transplantation therapy, vaccines, and antibody-based immunotherapies. In this review, we catalog the recent advances in antibody-based approaches under development and in the clinic for the treatment of C. difficile infection. By and large, inhibitory antibodies that recognize the primary C. difficile virulence factors, toxin A and toxin B, are the most popular passive immunotherapies under investigation. We provide a detailed summary of the toxin epitopes recognized by various antitoxin antibodies and discuss general trends on toxin inhibition efficacy. In addition, antibodies to other C. difficile targets, such as surface-layer proteins, binary toxin, motility factors, and adherence and colonization factors, are introduced in this review. PMID:27536153

  14. Disruption of the Gut Microbiome: Clostridium difficile Infection and the Threat of Antibiotic Resistance

    PubMed Central

    Johanesen, Priscilla A.; Mackin, Kate E.; Hutton, Melanie L.; Awad, Milena M.; Larcombe, Sarah; Amy, Jacob M.; Lyras, Dena

    2015-01-01

    Clostridium difficile is well recognized as the leading cause of antibiotic-associated diarrhea, having a significant impact in both health-care and community settings. Central to predisposition to C. difficile infection is disruption of the gut microbiome by antibiotics. Being a Gram-positive anaerobe, C. difficile is intrinsically resistant to a number of antibiotics. Mobile elements encoding antibiotic resistance determinants have also been characterized in this pathogen. While resistance to antibiotics currently used to treat C. difficile infection has not yet been detected, it may be only a matter of time before this occurs, as has been seen with other bacterial pathogens. This review will discuss C. difficile disease pathogenesis, the impact of antibiotic use on inducing disease susceptibility, and the role of antibiotic resistance and mobile elements in C. difficile epidemiology. PMID:26703737

  15. Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection

    PubMed Central

    Vincent, Caroline; Manges, Amee R.

    2015-01-01

    Clostridium difficile infection (CDI) is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT) is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material. PMID:27025623

  16. Epidemiology and factors associated with candidaemia following Clostridium difficile infection in adults within metropolitan Atlanta, 2009-2013.

    PubMed

    Vallabhaneni, S; Almendares, O; Farley, M M; Reno, J; Smith, Z T; Stein, B; Magill, S S; Smith, R M; Cleveland, A A; Lessa, F C

    2016-05-01

    We assessed prevalence of and risk factors for candidaemia following Clostridium difficile infection (CDI) using longitudinal population-based surveillance. Of 13 615 adults with CDI, 113 (0·8%) developed candidaemia in the 120 days following CDI. In a matched case-control analysis, severe CDI and CDI treatment with vancomycin + metronidazole were associated with development of candidaemia following CDI. PMID:26608090

  17. Clostridium difficile ribotype 033 colitis in a patient following broad-spectrum antibiotic treatment for KPCproducing Klebsiella pneumoniae infection, Italy.

    PubMed

    Grandesso, Stefano; Arena, Fabio; Eseme, Franklin Esoka; Panese, Sandro; Henrici De Angelis, Lucia; Spigaglia, Patrizia; Barbanti, Fabrizio; Rossolini, Gian Maria

    2016-09-01

    This report describes a case of Clostridium difficile ribotype 033 colitis in a patient treated with multiple antibiotics for KPC-producing Klebsiella pneumoniae pancreatitis. Diagnostic, clinical and therapeutic features are discussed. To the best of our knowledge, this is the first case of C. difficile ribotype 033 clinical infection reported from Italy. PMID:27602425

  18. Hospital-onset Clostridium difficile infection among solid organ transplant recipients.

    PubMed

    Donnelly, J P; Wang, H E; Locke, J E; Mannon, R B; Safford, M M; Baddley, J W

    2015-11-01

    Clostridium difficile infection (CDI) is a considerable health issue in the United States and represents the most common healthcare-associated infection. Solid organ transplant recipients are at increased risk of CDI, which can affect both graft and patient survival. However, little is known about the impact of CDI on health services utilization posttransplantation. We examined hospital-onset CDI from 2012 to 2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the United States. Infection was five times more common among transplant recipients than among general medicine inpatients (209 vs 40 per 10 000 discharges), and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional risk-standardized CDI varied more than 3-fold across high-volume hospitals (infection ratio 0.54-1.82, median 1.04, interquartile range 0.78-1.28). CDI was associated with increased 30-day readmission, transplant organ complications, cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were substantially higher than risk-standardized expected values (40 094 vs 22 843 days, costs $198 728 368 vs $154 020 528). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted. PMID:26484839

  19. Discovery of LFF571: An Investigational Agent for Clostridium difficile Infection

    SciTech Connect

    LaMarche, Matthew J.; Leeds, Jennifer A.; Amaral, Adam; Brewer, Jason T.; Bushell, Simon M.; Deng, Gejing; Dewhurst, Janetta M.; Ding, Jian; Dzink-Fox, JoAnne; Gamber, Gabriel; Jain, Akash; Lee, Kwangho; Lee, Lac; Lister, Troy; McKenney, David; Mullin, Steve; Osborne, Colin; Palestrant, Deborah; Patane, Michael A.; Rann, Elin M.; Sachdeva, Meena; Shao, Jian; Tiamfook, Stacey; Trzasko, Anna; Whitehead, Lewis; Yifru, Aregahegn; Yu, Donghui; Yan, Wanlin; Zhu, Qingming

    2012-11-09

    Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection.

  20. Clostridium Difficile Infection Worsen Outcome of Hospitalized Patients with Inflammatory Bowel Disease.

    PubMed

    Zhang, Ting; Lin, Qian-Yun; Fei, Jia-Xi; Zhang, Yan; Lin, Min-Yi; Jiang, Shuang-Hong; Wang, Pu; Chen, Ye

    2016-01-01

    The prevalence of Clostridium difficile infection (CDI) in patients suffering from inflammatory bowel disease (IBD) has increased rapidly over the past several decades in North America and Europe. However, the exact global epidemiology remains unclear because of insufficient data from developing countries. A total of 646 hospitalized adult IBD patients were enrolled; and their fresh stool specimens were obtained and used for Clostridium difficile detection. The incidence of CDI in Crohn's disease (CD) patients (12.7%) was significantly lower than that in Ulcerative disease (UC) patients (19.3%). Among the toxin types, A(+)B(+) strain was the most common. Length of stay, hospitalization frequency and bowel surgery rate were significantly higher in the CDI than in the non-CDI group in CD or UC patients. More patients in CDI-CD group were still in active and even clinical moderate or severe CD stage than non-CDI-CD group after 2 years of following-up. Fistula, antibiotics and infliximab usage likely increased the CDI rate in CD patients, Infliximab treatment was considered a risk factor in UC patients. CDI is an exacerbating public health issue that may influence IBD course, increase expenditures, and delay the remission of IBD patients. IBD patients with CDI require urgent attention. PMID:27417996

  1. Recent epidemiology of Clostridium difficile infection during hematopoietic stem cell transplantation

    PubMed Central

    Chopra, Teena; Chandrasekar, Pranatharthi; Salimnia, Hossein; Heilbrun, Lance K.; Smith, Daryn; Alangaden, George J.

    2013-01-01

    Given the limited information on Clostridium difficile infection (CDI) during hematopoietic stem cell transplantation (HSCT), we examined the recent epidemiology of CDI in HSCT recipients at our institution. During the two-yr retrospective study period (2005–2006), 361 transplants were performed: 60% allogeneic and 40% autologous. Among all hospitalized patients in a non-outbreak setting, CDI rates in HSCT recipients were ninefold higher than those in general patients and 1.4-fold higher than those in patients with cancer (24.0 vs. 2.6 vs. 16.8/10 000 patient-days respectively). Sixty-two episodes of CDI occurred in 51 (14%) HSCT recipients: 39 (18%) allogeneic vs. 12 (8%) autologous (p = 0.01). Almost half of CDI episodes occurred within 30 d post-HSCT and 22% before HSCT. Clostridium difficile toxin assay was initially positive in 28% of the first, 31% of the second and 27% of the third stool samples tested. All but one patient responded to therapy with metronidazole or vancomycin. Severe CDI occurred in one patient and recurrent CDI in two patients. CDI is common during HSCT especially in allogeneic transplants during the peri-HSCT period. Prospective studies to better define the epidemiology and identify unique risk factors for CDI and more accurate tests to confirm the diagnosis in this population are needed. PMID:20973823

  2. Clostridium Difficile Infection Worsen Outcome of Hospitalized Patients with Inflammatory Bowel Disease

    PubMed Central

    Zhang, Ting; Lin, Qian-Yun; Fei, Jia-Xi; Zhang, Yan; Lin, Min-Yi; Jiang, Shuang-Hong; Wang, Pu; Chen, Ye

    2016-01-01

    The prevalence of Clostridium difficile infection (CDI) in patients suffering from inflammatory bowel disease (IBD) has increased rapidly over the past several decades in North America and Europe. However, the exact global epidemiology remains unclear because of insufficient data from developing countries. A total of 646 hospitalized adult IBD patients were enrolled; and their fresh stool specimens were obtained and used for Clostridium difficile detection. The incidence of CDI in Crohn’s disease (CD) patients (12.7%) was significantly lower than that in Ulcerative disease (UC) patients (19.3%). Among the toxin types, A+B+ strain was the most common. Length of stay, hospitalization frequency and bowel surgery rate were significantly higher in the CDI than in the non-CDI group in CD or UC patients. More patients in CDI-CD group were still in active and even clinical moderate or severe CD stage than non-CDI-CD group after 2 years of following-up. Fistula, antibiotics and infliximab usage likely increased the CDI rate in CD patients, Infliximab treatment was considered a risk factor in UC patients. CDI is an exacerbating public health issue that may influence IBD course, increase expenditures, and delay the remission of IBD patients. IBD patients with CDI require urgent attention. PMID:27417996

  3. Clostridium difficile infection in Chilean patients submitted to hematopoietic stem cell transplantation

    PubMed Central

    Pilcante, Javier; Rojas, Patricio; Ernst, Daniel; Sarmiento, Mauricio; Ocqueteau, Mauricio; Bertin, Pablo; García, Maria; Rodriguez, Maria; Jara, Veronica; Ajenjo, Maria; Ramirez, Pablo

    2015-01-01

    Introduction Patients submitted to hematopoietic stem cell transplantation have an increased risk of Clostridium difficile infection and multiple risk factors have been identified. Published reports have indicated an incidence from 9% to 30% of transplant patients however to date there is no information about infection in these patients in Chile. Methods A retrospective analysis was performed of patients who developed C. difficile infection after hematopoietic stem cell transplantations from 2000 to 2013. Statistical analysis used the Statistical Package for the Social Sciences software. Results Two hundred and fifty patients were studied (mean age: 39 years; range: 17–69), with 147 (59%) receiving allogeneic transplants and 103 (41%) receiving autologous transplants. One hundred and ninety-two (77%) patients had diarrhea, with 25 (10%) cases of C. difficile infection being confirmed. Twenty infected patients had undergone allogeneic transplants, of which ten had acute lymphoblastic leukemia, three had acute myeloid leukemia and seven had other diseases (myelodysplastic syndrome, chronic myeloid leukemia, severe aplastic anemia). In the autologous transplant group, five patients had C. difficile infection; two had multiple myeloma, one had amyloidosis, one had acute myeloid leukemia and one had germinal carcinoma. The overall incidence of C. difficile infection was 4% within the first week, 6.4% in the first month and 10% in one year, with no difference in overall survival between infected and non-infected groups (72.0% vs. 67.6%, respectively; p-value = 0.56). Patients infected after allogeneic transplants had a slower time to neutrophil engraftment compared to non-infected patients (17.5 vs. 14.9 days, respectively; p-value = 0.008). In the autologous transplant group there was no significant difference in the neutrophil engraftment time between infected and non-infected patients (12.5 days vs. 11.8 days, respectively; p-value = 0.71). In the allogeneic

  4. [Life-threatening infections with a new strain of Clostridium difficile].

    PubMed

    Krausz, S; Bessems, M; Boermeester, M A; Kuijper, E J; Visser, C E; Speelman, P

    2005-09-17

    Three men, aged 39, 73, and 66 years, respectively, developed an infection with a new strain ofClostridium difficile, ribotype 027.C.difficile-associated diarrhoea (CDAD) occurred in two patients after multiple abdominal surgery and in the third patient one week after autologous haematopoietic cell transplantation. Within a few days, despite antibiotic therapy, all three patients developed severe (pseudomembranous) colitis with sepsis for which admission to the Intensive Care Unit was required. Two patients underwent (sub)total colectomy and received an intensive course of oral and/or rectal vancomycin. In all patients who develop diarrhoea in hospital, especially during or after treatment with antibiotics or chemotherapeutic agents, an infection with C. difficile ribotype 027 should be suspected. Recent outbreaks of this hypervirulent strain of C. difficile have been reported in Canada, the United States, United Kingdom, and The Netherlands. Demonstration of C. difficile toxin in faeces confirms the clinical suspicion of CDAD and ribotyping of the strain may reveal whether the 027 strain is present. For treatment of these 027 infections, vancomycin is preferred to metronidazole. After a severe course of colitis or in case of recurrence a 'tapering and pulse' course ofvancomycin can be prescribed; alternatively, treatment with bovine antibody-enriched whey may be considered. The introduction of this hypervirulent strain has led to reinforcement of the hygienic measures in accordance with the recommendations of the Dutch Working Party on Infection Prevention and a policy to deter the use of fluoroquinolones. PMID:16201595

  5. Microbiota-Regulated IL-25 Increases Eosinophil Number to Provide Protection during Clostridium difficile Infection.

    PubMed

    Buonomo, Erica L; Cowardin, Carrie A; Wilson, Madeline G; Saleh, Mahmoud M; Pramoonjago, Patcharin; Petri, William A

    2016-07-12

    Clostridium difficile infection (CDI) is the most common cause of hospital-acquired infection in the United States. Host susceptibility and the severity of infection are influenced by disruption of the microbiota and the immune response. However, how the microbiota regulate immune responses to mediate CDI outcome remains unclear. Here, we have investigated the role of the microbiota-linked cytokine IL-25 during infection. Intestinal IL-25 was suppressed during CDI in humans and mice. Restoration of IL-25 reduced CDI-associated mortality and tissue pathology even though equivalent levels of C. difficile bacteria and toxin remained in the gut. IL-25 protection was mediated by gut eosinophils, as demonstrated by an increase in intestinal eosinophils and a loss of IL-25 protection upon eosinophil depletion. These findings support a mechanism whereby the induction of IL-25-mediated eosinophilia can reduce host mortality during active CDI. This work may provide targets for future development of microbial or immune-based therapies. PMID:27346351

  6. Uterine Perforation with Intra-Abdominal Clostridium perfringens Gas Gangrene: A Rare and Fatal Infection

    PubMed Central

    Kashan, David; Muthu, Nagarajan; Davalos, Fidencio; Bernstein, Michael; Chendrasekhar, Akella

    2016-01-01

    Abstract Background: Clostridium perfringens gas gangrene is an extremely rare and fatal infection. Necrosis of the myometrium is rarely seen and has only been recorded in 18 cases to date. Of these 18 reported cases, only 5 have occurred in nonpregnant women. This article presents the 6th case of myometrium necrosis from C. perfringens. Case: A 72-year-old woman, gravida 2, para 2, presented with abdominal pain and vaginal bleeding. After examinations, laboratory testing, and several surgical interventions, she was found to have C. perfringens infection and advanced high-grade serous adenocarcinoma of the endometrium with >50% invasion into the myometrium. Results: Despite the surgical interventions and use of several antibiotics, this patient did not improve. She was weaned from treatment per her advance directive and died after weaning. Conclusions: Awareness of the many etiologies for peritonitis is of great importance when a fatal infection may be the cause of the condition. Correct diagnosis and proper treatment is essential for the survival of patients infected with C. perfringens. (J GYNECOL SURG 32:182) PMID:27274183

  7. The Ecology and Pathobiology of Clostridium difficile Infections: An Interdisciplinary Challenge

    PubMed Central

    Dubberke, Erik R.; Haslam, David B.; Lanzas, Cristina; Bobo, Linda D.; Burnham, Carey-Ann D.; Gröhn, Yrjö T.; Tarr, Phillip I.

    2013-01-01

    Summary Clostridium difficile is a well recognized pathogen of humans and animals. Although C. difficile was first identified over 70 years ago, much remains unknown in regards to the primary source of human acquisition and its pathobiology. These deficits in our knowledge have been intensified by dramatic increases in both the frequency and severity of disease in humans over the last decade. The changes in C. difficile epidemiology might be due to the emergence of a hypervirulent stain of C. difficile, aging of the population, altered risk of developing infection with newer medications, and/or increased exposure to C. difficile outside of hospitals. In recent years there have been numerous reports documenting C. difficile contamination of various foods, and reports of similarities between strains that infect animals and strains that infect humans as well. The purposes of this review are to highlight the many challenges to diagnosing, treating, and preventing C. difficile infection in humans, and to stress that collaboration between human and veterinary researchers is needed to control this pathogen. PMID:21223531

  8. The challenge of Clostridium difficile infection: Overview of clinical manifestations, diagnostic tools and therapeutic options.

    PubMed

    Postma, Nynke; Kiers, Dorien; Pickkers, Peter

    2015-12-01

    The most important infectious cause of antibiotic-associated diarrhoea and colitis is Clostridium difficile, which is a Gram-positive, anaerobic, spore-forming, toxin-producing bacillus. In this overview we will discuss the diagnostic and therapeutic management of patients presenting with suspected or proven C. difficile infection (CDI). The clinical spectrum varies from asymptomatic C. difficile carriers to fulminant colitis with multi-organ failure. The onset of symptoms is usually within 2 weeks after initiation of antibiotic treatment. Diagnosis is based on the combination of clinical symptoms and either a positive stool test for C. difficile toxins or endoscopic or histological findings of pseudomembranous colitis. There is no indication for treatment of asymptomatic carriers, but patients with proven CDI should be treated. Treatment consists of cessation of the provoking antibiotic treatment, secondary prevention by infection control strategies, and treatment with metronidazole or vancomycin. Treatment of recurring CDI, severe infection, the need for surgery, and novel alternative potential treatment strategies will be discussed. The concurrent increase in multiresistant colonisation and increasing numbers of asymptomatic carriers of C. difficile will lead to an increase of the situation in which patients with severe infections, treated with broad-spectrum antibiotics, will develop concurrent severe CDI. We will discuss possible therapy strategies for these patients. PMID:26612229

  9. Efficacy of a diagnostic and therapeutic algorithm for Clostridium difficile infection.

    PubMed

    Marukawa, Yohei; Komura, Takuya; Kagaya, Takashi; Ohta, Hajime; Unoura, Masashi

    2016-08-01

    In July 2012, metronidazole was approved for the treatment of Clostridium difficile infection (CDI). To clarify the selection criteria for the drug in terms of CDI severity, we established a diagnostic and therapeutic algorithm with reference to the SHEA-IDSA Clinical Practice Guidelines. We compared patients whose treatments were guided by the algorithm (29 cases, October 2012-September 2013) with patients treated prior to the development of the algorithm (37 cases, October 2011-September 2012). All cases treated with reference to the algorithm were diagnosed using enzyme immunoassay of C. difficile toxins A and B and glutamate dehydrogenase;an appropriate drug was prescribed in 93.1% of the cases. We found no significant between-group differences in the cure, recurrence, or complication rates. However, drug costs in cases wherein treatments were guided by the algorithm were markedly reduced. We have, thus, shown that algorithm-guided treatment is efficacious and cost-effective. PMID:27498935

  10. Gut solutions to a gut problem: bacteriocins, probiotics and bacteriophage for control of Clostridium difficile infection.

    PubMed

    Rea, Mary C; Alemayehu, Debebe; Ross, R Paul; Hill, Colin

    2013-09-01

    Clostridium difficile infection (CDI) is a major cause of morbidity and mortality among hospitalized patients and imposes a considerable financial burden on health service providers in both Europe and the USA. The incidence of CDI has dramatically increased in recent years, partly due to the emergence of a number of hypervirulent strains. The most commonly documented risk factors associated with CDIs are antibiotic usage leading to alterations of the gut microbiota, age >65 years and long-term hospital stay. Since standard therapies for antibiotic-associated diarrhoea and CDI have limited efficacy, there is now an urgent need for alternative therapeutics. In this review, we outline the current state of play with regard to the potential of gut-derived bacteriocins, probiotics and phage to act as antimicrobial agents against CDI in the human gut. PMID:23699066

  11. Peri-transplant clostridium difficile infections in patients undergoing allogeneic hematopoietic progenitor cell transplant.

