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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 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

  2. 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

  3. 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.

  4. Necrotic Enteritis in Chickens Associated with Clostridium sordellii.

    PubMed

    Rimoldi, Guillermo; Uzal, Francisco; Chin, R P; Palombo, Enzo A; Awad, Milena; Lyras, Dena; Shivaprasad, H L

    2015-09-01

    Three outbreaks of necrotic enteritis-like disease associated with Clostridium sordelii were diagnosed in commercial broiler chicken flocks with 18,000 to 31,000 birds between 18 and 26 days old. Clinical signs in the affected flocks included high mortality up to 2% a day, depression, and diarrhea. The main gross changes included segmental dilation of the small intestine with watery contents, gas, mucoid exudate, and roughened and uneven mucosa, occasionally covered with a pseudomembrane. Microscopic lesions in the small intestine were characterized by extensive areas of coagulative necrosis of the villi, fibrinous exudate in the lumen, and high numbers of large, Gram-positive rods, occasionally containing subterminal spores, seen in the necrotic tissue and lumen. These rods were identified as C. sordellii by immunohistochemistry. Clostridium sordellii was isolated in an almost pure culture from the intestine of affected birds. A retrospective study of commercial broiler chicken and turkey submissions to the California Animal Health and Food Safety Laboratory System revealed that C. sordellii had been isolated from intestinal lesions in outbreaks of necrotic enteritis-like disease in 8 of 39 cases, 5 times together with Clostridium perfringens and 3 times alone. The latter three cases are reported here.

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

    PubMed

    Kimura, Akiko C; Higa, Jeffrey I; Levin, Robert M; Simpson, Gail; Vargas, Yolanda; Vugia, Duc J

    2004-05-01

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

  6. Ulcerative enteritis-like disease associated with Clostridium sordellii in quail.

    PubMed

    Crespo, Rocio; Franca, Monique; Shivaprasad, H L

    2013-09-01

    A natural outbreak of ulcerative enteritis-like disease associated with Clostridium sordellii was diagnosed in two commercial quail flocks. Clinical signs in the quail included anorexia, weakness, and increased mortality in the flocks. Lesions in the intestine were characterized by ulcers covered with fibrinonecrotic exudate in the small intestine and occasional hemorrhages. There were also multifocal pale areas of necrosis in the liver. Clostridium sordellii was isolated from the intestine and liver. A retrospective study of avian cases submitted to the California Animal Health and Food Safety Laboratories revealed that C. sordellii had been isolated in 45 avian submissions, most commonly in chickens and turkeys. In most of these cases the birds were diagnosed with necrotic enteritis, with or without hepatitis. Clostridium sordellii has occasionally been associated with gangrenous dermatitis in poultry, but this is the first report of enteritis in an avian species.

  7. Detection of Clostridium sordellii strains expressing hemorrhagic toxin (TcsH) and implications for diagnostics and regulation of veterinary vaccines.

    PubMed

    Thiele, Teri L; Stuber, Tod P; Hauer, Paul J

    2013-10-17

    Clostridium sordellii is a Gram positive anaerobic bacterium that causes multiple disease syndromes in both humans and animals. As with many clostridial pathogens, toxins contribute to the virulence of C. sordellii. Two large toxins have been identified: a lethal toxin (TcsL) and a hemorrhagic toxin (TcsH) which are similar in structure and function to Clostridium difficile toxin B (TcdB) and toxin A (TcdA), respectively. While TcdA, TcdB, and TcsL have been extensively studied, relatively little is known about TcsH. This study elucidated the TcsH gene sequence using whole genome sequencing, compared the genotype with toxin expression of 52 C. sordellii strains, and examined the role of TcsH in batch release potency tests required for veterinary vaccines licensed in the United States and other testing utilizing WHO standard antitoxin. Data from this study will assist in future research to clarify the TcsH contribution to the pathogenesis of C. sordellii infections and may aid in the development of improved vaccines.

  8. EP4 and EP2 receptor activation of protein kinase A by prostaglandin E2 impairs macrophage phagocytosis of Clostridium sordellii

    PubMed Central

    Rogers, Lisa M.; Thelen, Tennille; Fordyce, Krystle; Bourdonnay, Emilie; Lewis, Casey; Yu, Han; Zhang, Junyong; Xie, Jingli; Serezani, Carlos H.; Peters-Golden, Marc; Aronoff, David M.

    2013-01-01

    Problem Clostridium sordellii causes endometrial infections but little is known regarding host defenses against this pathogen. Method of Study We tested the hypothesis that the immunoregulatory lipid prostaglandin (PG) E2 suppresses human macrophage clearance of C. sordellii through receptor-induced increases in intracellular cAMP. The THP-1 macrophage cell line was used to quantify C. sordellii phagocytosis. Results PGE2 increased cAMP levels, activated protein kinase A (PKA), and inhibited the class A scavenger receptor-dependent phagocytosis of C. sordellii. Activation of the EP2 and EP4 receptors increased intracellular cAMP and inhibited phagocytosis, with evidence favoring a more important role for EP4 over EP2. This was supported by EP receptor expression data and the use of pharmacological receptor antagonists. In addition, the PKA isoform RI appeared to be more important than RII in mediating the suppression of ingestion of C. sordellii. Conclusions The endogenous lipid mediator PGE2 impairs human innate immune responses against C. sordellii. PMID:23902376

  9. 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

  10. 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

  11. 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

  12. Degeneration and regeneration of murine skeletal neuromuscular junctions after intramuscular injection with a sublethal dose of Clostridium sordellii lethal toxin.

    PubMed

    Barbier, Julien; Popoff, Michel R; Molgó, Jordi

    2004-06-01

    Clostridium sordellii lethal toxin (LT), a 250-kDa protein which is the bacteria's major virulence factor, belongs to a family of large clostridial cytotoxins which glucosylate small GTP-binding proteins. Here, we report the results of our ex vivo analysis of the structure and function of skeletal neuromuscular tissue obtained from mice at various times after intramuscular injection of a sublethal dose of LT (0.25 ng/g of body wt). The toxin caused, within 24 h, pronounced localized edema, inflammation, myofibril disassembly, and degeneration of skeletal muscle fibers in the injected area, and it glucosylated the muscle tissue's small GTPases. Regeneration of the damaged fibers was evident 6 to 9 days postinjury and was completed by 60 days. The expression of dystrophin, laminin, and fast and neonatal myosin in regenerating fibers, detected by immunofluorescence microscopy, confirmed that LT does not impair the high regenerative capacity of murine skeletal muscle fibers. Functional studies revealed that LT affects muscle contractility and neuromuscular transmission. However, partial recovery of nerve-evoked muscle twitches and tetanic contractions was observed by day 15 postinjection, and extensive remodeling of the neuromuscular junction's nerve terminals and clusters of muscle acetylcholine receptors was still evident 30 days postinjection. In conclusion, to the best of our knowledge, this is the first report to characterize the degeneration and regeneration of skeletal neuromuscular tissue after in vivo exposure to a large clostridial cytotoxin. In addition, our data may provide an explanation for the severe neuromuscular alterations accompanying wound infections caused by C. sordellii.

  13. Degeneration and Regeneration of Murine Skeletal Neuromuscular Junctions after Intramuscular Injection with a Sublethal Dose of Clostridium sordellii Lethal Toxin

    PubMed Central

    Barbier, Julien; Popoff, Michel R.; Molgó, Jordi

    2004-01-01

    Clostridium sordellii lethal toxin (LT), a 250-kDa protein which is the bacteria's major virulence factor, belongs to a family of large clostridial cytotoxins which glucosylate small GTP-binding proteins. Here, we report the results of our ex vivo analysis of the structure and function of skeletal neuromuscular tissue obtained from mice at various times after intramuscular injection of a sublethal dose of LT (0.25 ng/g of body wt). The toxin caused, within 24 h, pronounced localized edema, inflammation, myofibril disassembly, and degeneration of skeletal muscle fibers in the injected area, and it glucosylated the muscle tissue's small GTPases. Regeneration of the damaged fibers was evident 6 to 9 days postinjury and was completed by 60 days. The expression of dystrophin, laminin, and fast and neonatal myosin in regenerating fibers, detected by immunofluorescence microscopy, confirmed that LT does not impair the high regenerative capacity of murine skeletal muscle fibers. Functional studies revealed that LT affects muscle contractility and neuromuscular transmission. However, partial recovery of nerve-evoked muscle twitches and tetanic contractions was observed by day 15 postinjection, and extensive remodeling of the neuromuscular junction's nerve terminals and clusters of muscle acetylcholine receptors was still evident 30 days postinjection. In conclusion, to the best of our knowledge, this is the first report to characterize the degeneration and regeneration of skeletal neuromuscular tissue after in vivo exposure to a large clostridial cytotoxin. In addition, our data may provide an explanation for the severe neuromuscular alterations accompanying wound infections caused by C. sordellii. PMID:15155613

  14. Paraclostridium benzoelyticum gen. nov. sp. nov., isolated from marine sediment and reclassification of Clostridium bifermentans as Paraclostridium bifermentans comb. nov. Proposal of a new genus Paeniclostridium gen. nov. to accommodate Clostridium sordellii and Clostridium ghonii.

    PubMed

    T S, Sasi Jyothsna; L, Tushar; Ch, Sasikala; Ch V, Ramana

    2016-01-05

    Twenty three rod shaped, endospore forming, Gram-stain-positive, obligately anaerobic bacteria were isolated from different marine sediment samples of Gujarat. All the twenty three strains have 16S rRNA gene sequence similarity of ~100%. Strain JC272T was designated as the type strain and has sequence similarity with Clostridium bifermentans ATCC638T (99.8%), Clostridium ghonii JCM1400T (98.0%), Clostridium sordellii ATCC9714T (97.9%) and other members of the genus Clostridium (<96.4%). C16:0, C18:0, C17:0, C16:1ω9C and iso-C16:0 are the major (>5%) fatty acids. Strain JC272T contains diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and unidentified amino lipids (AL1&AL2). However, genome based analysis of ANI and in silico DDH of strain JC272T with C. bifermentans ATCC 638T yielded values of 94.35% and 58.5+2.8%, respectively. G+C mol% of strain JC272T was 28.3%. Strain JC272T together with C. bifermentans fall outside Clostridium rRNA cluster I considered as Clostridium senso stricto. Based on ANI value, in-silico DDH, distinct morphological and physiological differences from the previously described taxa, we propose strain JC272T as a representative of a new genus and species in the family Clostridiaceae, for which the name Paraclostridium benzoelyticum gen. nov., sp. nov. is proposed. Type strain is JC272T (=KCTC15476T =LMG28745T). It is also proposed to transfer C. bifermentans to this new genus, as Paraclostridium bifermentans comb. nov. (type strain is ATCC638T =DSM14991T =JCM1386T). We also propose the genus Paeniclostridium gen. nov. to accommodate Clostridium sordellii and Clostridium ghonii as Paeniclostridium sordellii comb. nov. (type strain is ATCC9714T =LMG15708T =JCM3814T) and Paeniclostridium ghonii comb. nov. (type strain is ATCC25757T = DSM15049T =JCM1400T).

  15. Role of p38alpha/beta MAP Kinase in Cell Susceptibility to Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B

    PubMed Central

    Schelle, Ilona; Bruening, Janina; Buetepage, Mareike; Genth, Harald

    2016-01-01

    Lethal Toxin from Clostridium sordellii (TcsL), which is casually involved in the toxic shock syndrome and in gas gangrene, enters its target cells by receptor-mediated endocytosis. Inside the cell, TcsL mono-O-glucosylates and thereby inactivates Rac/Cdc42 and Ras subtype GTPases, resulting in actin reorganization and an activation of p38 MAP kinase. While a role of p38 MAP kinase in TcsL-induced cell death is well established, data on a role of p38 MAP kinase in TcsL-induced actin reorganization are not available. In this study, TcsL-induced Rac/Cdc42 glucosylation and actin reorganization are differentially analyzed in p38alpha−/− MSCV empty vector MEFs and the corresponding cell line with reconstituted p38alpha expression (p38alpha−/− MSCV p38alpha MEFs). Genetic deletion of p38alpha results in reduced susceptibility of cells to TcsL-induced Rac/Cdc42 glucosylation and actin reorganization. Furthermore, SB203580, a pyridinyl imidazole inhibitor of p38alpha/beta MAP kinase, also protects cells from TcsL-induced effects in both p38−/− MSCV empty vector MEFs and in p38alpha−/− MSCV p38alpha MEFs, suggesting that inhibition of p38beta contributes to the protective effect of SB203580. In contrast, the effects of the related C. difficile Toxin B are responsive neither to SB203580 treatment nor to p38alpha deletion. In conclusion, the protective effects of SB203580 and of p38alpha deletion are likely not based on inhibition of the toxins’ glucosyltransferase activity rather than on inhibited endocytic uptake of specifically TcsL into target cells. PMID:28025502

  16. Clostridium difficile Infection

    PubMed Central

    Heinlen, Latisha; Ballard, Jimmy D.

    2010-01-01

    Clostridium difficile is the leading cause of hospital-acquired diarrhea in Europe and North America and is a serious re-emerging pathogen. Recent outbreaks have led to increasing morbidity and mortality and have been associated with a new strain (BI/NAP1/027) of C. difficile that produces more toxin than historical strains. With the increasing incidence of C. difficile infection, clinicians have also seen a change in the epidemiology with increased infections in previously low-risk populations. This chapter highlights the current knowledge on C. difficile virulence, human disease, epidemic outbreaks, and optimal treatment strategies. PMID:20697257

  17. Transient expression of RhoA, -B, and -C GTPases in HeLa cells potentiates resistance to Clostridium difficile toxins A and B but not to Clostridium sordellii lethal toxin.

    PubMed Central

    Giry, M; Popoff, M R; von Eichel-Streiber, C; Boquet, P

    1995-01-01

    The bacterial pathogen Clostridium difficle synthesizes two high-molecular-weight toxins (A and B), which exhibit toxic effects in vivo and in vitro. Here, we present evidence that the major intracellular targets of these two toxins are the Rho GTPases. Overexpression of RhoA, RhoB, or RhoC GTPases in transfected HeLa cells conferred an increased resistance to toxins A and B, indicating that these toxins cause their cytopathic effects primarily by affecting Rho proteins. In addition, toxin A and B treatment appeared to result in modification of Rho, since Rho isolated from toxin-treated cells had a decreased ability to be ADP-ribosylated by Clostridium botulinum C3 exoenzyme. In contrast, the lethal toxin (LT) of Clostridium sordellii, although structurally and immunologically related to C. difficile toxin B, appeared to induce cytopathic effects independently of the Rho GTPases. Overexpression of RhoA in transfected HeLa cells did not protect them from the effect of LT, and Rho isolated from lysates of LT-treated cells was not resistant to modification by C3. Immunofluorescence studies showed that LT treatment caused a cytopathic effect that was very different from those described for C. difficile toxins A and B, resulting in an increase in cortical F-actin, with a concomitant decrease in the number of stress fibers, and in the formation of numerous microvilli containing the actin-bundling protein fimbrin/plastin. PMID:7558320

  18. 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

  19. 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

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

    2016-03-25

    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.

  20. 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 ...

  1. Management of Clostridium difficile Infection

    PubMed Central

    Al-Jashaami, Layth S.

    2016-01-01

    Since the discovery of Clostridium difficile infection (CDI) in the 1970s, there has been an increase in the incidence, severity, and recurrence rate of the disease. We reviewed the recent CDI literature in PubMed published before February 28, 2016 that focused on advances in therapy. Despite a large number of studies describing methods for diagnosing the disease, there is currently no definitive test that identifies this infection with certainty, which complicates therapy. Recommended therapy for CDI includes oral metronidazole for mild cases and oral vancomycin or fidaxomicin for moderate to severe cases, each given for 10 to 14 days. For infection with spore-forming C difficile, this length of treatment may be insufficient to lead to cure; however, continuing antibiotics for longer periods of time may unfavorably alter the microbiome, preventing recovery. Treatment with metronidazole has been associated with an increasing failure rate, and the only clear recommended form of metronidazole for treatment of CDI is the intravenous formulation for patients unable to take oral medications. For vancomycin or fidaxomicin treatment of first CDI recurrences, the drug used in the initial bout can be repeated. For second or future recurrences, vancomycin can be given in pulsed or tapered doses. New modalities of treatment, such as bacteriotherapy and immunotherapy, show promise for the treatment of recurrent CDI. PMID:27917075

  2. 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.

  3. Probiotics in Clostridium difficile Infection

    PubMed Central

    Na, Xi; Kelly, Ciaran

    2017-01-01

    Clostridium difficile infection (CDI) is one of the most prevalent nosocomial infections. A dramatic increase in the incidence and severity of CDI has been noted in the past decade. Current recommendations suggest metronidazole as first-line therapy in mild to moderately severe CDI and oral vancomycin in individuals with severe CDI, or when metronidazole fails or is contradicted. Alterations of the colonic microbiota, usually caused by antimicrobial therapy, seem to play a critical role in CDI pathogenesis. Probiotics are live microorganisms that confer a health benefit to the host, and have been used in CDI. Although a wide variety of probiotics have been studied, the exact role of probiotics in preventing and treating CDI is not clear. In this study, we reviewed the current literature and recommendations on the most commonly studied protiotic agents (Saccharomyces boulardii, Lactobacillus species, and probiotic mixtures) used to prevent or treat CDI. Lactobacillus-containing probiotic mixtures and S. boulardii may be effective in the prevention of CDI in high-risk antibiotic recipients but this finding is based on small, individual studies, and further, larger, well-controlled studies are needed to confirm preliminary positive findings and to better delineate the efficacy of probiotics in CDI prevention or treatment. PMID:21992956

  4. Fidaxomicin: in Clostridium difficile infection.

    PubMed

    Duggan, Sean T

    2011-12-24

    Fidaxomicin is a first-in-class macrocyclic antibacterial that primarily demonstrates activity against species of clostridia, predominantly Clostridium difficile, while having limited or no activity against normal faecal microflora. Fidaxomicin is minimally absorbed following oral administration and is excreted almost solely in the faeces. Fidaxomicin displayed a high level of antibacterial activity against C. difficile in vitro, with a minimum inhibitory concentration required to inhibit 90% of C. difficile strains of 0.125-0.5 μg/mL, and was ≈2- to 8-fold more active than vancomycin or metronidazole. Fidaxomicin demonstrated a prolonged postantibiotic effect against C. difficile relative to vancomycin and metronidazole. In two randomized, double-blind, phase III trials, oral fidaxomicin 200 mg every 12 hours for 10 days was no less effective than oral vancomycin 125 mg every 6 hours for 10 days in the treatment of C. difficile infection, based on noninferiority analyses of clinical cure rates (primary endpoint). Fidaxomicin therapy was associated with a significantly lower rate of recurrence, as well as a significantly higher rate of global cure (i.e. sustained clinical response; resolution of diarrhoea without recurrence) compared with vancomycin therapy in the two clinical trials. Fidaxomicin was generally well tolerated in patients with C. difficile infection, with a tolerability profile generally similar to that of vancomycin.

  5. Prevention of Infection Due to Clostridium difficile.

    PubMed

    Cooper, Christopher C; Jump, Robin L P; Chopra, Teena

    2016-12-01

    Clostridium difficile is one of the foremost nosocomial pathogens. Preventing infection is particularly challenging. Effective prevention efforts typically require a multifaceted bundled approach. A variety of infection control procedures may be advantageous, including strict hand decontamination with soap and water, contact precautions, and using chlorine-containing decontamination agents. Additionally, risk factor reduction can help reduce the burden of disease. The risk factor modification is principally accomplished though antibiotic stewardship programs. Unfortunately, most of the current evidence for prevention is in acute care settings. This review focuses on preventative approaches to reduce the incidence of Clostridium difficile infection in healthcare settings.

  6. Immunization strategies for Clostridium difficile infections.

    PubMed

    Rebeaud, Fabien; Bachmann, Martin F

    2012-04-01

    Clostridium difficile infection is a major cause of nosocomial disease in Western countries. The recent emergence of hypervirulent strains resistant to most antibiotics correlates with increasing disease incidence, severity and lethal outcomes. Current treatments rely on metronidazol and vancomycin, but the limited ability of these antibiotics to cure infection and prevent relapse highlights the need for new strategies. A better knowledge of the molecular mechanisms of the disease, the host immune response and identification of key virulence factors of Clostridium difficile now permits the development of new products specifically targeting the pathogen. Immune-based strategies relying on active vaccination or passive administration of antibody products are the focus of intense research and, today, the efficacy of monoclonal antibodies and of two vaccines are evaluated clinically. This review presents recent data, discusses the different strategies and highlights the challenges linked to the development of immunization strategies against this emerging threat.

  7. Clostridium difficile infection in older adults

    PubMed Central

    Jump, Robin LP

    2014-01-01

    Clostridium difficile infection, the most frequent cause of nosocomial diarrhea, disproportionately affects older adults. The two most important risk factors for developing C. difficile infection are antimicrobial exposure and age >65 years old. Risk factors specific to older adults are frequent interactions with healthcare systems and age-related changes in physiology, including immune senescence and changes to the gut microbiome. Metronidazole and oral vancomcyin are the mainstays of conventional treatment for C. difficile infection. Alternative therapies include fidaxomicin, a narrow-spectrum macrocyclic antibiotic, and fectal bacteriotherapy, which offers an excellent therapeutic outcome. Strategies to prevent C. difficile infections include enhanced infection control measures and reducing inappropriate antimicrobial use through stewardship. PMID:24955106

  8. Clostridium difficile Infection and Fecal Microbiota Transplant.

    PubMed

    Liubakka, Alyssa; Vaughn, Byron P

    2016-07-01

    Clostridium difficile infection (CDI) is a major source of morbidity and mortality for hospitalized patients. Although most patients have a clinical response to existing antimicrobial therapies, recurrent infection develops in up to 30% of patients. Fecal microbiota transplant is a novel approach to this complex problem, with an efficacy rate of nearly 90% in the setting of multiple recurrent CDI. This review covers the current epidemiology of CDI (including toxigenic and nontoxigenic strains, risk factors for infection, and recurrent infection), methods of diagnosis, existing first-line therapies in CDI, the role of fecal microbiota transplant for multiple recurrent CDIs, and the potential use of fecal microbial transplant for patients with severe or refractory infection.

  9. Chronic Clostridium botulinum infections in farmers.

    PubMed

    Rodloff, Arne C; Krüger, Monika

    2012-04-01

    Although botulism is usually an acute, often lethal disease that is caused by the ingestion of botulinum neurotoxin, there are also recognized forms like infant botulism, wound botulism, or "botulism of undefined origin" that are characterized by the fact that Clostridium botulinum colonizes the host and produces its toxin in the host. Evidence is presented here that a disease in cattle and in human care takers of diseased animals that has evolved over the past two decades, may be a chronic, visceral form of C. botulinum infection.

  10. Diagnosis of Clostridium difficile Infections in Children

    PubMed Central

    Leber, Amy L.

    2016-01-01

    The detection and diagnosis of Clostridium difficile infection in pediatric populations have some unique considerations in comparison to testing in adults. The testing methodologies, including toxigenic culture, cell cytotoxicity, antigen detection, and, more recently, molecular testing, are the same in all age groups. However, limited data exist on the specific performance characteristics in children. In this review, we focus on the challenges of testing in pediatric populations and assess the available data on test performance in these populations. Additionally, a review of the existing guidance for testing is provided. PMID:26912759

  11. Clostridium difficile infection: Updates in management.

    PubMed

    Tariq, Raseen; Khanna, Sahil

    2017-01-01

    Clostridium difficile was first identified in 1978 as a diarrhea-causing bacterium in humans. In the last three decades, C. difficile infection (CDI) has reached an epidemic state, both in health care and community settings worldwide. There has been substantial progress in the field of CDI, including identification of novel risk factors, presence of CDI in individuals not considered at risk previously, and treatment options including new drugs, monoclonal antibodies, and fecal microbiota transplantation. This review discusses epidemiology, novel and traditional risk factors, and updates in management for CDI.

  12. Investigational new treatments for Clostridium difficile infection.

    PubMed

    Ivarsson, Mattias E; Leroux, Jean-Christophe; Castagner, Bastien

    2015-05-01

    Significant progress has been made by industry and academia in the past two years to address the medical threats posed by Clostridium difficile infection. These developments provide an excellent example of how patient need has driven a surge of innovation in drug discovery. Indeed, only two drugs were approved for the infection in the past 30 years but there are 13 treatment candidates in clinical trials today. What makes the latter number even more remarkable is the diversity in the strategies represented (antibiotics, microbiota supplements, vaccines, antibiotic quenchers and passive immunization). In this review, we provide a snapshot of the current stage of these breakthroughs and argue that there is still room for further innovation in treating C. difficile infection.

  13. Clostridium difficile infection in horses: a review.

    PubMed

    Diab, S S; Songer, G; Uzal, F A

    2013-11-29

    Clostridium difficile is considered one of the most important causes of diarrhea and enterocolitis in horses. Foals and adult horses are equally susceptible to the infection. The highly resistant spore of C. difficile is the infectious unit of transmission, which occurs primarily via the fecal-oral route, with sources of infection including equine feces, contaminated soil, animal hospitals, and feces of other animals. Two major risk factors for the development of C. difficile associated disease (CDAD) in adult horses are hospitalization and antimicrobial treatment, although sporadically, cases of CDAD can occur in horses that have not received antimicrobials or been hospitalized. The most common antibiotics associated with CDAD in horses are erythromycin, trimethoprim/sulfonamides, β-lactam antimicrobials, clindamycin, rifampicin, and gentamicin. Clinical signs and intestinal lesions of CDAD infection are not specific and they cannot be used to distinguish infections by C. difficile from infections by other agents, such as Clostridium perfringens or Salmonella sp. The distribution of lesions throughout the intestinal tract seems to be age-dependent. Small intestine is invariably affected, and colon and cecum may or may not have lesions in foals<1-month old. Naturally acquired disease in older foals and adult horses has a more aboral distribution, affecting colon and sometimes cecum, but rarely the small intestine. Detection of toxin A, toxin B or both in intestinal contents or feces is considered the most reliable diagnostic criterion for CDAD in horses. Isolation of toxigenic strains of C. difficile from horses with intestinal disease is highly suggestive of CDAD. A better understanding of pathogenesis, reservoirs of infection, and vaccines and other methods of control is needed. Also further studies are recommended to investigate other possible predisposing factors and/or etiological agents of enteric diseases of horses.

  14. Tea and Recurrent Clostridium difficile Infection

    PubMed Central

    Starley, Brad; Galagan, Jack Carl; Yabes, Joseph Michael; Evans, Sara

    2016-01-01

    Background and Aims. Studies have shown effects of diet on gut microbiota. We aimed to identify foods associated with recurrent Clostridium difficile infection (CDI). Methods. In this cross-sectional survey, consecutive patients diagnosed with CDI were identified by electronic medical records. Colitis symptoms and positive Clostridium difficile assay were confirmed. Health-care onset-health-care facility associated CDI was excluded. Food surveys were mailed to 411 patients. Survey responses served as the primary outcome measure. Spearman's rank correlation identified risk factors for CDI recurrence. Results. Surveys were returned by 68 patients. Nineteen patients experienced CDI recurrence. Compared to patients without CDI recurrence, patients with CDI recurrence had more antibiotics prescribed preceding their infection (p = 0.003). Greater numbers of the latter also listed tea (p = 0.002), coffee (p = 0.013), and eggs (p = 0.013), on their 24-hour food recall. Logistic regression identified tea as the only food risk factor for CDI recurrence (adjusted OR: 5.71; 95% CI: 1.26–25.89). Conclusion. The present results indicate a possible association between tea and CDI recurrence. Additional studies are needed to characterize and confirm this association. PMID:27651790

  15. [Selected aspects of Clostridium difficile infection].

    PubMed

    Mehlich, Agnieszka; Górska, Sabina; Gamian, Andrzej; Myc, Andrzej

    2015-05-05

    Clostridium difficile pathogen is a cause of the most frequent nosocomial infection, which is antibiotic-associated diarrhea. Antibiotic treatment causes disruption of the microbiome balance, which makes the gut a friendly environment for the pathogen. It leads to pseudomembranous colitis, toxic megacolon and even death. Clostridium difficile infection (CDI) is particularly dangerous to elderly patients, leading to the highest mortality rate. C. difficile is equipped with many virulence factors such as toxin A and B, binary toxin CDT, flagellum, S-layer proteins, Cwp66 and GroEL proteins, protease Cwp84, fibronectin-binding protein and the ability to form biofilm and spores. Problems with anti-CDI therapy prompt researchers and clinicians to seek alternative ways of therapy. Identification of immunological epitopes in outer layer proteins and the use of them as antigens for anti-CDI vaccines would be a rational approach to prevent the disease, but unfortunately such vaccines are not available yet. In this article we review the course of the disease, virulence and risk factors. We summarize briefly epidemiological data and the latest achievements in CDI treatment.

  16. Clostridium difficile infection: monoclonal or polyclonal genesis?

    PubMed

    Hell, M; Permoser, M; Chmelizek, G; Kern, J M; Maass, M; Huhulescu, S; Indra, A; Allerberger, F

    2011-10-01

    Clostridium difficile is considered to be a leading cause of hospital-acquired diarrhea. C. difficile (CDI) infection shows a high rate of recurrence. There would have to be a predominantly monoclonal mechanism of CDI within individual patients in order for molecular epidemiologic tools such as polymerase chain reaction (PCR) ribotyping to be useful in outbreak investigation or differentiation between infection relapse versus re-infection. It was the aim of our study to determine whether CDI is of monoclonal or of polyclonal genesis. Between December 2009 and June 2010, 11 patients with nosocomial CDI were chosen arbitrarily. Five individual colonies of C. difficile were picked from each of the primary culture plates. Of 55 isolates gained, 47 were available for PCR ribotyping (eight isolates failed attempts to re-culture). Among these 47 isolates, eight different PCR ribotypes were identified. Only one of the 11 patients had a stool sample that yielded more than one ribotype (PCR ribotypes 438 and 232); this 67-year-old female cancer patient was already suffering from recurring diarrhea prior to the fatal episode of colitis which was subsequently investigated. We conclude that polyclonal infections may occasionally occur in patients with CDI. Our findings of predominantly monoclonal origin of CDI within patients suggest that molecular epidemiologic investigations can be used reliably for outbreak investigations or discrimination between relapse and re-infection.