    PubMed

    Agha, Aya; Sehgal, Alison; Lim, Matthew J; Weber, David; Hou, Jing-Zhou; Farah, Rafic; Raptis, Anastasios; Im, Annie; Dorritie, Kathleen; Marks, Stanley; Agha, Mounzer; Lim, Seah H

    2016-03-01

    Clostridium difficile infections (CDI) remain the leading cause of infectious diarrhea among hospitalized patients in this country. Patients with hematologic malignancies, especially those who undergo hematopoietic progenitor cell transplants are particularly at risk for developing CDI. One hundred and forty seven consecutive allogeneic hematopoietic progenitor cell transplants were analyzed for peri-transplant Clostridium difficile infections (PT-CDI). Sixteen patients (11%) developed PT-CDI (Median time = 7 days after transplant). The probability for developing PT-CDI during the peri-transplant period was 12.3%. History of CDI was strongly associated with the development of PT-CDI (P = 0.008) (OR = 5.48) (P = 0.017). These patients also developed PT-CDI much earlier than in those without a history (median 1 day vs. 8 days, P = 0.03). The probability for developing PT-CDI for those with a history was 39%. There was a trend toward significance (P = 0.065) between matched related donor grafts and the development of PT-CDI (OR = 0.245) (P = 0.08). Age, sex, diagnosis, transplant preparative regimens, Graft-versus-host disease (GVHD) prophylaxis, grade 3/4 acute GVHD, or use of antimicrobials within 8 weeks of transplant were not associated with PT-CDI. Non-CDI-related deaths occurred in one patient in the PT-CDI group and nine in the group without PT-CDI. In the remaining 139 patients, the length of hospital stay for those with PT-CDI was significantly longer than those without (mean 27 days vs. 22 days; P = 0.02). PMID:26661725

  12. Genome-Based Infection Tracking Reveals Dynamics of Clostridium difficile Transmission and Disease Recurrence

    PubMed Central

    Kumar, Nitin; Miyajima, Fabio; He, Miao; Roberts, Paul; Swale, Andrew; Ellison, Louise; Pickard, Derek; Smith, Godfrey; Molyneux, Rebecca; Dougan, Gordon; Parkhill, Julian; Wren, Brendan W.; Parry, Christopher M.; Pirmohamed, Munir; Lawley, Trevor D.

    2016-01-01

    Background. Accurate tracking of Clostridium difficile transmission within healthcare settings is key to its containment but is hindered by the lack of discriminatory power of standard genotyping methods. We describe a whole-genome phylogenetic-based method to track the transmission of individual clones in infected hospital patients from the epidemic C. difficile 027/ST1 lineage, and to distinguish between the 2 causes of recurrent disease, relapse (same strain), or reinfection (different strain). Methods. We monitored patients with C. difficile infection in a UK hospital over a 2-year period. We performed whole-genome sequencing and phylogenetic analysis of 108 strains isolated from symptomatic patients. High-resolution phylogeny was integrated with in-hospital transfers and contact data to create an infection network linking individual patients and specific hospital wards. Results. Epidemic C. difficile 027/ST1 caused the majority of infections during our sampling period. Integration of whole-genome single nucleotide polymorphism (SNP) phylogenetic analysis, which accurately discriminated between 27 distinct SNP genotypes, with patient movement and contact data identified 32 plausible transmission events, including ward-based contamination (66%) or direct donor–recipient contact (34%). Highly contagious donors were identified who contributed to the persistence of clones within distinct hospital wards and the spread of clones between wards, especially in areas of intense turnover. Recurrent cases were identified between 4 and 26 weeks, highlighting the limitation of the standard <8-week cutoff used for patient diagnosis and management. Conclusions. Genome-based infection tracking to monitor the persistence and spread of C. difficile within healthcare facilities could inform infection control and patient management. PMID:26683317

  13. Older Is Not Wiser, Immunologically Speaking: Effect of Aging on Host Response to Clostridium difficile Infections.

    PubMed

    Shin, Jae Hyun; High, Kevin P; Warren, Cirle A

    2016-07-01

    Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and a significant burden on the health care system. Aging has been identified in the literature as a risk factor for CDI as well as adverse outcome from CDI. Although this effect of advanced age on CDI could be partially explained by clinical factors associated with aging, biologic factors are important. Innate immune system, responsible for immediate response to acute infections, plays a major role in CDI pathogenesis. Impairment in function of innate immunity with aging, demonstrated in other infection models, may lead to worse outcome with CDI. C. difficile toxin-specific antibody response protects the host against initial and recurrent infections as shown in observational studies and clinical trial. Effect of aging on antibody response to CDI has not been demonstrated, but the results from vaccine studies in other infections suggest a negative effect on humoral immunity from aging. Although intestinal microbiota from healthy people confers resistance to CDI by preventing C. difficile colonization, changes in composition of microbiota with aging may affect that resistance and increase risk for CDI. There are also age-associated changes in physiology, especially of the gastrointestinal tract, that may play a role in CDI risk and outcomes. In this review, we will first discuss the epidemiology of CDI in the elderly people, then the alteration in innate immunity, humoral response, and microbiota that increases susceptibility to CDI and severe disease and lastly, the physiological and functional changes that may modify outcomes of infection. PMID:26809495

  14. Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection

    PubMed Central

    Leber, Andrew; Viladomiu, Monica; Hontecillas, Raquel; Abedi, Vida; Philipson, Casandra; Hoops, Stefan; Howard, Brad; Bassaganya-Riera, Josep

    2015-01-01

    Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17) effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg) cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions. PMID:26230099

  15. Clostridium difficile Infections amongst Patients with Haematological Malignancies: A Data Linkage Study

    PubMed Central

    Slimings, Claudia; Joske, David J. L.; Riley, Thomas V.

    2016-01-01

    Objectives Identify risk factors for Clostridium difficile infection (CDI) and assess CDI outcomes among Australian patients with a haematological malignancy. Methods A retrospective cohort study involving all patients admitted to hospitals in Western Australia with a haematological malignancy from July 2011 to June 2012. Hospital admission data were linked with all hospital investigated CDI case data. Potential risk factors were assessed by logistic regression. The risk of death within 60 and 90 days of CDI was assessed by Cox Proportional Hazards regression. Results There were 2085 patients of whom 65 had at least one CDI. Twenty percent of CDI cases were either community-acquired, indeterminate source or had only single-day admissions in the 28 days prior to CDI. Using logistic regression, having acute lymphocytic leukaemia, neutropenia and having had bacterial pneumonia or another bacterial infection were associated with CDI. CDI was associated with an increased risk of death within 60 and 90 days post CDI, but only two deaths had CDI recorded as an antecedent factor. Ribotyping information was available for 33 of the 65 CDIs. There were 19 different ribotypes identified. Conclusions Neutropenia was strongly associated with CDI. While having CDI is a risk factor for death, in many cases it may not be a direct contributor to death but may reflect patients having higher morbidity. A wide variety of C. difficile ribotypes were found and community-acquired infection may be under-estimated in these patients. PMID:27314498

  16. Struggling with recurrent Clostridium difficile infections: is donor faeces the solution?

    PubMed

    van Nood, E; Speelman, P; Kuijper, E J; Keller, J J

    2009-01-01

    Patients with recurrent Clostridium difficile infections (CDI) in hospitals and the community constitute an increasing treatment problem. While most patients with a first infection respond to either metronidazole or oral vancomycin, therapy in recurrent C. difficile infections tends to fail repeatedly. Lack of alternative treatment options can be a tremendous burden, both to patients and their treating physicians. Most guidelines recommend prolonged oral vancomycin pulse and or tapering schedules, but evidence-based treatment strategies are lacking. The role of immunoglobulins, whey prepared from vaccinated cows, probiotics or other antibiotics is unclear. Since 1958 several case series and case reports describe a treatment strategy where faecal infusions are successfully given for the treatment of recurrent CDI. Restoring intestinal flora has been historically thought of as the mechanism responsible for cure in these patients. In the literature, more than 150 patients have received faeces from a healthy donor, either infused through an enema, or through a nasoduodenal or nasogastric tube. We summarise the literature regarding treatment with donor faeces for recurrent CDI, and introduce the FECAL trial, currently open for inclusion. PMID:19712646

  17. Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories

    PubMed Central

    Carroll, Karen C.

    2013-01-01

    SUMMARY Clostridium difficile is a formidable nosocomial and community-acquired pathogen, causing clinical presentations ranging from asymptomatic colonization to self-limiting diarrhea to toxic megacolon and fulminant colitis. Since the early 2000s, the incidence of C. difficile disease has increased dramatically, and this is thought to be due to the emergence of new strain types. For many years, the mainstay of C. difficile disease diagnosis was enzyme immunoassays for detection of the C. difficile toxin(s), although it is now generally accepted that these assays lack sensitivity. A number of molecular assays are commercially available for the detection of C. difficile. This review covers the history and biology of C. difficile and provides an in-depth discussion of the laboratory methods used for the diagnosis of C. difficile infection (CDI). In addition, strain typing methods for C. difficile and the evolving epidemiology of colonization and infection with this organism are discussed. Finally, considerations for diagnosing C. difficile disease in special patient populations, such as children, oncology patients, transplant patients, and patients with inflammatory bowel disease, are described. As detection of C. difficile in clinical specimens does not always equate with disease, the diagnosis of C. difficile infection continues to be a challenge for both laboratories and clinicians. PMID:23824374

  18. Clostridium difficile Infection: A Rarity in Patients Receiving Chronic Antibiotic Treatment for Crohn’s Disease

    PubMed Central

    Roy, Abhik; Lichtiger, Simon

    2016-01-01

    Background Prolonged antibiotic use is limited by several adverse effects, one of which is Clostridium difficile infection (CDI). The aim of this study was to determine the incidence of CDI in patients receiving chronic antibiotic treatment for Crohn’s disease (CD). Methods We conducted a retrospective review of 100 patients with CD for which ≥6 months of outpatient antibiotic therapy was prescribed. Data were collected regarding demographics, CD phenotype, treatment history, and CDI. The incidence of CDI in our patient population was calculated and compared with historical controls. Results 100 patients were studied—60% of men, mean age 23.9 years at CD diagnosis. Eighty-two percent had disease involving the ileum, and 33% had disease involving the colon. The mean duration of antibiotic therapy was 39.6 months (range, 6–217 months). The most commonly prescribed classes of antibiotics were fluoroquinolones (84%), penicillins (57%), and cephalosporins (32%). Forty-nine percent of patients were treated with concomitant thiopurines, 45% with budesonide, and 41% with biologics. The overall incidence of CDI was 2%. This incidence of CDI was lower than previously reported for non-CD patients receiving chronic antibiotics for continuous-flow left ventricular assist device infections (12.5%) and orthopedic prosthesis infections (22.2%). Conclusions The incidence of CDI is rare in patients receiving chronic antibiotic treatment for CD, and it seems significantly lower than for non-CD populations reported in the literature. PMID:26650148

  19. Epidemiology of Clostridium difficile infection: results of a hospital-based study in Krakow, Poland.

    PubMed

    Czepiel, J; Kędzierska, J; Biesiada, G; Birczyńska, M; Perucki, W; Nowak, P; Garlicki, A

    2015-11-01

    Over the past two decades Clostridium difficile infection (CDI) has appeared as a major public health threat. We performed a retrospective study based on the records of patients hospitalized for CDI at the University Hospital in Krakow, Poland, between 2008 and 2014. In the study period, CDI occurred in 1009 individuals. There were 790 (78%) individuals who developed infection only once, whereas 219 (22%) developed infection more than once. The percentage of deaths within 14 days of CDI confirmation was 2·4%, with a mean age of 74·2 ± 15·9 years. Crude mortality was 12·9% in medical wards, 5·6% for surgical wards and 27·7% in the ICU setting. The time span between diagnosis and death was 5·1 days on average. Between 2008 and 2012 a 6·5-fold increase of CDI frequency with a posterior stabilization and even reduction in 2013 and 2014 was observed. According to the data analysed, 2/3 patients in our population developed CDI during their hospitalization even though they were admitted for different reasons. Medical wards pose a significantly higher risk of CDI than the surgical ones. Age is a risk factor for CDI recurrence. In the case of patients who died, death occurred shortly after diagnosis. The first CDI episode poses much higher risk of mortality than the consecutive ones. PMID:25858553

  20. Use of gas-liquid chromatography as a screening test for toxigenic Clostridium difficile in diarrhoeal stools.

    PubMed Central

    Pepersack, F; Labbe, M; Nonhoff, C; Schoutens, E

    1983-01-01

    In order to determine if gas-liquid chromatography (GLC) on concentrated stool extracts could be substituted to cell culture assay for cytotoxicity, we prospectively studied 154 diarrhoeal stools submitted for detection of Clostridium difficile toxin. Isocaproic-positive samples were cultured on egg yolk agar supplemented with cycloserine, cefoxitin and fructose for isolation of C difficile, and on egg yolk agar plus kanamycin for isolation of other clostridium species. Of the 154 samples, 129 were GLC-negative (height of the isocaproic peak less than 1.2 cm) and were toxin-negative. Twenty-five stools yielded isocaproic acid; C difficile isolated from 13 of them, six of which were also toxin-positive. Four other isocaproic-positive samples yielded C bifermentans and C sordellii; all were toxin-negative. These results indicate that a negative GLC is an excellent screening test for excluding C difficile infection; positive results must be checked by toxin testing and culture since they are not necessarily associated with the presence of C difficile or its toxin. PMID:6630574

  1. Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection

    PubMed Central

    Fuentes, Susana; van Nood, Els; Tims, Sebastian; Heikamp-de Jong, Ineke; ter Braak, Cajo JF; Keller, Josbert J; Zoetendal, Erwin G; de Vos, Willem M

    2014-01-01

    Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time. Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies. PMID:24577353

  2. Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection.

    PubMed

    Fuentes, Susana; van Nood, Els; Tims, Sebastian; Heikamp-de Jong, Ineke; ter Braak, Cajo J F; Keller, Josbert J; Zoetendal, Erwin G; de Vos, Willem M

    2014-08-01

    Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time. Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies. PMID:24577353

  3. Tests for the diagnosis of Clostridium difficile infection: the next generation.

    PubMed

    Carroll, Karen C

    2011-08-01

    impact of molecular tests on treatment and nosocomial spread of Clostridium difficile infections. PMID:21376826

  4. Faecal microbiota transplantation in recurrent Clostridium difficile infection: Recommendations from the French Group of Faecal microbiota Transplantation.

    PubMed

    Sokol, Harry; Galperine, Tatiana; Kapel, Nathalie; Bourlioux, Pierre; Seksik, Philippe; Barbut, Frederic; Scanzi, Julien; Chast, François; Batista, Rui; Joly, Francisca; Joly, Anne-Christine; Collignon, Anne; Guery, Benoit; Beaugerie, Laurent

    2016-03-01

    Faecal microbiota transplantation is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. In this context, faecal microbiota transplantation is beginning to be performed in France in clinical practice, while the rules governing this procedure have been defined in France only for clinical trials. To unify, secure, and evaluate practice in this field in France, the French Group of Faecal microbiota Transplantation (FGFT) was created in October 2014 with the support of the French National Society of Gastroenterology, the French Infectious Disease Society, and the National Academy of Pharmacy. We present here the deliberations of this group regarding the use of faecal microbiota transplantation for recurrent Clostridium difficile infection. The issues addressed are the indications, therapeutic sequence, delivery procedures, donor selection, methods and conditions of specimen preparation, and traceability. PMID:26433619

  5. Active and Secretory IgA-Coated Bacterial Fractions Elucidate Dysbiosis in Clostridium difficile Infection.

    PubMed

    Džunková, Mária; Moya, Andrés; Vázquez-Castellanos, Jorge F; Artacho, Alejandro; Chen, Xinhua; Kelly, Ciaran; D'Auria, Giuseppe

    2016-01-01

    The onset of Clostridium difficile infection (CDI) has been associated with treatment with wide-spectrum antibiotics. Antibiotic treatment alters the activity of gut commensals and may result in modified patterns of immune responses to pathogens. To study these mechanisms during CDI, we separated bacteria with high cellular RNA content (the active bacteria) and their inactive counterparts by fluorescence-activated cell sorting (FACS) of the fecal bacterial suspension. The gut dysbiosis due to the antibiotic treatment may result in modification of immune recognition of intestinal bacteria. The immune recognition patterns were assessed by FACS of bacterial fractions either coated or not with intestinal secretory immunoglobulin A (SIgA). We described the taxonomic distributions of these four bacterial fractions (active versus inactive and SIgA coated versus non-SIgA coated) by massive 16S rRNA gene amplicon sequencing and quantified the proportion of C. difficile toxin genes in the samples. The overall gut microbiome composition was more robustly influenced by antibiotics than by the C. difficile toxins. Bayesian networks revealed that the C. difficile cluster was preferentially SIgA coated during CDI. In contrast, in the CDI-negative group Fusobacterium was the characteristic genus of the SIgA-opsonized fraction. Lactobacillales and Clostridium cluster IV were mostly inactive in CDI-positive patients. In conclusion, although the proportion of C. difficile in the gut is very low, it is able to initiate infection during the gut dysbiosis caused by environmental stress (antibiotic treatment) as a consequence of decreased activity of the protective bacteria. IMPORTANCE C. difficile is a major enteric pathogen with worldwide distribution. Its expansion is associated with broad-spectrum antibiotics which disturb the normal gut microbiome. In this study, the DNA sequencing of highly active bacteria and bacteria opsonized by intestinal secretory immunoglobulin A (SIg

  6. Active and Secretory IgA-Coated Bacterial Fractions Elucidate Dysbiosis in Clostridium difficile Infection

    PubMed Central

    Moya, Andrés; Vázquez-Castellanos, Jorge F.; Artacho, Alejandro; Chen, Xinhua; Kelly, Ciaran

    2016-01-01

    ABSTRACT The onset of Clostridium difficile infection (CDI) has been associated with treatment with wide-spectrum antibiotics. Antibiotic treatment alters the activity of gut commensals and may result in modified patterns of immune responses to pathogens. To study these mechanisms during CDI, we separated bacteria with high cellular RNA content (the active bacteria) and their inactive counterparts by fluorescence-activated cell sorting (FACS) of the fecal bacterial suspension. The gut dysbiosis due to the antibiotic treatment may result in modification of immune recognition of intestinal bacteria. The immune recognition patterns were assessed by FACS of bacterial fractions either coated or not with intestinal secretory immunoglobulin A (SIgA). We described the taxonomic distributions of these four bacterial fractions (active versus inactive and SIgA coated versus non-SIgA coated) by massive 16S rRNA gene amplicon sequencing and quantified the proportion of C. difficile toxin genes in the samples. The overall gut microbiome composition was more robustly influenced by antibiotics than by the C. difficile toxins. Bayesian networks revealed that the C. difficile cluster was preferentially SIgA coated during CDI. In contrast, in the CDI-negative group Fusobacterium was the characteristic genus of the SIgA-opsonized fraction. Lactobacillales and Clostridium cluster IV were mostly inactive in CDI-positive patients. In conclusion, although the proportion of C. difficile in the gut is very low, it is able to initiate infection during the gut dysbiosis caused by environmental stress (antibiotic treatment) as a consequence of decreased activity of the protective bacteria. IMPORTANCE C. difficile is a major enteric pathogen with worldwide distribution. Its expansion is associated with broad-spectrum antibiotics which disturb the normal gut microbiome. In this study, the DNA sequencing of highly active bacteria and bacteria opsonized by intestinal secretory immunoglobulin

  7. Is the interleukin 8 promoter polymorphism rs4073/-251T >A associated with Clostridium difficile infection?

    PubMed

    Miyajima, Fabio; Swale, Andrew; Zhang, J Eunice; Alfirevic, Ana; Little, Margaret; Beeching, Nicholas J; Smith, Godfrey; Kolamunnage-Dona, Ruwanthi; Pirmohamed, Munir

    2014-06-01

    The interleukin 8 gene single-nucleotide polymorphism rs4073/-251T >A predisposes to Clostridium difficile infection (CDI), but this association has not been independently validated. In this study, we were unable to replicate this association in either a white cohort or by meta-analysis, suggesting that rs4073/-251T >A is unlikely to constitute a major risk factor for CDI. PMID:24633688

  8. Survey of diagnostic and typing capacity for Clostridium difficile infection in Europe, 2011 and 2014.

    PubMed

    van Dorp, Sofie M; Notermans, Daan W; Alblas, Jeroen; Gastmeier, Petra; Mentula, Silja; Nagy, Elisabeth; Spigaglia, Patrizia; Ivanova, Katiusha; Fitzpatrick, Fidelma; Barbut, Frédéric; Morris, Trefor; Wilcox, Mark H; Kinross, Pete; Suetens, Carl; Kuijper, Ed J

    2016-07-21

    Suboptimal laboratory diagnostics for Clostridium difficile infection (CDI) impedes its surveillance and control across Europe. We evaluated changes in local laboratory CDI diagnostics and changes in national diagnostic and typing capacity for CDI during the European C. difficile Infection Surveillance Network (ECDIS-Net) project, through cross-sectional surveys in 33 European countries in 2011 and 2014. In 2011, 126 (61%) of a convenience sample of 206 laboratories in 31 countries completed a survey on local diagnostics. In 2014, 84 (67%) of these 126 laboratories in 26 countries completed a follow-up survey. Among laboratories that participated in both surveys, use of CDI diagnostics deemed 'optimal' or 'acceptable' increased from 19% to 46% and from 10% to 15%, respectively (p  < 0.001). The survey of national capacity was completed by national coordinators of 31 and 32 countries in 2011 and 2014, respectively. Capacity for any C. difficile typing method increased from 22/31 countries in 2011 to 26/32 countries in 2014; for PCR ribotyping from 20/31 countries to 23/32 countries, and specifically for capillary PCR ribotyping from 7/31 countries to 16/32 countries. While our study indicates improved diagnostic capability and national capacity for capillary PCR ribotyping across European laboratories between 2011 and 2014, increased use of 'optimal' diagnostics should be promoted. PMID:27469624

  9. [Fecal microbiota transplantation in recurrent Clostridium difficile infections. Framework and pharmaceutical preparation aspects].

    PubMed

    Batista, R; Kapel, N; Megerlin, F; Chaumeil, J-C; Barbut, F; Bourlioux, P; Chast, F

    2015-09-01

    The fecal microbiota transplantation consists in introducing a preparation constituted by a dilution of stools of a healthy donor in the digestive tract of a patient recipient, to restore his intestinal physiological balance. This therapeutic approach was the subject of numerous studies showing its efficiency in the treatment of the recurrent infections with Clostridium difficile. The fecal microbiota transplantation has now a high level of clinical evidence, which explains that it appears in various international recommendations. In France, the fecal microbiota transplantation responds to the definition of a medication and can be executed as a pharmaceutical preparation or as an experimental drug for clinical trials under the responsibility of a hospital pharmacy. The objective of this paper is to propose a definition of a framework and to describe the methods of preparation of the fecal microbiota transplantation in the treatment of the recurrent infections with C. difficile and the interactions to consider for hospital pharmacies that do not have technical means to operate this technique. PMID:25825054

  10. Epidemiology, Diagnosis, and Management of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.

    PubMed

    Rao, Krishna; Higgins, Peter D R

    2016-07-01

    Clostridium difficile infection (CDI) is a major source of morbidity and mortality for the U.S. health care system and frequently complicates the course of inflammatory bowel disease (IBD). Patients with IBD are more likely to be colonized with C. difficile and develop active infection than the general population. They are also more likely to have severe CDI and develop subsequent complications such as IBD flare, colectomy, or death. Even after successful initial treatment and recovery, recurrent CDI is common. Management of CDI in IBD is fraught with diagnostic and therapeutic challenges because the clinical presentations of CDI and IBD flare have considerable overlap. Fecal microbiota transplantation can be successful in curing recurrent CDI when other treatments have failed, but may also trigger IBD flare and this warrants caution. New experimental treatments including vaccines, monoclonal antibodies, and nontoxigenic strains of C. difficile offer promise but are not yet available for clinicians. A better understanding of the complex relationship between the gut microbiota, CDI, and IBD is needed. PMID:27120571

  11. Fidaxomicin versus Vancomycin in the Treatment of Clostridium difficile Infection: Canadian Outcomes

    PubMed Central

    Lee, Christine; Louie, Thomas J.; Weiss, Karl; Valiquette, Louis; Gerson, Marvin; Arnott, Wendy; Gorbach, Sherwood L.

    2016-01-01

    Background. This analysis examined the efficacy of fidaxomicin versus vancomycin in 406 Canadian patients with Clostridium difficile infection (CDI), based on data from 2 randomized, clinical trials. Methods. Patients received fidaxomicin or vancomycin 1. Patients were assessed for clinical response recurrence of infection and sustained clinical response for 28 days after treatment completion. Patients at increased risk of recurrence were subjected to subgroup analyses. Results. Clinical response rates for fidaxomicin (90.0%) were noninferior to those with vancomycin (92.2%; 95% confidence interval for difference: −7.7, 3.5). However, fidaxomicin-treated patients had lower recurrence (14.4% versus 28.0%, p = 0.001) and higher sustained clinical response (77.1% versus 66.3%, p = 0.016). Compared with vancomycin, fidaxomicin was associated with lower recurrence rates in all subgroups, reaching statistical significance in patients with age ≥ 65 years (16.0% versus 30.9%, p = 0.026), concomitant antibiotic use (16.2% versus 38.7%, p = 0.036), and non-BI strains (11.8% versus 28.3%, p = 0.004). Higher sustained clinical response rates were observed for fidaxomicin compared with vancomycin in all subgroups; this was statistically significant in the non-BI subgroup (82.8% versus 69.1%, p = 0.021). Conclusions. In Canadian patients, fidaxomicin was superior to vancomycin in sustaining clinical response and reducing CDI recurrence. PMID:27366179

  12. Advanced chronic kidney disease: a strong risk factor for Clostridium difficile infection

    PubMed Central

    Kim, Sun Chul; Seo, Min Young; Lee, Jun Yong; Kim, Ki Tae; Cho, Eunjung; Kim, Myung-Gyu; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu

    2016-01-01

    Background/Aims: It has been suggested that chronic kidney disease (CKD) is a risk factor for Clostridium difficile infection (CDI) and is associated with increased mortality among patients infected with C. difficile. However, recent studies of the clinical impact of CKD on CDI in Asians are still insufficient. We sought to determine the relationship between CKD and CDI in a Korean population. Methods: This was a single-center, retrospective case-control study. In total, 171 patients with CDI were included as cases and 342 age- and gender-matched patients without CDI were used as controls. We compared the prevalence of CKD in the study sample and identified independent risk factors that could predict the development or prognosis of CDI. Results: Independent risk factors for CDI included stage IV to V CKD not requiring dialysis (odds ratio [OR], 2.90) and end-stage renal disease requiring dialysis (OR, 3.34). Patients with more advanced CKD (estimated glomerular filtration rate < 30) and CDI showed higher in-hospital mortality and poorer responses to the initial metronidazole therapy. Conclusions: More advanced CKD is an independent risk factor for CDI and is associated with higher in-hospital mortality and poor treatment responses in CDI patients. Thus, in CKD patients, careful attention should be paid to the occurrence of CDI and its management to improve the outcome of CDI. PMID:26767866

  13. Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients.

    PubMed

    Mani, S; Rybicki, L; Jagadeesh, D; Mossad, S B

    2016-05-01

    Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad-spectrum antibiotics and a complex interplay of preparative regimen and GvHD-induced gut mucosal damage. Our study evaluated risk factors (RF) for recurrent CDI in HSCT recipients given the ubiquity of traditional RF for CDI in this population. Of the 499 allogeneic HSCT recipients transplanted between 2005 and 2012, 61 (12%) developed CDI within 6 months before transplant or 2 years after transplant and were included in the analysis. Recurrent CDI occurred in 20 (33%) patients. One year incidence of CDI recurrence was 31%. Multivariable analyses identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (hazard ratio 1.96, 95% confidence interval 1.09-3.52, P=0.025). Most recurrences occurred within 6 months of the first CDI, and the recurrence of CDI was associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI. PMID:26726944

  14. Clostridium difficile Infection in Long-term Care Facilities: A Call to Action for Antimicrobial Stewardship.

    PubMed

    Chopra, Teena; Goldstein, Ellie J C

    2015-05-15

    Across the United States, the baby boomers are entering into their elderly years. As they are America's largest generation to do so to date, their need for care will greatly affect nursing homes, long-term care facilities, and long-term acute-care hospitals (LTACHs). Unfortunately, the rise of Clostridium difficile infection (CDI), particularly in extended-care facilities, might become the biggest obstacle in their care. Elderly extended-care-facility residents are at an elevated risk of CDI simply due to their advanced age and the fact that they are receiving care in an extended-care facility. LTACHs experience a high incidence rate of CDI, and these infections can lead to major complications for a patient's health. Other factors that contribute to higher risk for CDI include receiving multiple courses of antibiotics, longer length of antibiotic treatment, and previous CDI. Although this obstacle to proper care is great, some simple solutions are available to healthcare providers. Probiotics may help improve natural immunity in patients, and strict adherence to antimicrobial stewardship standards could help reduce this serious bacterial threat. PMID:25922404

  15. Mechanisms of Protection against Clostridium difficile Infection by the Monoclonal Antitoxin Antibodies Actoxumab and Bezlotoxumab

    PubMed Central

    Yang, Zhiyong; Ramsey, Jeremy; Hamza, Therwa; Zhang, Yongrong; Li, Shan; Yfantis, Harris G.; Lee, Dong; Hernandez, Lorraine D.; Seghezzi, Wolfgang; Furneisen, Jamie M.; Davis, Nicole M.

    2014-01-01

    Clostridium difficile infection (CDI) represents the most prevalent cause of antibiotic-associated gastrointestinal infections in health care facilities in the developed world. Disease symptoms are caused by the two homologous exotoxins, TcdA and TcdB. Standard therapy for CDI involves administration of antibiotics that are associated with a high rate of disease recurrence, highlighting the need for novel treatment paradigms that target the toxins rather than the organism itself. A combination of human monoclonal antibodies, actoxumab and bezlotoxumab, directed against TcdA and TcdB, respectively, has been shown to decrease the rate of recurrence in patients treated with standard-of-care antibiotics. However, the exact mechanism of antibody-mediated protection is poorly understood. In this study, we show that the antitoxin antibodies are protective in multiple murine models of CDI, including systemic and local (gut) toxin challenge models, as well as primary and recurrent models of infection in mice. Systemically administered actoxumab-bezlotoxumab prevents both the damage to the gut wall and the inflammatory response, which are associated with C. difficile in these models, including in mice challenged with a strain of the hypervirulent ribotype 027. Furthermore, mutant antibodies (N297Q) that do not bind to Fcγ receptors provide a level of protection similar to that of wild-type antibodies, demonstrating that the mechanism of protection is through direct neutralization of the toxins and does not involve host effector functions. These data provide a mechanistic basis for the prevention of recurrent disease observed in CDI patients in clinical trials. PMID:25486992

  16. Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection

    PubMed Central

    2016-01-01

    Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and

  17. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain.

    PubMed

    O'Connor, Jennifer R; Johnson, Stuart; Gerding, Dale N

    2009-05-01

    Rates and severity of Clostridium difficile infection (CDI) in hospitals in North America and Europe have increased since 2000 and correlate with dissemination of an epidemic strain characterized by higher than usual toxin A and B production, the presence of a third toxin, binary toxin, and high-level resistance to fluoroquinolone antibiotics. The strain, which is restriction endonuclease analysis group BI, pulse-field gel electrophoresis type NAP1, and polymerase chain reaction ribotype 027, is designated BI/NAP1/027. How this strain has become so widely distributed geographically and produces such severe CDI is the subject of active investigation. The deletion at position 117 of the tcdC gene, a repressor of toxin A and B production, is one possible contributor to increased levels of the toxins. The role of binary toxin is unknown. Recent isolates of BI/NAP1/027 were found to be resistant to fluoroquinolones, which is likely to contribute to the dissemination of this strain. Other virulence factors such as increased sporulation and surface layer protein adherence are also under investigation. Infections caused by this organism are particularly frequent among elderly hospitalized patients, in whom the attributable 30-day mortality is greater than 5%. Major risk factors for BI/NAP1/027 infection include advanced age, hospitalization, and exposure to specific antimicrobials, especially fluoroquinolones and cephalosporins. When CDI is severe, vancomycin treatment is more effective than metronidazole; for mild disease either agent can be used. Control of hospital outbreaks caused by BI/NAP1/027 is difficult but possible through a combination of barrier precautions, environmental cleaning, and antimicrobial stewardship. PMID:19457419

  18. Clostridium difficile infection, a descriptive analysis of solid organ transplant recipients at a single center.

    PubMed

    Tsapepas, Demetra S; Martin, Spencer T; Miao, Jennifer; Shah, Shreya A; Scheffert, Jenna; Fester, Keith; Ma, Karlene; Lat, Asma; Egan, Ron; McKeen, Jaclyn T

    2015-04-01

    Clostridium difficile is a bacterial enteric pathogen, which causes clinical disease among solid organ transplant (SOT) recipients. This large, single-center, retrospective study describes incidence, demographics, and impact of C. difficile infection (CDI) among adult SOT recipients, cardiac (n=5), lung (n=14), liver (n=9), renal (n=26), and multiorgan (n=9) patients transplanted and diagnosed with CDI (geneB PCR) between 9/2009 and 12/2012. The overall incidence of CDI in our population during the 40-month period of study was 4%. CDI incidence among cardiac, lung, liver, and renal transplant recipients was 1.9%, 7%, 2.7%, and 3.2%, respectively (P=0.03 between organ-types). Median time from transplant to CDI for all was 51 (14-249) days, with liver recipients having the shortest time to infection, median 36 (15-101) days, and lung recipients having a longer time to infection, median 136 (29-611) days. Antibiotic exposure within 3 months of CDI was evident in 45 of the 63 (71%) patients in this study, 80%, 79%, 100%, 58%, and 67% of cardiac, lung, liver, renal, and multiorgan transplant recipients, respectively. Most patients (83%) were hospitalized within the 3 months preceding CDI. Recipients were followed for a median time of 23 (16-31) months; at the time of last follow-up, 83% of allografts were functioning, and 86% of patients were alive. One death and 1 graft failure were causally related to CDI. CDI had an overall incidence of 4%; clinicians should have heightened awareness for CDI, especially among patients receiving antibiotics, with increased monitoring and aggressive management of CDI. PMID:25586932

  19. Analysis of Bacterial Communities during Clostridium difficile Infection in the Mouse

    PubMed Central

    Semenyuk, Ekaterina G.; Poroyko, Valeriy A.; Johnston, Pehga F.; Jones, Sara E.; Knight, Katherine L.; Gerding, Dale N.

    2015-01-01

    Clostridium difficile infection (CDI) is a major cause of health care-associated disease. CDI initiates with ingestion of C. difficile spores, germination in the gastrointestinal (GI) tract, and then colonization of the large intestine. The interactions between C. difficile cells and other bacteria and with host mucosa during CDI remain poorly understood. Here, we addressed the hypothesis that, in a mouse model of CDI, C. difficile resides in multicellular communities (biofilms) in association with host mucosa. To do this, we paraffin embedded and then sectioned the GI tracts of infected mice at various days postinfection (p.i.). We then used fluorescent in situ hybridization (FISH) with 16S rRNA probes targeting most bacteria as well as C. difficile specifically. The results revealed that C. difficile is present as a minority member of communities in the outer (loose) mucus layer, in the cecum and colon, starting at day 1 p.i. To generate FISH probes that identify bacteria within mucus-associated communities harboring C. difficile, we characterized bacterial populations in the infected mouse GI tract using 16S rRNA gene sequence analysis of bacterial DNA prepared from intestinal content. This analysis revealed the presence of genera of several families belonging to Bacteroidetes and Firmicutes. These data suggest that formation of multispecies communities associated with the mucus of the cecum and colon is an important early step in GI tract colonization. They raise the possibility that other bacterial species in these communities modulate the ability of C. difficile to successfully colonize and, thereby, cause disease. PMID:26324536

  20. Racial Differences in Clostridium difficile Infection Rates Are Attributable to Disparities in Health Care Access.

    PubMed

    Mao, Eric J; Kelly, Colleen R; Machan, Jason T

    2015-10-01

    This study confirms previously reported racial differences in Clostridium difficile infection (CDI) rates in the United States and explores the nature of those differences. We conducted a retrospective study using the 2010 Nationwide Inpatient Sample, the largest all-payer database of hospital discharges in the United States. We identified hospital stays most likely to include antibiotic treatment for infections, based on hospital discharge diagnoses, and we examined how CDI rates varied, in an attempt to distinguish between genotypic and environmental racial differences. Logistic regressions for the survey design were used to test hypotheses. Among patients likely to have received antibiotics, white patients had higher CDI rates than black, Hispanic, Asian, and Native American patients (P < 0.0001). CDI rates increased with higher income levels and were higher for hospitalizations paid by private insurance versus those paid by Medicaid or classified as self-pay or free care (P < 0.0001). Among patients admitted from skilled nursing facilities, where racial bias in health care access is less, racial differences in CDI rates disappeared (P = 1.0). Infected patients did not show racial differences in rates of complicated CDI or death (P = 1.0). Although white patients had greater CDI rates than nonwhite patients, racial differences in CDI rates disappeared in a population for which health care access was presumed to be less racially biased. This provides evidence that apparent racial differences in CDI risks may represent health care access disparities, rather than genotypic differences. CDI represents a deviation from the paradigm that increased health care access is associated with less morbidity. PMID:26248363

  1. Rapid diagnosis of Clostridium difficile infection by multiplex real-time PCR.

    PubMed

    Barbut, F; Monot, M; Rousseau, A; Cavelot, S; Simon, T; Burghoffer, B; Lalande, V; Tankovic, J; Petit, J-C; Dupuy, B; Eckert, C

    2011-10-01

    The gold standards for the diagnosis of Clostridium difficile infections (CDIs) are the cytotoxicity assay and the toxigenic culture. However, both methods are time-consuming and the results are not available before 24-48 h. We developed and evaluated a multiplex in-house real-time polymerase chain reaction (PCR) assay for the simultaneous detection of toxigenic strains of C. difficile and the presumptive identification of the epidemic NAP1/027/BI strain from stools. Amplifications were performed using specific primers for tcdB and tcdC on an ABI Prism 7300 (Applied Biosystems). The detection of amplicons was done using TaqMan probes. The analytical sensitivity of the multiplex real-time PCR for detecting tcdB was estimated to 10 CFU/g of stools. This assay was assessed from 881 consecutive unformed stools from patients suspected of having CDI. The gold standard was the toxigenic culture for the diagnosis of CDI and PCR ribotyping for the identification of the NAP1/027/BI strain. The prevalence of positive toxigenic culture was 9.31%. Compared to the toxigenic culture, the sensitivity, specificity, and positive and negative predictive values were 86.59%, 97.43%, 78.02%, and 98.57%, respectively, for the real-time PCR and 70.73%, 100%, 100%, and 97.08%, respectively, for the cytotoxicity assay. PMID:21487764

  2. Impacts of infection with different toxigenic Clostridium difficile strains on faecal microbiota in children

    PubMed Central

    Ling, Zongxin; Liu, Xia; Jia, Xiaoyun; Cheng, Yiwen; Luo, Yueqiu; Yuan, Li; Wang, Yuezhu; Zhao, Chunna; Guo, Shu; Li, Lanjuan; Xu, Xiwei; Xiang, Charlie

    2014-01-01

    Increasing evidence suggests that altered intestinal microbial composition and function result in an increased risk of Clostridium difficile-associated diarrhoea (CDAD); however, the specific changes of intestinal microbiota in children suffering from CDAD and their associations with C. difficile strain toxigenicity are poorly understood. High-throughput pyrosequencing showed that reduced faecal bacterial diversity and dramatic shifts of microbial composition were found in children with CDAD. The Firmicutes/Bacteroidetes ratio was increased significantly in patients with CDAD, which indicated that dysbiosis of faecal microbiota was closely associated with CDAD. C. difficile infection resulted in an increase in lactate-producing phylotypes, with a corresponding decrease in butyrate-producing bacteria. The decrease in butyrate and lactate buildup impaired intestinal colonisation resistance, which increased the susceptibility to C. difficile colonisation. Strains of C. difficile which were positive for both toxin A and toxin B reduced faecal bacterial diversity to a greater degree than strains that were only toxin B-positive, and were associated with unusually abundant Enterococcus, which implies that the C. difficile toxins have different impacts on the faecal microbiota of children. Greater understanding of the relationships between disruption of the normal faecal microbiota and colonisation with C. difficile that produces different toxins might lead to improved treatment. PMID:25501371

  3. Delirium and other clinical factors with Clostridium difficile infection that predict mortality in hospitalized patients

    PubMed Central

    Archbald-Pannone, Laurie R.; McMurry, Timothy L.; Guerrant, Richard L.; Warren, Cirle A.