  17. [Laboratory diagnosis of Clostridium difficile infection].

    PubMed

    Alcalá-Hernández, Luis; Mena-Ribas, Ana; Niubó-Bosh, Jordi; Marín-Arriaza, Mercedes

    2016-11-01

    Clostridium difficile is the leading cause of nosocomial diarrhoea in developed countries, and is one of the main aetiologic agents of community diarrhea. The eruption of the hypervirulent strain BI/NAP1/027 has given rise to an increase in the morbidity and mortality of C.difficile infection (CDI). This document aims to review the main clinical pictures of CDI and the laboratory diagnosis, including sampling, transport and storage of specimens, specimen processing, diagnostic procedures, antimicrobial susceptibility testing, and molecular characterisation of the isolates. The main purpose of the article is to develop a practical document that provides answers to the main questions that arise in the laboratory diagnosis of CDI.

  18. Therapeutic approaches for Clostridium difficile infections.

    PubMed

    Marsh, Jane W; Curry, Scott R

    2013-10-02

    Metronidazole and vancomycin remain the front-line therapies for most Clostridium difficile infections (CDI). However, recurrent CDI occurs in ∼ 25% of patients, causing significant morbidity and mortality and healthcare costs. For this population, traditional antibiotic therapies fail and new treatment options are greatly needed. The US Food and Drug Administration recently approved fidaxomicin for CDI treatment. This narrow-spectrum antibiotic preserves the normal gut microbiota and shows promise as a treatment for severe and recurrent CDI. Monoclonal antibodies and vaccines directed against toxin are currently in clinical trials and represent alternative, non-antibiotic therapies. Less traditional therapeutic interventions include bacteriotherapy with non-toxigenic C. difficile and fecal transplant. This commentary will provide an overview of current and forthcoming CDI therapies.

  19. 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 ...

  20. 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

  1. Fecal microbiota transplantation in the treatment of Clostridium difficile infections.

    PubMed

    Austin, Matthew; Mellow, Mark; Tierney, William M

    2014-06-01

    In recent years, Clostridium difficile infections have become more frequent, more severe, more refractory to standard treatment, and more likely to recur. Current antibiotic treatment regimens for Clostridium difficile infection alter the normal gut flora, which provide colonization resistance against Clostridium difficile. Over the past few years, there has been a marked increase in the knowledge of the gut microbiota and its role in health maintenance and disease causation. This has, fortuitously, coincided with the use of a unique microbial replacement therapy, fecal microbiota transplantation, in the treatment of patients with multiple recurrent Clostridium difficile infections. We briefly review current knowledge of the gut microbiota's functions. We then review the indications for use of fecal microbiota transplantation in Clostridium difficile infection, the techniques employed, and results of treatment. Fecal microbiota transplantation has been shown to be efficacious for patients with multiply recurrent Clostridium difficile infections (reported cure rates of 90%), with an excellent short-term safety profile, and has been included in the American College of Gastroenterology treatment guidelines for this troublesome disease.

  2. Current Status of Clostridium difficile Infection Epidemiology

    PubMed Central

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

    2012-01-01

    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

  3. 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

  4. Diagnosis and management of Clostridium difficile infection.

    PubMed

    Dupont, Herbert L

    2013-10-01

    Clostridium difficile infection (CDI) is increasing in frequency and severity in and out of the hospital, with a high probability of recurrence after treatment. The recent literature on CDI was reviewed using PubMed to include recent publications dealing with diagnosis and therapy. Real-time polymerase chain reaction is a sensitive and useful diagnostic test for CDI but there are growing concerns of false-positive test results if the rate of CDI is low in the patient population providing samples and/or if the population being studied commonly includes people with C difficile colonization. Recommended therapy of CDI includes oral metronidazole for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases, each given for 10 days. Colectomy is being performed more frequently in patients with fulminant CDI. For treatment of first recurrences the drug used in the first bout can be used again and for second recurrences longer courses of vancomycin often are given in a tapered dose or intermittently to allow gut flora reconstitution, or other treatments including fidaxomicin may be used. Bacteriotherapy with fecal transplantation is playing an increasing role in therapy of recurrent cases. Metagenomic studies of patients with CDI during successful therapy are needed to determine how best to protect the flora from assaults from antibacterial drugs and to develop optimal therapeutic approaches. Immunotherapy and immunoprophylaxis offer opportunities to prevent CDI, to speed up recovery from CDI, and to eliminate recurrent infection. Humanized monoclonal antitoxin antibodies and active immunization with vaccines against C difficile or its toxins are both in development and appear to be of potential value.

  5. Risk factors for Clostridium difficile infection in a hepatology ward.

    PubMed

    Vanjak, Dominique; Girault, Guillaume; Branger, Catherine; Rufat, Pierre; Valla, Dominique-Charles; Fantin, Bruno

    2007-02-01

    During 2001, Clostridium difficile infection was observed in 23 patients hospitalized in a hepatology ward (attack rate, 0.9%). Since strain typing ruled out a clonal dissemination, we performed a case-control study. In addition to antibiotic use as a risk factor, the C. difficile infection rate was higher among patients with autoimmune hepatitis (P<.01).

  6. Risk factors for Clostridium difficile infection in HIV-infected patients

    PubMed Central

    Imlay, Hannah; Kaul, Daniel; Rao, Krishna

    2016-01-01

    Background: Clostridium difficile infection is a healthcare-associated infection resulting in significant morbidity. Although immunosuppression is associated with Clostridium difficile infection acquisition and adverse outcomes, the epidemiology of Clostridium difficile infection in HIV-infected patients has been little studied in the era of antiretroviral therapy. This study identifies the risk factors for acquisition of Clostridium difficile infection in HIV-infected patients. Methods: A retrospective, propensity score–matched case–control study design was employed, with patients selected from our institution’s outpatient HIV clinic. Clostridium difficile infection cases were defined as having positive stool testing plus an appropriate clinical presentation. The propensity score was generated via multiple logistic regression from year of HIV diagnosis, age at first contact, duration of follow-up, gender, and initial CD4 count. Results: The 46 cases included were matched to a total of 180 controls. Prior antibiotic treatment was a significant predictor of Clostridium difficile infection (odds ratio: 13, 95% confidence interval: 3.49–48.8, p < .001) as was number of hospital admissions in the preceding year (odds ratio: 4.02, confidence interval: 1.81–8.94, p < .001). Having both proton pump inhibitor use and CD4 count <200 cells/µL significantly increased odds of Clostridium difficile infection in the multivariable model (odds ratio: 15.17, confidence interval: 1.31–175.9, p = .021). Conclusion: As in the general population, frequent hospitalizations and exposure to antimicrobials are independent predictors of Clostridium difficile infection acquisition in patients with HIV. Additionally, low CD4 count and proton pump inhibitor use are new potentially modifiable variables that can be targeted for prevention of Clostridium difficile infection in future interventional studies. PMID:28348742

  7. Using expert process to combat Clostridium difficile infections.

    PubMed

    Guerreiro, Isabelle; Achonu, Camille; Volkening, Grace; MacFarlane, Sam; McCreight, Liz; Egan, Cathy; Robertson, Jennifer; Garber, Gary

    2016-12-01

    In 2008, Clostridium difficile rates were increasing in Ontario, Canada, and in response, hospitals were mandated by the Ontario Ministry of Health to publicly report their C difficile infection (CDI) rates. In order to assist hospitals which had ongoing CDI outbreaks, a process of an external infection control resource team (ICRT) was introduced. This article describes the function and process of the ICRT, managed by Public Health Ontario, and reviews the lessons learned over the first 5 years of operation. These lessons may assist other hospitals in managing their own infection prevention and control outbreak.

  8. 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

  9. Fecal microbiota transplantation for the management of Clostridium difficile infection.

    PubMed

    Rao, Krishna; Young, Vincent B

    2015-03-01

    This article discusses the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). The disruption of the normal gut microbiota is central to the pathogenesis of CDI, and disruption persists in recurrent disease. The use of FMT for recurrent CDI is characterized by a high response rate and short term safety is excellent, although the long-term effects of FMT are as yet unknown.

  10. Clostridium difficile Infection in Pediatric Inflammatory Bowel Disease

    PubMed Central

    Sears, Cynthia L.; Oliva-Hemker, Maria

    2015-01-01

    Abstract: Children with inflammatory bowel disease (IBD) are disproportionately susceptible to Clostridium difficile infection (CDI) and the incidence is increasing. There has also been growing recognition of asymptomatic C. difficile colonization in pediatric IBD, which can sometimes be very difficult to distinguish from symptomatic C. difficile–associated disease in this population. In this study, we discuss the current knowledge of C. difficile infection in children with IBD, reviewing epidemiology, risk factors, and outcomes that often differ from the adult IBD population, and discuss the complexities and dilemmas of diagnosing and treating CDI in pediatric IBD. PMID:26689599

  11. Clostridium difficile infection in the elderly.

    PubMed

    Taslim, Hartono

    2009-07-01

    The aging society and the advanced of supportive treatment means that large numbers of elderly patients with risk factors for C difficile enterocolitis will continue to receive care in intensive care unit. Antibiotic resistance and older, sicker patients means that combination antibiotic therapy will become a trend in clinical setting. Age, several co-morbidities, and gastrointestinal surgery appear to be specific risk factors for C difficile infection. Diarrhea which is the only symptom in hospitalized patient should drive us to rethink about the possibility of C difficile infection especially in the elderly patient. Prudent use of antibiotic, infection control are strategies to prevent C difficile infection in clinical setting. Elderly patients who undergo gastrointestinal surgery have an increased rate of C difficile infection because of commonly used nasogastric tube. Gastrointestinal surgical patients typically have preoperative bowel preparation, receive oral preoperative antibiotics that are poorly absorbed, impaired bowel motility secondary to ileus, receive systemic preoperative antibiotics prophylaxis, and have variable lengths of no oral caloric intake during the preoperative period. The continued imprudent use of prolonged postoperative systemic antibiotics for presumed preventive purposes, particularly among the elderly and patients who have nasogastric tubes or other enteric tubes, appears to be a recipe for preventable infections with C difficile.

  12. Predictors of Clostridium difficile colitis infections in hospitals

    PubMed Central

    RICCIARDI, R.; HARRIMAN, K.; BAXTER, N. N.; HARTMAN, L. K.; TOWN, R. J.; VIRNIG, B. A.

    2008-01-01

    SUMMARY Hospital-level predictors of high rates of ‘Clostridium difficile-associated disease’ (CDAD) were evaluated in over 2300 hospitals across California, Arizona, and Minnesota. American Hospital Association data were used to determine hospital characteristics associated with high rates of CDAD. Significant correlations were found between hospital rates of CDAD, common infections and other identified pathogens. Hospitals in urban areas had higher average rates of CDAD; yet, irrespective of geographic location, hospital rates of CDAD were associated with other infections. In addition, hospitals with ‘high CDAD’ rates had slower turnover of beds and were more likely to offer transplant services. These results reveal large differences in rates of CDAD across regions. Hospitals with high rates of CDAD have high rates of other common infections, suggesting a need for broad infection control policies. PMID:17686193

  13. Clostridium difficile infection: A critical analysis of the guidance.

    PubMed

    Aziz, Ann-Marie

    A recent report by the Department of Health, Clostridium Difficile Infection: How to deal with the problem - a board to ward approach, is a revised set of guidelines based on best practice and key recommendations for the NHS to ensure the control of Clostridium difficile infection (CDI). It takes into account a national framework for clinical governance which did not previously exist, a framework that gives significant weight to infection control as a matter of patient safety, and highlights that all clinicians have a personal responsibility for infection prevention and control. It puts the onus on Trust management and PCTs to ensure that measures are in place to prevent and manage CDI according to best evidence. However, the report fails to explain how these measures will have an impact on finance and resources on an already burdened system. The author explains how much of the report is comparable with the one published in 1994, and highlights many of its limitations within the busy hospital setting. Reducing CDI is achievable, as many hospitals are showing large reductions in their CDI rates. Healthcare workers must be applauded for their success in reducing CDI, but there is more to be done.

  14. 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

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

    PubMed Central

    2009-01-01

    Clostridium septicum infections are generally associated with gastrointestinal or hematologic malignancies. We report the first case of hepatic metastases infection with Clostridium septicum that followed alcohol injection of liver lesion. Clinicians should consider this possibility in patients with underlying malignancy who present with hepatic abscess, as prompt surgical drainage and empiric antibiotics may be life saving. PMID:20072687

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

    PubMed

    Saleh, Neam; Sohail, Muhammad R; Hashmey, Rayhan H; Al Kaabi, Mohammed

    2009-12-31

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

  17. [Treating Clostridium difficile infection with faecal transplantation: donor microbiological testing].

    PubMed

    Russello, Giuseppe; Brovarone, Flavia; Bardaro, Marcellino; Carretto, Edoardo

    2014-03-01

    Clostridium difficile associated diseases (CDADs) or C. difficile infections (CDIs) are increasing in incidence, severity and mortality. Among patients with CDIs, those with recurrent disease are less responsive to traditional therapies with commonly used drugs, such as metronidazole and vancomycin. Faecal microbiota transplantation is an old therapeutic procedure that has been recently proposed as a safe and effective treatment for CDI patients non-responsive to antibiotic therapy. In this paper we discuss the microbiological procedures that should be performed on faecal microbiota donors.

  18. [Recurrent Clostridium difficile infection treated with faecal microbiota transplantation].

    PubMed

    Fløe, Andreas; Leutscher, Peter

    2014-02-17

    Treatment of severe Clostridium difficile infection (CDI) poses a clinical challenge. Emerging evidence supports the use of faecal microbiota transplantation (FMT). An 81-year-old man was admitted with a third recurrent episode of CDI within two months. Because of clinical deterioration with development of pancolitis in spite of two weeks of metronidazole and vanco-mycin treatment, FMT was performed using a duodenal tube. The patient recovered completely without further relapse during follow-up. FMT was shown to be an efficient adjuvant treatment of complicated CDI.

  19. The prospect for vaccines to prevent Clostridium difficile infection.

    PubMed

    Ghose, Chandrabali; Kelly, Ciarán P

    2015-03-01

    Clostridium difficile is a spore-forming anaerobic gram-positive organism that is the leading cause of antibiotic-associated nosocomial infectious diarrhea in the Western world. This article describes the evolving epidemiology of C difficile infection (CDI) in the twenty-first century, evaluates the importance of vaccines against the disease, and defines the roles of both innate and adaptive host immune responses in CDI. The effects of passive immunotherapy and active vaccination against CDI in both humans and animals are also discussed.

  20. Fecal microbiota transplantation and emerging treatments for Clostridium difficile infection.

    PubMed

    Gens, Krista D; Elshaboury, Ramy H; Holt, Jessica S

    2013-10-01

    Due to the increased incidence and recurrence of Clostridium difficile infection, health care providers are seeking new and alternative treatments to the standard antibiotic therapy. The objective of this article is to present a review on the background, microbiologic efficacy, clinical efficacy, and safety of fecal microbiota transplantation and to provide an overview of emerging treatment options currently under investigation. Emerging treatment options discussed include the use of monoclonal antibodies directed against toxins A and B, C difficile vaccination, and transplantation of nontoxigenic C difficile strains.

  1. Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology.

    PubMed

    Elliott, Briony; Androga, Grace O; Knight, Daniel R; Riley, Thomas V

    2017-04-01

    Over the recent decades, Clostridium difficile infection (CDI) has emerged as a global public health threat. Despite growing attention, C. difficile remains a poorly understood pathogen, however, the exquisite sensitivity offered by next generation sequencing (NGS) technology has enabled analysis of the genome of C. difficile, giving us access to massive genomic data on factors such as virulence, evolution, and genetic relatedness within C. difficile groups. NGS has also demonstrated excellence in investigations of outbreaks and disease transmission, in both small and large-scale applications. This review summarizes the molecular epidemiology, evolution, and phylogeny of C. difficile, one of the most important pathogens worldwide in the current antibiotic resistance era.

  2. Current concepts in the management of Clostridium tetani infection.

    PubMed

    Brook, Itzhak

    2008-06-01

    This review summarizes the microbiology, management and prevention of tetanus. Tetanus is an acute toxemic illness caused by Clostridium tetani infection at a laceration or break in the skin. It can also occur as a complication of burns, puerperal infections, umbilical stumps (tetanus neonatorum) and surgical-site infection. Tetanus is an intoxication, manifested mostly by neuromuscular dysfunction, caused by tetanal exotoxin (tetanospasmin), a potent exotoxin produced by C. tetani. It starts with tonic spasms of the skeletal muscles and is followed by paroxysmal contractions. The muscle stiffness initially involves the jaw (lockjaw) and neck and later becomes generalized. Treatment goals include interrupting the production of toxin, neutralizating the unbound toxin, controlling muscle spasms, managing dysautonomia and appropriate supportive management. Specific therapy includes intramuscular administration of tetanus immunoglobulin to neutralize circulating toxin before it binds to neuronal cell membranes. The disease can be prevented by immunization with tetanal toxoid and appropriate wound care.

  3. Clostridium difficile Infection in Children: Current State and Unanswered Questions

    PubMed Central

    Tamma, Pranita D.; Sandora, Thomas J.

    2012-01-01

    The incidence of Clostridium difficile infection (CDI) in children has increased over the past decade. In recent years, new and intriguing data on pediatric CDI have emerged. Community-onset infections are increasingly recognized, even in children who have not previously received antibiotics. A hypervirulent strain is responsible for up to 20% of pediatric CDI cases. Unique risk factors for CDI in children have been identified. Advances in diagnostic testing strategies, including the use of nucleic acid amplification tests, have raised new questions about the optimal approach to diagnosing CDI in children. Novel therapeutic options are available for adult patients with CDI, raising questions about the use of these agents in children. Updated recommendations about infection prevention and control measures are now available. We summarize these recent developments in pediatric CDI in this review and also highlight remaining knowledge gaps that should be addressed in future research efforts. PMID:23687578

  4. 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

  5. ECCMID 2016: addressing the burden of recurrent Clostridium difficile infections.

    PubMed

    Eckmann, Christian; Lyon, Sue

    2016-10-01

    26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), 9-12th April 2016, Amsterdam, The Netherlands The European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) is the annual scientific meeting of the European Society of Clinical Microbiology. ECCMID 2016, held in Amsterdam, The Netherlands, was attended by over 11,600 clinical microbiologists and infectious disease physicians from more than 120 countries. The Congress offered an essential opportunity to learn more about the diagnosis, prevention and treatment of healthcare-associated infections, especially those caused by Clostridium difficile. Recurrent C. difficile infections have an especially serious adverse impact on patients, their families and healthcare systems across Europe and around the world, and continue to be a cause for concern among ECCMID delegates and their colleagues responsible for managing vulnerable patients in acute hospitals and other healthcare facilities.

  6. Fecal microbiota transplantation in treating Clostridium difficile infection.

    PubMed

    Brown, William R

    2014-08-01

    Clostridium difficile infection (CDI) is an increasingly common and severe international health problem. Customary treatment of this infection, usually with antibiotics, is often ineffective and its recurrence is common. In recent years the treatment of recurrent or refractory CDI by the transfer of stool from an uninfected person, so called fecal "microbiota transplantation" has become recognized as effective and generally safe. The effectiveness of this novel treatment is incompletely defined but is likely to be due to its correction of the intestinal dysbiosis that characterizes the disease. Practical methods for the administration of the transplantation have been described. This review summarizes the current reported experiences with fecal microbiota transplantation in the treatment for CDI.

  7. Conventional and alternative treatment approaches for Clostridium difficile infection

    PubMed Central

    Aljarallah, Khalid M.

    2017-01-01

    Clostridium difficile-associated disease continues to be one of the leading health concerns worldwide. C. difficile is considered as a causative agent of nosocomial diarrhea that causes serious infection, which may result in death. The incidences of C. difficile infection (CDI) in developed countries have become increasingly high which may be attributed to the emergence of newer epidemic strains, extensive use of antibiotics, and limited alternative therapies. The available treatment options against CDI are expensive and promote resistance. Therefore, there is urgent need for new approaches to meet these challenges. This review discusses the current understanding of CDI, the existing clinical treatment strategies and future potential options as antidifficile agents based on the available published works. PMID:28293151

  8. 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

  9. Genome Sequence of Clostridium paraputrificum 373-A1 Isolated in Chile from a Patient Infected with Clostridium difficile

    PubMed Central

    Guerrero-Araya, Enzo; Plaza-Garrido, Angela; Díaz-Yañez, Fernando; Pizaro-Guajardo, Marjorie; Valenzuela, Sandro L.; Meneses, Claudio; Gil, Fernando

    2016-01-01

    Clostridium paraputrificum is a gut microbiota member reported in several cases of bacteremia and coinfections. So far, only one genome sequence of a C. paraputrificum (AGR2156) isolate is available. Here, we present the draft genome of C. paraputrificum strain 373-A1, isolated from stools from a patient with C. difficile infection. PMID:27811092

  10. Genome Sequence of Clostridium paraputrificum 373-A1 Isolated in Chile from a Patient Infected with Clostridium difficile.

    PubMed

    Guerrero-Araya, Enzo; Plaza-Garrido, Angela; Díaz-Yañez, Fernando; Pizaro-Guajardo, Marjorie; Valenzuela, Sandro L; Meneses, Claudio; Gil, Fernando; Castro-Nallar, Eduardo; Paredes-Sabja, Daniel

    2016-11-03

    Clostridium paraputrificum is a gut microbiota member reported in several cases of bacteremia and coinfections. So far, only one genome sequence of a C. paraputrificum (AGR2156) isolate is available. Here, we present the draft genome of C. paraputrificum strain 373-A1, isolated from stools from a patient with C. difficile infection.

  11. Clostridium difficile: Changing Epidemiology, Treatment and Infection Prevention Measures.

    PubMed

    Cecil, Jane A

    2012-12-01

    Clostridium difficile was first reported as a cause of antibiotic-associated colitis in 1978. In more recent years we have witnessed disturbing trends associated with C. difficile infection (CDI). CDI has become more common, affecting populations previously considered at low risk, more severe with an associated increase in mortality, and more difficult to treat with some patients experiencing multiple relapses and a reduced responsiveness to previously effective antibiotics. These trends have been coincident with the emergence of a new hypervirulent strain responsible for several outbreaks in the last decade. Fortunately, we have also seen promising developments, particularly with regard to testing and treatment. This review discusses recent changes in the epidemiology of CDI and recent developments in the testing, treatment and prevention of CDI.

  12. 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

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

    PubMed

    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.

  14. Challenges and opportunities in the management of Clostridium difficile infection.

    PubMed

    DuPont, Herbert L

    2014-11-01

    Clostridium difficile infection (CDI) is increasing in all regions of the world where sought. There is no gold standard for diagnosis of CDI, with available tests having limitations. Prevention of CDI will be seen with antibiotic stewardship, improved disinfection of hospitals and nursing homes, chemo- and immuno-prophylaxis and next generation probiotics. The important therapeutic agents are oral vancomycin and fidaxomicin with metronidazole being used only in mild cases or when oral therapy cannot be given. Current therapy of CDI for 10 days is associated with high rate of recurrence that may be prevented by prolonging initial therapy. Future treatment strategies will focus on drugs that inhibit C. difficile, reduce toxin activity and inflammation in the gut, and improve colonic flora diversity.

  15. Clostridium difficile Infection and Inflammatory Bowel Disease: A Review

    PubMed Central

    Sinh, Preetika; Barrett, Terrence A.; Yun, Laura

    2011-01-01

    The incidence of Clostridium difficile infection (CDI) has significantly increased in the last decade in the United States adding to the health care burden of the country. Patients with inflammatory bowel disease (IBD) have a higher prevalence of CDI and worse outcomes. In the past, the traditional risk factors for CDI were exposure to antibiotics and hospitalizations in elderly people. Today, it is not uncommon to diagnose CDI in a pregnant women or young adult who has no risk factors. C. difficile can be detected at the initial presentation of IBD, during a relapse or in asymptomatic carriers. It is important to keep a high index of suspicion for CDI in IBD patients and initiate prompt treatment to minimize complications. We summarize here the changing epidemiology, pathogenesis, risk factors, clinical features, and treatment of CDI in IBD. PMID:21915178

  16. Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis.

    PubMed

    Chan, Khee-Siang; Lee, Wen-Ying; Yu, Wen-Liang

    2016-12-01

    Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients with human immunodeficiency virus infection, organ transplantation, and malignancy receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents. However, CMV colitis is increasingly recognized in immunocompetent hosts. Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in apparently healthy individuals has been published in recent years, which could result in high morbidity and mortality. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with abdominal pain, watery, or especially bloody diarrhea, which could be refractory to standard treatment for CDI. As a characteristic of CDI, however, pseudomembranous colitis may be only caused by CMV infection. Real-time CMV-polymerase chain reaction (PCR) for blood and stool samples may be a useful and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal biopsies may increase the diagnostic yield of traditional histopathology. CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon, and colonic perforation, so that may necessitate pre-emptive antiviral treatment for those who are positive for CMV-PCR in blood and/or stool samples while pending histological diagnosis.

  17. Role of cephalosporins in the era of Clostridium difficile infection

    PubMed Central

    Wilcox, Mark H.; Chalmers, James D.; Nord, Carl E.; Freeman, Jane; Bouza, Emilio

    2017-01-01

    The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011–12 to 2012–13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes. PMID:27659735

  18. Role of cephalosporins in the era of Clostridium difficile infection.

    PubMed

    Wilcox, Mark H; Chalmers, James D; Nord, Carl E; Freeman, Jane; Bouza, Emilio

    2017-01-01

    The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011-12 to 2012-13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes.

  19. 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

  20. Clostridium difficile infection prevention: biotherapeutics, immunologics, and vaccines.

    PubMed

    Gerding, Dale N

    2012-01-01

    We are in the midst of a resurgence of Clostridium difficile infection (CDI) in North America and Europe for which morbidity and mortality are higher than ever seen. C. difficile has risen in frequency to become the most common healthcare-associated infection pathogen, exceeding methicillin-resistant Staphylococcus aureus in many hospitals. Protection against CDI is thought to be mediated first by the normal bacterial microbiota, supplemented by an adaptive immune antibody response directed primarily at C. difficile toxins. Treatment of CDI is with antimicrobials that also further disrupt the protective bacterial microbiota leaving the patient susceptible to recurrent CDI. In addition, patients most susceptible to CDI, the advanced elderly, may already have a limited immune response and fail to increase their adaptive immune response with infection. The importance of both of these protective modalities has been demonstrated by 1) the success of fecal microbiota to restore "colonization resistance" for patients with multiple recurrences of CDI, and 2) the marked reduction in CDI recurrences with the use of intravenous monoclonal antibodies directed against toxin A and toxin B as an adjunct to antimicrobial treatment. Anti-toxin vaccines, passive monoclonal anti-toxin antibodies, and non-toxigenic C. difficile (to restore colonization resistance) are already undergoing patient clinical trials. The opportunity to prevent CDI is compelling and future research should focus on understanding the critical elements of the microbiota needed to restore colonization resistance and on development of novel immunologic strategies that include systemic and mucosal vaccines and passive immune modulators.

  1. Advances in the Microbiome: Applications to Clostridium difficile Infection

    PubMed Central

    Culligan, Eamonn P.; Sleator, Roy D.

    2016-01-01

    Clostridium difficile is a major cause of morbidity and mortality worldwide, causing over 400,000 infections and approximately 29,000 deaths in the United States alone each year. C. difficile is the most common cause of nosocomial diarrhoea in the developed world, and, in recent years, the emergence of hyper-virulent (mainly ribotypes 027 and 078, sometimes characterised by increased toxin production), epidemic strains and an increase in the number of community-acquired infections has caused further concern. Antibiotic therapy with metronidazole, vancomycin or fidaxomicin is the primary treatment for C. difficile infection (CDI). However, CDI is unique, in that, antibiotic use is also a major risk factor for acquiring CDI or recurrent CDI due to disruption of the normal gut microbiota. Therefore, there is an urgent need for alternative, non-antibiotic therapeutics to treat or prevent CDI. Here, we review a number of such potential treatments which have emerged from advances in the field of microbiome research. PMID:27657145

  2. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... potency using the toxin-neutralization test provided in this paragraph. (1) When used in this test, the... antitoxin content of the rabbit serums shall be determined by the serum neutralization test as follows: (i....0 Lo doses of Standard Toxin die, the results of the serum neutralization test are inconclusive...

  3. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... potency using the toxin-neutralization test provided in this paragraph. (1) When used in this test, the... antitoxin content of the rabbit serums shall be determined by the serum neutralization test as follows: (i....0 Lo doses of Standard Toxin die, the results of the serum neutralization test are inconclusive...

  4. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... potency using the toxin-neutralization test provided in this paragraph. (1) When used in this test, the... antitoxin content of the rabbit serums shall be determined by the serum neutralization test as follows: (i....0 Lo doses of Standard Toxin die, the results of the serum neutralization test are inconclusive...

  5. 9 CFR 113.109 - Clostridium Sordellii Bacterin-Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... potency using the toxin-neutralization test provided in this paragraph. (1) When used in this test, the... antitoxin content of the rabbit serums shall be determined by the serum neutralization test as follows: (i....0 Lo doses of Standard Toxin die, the results of the serum neutralization test are inconclusive...

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Inspection Service. (vi) Diluent. The solution used to make proper dilutions prescribed in this test. Such solutions shall be made by dissolving 1 gram of peptone and 0.25 gram of sodium chloride in each 100 ml of....0 International Unit of Standard Antitoxin with 1.0 L+ dose of diluted Standard Toxin. Each...

  7. 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

  8. 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

  9. 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

  10. Fecal microbiota transplantation for management of Clostridium difficile infection.

    PubMed

    Vaishnavi, Chetana

    2014-07-01

    The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.

  11. Current knowledge on the laboratory diagnosis of Clostridium difficile infection.

    PubMed

    Martínez-Meléndez, Adrián; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Maldonado-Garza, Héctor Jesús; Villarreal-Treviño, Licet; Garza-González, Elvira

    2017-03-07

    Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI.

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

    PubMed

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

    2014-01-01

    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.

  13. Breakthroughs in the treatment and prevention of Clostridium difficile infection.

    PubMed

    Kociolek, Larry K; Gerding, Dale N

    2016-03-01

    This Review summarizes the latest advances in the treatment and prevention of Clostridium difficile infection (CDI), which is now the most common health-care-associated infection in the USA. As traditional, standard CDI antibiotic therapies (metronidazole and vancomycin) are limited by their broad spectrum and further perturbation of the intestinal microbiota, which result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are needed. Emerging CDI therapies are focused on limiting further perturbation of the intestinal microbiota and/or restoring the microbiota to its pre-morbid state, reducing colonization of the intestinal tract by toxigenic strains of C. difficile and bolstering the host immune response against C. difficile toxins. Fidaxomicin is associated with reduced CDI recurrences, and other emerging narrow-spectrum CDI antibiotic therapies might eventually demonstrate a similar benefit. Prevention of intestinal colonization of toxigenic strains of C. difficile can be achieved through restoration of the intestinal microbiota with faecal microbiota transplantation, as well as by colonizing the gut with nontoxigenic C. difficile strains. Finally, emerging immunological therapies, including monoclonal antibodies and vaccines against C. difficile toxins, might protect against CDI and subsequent CDI recurrences. The available clinical data for these emerging therapies, and their relative advantages and disadvantages, are described.

  14. Clostridium difficile infection: current, forgotten and emerging treatment options.

    PubMed

    Drekonja, Dimitri M

    2014-09-01

    Clostridium difficile infection (CDI) has increased in incidence and severity, and is now among the most common nosocomial infections. Several agents are available for the initial treatment of CDI, some of which are rarely used, and none of which is clearly superior for initial clinical cure. Fidaxomicin appears to offer a benefit in terms of preventing recurrent disease, although the cost-benefit ratio is debated. Recurrent CDI is a major challenge, occurring after 15-30% of initial episodes. The treatment of recurrent CDI is difficult, with sparse evidence available to support any particular agent. Fecal microbiota therapy, also known as 'stool transplantation', appears to be highly effective, although availability is currently limited, and the regulatory environment is in flux. Synthetic stool products and an orally available fecal microbiota therapy product are both under investigation, which may address the problem of availability. As with most infectious diseases, an effective vaccine would be a welcome addition to our armamentarium, but none is currently available.

  15. Current knowledge on the laboratory diagnosis of Clostridium difficile infection

    PubMed Central

    Martínez-Meléndez, Adrián; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Maldonado-Garza, Héctor Jesús; Villarreal-Treviño, Licet; Garza-González, Elvira

    2017-01-01

    Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI. PMID:28321156

  16. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.

    PubMed

    Wilcox, Mark H; Gerding, Dale N; Poxton, Ian R; Kelly, Ciaran; Nathan, Richard; Birch, Thomas; Cornely, Oliver A; Rahav, Galia; Bouza, Emilio; Lee, Christine; Jenkin, Grant; Jensen, Werner; Kim, You-Sun; Yoshida, Junichi; Gabryelski, Lori; Pedley, Alison; Eves, Karen; Tipping, Robert; Guris, Dalya; Kartsonis, Nicholas; Dorr, Mary-Beth

    2017-01-26

    Background Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. Methods We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. Results In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, -9.9 percentage points; 95% CI, -15.5 to -4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, -11.6 percentage points; 95% CI, -17.4 to -5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, -10.7 percentage points; 95% CI, -16.4 to -5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab

  17. Life-threatening clostridial infections.

    PubMed

    Stevens, Dennis L; Aldape, Michael J; Bryant, Amy E

    2012-04-01

    Life-threatening soft tissue infections caused by Clostridium species have been described in the medical literature for hundreds of years largely because of their fulminant nature, distinctive clinical presentations and complex management issues. The Clostridium species perfringens, septicum and histolyticum are the principal causes of trauma-associated gas gangrene and their incidence increases dramatically in times of war, hurricanes, earthquakes and other mass casualty conditions. Recently, there has also been an increased incidence of spontaneous gas gangrene caused by Clostridium septicum in association with gastrointestinal abnormalities and neutropenia. Similarly, over the last 15 years there has been increased recognition of a toxic shock-like syndrome associated with Clostridium sordellii in individuals skin-popping black tar heroin, in women undergoing childbirth or other gynecologic procedures including medically-induced abortion. Like their cousins Clostridium tetanus and Clostridium botulinum, the pathogenesis of these clostridial infections is largely the consequence of potent exotoxin production. Strategies to inhibit toxin production, neutralize circulating toxins and prevent their interaction with cells of the innate immune response are sorely needed. Recent studies have elucidated novel targets that may hold promise for newer therapeutic modalities.

  18. Clostridium difficile infection in the hospitalized pediatric population: increasing trend in disease incidence.

    PubMed

    Deshpande, Abhishek; Pant, Chaitanya; Anderson, Michael P; Donskey, Curtis J; Sferra, Thomas J

    2013-10-01

    To determine whether the incidence of Clostridium difficile infection continues to increase in hospitalized pediatric patients, we evaluated data from a United States national inpatient database. For the period of 2003 to 2009, we found an increasing trend in the incidence of C. difficile infection. These data suggest greater effort be given to prevent and treat this infection in children.

  19. 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

  20. 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.

  1. Thrombocytopenia in hospitalized patients with severe clostridium difficile infection.

    PubMed

    Fountain, Eric M; Moses, Maggie C; Park, Lawrence P; Woods, Christopher W; Arepally, Gowthami M

    2017-01-01

    Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea and colitis. The incidence and prognostic significance of thrombocytopenia as related to mode of acquisition (hospital vs. community), NAP1/027 strain, and disease severity has not been examined. We performed a single-institution retrospective analysis of all adult inpatients from 2013 to 2014 diagnosed with CDI during their hospitalization to document the incidence/prevalence of thrombocytopenia and associated outcomes. Severe disease was defined by a composite endpoint of inpatient death, death within 30 days of discharge, presence of septic shock, or need for colectomy during hospitalization. Of the 533 patients diagnosed with CDI, moderate thrombocytopenia (platelet count <100 × 10(9)/L at time of CDI diagnosis) was present in 15 % of the total cohort and incident thrombocytopenia developed in 3 % of patients after admission. Thrombocytopenia was more common in hospital-acquired disease and associated with increased length of stay, but was not associated with treatment failure. Those with moderate thrombocytopenia were more likely to have severe disease, after controlling for white blood cell count, albumin, and creatinine. Moderate thrombocytopenia is associated with poor prognosis and is a potential risk stratification tool for severe CDI.

  2. Host response to Clostridium difficile infection: Diagnostics and detection.

    PubMed

    Usacheva, Elena A; Jin, Jian-P; Peterson, Lance R

    2016-12-01

    Clostridium difficile infection (CDI) is a significant healthcare concern worldwide, and C. difficile is recognised as the most frequent aetiological agent of infectious healthcare-associated diarrhoea in hospitalised adult patients. The clinical manifestation of CDI varies from self-limited diarrhoea to life-threatening colitis. Such a broad disease spectrum can be explained by the impact of host factors. Currently, a complex CDI aetiology is widely accepted, acknowledging the interaction between bacteria and the host. C. difficile strains producing clostridial toxins A and B are considered toxigenic and can cause disease; those not producing the toxins are non-pathogenic. A person colonised with a toxigenic strain will not necessarily develop CDI. It is imperative to recognise patients with active disease from those only colonised with this pathogen and to implement appropriate treatment. This can be achieved by diagnostics that rely on host factors specific to CDI. This review will focus on major aspects of CDI pathogenesis and molecular mechanisms, describing host factors in disease progression and assessment of the host response in order to facilitate the development of CDI-specific diagnostics.

  3. Fidaxomicin--the new drug for Clostridium difficile infection.

    PubMed

    Vaishnavi, Chetana

    2015-04-01

    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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. A bundle strategy including patient hand hygiene to decrease clostridium difficile infections.

    PubMed

    Pokrywka, Marian; Feigel, Jody; Douglas, Barbara; Grossberger, Susan; Hensler, Amelia; Hensler, Amelia; Weber, David

    2014-01-01

    Prevention strategies for Clostridium difficile infection traditionally have addressed barrier precautions, environmental disinfection, and health care worker hand hygiene. When applied as a bundle, this approach has been used widely as an evidence-based strategy to prevent hospital-acquired C. difficile infection. Expanding the bundle to include patient hand hygiene is a nurse-driven approach to prevent C. difficile transmission.

  9. Clostridium difficile infection aggravates colitis in interleukin 10-deficient mice

    PubMed Central

    Kim, Mi Na; Koh, Seong-Joon; Kim, Jung Mogg; Im, Jong Pil; Jung, Hyun Chae; Kim, Joo Sung

    2014-01-01

    AIM: To investigate the effect of Clostridium difficile (C. difficile) infection in an interleukin 10-deficient (IL-10-/-) mouse model of inflammatory bowel disease. METHODS: Bone marrow-derived dendritic cells isolated from wild type (WT) and IL-10-/-mice were stimulated for 4 h with C. difficile toxin A (200 μg/mL), and gene expression of interferon (IFN)-γ, IL-12 and IL-23 was determined by real-time reverse transcription polymerase chain reaction. WT and IL-10-/- mice (n = 20 each) were exposed to an antibiotic cocktail for three days and then were injected with clindamycin (i.p.). Mice (n = 10 WT, 10 IL-10-/-) were then challenged with oral administration of C. difficile (1 × 105 colony forming units of strain VPI 10463). Animals were monitored daily for 7 d for signs of colitis. Colonic tissue samples were evaluated for cytokine gene expression and histopathologic analysis. RESULTS: C. difficile toxin A treatment induced IFN-γ gene expression to a level that was significantly higher in BDMCs from IL-10-/- compared to those from WT mice (P < 0.05). However, expression of IL-12 and IL-23 was not different among the groups. Following C. difficile administration, mice developed diarrhea and lost weight within 2-3 d. Weight loss was significantly greater in IL-10-/- compared to WT mice (P < 0.05). C. difficile infection induced histopathologic features typical of colitis in both IL-10-/- and WT mice. The histopathologic severity score was significantly higher in the IL-10-/- than in WT mice (mean ± standard error; 5.50 ± 0.53 vs 2.44 ± 0.46; P < 0.05). This was accompanied by a significantly greater increase in IFN-γ gene expression in colonic tissues from IL-10-/- than from WT mice challenged with C. difficile (P < 0.05). CONCLUSION: These results indicate that colitis is more severe after C. difficile infection in IL-10-/-mice, and that IFN-γ expression is involved in this process. PMID:25493020

  10. Role of Microbiota and Innate Immunity in Recurrent Clostridium difficile Infection

    PubMed Central

    Bibbò, Stefano; Lopetuso, Loris Riccardo; Ianiro, Gianluca; Di Rienzo, Teresa; Gasbarrini, Antonio

    2014-01-01

    Recurrent Clostridium difficile infection represents a burdensome clinical issue whose epidemiology is increasing worldwide. The pathogenesis is not yet completely known. Recent observations suggest that the alteration of the intestinal microbiota and impaired innate immunity may play a leading role in the development of recurrent infection. Various factors can cause dysbiosis. The causes most involved in the process are antibiotics, NSAIDs, acid suppressing therapies, and age. Gut microbiota impairment can favor Clostridium difficile infection through several mechanisms, such as the alteration of fermentative metabolism (especially SCFAs), the alteration of bile acid metabolism, and the imbalance of antimicrobial substances production. These factors alter the intestinal homeostasis promoting the development of an ecological niche for Clostridium difficile and of the modulation of immune response. Moreover, the intestinal dysbiosis can promote a proinflammatory environment, whereas Clostridium difficile itself modulates the innate immunity through both toxin-dependent and toxin-independent mechanisms. In this narrative review, we discuss how the intestinal microbiota modifications and the modulation of innate immune response can lead to and exacerbate Clostridium difficile infection. PMID:24995345

  11. Recurrent Clostridium difficile infection among Medicare patients in nursing homes

    PubMed Central

    Zilberberg, Marya D.; Shorr, Andrew F.; Jesdale, William M.; Tjia, Jennifer; Lapane, Kate

    2017-01-01

    Abstract We explored the epidemiology and outcomes of Clostridium difficile infection (CDI) recurrence among Medicare patients in a nursing home (NH) whose CDI originated in acute care hospitals. We conducted a retrospective, population-based matched cohort combining Medicare claims with Minimum Data Set 3.0, including all hospitalized patients age ≥65 years transferred to an NH after hospitalization with CDI 1/2011-11/2012. Incident CDI was defined as ICD-9-CM code 008.45 with no others in prior 60 days. CDI recurrence was defined as (within 60 days of last day of CDI treatment): oral metronidazole, oral vancomycin, or fidaxomicin for ≥3 days in part D file; or an ICD-9-CM code for CDI (008.45) during a rehospitalization. Cox proportional hazards and linear models, adjusted for age, gender, race, and comorbidities, examined mortality within 60 days and excess hospital days and costs, in patients with recurrent CDI compared to those without. Among 14,472 survivors of index CDI hospitalization discharged to an NH, 4775 suffered a recurrence. Demographics and clinical characteristics at baseline were similar, as was the risk of death (24.2% with vs 24.4% without). Median number of hospitalizations was 2 (IQR 1–3) among those with and 0 (IQR 0–1) among those without recurrence. Adjusted excess hospital days per patient were 20.3 (95% CI 19.1–21.4) and Medicare reimbursements $12,043 (95% CI $11,469–$12,617) in the group with a recurrence. Although recurrent CDI did not increase the risk of death, it was associated with a far higher risk of rehospitalization, excess hospital days, and costs to Medicare. PMID:28272217

  12. Development of Clostridium septicum gas gangrene as an adverse effect of clindamycin-induced Clostridium difficile infection in a pediatric patient.

    PubMed

    Kiser, Casey J; Urish, Kenneth L; Boateng, Henry A

    2014-09-01

    Clostridium myonecrosis or gas gangrene is a life-threatening infection characterized by either traumatic or atraumatic etiology. It has been widely described in patients with traumatic open wounds and in immunocompromised patients, including malignancy. A third source can result from natural flora in the gastrointestinal tract after bowel ischemia. This is a rare occurrence and is even less commonly described in the pediatric population. We present a pediatric patient who developed Clostridium septicum myonecrosis as an iatrogenic complication from clindamycin-induced Clostridium difficile ischemic colitis.

  13. Clostridium perfringens type A netF and netE positive and Clostridium difficile co-infection in two adult dogs.

    PubMed

    Diniz, Amanda Nádia; Silva, Rodrigo Otávio Silveira; Oliveira Junior, Carlos Augusto; Pierezan, Felipe; Lobato, Francisco Carlos Faria

    2016-04-01

    The aim of this study was to report two cases of Clostridium perfringens type A and Clostridium difficile co-infection in adult dogs. Both animals were positive for A/B toxin. Toxigenic C. difficile and C. perfringens type A positive for NetE and NetF-encoding genes were isolated. This report reinforces the necessity of studying a possible synergism of C. difficile and C. perfringens in enteric disorders.

  14. Effect of cobra venom factor on experimental infection of mice against Clostridium chauvoei.

    PubMed

    Tamura, Y; Kijima, M; Suzuki, S; Takahashi, T; Nakamura, M

    1992-10-01

    The effect of cobra venom factor (CoVF) treatment was examined to clarify the mechanism of resistance of mice to Clostridium chauvoei infection. In CoVF-treated mice inoculated with spores of C. chauvoei, no death occurred and the organisms in the infected muscle progressively decreased, similar to that of non-treated control mice. These results indicated that C3 did not play a significant role in the resistance of mice against C. chauvoei infection.

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

    PubMed

    Uzal, F A

    2004-04-01

    Clostridium perfringens produces disease in sheep, goats and other animal species, most of which are generically called enterotoxemias. This micro-organism 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 in large numbers and produces several potent toxins that are absorbed into the general circulation or act locally with usually devastating effects on the host. History, clinical signs and gross post-mortem findings are useful tools for establishing a presumptive diagnosis of enterotoxaemia by C. perfringens in sheep and goats, although no definitive diagnosis of these diseases can be made without laboratory confirmation. Because all types of C. perfringens can be normal inhabitants of the intestine of most animals, culture of this micro-organism from intestinal contents of animals has no diagnostic value unless a colony count is performed and large numbers (usually more than 10(4)-10(7)CFU/g) of C. perfringens are found. The most accepted criterion in establishing a definitive diagnosis of enterotoxaemia by C. perfringens is the detection of its toxins in intestinal contents. However, some of the major toxins of C. perfringens (i.e. epsilon toxin) can also be found, albeit in small amounts, in the small intestine of clinically normal sheep, and this poses a diagnostic challenge. In such cases the histopathology of the brain must be used as an alternative diagnostic tool, since the lesions produced by epsilon toxin in the brains of sheep and goats are unique and pathognomonic for C. perfringens type D enterotoxaemia. Ancillary tests, such as measurement of urine glucose or observation of Gram stained smears of intestinal mucosa can be used and, although they have a presumptive diagnostic value when positive, they cannot be used to rule out a diagnosis of enterotoxaemia if they are negative. In conclusion, the

  16. Implementing automated surveillance for tracking Clostridium difficile infection at multiple healthcare facilities.

    PubMed

    Dubberke, Erik R; Nyazee, Humaa A; Yokoe, Deborah S; Mayer, Jeanmarie; Stevenson, Kurt B; Mangino, Julie E; Khan, Yosef M; Fraser, Victoria J

    2012-03-01

    Automated surveillance using electronically available data has been found to be accurate and save time. An automated Clostridium difficile infection (CDI) surveillance algorithm was validated at 4 Centers for Disease Control and Prevention Epicenter hospitals. Electronic surveillance was highly sensitive, specific, and showed good to excellent agreement for hospital-onset; community-onset, study facility-associated; indeterminate; and recurrent CDI.

  17. Clostridium difficile infection in children with inflammatory bowel disease: current evidence.

    PubMed

    Banaszkiewicz, Aleksandra; Pituch, Hanna

    2014-01-01

    Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease of the gastrointestinal tract that develops in genetically susceptible individuals. Questions about the role of infections in the development and exacerbations of inflammatory bowel disease remain unanswered. Among numerous bacteria that have been linked to IBD, the most frequently associated is Clostridium difficile. Clinical symptoms of C. difficile infection and an exacerbation of inflammatory bowel disease are often indistinguishable. In cases of diarrhea in patients with IBD and C. difficile infection, antibiotic treatment is recommended. This review attempts to summarize C. difficile infection's epidemiology and clinical features and describes current evidence on treatment of C. difficile infection in children with IBD.

  18. A case of toxic megacolon caused by clostridium difficile infection and treated with fecal microbiota transplantation.

    PubMed

    Gweon, Tae Geun; Lee, Kyung Jin; Kang, Dong Hoon; Park, Sung Soo; Kim, Kyung Hoon; Seong, Hyeon Jin; Ban, Tae Hyun; Moon, Sung Jin; Kim, Jin Su; Kim, Sang Woo

    2015-03-01

    Clostridium difficile infection. The mortality rate of fulminant C. difficile infection is reported to be as high as 50%. Fecal microbiota transplantation is a highly effective treatment in patients with recurrent or refractory C. difficile infection. However, there are few published articles on the use of such transplantation for fulminant C. difficile infection. Here, we report on a patient with toxic megacolon complicated by C. difficile infection who was treated successfully with fecal mi-crobiota transplantation. (Gut Liver, 2015;9:247-250).

  19. Viral co-infections are common and are associated with higher bacterial burden in children with clostridium difficile infection.

    PubMed

    El Feghaly, Rana E; Stauber, Jennifer L; Tarr, Phillip I; Haslam, David B

    2013-12-01

    Clostridium difficile infections in children are increasing. In this cohort study, we enrolled 62 children with diarrhea and C difficile. We performed polymerase chain reaction assays to detect viral agents of gastroenteritis and quantify C difficile burden. Fifteen (24%) children diagnosed as having C difficile infection had a concomitant viral co-infection. These patients tended to be younger and had a higher C difficile bacterial burden than children with no viral co-infections (median difference = 565,957 cfu/mL; P = 0.011), but were clinically indistinguishable. The contribution of viral co-infection to C difficile disease in children warrants future investigation.

  20. 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.

  1. [Septic shock due to a community acquired Clostridium difficile infection. A case study and a review of the literature].

    PubMed

    Bermejo, C; Maseda, E; Salgado, P; Gabilondo, G; Gilsanz, F

    2014-04-01

    The epidemiology of Clostridium difficile infection has changed in the past decade. The incidence rate of community acquired cases has increased in patients with no typical risk factors. We present a patient who was diagnosed with community-acquired Clostridium difficile infection who presented with acute abdominal pain, and subsequently developed acute renal failure and septic shock. We describe the diagnosis, treatment and outcome and brief review of the literature.

  2. What is the current role of algorithmic approaches for diagnosis of Clostridium difficile infection?

    PubMed

    Wilcox, Mark H; Planche, Tim; Fang, Ferric C; Gilligan, Peter

    2010-12-01

    With the recognition of several serious outbreaks of Clostridium difficile infection in the industrialized world coupled with the development of new testing technologies for detection of this organism, there has been renewed interest in the laboratory diagnosis of C. difficile infection. Two factors seem to have driven much of this interest. First, the recognition that immunoassays for detection of C. difficile toxins A and B, for many years the most widely used tests for C. difficile infection diagnosis, were perhaps not as sensitive as previously believed at a time when attributed deaths to C. difficile infections were showing a remarkable rise. Second, the availability of FDA-approved commercial and laboratory-developed PCR assays which could detect toxigenic strains of C. difficile provided a novel and promising testing approach for diagnosing this infection. In this point-counterpoint on the laboratory diagnosis of C. difficile infection, we have asked two experts in C. difficile infection diagnosis, Ferric Fang, who has recently published two articles in the Journal of Clinical Microbiology advocating the use of PCR as a standalone test (see this author's references 12 and 28), and Mark Wilcox, who played a key role in developing the IDSA/SHEA guidelines on Clostridium difficile infection (see Wilcox and Planche's reference 1), along with his colleague, Tim Planche, to address the following question: what is the current role of algorithmic approaches to the diagnosis of C. difficile infection?

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

    PubMed

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

    2015-10-19

    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.

  4. 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

  5. Evidence-based medicine concerning efficacy of vaccination against Clostridium chauvoei infection in cattle.

    PubMed

    Uzal, Francisco A

    2012-03-01

    Clostridium chauvoei infections occur frequently in cattle and produce disease end lethality. Vaccination is frequently used to prevent occurrence of these infections. Although the literature on blackleg is voluminous, scientific evidence on the efficacy of vaccination against C chauvoei to prevent diseases and lethality in cattle is scant. This study demonstrates that the evidence of efficacy of C chauvoei vaccines to prevent infection by this microorganism in cattle is poor to moderate. A greater participation of practitioners in clinical research and greater access to informational tools such as systematic reviews must be part of the objectives of veterinary medicine.

  6. 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.

  7. Clostridium difficile infection in a patient with Crohn disease.

    PubMed

    Hsu, Chien-Hui; Jeng, Yung-Ming; Ni, Yen-Hsuan

    2012-06-01

    Crohn disease is a chronic inflammatory disorder, which is rare in pediatric patients. The definite etiology and mechanism to induce an acute exacerbation of Crohn disease remains mostly unknown. The authors report on a 14-year-old girl with Crohn disease who has acute gastrointestinal symptoms caused by toxin A-producing Clostridium difficile, which mimicked a flare-up of Crohn disease. There was no preceding antibiotic prescription before the episode. The disease activity did not improve after steroid treatment, which is unusual for Crohn disease. However, all symptoms were dramatically relieved after eradication of C difficile, and led to a symptom-free period for more than 3 years. This case report aims to address the unusual presentation of a usual pathogen, C difficile, in a pediatric patient with Crohn disease.

  8. 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

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

    PubMed

    Mullish, B H; Marchesi, J R; Thursz, M R; Williams, H R T

    2015-05-01

    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.

  10. 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.

  11. A Comparison of Current Guidelines of Five International Societies on Clostridium difficile Infection Management.

    PubMed

    Fehér, Csaba; Mensa, Josep

    2016-09-01

    Clostridium difficile infection (CDI) is increasingly recognized as an emerging healthcare problem of elevated importance. Prevention and treatment strategies are constantly evolving along with the apperance of new scientific evidence and novel treatment methods, which is well-reflected in the differences among consecutive international guidelines. In this article, we summarize and compare current guidelines of five international medical societies on CDI management, and discuss some of the controversial and currently unresolved aspects which should be addressed by future research.

  12. Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.

    PubMed

    Woodworth, Michael H; Neish, Emma M; Miller, Nancy S; Dhere, Tanvi; Burd, Eileen M; Carpentieri, Cynthia; Sitchenko, Kaitlin L; Kraft, Colleen S

    2017-04-01

    Fecal microbiota transplantation is an efficacious and inexpensive therapy for recurrent Clostridium difficile infection, yet its safety is thought to depend on appropriate fecal donor screening. FDA guidance for regulation of this procedure is in flux, but screening and manufacture of fecal material from asymptomatic donors present many challenges to clinical laboratories. This minireview summarizes FDA regulatory changes, principles of donor selection, and recommended laboratory screening practices for fecal microbiota transplantation.

  13. 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.

  14. 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.

  15. Fecal microbiota transplantation via nasogastric tube for recurrent clostridium difficile infection in pediatric patients.

    PubMed

    Kronman, Matthew P; Nielson, Heather J; Adler, Amanda L; Giefer, Matthew J; Wahbeh, Ghassan; Singh, Namita; Zerr, Danielle M; Suskind, David L

    2015-01-01

    Fecal microbiota transplantation (FMT) is a safe and effective therapy for adults with recurrent Clostridium difficile colitis, but data regarding FMT in children are limited and focus on colonoscopic administration of FMT. We present 10 consecutive children who received FMT via nasogastric tube for treatment of recurrent C difficile infection. Median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. Median follow-up was 44 days, and 90% of patients resolved their C difficile infection; one patient relapsed 2 months later after receiving antibiotics. FMT via nasogastric tube appears safe, well tolerated, and effective in treating pediatric recurrent C difficile colitis.

  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.

  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. Immunization of hamsters against Clostridium difficile infection using the Cwp84 protease as an antigen.

    PubMed

    Péchiné, Séverine; Denève, Cécile; Le Monnier, Alban; Hoys, Sandra; Janoir, Claire; Collignon, Anne

    2011-10-01

    Clostridium difficile is a pathogen responsible for diarrhoea and colitis, particularly after antibiotic treatment. We evaluated the C. difficile protease Cwp84, found to be associated with the S-layer proteins, as a vaccine antigen to limit the C. difficile intestinal colonization and therefore the development of the infection in a clindamycin-treated hamster model. First, we evaluated the immune response and the animal protection against death induced by several immunization routes: rectal, intragastric and subcutaneous. Antibody production was variable according to the immunization routes. In addition, serum Cwp84 antibody titres did not always correlate with animal protection after challenge with a toxigenic C. difficile strain. The best survival rate was observed with the rectal route of immunization. Then, in a second assay, we selected this immunization route to perform a larger immunization assay including a Cwp84 immunized group and a control group. Clostridium difficile intestinal colonization and survival rate, as well as the immune response were examined. Clostridium difficile hamster challenge resulted in a 26% weaker and slower C. difficile intestinal colonization in the immunized group. Furthermore, hamster survival in the Cwp84 immunized group was 33% greater than that of the control group, with a significant statistical difference.

  19. Structural and functional changes in the gut microbiota associated to Clostridium difficile infection

    PubMed Central

    Pérez-Cobas, Ana E.; Artacho, Alejandro; Ott, Stephan J.; Moya, Andrés; Gosalbes, María J.; Latorre, Amparo

    2014-01-01

    Antibiotic therapy is a causative agent of severe disturbances in microbial communities. In healthy individuals, the gut microbiota prevents infection by harmful microorganisms through direct inhibition (releasing antimicrobial compounds), competition, or stimulation of the host's immune defenses. However, widespread antibiotic use has resulted in short- and long-term shifts in the gut microbiota structure, leading to a loss in colonization resistance in some cases. Consequently, some patients develop Clostridium difficile infection (CDI) after taking an antibiotic (AB) and, at present, this opportunistic pathogen is one of the main causes of antibiotic-associated diarrhea in hospitalized patients. Here, we analyze the composition and functional differences in the gut microbiota of C. difficile infected (CDI) vs. non-infected patients, both patient groups having been treated with AB therapy. To do so we used 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. Samples were taken before, during and after AB treatment and were checked for the presence of the pathogen. We performed different analyses and comparisons between infected (CD+) vs. non-infected (CD−) samples, allowing proposing putative candidate taxa and functions that might protect against C. difficile colonization. Most of these potentially protective taxa belonged to the Firmicutes phylum, mainly to the order Clostridiales, while some candidate protective functions were related to aromatic amino acid biosynthesis and stress response mechanisms. We also found that CDI patients showed, in general, lower diversity and richness than non-infected, as well as an overrepresentation of members of the families Bacteroidaceae, Enterococcaceae, Lactobacillaceae and Clostridium clusters XI and XIVa. Regarding metabolic functions, we detected higher abundance of genes involved in the transport and binding of carbohydrates, ions, and others compounds as a response to an antibiotic environment. PMID

  20. Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient.

    PubMed

    Neemann, K; Eichele, D D; Smith, P W; Bociek, R; Akhtari, M; Freifeld, A

    2012-12-01

    We present a case of severe Clostridium difficile infection (CDI) in a non-neutropenic allogeneic hematopoietic stem cell transplant recipient who was treated successfully with fecal microbiota therapy after standard pharmacologic therapy had failed. Following naso-jejunal instillation of donor stool, the patient's symptoms resolved within 48 h. Bowel resection was averted. This is the first case in the literature, to our knowledge, to describe fecal microbiota therapy in a profoundly immunocompromised host with severe CDI. We propose that fecal microbiota therapy be considered as a therapeutic option in immunosuppressed patients with refractory severe CDI.