    2015-01-01

    Background Clostridium difficile infection (CDI) severity has increased, especially among hospitalized elderly. We evaluated clinical factors to predict mortality following CDI. Methods We collected data from inpatients diagnosed with CDI at US academic medical center (HSR-IRB# 13630). We evaluated age, Charlson comorbidity index (CCI), admission from a long-term care facility (LTCF), intensive care unit (ICU) at time of diagnosis, white blood cell count (WBC), blood urea nitrogen (BUN), low body mass index (BMI), and delirium as possible predictors. A parsimonious predictive model was chosen using Akaike information criterion (AIC) and a best subsets model selection algorithm. Area under the ROC curve was used to assess the model’s comparative; with AIC as selection criterion for all subsets to measure fit and control for over-fitting. Results From 362 subjects, the selected model included CCI, WBC, BUN, ICU, and delirium. The logistic regression coefficients were converted to a points scale and calibrated so that each unit on the CCI contributed 2 points, ICU contributed 5, unit of WBC (natural log scale) contributed 3, unit of BUN contributed 5, and delirium contributed 11. Discussion Our model shows substantial ability to predict short term mortality in patients hospitalized with CDI. Conclusion Patients who were diagnosed in the ICU and developed delirium are at highest risk for dying within 30 days of CDI diagnosis. PMID:25920706

  4. Serum 25-Hydroxyvitamin D Levels are not Associated with Adverse Outcomes in Clostridium Difficile Infection

    PubMed Central

    Micic, Dejan; Rao, Krishna; Trindade, Bruno Caetano; Walk, Seth T.; Chenoweth, Elizabeth; Jain, Ruchika; Trivedi, Itishree; Santhosh, Kavitha; Young, Vincent B.; Aronoff, David M.

    2015-01-01

    Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI. PMID:26500740

  5. Healthcare Resource Utilization for Recurrent Clostridium difficile Infection in a Large University Hospital in Houston, Texas

    PubMed Central

    Aitken, Samuel L.; Joseph, Tiby B.; Shah, Dhara N.; Lasco, Todd M.; Palmer, Hannah R.; DuPont, Herbert L.; Xie, Yang; Garey, Kevin W.

    2014-01-01

    Background There are limited data examining healthcare resource utilization in patients with recurrent Clostridium difficile infection (CDI). Methods Patients with CDI at a tertiary-care hospital in Houston, TX, were prospectively enrolled into an observational cohort study. Recurrence was assessed via follow-up phone calls. Patients with one or more recurrence were included in this study. The location at which healthcare was obtained by patients with recurrent CDI was identified along with hospital length of stay. CDI-attributable readmissions, defined as a positive toxin test within 48 hours of admission and a primary CDI diagnosis, were also assessed. Results 372 primary cases of CDI were identified of whom 64 (17.2%) experienced at least one CDI recurrence. Twelve of 64 patients experienced 18 further episodes of CDI recurrence. Of these 64 patients, 33 (50.8%) patients with recurrent CDI were readmitted of which 6 (18.2%) required ICU care, 29 (45.3%) had outpatient care only, and 2 (3.1%) had an ED visit. Nineteen (55.9%) readmissions were defined as CDI-attributable. For patients with CDI-attributable readmission, the average length of stay was 6±6 days. Conclusion Recurrent CDI leads to significant healthcare resource utilization. Methods of reducing the burden of recurrent CDI should be further studied. PMID:25057871

  6. Standardised surveillance of Clostridium difficile infection in European acute care hospitals: a pilot study, 2013.

    PubMed

    van Dorp, Sofie M; Kinross, Pete; Gastmeier, Petra; Behnke, Michael; Kola, Axel; Delmée, Michel; Pavelkovich, Anastasia; Mentula, Silja; Barbut, Frédéric; Hajdu, Agnes; Ingebretsen, André; Pituch, Hanna; Macovei, Ioana S; Jovanović, Milica; Wiuff, Camilla; Schmid, Daniela; Olsen, Katharina Ep; Wilcox, Mark H; Suetens, Carl; Kuijper, Ed J

    2016-07-21

    Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a 'minimal' option (aggregated hospital data), a 'light' option (including patient data for CDI cases) and an 'enhanced' option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe. PMID:27472820

  7. Gastrointestinal dysbiosis and the use of fecal microbial transplantation in Clostridium difficile infection

    PubMed Central

    Schenck, L Patrick; Beck, Paul L; MacDonald, Justin A

    2015-01-01

    The impact of antibiotics on the human gut microbiota is a significant concern. Antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. Clostridium difficile infections (CDI) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. Studies show that variability in the innate host response may in part impact upon CDI severity in patients. That being said, CDI is a disease that shows the most prominent links to alterations to the gut microbiota, in both cause and treatment. With recurrence rates still relatively high, it is important to explore alternative therapies to CDI. Fecal microbiota transplantation (FMT) and other types of bacteriotherapy have become exciting avenues of treatment for CDI. Recent clinical trials have generated excitement for the use of FMT as a therapeutic option for CDI; however, the exact components of the human gut microbiota needed for protection against CDI have remained elusive. Additional investigations on the effects of antibiotics on the human gut microbiota and subsequent CDI will help reduce the socioeconomic burden of CDI and potentially lead to new therapeutic modalities. PMID:26600975

  8. Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond

    PubMed Central

    Borody, Thomas J.; Peattie, Debra; Mitchell, Scott W.

    2015-01-01

    Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases. PMID:27025624

  9. DNA detection of Clostridium difficile infection based on real-time resistance measurement.

    PubMed

    Liu, C; Jiang, D N; Xiang, G M; Luo, F K; Liu, L L; Yu, J C; Pu, X Y

    2013-01-01

    We used a newly developed electrochemical method, real-time resistance measurement, based on loop-mediated isothermal amplification (LAMP), with real-time resistance monitoring and derivative analysis. DNA extracted from specimens was amplified through LAMP reaction. The 2 products of LAMP, DNA and pyrophosphate, both are negative ions; they combine with positive dye (crystal violet) and positive ions (Mg(2+)), which leads to an increase in the resistivity of the reaction liquid. The changes of resistivity were measured in real-time with a specially designed resistance electrode, to detect Clostridium difficile DNA. We found that electrochemical detection of C. difficile could be completed in 0.5-1 h, with a detection limit of 10(2) CFU/mL, with high accuracy (95.0%), sensitivity (91.1%), and specificity (97.3%) compared to PCR methods. C. difficile is commonly associated with antibiotic-induced diarrhea. Due to the difficulty in performing anaerobic culture and cytotoxicity neutralization assays, a simple, rapid, sensitive, and accurate method is preferred. We conclude that real-time resistance measurement is a rapid, sensitive, and stable method for the diagnosis of C. difficile infection that could be applied to gene chips and pocket instruments. PMID:24065671

  10. Excretion of Host DNA in Feces Is Associated with Risk of Clostridium difficile Infection

    PubMed Central

    Loo, Vivian G.; Dewar, Ken; Manges, Amee R.

    2015-01-01

    Clostridium difficile infection (CDI) is intricately linked to the health of the gastrointestinal tract and its indigenous microbiota. In this study, we assessed whether fecal excretion of host DNA is associated with CDI development. Assuming that shedding of epithelial cell increases in the inflamed intestine, we used human DNA excretion as a marker of intestinal insult. Whole-genome shotgun sequencing was employed to quantify host DNA excretion and evaluate bacterial content in fecal samples collected from patients with incipient CDI, hospitalized controls, and healthy subjects. Human DNA excretion was significantly increased in patients admitted to the hospital for a gastrointestinal ailment, as well as prior to an episode of CDI. In multivariable analyses, human read abundance was independently associated with CDI development. Host DNA proportions were negatively correlated with intestinal microbiota diversity. Enterococcus and Escherichia were enriched in patients excreting high quantities of human DNA, while Ruminococcus and Odoribacter were depleted. These findings suggest that intestinal inflammation can occur prior to CDI development and may influence patient susceptibility to CDI. The quantification of human DNA in feces could serve as a simple and noninvasive approach to assess bowel inflammation and identify patients at risk of CDI. PMID:26090486

  11. Gut microbiota composition and Clostridium difficile infection in hospitalized elderly individuals: a metagenomic study.

    PubMed

    Milani, Christian; Ticinesi, Andrea; Gerritsen, Jacoline; Nouvenne, Antonio; Lugli, Gabriele Andrea; Mancabelli, Leonardo; Turroni, Francesca; Duranti, Sabrina; Mangifesta, Marta; Viappiani, Alice; Ferrario, Chiara; Maggio, Marcello; Lauretani, Fulvio; De Vos, Willem; van Sinderen, Douwe; Meschi, Tiziana; Ventura, Marco

    2016-01-01

    The gut microbiota composition of elderly hospitalized patients with Clostridium difficile infection (CDI) exposed to previous antibiotic treatment is still poorly investigated. The aim of this study was to compare the microbiota composition by means of 16S rRNA microbial profiling among three groups of hospitalized elderly patients (age ≥ 65) under standard diet including 25 CDI-positive (CDI group), 29 CDI-negative exposed to antibiotic treatment (AB+ group) and 30 CDI-negative subjects not on antibiotic treatment (AB- group). The functional properties of the gut microbiomes of CDI-positive vs CDI-negative subjects were also assessed by shotgun metagenomics. A significantly lower microbial diversity was detected in CDI samples, whose microbiomes clustered separately from CDI-negative specimens. CDI was associated with a significant under-representation of gut commensals with putative protective functionalities, including Bacteroides, Alistipes, Lachnospira and Barnesiella, and over-representation of opportunistic pathogens. These findings were confirmed by functional shotgun metagenomics analyses, including an in-depth profiling of the Peptostreptococcaceae family. In CDI-negative patients, antibiotic treatment was associated with significant depletion of few commensals like Alistipes, but not with a reduction in species richness. A better understanding of the correlations between CDI and the microbiota in high-risk elderly subjects may contribute to identify therapeutic targets for CDI. PMID:27166072

  12. Impacts of infection with different toxigenic Clostridium difficile strains on faecal microbiota in children

    NASA Astrophysics Data System (ADS)

    Ling, Zongxin; Liu, Xia; Jia, Xiaoyun; Cheng, Yiwen; Luo, Yueqiu; Yuan, Li; Wang, Yuezhu; Zhao, Chunna; Guo, Shu; Li, Lanjuan; Xu, Xiwei; Xiang, Charlie

    2014-12-01

    Increasing evidence suggests that altered intestinal microbial composition and function result in an increased risk of Clostridium difficile-associated diarrhoea (CDAD); however, the specific changes of intestinal microbiota in children suffering from CDAD and their associations with C. difficile strain toxigenicity are poorly understood. High-throughput pyrosequencing showed that reduced faecal bacterial diversity and dramatic shifts of microbial composition were found in children with CDAD. The Firmicutes/Bacteroidetes ratio was increased significantly in patients with CDAD, which indicated that dysbiosis of faecal microbiota was closely associated with CDAD. C. difficile infection resulted in an increase in lactate-producing phylotypes, with a corresponding decrease in butyrate-producing bacteria. The decrease in butyrate and lactate buildup impaired intestinal colonisation resistance, which increased the susceptibility to C. difficile colonisation. Strains of C. difficile which were positive for both toxin A and toxin B reduced faecal bacterial diversity to a greater degree than strains that were only toxin B-positive, and were associated with unusually abundant Enterococcus, which implies that the C. difficile toxins have different impacts on the faecal microbiota of children. Greater understanding of the relationships between disruption of the normal faecal microbiota and colonisation with C. difficile that produces different toxins might lead to improved treatment.

  13. Decreasing Clostridium difficile Infections by an Antimicrobial Stewardship Program That Reduces Moxifloxacin Use

    PubMed Central

    Equiluz-Bruck, Susanne; Fudel, Marta; Reiter, Ingun; Schmid, Andrea; Singer, Erna; Chott, Andreas

    2014-01-01

    Clostridium difficile infections (CDI) in hospitalized patients are known to be closely related to antibiotic exposure. Although several substances can cause CDI, the risk differs between individual agents. In Vienna and other eastern parts of Austria, CDI ribotype 027 is currently highly prevalent. This ribotype has the characteristic of intrinsic moxifloxacin resistance. Therefore, we hypothesized that moxifloxacin restriction can decrease the number of CDI cases in hospitalized patients. Our antibiotic stewardship (ABS) group applied an information campaign on CDI and formal restriction of moxifloxacin in Wilhelminenspital (Vienna, Austria), a 1,000- bed tertiary care hospital. The preintervention period (period 1) was January through May 2013, and the intervention period (period 2) was June through December 2013. We recorded the defined daily doses (DDD) of moxifloxacin and the number of CDI patients/month. Moxifloxacin use was reduced from a mean (± standard error of the mean [SEM]) of 1,038 ± 109 DDD per month (period 1) to 42 ± 10 DDD per month (period 2) (P = 0.0045). Total antibiotic use was not affected. The mean (±SEM) numbers of CDI cases in period 1 were 59 ± 3 per month and in period 2 were 32 ± 3 per month (46% reduction; P = 0.0044). Reducing moxifloxacin use in combination with providing structured information on CDI was associated with an immediate decrease in CDI rates in this large community teaching hospital. PMID:24936597

  14. Clostridium difficile infections in a Shanghai hospital: antimicrobial resistance, toxin profiles and ribotypes.

    PubMed

    Huang, Haihui; Wu, Shi; Wang, Minggui; Zhang, Yingyuan; Fang, Hong; Palmgren, Ann-Chatrin; Weintraub, Andrej; Nord, Carl Erik

    2009-04-01

    The incidence of Clostridium difficile infection (CDI) has risen markedly since 2003, however data from China are limited. A 1-year study was conducted at the University Hospital Huashan to characterise clinical isolates of C. difficile. Of 74 isolates, 56 were from the first episode of CDI (43 A(+)B(+) and 13 A(-)B(+)), 5 were from recurrences and 13 were toxin-negative. No binary toxin or TcdC deletion was detected. All strains were susceptible to metronidazole, vancomycin, meropenem and piperacillin/tazobactam. Resistance to moxifloxacin, ciprofloxacin, levofloxacin, erythromycin, clindamycin, tetracycline, rifampicin and fusidic acid was found in 46.4%, 100%, 60.7%, 71.4%, 71.4%, 35.7%, 25.0% and 17.9% of the isolates, respectively. All moxifloxacin-resistant isolates carried a mutation in either gyrA, gyrB or both. Fourteen different polymerase chain reaction ribotypes were identified, with a specific clone (SH II) accounting for 25% of isolates. No isolates belonged to ribotype 027. The present study is the first systematic survey of clinical C. difficile isolates in China. Further surveillance is required to detect clustering of cases and to monitor the emergence of specific highly virulent clones and resistance. PMID:19097757

  15. Gut microbiota composition and Clostridium difficile infection in hospitalized elderly individuals: a metagenomic study

    PubMed Central

    Milani, Christian; Ticinesi, Andrea; Gerritsen, Jacoline; Nouvenne, Antonio; Lugli, Gabriele Andrea; Mancabelli, Leonardo; Turroni, Francesca; Duranti, Sabrina; Mangifesta, Marta; Viappiani, Alice; Ferrario, Chiara; Maggio, Marcello; Lauretani, Fulvio; De Vos, Willem; van Sinderen, Douwe; Meschi, Tiziana; Ventura, Marco

    2016-01-01

    The gut microbiota composition of elderly hospitalized patients with Clostridium difficile infection (CDI) exposed to previous antibiotic treatment is still poorly investigated. The aim of this study was to compare the microbiota composition by means of 16S rRNA microbial profiling among three groups of hospitalized elderly patients (age ≥ 65) under standard diet including 25 CDI-positive (CDI group), 29 CDI-negative exposed to antibiotic treatment (AB+ group) and 30 CDI-negative subjects not on antibiotic treatment (AB− group). The functional properties of the gut microbiomes of CDI-positive vs CDI-negative subjects were also assessed by shotgun metagenomics. A significantly lower microbial diversity was detected in CDI samples, whose microbiomes clustered separately from CDI-negative specimens. CDI was associated with a significant under-representation of gut commensals with putative protective functionalities, including Bacteroides, Alistipes, Lachnospira and Barnesiella, and over-representation of opportunistic pathogens. These findings were confirmed by functional shotgun metagenomics analyses, including an in-depth profiling of the Peptostreptococcaceae family. In CDI-negative patients, antibiotic treatment was associated with significant depletion of few commensals like Alistipes, but not with a reduction in species richness. A better understanding of the correlations between CDI and the microbiota in high-risk elderly subjects may contribute to identify therapeutic targets for CDI. PMID:27166072

  16. Probiotics in Clostridium difficile infection: reviewing the need for a multistrain probiotic.

    PubMed

    Hell, M; Bernhofer, C; Stalzer, P; Kern, J M; Claassen, E

    2013-03-01

    In the past two years an enormous amount of molecular, genetic, metabolomic and mechanistic data on the host-bacterium interaction, a healthy gut microbiota and a possible role for probiotics in Clostridium difficile infection (CDI) has been accumulated. Also, new hypervirulent strains of C. difficile have emerged. Yet, clinical trials in CDI have been less promising than in antibiotic associated diarrhoea in general, with more meta-analysis than primary papers on CDI-clinical-trials. The fact that C. difficile is a spore former, producing at least three different toxins has not yet been incorporated in the rational design of probiotics for (recurrent) CDI. Here we postulate that the plethora of effects of C. difficile and the vast amount of data on the role of commensal gut residents and probiotics point towards a multistrain mixture of probiotics to reduce CDI, but also to limit (nosocomial) transmission and/or endogenous reinfection. On the basis of a retrospective chart review of a series of ten CDI patients where recurrence was expected, all patients on adjunctive probiotic therapy with multistrain cocktail (Ecologic®AAD/OMNiBiOTiC® 10) showed complete clinical resolution. This result, and recent success in faecal transplants in CDI treatment, are supportive for the rational design of multistrain probiotics for CDI. PMID:23434948

  17. Clostridium difficile infection in a French university hospital: Eight years of prospective surveillance study.

    PubMed

    Khanafer, Nagham; Oltra, Luc; Hulin, Monique; Dauwalder, Olivier; Vandenesch, Francois; Vanhems, Philippe

    2016-06-01

    The epidemiology of Clostridium difficile infection (CDI) has changed with an increase in incidence and severity. Prospective surveillance was therefore implemented in a French university hospital to monitor the characteristics of patients at risk and to recognize local trends. Between 2007 and 2014, all hospitalized patients (≥18 years) with CDI were included. During the survey, the mean incidence rate of CDI was 2.9 per 10,000 hospital-days. In all, 590 patients were included. Most of the episodes were healthcare-associated (76.1%). The remaining cases were community-acquired (18.1%) and unknown (5.9%). The comparison with healthcare-associated cases showed that the community-acquired group had a lower rate of antimicrobial exposure (P < 0.001), proton pump inhibitor (P < 0.001), and immunosuppressive drugs (P = 0.02). Over the study period, death occurred in 61 patients (10.3%), with 18 (29.5%) being related to CDI according to the physician in charge of the patient. Active surveillance of CDI is required to obtain an accurate picture of the real dimensions of CDI. PMID:27281101

  18. Prospects for flavonoid and related phytochemicals as nature-inspired treatments for Clostridium difficile infection

    PubMed Central

    Wu, Xiaoqian; Alam, Zahidul; Feng, Li; Tsutsumi, Lissa S.; Sun, Dianqing; Hurdle, Julian G.

    2013-01-01

    Aims There is a need for novel treatments for Clostridium difficile infection (CDI). Antibacterial flavonoids are part of a large family of polyphenol phytochemicals with a long history of use in ethnomedicine, but are unexamined against C. difficile. We explored their anti-difficile properties. Methods and Results Anti-difficile activities were determined for several naturally occurring flavonoids, olympicin A and synthetic 4-chromanone and chalcone analogs. With the exception of olympicin A, most naturally occurring phytochemicals tested were poorly active. Diversified synthetic flavonoids resembling olympicin A retained anti-difficile activity, suggesting olympicin A could act as a pharmacophore to obtain novel agents. They also demonstrated concentration dependent killing of logarithmic and stationary phase cultures and reduced sporulation and toxin production. Olympicin A and some synthetic flavonoids dissipated the bacterial transmembrane potential. Interestingly, mutants could only be selected with the analog 207 at a frequency of 10-9. Conclusions Based on the potent anti-difficile properties of olympicin A and modified flavonoids, further exploration of this class of phytochemicals is warranted. Significance and Impact of the Study CDI is a major problem in developed countries. These studies point to there being an avenue for optimizing plant-derived flavonoids, and related antibacterial phytochemicals, as nature-inspired approaches to treat CDI. PMID:24479135

  19. Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond.