  1. IgG antibody response to toxins A and B in patients with Clostridium difficile infection.

    PubMed

    Wullt, M; Norén, T; Ljungh, A; Åkerlund, T

    2012-09-01

    IgG antibodies against Clostridium difficile toxins A and B were followed in controls and in patients with an initial C. difficile infection (CDI). Of the 50 CDI patients, 38 were cured and 12 developed recurrence. Compared to controls, patients had significantly lower anti-toxin A and B IgGs at inclusion, but the subsequent levels rose slightly regardless of clinical outcome. The results imply that the general serum reactivity against toxins A and B in the population reduces the risk of CDI, which suggests implications for vaccine strategies.

  2. Concurrent swine erysipelas and Clostridium novyi infections associated with sow mortality in outdoor sows in Kenya.

    PubMed

    Friendship, C R; Bilkei, G

    2007-05-01

    A sudden increase in sow mortality was reported from a large outdoor pig-breeding unit in Kenya. The sows showed pyrexia and diamond shaped to confluent skin lesions ante-mortem. Gross pathological examination of the carcases was performed and organ samples (heart, liver, kidney, spleen, mandible lymph nodes) were sent for further diagnostic investigation. Based upon the clinical, gross- and microscopic-pathological signs, bacteriological findings and toxin testing, concurrent infection with Erysipelothrix rhusiopathiae and Clostridium novyi was diagnosed as the cause of the sow mortality.

  3. 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

  4. THE POWER OF POOP: FECAL MICROBIOTA TRANSPLANTATION FOR CLOSTRIDIUM DIFFICILE INFECTION.

    PubMed

    Edmond, Michael B

    2016-01-01

    The human gut is colonized with 200 to 1,000 bacterial species. Administration of antibiotics reduces the diversity of the intestinal microbiota, reduces colonization resistance, and can lead to infection with Clostridium difficile. These infections have become more prevalent and increasingly patients are experiencing multiple recurrences that are incurable with standard treatment. Although fecal microbiota transplantation (FMT) has been used for centuries in human and veterinary medicine, only recently has it be shown to be highly effective for recurrent C. difficile infection. The goal of FMT is to re-introduce a complete, stable community of gut microorganisms to repair or replace the disrupted native microbiota. FMT can be delivered via nasoenteric tube, colonoscopy, or enema. Despite a cure rate approximating 90%, many barriers to FMT have limited its availability to patients. The recent development of a not-for-profit stool bank has helped to make this therapy more accessible. Additional indications for FMT are currently under investigation.

  5. Toxic megacolon from fulminant Clostridium difficile infection induced by topical silver sulphadiazine.

    PubMed

    Tan, Christopher B; Rajan, Dhyan; Shah, Mitanshu; Ahmed, Shadab; Freedman, Lester; Rizvon, Kaleem; Mustacchia, Paul

    2012-08-08

    Pseudomembranous colitis and toxic megacolon (TM) are well-known complications of Clostridium difficile infections. Systemic antibiotic is considered as the major risk factor for the development of C difficile colitis. However, topical antibiotics are rarely associated with the infection. As previously thought, the use of topical antibiotic is capable of systemic absorption in damaged and denuded skin; sufficient enough to suppress the normal bowel flora. Here, we present an unusual case of TM from C difficile infection induced by topical silver sulphadiazine in a 60-year-old man with immune-bullous pemphigus vulgaris. The diagnosis is further complicated by the absence of diarrhoea as the initial presentation. Despite adequate medical and surgical intervention, the patient had an unfavourable outcome.

  6. A Review of Clostridium difficile Infection at the University Hospital of the West Indies, Jamaica

    PubMed Central

    Clare-Pascoe, N; Lee, MG; Murphy, T; Nicholson, A; Ferguson, TS

    2015-01-01

    ABSTRACT Objectives: This study examined the frequency of Clostridium difficile infection (CDI) among hospital admission and diarrhoeal stool samples over a six-year period. Methods: A review of all suspected cases of C difficile positive patients from 2007 to 2012 at the University Hospital of the West Indies (UHWI), Jamaica, was performed. Clostridium difficile infection was confirmed by clinical features and a positive enzyme-linked immunosorbent assay (ELISA) stool test for Clostridium Toxins A and B. The demographics, clinical features, risk factors, treatment and outcomes were also collated. Results: There were 56 patients reviewed. The most commonly affected age group was 40–59 years of age. The proportion of CDI cases per total stool samples increased from 0.5% in 2007 to 5.9% in 2010 then fell to 2.2% in 2011 but increased again to 4.3% in 2012. The proportion of cases per total UHWI admissions also increased from 0.12 cases per 1000 admissions in 2007 to 1.16 in 2010 and 1.36 in 2012 (p < 0.001). Most CDI cases were nosocomial (76% males, 48.6% females). Co-morbidities included hypertension and end-stage renal disease. Ceftazidime was the most common antibiotic associated with the development of CDI. Resolution occurred in 62.5% of patients. Duration of hospital stay was longer in males than females (≥ 21 versus < 7 days) and males had more adverse outcomes, with death in 23.8% versus 11.4%. Conclusion: There has been an increase in the frequency of CDI at UHWI with a greater than expected frequency of community acquired CDI. Increased awareness is needed of the increasing risk for CDI and measures must be taken to prevent the disease, especially in hospitalized patients. PMID:26624597

  7. Development and Evaluation of an Ovine Antibody-Based Platform for Treatment of Clostridium difficile Infection

    PubMed Central

    Roberts, April; McGlashan, Joanna; Al-Abdulla, Ibrahim; Ling, Roger; Denton, Harriet; Green, Steve; Coxon, Ruth; Landon, John

    2012-01-01

    Treatment of Clostridium difficile is a major problem as a hospital-associated infection which can cause severe, recurrent diarrhea. The currently available antibiotics are not effective in all cases and alternative treatments are required. In the present study, an ovine antibody-based platform for passive immunotherapy of C. difficile infection is described. Antibodies with high toxin-neutralizing titers were generated against C. difficile toxins A and B and were shown to neutralize three sequence variants of these toxins (toxinotypes) which are prevalent in human C. difficile infection. Passive immunization of hamsters with a mixture of toxin A and B antibodies protected them from a challenge with C. difficile spores in a dose-dependent manner. Antibodies to both toxins A and B were required for protection. The administration of toxin A and B antibodies up to 24 h postchallenge was found to reduce significantly the onset of C. difficile infection compared to nonimmunized controls. Protection from infection was also demonstrated with key disease isolates (ribotypes 027 and 078), which are members of the hypervirulent C. difficile clade. The ribotype 027 and 078 strains also have the capacity to produce an active binary toxin and these data suggest that neutralization of this toxin is unnecessary for the management of infection induced by these strains. In summary, the data suggest that ovine toxin A and B antibodies may be effective in the treatment of C. difficile infection; their potential use for the management of severe, fulminant cases is discussed. PMID:22144483

  8. Molecular basis of early stages of Clostridium difficile infection: germination and colonization.

    PubMed

    Sarker, Mahfuzur R; Paredes-Sabja, Daniel

    2012-08-01

    Clostridium difficile infections (CDIs) occur when antibiotic therapy disrupts the gastrointestinal flora, favoring infected C. difficile spores to germinate, outgrow, colonize and produce toxins. During CDI, C. difficile vegetative cells initiate the process of sporulation allowing a fraction of the spores to remain adhered to the intestinal surfaces. These spores, which are unaffected by antibiotic therapy commonly used for CDIs, then germinate, outgrow and recolonize the host's GI tract causing relapse of CDI. Consequently, the germination and colonization processes can be considered as the earliest and most essential steps for the development as well as relapse of CDI. The aim of this review is to provide an overview on the molecular basis involved in C. difficile spore germination and colonization.

  9. 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

  10. Complicated fecal microbiota transplantation in a tetraplegic patient with severe Clostridium difficile infection.

    PubMed

    Brechmann, Thorsten; Swol, Justyna; Knop-Hammad, Veronika; Willert, Jörg; Aach, Mirko; Cruciger, Oliver; Schmiegel, Wolff; Schildhauer, Thomas A; Hamsen, Uwe

    2015-03-28

    A 65-year-old male suffering from acute spinal cord injury leading to incomplete tetraplegia presented with severe recurrent Clostridium difficile (C. difficile) infection subsequent to antibiotic treatment for pneumonia. After a history of ineffective antimicrobial therapies, including metronidazole, vancomycin, fidaxomicin, rifaximin and tigecycline, leading to several relapses, the patient underwent colonoscopic fecal microbiota transplantation from his healthy son. Four days subsequent to the procedure, the patient showed a systemic inflammation response syndrome. Without detecting an infectious cause, the patient received antimicrobial treatment, including tigecycline, metronidazole, vancomycin via polyethylene glycol and an additional enema for a period of seven days, leading to a prompt recovery and no reported C. difficile infection relapse during a 12 wk follow up.

  11. The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease?

    PubMed Central

    Bien, Justyna; Palagani, Vindhya

    2013-01-01

    Gut microbiota is a compilation of microorganisms dwelling in the entire mammalian gastrointestinal tract. They display a symbiotic relationship with the host contributing to its intestinal health and disease. Even a slight fluctuation in this equipoise may be deleterious to the host, leading to many pathological conditions like Clostridium difficile infection or inflammatory bowel disease (IBD). In this review, we focus on the role of microbial dysbiosis in initiation of C. difficile infection and IBD, and we also touch upon the role of specific pathogens, particularly C. difficile, as causative agents of IBD. We also discuss the molecular mechanisms activated by C. difficile that contribute to the development and exacerbation of gastrointestinal disorders. PMID:23320050

  12. 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

  13. The potential beneficial role of faecal microbiota transplantation in diseases other than Clostridium difficile infection.

    PubMed

    Singh, R; Nieuwdorp, M; ten Berge, I J M; Bemelman, F J; Geerlings, S E

    2014-11-01

    This review gives an outline of the indications for faecal microbiota transplantation (FMT) for diseases other than Clostridium difficile (C. difficile) infection. The remarkable efficacy of FMT against C. difficile infection has already been demonstrated. The use of FMT for other diseases, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and metabolic syndrome, is now being evaluated. The currently available data suggest that FMT might be beneficial for IBD (including ulcerative colitis and, to some extent, Crohn's disease), IBS, and insulin resistance. Several randomized clinical trials are currently being performed, and data are eagerly awaited. A new field of research for the implementation of FMT is the eradication of pathogenic and multiresistant enteric microorganisms. A few animal studies have been performed within this field, but hardly any research data from human studies are available at present.

  14. 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

  15. The role of immunoglobulin for the treatment of Clostridium difficile infection: a systematic review.

    PubMed

    O'Horo, John; Safdar, Nasia

    2009-11-01

    Clostridium difficile is the most common infectious cause of nosocomial healthcare-associated diarrhea. The increasing prevalence of C difficile, spread in the community, virulence and frequent relapse has created an urgent need to identify new effective treatments for C. difficile infection. Among these, intravenous immunoglobulin (IVIG) is used for cases of severe C. difficile infection. We undertook a systematic review to examine the published literature pertaining to the use of immunoglobulin for C. difficile infection. Four retrospective studies and five case reports that addressed the use of IVIG for the treatment of C. difficile infection were identified. One study on the use of oral immunoglobulin was identified. Although overall there appear to be benefits to using IVIG in recurrent severe disease, the small sample sizes and lack of control groups in three of the four studies do not allow recommendations to be made regarding the use of immunoglobulin in C. difficile infection. Further research is urgently needed to clarify the role of immunoglobulin--intravenous or oral--for the treatment of C. difficile infection.

  16. Treatment of Clostridium difficile infection: a national survey of clinician recommendations and the use of faecal microbiota transplantation.

    PubMed

    Prior, A R; Kevans, D; McDowell, L; Cudmore, S; Fitzpatrick, F

    2016-10-14

    Adherence to Clostridium difficile infection treatment guidelines is associated with lower recurrence rates and mortality as well as cost savings. This survey of Irish clinicians indicates that patients are managed using a variety of approaches. Faecal microbiota transplantation is potentially underused despite its recommendation in national and European guidelines.

  17. An enhanced DNA fingerprinting service to investigate potential Clostridium difficile infection case clusters sharing the same PCR ribotype.

    PubMed

    Fawley, Warren N; Wilcox, Mark H

    2011-12-01

    Of 53 potential Clostridium difficile infection (CDI) case clusters/outbreaks, affecting 2 to 41 patients in 27 institutions, 19% comprised unrelated isolates and 34% had highly related and distinct isolates as shown by multilocus variable-number tandem-repeat analysis, despite sharing a common ribotype. These findings emphasize the value of enhanced fingerprinting to confirm or refute suspected CDI case clusters.

  18. 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

  19. Hospital-Onset Clostridium difficile Infection among Solid Organ Transplant Recipients

    PubMed Central

    Donnelly, John P.; Wang, Henry E.; Locke, Jayme E.; Mannon, Roslyn B.; Safford, Monika M.; Baddley, John W.

    2017-01-01

    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 impact graft as well as patient survival. However, little is known about the impact of CDI on health services utilization post-transplant. We examined hospital-onset CDI from 2012-2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the US. Infection was five times more common among transplant recipients compared to general 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 three-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 and 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; $198,728,368 vs. $154,020,528 costs). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted. PMID:26484839

  20. 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.

  1. Successful use of nitazoxanide in the treatment of recurrent Clostridium difficile infection

    PubMed Central

    Rafiullah, Fnu; Kanwal, Sunil; Majeed, Usman M; Korsten, Mark A; Cheema, Faisal H; Luthra, Munish; Sohail, Muhammad Rizwan

    2011-01-01

    A 78-year-old, retired Caucasian male presented in emergency room with 3 days history of progressive watery diarrhoea. Two weeks earlier, he received intravenous levofloxacin for community acquired pneumonia. The patient was diagnosed as severe Clostridium difficile infection based on clinical presentation, labs and imaging studies. The patient was initially treated with intravenous metronidazole and oral vancomycin. While awaiting subacute rehabilitation placement, the patient relapsed twice. After first recurrence the patient was treated with 2 weeks of oral nitazoxanide. After second recurrence, the patient was treated 2 weeks of nitazoxanide followed by tapering dose of vancomycin. The patient was followed and no relapse was reported at 1 year follow-up visit. PMID:22674696

  2. Serum markers for severe Clostridium difficile infection in immunosuppressed hospitalized patients.

    PubMed

    Pant, Chaitanya; Sferra, Thomas J; Ondrade, Christina; Bass, Pat F; Deshpande, Abhishek; Burton, Cary V

    2011-01-01

    Clostridium difficile infection (CDI) has emerged as the leading cause of nosocomial diarrhea in the developed world. The prompt recognition of severe CDI is essential in providing early aggressive therapy. Though previous studies have identified leukocytosis, azotemia, and hypoalbuminemia as markers to differentiate severe from non-severe CDI in the general patient population, there is little data in immunosuppressed patients. We conducted a retrospective chart review of immunosuppressed patients with CDI to identify serum markers associated with severe CDI. Twenty-nine immunosuppressed patients with CDI (nine with severe disease) were identified. Those with severe disease were older and had evidence of renal dysfunction. The white blood cell count, platelet, and albumin levels were the same in the severe and non-severe immunosuppressed CDI patients. Therefore, recognized serum markers of severe CDI are not universally useful in immunosuppressed patients. Moreover, the clinician must be aware that immunosuppressed patients can develop severe CDI while remaining leukopenic.

  3. Establishing a Fecal Microbiota Transplant Service for the Treatment of Clostridium difficile Infection.

    PubMed

    Costello, Samuel P; Tucker, Emily C; La Brooy, Justin; Schoeman, Mark N; Andrews, Jane M

    2016-04-01

    Recurrent or refractory Clostridium difficile infection (CDI) has become an increasing problem in the past decade. Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent CDI; however, a number of technical, logistical, and regulatory issues have hampered the development of an FMT capability at many hospitals. The development of a frozen stool bank of screened donor stool is an important step in the standardization of the procedure. This gives clinicians rapid access to thoroughly screened donor stool when needed, without the ethical and logistical problems associated with patient-selected donors. We describe the practicalities of establishing such a service using a stool bank of prescreened donor stool including detail regarding donor recruitment and screening, stool preparation, and delivery of the FMT.

  4. Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection.

    PubMed

    Dutta, Sudhir K; Girotra, Mohit; Garg, Shashank; Dutta, Anand; von Rosenvinge, Erik C; Maddox, Cynthia; Song, Yang; Bartlett, John G; Vinayek, Rakesh; Fricke, W Florian

    2014-09-01

    The prevalence of recurrent Clostridium difficile infection (RCDI) is increasing; fecal microbiota transplantation (FMT) is an effective therapy. However, there have been no studies of the efficacy of a single session of combined enteral and colonic FMT or characterizations of changes in the microbiota between donors and recipients. We performed a study of 27 patients with RCDI who were given a fixed volume of processed fecal filtrate via enteroscopy and colonoscopy in a single session. Patients were closely monitored, and fecal samples were collected from 2 patient-donor pairs for 16S rRNA analysis. All patients had reduced stool frequency, abdominal pain, white blood cell counts, and elimination of fecal C difficile toxin (P < .05). FMT increased microbial diversity, increasing proportions of Lachnospiraceae (phylum Firmicutes) and reducing proportions of Enterobacteriaceae. FMT was associated with marked changes in the composition of fecal microbiota in 2 patients with RCDI.

  5. Synthetic Lipoteichoic Acid Glycans Are Potential Vaccine Candidates to Protect from Clostridium difficile Infections.

    PubMed

    Broecker, Felix; Martin, Christopher E; Wegner, Erik; Mattner, Jochen; Baek, Ju Yuel; Pereira, Claney L; Anish, Chakkumkal; Seeberger, Peter H

    2016-08-18

    Infections with Clostridium difficile increasingly cause morbidity and mortality worldwide. Bacterial surface glycans including lipoteichoic acid (LTA) were identified as auspicious vaccine antigens to prevent colonization. Here, we report on the potential of synthetic LTA glycans as vaccine candidates. We identified LTA-specific antibodies in the blood of C. difficile patients. Therefore, we evaluated the immunogenicity of a semi-synthetic LTA-CRM197 glycoconjugate. The conjugate elicited LTA-specific antibodies in mice that recognized natural LTA epitopes on the surface of C. difficile bacteria and inhibited intestinal colonization of C. difficile in mice in vivo. Our findings underscore the promise of synthetic LTA glycans as C. difficile vaccine candidates.

  6. 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.

  7. 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.

  8. How do Clostridium difficile infections affect nurses' everyday hospital work: A qualitative study.

    PubMed

    Guillemin, Isabelle; Marrel, Alexia; Beriot-Mathiot, Axelle; Doucet, Carole; Kazoglou, Odysseas; Luxemburger, Christine; Reygrobellet, Camille; Arnould, Benoit

    2015-05-01

    This qualitative study explored the impact of Clostridium difficile infections on nurses' everyday work in the hospital. Twelve nurses (six in France and six in the United States) were interviewed in depth using a semi-structured interview guide. Thematic analysis of the interviews was performed. Managing diarrhoea and taking precautionary measures for infection control were the two most inconvenient aspects nurses reported with C. difficile patient management. Precautions included contact isolation, hand hygiene and reorganization/coordination of nursing care and ward. Precautions were time consuming and significantly increased nurses' workload when combined with caring for patients with uncontrollable, frequent bouts of diarrhoea. Management of C. difficile infection is extremely burdensome for nurses in their everyday work and disruptive to hospital organizations as a whole. Prevention of C. difficile infections, together with coordinated team work and communication, would therefore contribute to decreasing nurses' workload and the burden to health-care facilities associated with caring for these patients.

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

    PubMed

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

    2016-06-01

    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).

  10. 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

  11. 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

  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. Faecal microbiota transplantation for Clostridium difficile infection in the United Kingdom.

    PubMed

    Porter, R J; Fogg, C

    2015-06-01

    Faecal microbiota transplantation (FMT) has been shown to be highly effective in treating recurrent Clostridium difficile infection, but to date there have been no data from the United Kingdom. An electronic survey was developed at Portsmouth Hospitals' National Health Service (NHS) Trust and sent out to UK hospital specialists utilizing the contact databases of the British Infection Association and the Royal College of Gastroenterologists. A total of 162 responses were received, representing nearly one in every seven of the United Kingdom's infection specialists and a response from one in every two UK NHS acute trusts or boards. Ninety-six per cent believe that the evidence base supports the use of FMT, and 94% reported consulting on at least one patient a year in whom they would recommend FMT. However, only 22% reported FMT use in their institution in the last 10 years, and 6% reported performing more than ten FMTs in the last 10 years. Concerns with patient acceptance, donor selection, availability of screened faecal solution, feasibility of procedure and availability of local expertise were reported as inhibiting the use of FMT. More than 90% of respondents would like access to regional guidelines, prescreened faecal solution and expert advice to facilitate implementation, and more than two thirds of respondents would support a regional FMT referral centre. A large gap exists in the United Kingdom between physicians desire to use FMT and the ability and facilities to provide it as a therapy at the bedside.

  14. 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

  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. Clinical Characteristics and Treatment Outcomes of Clostridium difficile Infections by PCR Ribotype 017 and 018 Strains

    PubMed Central

    Kim, Yeonjae; Pai, Hyunjoo

    2016-01-01

    The objective of this study was to identify the clinical characteristics of Clostridium difficile infections (CDIs) caused by toxin A-negative/toxin B-positive (A-B+) PCR ribotype 017 (R017) and A+B+ ribotype 018 (R018) strains, prevalent in Asian countries. From February 2010 through January 2013, all CDI patients in our hospital were enrolled; their medical records were retrospectively reviewed, and the isolates were characterized by toxigenic culture and PCR ribotyping. Based on the ribotypes, a total of 510 cases were categorized as R017 (139, 27.3%), R018 (157, 30.8%) and other ribotypes groups (214, 42.0%), and clinical variables were compared between R017 and other ribotypes, R018 and other ribotypes and R018 and R017 groups. The patients with R017 infections had a higher mean Charlson’s comorbidity index (OR 1.1, 1–1.21, p = 0.05), lower serum albumin (OR 0.47, 0.31–0.73, p = 0.001) and lower CRP levels (OR 0.96, 0.92–0.99, p = 0.022) than those with other ribotypes. R018 infections caused more azotemia (OR 4.06, 1.28–12.91, p = 0.018) and more frequent severe CDI (OR 1.87, 1.12–3.13, p = 0.016) than the other ribotypes infections. R017 and R018 infections were more often associated with toxin positive stools (OR 2.94, 1.65–4.09, p<0.001; OR 4.55, 2.82–7.33, p<0.001). In terms of treatment outcomes, R017 infections caused a marginally higher 30-day mortality than other ribotypes infection. In a final multiple logistic regression model, 30-day mortality was associated with leukocytosis (OR 2.45, 1.0–6.01, p = 0.05) and hypoalbuminemia (OR 4.57, 1.83–11.39, p = 0.001), but only marginally with R017 infection (OR 2.14, 0.88–5.22, p = 0.094). In conclusion, infections by C. difficile R018 strains tend to cause more severe disease, while there was a trend for higher mortality with R017 infections. PMID:28002482

  17. 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.

  18. Pharmacokinetics of LFF571 and Vancomycin in Patients with Moderate Clostridium difficile Infections

    PubMed Central

    Bhansali, Suraj G.; Mullane, Kathleen; Ting, Lillian S. L.; Leeds, Jennifer A.; Dabovic, Kristina; Praestgaard, Jens

    2014-01-01

    Clostridium difficile infection causes diarrheal disease with potentially fatal complications. Although treatments are available, including vancomycin, metronidazole, and fidaxomicin, the recurrence of disease after therapy remains a problem. LFF571 is a novel thiopeptide antibacterial that shows in vitro potency against C. difficile that is comparable to or greater than that of other clinically used antibiotics. Here, we compare the pharmacokinetics (PK) of LFF571 and vancomycin in patients with C. difficile infection as part of an early efficacy study. This multicenter, randomized, evaluator-blind, and active-controlled study evaluated the safety, efficacy, and pharmacokinetics of LFF571 in adults with primary episodes or first relapses of moderate C. difficile infections. Patients were randomized to receive 200 mg of LFF571 or 125 mg of vancomycin four times daily for 10 days. The PK parameters were calculated from drug concentrations measured in serum and fecal samples. The systemic exposure following oral administration of 200 mg of LFF571 four times per day for 10 days in patients with C. difficile infection was limited. The highest LFF571 serum concentration observed was 41.7 ng/ml, whereas the levels in feces at the end of treatment were between 107 and 12,900 μg/g. In comparison, the peak vancomycin level observed in serum was considerably higher, at 2.73 μg/ml; the levels of vancomycin in feces were not measured. Similar to healthy volunteers, patients with C. difficile infections exhibited high fecal concentrations and low serum levels of LFF571. These results are consistent with the retention of LFF571 in the lumen of the gastrointestinal tract. (This study has been registered at ClinicalTrials.gov under registration no. NCT01232595.) PMID:25534724

  19. Effect of continuous sub-culturing on infectivity of Clostridium perfringens ATCC13124 in mouse gas gangrene model.

    PubMed

    Kumar, Ravi Bhushan; Alam, Syed Imteyaz

    2017-02-17

    Clostridium perfringens is a Validated Biological Agent and a pathogen of medical, veterinary, and military significance. Gas gangrene is the most destructive of all the clostridial diseases and is caused by C. perfringens type A strains wherein the infection spreads quickly (several inches per hour) with production of gas. Influence of repeated in vitro cultivation on the infectivity of C. perfringens was investigated by comparing the surface proteins of laboratory strain and repository strains of the bacterium using 2DE-MS approach. In order to optimize host-pathogen interaction during experimental gas gangrene infection, we also explored the role of particulate matrix on ability of C. perfringens to cause gas gangrene.

  20. 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

  1. 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.

  2. Faecal transplantation for the treatment of Clostridium difficile infection: a review.

    PubMed

    McCune, V L; Struthers, J K; Hawkey, P M

    2014-03-01

    Clostridium difficile infection (CDI) remains a major healthcare burden despite recent global falls in its prevalence. The risk of recurrence is high when using antibiotics such as vancomycin, particularly in already recurrent disease. In light of this, new therapy options are being perused, including novel antibiotics such as fidaxomicin, probiotics, intravenous immunoglobulin and faecal transplantation. Faecal transplantation, referred to here as human probiotic infusion (HPI), is attracting an increasing amount of interest from physicians and patients. Its use has been documented in ca. 500 cases for the treatment of CDI, with overall efficacy rates reported to be ca. 91%. The first randomised controlled trial (RCT) demonstrated that HPI was superior to a 14-day course of vancomycin (89% vs. 31%; P<0.001) and reported no deaths or serious adverse events. Safety and patient acceptability are often cited as limitations to the widespread use of this technique. However, data suggest that the short-term safety profile is encouraging, and concerns over patient acceptability are not warranted in the majority of cases. It seems appropriate to treat an infection which is caused by a major disturbance in the gut microbiota with a treatment that reverses this disturbance, rather than antibiotics that may exacerbate the problem. However, to fully understand the role of HPI in the management of CDI, further RCTs are needed with comparator antibiotics such as fidaxomicin and to establish the most efficacious HPI protocol for administration and preparation.

  3. Animal models to study the pathogenesis of human and animal Clostridium perfringens infections

    PubMed Central

    Uzal, Francisco A.; McClane, Bruce A.; Cheung, Jackie K.; Theoret, James; Garcia, Jorge P.; Moore, Robert J.; Rood, Julian I.

    2016-01-01

    The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats. PMID:25770894

  4. Dietary Zinc Alters the Microbiota and Decreases Resistance to Clostridium difficile Infection

    PubMed Central

    Zackular, Joseph P.; Moore, Jessica L.; Jordan, Ashley T.; Juttukonda, Lillian J.; Noto, Michael J.; Nicholson, Maribeth R.; Crews, Jonathan D.; Semler, Matthew W.; Zhang, Yaofang; Ware, Lorraine B.; Washington, M. Kay; Chazin, Walter J.; Caprioli, Richard M.; Skaar, Eric P.

    2016-01-01

    Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide1. Over the past decade, incidence, severity, and costs associated with C. difficile infection (CDI) have increased dramatically2. CDI is most commonly initiated by antibiotic-mediated disruption of the gut microbiota; however, non-antibiotic associated CDI cases are well documented and on the rise3,4. This suggests that unexplored environmental, nutrient, and host factors likely influence CDI. Here we show that excess dietary zinc (Zn) significantly alters the gut microbiota and in turn reduces the threshold of antibiotics needed to confer susceptibility to C. difficile infection. In mice colonized with C. difficile, excess dietary Zn severely exacerbates C. difficile-associated disease by increasing toxin activity and altering the host immune response. In addition, we show that the Zn binding S100 protein calprotectin is antimicrobial against C. difficile and an essential component of the innate immune response to CDI. Together, these data suggest that nutrient Zn levels play a key role in determining susceptibility to CDI and severity of disease, and that calprotectin-mediated metal limitation is an important factor in the host immune response to C. difficile. PMID:27668938

  5. [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.

  6. Animal models to study the pathogenesis of human and animal Clostridium perfringens infections.

    PubMed

    Uzal, Francisco A; McClane, Bruce A; Cheung, Jackie K; Theoret, James; Garcia, Jorge P; Moore, Robert J; Rood, Julian I

    2015-08-31

    The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats.

  7. Design and Purification of Subunit Vaccines for Prevention of Clostridium difficile Infection.

    PubMed

    Karczewski, Jerzy; Bodmer, Jean-Luc; Cook, James C; Xoconostle, Rachel F; Nahas, Debbie D; Joyce, Joseph G; Heinrichs, Jon H; Secore, Susan

    2016-01-01

    Clostridium difficile is a gram-positive bacterium responsible for a large proportion of nosocomial infections in the developed world. C. difficile secretes toxins A and B (TcdA and TcdB) and both toxins act synergistically to induce a spectrum of pathological responses in infected individuals ranging from pseudomembranous colitis to C. difficile-associated diarrhea. Toxins A and B have been actively investigated as components of prophylactic vaccine as well as targets for therapeutic intervention with antibodies. Expression of such toxins by recombinant technology is often difficult and may require special handling and adherence to strict safety regulations during the manufacturing process due to the inherent toxicity of the proteins. Both toxins are large proteins (308 kDa and 270 kDa, respectively) and contain distinct domains mediating cell attachment, cellular translocation, and enzymatic (glucosidase) activity. Here we describe methods to produce fragments of Toxin B for their subsequent evaluation as components of experimental C. difficile vaccines. Methods presented include selection of fragments encompassing distinct functional regions of Toxin B, purification methods to yield high quality proteins, and analytical evaluation techniques. The approach presented focuses on Toxin B but could be applied to the other component, Toxin A, and/or to any difficult to express or toxic protein.

  8. 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.

  9. Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection.

    PubMed

    Ross, Caná L; Spinler, Jennifer K; Savidge, Tor C

    2016-10-01

    Alteration of the gut microbial community structure and function through antibiotic use increases susceptibility to colonization by Clostridium difficile and other enteric pathogens. However, the mechanisms that mediate colonization resistance remain elusive. As the leading definable cause of infectious diarrhea, toxigenic C. difficile represents a burden for patients and health care systems, underscoring the need for better diagnostics and treatment strategies. Next-generation sequence data has increased our understanding of how the gut microbiota is influenced by many factors including diet, disease, aging and drugs. However, a microbial-based biomarker differentiating C. difficile infection from antibiotic-associated diarrhea has not been identified. Metabolomics profiling, which is highly responsive to changes in physiological conditions, have shown promise in differentiating subtle disease phenotypes that exhibit a nearly identical microbiome community structure, suggesting metabolite-based biomarkers may be an ideal diagnostic for identifying patients with CDI. This review focuses on the current understanding of structural and functional changes to the gut microbiota during C. difficile infection obtained from studies assessing the microbiome and metabolome of samples from patients and murine models.

  10. Increasing rates in Clostridium difficile infection (CDI) among hospitalised patients, Spain 1999-2007.

    PubMed

    Asensio, A; Vaque-Rafart, J; Calbo-Torrecillas, F; Gestal-Otero, J J; López-Fernández, F; Trilla-Garcia, A; Canton, R

    2008-07-31

    Limited information is available on the burden and epidemiology of Clostridium difficile infection (CDI) in Spain. The present report communicates the secular trends in prevalence of CDI among hospitalised patients in Spain from 1999 through 2007. Data were obtained through the EPINE study (Estudio de prevalencia de las infecciones nosocomiales en los hospitales españoles), a point prevalence study series of nosocomial infections among patients admitted to hospital in Spain. A total of 378 cases with CDI were identified. Median age was 74 years. Prevalence rates of CDI increased from 3.9 to 12.2 cases per 10,000 hospitalised patients and showed a significantly increasing secular trend from 1999 through 2007 (prevalence rate ratio per each year increment 1.09; 95% CI 1.05 - 1.14). Percentage of hospitalised patients receiving antimicrobials increased linearly from 36.0% in 1999 to 40.7% in 2007 (p <0.001) and was strongly correlated to CDI prevalence (R square = 0.73; regression coefficient =1.194, 95% CI= 1.192 - 1.196).

  11. 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.

  12. Infection prevention and control of Clostridium difficile: a global review of guidelines, strategies, and recommendations

    PubMed Central

    Balsells, Evelyn; Filipescu, Teodora; Kyaw, Moe H.; Wiuff, Camilla; Campbell, Harry; Nair, Harish

    2016-01-01

    Background Clostridium difficile is the leading cause of health care–associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance. Methods We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI–targeted IPC recommendations and describe the assessment of evidence in available guidelines. Results We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long–term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported “strong” recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality. Conclusion Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations. PMID:28028434

  13. Insight into alteration of gut microbiota in Clostridium difficile infection and asymptomatic C. difficile colonization.

    PubMed

    Zhang, Lihua; Dong, Danfeng; Jiang, Cen; Li, Zhen; Wang, Xuefeng; Peng, Yibing

    2015-08-01

    Clostridium difficile is well recognized as the common pathogen of nosocomial diarrhea, meanwhile, asymptomatic colonization with C. difficile in part of the population has also drawn public attention. Although gut microbiota is known to play an important role in the pathogenesis of C. difficile infection (CDI), whether there is any alteration of gut microbial composition in asymptomatic C. difficile carriers hasn't been clearly described. The purpose of this study was to explore the differences in gut microbiome among CDI patients, asymptomatic C. difficile carriers and healthy individuals. We performed fecal microbiota analysis on the samples of eight CDI patients, eight asymptomatic C. difficile carriers and nine healthy subjects using 16S rRNA gene pyrosequencing. CDI patients and asymptomatic carriers showed reduced microbial richness and diversity compared with healthy subjects, accompanied with a paucity of phylum Bacteroidetes and Firmicutes as well as an overabundance of Proteobacteria. Some normally commensal bacteria, especially butyrate producers, were significantly depleted in CDI patients and asymptomatic carriers. Furthermore, the differences observed in microbial community structure between CDI patients and asymptomatic carriers suggested that the gut microbiota may be a potential factor of disease state for CDI. Our study demonstrates the characterization and diversity of gut microbiota in CDI and asymptomatic C. difficile colonization, which will provide new ideas for surveillance of the disease state and development of microbiota-targeted agents for CDI prevention and treatment.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Clostridium difficile infection: update on emerging antibiotic treatment options and antibiotic resistance

    PubMed Central

    Shah, Dhara; Dang, Minh-Duc; Hasbun, Rodrigo; Koo, Hoonmo L; Jiang, Zhi-Dong; DuPont, Herbert L; Garey, Kevin W

    2010-01-01

    Clostridium difficile infection (CDI) is the most common cause of identifiable diarrhea in hospitalized patients. The incidence and severity of CDIs are increasing. The increased incidence and severity of the disease has sparked interest in the optimal treatment of CDI as well as the use of new therapies and drug discovery. Current treatment strategies are inadequate with decreased response rates to metronidazole, and high recurrence rates with the use of metronidazole and oral vancomycin. Although incidence rates continue to be low, in vitro resistance to antibiotics used for the treatment of CDI has been noted. Recently, important data has emerged on new anti-C. difficile antibiotics such as rifaximin, rifalazil, fidaxomicin, nitazoxanide, tigecycline and ramoplanin. The purpose of this review is to provide an update on the in vitro susceptibility and new antibiotic treatment options for CDI. This review will focus primarily on scientific studies published in the last 36 months in order to provide an up-to-date review on the topic. PMID:20455684

  19. 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.

  20. Clinical approach to severe Clostridium difficile infection: update for the hospital practitioner.

    PubMed

    Pant, Chaitanya; Sferra, Thomas J; Deshpande, Abhishek; Minocha, Anil

    2011-12-01

    The rising incidence of Clostridium difficile (C. difficile) infection or CDI is now a problem of pandemic proportions. The NAP1 hypervirulent strain of C. difficile is responsible for a majority of recent epidemics and the widespread use of fluoroquinolone antibiotics may have facilitated the selective proliferation of this strain. The NAP1 strain also is more likely to cause severe and fulminant colitis characterized by marked leukocytosis, renal failure, hemodynamic instability, and toxic megacolon. No single test suffices to diagnose severe CDI, instead; the clinician must rely on a combination of clinical acumen, laboratory testing, and radiologic and endoscopic modalities. Although oral vancomycin and metronidazole are considered standard therapies in the medical management of CDI, recently it has been demonstrated that vancomycin is the more effective antibiotic in cases of severe disease. Moreover, early surgical consultation is necessary in patients who do not respond to medical therapy or who demonstrate rising white blood cell counts or hemodynamic instability indicative of fulminant colitis. Subtotal colectomy with end ileostomy is the procedure of choice for fulminant colitis. When applied to select patients in a judicious and timely fashion, surgery can be a life-saving intervention. In addition to these therapeutic approaches, several investigational treatments including novel antibiotics, fecal bacteriotherapy and immunotherapy have shown promise in the care of patients with severe CDI.

  1. A prospective study of community-associated Clostridium difficile infection in Kuwait: Epidemiology and ribotypes.

    PubMed

    Jamal, Wafaa; Pauline, Eunice; Rotimi, Vincent

    2015-10-01

    Clostridium difficile infection (CDI) is increasingly recognized as a significant community acquired pathogen that causes disease in the community. The aim of the study was to investigate prospectively the incidence of community-acquired-CDI (CA-CDI) in Kuwait. Of the 2584 patients with diarrhea, 16 (0.62%) were confirmed cases of CA-CDI. The other notable pathogens were Salmonella spp. (0.39%) and Campylobacter spp. (0.23%). The mean age was 39 years and the CDI was mild. Exposure to antibiotics in the previous 12 weeks, contact with infant aged <2 years and history of foreign travel was significantly associated with CA-CDI (P < 0.001; P < 0.0001; P < 0.002, respectively). Detected PCR ribotypes were 139 (n = 4) and 014, 056, 070, 097 and 179 (each n = 2). CA-CDI in Kuwait is more likely to occur in younger age and associated with ribotype 139. CA-CDI is not a common problem in Kuwait however extra vigilance must be maintained to detect it in the community even without traditional predisposing factors.

  2. Point-Counterpoint: What Is the Optimal Approach for Detection of Clostridium difficile Infection?

    PubMed

    Fang, Ferric C; Polage, Christopher R; Wilcox, Mark H

    2017-03-01

    INTRODUCTIONIn 2010, we published an initial Point-Counterpoint on the laboratory diagnosis of Clostridium difficile infection (CDI). At that time, nucleic acid amplification tests (NAATs) were just becoming commercially available, and the idea of algorithmic approaches to CDI was being explored. Now, there are numerous NAATs in the marketplace, and based on recent proficiency test surveys, they have become the predominant method used for CDI diagnosis in the United States. At the same time, there is a body of literature that suggests that NAATs lack clinical specificity and thus inflate CDI rates. Hospital administrators are taking note of institutional CDI rates because they are publicly reported. They have become an important metric impacting hospital safety ratings and value-based purchasing; hospitals may have millions of dollars of reimbursement at risk. In this Point-Counterpoint using a frequently asked question approach, Ferric Fang of the University of Washington, who has been a consistent advocate for a NAAT-only approach for CDI diagnosis, will discuss the value of a NAAT-only approach, while Christopher Polage of the University of California Davis and Mark Wilcox of Leeds University, Leeds, United Kingdom, each of whom has recently written important articles on the value of toxin detection in the diagnosis, will discuss the impact of toxin detection in CDI diagnosis.

  3. 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

  4. Cadazolid: A new hope in the treatment of Clostridium difficile infection.

    PubMed

    Kali, Arunava; Charles, Marie Victor Pravin; Srirangaraj, Srirangaraj

    2015-01-01

    Clostridium difficile infection (CDI) is a potential life-threatening consequence of antibiotic therapy. Although the risk increases with duration of treatment, it can also occur after a short treatment course. In addition to broad-spectrum antibiotics, anti-neoplastic agents, proton pump inhibitors, H(2) blockers, and several other drugs have been reported to induce intestinal dysbiosis, which is central to the pathogenesis of CDI. There is an increase in incidence and mortality attributed to CDI globally. Moreover, the epidemiology of C. difficile-associated diseases has changed significantly with an increasing occurrence of community-acquired CDI. Metronidazole and oral vancomycin are the first-line antibiotics used to treat CDI. However, metronidazole has limited effectiveness in severe cases and vancomycin use is associated with increasing risk of vancomycin resistance among Enterococcus spp. Cadazolid, a novel oxazolidinone antibiotic, has recently shown potent antimicrobial activity against C. difficile and has a lower propensity to induce resistance. The implications of its use in treating CDI have been reviewed based on current evidence.

  5. Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials.

    PubMed

    Crook, Derrick W; Walker, A Sarah; Kean, Yin; Weiss, Karl; Cornely, Oliver A; Miller, Mark A; Esposito, Roberto; Louie, Thomas J; Stoesser, Nicole E; Young, Bernadette C; Angus, Brian J; Gorbach, Sherwood L; Peto, Timothy E A

    2012-08-01

    Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40% (95% confidence interval [CI], 26%-51%; P < .0001) compared with vancomycin through day 40. A 37% (95% CI, 2%-60%; P = .037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P = .50 vs 13-40 days), driven by 7 (1.2%) fidaxomicin versus 17 (2.9%) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P < .01). Fidaxomicin has the potential to substantially improve outcomes from CDI.

  6. Fidaxomicin Versus Vancomycin for Clostridium difficile Infection: Meta-analysis of Pivotal Randomized Controlled Trials

    PubMed Central

    Crook, Derrick W.; Walker, A. Sarah; Kean, Yin; Weiss, Karl; Cornely, Oliver A.; Miller, Mark A.; Esposito, Roberto; Louie, Thomas J.; Stoesser, Nicole E.; Young, Bernadette C.; Angus, Brian J.; Gorbach, Sherwood L.; Peto, Timothy E. A.

    2012-01-01

    Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40% (95% confidence interval [CI], 26%–51%; P < .0001) compared with vancomycin through day 40. A 37% (95% CI, 2%–60%; P = .037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P = .50 vs 13–40 days), driven by 7 (1.2%) fidaxomicin versus 17 (2.9%) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P < .01). Fidaxomicin has the potential to substantially improve outcomes from CDI. PMID:22752871

  7. 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.

  8. Biofilms of Clostridium species.

    PubMed

    Pantaléon, Véronique; Bouttier, Sylvie; Soavelomandroso, Anna Philibertine; Janoir, Claire; Candela, Thomas

    2014-12-01

    The biofilm is a microbial community embedded in a synthesized matrix and is the main bacterial way of life. A biofilm adheres on surfaces or is found on interfaces. It protects bacteria from the environment, toxic molecules and may have a role in virulence. Clostridium species are spread throughout both environments and hosts, but their biofilms have not been extensively described in comparison with other bacterial species. In this review we describe all biofilms formed by Clostridium species during both industrial processes and in mammals where biofilms may be formed either during infections or associated to microbiota in the gut. We have specifically focussed on Clostridium difficile and Clostridium perfringens biofilms, which have been studied in vitro. Regulatory processes including sporulation and germination highlight how these Clostridium species live in biofilms. Furthermore, biofilms may have a role in the survival and spreading of Clostridium species.

  9. Perceptions of fecal microbiota transplantation for Clostridium difficile infection: factors that predict acceptance

    PubMed Central

    Park, Leslie; Mone, Anjali; Price, Jennifer C.; Tzimas, Demetrios; Hirsh, Jacqueline; Poles, Michael A.; Malter, Lisa; Chen, Lea Ann

    2017-01-01

    Background Despite the effectiveness of fecal microbiota transplantation (FMT) for treating recurrent Clostridium difficile (C. difficile) infection, some patients are reluctant to accept this therapy. Our study examined attitudes towards FMT and factors that contribute to patients’ acceptance of this treatment. Methods We distributed patient surveys at a Veterans Affairs hospital, a public hospital, and an academic faculty practice. Multivariable logistic regression was performed, adjusting for factors associated with FMT acceptance on univariate analysis and prior experience with C. difficile infection. Results Of 267 patients, only 12% knew of FMT prior to the survey, but 77% would undergo the procedure if medically indicated. On multivariable analysis, those with children and with college degrees or higher were more likely to agree to FMT (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.02-4.35; OR 2.27, 95% CI 1.11-4.60 respectively). Sixty-five respondents (71%) chose colonoscopy as the preferred vehicle for FMT, while nasogastric tube was least preferred. Disease transmission was the most common concern (30%, n=242), and FMT success rate was the least selected concern (9.1%). Conclusions Most patients in a diverse sample of gastroenterology clinics had no prior knowledge of FMT, but were receptive to the procedure. Having children and higher education levels were predictors for FMT acceptance. Our findings suggest that barriers to FMT utilization may be overcome with counseling about safety concerns. More data on the risk of transmitting diseases or clinical characteristics, such as obesity, through FMT are needed and will be important for the acceptance of this procedure. PMID:28042242

  10. Clostridium Difficile Infection in Acute Care Hospitals: Systematic Review and Best Practices for Prevention.

    PubMed

    Louh, Irene K; Greendyke, William G; Hermann, Emilia A; Davidson, Karina W; Falzon, Louise; Vawdrey, David K; Shaffer, Jonathan A; Calfee, David P; Furuya, E Yoko; Ting, Henry H

    2017-04-01

    OBJECTIVE Prevention of Clostridium difficile infection (CDI) in acute-care hospitals is a priority for hospitals and clinicians. We performed a qualitative systematic review to update the evidence on interventions to prevent CDI published since 2009. DESIGN We searched Ovid, MEDLINE, EMBASE, The Cochrane Library, CINAHL, the ISI Web of Knowledge, and grey literature databases from January 1, 2009 to August 1, 2015. SETTING We included studies performed in acute-care hospitals. PATIENTS OR PARTICIPANTS We included studies conducted on hospitalized patients that investigated the impact of specific interventions on CDI rates. INTERVENTIONS We used the QI-Minimum Quality Criteria Set (QI-MQCS) to assess the quality of included studies. Interventions were grouped thematically: environmental disinfection, antimicrobial stewardship, hand hygiene, chlorhexidine bathing, probiotics, bundled approaches, and others. A meta-analysis was performed when possible. RESULTS Of 3,236 articles screened, 261 met the criteria for full-text review and 46 studies were ultimately included. The average quality rating was 82% according to the QI-MQCS. The most effective interventions, resulting in a 45% to 85% reduction in CDI, included daily to twice daily disinfection of high-touch surfaces (including bed rails) and terminal cleaning of patient rooms with chlorine-based products. Bundled interventions and antimicrobial stewardship showed promise for reducing CDI rates. Chlorhexidine bathing and intensified hand-hygiene practices were not effective for reducing CDI rates. CONCLUSIONS Daily and terminal cleaning of patient rooms using chlorine-based products were most effective in reducing CDI rates in hospitals. Further studies are needed to identify the components of bundled interventions that reduce CDI rates. Infect Control Hosp Epidemiol 2017;38:476-482.

  11. Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections.

    PubMed

    McFarland, Lynne Vernice; Ozen, Metehan; Dinleyici, Ener Cagri; Goh, Shan

    2016-03-21

    Antibiotic-associated diarrhea (AAD) and Clostridium difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.

  12. Risk for Clostridium difficile Infection After Allogeneic Hematopoietic Cell Transplant Remains Elevated in the Postengraftment Period

    PubMed Central

    Dubberke, Erik R.; Reske, Kimberly A.; Olsen, Margaret A.; Bommarito, Kerry M.; Seiler, Sondra; Silveira, Fernanda P.; Chiller, Tom M.; DiPersio, John; Fraser, Victoria J.

    2017-01-01

    Background Clostridium difficile infection (CDI) is a frequent cause of diarrhea among allogeneic hematopoietic cell transplant (HCT) recipients. It is unknown whether risk factors for CDI vary by time posttransplant. Methods We performed a 3-year prospective cohort study of CDI in allogeneic HCT recipients. Participants were enrolled during their transplant hospitalizations. Clinical assessments were performed weekly during hospitalizations and for 12 weeks posttransplant, and monthly for 30 months thereafter. Data were collected through patient interviews and chart review, and included CDI diagnosis, demographics, transplant characteristics, medications, infections, and outcomes. CDI cases were included if they occurred within 1 year of HCT and were stratified by time from transplant. Multivariable logistic regression was used to determine risk factors for CDI. Results One hundred eighty-seven allogeneic HCT recipients were enrolled, including 63 (34%) patients who developed CDI. 38 (60%) CDI cases occurred during the preengraftment period (days 0-30 post-HCT) and 25 (40%) postengraftment (day >30). Lack of any preexisting comorbid disease was significantly associated with lower risk of CDI preengraftment (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.9). Relapsed underlying disease (OR, 6.7; 95% CI, 1.3-33.1), receipt of any high-risk antimicrobials (OR, 11.8; 95% CI, 2.9-47.8), and graft-versus-host disease (OR, 7.8; 95% CI, 2.0-30.2) were significant independent risk factors for CDI postengraftment. Conclusions A large portion of CDI cases occurred during the postengraftment period in allogeneic HCT recipients, suggesting that surveillance for CDI should continue beyond the transplant hospitalization and preengraftment period. Patients with continued high underlying severity of illness were at increased risk of CDI postengraftment.

  13. 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

  14. 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.

  15. Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.

    PubMed

    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

  16. 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

  17. Role of the leukocyte response in normal and immunocompromised host after Clostridium difficile infection.

    PubMed

    Vargas, Edwin; Apewokin, Senu; Madan, Rajat

    2017-02-20

    Clostridium difficile is the leading cause of healthcare-associated infections in the United States. Clinically, C. difficile-associated disease can present as asymptomatic colonization, self-limited diarrheal illness or severe colitis (that may result in death). This variability in disease course and outcomes suggests that host factors play an important role as key determinants of disease severity. Currently, there are several scoring indices to estimate severity of C. difficile-associated disease. Leukocytosis and renal failure are considered to be the most important predictors of C. difficile disease severity in hosts with a normal immune system. The degree of leukocytosis which is considered significant for severe disease and how it is scored vary amongst scoring indices. None of the scores have been prospectively validated, and while total WBC count is useful to estimate the magnitude of the host response in most patient populations, in immune-compromised patients like those receiving chemotherapy, solid organ transplant patients or hematopoietic stem cell transplants the WBC response can be variable or even absent making this marker of severity difficult to interpret. Other cellular subsets like neutrophils, eosinophils and lymphocytes provide important information about the host immune status and play an important role in the immune response against C. difficile infection. However, under the current scoring systems the role of these cellular subsets have been underestimated and only total white blood cell counts are taken into account. In this review we highlight the role of host leukocyte response to C. difficile challenge in the normal and immunocompromised host, and propose possible ways that would allow for a better representation of the different immune cell subsets (neutrophils, lymphocytes and eosinophils) in the current scoring indices.

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

    PubMed Central

    Bobr, Aleh; Kuskowski, Michael A.; Johnston, Brian D.; Sadowsky, Michael J.; Khoruts, Alexander

    2016-01-01

    Recurrent Clostridium difficile infection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). Although C. difficile spores 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 of C. 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

  19. Antibiotics for Treatment of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease.

    PubMed

    Horton, Henry A; Dezfoli, Seper; Berel, Dror; Hirsch, Julianna; Ippoliti, Andrew; McGovern, Dermot; Kaur, Manreet; Shih, David; Dubinsky, Marla; Targan, Stephan R; Fleshner, Phillip; Vasiliauskas, Eric A; Grein, Jonathan; Murthy, Rekha; Melmed, Gil Y

    2014-09-01

    Patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn's disease (CD), have worse outcomes with Clostridium difficile infection (CDI), including increased readmissions, colectomy, and death. Oral vancomycin is recommended for the treatment of severe CDI, while metronidazole is the standard of care for nonsevere infection. We aimed to assess treatment outcomes of CDI in IBD. We conducted a retrospective observational study of inpatients with CDI and IBD from January 2006 through December 2010. CDI severity was assessed using published criteria. Outcomes included readmission for CDI within 30 days and 12 weeks, length of stay, colectomy, and death. A total of 114 patients met inclusion criteria (UC, 62; CD, 52). Thirty-day readmissions were more common among UC than CD patients (24.2% versus 9.6%; P=0.04). Same-admission colectomy occurred in 27.4% of UC patients and 0% of CD patients (P<0.01). Severe CDI was more common among UC than CD patients (32.2% versus 19.4%; P=0.12) but not statistically significant. Two patients died from CDI-associated complications (UC, 1; CD, 1). Patients with UC and nonsevere CDI had fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen compared to those treated with metronidazole (30-day readmissions, 31.0% versus 0% [P=0.04]; length of stay, 13.62 days versus 6.38 days [P=0.02]). Patients with UC and nonsevere CDI have fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen relative to those treated with metronidazole alone. Patients with ulcerative colitis and CDI should be treated with vancomycin.

  20. 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.

  1. High resolution melt analysis to track infections due to ribotype 027 Clostridium difficile.

    PubMed

    Grando, Danilla; Said, Mohamed M; Mayall, Barrie C; Gurtler, Volker

    2012-05-01

    The increased prevalence of hypervirulent ribotype 027 Clostridium difficile requires rapid identification of isolates in order to implement timely infection control strategies. High resolution melt (HRM) analysis of PCR products can identify strain variation amongst genera of bacteria. The intergenic (16S-23S rDNA) spacer region contains sequence regions conserved within genera and other sequence region variables between species within genera. We wished to investigate whether HRM analysis of PCR ribotyping products could identify ribotype 027 C. difficile. Ribotyping was performed on 93 clinical isolates and five control strains and band patterns were analysed using GelCompar II (Applied Maths, USA). Real-time PCR using ribotyping primers was performed and normalised melt curves were generated. The HRM data was then imported into ScreenClust software (QIAGEN) to generate principal component analysis graphs depicting clustered relationships of strains. Ribotyping produced clear PCR bands for 88/98 isolates tested. Dendrograms generated by GelCompar showed a diversity of ribotype patterns amongst these 88 isolates with 18 groups identified with 70% homology. One clinical isolate showed 100% homology with the control 027 strains. ScreenClust analysis of the same 88 HRM results showed clustering of isolates, with 027 strains identifiable as a unique cluster. HRM analysis correctly identified the control 027 stains and the clinical isolate shown to be 027. HRM combined with ScreenClust analysis of real-time PCR products of the 16S-23S rDNA spacer region successfully identified ribotype 027 strains. For infection control purposes this was achieved within 2-3 h of colony isolation.

  2. 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

  3. 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.

  4. Clostridium difficile Associated Risk of Death Score (CARDS): A novel severity score to predict mortality among hospitalized patients with Clostridium difficile infection

    PubMed Central

    Kassam, Zain; Fabersunne, Camila Cribb; Smith, Mark B.; Alm, Eric J.; Kaplan, Gilaad G.; Nguyen, Geoffrey C.; Ananthakrishnan, Ashwin N.

    2016-01-01

    Background Clostridium difficile infection (CDI) is public health threat and associated with significant mortality. However, there is a paucity of objectively derived CDI severity scoring systems to predict mortality. Aims To develop a novel CDI risk score to predict mortality entitled: Clostridium difficile Associated Risk of Death Score (CARDS). Methods We obtained data from the United States 2011 Nationwide Inpatient Sample (NIS) database. All CDI-associated hospitalizations were identified using discharge codes (ICD-9-CM, 008.45). Multivariate logistic regression was utilized to identify independent predictors of mortality. CARDS was calculated by assigning a numeric weight to each parameter based on their odds ratio in the final logistic model. Predictive properties of model discrimination were assessed using the c-statistic and validated in an independent sample using the 2010 NIS database. Results We identified 77,776 hospitalizations, yielding an estimate of 374,747 cases with an associated diagnosis of CDI in the United States, 8% of whom died in the hospital. The 8 severity score predictors were identified on multivariate analysis: age, cardiopulmonary disease, malignancy, diabetes, inflammatory bowel disease, acute renal failure, liver disease and ICU admission, with weights ranging from −1 (for diabetes) to 5 (for ICU admission). The overall risk score in the cohort ranged from 0 to 18. Mortality increased significantly as CARDS increased. CDI-associated mortality was 1.2% with a CARDS of 0 compared to 100% with CARDS of 18. The model performed equally well in our validation cohort. Conclusion CARDS is a promising simple severity score to predict mortality among those hospitalized with CDI. PMID:26849527

  5. Patterns of antibiotic use and risk of hospital admission because of Clostridium difficile infection

    PubMed Central

    Dial, Sandra; Kezouh, Abbas; Dascal, Andre; Barkun, Alan; Suissa, Samy

    2008-01-01

    Background Previous observations have indicated that infection with Clostridium difficile occurs almost exclusively after exposure to antibiotics, but more recent observations have suggested that prior antibiotic exposure may be less frequent among cases of community-acquired disease. Methods We used 2 linked health databases to perform a matched, nested case–control study of elderly patients admitted to hospital with community-acquired C. difficile infection. For each of 836 cases among people 65 years of age or older, we selected 10 controls. We determined the proportion of cases that occurred without prior antibiotic exposure and estimated the risk related to exposure to different antibiotics and the duration of increased risk. Results Of the 836 cases, 442 (52.9%) had no exposure to antibiotics in the 45-day period before the index date, and 382 (45.7%) had no exposure in the 90-day period before the index date. Antibiotic exposure was associated with a rate ratio (RR) of 10.6 (95% confidence interval [CI] 8.9–12.8). Clindamycin (RR 31.8, 95% CI 17.6–57.6), cephalosporins (RR 14.9, 95% CI 10.9–20.3) and gatifloxacin (RR 16.7, 95% CI 8.3–33.6) were associated with the highest risk. The RR for C. difficile infection associated with antibiotic exposure declined from 15.4 (95% CI 12.2–19.3) by about 20 days after exposure to 3.2 (95% CI 2.0–5.0) after 45 days. Use of a proton pump inhibitor was associated with increased risk (RR 1.6, 95% CI 1.3–2.0), as were concurrent diagnoses of inflammatory bowel disease (RR 4.1, 95% CI 2.6–6.6), irritable bowel syndrome (RR 3.4, 95% CI 2.3–5.0) and renal failure (RR 1.7, 95% CI 1.2–2.2). Interpretation Community-acquired C. difficile infection occurred in a substantial proportion of individuals with no recent exposure to antibiotics. Among patients who had been exposed to antibiotics, the risk declined markedly by 45 days after discontinuation of use. PMID:18838451

  6. 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

  7. Interleukin-22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice.

    PubMed

    Sadighi Akha, Amir A; McDermott, Andrew J; Theriot, Casey M; Carlson, Paul E; Frank, Charles R; McDonald, Roderick A; Falkowski, Nicole R; Bergin, Ingrid L; Young, Vincent B; Huffnagle, Gary B

    2015-04-01

    Our previous work has shown the significant up-regulation of Il22 and increased phosphorylation of signal transducer and activator of transcription 3 (STAT3) as part of the mucosal inflammatory response to Clostridium difficile infection in mice. Others have shown that phosphorylation of STAT3 at mucosal surfaces includes interleukin-22 (IL-22) and CD160-mediated components. The current study sought to determine the potential role(s) of IL-22 and/or CD160 in the mucosal response to C. difficile infection. Clostridium difficile-infected mice treated with anti-IL-22, anti-CD160 or a combination of the two showed significantly reduced STAT3 phosphorylation in comparison to C. difficile-infected mice that had not received either antibody. In addition, C. difficile-infected mice treated with anti-IL-22/CD160 induced a smaller set of genes, and at significantly lower levels than the untreated C. difficile-infected mice. The affected genes included pro-inflammatory chemokines and cytokines, and anti-microbial peptides. Furthermore, histopathological and flow cytometric assessments both showed a significantly reduced influx of neutrophils in C. difficile-infected mice treated with anti-IL-22/CD160. These data demonstrate that IL-22 and CD160 are together responsible for a significant fraction of the colonic STAT3 phosphorylation in C. difficile infection. They also underscore the additive effects of IL-22 and CD160 in mediating both the pro-inflammatory and pro-survival aspects of the host mucosal response in this infection.