    PubMed

    Borody, Thomas J; Peattie, Debra; Mitchell, Scott W

    2015-01-01

    Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases. PMID:27025624

  20. Development and application of an oral challenge mouse model for studying Clostridium perfringens type D infection.

    PubMed

    Fernandez-Miyakawa, Mariano E; Sayeed, Sameera; Fisher, Derek J; Poon, Rachael; Adams, Vicki; Rood, Julian I; McClane, Bruce A; Saputo, Julian; Uzal, Francisco A

    2007-09-01

    Clostridium perfringens type D isolates cause enterotoxemia in sheep, goats, and probably cattle. While the major disease signs and lesions of type D animal disease are usually attributed to epsilon toxin, a class B select agent, these bacteria typically produce several lethal toxins. Understanding of disease pathogenesis and development of improved vaccines are hindered by the lack of a small-animal model mimicking natural disease caused by type D isolates. Addressing this need, we developed an oral challenge mouse model of C. perfringens type D enterotoxemia. When BALB/c mice with a sealed anus were inoculated by intragastric gavage with type D isolates, 7 of 10 type D isolates were lethal, as defined by spontaneous death or severe clinical signs necessitating euthanasia. The lethalities of the seven type D isolates varied between 14 and 100%. Clinical signs in the lethally challenged mice included seizures, convulsions, hyperexcitability, and/or depression. Mild intestinal gas distention and brain edema were observed at necropsy in a few mice, while histology showed multifocal acute tubular necrosis of the kidney and edema in the lungs of most challenged mice that developed a clinical response. When the lethality of type D isolates in this model was compared with in vitro toxin production, only a limited correlation was observed. However, mice could be protected against lethality by intravenous passive immunization with an epsilon toxin antibody prior to oral challenge. This study provides an economical new model for studying the pathogenesis of C. perfringens type D infections. PMID:17562765

  1. Recent progress in understanding the pathogenesis of Clostridium perfringens type C infections

    PubMed Central

    McClane, B. A.

    2011-01-01

    Clostridium perfringens type C causes necrotizing enteritis in humans and several other animal species. Type C isolates must produce at least beta toxin (CPB) and alpha toxin (CPA) and most strains produce several other toxins including perfringolysin O (PFO) and TpeL. However, current evidence indicates that CPB is the main virulence factor for type C infections. Most of this evidence is based upon the loss of virulence shown by isogenic type C CPB knock out mutants on cells, and also in rabbit intestinal loops and in mouse models. This virulence is regained when these mutants are complemented with the wild-type cpb gene. Many type C isolates respond to close contact with enterocyte-like Caco-2 cells by producing all toxins, except TpeL, much more rapidly than occurs during in vitro growth. This in vivo effect involves rapid transcriptional upregulation of the cpb, cpb2, pfoA and plc toxin genes. Rapid Caco-2 cell-induced upregulation of CPB and PFO production involves the VirS/VirR two-component system, since upregulated in vivo transcription of the pfoA and cpb genes was blocked by inactivating the virR gene and was reversible by complementation to restore VirR expression. PMID:21420802

  2. View from the front lines: an emergency medicine perspective on clostridial infections in injection drug users.

    PubMed

    Gonzales y Tucker, Richard Diego; Frazee, Bradley

    2014-12-01

    Injection drug use (IDU), specifically non-intravenous "skin-popping" of heroin, seems to provide optimal conditions for Clostridial infection and toxin production. IDU is therefore a major risk factor for wound botulism and Clostridial necrotizing soft tissue infections (NSTI) and continues to be linked to cases of tetanus. Case clusters of all 3 diseases have occurred among IDUs in Western U.S. and Europe. Medical personnel who care for the IDU population must be thoroughly familiar with the clinical presentation and management of these diseases. Wound botulism presents with bulbar symptoms and signs that are easily overlooked; rapid acquisition and administration of antitoxin can prevent neuromuscular respiratory failure. In addition to Clostridium perfringens, IDU-related NSTIs can be caused by Clostridium sordellii and Clostridium novyi, which may share a distinct clinical presentation. Early definitive NSTI management, which decreases mortality, requires a low index of suspicion on the part of emergency physicians and low threshold for surgical exploration and debridement on the part of the surgeon. Tetanus should be preventable in the IDU population through careful attention to vaccination status. PMID:25230330

  3. Enhanced surveillance of Clostridium difficile infection occurring outside hospital, England, 2011 to 2013.

    PubMed

    Fawley, Warren N; Davies, Kerrie A; Morris, Trefor; Parnell, Peter; Howe, Robin; Wilcox, Mark H

    2016-07-21

    There are limited national epidemiological data for community-associated (CA)-Clostridium difficile infections (CDIs). Between March 2011 and March 2013, laboratories in England submitted to the Clostridium difficile Ribotyping Network (CDRN) up to 10 diarrhoeal faecal samples from successive patients with CA-CDI, defined here as C. difficile toxin-positive diarrhoea commencing outside hospital (or less than 48 hours after hospital admission), including those cases associated with community-based residential care, with no discharge from hospital within the previous 12 weeks. Patient demographics and C. difficile PCR ribotypes were compared for CA-CDIs in our study and presumed healthcare-associated (HA) CDIs via CDRN. Ribotype diversity indices, ranking and relative prevalences were very similar in CA- vs HA-CDIs, although ribotypes 002 (p ≤ 0.0001),020 (p = 0.009) and 056 (p < 0.0001) predominated in CA-CDIs; ribotype 027 (p = 0.01) predominated in HA-CDIs. Epidemic ribotypes 027 and 078 predominated in institutional residents with CDI (including care/nursing homes) compared with people with CDI living at home. Ribotype diversity decreased with increasing age in HA-CDIs, but not in CA-CDIs. Ribotype 078 CA-CDIs were significantly more common in elderly people (3.4% (6/174) vs 8.7% (45/519) in those aged < 65 and ≥ 65 years, respectively; p = 0.019). No antibiotics were prescribed in the previous four weeks in about twofold more CA-CDI vs HAs (38.6% (129/334) vs 20.3% (1,226/6,028); p < 0.0001). We found very similar ribotype distributions in CA- and HA-CDIs, although a few ribotypes significantly predominated in one setting. These national data emphasise the close interplay between, and likely common reservoirs for, CDIs, particularly when epidemic strains are not dominant. PMID:27487436

  4. Prevention of Clostridium difficile Infection: A Systematic Survey of Clinical Practice Guidelines.

    PubMed

    Lytvyn, Lyubov; Mertz, Dominik; Sadeghirad, Behnam; Alaklobi, Faisal; Selva, Anna; Alonso-Coello, Pablo; Johnston, Bradley C

    2016-08-01

    BACKGROUND Clostridium difficile infection (CDI) is the most common cause of hospital-acquired infectious diarrhea. OBJECTIVE To analyze the methodological quality, content, and supporting evidence among clinical practice guidelines (CPGs) on CDI prevention. DESIGN AND SETTING We searched medical databases and gray literature for CPGs on CDI prevention published January 2004-January 2015. Three reviewers independently screened articles and rated CPG quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, composed of 23 items, rated 1-7, within 6 domains. We reported each domain score as a percentage of its maximum possible score and standardized range. We summarized recommendations, extracted their supporting articles, and rated individually the level of evidence using the Oxford Centre for Evidence-Based Medicine Levels of Evidence. RESULTS Of 2,578 articles screened, 5 guidelines met inclusion criteria. Median AGREE II scores and interquartile ranges were: clarity of presentation, 75.9% (75.9%-79.6%); scope and purpose, 74.1% (68.5%-85.2%); editorial independence, 63.9% (47.2%-66.7%); applicability, 43.1% (19.4%-55.6%); stakeholder involvement, 40.7% (38.9%-44.4%); and rigor of development, 18.1% (17.4%-35.4%). CPGs addressed several common strategies for CDI prevention, including antibiotic stewardship, hypochlorite solutions, probiotic prophylaxis, and bundle strategies. Recommendations were often not consistent with evidence, and most were based on low-level studies. CONCLUSION CPGs did not adhere well to AGREE II reporting standards. Furthermore, there was limited transparency in moving from evidence to recommendations. CDI prevention CPGs need to better adhere to AGREE-II and be transparent in moving from evidence to recommendations, and recommendations need to be consistent with available evidence. Infect Control Hosp Epidemiol 2016;37:901-908. PMID:27267201

  5. Storage Duration of Red Blood Cell Transfusion and Clostridium difficile Infection: A Within Person Comparison

    PubMed Central

    Rogers, Mary A. M.; Micic, Dejan; Blumberg, Neil; Young, Vincent B.; Aronoff, David M.

    2014-01-01

    Objective Randomized controlled trials demonstrated that red blood cell (RBC) transfusion elevates the risk of infection, and trials are underway to evaluate whether RBC storage affects outcomes. We previously reported that transfusion predicts Clostridium difficile infection (CDI) and, therefore, planned an investigation to examine this further using a more robust design. Design Within-person case-crossover study. Hospitalizations in which CDI developed (n = 406) were compared to hospitalizations for the same individuals in which CDI did not occur (n = 949). Transfusion volume and storage duration were assessed prior to the onset of CDI. Setting University of Michigan Health System. Patients Participants were individuals with a diagnosis of CDI from July 2009 through June 2012. Measurements and Main Results During the hospitalizations when CDI occurred, 34.7% of the patients received allogeneic RBC transfusions (mean volume, 688 ml) compared to 19.0% of patients in hospitalizations without CDI (mean volume, 180 ml). The odds of healthcare-associated CDI increased by 76% (95% CI 1.39–2.23) for every liter of RBCs transfused and was elevated in both nonsurgical (OR = 1.90) and surgical (OR = 1.86) hospitalizations. In patients who received RBC transfusions, the odds of developing CDI increased by 6% for every additional day of RBC stored and by 53% for every week of additional storage (P = 0.002). Conclusions Hospitalizations in which a patient received a greater volume of RBC transfusions were more likely to be associated with the development of CDI. RBC units stored for a longer duration were associated with the development of healthcare-associated CDI after adjustment for RBC volume. PMID:24586694

  6. Decreased Functional Status as a Risk Factor for Severe Clostridium difficile Infection among Hospitalized Older Adults

    PubMed Central

    Rao, Krishna; Micic, Dejan; Chenoweth, Elizabeth; Deng, Lili; Galecki, Andrzej T.; Ring, Cathrin; Young, Vincent B.; Aronoff, David M.; Malani, Preeti N.

    2013-01-01

    Background Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in hospitalized older adults, who are among the patients at highest risk of severe infection. The role of impaired functional status as a risk factor for severe CDI remains poorly understood. Design Prospective cohort study. Setting The University of Michigan Health System, a 930-bed tertiary care hospital. Participants Hospitalized patients with CDI, age ≥50 years. Measurements Included demographics; clinical characteristics; and a composite outcome, the CDI severity score: fever [T >38°C]; acute organ dysfunction; white blood cell count >15 000/mm3; lack of response to therapy; intensive care unit admission, need for colectomy, or death due to CDI. Pre-admission functional status was assessed by ability to perform activities of daily living (ADLs); patients were assigned to an ADL Class (independent, some assistance, or full assistance). Secondary outcomes included length of stay; 90-day mortality and readmission; and CDI recurrence. Results We identified 90 hospitalized patients with CDI (mean age 66.6 [± SD 10.2]). Fifty-eight patients (64.4%) had severe CDI as measured by a positive severity score. At baseline, 25 (27.8%) required assistance with ADLs. On univariate analysis, an ADL Class of “full assistance” was associated with severity score (OR 7, CI 95 1.83–26.79, P = .004). In a multivariable model which included age, ADL Class, congestive heart failure, diabetes mellitus, depression, weighted Charlson-Deyo comorbidity score, immunosuppression, prior CDI, and PPI use, an ADL Class of “full assistance” retained its association with severity score (OR 8.1, CI 95 1.24–52.95, P = .029). ADL Class was not associated with secondary outcomes. Conclusion Among this cohort of hospitalized older adults, impaired functional status was an independent risk factor for severe CDI. PMID:24083842

  7. Prospective study of Clostridium difficile infections in Europe with phenotypic and genotypic characterisation of the isolates.

    PubMed

    Barbut, F; Mastrantonio, P; Delmée, M; Brazier, J; Kuijper, E; Poxton, I

    2007-11-01

    A 2-month prospective study of Clostridium difficile infections was conducted in 38 hospitals from 14 different European countries in order to obtain an overview of the phenotypic and genotypic features of clinical isolates of C. difficile during 2005. Of 411 isolates from diarrhoeagenic patients with suspected C. difficile-associated diarrhoea (CDAD), 354 were toxigenic, of which 86 (24.3%) were toxin-variant strains. Major toxinotypes included toxinotypes 0 (n = 268), V (n = 28), VIII (n = 22) and III (n = 25). MICs of metronidazole, vancomycin, erythromycin, clindamycin, moxifloxacin and tetracycline were determined using the Etest method. All the toxigenic strains were fully-susceptible to metronidazole and vancomycin. Resistance to erythromycin, clindamycin, tetracycline and moxifloxacin was found in 44.4%, 46.1%, 9.2% and 37.5% of the isolates, respectively. Sixty-six different PCR ribotypes were characterised, with the 027 epidemic strain accounting for 6.2% of isolates. This strain was positive for binary toxin genes, had an 18-bp deletion in the tcdC gene, and was resistant to both erythromycin and moxifloxacin. The mean incidence of CDAD was 2.45 cases/10 000 patient-days, but this figure varied widely among the participating hospitals. Patients infected with the 027 strain were more likely to have a severe disease (OR 3.29, 95% CI 1.19-9.16, p 0.008) and to have been specifically treated with metronidazole or vancomycin (OR 7.46, 95% CI 1.02-154, p 0.02). Ongoing epidemiological surveillance of cases of CDAD, with periodic characterisation of the strains involved, is required to detect clustering of cases in time and space and to monitor the emergence of specific highly virulent clones. PMID:17850341

  8. Clostridium difficile infection diagnosis in a paediatric population: comparison of methodologies.

    PubMed

    Hart, J; Putsathit, P; Knight, D R; Sammels, L; Riley, T V; Keil, A

    2014-09-01

    The increasing incidence of Clostridium difficile infection (CDI) in paediatric hospitalised populations, combined with the emergence of hypervirulent strains, community-acquired CDI and the need for prompt treatment and infection control, makes the rapid, accurate diagnosis of CDI crucial. We validated commonly used C. difficile diagnostic tests in a paediatric hospital population. From October 2011 to January 2012, 150 consecutive stools were collected from 75 patients at a tertiary paediatric hospital in Perth, Western Australia. Stools were tested using: C. Diff Quik Chek Complete, Illumigene C. difficile, GeneOhm Cdiff, cycloserine cefoxitin fructose agar (CCFA) culture, and cell culture cytotoxin neutralisation assay (CCNA). The reference standard was growth on CCFA or Cdiff Chromagar and PCR on isolates to detect tcdA, tcdB, cdtA, and cdtB. Isolates were PCR ribotyped. The prevalence of CDI was high (43 % of patients). Quik Chek Complete glutamate dehydrogenase (GDH) demonstrated a low negative predictive value (NPV) (93 %). Both CCNA and Quik Chek Complete toxin A/B had poor sensitivity (33 % and 29 % respectively). Molecular methods both had 89 % sensitivity. Algorithms using GDH + Illumigene or GeneOhm reduced the sensitivity to 85 % and 83 % respectively. Ribotype UK014/20 predominated. GDH NPV and GeneOhm and Illumigene sensitivities were reduced compared with adult studies. Quik Chek Complete and CCNA cannot reliably detect toxigenic CDI. A GDH first algorithm showed reduced sensitivity. In a high prevalence paediatric population, molecular methods alone are recommended over the use of GDH algorithm or culture and CCNA, as they demonstrate the best test performance characteristics. PMID:24781004

  9. Association Between Outpatient Antibiotic Prescribing Practices and Community-Associated Clostridium difficile Infection

    PubMed Central

    Dantes, Raymund; Mu, Yi; Hicks, Lauri A.; Cohen, Jessica; Bamberg, Wendy; Beldavs, Zintars G.; Dumyati, Ghinwa; Farley, Monica M.; Holzbauer, Stacy; Meek, James; Phipps, Erin; Wilson, Lucy; Winston, Lisa G.; McDonald, L. Clifford; Lessa, Fernanda C.

    2015-01-01

    Background. Antibiotic use predisposes patients to Clostridium difficile infections (CDI), and approximately 32% of these infections are community-associated (CA) CDI. The population-level impact of antibiotic use on adult CA-CDI rates is not well described. Methods. We used 2011 active population- and laboratory-based surveillance data from 9 US geographic locations to identify adult CA-CDI cases, defined as C difficile-positive stool specimens (by toxin or molecular assay) collected from outpatients or from patients ≤3 days after hospital admission. All patients were surveillance area residents and aged ≥20 years with no positive test ≤8 weeks prior and no overnight stay in a healthcare facility ≤12 weeks prior. Outpatient oral antibiotic prescriptions dispensed in 2010 were obtained from the IMS Health Xponent database. Regression models examined the association between outpatient antibiotic prescribing and adult CA-CDI rates. Methods. Healthcare providers prescribed 5.2 million courses of antibiotics among adults in the surveillance population in 2010, for an average of 0.73 per person. Across surveillance sites, antibiotic prescription rates (0.50–0.88 prescriptions per capita) and unadjusted CA-CDI rates (40.7–139.3 cases per 100 000 persons) varied. In regression modeling, reducing antibiotic prescribing rates by 10% among persons ≥20 years old was associated with a 17% (95% confidence interval, 6.0%–26.3%; P = .032) decrease in CA-CDI rates after adjusting for age, gender, race, and type of diagnostic assay. Reductions in prescribing penicillins and amoxicillin/clavulanic acid were associated with the greatest decreases in CA-CDI rates. Conclusions and Relevance. Community-associated CDI prevention should include reducing unnecessary outpatient antibiotic use. A modest reduction of 10% in outpatient antibiotic prescribing can have a disproportionate impact on reducing CA-CDI rates. PMID:26509182

  10. Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients.

    PubMed

    Webb, B J; Brunner, A; Ford, C D; Gazdik, M A; Petersen, F B; Hoda, D

    2016-08-01

    Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor-derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25-75 interquartile range [IQR] 38-791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long-term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso-jejunal route in 6 of the 7 patients. Mean follow-up was 265 days (IQR 51-288). Minor post-FMT adverse effects included self-limited bloating and urgency. One patient was suspected of having post-FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all-cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft-versus-host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects. PMID:27214585

  11. Environmental Contamination in Households of Patients with Recurrent Clostridium difficile Infection.

    PubMed

    Shaughnessy, Megan K; Bobr, Aleh; Kuskowski, Michael A; Johnston, Brian D; Sadowsky, Michael J; Khoruts, Alexander; Johnson, James R

    2016-05-01

    Recurrent Clostridium difficile infection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). Although C. difficilespores persist in the hospital environment and cause infection, little is known about their potential presence or importance in the household environment. Households of R-CDI subjects in the peri-FMT period and of geographically matched and age-matched controls were analyzed for the presence ofC. difficile Household environmental surfaces and fecal samples from humans and pets in the household were examined. Households of post-FMT subjects were also examined (environmental surfaces only). Participants were surveyed regarding their personal history and household cleaning habits. Species identity and molecular characteristics of presumptive C. difficile isolates from environmental and fecal samples were determined by using the Pro kit (Remel, USA), Gram staining, PCR, toxinotyping, tcdC gene sequencing, and pulsed-field gel electrophoresis (PFGE). Environmental cultures detected C. difficile on ≥1 surface in 8/8 (100%) peri-FMT households, versus 3/8 (38%) post-FMT households and 3/8 (38%) control households (P= 0.025). The most common C. difficile-positive sites were the vacuum (11/27; 41%), toilet (8/30; 27%), and bathroom sink (5/29; 17%).C. difficile was detected in 3/36 (8%) fecal samples (two R-CDI subjects and one household member). Nine (90%) of 10 households with multiple C. difficile-positive samples had a single genotype present each. In conclusion,C. difficile was found in the household environment of R-CDI patients, but whether it was found as a cause or consequence of R-CDI is unknown. If household contamination leads to R-CDI, effective decontamination may be protective. PMID:26921425

  12. Risk Factors for Recurrence, Complications and Mortality in Clostridium difficile Infection: A Systematic Review

    PubMed Central

    Abou Chakra, Claire Nour; Pepin, Jacques; Sirard, Stephanie; Valiquette, Louis

    2014-01-01

    Background Clostridium difficile infection (CDI) can lead to complications, recurrence, and death. Numerous studies have assessed risk factors for these unfavourable outcomes, but systematic reviews or meta-analyses published so far were limited in scope or in quality. Methods A systematic review was completed according to PRISMA guidelines. An electronic search in five databases was performed. Studies published until October 2013 were included if risk factors for at least one CDI outcome were assessed with multivariate analyses. Results 68 studies were included: 24 assessed risk factors for recurrence, 18 for complicated CDI, 8 for treatment failure, and 30 for mortality. Most studies accounted for mortality in the definition of complicated CDI. Important variables were inconsistently reported, such as previous episodes and use of antibiotics. Substantial heterogeneity and methodological limitations were noted, mainly in the sample size, the definition of the outcomes and periods of follow-up, precluding a meta-analysis. Older age, use of antibiotics after diagnosis, use of proton pump inhibitors, and strain type were the most frequent risk factors for recurrence. Older age, leucocytosis, renal failure and co-morbidities were frequent risk factors for complicated CDI. When considered alone, mortality was associated with age, co-morbidities, hypo-albuminemia, leucocytosis, acute renal failure, and infection with ribotype 027. Conclusion Laboratory parameters currently used in European and American guidelines to define patients at risk of a complicated CDI are adequate. Strategies for the management of CDI should be tailored according to the age of the patient, biological markers of severity, and underlying co-morbidities. PMID:24897375