  8. 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

  9. Non-inferiority of pulsed xenon UV light versus bleach for reducing environmental Clostridium difficile contamination on high-touch surfaces in Clostridium difficile infection isolation rooms.

    PubMed

    Ghantoji, Shashank S; Stibich, Mark; Stachowiak, Julie; Cantu, Sherry; Adachi, Javier A; Raad, Issam I; Chemaly, Roy F

    2015-02-01

    The standard for Clostridium difficile surface decontamination is bleach solution at a concentration of 10 % of sodium hypochlorite. Pulsed xenon UV light (PX-UV) is a means of quickly producing germicidal UV that has been shown to be effective in reducing environmental contamination by C. difficile spores. The purpose of this study was to investigate whether PX-UV was equivalent to bleach for decontamination of surfaces in C. difficile infection isolation rooms. High-touch surfaces in rooms previously occupied by C. difficile infected patients were sampled after discharge but before and after cleaning using either bleach or non-bleach cleaning followed by 15 min of PX-UV treatment. A total of 298 samples were collected by using a moistened wipe specifically designed for the removal of spores. Prior to disinfection, the mean contamination level was 2.39 c.f.u. for bleach rooms and 22.97 for UV rooms. After disinfection, the mean level of contamination for bleach was 0.71 c.f.u. (P = 0.1380), and 1.19 c.f.u. (P = 0.0017) for PX-UV disinfected rooms. The difference in final contamination levels between the two cleaning protocols was not significantly different (P = 0.9838). PX-UV disinfection appears to be at least equivalent to bleach in the ability to decrease environmental contamination with C. difficile spores. Larger studies are needed to validate this conclusion.

  10. 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

  11. Toxin-Mediated Paracellular Transport of Antitoxin Antibodies Facilitates Protection against Clostridium difficile Infection

    PubMed Central

    Zhang, Z.; Chen, X.; Hernandez, L. D.; Lipari, P.; Flattery, A.; Chen, S.-C.; Kramer, S.; Polishook, J. D.; Racine, F.; Cape, H.; Kelly, C. P.

    2014-01-01

    The exotoxins TcdA and TcdB are the major virulence factors of Clostridium difficile. Circulating neutralizing antitoxin antibodies are protective in C. difficile infection (CDI), as demonstrated, in part, by the protective effects of actoxumab and bezlotoxumab, which bind to and neutralize TcdA and TcdB, respectively. The question of how systemic IgG antibodies neutralize toxins in the gut lumen remains unresolved, although it has been suggested that the Fc receptor FcRn may be involved in active antibody transport across the gut epithelium. In this study, we demonstrated that genetic ablation of FcRn and excess irrelevant human IgG have no impact on actoxumab-bezlotoxumab-mediated protection in murine and hamster models of CDI, suggesting that Fc-dependent transport of antibodies across the gut wall is not required for efficacy. Tissue distribution studies in hamsters suggest, rather, that the transport of antibodies depends on toxin-induced damage to the gut lining. In an in vitro two-dimensional culture system that mimics the architecture of the intestinal mucosal epithelium, toxins on the apical side of epithelial cell monolayers are neutralized by basolateral antibodies, and antibody transport across the cell layer is dramatically increased upon addition of toxin to the apical side. Similar data were obtained with F(ab′)2 fragments, which lack an Fc domain, consistent with FcRn-independent paracellular, rather than transcellular, transport of antibodies. Kinetic studies show that initial damage caused by apical toxin is required for efficient neutralization by basolateral antibodies. These data may represent a general mechanism of humoral response-mediated protection against enteric pathogens. PMID:25385797

  12. Effect of Lactobacillus acidophilus & epidermal growth factor on experimentally induced Clostridium difficile infection

    PubMed Central

    Kaur, Sukhminderjit; Vaishnavi, Chetana; Prasad, Kaushal Kishor; Ray, Pallab; Kochhar, Rakesh

    2011-01-01

    Background & objectives: Clostridium difficile-associated disease (CDAD) remains an important nosocomial ailment. Antimicrobial therapy used for CDAD gives inconsistent results. This experimental study was planned to investigate the beneficial effects of Lactobacillus acidophilus and epidermal growth factor (EGF) for CDAD management. Methods: Among 10 groups of BALB/c mice (6 in each), group 1 served as controls receiving no inoculum. Animals in groups 2-10 received C. difficile, those in groups 3, 6 and 9 received L. acidophilus and those in groups 4, 7 and 10 received EGF after C. difficile inoculation. Animals in groups 5-7 were pre-treated with ampicillin and those in groups 8-10 with lansoprazole prior to C. difficile. The animals were killed and investigated for colonisation by C. difficile and toxin production, myeloperoxidase (MPO) activity and histopathology. Results: Colonisation by C. difficile was found to be significantly different (P<0.001) in the various groups. C. difficile toxin titres and MPO activity were significantly lower in animals given L. acidophilus and EGF after ampicillin (groups 6 and 7) and lansoprazole (groups 9 and 10). The severity of acute inflammation was also significantly less (P<0.05) in caecal and colonic segments of animals in groups 6 and 7 compared to those in group 5. Although the severity of acute inflammation was less in the caecal and colonic segment of animals in groups 9 and 10, the reduction was not significant compared to group 8. Interpretation & conclusions: Our findings showed that the administration of L. acidophilus and EGF reduced the severity of C. difficile infection in the experimental animals. PMID:21537099

  13. Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile

    PubMed Central

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

    2014-01-01

    Clostridium difficile infection (CDI) is principally responsible for hospital acquired, antibiotic-induced diarrhea and colitis and represents a significant financial burden on our healthcare system. Little is known about C. difficile proliferation requirements, and a better understanding of these parameters is critical for development of new therapeutic targets. In cell lines, C. difficile toxin B has been shown to inhibit Na+/H+ exchanger 3 (NHE3) and loss of NHE3 in mice results in an altered intestinal environment coupled with a transformed gut microbiota composition. However, this has yet to be established in vivo in humans. We hypothesize that C. difficile toxin inhibits NHE3, resulting in alteration of the intestinal environment and gut microbiota. Our results demonstrate that CDI patient biopsy specimens have decreased NHE3 expression and CDI stool has elevated Na+ and is more alkaline compared with stool from healthy individuals. CDI stool microbiota have increased Bacteroidetes and Proteobacteria and decreased Firmicutes phyla compared with healthy subjects. In vitro, C. difficile grows optimally in the presence of elevated Na+ and alkaline pH, conditions that correlate to changes observed in CDI patients. To confirm that inhibition of NHE3 was specific to C. difficile, human intestinal organoids (HIOs) were injected with C. difficile or healthy and CDI stool supernatant. Injection of C. difficile and CDI stool decreased NHE3 mRNA and protein expression compared with healthy stool and control HIOs. Together these data demonstrate that C. difficile inhibits NHE3 in vivo, which creates an altered environment favored by C. difficile. PMID:25552580

  14. Elevated Fecal Calprotectin Associates with Adverse Outcomes from Clostridium difficile Infection in Older Adults

    PubMed Central

    Rao, Krishna; Santhosh, Kavitha; Mogle, Jill A.; Higgins, Peter D. R.; Young, Vincent B.

    2016-01-01

    Background Clostridium difficile infection (CDI) causes a mild to moderate colitis in most patients, but some, especially older adults, develop severe, adverse outcomes. Biomarkers predicting outcomes are needed to optimize treatments. This study tested whether fecal calprotectin associated with a composite primary outcome of complicated CDI (intensive care unit admission, colectomy, or death due to CDI within 30 days of diagnosis) and/or 8-week recurrence. Methods Stool was collected in Cary-Blair media at the time of diagnosis from inpatients of age >60 years that tested positive for C. difficile (enzyme immunoassay [EIA] for toxin A/B or polymerase chain reaction for the tcdB gene). Fecal calprotectin was measured and normalized to solid stool weight. Analysis was performed using logistic regression. Variables were selected for the final model using likelihood ratio tests. Results Fifty patients were included with a mean age 72.8 (± 7.5), and 13 (26%) developed the primary outcome. Clinical variables such as age, gender, and comorbid disease did not associate with complicated CDI/recurrence, nor did traditional biomarkers such as serum albumin or white blood cell count. A high normalized fecal calprotectin (>2000 µg/g) associated with the primary outcome in the final model after adjustment for gender and detectable fecal toxin(s) by EIA (OR 24.9, 95% CI 2.4–257.9, P=.007) with a specificity of 91.9%. Conclusion This study provides evidence that fecal calprotectin level associates with complications from CDI in older adults. Further studies are required to validate these findings in larger cohorts and incorporate them into clinical prediction algorithms. PMID:27206404

  15. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection.

    PubMed

    Brown, Kevin A; Khanafer, Nagham; Daneman, Nick; Fisman, David N

    2013-05-01

    The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.

  16. Alteration of the Murine Gastrointestinal Microbiota by Tigecycline Leads to Increased Susceptibility to Clostridium difficile Infection

    PubMed Central

    Bassis, Christine M.; Young, Vincent B.

    2014-01-01

    Antibiotics can play dual roles in Clostridium difficile infection (CDI); antibiotic treatment increases the risk of CDI, and antibiotics are used to treat CDI. The glycylcycline antibiotic tigecycline has broad antimicrobial activity, yet it is rarely associated with the development of CDI, presumably due to its activity against C. difficile. In this study, we investigated how tigecycline treatment affects the structure of the gut microbiota and susceptibility to CDI by treating mice with tigecycline (n = 20) or saline (n = 8) for 10 days. A sequence analysis of the bacterial 16S rRNA gene amplicons was used to monitor changes in the fecal microbiota. A subset of the mice was followed for 5 weeks after the end of treatment. The remaining mice were challenged with C. difficile strain VPI 10463 spores 2 days after the tigecycline treatment ended. Tigecycline treatment resulted in major shifts in the gut microbiota, including large decreases in Bacteroidetes levels and large increases in Proteobacteria levels. Mice with tigecycline-altered microbial communities were susceptible to challenge with C. difficile spores and developed clinical signs of severe CDI. Five weeks after the cessation of tigecycline treatment, the recovery of the bacterial community was incomplete and diversity was lower than in the untreated controls. Antibiotics with intrinsic activity against C. difficile can still alter the microbiota in a way that leads to susceptibility to CDI after discontinuation of the drug. These results indicate that microbiotic dynamics are key in the development of CDI, and a better understanding of these dynamics may lead to better strategies to prevent and treat this disease. PMID:24590475

  17. Impact of vancomycin faecal concentrations on clinical and microbiological outcomes in Clostridium difficile infection.

    PubMed

    Thabit, Abrar K; Nicolau, David P

    2015-08-01

    To assess the impact of faecal vancomycin concentrations on clinical and microbiological outcomes in patients with Clostridium difficile infection (CDI) and whether these concentrations vary with stool consistency and frequency, faecal concentrations of vancomycin were measured in stools collected at various times from patients initiated on 125mg every 6h (q6h) for 10 days. Stool consistency and frequency were determined over the course of therapy. Clinical and microbiological outcomes were assessed during therapy, at the end of therapy (EOT) and during a 19-38-day follow-up visit. Faecal vancomycin concentrations in 55 stool samples from 15 patients ranged from 175-6299μg/g at Days 3-5 of therapy (midpoint), 17-5277μg/g at EOT and 0-70μg/g at follow-up. Clinical cure or failure at EOT and at follow-up was not dependent on vancomycin concentrations measured at the midpoint (P=0.72) or at EOT (P=0.76). Likewise, concentrations at EOT and at follow-up did not predict colonisation at follow-up (P=0.85 and 0.71, respectively). Faecal vancomycin concentrations during the course of therapy (Days 3-5) did not differ with either stool consistency or frequency (P=0.94 and 0.16, respectively). However, after completion of therapy, patients with more frequent stools showed higher concentrations than patients with less frequent stools (P=0.04). Oral vancomycin 125mg q6h led to faecal concentrations that did not predict clinical outcomes of CDI in terms of cure or gut colonisation and did not vary with stool consistency and frequency.

  18. 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.

  19. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection.

    PubMed

    Weingarden, Alexa R; Chen, Chi; Bobr, Aleh; Yao, Dan; Lu, Yuwei; Nelson, Valerie M; Sadowsky, Michael J; Khoruts, Alexander

    2014-02-15

    Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.

  20. 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.

  1. Incorrect diagnosis of Clostridium difficile infection in a university hospital in Japan.

    PubMed

    Mori, Nobuaki; Yoshizawa, Sadako; Saga, Tomoo; Ishii, Yoshikazu; Murakami, Hinako; Iwata, Morihiro; Collins, Deirdre A; Riley, Thomas V; Tateda, Kazuhiro

    2015-10-01

    Physicians often fail to suspect Clostridium difficile infection (CDI) and many microbiology laboratories use suboptimal diagnostic techniques. To estimate the extent of and reasons for incorrect diagnosis of CDI in Japan, we investigated toxigenic C. difficile isolated from all stool culture samples and clinical course. Over a 12-month period in 2010, all stool culture samples (n = 975) submitted from inpatients in a university hospital in Japan were cultured for C. difficile and routine microbiological testing was conducted. In total, 177 C. difficile isolates were recovered, and 127 isolates were toxigenic. Among the toxin-A-positive/toxin-B-positive isolates, 12 were also positive for the binary toxin gene. However, clinically important ribotypes, such as 027 and 078, were not identified. A total of 58 (45.7%) cases with toxigenic C. difficile had unformed stool, and the incidence CDI was 1.6 cases per 10,000 patient-days. Of these 58 cases, 40 were not diagnosed in routine testing due to a lack of clinical suspicion (24.1%, 14/58) or a negative C. difficile toxin assay result (44.8%, 26/58). A stool toxin assay was performed in 54 patients (78.2%, 54/69) who did not have unformed stool. The present study demonstrated that a significant number of CDI cases in Japan might be overlooked or misdiagnosed in clinical practice due to a lack of clinical suspicion and limitations of microbiological testing for CDI in Japan. Providing education to promote awareness of CDI among physicians is important to improve the accuracy of diagnosis in Japan.

  2. 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

  3. Recurrent Clostridium difficile infection among Medicare patients in nursing homes: A population-based cohort study.

    PubMed

    Zilberberg, Marya D; Shorr, Andrew F; Jesdale, William M; Tjia, Jennifer; Lapane, Kate

    2017-03-01

    We explored the epidemiology and outcomes of Clostridium difficile infection (CDI) recurrence among Medicare patients in a nursing home (NH) whose CDI originated in acute care hospitals.We conducted a retrospective, population-based matched cohort combining Medicare claims with Minimum Data Set 3.0, including all hospitalized patients age ≥65 years transferred to an NH after hospitalization with CDI 1/2011-11/2012. Incident CDI was defined as ICD-9-CM code 008.45 with no others in prior 60 days. CDI recurrence was defined as (within 60 days of last day of CDI treatment): oral metronidazole, oral vancomycin, or fidaxomicin for ≥3 days in part D file; or an ICD-9-CM code for CDI (008.45) during a rehospitalization. Cox proportional hazards and linear models, adjusted for age, gender, race, and comorbidities, examined mortality within 60 days and excess hospital days and costs, in patients with recurrent CDI compared to those without.Among 14,472 survivors of index CDI hospitalization discharged to an NH, 4775 suffered a recurrence. Demographics and clinical characteristics at baseline were similar, as was the risk of death (24.2% with vs 24.4% without). Median number of hospitalizations was 2 (IQR 1-3) among those with and 0 (IQR 0-1) among those without recurrence. Adjusted excess hospital days per patient were 20.3 (95% CI 19.1-21.4) and Medicare reimbursements $12,043 (95% CI $11,469-$12,617) in the group with a recurrence.Although recurrent CDI did not increase the risk of death, it was associated with a far higher risk of rehospitalization, excess hospital days, and costs to Medicare.

  4. The undiagnosed cases of Clostridium difficile infection in a whole nation: where is the problem?

    PubMed

    Alcalá, L; Martín, A; Marín, M; Sánchez-Somolinos, M; Catalán, P; Peláez, T; Bouza, E

    2012-07-01

    Underdiagnosis of Clostridium difficile infection (CDI) because of lack of clinical suspicion or the use of non-sensitive diagnostic techniques is a known problem whose real magnitude has not yet been quantified. In order to estimate the extent of this underdiagnosis, we performed C. difficile cultures on all unformed stool specimens sent-irrespective of the type of request-to a series of laboratories in Spain on a single day. The specimens were cultured, and isolates were characterized at a central reference laboratory. A total of 807 specimens from 730 patients aged ≥ 2 years were selected from 118 laboratories covering 75.4% of the Spanish population. The estimated rate of hospital-acquired CDI was 2.4 episodes per 1000 admissions or 3.8 episodes per 10,000 patient-days. Only half of the episodes occurred in patients hospitalized for >2 days. Two of every three episodes went undiagnosed or were misdiagnosed, owing to non-sensitive diagnostic tests (19.0%) or lack of clinical suspicion and request (47.6%; mostly young people or non-hospitalized patients). The main ribotypes were 014/020 (20.5%), 001 (18.2%), and 126/078 (18.2%). No ribotype 027 strains were detected. Strains were fully susceptible to metronidazole and vancomycin. CDI was underdiagnosed in diarrhoeic stools in a high proportion of episodes, owing to the use of non-sensitive techniques or lack of clinical suspicion, particularly in people aged <65 years or patients with community-acquired diarrhoea. C. difficile toxins should be routinely sought in unformed stools of any origin sent for microbiological diagnosis. The ribotype 027 clone has not yet disseminated in Spain.

  5. Determinants of Clostridium difficile Infection Incidence Across Diverse United States Geographic Locations

    PubMed Central

    Lessa, Fernanda C.; Mu, Yi; Winston, Lisa G.; Dumyati, Ghinwa K.; Farley, Monica M.; Beldavs, Zintars G.; Kast, Kelly; Holzbauer, Stacy M.; Meek, James I.; Cohen, Jessica; McDonald, L. Clifford; Fridkin, Scott K.

    2014-01-01

    Background  Clostridium difficile infection (CDI) is no longer restricted to hospital settings, and population-based incidence measures are needed. Understanding the determinants of CDI incidence will allow for more meaningful comparisons of rates and accurate national estimates. Methods  Data from active population- and laboratory-based CDI surveillance in 7 US states were used to identify CDI cases (ie, residents with positive C difficile stool specimen without a positive test in the prior 8 weeks). Cases were classified as community-associated (CA) if stool was collected as outpatients or ≤3 days of admission and no overnight healthcare facility stay in the past 12 weeks; otherwise, cases were classified as healthcare-associated (HA). Two regression models, one for CA-CDI and another for HA-CDI, were built to evaluate predictors of high CDI incidence. Site-specific incidence was adjusted based on the regression models. Results  Of 10 062 cases identified, 32% were CA. Crude incidence varied by geographic area; CA-CDI ranged from 28.2 to 79.1/100 000 and HA-CDI ranged from 45.7 to 155.9/100 000. Independent predictors of higher CA-CDI incidence were older age, white race, female gender, and nucleic acid amplification test (NAAT) use. For HA-CDI, older age and a greater number of inpatient-days were predictors. After adjusting for relevant predictors, the range of incidence narrowed greatly; CA-CDI rates ranged from 30.7 to 41.3/100 000 and HA-CDI rates ranged from 58.5 to 94.8/100 000. Conclusions  Differences in CDI incidence across geographic areas can be partially explained by differences in NAAT use, age, race, sex, and inpatient-days. Variation in antimicrobial use may contribute to the remaining differences in incidence. PMID:25734120

  6. A chimeric toxin vaccine protects against primary and recurrent Clostridium difficile infection.

    PubMed

    Wang, Haiying; Sun, Xingmin; Zhang, Yongrong; Li, Shan; Chen, Kevin; Shi, Lianfa; Nie, Weijia; Kumar, Raj; Tzipori, Saul; Wang, Jufang; Savidge, Tor; Feng, Hanping

    2012-08-01

    The global emergence of Clostridium difficile infection (CDI) has contributed to the recent surge in severe antibiotic-associated diarrhea and colonic inflammation. C. difficile produces two homologous glucosylating exotoxins, TcdA and TcdB, both of which are pathogenic and require neutralization to prevent disease occurrence. However, because of their large size and complex multifunctional domain structures, it has been a challenge to produce native recombinant toxins that may serve as vaccine candidates. Here, we describe a novel chimeric toxin vaccine that retains major neutralizing epitopes from both toxins and confers complete protection against primary and recurrent CDI in mice. Using a nonpathogenic Bacillus megaterium expression system, we generated glucosyltransferase-deficient holotoxins and demonstrated their loss of toxicity. The atoxic holotoxins induced potent antitoxin neutralizing antibodies showing little cross-immunogenicity or protection between TcdA and TcdB. To facilitate simultaneous protection against both toxins, we generated an active clostridial toxin chimera by switching the receptor binding domain of TcdB with that of TcdA. The toxin chimera was fully cytotoxic and showed potent proinflammatory activities. This toxicity was essentially abolished in a glucosyltransferase-deficient toxin chimera, cTxAB. Parenteral immunization of mice or hamsters with cTxAB induced rapid and potent neutralizing antibodies against both toxins. Complete and long-lasting disease protection was conferred by cTxAB vaccinations against both laboratory and hypervirulent C. difficile strains. Finally, prophylactic cTxAB vaccination prevented spore-induced disease relapse, which constitutes one of the most significant clinical issues in CDI. Thus, the rational design of recombinant chimeric toxins provides a novel approach for protecting individuals at high risk of developing CDI.

  7. 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.

  8. Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole.

    PubMed

    Pham, Vy P; Luce, Andrea M; Ruppelt, Sara C; Wei, Wenjing; Aitken, Samuel L; Musick, William L; Roux, Ryan K; Garey, Kevin W

    2015-10-01

    Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ± 18 years (Charlson comorbidity index, 3.8 ± 2.4; Horn's index, 1.7 ± 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole.

  9. Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile.

    PubMed

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

    2015-03-15

    Clostridium difficile infection (CDI) is principally responsible for hospital acquired, antibiotic-induced diarrhea and colitis and represents a significant financial burden on our healthcare system. Little is known about C. difficile proliferation requirements, and a better understanding of these parameters is critical for development of new therapeutic targets. In cell lines, C. difficile toxin B has been shown to inhibit Na(+)/H(+) exchanger 3 (NHE3) and loss of NHE3 in mice results in an altered intestinal environment coupled with a transformed gut microbiota composition. However, this has yet to be established in vivo in humans. We hypothesize that C. difficile toxin inhibits NHE3, resulting in alteration of the intestinal environment and gut microbiota. Our results demonstrate that CDI patient biopsy specimens have decreased NHE3 expression and CDI stool has elevated Na(+) and is more alkaline compared with stool from healthy individuals. CDI stool microbiota have increased Bacteroidetes and Proteobacteria and decreased Firmicutes phyla compared with healthy subjects. In vitro, C. difficile grows optimally in the presence of elevated Na(+) and alkaline pH, conditions that correlate to changes observed in CDI patients. To confirm that inhibition of NHE3 was specific to C. difficile, human intestinal organoids (HIOs) were injected with C. difficile or healthy and CDI stool supernatant. Injection of C. difficile and CDI stool decreased NHE3 mRNA and protein expression compared with healthy stool and control HIOs. Together these data demonstrate that C. difficile inhibits NHE3 in vivo, which creates an altered environment favored by C. difficile.

  10. Impact of Targeted Educational Interventions on Clostridium difficile Infection Treatment in Critically Ill Adults.

    PubMed

    Hammond, Drayton A; Hughes, Catherine A; Painter, Jacob T; Pennick, Rose E; Chatterjee, Kshitij; Boye, Bradley; Meena, Nikhil

    2016-12-01

    Background: Clostridium difficile infection (CDI) is a growing clinical and economic burden throughout the world. Pharmacists often are members of the primary care team in the intensive care unit (ICU) setting; however, the impact of pharmacists educating other health care providers on appropriateness of CDI treatment has not been previously examined. Objective: This study was performed to determine the impact of structured educational interventions on CDI treatment on appropriateness of CDI treatment and clinical outcomes. Methods: This was a single-center, retrospective, cohort study of patients with CDI in the medical ICU at an academic medical center between January and June 2014 (pre-period) and 2015 (post-period). All patients were evaluated for appropriate CDI treatment before and after implementing pharmacist-provided educational interventions on CDI treatment. Results: Patients in the post-period were prescribed appropriate CDI treatment more frequently than patients in the pre-period (91.7% vs 41.7%; p = .03) and received fewer inappropriate doses of a CDI treatment agent (14 doses vs 30 doses). Patients in the pre-period had a shorter ICU length of stay [1.5 days (range, 1-19) vs 3.5 days (range, 2-36); p = .01] and a similar hospital length of stay [9.5 days (range, 4-24) vs 11.5 days (range, 3-56); p = .30]. Total time spent providing interventions was 4 hours. Conclusion: Patients had appropriate CDI treatment initiated more frequently in the post-period. This low-cost intervention strategy should be easy to implement in institutions where pharmacists interact with physicians during clinical rounds and should be evaluated in institutions where interactions between pharmacists and physicians occur more frequently in non-rounding situations.

  11. 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

  12. 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

    2016-03-01

    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.

  13. A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation.

    PubMed

    Kim, Ji Eun; Gweon, Tae-Geun; Yeo, Chang Dong; Cho, Young-Seok; Kim, Gi Jun; Kim, Jae Young; Kim, Jong Wook; Kim, Hyunho; Lee, Hye Won; Lim, Taeseok; Ham, Hyoju; Oh, Hyun Jin; Lee, Yeongbok; Byeon, Jaeho; Park, Sung Soo

    2014-09-21

    Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia. Clostridium difficile infection (CDI) is a common nosocomial diarrheal disease. Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI. The use of broad-spectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome. Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI. Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.

  14. 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

  15. 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

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

    PubMed Central

    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.

    2016-01-01

    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

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

    PubMed

    Alsammani, Mohamed Alkhatim; Ahmed, Salah Roshdy; Alsheeha, Muneera A; Saadia, Zaheera; Khairi, Somia A

    2012-07-01

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

  18. 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

  19. Mathematical Modeling of the Transmission Dynamics of Clostridium difficile Infection and Colonization in Healthcare Settings: A Systematic Review

    PubMed Central

    Gingras, Guillaume; Guertin, Marie-Hélène; Laprise, Jean-François; Drolet, Mélanie; Brisson, Marc

    2016-01-01

    Background We conducted a systematic review of mathematical models of transmission dynamic of Clostridium difficile infection (CDI) in healthcare settings, to provide an overview of existing models and their assessment of different CDI control strategies. Methods We searched MEDLINE, EMBASE and Web of Science up to February 3, 2016 for transmission-dynamic models of Clostridium difficile in healthcare settings. The models were compared based on their natural history representation of Clostridium difficile, which could include health states (S-E-A-I-R-D: Susceptible-Exposed-Asymptomatic-Infectious-Resistant-Deceased) and the possibility to include healthcare workers and visitors (vectors of transmission). Effectiveness of interventions was compared using the relative reduction (compared to no intervention or current practice) in outcomes such as incidence of colonization, CDI, CDI recurrence, CDI mortality, and length of stay. Results Nine studies describing six different models met the inclusion criteria. Over time, the models have generally increased in complexity in terms of natural history and transmission dynamics and number/complexity of interventions/bundles of interventions examined. The models were categorized into four groups with respect to their natural history representation: S-A-I-R, S-E-A-I, S-A-I, and S-E-A-I-R-D. Seven studies examined the impact of CDI control strategies. Interventions aimed at controlling the transmission, lowering CDI vulnerability and reducing the risk of recurrence/mortality were predicted to reduce CDI incidence by 3–49%, 5–43% and 5–29%, respectively. Bundles of interventions were predicted to reduce CDI incidence by 14–84%. Conclusions Although CDI is a major public health problem, there are very few published transmission-dynamic models of Clostridium difficile. Published models vary substantially in the interventions examined, the outcome measures used and the representation of the natural history of Clostridium

  20. Functional Intestinal Bile Acid 7α-Dehydroxylation by Clostridium scindens Associated with Protection from Clostridium difficile Infection in a Gnotobiotic Mouse Model

    PubMed Central

    Studer, Nicolas; Desharnais, Lyne; Beutler, Markus; Brugiroux, Sandrine; Terrazos, Miguel A.; Menin, Laure; Schürch, Christian M.; McCoy, Kathy D.; Kuehne, Sarah A.; Minton, Nigel P.; Stecher, Bärbel; Bernier-Latmani, Rizlan; Hapfelmeier, Siegfried

    2016-01-01

    Bile acids, important mediators of lipid absorption, also act as hormone-like regulators and as antimicrobial molecules. In all these functions their potency is modulated by a variety of chemical modifications catalyzed by bacteria of the healthy gut microbiota, generating a complex variety of secondary bile acids. Intestinal commensal organisms are well-adapted to normal concentrations of bile acids in the gut. In contrast, physiological concentrations of the various intestinal bile acid species play an important role in the resistance to intestinal colonization by pathogens such as Clostridium difficile. Antibiotic therapy can perturb the gut microbiota and thereby impair the production of protective secondary bile acids. The most important bile acid transformation is 7α-dehydroxylation, producing deoxycholic acid (DCA) and lithocholic acid (LCA). The enzymatic pathway carrying out 7α-dehydroxylation is restricted to a narrow phylogenetic group of commensal bacteria, the best-characterized of which is Clostridium scindens. Like many other intestinal commensal species, 7-dehydroxylating bacteria are understudied in vivo. Conventional animals contain variable and uncharacterized indigenous 7α-dehydroxylating organisms that cannot be selectively removed, making controlled colonization with a specific strain in the context of an undisturbed microbiota unfeasible. In the present study, we used a recently established, standardized gnotobiotic mouse model that is stably associated with a simplified murine 12-species “oligo-mouse microbiota” (Oligo-MM12). It is representative of the major murine intestinal bacterial phyla, but is deficient for 7α-dehydroxylation. We find that the Oligo-MM12 consortium carries out bile acid deconjugation, a prerequisite for 7α-dehydroxylation, and confers no resistance to C. difficile infection (CDI). Amendment of Oligo-MM12 with C. scindens normalized the large intestinal bile acid composition by reconstituting 7

  1. [Successful treatment of life-threatening, treatment resistant Clostridium difficile infection associated pseudomembranous colitis with faecal transplantation].