  13. Microbiota Dynamics in Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

    PubMed Central

    Song, Yang; Garg, Shashank; Girotra, Mohit; Maddox, Cynthia; von Rosenvinge, Erik C.; Dutta, Anand; Dutta, Sudhir; Fricke, W. Florian

    2013-01-01

    Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) is an alternate treatment option for recurrent C. difficile infection (RCDI) refractory to antibiotic therapy. It has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health consequences of FMT remain a concern, as the effects of the transplanted microbiota on the patient remain unknown. To shed light on microbial events associated with RCDI and treatment by FMT, we performed fecal microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of healthy donors and RCDI patients treated successfully by FMT. Post-FMT patient and healthy donor samples collected up to one year after FMT were studied longitudinally, including one post-FMT patient with antibiotic-associated relapse three months after FMT. This analysis allowed us not only to confirm prior reports that RCDI is associated with reduced diversity and compositional changes in the fecal microbiota, but also to characterize previously undocumented post-FMT microbiota dynamics. Members of the Streptococcaceae, Enterococcaceae, or Enterobacteriaceae were significantly increased and putative butyrate producers, such as Lachnospiraceae and Ruminococcaceae were significantly reduced in samples from RCDI patients before FMT as compared to post-FMT patient and healthy donor samples. RCDI patient samples showed more case-specific variations than post-FMT patient and healthy donor samples. However, none of the bacterial groups were invariably associated with RCDI or successful treatment by FMT. Overall microbiota compositions in post-FMT patients, specifically abundances of the above-mentioned Firmicutes, continued to change for at least 16 weeks after FMT, suggesting that full microbiota

  14. Clostridium difficile Infections in Veterans Health Administration Long-Term Care Facilities.

    PubMed

    Reeves, Jeffrey S; Evans, Martin E; Simbartl, Loretta A; Kralovic, Stephen M; Kelly, Allison A; Jain, Rajiv; Roselle, Gary A

    2016-03-01

    OBJECTIVE A nationwide initiative was implemented in February 2014 to decrease Clostridium difficile infections (CDI) in Veterans Affairs (VA) long-term care facilities. We report a baseline of national CDI data collected during the 2 years before the Initiative. METHODS Personnel at each of 122 reporting sites entered monthly retrospective CDI case data from February 2012 through January 2014 into a national database using case definitions similar to those used in the National Healthcare Safety Network Multidrug-Resistant Organism/CDI module. The data were evaluated using Poisson regression models to examine infection occurrences over time while accounting for admission prevalence and type of diagnostic test. RESULTS During the 24-month analysis period, there were 100,800 admissions, 6,976,121 resident days, and 1,558 CDI cases. The pooled CDI admission prevalence rate (including recurrent cases) was 0.38 per 100 admissions, and the pooled nonduplicate/nonrecurrent community-onset rate was 0.17 per 100 admissions. The pooled long-term care facility-onset rate and the clinically confirmed (ie, diarrhea or evidence of pseudomembranous colitis) long-term care facility-onset rate were 1.98 and 1.78 per 10,000 resident days, respectively. Accounting for diagnostic test type, the long-term care facility-onset rate declined significantly (P=.05), but the clinically confirmed long-term care facility-onset rate did not. CONCLUSIONS VA long-term care facility CDI rates were comparable to those in recent reports from other long-term care facilities. The significant decline in the long-term care facility-onset rate but not in the clinically confirmed long-term care facility-onset rate may have been due to less testing of asymptomatic patients. Efforts to decrease CDI rates in long-term care facilities are necessary as part of a coordinated approach to decrease healthcare-associated infections. Infect. Control Hosp. Epidemiol. 2016;37(3):295-300. PMID:26686361

  15. Performance management of Clostridium difficile infection in hospitals - The carrot or stick approach?

    PubMed

    Fitzpatrick, Fidelma; Riordan, Mary O

    2016-02-01

    Public and political pressure for healthcare quality indicator monitoring, specifically healthcare-associated infection (HAI) has intensified the debate regarding the merits of public reporting and target setting as policy approaches. This paper reviews the evidence for these approaches with a focus on HAI, including Clostridium difficile infection (CDI). Healthcare key performance indicators (KPIs) and associated targets have been used widely with little evaluation. While targets are associated with some HAI reductions including CDI, as their control is multi-factorial, it is likely that reductions are due to numerous, concurrent control measures. Targets may help tackle organizational-wide issues that require high level management engagement and have contributed to the increased access and influence of infection control teams. HAI public reporting has also gained traction and is mandatory in many countries despite little scientific evaluation. CDI is one of the KPIs used but there is little consensus as to the best KPI for public reporting. Countries without public reporting have also seen improvements. Using indicator-based strategies rather than evidence-based ones risk improving the KPI but not necessarily quality of care. 'Bottom-up' approaches focussing on quality improvement and innovation generated by front line staff are seen as a lever for sustainable change. Positive deviance, where the resourcefulness and problem solving abilities of staff is harnessed, enables 'bottom-up' changes with process and outcome improvements. As implementation of best practice in healthcare is dependent on behavioural and cultural change, it is most likely that a combination of 'top-down' and 'bottom-up' approaches are required for sustainable improvement. This combined approach was used to improve staff influenza vaccination rates. Regulation may initially direct the spot-light onto infection control needs but true sustainable HAI reduction will only be fostered with

  16. Hospital Clostridium difficile Infection Rates and Prediction of Length of Stay in Patients Without C. difficile Infection.

    PubMed

    Miller, Aaron C; Polgreen, Linnea A; Cavanaugh, Joseph E; Polgreen, Philip M

    2016-04-01

    BACKGROUND Inpatient length of stay (LOS) has been used as a measure of hospital quality and efficiency. Patients with Clostridium difficile infections (CDI) have longer LOS. OBJECTIVE To describe the relationship between hospital CDI incidence and the LOS of patients without CDI. DESIGN Retrospective cohort analysis. METHODS We predicted average LOS for patients without CDI at both the hospital and patient level using hospital CDI incidence. We also controlled for hospital characteristics (eg, bed size) and patient characteristics (eg, comorbidities, age). SETTING Healthcare Cost and Utilization Project Nationwide Inpatient Sample, 2009-2011. PATIENTS The Nationwide Inpatient Sample includes patients from a 20% sample of all nonfederal US hospitals. RESULTS Inpatient LOS was significantly longer (P<.001) at hospitals with greater CDI incidence at both the hospital and individual level. At a hospital level, a percentage point increase in the CDI incidence rate was associated with more than an additional day's stay (between 1.19 and 1.61 days). At the individual level, controlling for all observable variables, a percentage point increase in the CDI incidence rate at their hospital was also associated with longer LOS (between 0.6 and 1.05 additional days). Hospital CDI incidence had a larger impact on LOS than many other commonly used predictors of LOS. CONCLUSION CDI rates are a predictor of LOS in patients without CDI at an individual and institutional level. CDI rates are easy to measure and report and thus may provide an important marker for hospital efficiency and/or quality. Infect. Control Hosp. Epidemiol. 2016;37(4):404-410. PMID:26858126

  17. Antimicrobial Resistance and Reduced Susceptibility in Clostridium difficile: Potential Consequences for Induction, Treatment, and Recurrence of C. difficile Infection

    PubMed Central

    Baines, Simon D.; Wilcox, Mark H.

    2015-01-01

    Clostridium difficile infection (CDI) remains a substantial burden on healthcare systems and is likely to remain so given our reliance on antimicrobial therapies to treat bacterial infections, especially in an aging population in whom multiple co-morbidities are common. Antimicrobial agents are a key component in the aetiology of CDI, both in the establishment of the infection and also in its treatment. The purpose of this review is to summarise the role of antimicrobial agents in primary and recurrent CDI; assessing why certain antimicrobial classes may predispose to the induction of CDI according to a balance between antimicrobial activity against the gut microflora and C. difficile. Considering these aspects of CDI is important in both the prevention of the infection and in the development of new antimicrobial treatments. PMID:27025625

  18. Fidaxomicin: A novel agent for the treatment of Clostridium difficile infection

    PubMed Central

    Zhanel, George G; Walkty, Andrew J; Karlowsky, James A

    2015-01-01

    BACKGROUND: Due to the limitations of existing treatment options for Clostridium difficile infection (CDI), new therapies are needed. OBJECTIVE: To review the available data on fidaxomicin regarding chemistry, mechanisms of action and resistance, in vitro activity, pharmacokinetic and pharmacodynamic properties, efficacy and safety in clinical trials, and place in therapy. METHODS: A search of PubMed using the terms “fidaxomicin”, “OPT-80”, “PAR-101”, “OP-1118”, “difimicin”, “tiacumicin” and “lipiarmycin” was performed. All English-language articles from January 1983 to November 2014 were reviewed, as well as bibliographies of all articles. RESULTS: Fidaxomicin is the first macrocyclic lactone antibiotic with activity versus C difficile. It inhibits RNA polymerase, therefore, preventing transcription. Fidaxomicin (and its active metabolite OP-1118) is bactericidal against C difficile and exhibits a prolonged postantibiotic effect (approximately 10 h). Other than for C difficile, fidaxomicin demonstrated only moderate inhibitory activity against Gram-positive bacteria and was a poor inhibitor of normal colonic flora, including anaerobes and enteric Gram-negative bacilli. After oral administration (200 mg two times per day for 10 days), fidaxomicin achieved low serum concentration levels but high fecal concentration levels (mean approximately 1400 μg/g stool). Phase 3 clinical trials involving adults with CDI demonstrated that 200 mg fidaxomicin twice daily for 10 days was noninferior to 125 mg oral vancomycin four times daily for 10 days in regard to clinical response at the end of therapy. Fidaxomicin was, however, reported to be superior to oral vancomycin in reducing recurrent CDI and achieving a sustained clinical response (assessed at day 28) for patients infected with non-BI/NAP1/027 strains. CONCLUSION: Fidaxomicin was noninferior to oral vancomycin with regard to clinical response at the end of CDI therapy. Fidaxomicin has been

  19. [Oncologic aspects of Clostridium difficile].

    PubMed

    Telekes, András

    2016-07-01

    Clostridium difficile infection is one of the most frequent among cancer patients. Its diagnosis is complicated by the fact that the symptoms of the infection and the side effects of the anticancer treatments could be similar. Chemotherapy itself might facilitate Clostridium difficile infection. Several risk factors are known but Clostridium difficile infection can develop in the absence of these. Neutreopenia is a risk factor for fatal Clostridium difficile infection and also the side effect of chemotherapy. Therefore, if symptoms of the potential infection develop (eg. diarrhoea more than three times a day, fever above 38.5 °C, colitis, rapid increase of serum creatinin) Clostridium difficile infection should be excluded. If the infection is confirmed it should be managed in the most efficient way. Orv. Hetil., 2016, 157(28), 1110-1116. PMID:27397423

  20. Calprotectin and lactoferrin faecal levels in patients with Clostridium difficile infection (CDI): a prospective cohort study.

    PubMed

    Swale, Andrew; Miyajima, Fabio; Roberts, Paul; Hall, Amanda; Little, Margaret; Beadsworth, Mike B J; Beeching, Nick J; Kolamunnage-Dona, Ruwanthi; Parry, Chris M; Pirmohamed, Munir

    2014-01-01

    Measurement of both calprotectin and lactoferrin in faeces has successfully been used to discriminate between functional and inflammatory bowel conditions, but evidence is limited for Clostridium difficile infection (CDI). We prospectively recruited a cohort of 164 CDI cases and 52 controls with antibiotic-associated diarrhoea (AAD). Information on disease severity, duration of symptoms, 30-day mortality and 90-day recurrence as markers of complicated CDI were recorded. Specimens were subject to microbiological culture and PCR-ribotyping. Levels of faecal calprotectin (FC) and lactoferrin (FL) were measured by ELISA. Statistical analysis was conducted using percentile categorisation. ROC curve analysis was employed to determine optimal cut-off values. Both markers were highly correlated with each other (r2 = 0.74) and elevated in cases compared to controls (p<0.0001; ROC>0.85), although we observed a large amount of variability across both groups. The optimal case-control cut-off point was 148 mg/kg for FC and 8.1 ng/µl for FL. Median values for FL in CDI cases were significantly greater in patients suffering from severe disease compared to non-severe disease (104.6 vs. 40.1 ng/µl, p = 0.02), but were not significant for FC (969.3 vs. 512.7 mg/kg, p = 0.09). Neither marker was associated with 90-day recurrence, prolonged CDI symptoms, positive culture results and colonisation by ribotype 027. Both FC and FL distinguished between CDI cases and AAD controls. Although FL was associated with disease severity in CDI patients, this showed high inter-individual variability and was an isolated finding. Thus, FC and FL are unlikely to be useful as biomarkers of complicated CDI disease. PMID:25170963

  1. Epidemiology and Outcomes of Clostridium difficile Infections in Hematopoietic Stem Cell Transplant Recipients

    PubMed Central

    Alonso, Carolyn D.; Treadway, Suzanne B.; Hanna, David B.; Huff, Carol Ann; Neofytos, Dionissios; Carroll, Karen C.

    2012-01-01

    Background. Clostridium difficile is the leading cause of infectious diarrhea among hospitalized patients and is a major concern for patients undergoing hematopoietic stem cell transplantation (HSCT). Risk factors and the natural history of C. difficile infection (CDI) are poorly understood in this population. Methods. We performed a retrospective nested case-control study to describe the epidemiology, timing, and risk factors for CDI among adult patients who received HSCTs at our center from January 2003 through December 2008. Results. The overall 1-year incidence of CDI was 9.2% among HSCTs performed (n = 999). The median time to diagnosis of CDI was short among both autologous and allogeneic HSCT recipients (6.5 days and 33 days, respectively). Risk factors for CDI in allogeneic HSCT recipients included receipt of chemotherapy prior to conditioning for HSCT, broad-spectrum antimicrobial use, and acute graft-versus-host disease (GVHD; adjusted odds ratio [AOR], 4.45; 95% confidence interval [CI], 1.54–12.84; P = .006). There was a strong relationship between early CDI and subsequent development of gastrointestinal tract GVHD in the year following allogeneic HSCT (P < .001). Gastrointestinal GVHD was also strongly associated with an increased risk for recurrent CDI (AOR, 4.23 [95% CI, 1.20–14.86]; P = .02). Conclusions. These results highlight the high incidence and early timing of CDI after HSCT. Early timing, coupled with the noted risk of pretransplant chemotherapy, suggests that the natural history of disease in some patients may involve colonization prior to HSCT. A potentially important interplay between CDI and GVHD involving the gastrointestinal tract was observed. PMID:22412059

  2. Association between Clostridium difficile infection and antimicrobial usage in a large group of English hospitals

    PubMed Central

    Pereira, Joao B; Farragher, Tracey M; Tully, Mary P; Cooke, Jonathan

    2014-01-01

    Aims This study aimed to determine the association between the reduction in the number of Clostridium difficile infection (CDI) cases reported by the English National Health Service (NHS) hospitals and concurrent antimicrobial use. Methods A retrospective ecological study for January 2005 to December 2008 was conducted using data from 26 of the 29 NHS trusts (i.e. a trust manages one or more hospitals) located in the North West Strategic Health Authority of England. Antimicrobial use data, for patients of all ages, were provided by IMS Health, and CDI case data for patients aged ≥65 years were provided by the Health Protection Agency. Antimicrobial use was converted into defined daily doses (DDDs). The overall association between antimicrobial use and CDI for the trusts was investigated using multilevel models. Results Our study shows a positive significant association between the CDI cases and the use of the following antimicrobials: ‘third-generation cephalosporins’ [11.62 CDI cases per 1000 DDDs; 95% confidence interval (CI), 5.92–17.31]; ‘fluoroquinolones’ (4.79 CDI cases per 1000 DDDs; 95% CI, 2.83–6.74); and ‘second-generation cephalosporins’ (4.25 CDI cases per 1000 DDDs; 95% CI, 1.66–6.83). The strength of this association was not significantly different (95% CI) among the antimicrobial groups. Conclusions This study shows that the reduction in the number of CDI cases reported by the English NHS hospitals is associated with concurrent reductions in antimicrobial use. This means that the number of CDI cases over time decreased in a similar fashion to the usage of various antimicrobials. PMID:24868578

  3. The effect of polydextrose and probiotic lactobacilli in a Clostridium difficile–infected human colonic model

    PubMed Central

    Forssten, Sofia D.; Röytiö, Henna; Hibberd, Ashley A.; Ouwehand, Arthur C.

    2015-01-01

    Background Clostridium difficile is a natural resident of the intestinal microbiota; however, it becomes harmful when the normal intestinal microbiota is disrupted, and overgrowth and toxin production occurs. The toxins can cause bloating and diarrhoea, which may cause severe disease and have the potential to cause outbreaks in hospitals and other healthcare settings. Normally, antibiotic agents are used for treatment, although for some of the patients, these treatments provide only a temporary relief with a recurrence of C. difficile–associated diarrhoea. Objective The effects of polydextrose (PDX), Lactobacillus acidophilus NCFM, and L. paracasei Lpc-37 on the growth of C. difficile were investigated in an in vitro model of infected human large intestine. Design The semi-continuous colonic model is composed of four connected vessels inoculated with human faecal microbes and spiked with pathogenic C. difficile (DSM 1296). PDX in two concentrations (2 and 4%), NCFM, and Lpc-37 were fed to the system during the 2-day simulation, and the growth of C. difficile and several other microbial groups were monitored using quantitative polymerase chain reaction (qPCR) and 16S rDNA sequencing. Results The microbial community structure of the simulation samples was closely grouped according to treatment, and the largest shifts in the microbial composition were seen with PDX. The microbial diversity decreased significantly with 4% PDX, and the OTU containing C. difficile was significantly (p<0.01) decreased when compared to control and lactobacilli treatments. The mean numbers of C. difficile also decreased as detected by qPCR, although the reduction did not reach statistical significance. Conclusions The treatments influenced the colonic microbiota, and a trend for reduced numbers of C. difficile as well as alterations of several microbial groups could be detected. This suggests that PDX may be able to modulate the composition and/or function of the colonic microbiota in

  4. Minimal systemic and high faecal exposure to cadazolid in patients with severe Clostridium difficile infection.

    PubMed

    Gehin, Martine; Desnica, Boško; Dingemanse, Jasper

    2015-11-01

    Cadazolid is under development as an oral treatment for Clostridium difficile infection (CDI), which is the most common infectious cause of antibiotic-associated diarrhoea. Low systemic cadazolid exposures were previously reported in healthy subjects following both single and multiple oral dosing. The main objective of this study was to investigate systemic cadazolid exposure in patients with severe CDI with potential disrupted lining of the gastrointestinal tract. A single 3000 mg oral dose of cadazolid was administered to six patients with microbiologically-confirmed severe CDI. Plasma and faeces were collected up to 144 h post-dose for determination of cadazolid concentrations. Safety assessments were conducted over the 144-h investigational period. Cadazolid was well tolerated in patients with severe CDI, with no reported drug-related adverse events. Cadazolid systemic exposure following a single 3000 mg oral dose was very low, with a peak plasma concentration (C(max)) of 2.64 ng/mL and an area under the concentration-time curve (AUC(0-144)) of 125 ng×h/mL. The median peak daily faecal cadazolid concentration was 5675 times the C. difficile MIC(90) of 0.25 mg/L. In subjects with severe CDI, cadazolid systemic exposure was very low following a single high oral dose. Cadazolid plasma concentrations were similar in magnitude to those previously reported for healthy subjects, whereas total systemic exposure was ca. 5-6 times higher, but was still low. Peak daily faecal cadazolid concentrations were 5675 times the 0.25 mg/L C. difficile MIC(90), and on Day 4 five of the six patients presented a daily faecal cadazolid concentration ≥1651 times the MIC(90) [ClinicalTrial.gov ID: NCT02053181]. PMID:26419191

  5. Clostridium difficile Infection in Hospitalized Liver Transplant Patients: A Nationwide Analysis

    PubMed Central

    Ali, Muhammad; Ananthakrishnan, Ashwin N.; Ahmad, Shahryar; Kumar, Nilay; Kumar, Gagan; Saeian, Kia

    2012-01-01

    Introduction Incidence of Clostridium difficile infection (CDI) is increasing among hospitalized patients. Liver transplant patients are at higher risk for acquiring CDI. Small, single-center studies, but no nation-wide analyses, have assessed this association. Methods We used the Healthcare Cost and Utilization Project- Nationwide Inpatient Sample (HCUP-NIS) from years 2004–2008 for this retrospective cross sectional study. Patients with any discharge diagnosis of liver transplant comprised the study population and were identified using ICD-9-CM codes. Those with a discharge diagnosis of CDI were considered cases. Our primary outcomes were prevalence of CDI and effect of CDI on inpatient mortality. Our secondary outcomes included length of stay and hospitalization charges. Regression analysis was used to derive odds ratios adjusted for potential confounders. Results There were 193,714 discharges with a diagnosis of liver transplant from 2004–2008. Prevalence of CDI was 2.7% in liver transplant population compared to 0.9% in non liver transplant population (p <0.001). Most of the liver transplant patients were in the 50–64 age group. Liver transplant patients were at higher odds of developing CDI (OR 2.88, 95% CI 2.68–3.10). Increasing age, increasing comorbidity, IBD and NG tube placement were also independent risk factors for CDI. CDI in liver transplant was associated with a higher mortality, 5.5% as compared to 2.3% in liver transplant only population (adjusted OR 1.7, 95% CI 1.3–2.2). Conclusions Liver transplant patients have a higher prevalence of CDI as compared to non liver transplant patients (2.7% vs. 0.9%).CDI was an independent risk factor for mortality in liver transplant population. PMID:22505356

  6. Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With Recurrent Clostridium difficile Infection

    PubMed Central

    Millan, Braden; Park, Heekuk; Hotte, Naomi; Mathieu, Olivier; Burguiere, Pierre; Tompkins, Thomas A.; Kao, Dina; Madsen, Karen L.

    2016-01-01

    Background. Recurrent Clostridium difficile infection (RCDI) is associated with repeated antibiotic treatment and the enhanced growth of antibiotic-resistant microbes. This study tested the hypothesis that patients with RCDI would harbor large numbers of antibiotic-resistant microbes and that fecal microbiota transplantation (FMT) would reduce the number of antibiotic-resistant genes. Methods. In a single center study, patients with RCDI (n = 20) received FMT from universal donors via colonoscopy. Stool samples were collected from donors (n = 3) and patients prior to and following FMT. DNA was extracted and shotgun metagenomics performed. Results as well as assembled libraries from a healthy cohort (n = 87) obtained from the Human Microbiome Project were aligned against the NCBI bacterial taxonomy database and the Comprehensive Antibiotic Resistance Database. Results were corroborated through a DNA microarray containing 354 antibiotic resistance (ABR) genes. Results. RCDI patients had a greater number and diversity of ABR genes compared with donors and healthy controls. Beta-lactam, multidrug efflux pumps, fluoroquinolone, and antibiotic inactivation ABR genes were increased in RCDI patients, although donors primarily had tetracycline resistance. RCDI patients were dominated by Proteobacteria with Escherichia coli and Klebsiella most prevalent. FMT resulted in a resolution of symptoms that correlated directly with a decreased number and diversity of ABR genes and increased Bacteroidetes and Firmicutes with reduced Proteobacteria. ABR gene profiles were maintained in recipients for up to a year following FMT. Conclusions. RCDI patients have increased numbers of antibiotic-resistant organisms. FMT is effective in the eradication of pathogenic antibiotic-resistant organisms and elimination of ABR genes. PMID:27025836

  7. Cost-Effectiveness Analysis of Six Strategies to Treat Recurrent Clostridium difficile Infection

    PubMed Central

    Lapointe-Shaw, Lauren; Tran, Kim L.; Coyte, Peter C.; Hancock-Howard, Rebecca L.; Powis, Jeff; Poutanen, Susan M.; Hota, Susy

    2016-01-01

    Objective To assess the cost-effectiveness of six treatment strategies for patients diagnosed with recurrent Clostridium difficile infection (CDI) in Canada: 1. oral metronidazole; 2. oral vancomycin; 3.oral fidaxomicin; 4. fecal transplantation by enema; 5. fecal transplantation by nasogastric tube; and 6. fecal transplantation by colonoscopy. Perspective Public insurer for all hospital and physician services. Setting Ontario, Canada. Methods A decision analytic model was used to model costs and lifetime health effects of each strategy for a typical patient experiencing up to three recurrences, over 18 weeks. Recurrence data and utilities were obtained from published sources. Cost data was obtained from published sources and hospitals in Toronto, Canada. The willingness-to-pay threshold was $50,000/QALY gained. Results Fecal transplantation by colonoscopy dominated all other strategies in the base case, as it was less costly and more effective than all alternatives. After accounting for uncertainty in all model parameters, there was an 87% probability that fecal transplantation by colonoscopy was the most beneficial strategy. If colonoscopy was not available, fecal transplantation by enema was cost-effective at $1,708 per QALY gained, compared to metronidazole. In addition, fecal transplantation by enema was the preferred strategy if the probability of recurrence following this strategy was below 8.7%. If fecal transplantation by any means was unavailable, fidaxomicin was cost-effective at an additional cost of $25,968 per QALY gained, compared to metronidazole. Conclusion Fecal transplantation by colonoscopy (or enema, if colonoscopy is unavailable) is cost-effective for treating recurrent CDI in Canada. Where fecal transplantation is not available, fidaxomicin is also cost-effective. PMID:26901316

  8. Comparison of real-time PCR techniques to cytotoxigenic culture methods for diagnosing Clostridium difficile infection.

    PubMed

    Knetsch, C W; Bakker, D; de Boer, R F; Sanders, I; Hofs, S; Kooistra-Smid, A M D; Corver, J; Eastwood, K; Wilcox, M H; Kuijper, E J

    2011-01-01

    In the past decade, the incidence of Clostridium difficile infections (CDI) with a more severe course has increased in Europe and North America. Assays that are capable of rapidly diagnosing CDI are essential. Two real-time PCRs (LUMC and LvI) targeting C. difficile toxin genes (tcdB, and tcdA and tcdB, respectively) were compared with the BD GeneOhm PCR (targeting the tcdB gene), using cytotoxigenic culture as a gold standard. In addition, a real-time PCR targeting the tcdC frameshift mutation at position 117 (Δ117 PCR) was evaluated for detecting toxigenic C. difficile and the presence of PCR ribotype 027 in stool samples. In total, 526 diarrheal samples were prospectively collected and included in the study. Compared with those for cytotoxigenic culture, sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were for PCR LUMC 96.0%, 88.0%, 66.0%, and 98.9%, for PCR LvI 100.0%, 89.4%, 69.7%, and 100.0%, for PCR Δ117 98.0%, 90.7%, 71.9%, and 99.5%, and for PCR BD GeneOhm 88.3%, 96.9%, 86.5%, and 97.4%. Compared to those with feces samples cultured positive for C. difficile type 027, the sensitivity, specificity, PPV, and NPV of the Δ117 PCR were 95.2%, 96.2%, 87.0%, and 98.7%. We conclude that all real-time PCRs can be applied as a first screening test in an algorithm for diagnosing CDI. However, the low PPVs hinder the use of the assays as stand-alone tests. Furthermore, the Δ117 PCR may provide valuable information for minimizing the spread of the epidemic C. difficile PCR ribotype 027. PMID:20980562

  9. Epidemiology, outcomes, and predictors of mortality in hospitalized adults with Clostridium difficile infection.

    PubMed

    Khanna, Sahil; Gupta, Arjun; Baddour, Larry M; Pardi, Darrell S

    2016-08-01

    Studies have demonstrated an increasing Clostridium difficile infection (CDI) incidence in hospitals and the community, with increasing morbidity and mortality. In this study, we analyzed data from the National Hospital Discharge Survey (NHDS) to evaluate CDI epidemiology, outcomes, and predictors of mortality in hospitalized adults. We identified cases of CDI (and associated comorbid conditions) from NHDS data from 2005 through 2009 using ICD-9 codes. Weighted univariate and multivariate analyses were performed to ascertain CDI incidence, associations between CDI and outcomes [length of stay (LOS), colectomy, all-cause in-hospital mortality, and discharge to a care facility], and predictors of all-cause in-hospital mortality. Of an estimated 162 million adult inpatients, 1.26 million (0.8 %) had CDI. The overall CDI incidence is 77.8/10,000 hospitalizations, with no statistically significant change over the study period. On multivariate analysis, after adjusting for age, gender, and comorbid conditions, CDI is an independent predictor of longer LOS (mean difference, 2.35 days), all-cause mortality [odds ratio (OR) 1.45], colectomy (OR 1.41), and discharge to a care facility (OR 2.12) (all P < 0.001). Elderly patients have a higher CDI incidence and worse outcomes than younger adults. The strongest predictors of all-cause mortality in patients with CDI include age 65 years or older, colectomy, and coagulation abnormalities. Despite stable CDI incidence and advances in management, CDI is associated with increased LOS, colectomy, all-cause in-hospital mortality, and discharge to a care facility in hospitalized, especially elderly, adults. Age older than 65 years should be added to the severity criteria for CDI. PMID:26694494

  10. Persistence of Clostridium difficile RT 237 infection in a Western Australian piggery.

    PubMed

    Moono, Peter; Putsathit, Papanin; Knight, Daniel R; Squire, Michele M; Hampson, David J; Foster, Niki F; Riley, Thomas V

    2016-02-01

    Clostridium difficile is commonly associated with healthcare-related infections in humans, and is an emerging pathogen in food animal species. There is potential for transmission of C. difficile from animals or animal products to humans. This study aimed to determine if C. difficile RT 237 had persisted in a Western Australian piggery or if there had been a temporal change in C. difficile diversity. C. difficile carriage in litters with and without diarrhea was investigated, as was the acquisition of C. difficile over time using cohort surveys. Rectal swabs were obtained from piglets aged 1-10 days to determine prevalence of C. difficile carriage and samples were obtained from 20 piglets on days 1, 7, 13, 20, and 42 of life to determine duration of shedding. Isolation of C. difficile from feces was achieved by selective enrichment culture. All isolates were characterized by standard molecular typing. Antimicrobial susceptibility testing was performed on selected isolates (n = 29). Diarrheic piglets were more likely to shed C. difficile than the non-diseased (p = 0.0124, χ2). In the cohort study, C. difficile was isolated from 40% samples on day 1, 50% on day 7, 20% on day 13, and 0% on days 20 and 42. All isolates were RT 237 and no antimicrobial resistance was detected. The decline of shedding of C. difficile to zero has public health implications because slaughter age pigs have a low likelihood of spreading C. difficile to consumers via pig meat. PMID:26679487

  11. Molecular Epidemiology of Clostridium difficile Infection in a Large Teaching Hospital in Thailand

    PubMed Central

    Ngamskulrungroj, Popchai; Sanmee, Sittinee; Pusathit, Papanin; Piewngam, Pipat; Elliott, Briony; Riley, Thomas V.; Kiratisin, Pattarachai

    2015-01-01

    Clostridium difficile infection (CDI) is a leading cause of healthcare-associated morbidity and mortality worldwide. In Thailand, CDI exhibits low recurrence and mortality and its molecular epidemiology is unknown. CDI surveillance was conducted in a tertiary facility (Siriraj Hospital, Bangkok). A total of 53 toxigenic C. difficile strains from Thai patients were analyzed by multi-locus sequence typing (MLST), PCR ribotyping, and pulse-field gel electrophoresis (PFGE). The mean age of the cohort was 64 years and 62.3% were female; 37.7% of patients were exposed to > two antibiotics prior to a diagnosis of CDI, with beta-lactams the most commonly used drug (56.3%). Metronidazole was used most commonly (77.5%; success rate 83.9%), and non-responders were treated with vancomycin (success rate 100%). None of the isolates carried binary toxin genes. Most isolates (98.2–100%) were susceptible to metronidazole, vancomycin, tigecycline and daptomycin. There were 11 sequence types (STs), 13 ribotypes (RTs) and four PFGE types. Six previously identified STs (ST12, ST13, ST14, ST33, ST41 and ST45) and five novel STs unique to Thailand (ST66, ST67, ST68, ST69 and ST70) were identified. PCR RTs UK 017 (ST45) (45.3%) and UK 014/020 (ST33) (24.5%) were the most common. High concordance was observed between the MLST and ribotyping results (p<0.001). C. difficile isolates from Thai patients were highly susceptible to standard antimicrobial agents. In conclusion, the five STs indicate the high genetic diversity and unique polymorphisms in Thailand. Moreover, the emergence of antimicrobial resistance to vancomycin warranted continuous surveillance to prevent further spread of the toxigenic C. difficile isolates. PMID:26000789

  12. Impact of clinical awareness and diagnostic tests on the underdiagnosis of Clostridium difficile infection.

    PubMed

    Alcalá, L; Reigadas, E; Marín, M; Martín, A; Catalán, P; Bouza, E

    2015-08-01

    A multicenter study of Clostridium difficile infection (CDI) performed during 2008 in Spain revealed that two of every three episodes went undiagnosed or were misdiagnosed owing to nonsensitive diagnostic tests or lack of clinical suspicion and request. Since then, efforts have been made to improve the diagnostic tests used by laboratories and to increase the awareness of this disease among both clinicians and microbiologists. Our objective was to evaluate the impact of these efforts by assessing the current magnitude of underdiagnosis of CDI in Spain using two point-prevalence studies performed on one day each in January and July of 2013. A total of 111 Spanish laboratories selected all unformed stool specimens received for microbiological diagnosis on these days, and toxigenic culture was performed at a central reference laboratory. Toxigenic isolates were characterized both pheno- and genotypically. The reference laboratory detected 103 episodes of CDI in patients aged 2 years or more. Half (50.5 %) of the episodes were not diagnosed in the participating laboratories, owing to insensitive diagnostic tests (15.5 %) or the lack of clinical suspicion and request (35.0 %). The main ribotypes were 014, 078/126, 001/072, and 106. Ribotype 027 caused 2.9 % of all cases. Despite all the interventions undertaken, CDI remains a highly neglected disease because of the lack of sensitive diagnostic tests in some institutions and, especially, the absence of clinical suspicion, mainly in patients with community-associated CDI. Toxigenic C. difficile should be routinely sought in unformed stools sent for microbiological diagnosis, regardless of their origin. PMID:25904126

  13. Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection

    PubMed Central

    Chilton, C. H.; Crowther, G. S.; Śpiewak, K.; Brindell, M.; Singh, G.; Wilcox, M. H.; Monaghan, T. M.

    2016-01-01

    Objectives Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth. This study evaluated the comparative effects of iron-depleted (1% Fe3+ saturated) bovine apo-lactoferrin (apo-bLf) and iron-saturated (85% Fe3+ saturated) bovine holo-lactoferrin (holo-bLf) in a human in vitro gut model that simulates CDI. Methods Two parallel triple-stage chemostat gut models were inoculated with pooled human faeces and spiked with C. difficile spores (strain 027 210, PCR ribotype 027). Holo- or apo-bLf was instilled (5 mg/mL, once daily) for 35 days. After 7 days, clindamycin was instilled (33.9 mg/L, four times daily) to induce simulated CDI. Indigenous microflora populations, C. difficile total counts and spores, cytotoxin titres, short chain fatty acid concentrations, biometal concentrations, lactoferrin concentration and iron content of lactoferrin were monitored daily. Results In the apo-bLf model, germination of C. difficile spores occurred 6 days post instillation of clindamycin, followed by rapid vegetative cell proliferation and detectable toxin production. By contrast, in the holo-bLf model, only a modest vegetative cell population was observed until 16 days post antibiotic administration. Notably, no toxin was detected in this model. In separate batch culture experiments, holo-bLf prevented C. difficile vegetative cell growth and toxin production, whereas apo-bLf and iron alone did not. Conclusions Holo-bLf, but not apo-bLf, delayed C. difficile growth and prevented toxin production in a human gut model of CDI. This inhibitory effect may be iron independent. These observations suggest that bLf in its iron-saturated state could be used as a novel preventative or treatment strategy for CDI. PMID:26759363

  14. Development of a recombinant toxin fragment vaccine for Clostridium difficile infection.

    PubMed

    Karczewski, Jerzy; Zorman, Julie; Wang, Su; Miezeiewski, Matthew; Xie, Jinfu; Soring, Keri; Petrescu, Ioan; Rogers, Irene; Thiriot, David S; Cook, James C; Chamberlin, Mihaela; Xoconostle, Rachel F; Nahas, Debbie D; Joyce, Joseph G; Bodmer, Jean-Luc; Heinrichs, Jon H; Secore, Susan

    2014-05-19

    Clostridium difficile infection (CDI) is the major cause of antibiotic-associated diarrhea and pseudomembranous colitis, a disease associated with significant morbidity and mortality. The disease is mostly of nosocomial origin, with elderly patients undergoing anti-microbial therapy being particularly at risk. C. difficile produces two large toxins: Toxin A (TcdA) and Toxin B (TcdB). The two toxins act synergistically to damage and impair the colonic epithelium, and are primarily responsible for the pathogenesis associated with CDI. The feasibility of toxin-based vaccination against C. difficile is being vigorously investigated. A vaccine based on formaldehyde-inactivated Toxin A and Toxin B (toxoids) was reported to be safe and immunogenic in healthy volunteers and is now undergoing evaluation in clinical efficacy trials. In order to eliminate cytotoxic effects, a chemical inactivation step must be included in the manufacturing process of this toxin-based vaccine. In addition, the large-scale production of highly toxic antigens could be a challenging and costly process. Vaccines based on non-toxic fragments of genetically engineered versions of the toxins alleviate most of these limitations. We have evaluated a vaccine assembled from two recombinant fragments of TcdB and explored their potential as components of a novel experimental vaccine against CDI. Golden Syrian hamsters vaccinated with recombinant fragments of TcdB combined with full length TcdA (Toxoid A) developed high titer IgG responses and potent neutralizing antibody titers. We also show here that the recombinant vaccine protected animals against lethal challenge with C. difficile spores, with efficacy equivalent to the toxoid vaccine. The development of a two-segment recombinant vaccine could provide several advantages over toxoid TcdA/TcdB such as improvements in manufacturability. PMID:24662701

  15. A Detrimental Role of Immunosuppressive Drug, Dexamethasone, During Clostridium difficile Infection in Association with a Gastrointestinal Microbial Shift

    PubMed Central

    Kim, Hyeun Bum; Wang, Yuankai; Sun, Xingmin

    2016-01-01

    We investigated the increased risk of Clostridium difficile infection (CDI) caused by the combined use of antibiotics and an immunosuppressive drug in a mouse model. Our data showed that an approximate return to pretreatment conditions of gut microbiota occurred within days after cessation of the antibiotic treatment, whereas the recovery of gut microbiota was delayed with the combined treatment of antibiotics and dexamethasone, leading to an increased severity of CDI. An alteration of gut microbiota is a key player in CDI. Therefore, our data implied that immunosuppressive drugs can increase the risk of CDI through the delayed recovery of altered gut microbiota. PMID:26809802

  16. A Detrimental Role of Immunosuppressive Drug, Dexamethasone, During Clostridium difficile Infection in Association with a Gastrointestinal Microbial Shift.

    PubMed

    Kim, Hyeun Bum; Wang, Yuankai; Sun, Xingmin

    2016-03-28

    We investigated the increased risk of Clostridium difficile infection (CDI) caused by the combined use of antibiotics and an immunosuppressive drug in a mouse model. Our data showed that an approximate return to pretreatment conditions of gut microbiota occurred within days after cessation of the antibiotic treatment, whereas the recovery of gut microbiota was delayed with the combined treatment of antibiotics and dexamethasone, leading to an increased severity of CDI. An alteration of gut microbiota is a key player in CDI. Therefore, our data implied that immunosuppressive drugs can increase the risk of CDI through the delayed recovery of altered gut microbiota. PMID:26809802

  17. Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background Fecal microbiota therapy is increasingly being used to treat patients with Clostridium difficile infection. This health technology assessment primarily evaluated the effectiveness and cost-effectiveness of fecal microbiota therapy compared with the usual treatment (antibiotic therapy). Methods We performed a literature search using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database. For the economic review, we applied economic filters to these search results. We also searched the websites of agencies for other health technology assessments. We conducted a meta-analysis to analyze effectiveness. The quality of the body of evidence for each outcome was examined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Using a step-wise, structural methodology, we determined the overall quality to be high, moderate, low, or very low. We used a survey to examine physicians’ perception of patients’ lived experience, and a modified grounded theory method to analyze information from the survey. Results For the review of clinical effectiveness, 16 of 1,173 citations met the inclusion criteria. A meta-analysis of two randomized controlled trials found that fecal microbiota therapy significantly improved diarrhea associated with recurrent C. difficile infection versus treatment with vancomycin (relative risk 3.24, 95% confidence interval [CI] 1.85–5.68) (GRADE: moderate). While fecal microbiota therapy is not associated with a significant decrease in mortality compared with antibiotic therapy (relative risk 0.69, 95% CI 0.14–3.39) (GRADE: low), it is associated with a significant increase in adverse events (e.g., short-term diarrhea, relative risk 30.76, 95% CI 4.46–212.44; abdominal cramping, relative risk 14

  18. A Tetraspecific VHH-Based Neutralizing Antibody Modifies Disease Outcome in Three Animal Models of Clostridium difficile Infection.