    PubMed

    Nagy, Gergely György; Várvölgyi, Csaba; Paragh, György

    2012-12-30

    Due to world-wide spread of hypervirulent and antibiotic resistant Clostridium difficile strains, the incidence of these infections are dramatically increasing in Hungary with appalling mortality and recurrence rates. Authors present a case of a 59-year-old patient who developed a severe, relapsing pseudomembranous colitis after antibiotic treatment. Life-threatening symptoms of fulminant colitis were successfully treated with prolonged administration of metronidazole and vancomycin, careful supportive therapy and weeks of intensive care. However, a well-documented, severe relapse developed within a week and this time faecal bacteriotherapy was performed. This treatment resulted in a complete cure without any further antibiotic treatment. In relation to this life-saving faecal transplantation, methodology and indications are briefly discussed. In addition, microbiological issues, epidemiological data and threats associated with antibiotic treatment of Clostridium difficile infections are also covered. Finally, relevant professional societies are urged to prepare a national protocol for faecal transplantation, which could allow introduction of this valuable, cost-effective procedure into the routine clinical practice.

  2. Detection of mixed infection from bacterial whole genome sequence data allows assessment of its role in Clostridium difficile transmission.

    PubMed

    Eyre, David W; Cule, Madeleine L; Griffiths, David; Crook, Derrick W; Peto, Tim E A; Walker, A Sarah; Wilson, Daniel J

    2013-01-01

    Bacterial whole genome sequencing offers the prospect of rapid and high precision investigation of infectious disease outbreaks. Close genetic relationships between microorganisms isolated from different infected cases suggest transmission is a strong possibility, whereas transmission between cases with genetically distinct bacterial isolates can be excluded. However, undetected mixed infections-infection with ≥2 unrelated strains of the same species where only one is sequenced-potentially impairs exclusion of transmission with certainty, and may therefore limit the utility of this technique. We investigated the problem by developing a computationally efficient method for detecting mixed infection without the need for resource-intensive independent sequencing of multiple bacterial colonies. Given the relatively low density of single nucleotide polymorphisms within bacterial sequence data, direct reconstruction of mixed infection haplotypes from current short-read sequence data is not consistently possible. We therefore use a two-step maximum likelihood-based approach, assuming each sample contains up to two infecting strains. We jointly estimate the proportion of the infection arising from the dominant and minor strains, and the sequence divergence between these strains. In cases where mixed infection is confirmed, the dominant and minor haplotypes are then matched to a database of previously sequenced local isolates. We demonstrate the performance of our algorithm with in silico and in vitro mixed infection experiments, and apply it to transmission of an important healthcare-associated pathogen, Clostridium difficile. Using hospital ward movement data in a previously described stochastic transmission model, 15 pairs of cases enriched for likely transmission events associated with mixed infection were selected. Our method identified four previously undetected mixed infections, and a previously undetected transmission event, but no direct transmission between the

  3. Identification of Risk Factors for the Development of Clostridium difficile-Associated Diarrhea Following Treatment of Polymicrobial Surgical Infections

    PubMed Central

    Metzger, Rosemarie; Swenson, Brian R.; Bonatti, Hugo; Hedrick, Traci L.; Hranjec, Tjasa; Popovsky, Kimberley A.; Pruett, Timothy L.; Sawyer, Robert G.

    2011-01-01

    Objective To identify risk factors for Clostridium difficile-associated diarrhea (CDAD) in surgical patients following treatment of polymicrobial infections. Summary Background Data Infections among surgical patients are frequently anaerobic or mixed aerobic-anaerobic infections and are therefore subject to polymicrobial antibiotic coverage, including metronidazole. While multiple antibiotics are known to contribute to the development of CDAD, the role of preventive antibiotics is unproven. Methods An 11-year dataset of consecutive infections treated in surgical patients at a single hospital was reviewed. All intra-abdominal, surgical site, or skin/skin structure infections were identified. Each infection was evaluated for antibiotic coverage and subsequent CDAD. Antibiotic usage was assessed using χ2 analysis. A multiple logistic regression was used to identify independent predictors of CDAD. Results A total of 4178 intra-abdominal, surgical site, or skin/skin structure infections were identified. Of these infections, 98 were followed by CDAD. Only carbapenem use affected the incidence of CDAD: 3.5% of infections treated with a carbapenem were followed by CDAD, whereas only 2.1% of infections treated without carbapenems were followed by CDAD (P = 0.04). Metronidazole had no association with future CDAD. Only age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independently associated with CDAD by multiple logistic regression analysis. Conclusions Older patients with a high severity of illness are at greatest risk for developing CDAD following treatment of polymicrobial infections. No specific antibiotic class, including fluoroquinolones, is associated with an increased incidence of CDAD in this population. Although use of metronidazole in the treatment of polymicrobial infections is appropriate for anaerobic coverage, it does not reduce the risk of future CDAD. PMID:20101175

  4. 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...

  5. Outcomes in children with Clostridium difficile infection: results from a nationwide survey

    PubMed Central

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

    2016-01-01

    Objective: Hospital- and population-based studies demonstrate an increasing incidence of Clostridium difficile infection (CDI) in adults and children; although pediatric CDI outcomes are incompletely understood. We analysed United States National Hospital Discharge Survey (NHDS) data to study CDI in hospitalized children. Methods: NHDS data for 2005–2009 (demographics, diagnoses and discharge status) were obtained; cases and comorbidities were identified using ICD-9 codes. Weighted univariate and multivariate analyses were performed to ascertain incidence of CDI; associations between CDI and outcomes [length of stay (LOS), colectomy, all-cause in-hospital mortality and discharge to a care facility (DTCF)]. Results: Of an estimated 13.8 million pediatric inpatients; 46 176 had CDI; median age was 3 years; overall incidence was 33.5/10 000 hospitalizations. The annual frequency of CDI did not vary from 2005 to 2009 (0.24–0.43%; P = 0.64). On univariate analyses, children with CDI had a longer median LOS (6 vs 2 days), higher rates of colectomy [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.7–2.4], mortality (OR 2.5; 95% CI 2.3–2.7), and DTCF (OR 1.6; 95% CI 1.6–1.7) (all P < 0.0001). After adjusting for age, sex and comorbidities, CDI was an independent and the strongest predictor of increased LOS (adjusted mean difference, 6.4 days; 95% CI 5.4–7.4), higher rates of colectomy (OR 2.1; 95% CI 1.8–2.5), mortality (OR 2.3; 95% CI 2.2–2.5), and DTCF (OR 1.7; 95% CI 1.6–1.8) (all P < 0.0001). On excluding infants from the analysis, children with CDI had higher rates of mortality, DTCF and longer LOS than children without CDI. Conclusions: Despite increased awareness and advancements in management, CDI remains a significant problem and is associated with increased LOS, colectomy, in-hospital mortality and DTCF in hospitalized children. PMID:27081152

  6. 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

  7. Innate Immune Defenses Mediated by Two ILC Subsets are Critical for Protection Against Acute Clostridium difficile Infection

    PubMed Central

    Abt, Michael C.; Lewis, Brittany B.; Caballero, Silvia; Xiong, Huizhong; Carter, Rebecca A.; Sušac, Bože; Ling, Lilan; Leiner, Ingrid; Pamer, Eric G.

    2015-01-01

    Summary Infection with the opportunistic enteric pathogen Clostridium difficile is an increasingly common clinical complication that follows antibiotic treatment-induced gut microbiota perturbation. Innate lymphoid cells (ILCs) are early responders to enteric pathogens; however, their role during C. difficile infection is undefined. To identify immune pathways that mediate recovery from C. difficile infection, we challenged C57BL/6, Rag1−/−, which lack T and B cells, and Rag2−/− Il2rg−/− (Ragγc−/−) mice, which additionally lack ILCs, with C. difficile. In contrast to Rag1−/− mice, ILC-deficient Ragγc−/− mice rapidly succumbed to infection. Rag1−/−, but not Ragγc−/− mice, upregulate expression of ILC1 or ILC3 associated proteins following C. difficile infection. Protection against infection was restored by transferring ILCs into Ragγc−/− mice. While ILC3s made a minor contribution to resistance, loss of IFN-γ or T-bet-expressing ILC1s in Rag1−/− mice increased susceptibility to C. difficile. These data demonstrate a critical role for ILC1s in defense against C. difficile. PMID:26159718

  8. Embryonated chicken eggs as an alternative model for mixed Clostridium perfringens and Eimeria tenella infection in chickens.

    PubMed

    Alnassan, Alaa Aldin; Shehata, Awad Ali; Kotsch, Marianne; Lendner, Matthias; Daugschies, Arwid; Bangoura, Berit

    2013-06-01

    The chorioallantoic membrane (CAM) of chicken embryo eggs is a suitable model for viral and bacterial infections. In the present study, a new approach for testing the pathogenesis and virulence of Clostridium perfringens and Eimeria tenella dual infections as a model using the CAM of embryonated chicken eggs was developed. For this purpose, 24 specific pathogen-free (SPF) embryonated chicken eggs were divided into four groups (n = 6) and designated group E, group CP, group CPE, and NC. Sporozoites of E. tenella (20,000 sporozoites) were inoculated into 10-day-old embryonated SPF chicken eggs (groups E and CPE) via allantoic sac route. At 15-day-old, eggs of groups CP and CPE were infected with 10 (4)  cfu C. perfringens via the same route. Assessment of pathogenicity was assessed using gross and histopathological lesions. Embryo mortality reached 17 % after mono-infection with C. perfringens and/or E. tenella and 50 % in the mixed-infected group. Lesions in the CAMs were most numerous and most severe in co-infected eggs (group CPE), reaching the maximum score of 3 in 50 % of the inoculated eggs (P < 0.01). In Eimeria spp.-infected eggs (group E), lesions of score were between 1 and 2. Mono-infection with C. perfringens did not lead to a significant occurrence of lesions. Histopathological investigations of the CAM revealed clusters of Gram-positive bacteria, infiltration with leukocytes, lymphocytes, and developmental stages of E. tenella in the co-infected group. These data suggest that embryonated eggs could be an in ovo model for studying the pathogenesis of mixed infection with Eimeria and C. perfringens.

  9. Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent Clostridium difficile Infection following Fecal Microbiota Transplantation

    PubMed Central

    Staley, Christopher; Kelly, Colleen R.; Brandt, Lawrence J.; Khoruts, Alexander

    2016-01-01

    ABSTRACT Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT), using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing. As previously reported, the success of heterologous FMT (90%) was superior to that of autologous FMT (43%) (P = 0.019), and post-FMT intestinal bacterial communities differed significantly between treatment arms (P < 0.001). Subjects cured by autologous FMT typically had greater abundances of the Clostridium XIVa clade and Holdemania bacteria prior to treatment, and the relative abundances of these groups increased significantly after FMT compared to heterologous FMT and pre-FMT samples. The typical shift to post-FMT, donor-like assemblages, featuring high relative abundances of genera within the Bacteroidetes and Firmicutes phyla, was not observed in the autologous FMT subjects. Autologous FMT patient bacterial communities were significantly different in composition than those for heterologous FMT patients and donors (P < 0.001). The SourceTracker program, which employs a Bayesian algorithm to determine source contributions to sink communities, showed that patients initially treated by heterologous FMT had significantly higher percentages of engraftment (i.e., similarity to donor communities, mean value of 74%) compared to those who suffered recurrence following autologous FMT (1%) (P ≤ 0.013). The findings of this study suggest that complete donor engraftment may be not necessary if functionally critical taxa are present in subjects following antibiotic therapy. PMID:27999162

  10. Osteosynthesis-associated bone infection caused by a nonproteolytic, nontoxigenic Clostridium botulinum-like strain.

    PubMed

    Carlier, Jean-Philippe; K'ouas, Guylène; Lozniewski, Alain; Sirveaux, François; Cailloux, Philippe; Mory, Francine

    2004-01-01

    A nonproteolytic, nontoxigenic Clostridium botulinum strain identified by conventional and molecular techniques as type B-, E-, or F-like (BEF-like) was isolated from a human postsurgical wound. All previous reports of such strains have been from environmental sources. Since toxin production is the main taxonomic denominator for C. botulinum, a new name is needed for nonproteolytic, nontoxigenic BEF-like clinical isolates.

  11. Long-Term Follow-Up of Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infection in a Dual Solid Organ Transplant Recipient.

    PubMed

    Bilal, Mohammad; Khehra, Raman; Strahotin, Cristina; Mitre, Ricardo

    2015-01-01

    Clostridium difficile infection is one of the most frequent causes of healthcare-associated infections, and its rates are also increasing in the community. Mounting evidence suggests that fecal microbiota transplantation (FMT) may be effective; however, as there is paucity of data regarding the use of FMT in patients with solid organ transplants, we present a case of successful FMT in a patient with dual solid organ transplant.

  12. Co-infection as a confounder for the role of Clostridium difficile infection in children with diarrhoea: a summary of the literature.

    PubMed

    de Graaf, H; Pai, S; Burns, D A; Karas, J A; Enoch, D A; Faust, S N

    2015-07-01

    Although Clostridium difficile is a major cause of antibiotic-associated diarrhoea in adults, the incidence and severity of C. difficile infection (CDI) in children is unclear. One complicating factor in assessing the role of CDI in children is the possibility of co-infection with other gastrointestinal pathogens. In this review, we summarise the literature concerning C. difficile co-infections in young children, in an attempt to discuss the rate of co-infections and their potential role in the severity of CDI clinical presentation. We identified 31 studies where co-infections were analysed, comprising 1,718 patients with positive C. difficile tests. The pooled percentage of reported co-infections was 20.7% (range 0-100%). Viral co-infections were most commonly reported (46%), with bacteria and parasites accounting for 14.9% and 0.01% of cases, respectively. However, the panel of co-infections tested for varied considerably among studies and 38% of stated co-infections did not have a pathogen reported. Substantial variation in how and when tests for gastrointestinal co-infections are carried out, small sample sizes and a lack of clear CDI case definitions preclude meaningful conclusions on the true rate of co-infections in this patient population. This review suggests that co-infections may be common in children with diarrhoea who tested positive for C. difficile. Given a lack of CDI case definitions, especially in young children under the age of 5 years, a broad panel of pathogens should be tested for to exclude other microbiological causes. However, the summarised poor quality of the available literature on this subject highlights a need for further studies.

  13. Faecal microbiota transplantation for recurring Clostridium difficile infection in a patient with Crohn's disease and ileorectal anastomosis.

    PubMed

    Oppfeldt, Asser Mathiassen; Dahlerup, Jens F; Christensen, Lisbet A; Hvas, Christian L

    2016-09-23

    Faecal microbiota transplantation (FMT) is increasingly being used to treat refractory and recurring Clostridium difficile infection (CDI). Although FMT appears to be safe and highly effective in patients with a preserved colon and immunocompetence, its use in patients with inflammatory bowel disease (IBD) who are on immunomodulating therapies is controversial. In particular, patients who have undergone colectomy may have different treatment responses to FMT. In this case report, we describe the successful use of FMT in a female patient aged 19 years with Crohn's disease who underwent ileorectal anastomosis following colectomy. She had recurrent CDIs that were refractory to metronidazole, pulse-tapered vancomycin and fidaxomicin treatments. She underwent 2 FMTs, which were performed via sigmoidoscopy; her mother served as a donor. Follow-up was conducted for 12 months and indicated sustained remission of CDI.

  14. Isolation and identification of Clostridium spp. from infections associated with the injection of drugs: experiences of a microbiological investigation team.

    PubMed

    Brazier, J S; Duerden, B I; Hall, V; Salmon, J E; Hood, J; Brett, M M; McLauchlin, J; George, R C

    2002-11-01

    Pathogenic species of the genus Clostridium may contaminate the materials used in the injection of drugs and under the right conditions may cause serious or life-threatening disease. C. novyi type A was implicated in an outbreak of severe infection with high mortality in injecting drug users who injected heroin extravascularly. The isolation of such highly oxygen-sensitive clostridia from clinical material may require adherence to enhanced methods and, once isolated, commercially available anaerobe identification kits alone may not give an accurate identification. Additional phenotypic tests that are useful in recognising the main pathogenic species are described. Differentiation of C. novyi type A from C. botulinum type C in reference laboratories was based on 16S rDNA sequence data and specific neutralisation of cytopathic effects in tissue culture.

  15. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

    PubMed Central

    Theriot, Casey M.; Koenigsknecht, Mark J.; Carlson, Paul E.; Hatton, Gabrielle E.; Nelson, Adam M.; Li, Bo; Huffnagle, Gary B.; Li, Jun; Young, Vincent B.

    2014-01-01

    Antibiotics can have significant and long lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids, and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including primary bile acid taurocholate for germination, and carbon sources mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth. PMID:24445449

  16. Outcome of relapsing Clostridium difficile infections do not correlate with virulence-, spore- and vegetative cell-associated phenotypes.

    PubMed

    Plaza-Garrido, Ángela; Miranda-Cárdenas, Camila; Castro-Córdova, Pablo; Olguín-Araneda, Valeria; Cofré-Araneda, Glenda; Hernández-Rocha, Cristian; Carman, Robert; Ibáñez, Patricio; Fawley, Warren N; Wilcox, Mark H; Gil, Fernando; Calderón, Iván L; Fuentes, Juan A; Guzmán-Durán, Ana María; Alvarez-Lobos, Manuel; Paredes-Sabja, Daniel

    2015-12-01

    One of the main clinical challenges of Clostridium difficile infections (CDI) is the high rate of relapse episodes. The main determinants involved in relapse of CDI include the presence of antibiotic-resistant C. difficile spores in the colonic environment and a permanent state of dysbiosis of the microbiota caused by antibiotic therapy. A possible scenario is that phenotypes related to the persistence of C. difficile spores might contribute to relapsing infections. In this study, 8 C. difficile isolates recovered from 4 cases with relapsing infection, and 9 isolates recovered from single infection cases were analyzed for PCR ribotyping and the presence of tcdA, tcdB and cdtAB genes. Factors associated to spore persistence, sporulation, spore adherence and biofilm formation and sporulation during biofilm formation were characterized. We also evaluated motility and cytotoxicity. However, we observed no significant difference in the analyzed phenotypes among the different clinical outcomes, most likely due to the high variability observed among strains within clinical backgrounds in each phenotype and the small sample size. It is noteworthy that C. difficile spores adhered to similar extents to undifferentiated and differentiated Caco-2 cells. By contrast, spores of all clinical isolates tested had increased germination efficiency in presence of taurocholate, while decreased sporulation rate during biofilm development in the presence of glucose. In conclusion, these results show that, at least in this cohort of patients, the described phenotypes are not detrimental in the clinical outcome of the disease.

  17. Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared With Metronidazole.

    PubMed

    Lewis, Brittany B; Buffie, Charlie G; Carter, Rebecca A; Leiner, Ingrid; Toussaint, Nora C; Miller, Liza C; Gobourne, Asia; Ling, Lilan; Pamer, Eric G

    2015-11-15

    Antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as Clostridium difficile. Metronidazole or oral vancomycin can cure C. difficile infection, and administration of these agents to prevent C. difficile infection in high-risk patients, although not sanctioned by Infectious Disease Society of America guidelines, has been considered. The relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance are unknown. We investigated the effect of brief treatment with metronidazole and/or oral vancomycin on susceptibility to C. difficile, vancomycin-resistant Enterococcus, carbapenem-resistant Klebsiella pneumoniae, and Escherichia coli infection in mice. Although metronidazole resulted in transient loss of colonization resistance, oral vancomycin markedly disrupted the microbiota, leading to prolonged loss of colonization resistance to C. difficile infection and dense colonization by vancomycin-resistant Enterococcus, K. pneumoniae, and E. coli. Our results demonstrate that vancomycin, and to a lesser extent metronidazole, are associated with marked intestinal microbiota destruction and greater risk of colonization by nosocomial pathogens.

  18. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection

    PubMed Central

    Antharam, Vijay C.; McEwen, Daniel C.; Garrett, Timothy J.; Dossey, Aaron T.; Li, Eric C.; Kozlov, Andrew N.; Mesbah, Zhubene; Wang, Gary P.

    2016-01-01

    Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism. PMID:26871580

  19. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

    PubMed

    Antharam, Vijay C; McEwen, Daniel C; Garrett, Timothy J; Dossey, Aaron T; Li, Eric C; Kozlov, Andrew N; Mesbah, Zhubene; Wang, Gary P

    2016-01-01

    Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

  20. [Bilateral anomaly in the style of Sciopemyia sordellii (Shannon & Del Ponte) (Diptera, Psychodidae)].

    PubMed

    Cutolo, André Antonio; Zuben, Claudio José Von; Galati, Eunice Aparecida Bianchi

    2009-01-01

    This paper presents a male specimen of Sciopemyia sordellii with a rare bilateral anomaly, consisting in eight spines in a style and five in the other. Tis species has four spines in each style as its normal number. The specimen was captured using a CDC light trap, in a forested area in the State Park "Floresta Estadual Edmundo Navarro de Andrade", in May 2004, located in the city of Rio Claro, São Paulo State, Brazil. Similar anomaly was once described but this is the first specimen found with a bilateral alteration. It may cause confusion in taxonomic identification and even lead to description of new species, increasing the number of synonymies.

  1. A meta-analysis of metronidazole and vancomycin for the treatment of Clostridium difficile infection, stratified by disease severity.

    PubMed

    Di, Xiuzhen; Bai, Nan; Zhang, Xin; Liu, Bin; Ni, Wentao; Wang, Jin; Wang, Kai; Liang, Beibei; Liu, Youning; Wang, Rui

    2015-01-01

    The aim of this meta-analysis was to compare the efficacy of metronidazole and vancomycin for the treatment of Clostridium difficile infection, especially to investigate which agent was superior for treating either mild or severe C. difficile infection. A meta-analysis of randomized controlled trials and cohort studies identified in Pubmed, Embase, and the Cochrane Library was conducted. Four randomized controlled trials and two cohort studies involving 1218 patients were included in this meta-analysis. Metronidazole was inferior to vancomycin for treating C. difficile infection in terms of both initial clinical cure rates (risk ratio, RR=0.91, 95% confidence interval, CI=0.84-0.98, p=0.02) and sustained cure rates (RR=0.88, 95% CI=0.82-0.96, p=0.003). For mild C. difficile infection, the efficacy of metronidazole and vancomycin resulted in similar clinical cure rates (RR=0.94, 95% CI=0.84-1.04, p=0.21) and sustained cure rates (RR=0.93, 95% CI=0.83-1.05, p=0.26). For severe C. difficile infection the efficacy of vancomycin was superior to metronidazole in terms of clinical cure rates (RR=0.81, 95% CI=0.69-0.95, p=0.009), whereas sustained cure rates were similar (RR=0.86, 95% CI=0.72-1.02, p=0.08). Regarding microbiological cure metronidazole therapy was as effective as vancomycin therapy (RR=0.88, 95% CI=0.64-1.21, p=0.43). Recurrence rates with metronidazole and vancomycin for both mild C. difficile infection (RR=0.95, 95% CI=0.56-1.60, p=0.85) and severe C. difficile infection (RR=1.27, 95% CI=0.85-1.91, p=0.25) were not different. Likewise, no difference in all-cause mortality was found as well (RR=0.87, 95% CI=0.56-1.35, p=0.53). In conclusion, vancomycin provides improved initial clinical and sustained cure rates in patients with C. difficile infection compared with metronidazole, especially in patients with severe C. difficile infection. In view of these data, vancomycin may be considered first line therapy for severe C. difficile infection.

  2. A paralytic-like disease of the ostrich (Struthio camelus masaicus) associated with Clostridium chauvoei infection.

    PubMed

    Lublin, A; Mechani, S; Horowitz, H I; Weisman, Y

    1993-03-13

    Two adult Masai ostriches in a zoological collection became recumbent. The birds could not raise the neck or the head, had difficulties in breathing, and died eight and 13 days, respectively, after the first clinical signs appeared. On post mortem examination the heart had a globous appearance accompanied by gelatinous atrophy. The lungs were hyperaemic and oedematic, while the intestines had prominent haemorrhages in their mucosa. The liver and kidney were enlarged, and the former had also necrotic foci. Smears taken from the hyperaemic regions of the intestines and the necrotic foci of the liver were positive to Clostridium chauvoei after staining with specific fluorescein-labelled antiserum. No other pathogenic agents were identified or isolated from these birds. This report appears to be the first of a pathogenic condition associated with C chauvoei in an avian species.

  3. Microbial and metabolic interactions between the gastrointestinal tract and Clostridium difficile infection

    PubMed Central

    Theriot, Casey M; Young, Vincent B

    2014-01-01

    Antibiotics disturb the gastrointestinal tract microbiota and in turn reduce colonization resistance against Clostridium difficile. The mechanism for this loss of colonization resistance is still unknown but likely reflects structural (microbial) and functional (metabolic) changes to the gastrointestinal tract. Members of the gut microbial community shape intestinal metabolism that provides nutrients and ultimately supports host immunity. This review will discuss how antibiotics alter the structure of the gut microbiota and how this impacts bacterial metabolism in the gut. It will also explore the chemical requirements for C. difficile germination, growth, toxin production and sporulation. Many of the metabolites that influence C. difficile physiology are products of gut microbial metabolism including bile acids, carbohydrates and amino acids. To restore colonization resistance against C. difficile after antibiotics a targeted approach restoring both the structure and function of the gastrointestinal tract is needed. PMID:24335555

  4. Association between Key-Gaskell syndrome and infection by Clostridium botulinum type C/D.

    PubMed

    Nunn, F; Cave, T A; Knottenbelt, C; Poxton, I R

    2004-07-24

    There is growing evidence that equine dysautonomia is a toxicoinfection with Clostridium botulinum type C. The possibility that feline dysautonomia has the same aetiology was investigated by attempting to detect botulinum type C neurotoxin in the food, faeces and the contents of the ileum of affected cats, and by serology. The toxin was detected directly in four of eight affected cats and after enrichment in seven of them, and in their dried food. No toxin was detected in healthy control cats or in their tinned food. Recent exposure to the organism was assessed by the detection of immunoglobulin A (IgA) in the faeces of healthy control cats and affected cats. The levels of IgA antibodies to the toxin and to surface antigens of C. botulinum type C in the faeces of the affected cats 14 weeks after the outbreak were significantly higher than in the faeces of the control cats.

  5. Equine colitis X associated with infection by Clostridium difficile NAP1/027.

    PubMed

    Songer, J Glenn; Trinh, H T; Dial, Sharon M; Brazier, Jon S; Glock, Robert D

    2009-05-01

    A 14-year-old Quarter Horse with a 48-hr history of colic was euthanized after failure to respond to treatment. At necropsy, cecal and colonic mucosae were congested throughout, and there was segmental edema and significant thickening of the intestinal wall. Excessive numbers of mononuclear cells were found in mucosal lamina propria. Submucosal hemorrhage was diffuse and extensive, and Clostridium difficile toxins A and B were detected. Large numbers of C. difficile were isolated, and genetic characterization revealed them to be North American pulsed-field gel electrophoresis type 1, polymerase chain reaction ribotype 027, and toxinotype III. Genes for the binary toxin were present, and toxin negative-regulator tcdC contained an 18-bp deletion. This genotype comprises the current human "epidemic strain," which is associated with human C. difficile-associated disease of greater than historical severity. The diagnosis was peracute typhlocolitis, with lesions and history typical of those attributed to colitis X.

  6. Prolongation of length of stay and Clostridium difficile infection: a review of the methods used to examine length of stay due to healthcare associated infections

    PubMed Central

    2012-01-01

    Background It is believed that Clostridium difficile infection (CDI) contributes to a prolongation of length of stay (LOS). Recent literature suggests that models previously used to determine LOS due to infection have overestimated LOS, compared to newer statistical models. The purpose of this review is to understand the impact that CDI has on LOS and in doing so, describe the methodological approaches used. Aim First, to investigate and describe the reported prolongation of LOS in hospitalised patients with CDI. Second, to describe the methodologies used for determining excess LOS. Methods An integrative review method was used. Papers were reviewed and analysed individually and themes were combined using integrative methods. Results Findings from all studies suggested that CDI contributes to a longer LOS in hospital. In studies that compared persons with and without CDI, the difference in the LOS between the two groups ranged from 2.8days to 16.1days. Potential limitations with data analysis were identified, given that no study fully addressed the issue of a time-dependent bias when examining the LOS. Recent literature suggests that a multi-state model should be used to manage the issue of time-dependent bias. Conclusion Studies examining LOS attributed to CDI varied considerably in design and data collected. Future studies examining LOS related to CDI and other healthcare associated infections should consider capturing the timing of infection in order to be able to employ a multi-state model for data analysis. PMID:22958238

  7. The correlation between Clostridium-difficile infection and human gut concentrations of Bacteroidetes phylum and clostridial species.

    PubMed

    Goldberg, E; Amir, I; Zafran, M; Gophna, U; Samra, Z; Pitlik, S; Bishara, J

    2014-03-01

    We aimed to assess differences in bacterial intensities of Bacteroidetes phylum and different clostridial species in the human intestines with respect to C. difficile infection. Patients with a stool assay for C. difficile toxin were identified via the microbiology laboratory in our institute. Bacterial populations were quantified from stool samples of four groups of patients: Group I-patients with C. difficile associated diarrhea (CDAD); Group II-asymptomatic C. difficile carriers; Group III-patients with non-C. difficile diarrhea; Group IV-patients with no diarrhea and negative stool samples for the C. difficile toxin (control group). Stool was examined for three genes-C. difficile toxin A gene, 16S rRNA gene from Clostridium thermocellum representing other clostridial species, and 16S rRNA gene from Bacteroides fragilis representing the Bacteroidetes phylum. Fifty-nine patients underwent analysis of the stool (CDAD group 14, carriers group 14, non-C. difficile diarrhea group 16, control group 15). C. difficile concentration was highest in the CDAD group, followed by the carriers group. Higher concentrations of both clostridial species and Bacteriodetes were observed in the control and non-C. difficile diarrhea groups compared to the CDAD and carriers groups. We demonstrated an inverse association between infection with C. difficile and the abundance of Bacteroidetes phylum and other clostridial species in human intestines. Studies with larger samples and broader diagnostic procedures are needed in order to better explore and understand this association.