    PubMed

    Schmidt, Diane J; Beamer, Gillian; Tremblay, Jacqueline M; Steele, Jennifer A; Kim, Hyeun Bum; Wang, Yaunkai; Debatis, Michele; Sun, Xingmin; Kashentseva, Elena A; Dmitriev, Igor P; Curiel, David T; Shoemaker, Charles B; Tzipori, Saul

    2016-09-01

    Clostridium difficile infection (CDI), a leading cause of nosocomial infection, is a serious disease in North America, Europe, and Asia. CDI varies greatly from asymptomatic carriage to life-threatening diarrhea, toxic megacolon, and toxemia. The incidence of community-acquired infection has increased due to the emergence of hypervirulent antibiotic-resistant strains. These new strains contribute to the frequent occurrence of disease relapse, complicating treatment, increasing hospital stays, and increasing morbidity and mortality among patients. Therefore, it is critical to develop new therapeutic approaches that bypass the development of antimicrobial resistance and avoid disruption of gut microflora. Here, we describe the construction of a single heteromultimeric VHH-based neutralizing agent (VNA) that targets the two primary virulence factors of Clostridium difficile, toxins A (TcdA) and B (TcdB). Designated VNA2-Tcd, this agent has subnanomolar toxin neutralization potencies for both C. difficile toxins in cell assays. When given systemically by parenteral administration, VNA2-Tcd protected against CDI in gnotobiotic piglets and mice and to a lesser extent in hamsters. Protection from CDI was also observed in gnotobiotic piglets treated by gene therapy with an adenovirus that promoted the expression of VNA2-Tcd. PMID:27413067

  19. Understanding the Current State of Infection Prevention to Prevent Clostridium difficile Infection: A Human Factors and Systems Engineering Approach

    PubMed Central

    Yanke, Eric; Zellmer, Caroline; Van Hoof, Sarah; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

    2015-01-01

    Background Achieving and sustaining high levels of healthcare worker (HCW) compliance with contact isolation precautions is challenging. The aim of this study was to determine HCW work system barriers to, and facilitators of, adherence to contact isolation for patients with suspected or confirmed Clostridium difficile infection (CDI) using a human factors and systems engineering approach. Methods Prospective cohort study from September 2013 to November 2013 at a large academic medical center (hospital A) and an affiliated Veterans Administration (VA) hospital (hospital B). A human factors engineering (HFE) model for patient safety – the Systems Engineering Initiative for Patient Safety (SEIPS) model – was used to guide work system analysis and direct observation data collection. 288 observations were conducted. HCWs and visitors were assessed for compliance with all components of contact isolation precautions (hand hygiene, gowning, and gloving) before and after patient contact. Time required to complete contact isolation precautions was measured and adequacy of contact isolation supplies was assessed. Results Full compliance with contact isolation precautions was low at both hospitals: hospital A, 7%; hospital B, 22%. Lack of appropriate hand hygiene prior to room entry (Compliance: hospital A, 18%; hospital B, 29%) was the most common reason for lack of full compliance. More time was required for full compliance as compared to compliance with no components of contact isolation precautions before patient room entry, inside patient room, and after patient room exit (59.9 sec vs. 3.2 sec; P < .001; 507.3 sec vs. 149.7 sec; P = .006; 15.2 sec vs. 1.3 sec; P < .001). Compliance was lower when contact isolation supplies were inadequate (4% vs. 16%; P = .005). Conclusions Adherence to contact isolation precautions for CDI is a complex, time-consuming process. HFE analysis indicates multiple work system components serve as barriers and facilitators to full compliance

  20. Excess Mortality Attributable to Clostridium difficile and Risk Factors for Infection in an Historic Cohort of Hospitalised Patients Followed Up in the United Kingdom Death Register

    PubMed Central

    2016-01-01

    Methods We compared time from hospital admission to death in a probability sample of 100 Clostridium difficile infected cases and a probability sample of 98 non-cases admitted to an English teaching hospital between 2005 and 2007 with follow up in the UK national death register using survival analysis. Results Clostridium difficile infection was associated with a 50% increased risk of death (Hazard Ratio 1.51 (95% CI: 1.05–2.19 p = 0.03) at between five to eight years in Cox Regression analysis adjusting for age, sex, Charlson comorbidity index, diagnosis of a malignant condition and insertion of a nasogastric tube during admission. Acquisition of Clostridium difficile infection was independently associated with an almost six fold higher odds of being admitted with a diagnosis of infection of any other type (OR 5.79 (2.19, 15.25) p<0.001). Conclusions Our results strongly support continued priority being given to improve prevention and treatment of Clostridium difficile infection in the English National Health Service particularly in patients admitted with an infection. Our results may be applicable to other health systems. PMID:26999613

  1. Outbreak of Clostridium difficile 027 infection in Vienna, Austria 2008-2009.

    PubMed

    Indra, A; Huhulescu, S; Fiedler, A; Kernbichler, S; Blaschitz, M; Allerberger, F

    2009-04-30

    From November 2008 to 15 April 2009, 36 isolates of CD027 identified in Austria, all originating from four hospitals in Vienna. All isolates were positive for toxin A, toxin B and the binary toxin, and showed a characteristic 18 bp deletion in the tcdC gene. Clostridium difficile is an anaerobic spore-forming bacterium. Some strains may cause diarrhoea due to formation of toxins. Symptomatic C. difficile infection (CDI) is primarily linked with hospital admission and antibiotic treatment, although antibiotic exposure is neither necessary nor sufficient for CDI [1,2]. In Belgium, for instance, one third of CDI cases reported in the hospital surveillance system are not hospital-associated [3]. Symptoms range from mild diarrhoea to serious manifestations such as pseudomembranous colitis, toxic megacolon or perforation of the colon. C. difficile challenges hygiene standards as it is forms spores. The risk of infection rises with increasing age, underlying disease and immunodeficiency [4]. In recent years, a particularly virulent strain, ribotype 027 (CD027), has emerged in a number of countries, particularly in connection with hospital outbreaks, but also in community-acquired diarrhoea cases [5]. The risk of serious disease and death associated with CD027 exceeds that of other C. difficile strains. The classical CD027 is characterised - among other things - by an increased production of toxins A and B, production of a binary toxin and resistance to newer fluoroquinolones such as moxifloxacin. The first three Austrian cases of CD027 occurred in 2006 and in March 2008 [6,7]. Since August 2006, the Austrian National Reference Centre for C. difficile has ribotyped approximately 2,700 human C. difficile isolates received from all nine Austrian provinces. In recent months, a drastic increase in CD027 cases has been noted, all originating from four hospitals in Vienna. From November 2008 to 15 April 2009, 36 isolates of CD027 were received at the National Reference Centre

  2. An exploratory study to evaluate Clostridium difficile polymerase chain reaction ribotypes and infection outcomes

    PubMed Central

    Thabit, Abrar K; Nicolau, David P

    2016-01-01

    Background Clostridium difficile infection ranges from mild to severe prolonged diarrhea with systemic symptoms. Previous studies have assessed the correlation of some disease severity parameters to C. difficile ribotypes. However, certain clinical parameters of interest have not yet been evaluated. Aim We conducted an exploratory study to evaluate the correlation of C. difficile ribotypes to parameters not assessed previously, notably days to diarrhea resolution (in terms of days to formed stools and days to less than three stools per day), length of hospital stay, 30-day recurrence rates, and 30-day readmission rates. Additional severity parameters evaluated include leukocytosis, serum creatinine, fever, and nausea/vomiting. Methods Polymerase chain reaction ribotyping was performed on C. difficile isolates from baseline stool samples of 29 patients. A retrospective chart review was conducted to assess the parameters of interest. Results The most common ribotypes were 027 (38%), 014/020 (21%), and 106/174 (21%). Numerically, 027 ribotype patients required more days to less than three stools per day versus 014/020 and 106/174 ribotype patients (P=0.2). The three ribotypes were similar regarding time to formed stools, duration of hospitalization, and 30-day readmission rate (P=0.2, 0.6, and 0.8, respectively). Recurrence within 30 days occurred in two patients with 027 and two patients with 014/020 (P=0.6). Leukocytosis and fever were more prominent with 027 than with 014/020 and 106/174 (P=0.04 for both parameters), although the degree of nausea/vomiting did not differ between the three groups (P=0.3). A serum creatinine level ≥1.5 times the premorbid level was seen in only three patients, each infected with a different ribotype. Conclusion Although these data provide a baseline assessment of outcomes to aid in the design of future studies, the diversity of C. difficile ribotypes within the population must be considered, and additional work with other ribotypes

  3. Non-Clostridium perfringens infectious agents producing necrotic enteritis-like lesions in poultry.

    PubMed

    Uzal, F A; Sentíes-Cué, C G; Rimoldi, G; Shivaprasad, H L

    2016-06-01

    Necrotic enteritis (NE) produced by Clostridium perfringens is amongst the most prevalent enteric diseases of chickens and turkeys. However, several other bacterial, parasitic and viral agents can cause clinical signs, gross and microscopic lesions in poultry very similar to those of NE and the diseases produced by those agents need to be differentiated from NE. The main differential diagnoses for C. perfringens NE include bacterial (Clostridium colinum, Clostridium sordellii, Clostridium difficile, Pasteurella multocida, Brachyspira spp.), parasitic (Eimeria spp., Histomonas meleagridis) and viral (Duck Herpesvirus type 1, Avian Paramyxovirus type 1) diseases. Confirmation of the diagnosis of these diseases requires identification of the aetiological agents by morphological, cultural and/or molecular methods. PMID:27009483

  4. The evolution of Clostridium difficile infection in cancer patients: epidemiology, pathophysiology, and guidelines for prevention and management.

    PubMed

    Khan, Areej; Raza, Shahzad; Batul, Syeda A; Khan, Monis; Aksoy, Tulay; Baig, Mahadi A; Berger, Barbara J

    2012-08-01

    Clostridium difficile infection (CDI) has emerged as a significant challenge to the healthcare system. The availability of anti-cancer chemotherapeutic regimens has contemporaneously resulted in a larger population of patients who are susceptible to CDI. The outbreak of a novel, hypervirulent, resistant strain, NAP-1/027 as well as resistance to antibiotic therapy have further contributed to an increase in prevalence as well as in disease severity. Recent data show high fatality rates in cancer patients with CDI. In this review, we have discussed the incidence, epidemiology, pathophysiology, clinical signs and symptoms and therapeutic guidelines for patients who are on chemotherapy and present with CDI and highlighted clinical reports documenting severe CDI associated with chemotherapeutic agents such as methotrexate, 5FU, cisplatin, carboplatin, paclitaxel, vinorelbine and cyclophosphamide. The review article also has the discussion of patents pertaining to infections caused by Clostridium difficile in cancer patients. We underscore the urgent need for early recognition and diagnosis of CDI in cancer patients and for the design and implementation of randomized clinical trials of new treatment modalities in the management of chemotherapy- associated CDI. PMID:22792862

  5. Sentinel community Clostridium difficile infection (CDI) surveillance in Scotland, April 2013 to March 2014.

    PubMed

    Banks, A; Brown, Derek J; Mather, Henry; Coia, John E; Wiuff, Camilla

    2016-02-01

    Surveillance of Clostridium difficile infection (CDI) in Scotland does not currently distinguish between CDI cases from hospitals and the community. Therefore, the incidence of CDI in the community is unknown, and the burden of disease and the relationship with the hospital/healthcare setting is not well understood. A one-year sentinel community surveillance programme was initiated in collaboration with five Scottish health boards in 2013 (representing 36% of all CDI cases reported in Scotland). Inclusion criteria were all cases aged ≥15 years with a CDI diagnosis in the community or within 48 h following admission to hospital. CDI cases were categorised according to definitions used by the European Centre for Disease Prevention and Control. 256 CDI cases met the inclusion criteria, of which 158 (62%) were community-associated cases (CA-CDI). This represented 26% of all cases reported during the surveillance period by the participating health boards (n = 614). The overall CA-CDI incidence rate was 9.9 per 100 000 population per year. CA-CDI cases were more likely to be female and younger, compared to hospital acquired cases (HA-CDI). The total proportion of cases that had onset in the community was 27%. Ribotypes 015, 002, 078 and 005 were the most common types isolated from both CA-CDI and HA-CDI cases. There were no statistically significant differences between the proportion of types that were either CA-CDI or HA-CDI. Of the CA-CDI cases, 37% had not received antibiotics in the 12 weeks preceding CDI diagnosis, 4% were resident in care homes, and the case-fatality rate for CA-CDI cases was 5.6% (with a 30-day mortality rate for CA-CDI of 0.44 per 100 000 population per year). This study has shown that a substantial proportion of CDI cases reported in Scotland are community associated and that there are close links between the community and healthcare settings. It is therefore essential to monitor the trends in CDI in the community at a national level. The

  6. Relationship Between Bacterial Strain Type, Host Biomarkers, and Mortality in Clostridium difficile Infection

    PubMed Central

    Walker, A. Sarah; Eyre, David W.; Wyllie, David H.; Dingle, Kate E.; Griffiths, David; Shine, Brian; Oakley, Sarah; O'Connor, Lily; Finney, John; Vaughan, Alison; Crook, Derrick W.; Wilcox, Mark H.; Peto, Tim E. A.

    2013-01-01

    Background. Despite substantial interest in biomarkers, their impact on clinical outcomes and variation with bacterial strain has rarely been explored using integrated databases. Methods. From September 2006 to May 2011, strains isolated from Clostridium difficile toxin enzyme immunoassay (EIA)–positive fecal samples from Oxfordshire, United Kingdom (approximately 600 000 people) underwent multilocus sequence typing. Fourteen-day mortality and levels of 15 baseline biomarkers were compared between consecutive C. difficile infections (CDIs) from different clades/sequence types (STs) and EIA-negative controls using Cox and normal regression adjusted for demographic/clinical factors. Results. Fourteen-day mortality was 13% in 2222 adults with 2745 EIA-positive samples (median, 78 years) vs 5% in 20 722 adults with 27 550 EIA-negative samples (median, 74 years) (absolute attributable mortality, 7.7%; 95% CI, 6.4%–9.0%). Mortality was highest in clade 5 CDIs (25% [16 of 63]; polymerase chain reaction (PCR) ribotype 078/ST 11), then clade 2 (20% [111 of 560]; 99% PCR ribotype 027/ST 1) versus clade 1 (12% [137 of 1168]; adjusted P < .0001). Within clade 1, 14-day mortality was only 4% (3 of 84) in ST 44 (PCR ribotype 015) (adjusted P = .05 vs other clade 1). Mean baseline neutrophil counts also varied significantly by genotype: 12.4, 11.6, and 9.5 × 109 neutrophils/L for clades 5, 2 and 1, respectively, vs 7.0 × 109 neutrophils/L in EIA-negative controls (P < .0001) and 7.9 × 109 neutrophils/L in ST 44 (P = .08). There were strong associations between C. difficile-type-specific effects on mortality and neutrophil/white cell counts (rho = 0.48), C-reactive-protein (rho = 0.43), eosinophil counts (rho = −0.45), and serum albumin (rho = −0.47). Biomarkers predicted 30%–40% of clade-specific mortality differences. Conclusions. C. difficile genotype predicts mortality, and excess mortality correlates with genotype-specific changes in biomarkers, strongly

  7. The interplay between microbiome dynamics and pathogen dynamics in a murine model of Clostridium difficile Infection.

    PubMed

    Reeves, Angela E; Theriot, Casey M; Bergin, Ingrid L; Huffnagle, Gary B; Schloss, Patrick D; Young, Vincent B

    2011-01-01

    Clostridium difficile infection (CDI) arises in the setting of antibiotic administration where disruption of the normal indigenous gut microbiota leads to susceptibility to C. difficile colonization and colitis. Using a murine model of CDI, we demonstrate that changes in the community structure of the indigenous gut microbiota are associated with the loss of colonization resistance against C. difficile. Several antibiotic regimens were tested in combination for the ability to overcome colonization resistance, including a five antibiotic cocktail consisting of kanamycin, gentamicin, colistin, metronidazole, and vancomycin administered in drinking water for three days, a single intraperitoneal dose of clindamycin or 10 days of cefoperazone in drinking water. Following antibiotic treatment animals were challenged with 105 colony forming units of C. difficile strain VPI 10463 via oral gavage. Animals that received the antibiotic cocktail and clindamycin prior to C. difficile challenge followed one of two clinical courses, either becoming clinically ill and moribund within 2-4 days post challenge, or remaining clinically well. Animals that became clinically ill developed histologically severe colitis. These histopathologic findings were significantly less severe in animals that remained clinically well. Analysis of 16S rRNA gene sequences retrieved from gut tissue at necropsy demonstrated that Proteobacteria dominated the gut microbiota in clinically ill animals. In contrast, the gut microbial community of clinically well animals more closely resembled untreated animals, which were dominated by members of the Firmicutes. All animals that received cefoperazone treatment prior to C. difficile challenge were clinically ill and moribund by 2-5 days post challenge in a dose dependent manner. The gut communities in these animals were dominated by C.difficile suggesting that cefoperazone treatment resulted in a greater loss in colonization resistance. Thus, the severity of

  8. Flooding and Health Care Visits for Clostridium Difficile Infection: A Case-Crossover Analysis

    EPA Science Inventory

    Floods can contaminate potable water and other resources, thus increasing the potential for fecal-oral transmission of pathogens. Clostridium difficile is a bacterium that can spread by water and cause acute gastrointestinal illness. It often affects older adults who are hospital...

  9. Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for identification of Clostridium species isolated from Saudi Arabia.

    PubMed

    AlMogbel, Mohammed Suliman

    2016-01-01

    The aim of this study was to identify different Clostridium spp. isolated from currency notes from the Ha'il region of Saudi Arabia in September 2014 using MALDI-TOF-MS. Clostridium spp. were identified by Bruker MALDI-TOF-MS and compared with VITEK 2. The confirmation of the presence of different Clostridium spp. was performed by determining the sequence of the 16S ribosomal RNA gene. In this study, 144 Clostridium spp. were isolated. Among these specimens, MALDI-TOF-MS could identify 88.8% (128/144) of the isolates to the species level and 92.3% (133/144) to the genus level, whereas, VITEK 2 identified 77.7% of the (112/144) isolates. The correct identification of the 144 isolates was performed by sequence analysis of the 500bp 16S rRNA gene. The most common Clostridium spp. identified were Clostridium perfringens (67.36%), Clostridium subterminale (14.58%), Clostridium sordellii (9%) and Clostridium sporogenes (9%). The results of this study demonstrate that MALDI-TOF-MS is a rapid, accurate and user friendly technique for the identification of Clostridium spp. Additionally, MALDI-TOF-MS has advantages over VITEK 2 in the identification of fastidious micro-organisms, such as Clostridium spp. Incorporating this technique into routine microbiology would lead to more successful and rapid identification of pathogenic and difficult to identify micro-organisms. PMID:26991272

  10. Deciphering Adaptation Strategies of the Epidemic Clostridium difficile 027 Strain during Infection through In Vivo Transcriptional Analysis

    PubMed Central

    Kansau, Imad; Barketi-Klai, Amira; Monot, Marc; Hoys, Sandra; Dupuy, Bruno; Janoir, Claire; Collignon, Anne

    2016-01-01

    Clostridium difficile is responsible for a wide spectrum of infection from asymptomatic carriage to severe, relapsing colitis. Since 2003, C. difficile infections have increased with a higher morbidity and mortality due to the emergence of epidemic and hypervirulent C. difficile strains such as those of the epidemic lineage 027/BI/NAP1. To decipher the hypervirulence and epidemicity of 027 strains, we analyzed gene expression profiles of the R20291 027 strain using a monoxenic mouse model during the first 38h of infection. A total of 741 genes were differentially expressed during the course of infection. They are mainly distributed in functional categories involved in host adaptation. Several genes of PTS and ABC transporters were significantly regulated during the infection, underlying the ability of strain R20291 to adapt its metabolism according to nutrient availability in the digestive tract. In this animal model, despite the early sporulation process, sporulation efficiency seems to indicate that growth of R20291 vegetative cells versus spores were favored during infection. The bacterial mechanisms associated to adaptability and flexibility within the gut environment, in addition to the virulence factor expression and antibiotic resistance, should contribute to the epidemicity and hypervirulence of the C. difficile 027 strains. PMID:27351947