  8. Epsilon Toxin Is Essential for the Virulence of Clostridium perfringens Type D Infection in Sheep, Goats, and Mice

    PubMed Central

    Garcia, J. P.; Adams, V.; Beingesser, J.; Hughes, M. L.; Poon, R.; Lyras, D.; Hill, A.; McClane, B. A.; Rood, J. I.

    2013-01-01

    Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis. PMID:23630957

  9. Microbial composition analysis of Clostridium difficile infections in an ulcerative colitis patient treated with multiple fecal microbiota transplantations.

    PubMed

    Brace, Chantalle; Gloor, Gregory B; Ropeleski, Mark; Allen-Vercoe, Emma; Petrof, Elaine O

    2014-09-01

    Fecal microbiota transplantation (FMT) is a promising therapy for Clostridium difficile infection (CDI). However, questions remain regarding efficacy and safety in inflammatory bowel disease (IBD) patients, as well as longitudinal stability of donor stool composition. This report describes an IBD patient with two CDIs 18 months apart, each successfully treated with FMT with no IBD flares or complications. Microbiome composition analysis of patient samples during each infection revealed low-diversity microbiota patterns similar to those previously described in non-IBD patients with CDI and active IBD alone. Samples taken after each transplant demonstrated quick remodeling towards the donor's sample composition coinciding with symptom resolution. Of note, samples taken from the same donor 18 months apart reflected marked differences in microbiota abundances, suggesting that the use of single donors in FMT programs offers little benefit in ensuring predictability of donor stool composition over time. This report describes similar microbial composition patterns during CDI in IBD patients to those described previously in non-IBD patients, and supports FMT as safe and effective treatment for recurring CDI in this patient population.

  10. Human Clostridium difficile infection caused by a livestock-associated PCR ribotype 237 strain in Western Australia

    PubMed Central

    Mc Govern, Alan M.; Foster, Niki F.; Pereira, Lynette A.; Knight, Daniel R.; Elliott, Briony; Chang, Barbara J.

    2016-01-01

    Introduction: Clostridium difficile infection (CDI) is a significant gastrointestinal disease in the developed world and increasingly recognised as a zoonotic infection. In North America and Europe, the PCR ribotype (RT) 078 strain of C. difficile is commonly found in production animals and as a cause of disease in humans although proof of transmission from animals is lacking. This strain is absent in Australian livestock. We report a case of human CDI caused by a strain of C. difficile belonging to known Australian livestock-associated RT 237. Case presentation: A young male was admitted for multiple trauma following a motor vehicle accident and placed on piperacillin/tazobactam for pneumonia. After 4 days of treatment, he developed symptoms of CDI, which was confirmed in the laboratory. His symptoms resolved after 6 days of intravenous metronidazole. The strain of C. difficile isolated was identified as RT 237, an unusual RT previously found in with several Western Australia piggeries. Conclusion: This case of CDI caused by an unusual livestock-associated C. difficile RT 237 supports the hypothesis of zoonotic transmission. The case highlights the potential of livestock to act as reservoir for C. difficile and the need for continued surveillance of CDI in both human and animal populations. PMID:28348781

  11. Epidemiological and pathobiological profiles of Clostridium perfringens infections: review of consecutive series of 33 cases over a 13-year period

    PubMed Central

    Shindo, Yuji; Dobashi, Yoh; Sakai, Toshiyasu; Monma, Chie; Miyatani, Hiroyuki; Yoshida, Yukio

    2015-01-01

    Background: Although Clostridium perfringens (C. perfringens) is well known as the causative agent of several forms of enteric disease, precise epidemiological and pathobiological aspects are still unknown. Methods: We retrospectively reviewed the culture results of samples collected in our hospital from 2001 through 2013. In addition, for the detection and toxinogenic typing of C. perfringens, polymerase-chain-reaction amplification (PCR)-based rapid analysis was performed in 6 cases using DNA extracted from paraffin-embedded tissues. Results: A total of 35 samples from 33 cases were positive for C. perfringens, representing an incidence of 0.017% (35/205, 114). Among 33 patients, 21 patients manifested sepsis and 7 patients had bacteremia. One of the septic cases was complicated by fatal intravascular hemolysis and thus, the prevalence was estimated at 3.0% among C. perfringens infections (1/33). The direct causative disease or state for C. perfringens infection was identified in 18 patients: surgery or intervention for cancers, 8 patients; chemotherapy for cancer, 2 patients; surgery or intervention for non-neoplastic disease, 6 patients; liver cirrhosis, 3 patients, etc. PCR-based toxinogenic typing of C. perfringens detected the alpha-toxin gene only in tissue from a patient who died of massive hemolysis; none of the toxin genes could be amplified in the other 5 cases examined. Conclusions: The prevalence of overt C. perfringens infection is low, but upon detection, infected patients should be carefully monitored for fatal acute hemolysis caused by type A C. perfringens. Furthermore, PCR-based rapid detection of C. perfringens and toxinogenic typing by archival pathological material is applicable as a diagnostic tool. PMID:25755747

  12. A novel multi-strain probiotic and synbiotic supplement for prevention of Clostridium difficile infection in a murine model.

    PubMed

    Kondepudi, Kanthi Kiran; Ambalam, Padma; Karagin, Peren H; Nilsson, Ingrid; Wadström, Torkel; Ljungh, Åsa

    2014-10-01

    The protective effect of a multi-strain probiotic and synbiotic formulation was evaluated in C57BL/6 mice infected with Clostridium difficile (CD) NAP1/027. Antibiotic-treated mice were divided into the following four groups: Group 1, fed with a synbiotic formulation consisting of Lactobacillus plantarum F44, L. paracasei F8, Bifidobacterium breve 46, B. lactis 8:8, galacto-oligosaccharides, isomalto-oligosaccharides, and resistant starch; Group 2, fed with the same four probiotic strains as Group 1; Group 3, fed with the same prebiotic supplements as Group 1 for 7 days before CD infection; and Group 4 (control group) antibiotic treated and infected with NAP1/027 strain. Feces and cecal contents were collected for microbial cell viability, quantitative PCR (qPCR), toxin analyses and histopathology. Synbiotics- and probiotics-fed mice showed a significant increase in total bifidobacteria (P < 0.05). The total lactobacilli count was increased in Group 1. Tests for cecal toxins were negative in Group 2 mice, whereas one sample each from Group 1 and 3 was positive. qPCR of cecal contents showed significant reduction in NAP1/027 DNA copies in Groups 1 and 2 and significantly higher numbers of B. breve 46, L. plantarum F44, and L. paracasei F8 in Groups 1 and 2 (P < 0.05); these changes were much less pronounced in Groups 3 and 4. Our findings indicate that the newly developed synbiotic or multi-strain probiotic formulation confers protection against NAP1/027 infection in C57BL/6 mice. This holds promise for performing human studies.

  13. Clostridium chauvoei in hens.

    PubMed

    Prukner-Radovcic, E; Milakovic-Novak, L; Ivesa-Petricevic, S; Grgic, N

    1995-03-01

    The bacterium Clostridium chauvoei causes disease in certain animals, most frequently in cattle and sheep. It occurs rarely in pigs, while equines and poultry appear to be resistant to infection. Two cases are presented in which C. chauvoei was isolated from disease of complex aetiology in hens. In Case I, 15-week-old light hybrid chickens were affected with chronic respiratory disease, coccidiosis, ascariasis and inflammation of the skin on the head, with necrosis of the comb. Growth was uneven and mortality reached 24%. Clostridium chauvoei was isolated from two of three combs examined. In Case II a flock of broiler breeders aged 11 weeks developed coccidiosis and, owing to disease or death, 60% were excluded from production. Clostridium chauvoei was isolated from all of 10 livers examined. These results demonstrate that C. chauvoei can infect chickens and that its possible role as a pathogen under certain circumstances should be further investigated.

  14. Effect of 3',5'-cyclic diguanylic acid in a broiler Clostridium perfringens infection model.

    PubMed

    Fatima, Mussarat; Rempel, Heidi; Kuang, Xiaomei Tallie; Allen, Kevin J; Cheng, Kimberly M; Malouin, François; Diarra, Moussa S

    2013-10-01

    In an effort to explore strategies to control Clostridium perfringens, we investigated the synergistic effect of a ubiquitous bacterial second messenger 3',5'-cyclic diguanylic acid (c-di-GMP) with penicillin G in a broiler challenge model. All chicks were inoculated in the crop by gavage on d 14, 15, and 16 with a mixture of 4 C. perfringens strains. Birds were treated with saline (control group) or 20 nmol of c-di-GMP by gavage or intramuscularly (IM) on d 24, all in conjunction with penicillin G in water for 5 d. Weekly samplings of ceca and ileum were performed on d 21 to 35 for C. perfringens and Lactobacillus enumeration. On d 35 of age, the IM treatment significantly (P < 0.05) reduced C. perfringens in the ceca, suggesting possible synergistic activity between penicillin G and c-di-GMP against C. perfringens in broiler ceca. Moreover, analysis of ceca DNA for the presence of a series of C. perfringens virulence genes showed a prevalence of 30% for the Clostridium perfringens alpha-toxin gene (cpa) from d 21 to 35 in the IM-treated group, whereas the occurrence of the cpa gene increased from 10 to 60% in the other 2 groups (control and gavage) from d 21 to 35. Detection of β-lactamase genes (blaCMY-2, blaSHV, and blaTEM) indicative of gram-negative bacteria in the same samples from d 21 to 35 did not show significant treatment effects. Amplified fragment-length polymorphism showed a predominant 92% similarity between the ceca of 21-d-old control birds and the 35-d-old IM-treated c-di-GMP group. This suggests that c-di-GMP IM treatment might be effective at restoring the normal microflora of the host on d 35 after being challenged by C. perfringens. Our results suggest that c-di-GMP can reduce the colonization of C. perfringens in the gut without increasing the selection pressure for some β-lactamase genes or altering the commensal bacterial population.

  15. Epidemiology of Clostridium difficile infection in two tertiary-care hospitals in Perth, Western Australia: a cross-sectional study.

    PubMed

    Foster, N F; Collins, D A; Ditchburn, S L; Duncan, C N; van Schalkwyk, J W; Golledge, C L; Keed, A B R; Riley, T V

    2014-05-01

    The epidemiology of Clostridium difficile infection (CDI) has changed over time and between countries. It is therefore essential to monitor the characteristics of patients at risk of infection and the circulating strains to recognize local and global trends, and improve patient management. From December 2011 to May 2012 we conducted a prospective, observational epidemiological study of patients with laboratory-confirmed CDI at two tertiary teaching hospitals in Perth, Western Australia to determine CDI incidence and risk factors in an Australian setting. The incidence of CDI varied from 5.2 to 8.1 cases/10 000 occupied bed days (OBDs) at one hospital and from 3.9 to 16.3/10 000 OBDs at the second hospital. In total, 80 patients with laboratory-confirmed CDI met eligibility criteria and consented to be in the study. More than half (53.8%) had hospital-onset disease, 28.8% had community-onset and healthcare facility-associated disease and 7.5% were community-associated infections according to the definitions used. Severe CDI was observed in 40.0% of these cases but the 30-day mortality rate for all cases was only 2.5%. Besides a shorter length of stay among cases of community-onset CDI, no characteristics were identified that were significantly associated with community-onset or severe CDI. From 70 isolates, 34 different ribotypes were identified. The predominant ribotypes were 014 (24.3%), 020 (5.7%), 056 (5.7%) and 070 (5.7%). Whereas this study suggests that the characteristics of CDI cases in Australia are not markedly different from those in other developed countries, the increase in CDI rate observed emphasizes the importance of surveillance.

  16. Clostridium perfringens infection among inmates at a county jail--Wisconsin, August 2008.

    PubMed

    2009-02-20

    On August 8, 2008, employees at a Wisconsin county jail noted nausea, vomiting, and diarrhea among more than 100 inmates during the early morning inspection. Seven inmates were seen by the jail nurse that morning. Following jail protocol, guards gave at least 60 inmates bismuth subsalicylate to relieve symptoms, and the jail nurse notified local health department staff members, who suspected a foodborne outbreak at the jail and initiated an investigation. This report summarizes the findings of an investigation by the Wisconsin Division of Public Health (WDPH) and the local health department, which determined the outbreak was caused by eating casserole containing ground turkey and beef (relative risk [RR] = 25.1) that was served during the evening meal on August 7. Clostridium perfringens enterotoxin was detected in stool samples collected from six ill inmates, and 43,000 CFU/g of the organism were isolated from a remaining sample of casserole. An environmental investigation determined the casserole was made with food items that were prepared and stored improperly. Proper food preparation and storage methods are especially important in large institutions such as jails and prisons, where large amounts of foods are prepared and served at one time.

  17. Molecular characterization of nosocomial Clostridium difficile infection in pediatric ward in Iran.

    PubMed

    Khoshdel, Abolfazl; Habibian, Roya; Parvin, Neda; Doosti, Abbas; Famouri, Fatemeh; Eshraghi, Ali; Hafizi, Massoud

    2015-01-01

    Clostridium difficile is recognized as a major cause of nosocomial acquired antibiotic-associated diarrhea and pseudomembranous colitis. It is a significant financial burden on modern healthcare resources. This study aimed to assess the molecular characterization of C. difficile strains isolated from children under 5 years old suffered from nosocomial diarrhea. One hundred diarrheic and 130 non-diarrheic fecal samples were collected from pediatrics less than 5 years old. Samples were cultured and C. difficile isolates were subjected to the PCR technique to study the distribution of ribotypes of C. difficile using P3 and P5 primers. Fifty-two out of 100 samples (52 %) were positive for C. difficile. The prevalence of bacterium in healthy children was 4.61 %. Total prevalence of C. difficile in diarrheic girls and boys were 48.9 and 54.7 %, respectively. Thirteen to twenty-four month age children had the highest prevalence of C. difficile. The most commonly detected ribotypes in the C. difficile isolates of Iranian pediatrics were RT027 (11.52 %), R1 (9.61 %) and R13 (7.68 %). The ribotypes of all of the six bacterial isolates of healthy children was not diagnosed. According to the presence of C. difficile and R27 ribotype, a continued genotype surveillance of this bacterium is necessary to monitor changes in the prevalence of certain strains and to identify the emergence of new strains that could affect future vaccine strategies.

  18. Efficacy of fecal microbiota transplantation in 2 children with recurrent Clostridium difficile infection and its impact on their growth and gut microbiome.

    PubMed

    Walia, Ritu; Garg, Shashank; Song, Yang; Girotra, Mohit; Cuffari, Carmen; Fricke, Wolfgang Florian; Dutta, Sudhir K

    2014-11-01

    Fecal microbiota transplantation (FMT) is recognized as an alternative therapeutic modality for recurrent Clostridium difficile infection (RCDI); however, data on its efficacy in children are lacking, including its effect on their growth and fecal microbiota. We report on 2 young children (<3 years old) who failed available therapeutics for RCDI, but responded remarkably well to FMT. Besides resolution of clinical features of C difficile infection (CDI), FMT administration led to marked improvement in their growth, along with increased microbiota diversity, especially proportion of Bacteroides. Our 2 cases illustrate the efficacy of FMT in children with RCDI and its positive effect on their growth and gut microbiota.

  19. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection.

    PubMed

    Crobach, M J T; Planche, T; Eckert, C; Barbut, F; Terveer, E M; Dekkers, O M; Wilcox, M H; Kuijper, E J

    2016-08-01

    In 2009 the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnosing Clostridium difficile infection (CDI) was launched. Since then newer tests for diagnosing CDI have become available, especially nucleic acid amplification tests. The main objectives of this update of the guidance document are to summarize the currently available evidence concerning laboratory diagnosis of CDI and to formulate and revise recommendations to optimize CDI testing. This update is essential to improve the diagnosis of CDI and to improve uniformity in CDI diagnosis for surveillance purposes among Europe. An electronic search for literature concerning the laboratory diagnosis of CDI was performed. Studies evaluating a commercial laboratory test compared to a reference test were also included in a meta-analysis. The commercial tests that were evaluated included enzyme immunoassays (EIAs) detecting glutamate dehydrogenase, EIAs detecting toxins A and B and nucleic acid amplification tests. Recommendations were formulated by an executive committee, and the strength of recommendations and quality of evidence were graded using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. No single commercial test can be used as a stand-alone test for diagnosing CDI as a result of inadequate positive predictive values at low CDI prevalence. Therefore, the use of a two-step algorithm is recommended. Samples without free toxin detected by toxins A and B EIA but with positive glutamate dehydrogenase EIA, nucleic acid amplification test or toxigenic culture results need clinical evaluation to discern CDI from asymptomatic carriage.

  20. The co-seasonality of pneumonia and influenza with Clostridium difficile infection in the United States, 1993-2008.

    PubMed

    Brown, Kevin A; Daneman, Nick; Arora, Paul; Moineddin, Rahim; Fisman, David N

    2013-07-01

    Seasonal variations in the incidence of pneumonia and influenza are associated with nosocomial Clostridium difficile infection (CDI) incidence, but the reasons why remain unclear. Our objective was to consider the impact of pneumonia and influenza timing and severity on CDI incidence. We conducted a retrospective cohort study using the US National Hospital Discharge Survey sample. Hospitalized patients with a diagnosis of CDI or pneumonia and influenza between 1993 and 2008 were identified from the National Hospital Discharge Survey data set. Poisson regression models of monthly CDI incidence were used to measure 1) the time lag between the annual pneumonia and influenza prevalence peak and the annual CDI incidence peak and 2) the lagged effect of pneumonia and influenza prevalence on CDI incidence. CDI was identified in 18,465 discharges (8.52 per 1,000 discharges). Peak pneumonia prevalence preceded peak CDI incidence by 9.14 weeks (95% confidence interval: 4.61, 13.67). A 1% increase in pneumonia prevalence was associated with a cumulative effect of 11.3% over a 6-month lag period (relative risk = 1.113, 95% confidence interval: 1.073, 1.153). Future research could seek to understand which mediating pathways, including changes in broad-spectrum antibiotic prescribing and hospital crowding, are most responsible for the associated changes in incidence.

  1. The incidence and drug resistance of Clostridium difficile infection in Mainland China: a systematic review and meta-analysis

    PubMed Central

    Tang, Chenjie; Cui, Lunbiao; Xu, Yuqiao; Xie, Le; Sun, Pengfei; Liu, Chengcheng; Xia, Wenying; Liu, Genyan

    2016-01-01

    It has been widely reported that the incidence and severity of Clostridium difficile infection (CDI) have increased dramatically in North America and Europe. However, little is known about CDI in Mainland China. In this study, we aimed to investigate the incidence of CDI and the main epidemic and drug-resistant strains of C. difficile in Mainland China through meta-analysis of related studies published after the year 2010. A total of 51 eligible studies were included. The pooled incidence of toxigenic C. difficile among patients with diarrhoea was 14% (95% CI = 12–16%). In Mainland China, ST-37 and ST-3 were the most prevalent strains; fortunately, hypervirulent strains, such as ST-1 (BI/NAP1/027) and ST-11 (RT 078), have only occurred sporadically to date. The rates of C. difficile resistance to ciprofloxacin (98.3%; 95% CI = 96.9–99.7%), clindamycin (81.7%; 95% CI = 76.1–87.3%) and erythromycin (80.2%; 95% CI = 73.5–86.9%) are higher than in other counties; however, none of the C. difficile isolates reported in Mainland China were resistant to metronidazole (n/N = 0/960), vancomycin (n/N = 0/960), tigecycline (n/N = 0/41) or piperacillin/tazobactam(n/N = 0/288). PMID:27897206

  2. Association between Proton Pump Inhibitor Therapy and Clostridium difficile Infection: A Contemporary Systematic Review and Meta-Analysis

    PubMed Central

    Tleyjeh, Imad M.; Alasmari, Faisal A.; Garbati, Musa A.; AlGhamdi, Mushabab; Khan, Abdur Rahman; Tannir, Mohamad Al; Erwin, Patricia J.; Ibrahim, Talal; AlLehibi, Abed; Baddour, Larry M.; Sutton, Alex J.

    2012-01-01

    Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship. PMID:23236397

  3. Clostridium difficile PCR ribotypes 001 and 176 - the common denominator of C. difficile infection epidemiology in the Czech Republic, 2014.

    PubMed

    Krutova, Marcela; Matejkova, Jana; Kuijper, Ed J; Drevinek, Pavel; Nyc, Otakar

    2016-07-21

    In 2014, 18 hospitals in the Czech Republic participated in a survey of the incidence of Clostridium difficile infections (CDI) in the country. The mean CDI incidence was 6.1 (standard deviation (SD):7.2) cases per 10,000 patient bed-days and 37.8 cases (SD: 41.4) per 10,000 admissions. The mean CDI testing frequency was 39.5 tests (SD: 25.4) per 10,000 patient bed-days and 255.8 tests (SD: 164.0) per 10,000 admissions. A total of 774 C. difficile isolates were investigated, of which 225 (29%) belonged to PCR ribotype 176, and 184 isolates (24%) belonged to PCR ribotype 001. Multilocus variable-number tandem repeat analysis (MLVA) revealed 27 clonal complexes formed by 84% (190/225) of PCR ribotype 176 isolates, and 14 clonal complexes formed by 77% (141/184) of PCR ribotype 001 isolates. Clonal clusters of PCR ribotypes 176 and 001 were observed in 11 and 7 hospitals, respectively. Our data demonstrate the spread of two C. difficile PCR ribotypes within 18 hospitals in the Czech Republic, stressing the importance of standardising CDI testing protocols and implementing mandatory CDI surveillance in the country.

  4. Investigating the candidacy of a lipoteichoic acid-based glycoconjugate as a vaccine to combat Clostridium difficile infection.

    PubMed

    Cox, Andrew D; St Michael, Frank; Aubry, Annie; Cairns, Chantelle M; Strong, Philippa C R; Hayes, Alexander C; Logan, Susan M

    2013-12-01

    A lipoteichoic acid has recently been shown to be conserved in the majority of strains from Clostridium difficile and as such is being considered as a possible vaccine antigen. In this study we examine the candidacy of the conserved lipoteichoic acid by demonstrating that it is possible to elicit antibodies against C. difficile strains following immunisation of rabbits and mice with glycoconjugates elaborating the conserved lipoteichoic acid antigen. The present study describes a conjugation strategy that utilises an amino functionality, present at approximately 33 % substitution of the N-acetyl-glucosamine residues within the LTA polymer repeating unit, as the attachment point for conjugation. A maleimide-thiol linker strategy with the maleimide linker on the carboxyl residues of the carrier protein and the thiol linker on the carbohydrate was employed. Immunisation derived antisera from rabbits and mice, recognised all strains of C. difficile vegetative cells examined, despite an immune response to the linkers also being observed. These sera recognised live cells in an immunofluorescence assay and were also able to recognise the spore form of the bacterium. This study has illustrated that the LTA polymer is a highly conserved surface polymer of C. difficile that is easily accessible to the immune system and as such merits consideration as a vaccine antigen to combat C. difficile infection.

  5. Risk factors for Clostridium difficile infection in hemato-oncological patients: A case control study in 144 patients

    PubMed Central

    Fuereder, Thorsten; Koni, Danjel; Gleiss, Andreas; Kundi, Michael; Makristathis, Athanasios; Zielinski, Christoph; Steininger, Christoph

    2016-01-01

    Evidence on risk factors for Clostridium difficile infection (CDI) in hemato-oncologic patients is conflicting. We studied risk factors for CDI in a large, well-characterized cohort of hemato-oncological patients. 144 hemato-oncological patients were identified in this retrospective, single center study with a microbiologically confirmed CDI-associated diarrhea. Patients were compared with 144 age and sex matched hemato-oncologic patients with CDI negative diarrhea. Risk factors such as prior antimicrobial therapy, type of disease, chemotherapy and survival were evaluated. CDI-positive patients received more frequently any antimicrobial agent and antimicrobial combination therapy than CDI-negative patients (79% vs. 67%; OR = 2.26, p = 0.038 and OR = 2.62, p = 0.003, respectively). CDI positive patients were treated more frequently with antimicrobial agents active against C. difficile than CDI negative ones (25% vs. 13%; OR = 2.2, p = 0.039). The interval between last chemotherapy and onset of diarrhea was significantly shorter in patients without CDI (median, 17 days vs 36 days; p < 0.001). Our study demonstrates that chemotherapy is not a significant risk factor for CDI but for early onset CDI negative diarrhea. The predominant modifiable risk factor for CDI is in hemato-oncological patients antimicrobial treatment. These findings should be taken into account in the daily clinical practice to avoid CDI associated complications and excess health care costs. PMID:27510591

  6. Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013.

    PubMed

    Davies, Kerrie A; Ashwin, Helen; Longshaw, Christopher M; Burns, David A; Davis, Georgina L; Wilcox, Mark H

    2016-07-21

    Clostridium difficile infection (CDI) is the major cause of infective diarrhoea in healthcare environments. As part of the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), the largest C. difficile epidemiological study of its type, PCR ribotype distribution of C. difficile isolates in Europe was investigated. PCR ribotyping was performed on 1,196 C. difficile isolates from diarrhoeal samples sent to the European coordinating laboratory in 2012-13 and 2013 (from two sampling days) by 482 participating hospitals from 19 European countries. A total of 125 ribotypes were identified, of which ribotypes 027 (19%, n =222), 001/072 (11%, n = 134) and 014/020 (10%, n = 119) were the most prevalent. Distinct regional patterns of ribotype distribution were noted. Of 596 isolates from patients with toxin-positive stools (CDI cases), ribotype 027 accounted for 22% (32/144) of infections in cases aged from 18 to less than 65 years, but the prevalence decreased in those aged ≥ 65 years (14% (59/412)) and further decreased in those aged ≥ 81 years (9% (18/195)). The prevalence of ribotype 027 and 176, but not other epidemic strains, was inversely proportional to overall ribotype diversity (R(2) = 0.717). This study highlights an increased diversity of C. difficile ribotypes across Europe compared with previous studies, with considerable intercountry variation in ribotype distribution. Continuous surveillance programmes are necessary to monitor the changing epidemiology of C. difficile.

  7. Myonecrosis by Clostridium septicum in a dog, diagnosed by a new multiplex-PCR.

    PubMed

    Ribeiro, Márcio Garcia; Silva, Rodrigo Otávio Silveira; Pires, Prhiscylla Sadanã; Martinho, Anna Paula Vitirito; Lucas, Thays Mizuki; Teixeira, Ana Izabel Passarela; Paes, Antonio Carlos; Barros, Claudenice Batista; Lobato, Francisco Carlos Faria

    2012-10-01

    Clostridial myositis is an acute, generally fatal toxemia that is considered to be rare in pet animals. The present report describes an unusual canine clostridial myositis that was diagnosed by a new multiplex-PCR (mPCR) designed for simultaneous identification of Clostridium sordellii, Clostridium septicum, Clostridium perfringens type A, Clostridium chauvoei, and Clostridium novyi type A. A ten-month-old male Rottweiler dog, that had displayed lameness and swelling of the left limb for 12 h, was admitted to a veterinary hospital. The animal was weak, dyspneic and hyperthermic, and a clinical examination indicated the presence of gas and edema in the limb. Despite emergency treatment, the animal died in only a few minutes. Samples of muscular tissue from the necrotic area were aseptically collected and plated onto defibrinated sheep blood agar (5%) in anaerobic conditions. Colonies suggestive of Clostridium spp. were submitted to testing by multiplex-PCR. Impression smears of the tissues, visualized with Gram and also with panoptic stains, revealed long rod-shaped organisms, and specimens also tested positive using the fluorescent antibody technique (FAT). The FAT and mPCR tests enabled a diagnosis of C. septicum myonecrosis in the dog.

  8. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection.

    PubMed

    Debast, S B; Bauer, M P; Kuijper, E J

    2014-03-01

    In 2009 the first European Society of Clinical Microbiology and Infection (ESCMID) treatment guidance document for Clostridium difficile infection (CDI) was published. The guideline has been applied widely in clinical practice. In this document an update and review on the comparative effectiveness of the currently available treatment modalities of CDI is given, thereby providing evidence-based recommendations on this issue. A computerized literature search was carried out to investigate randomized and non-randomized trials investigating the effect of an intervention on the clinical outcome of CDI. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The ESCMID and an international team of experts from 11 European countries supported the process. To improve clinical guidance in the treatment of CDI, recommendations are specified for various patient groups, e.g. initial non-severe disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences and treatment of CDI when oral administration is not possible. Treatment options that are reviewed include: antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and faecal or bacterial intestinal transplantation. Except for very mild CDI that is clearly induced by antibiotic usage antibiotic treatment is advised. The main antibiotics that are recommended are metronidazole, vancomycin and fidaxomicin. Faecal transplantation is strongly recommended for multiple recurrent CDI. In case of perforation of the colon and/or systemic inflammation and deteriorating clinical condition despite antibiotic therapy, total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended.

  9. Novel Riboswitch-Binding Flavin Analog That Protects Mice against Clostridium difficile Infection without Inhibiting Cecal Flora

    PubMed Central

    Megyola, Cynthia; Plummer, Mark; Osterman, David; O'Connell, Tim; Aristoff, Paul; Quinn, Cheryl; Chrusciel, R. Alan; Poel, Toni J.; Schostarez, Heinrich J.; Stewart, Catherine A.; Walker, Daniel P.; Wuts, Peter G. M.

    2015-01-01

    Novel mechanisms of action and new chemical scaffolds are needed to rejuvenate antibacterial drug discovery, and riboswitch regulators of bacterial gene expression are a promising class of targets for the discovery of new leads. Herein, we report the characterization of 5-(3-(4-fluorophenyl)butyl)-7,8-dimethylpyrido[3,4-b]quinoxaline-1,3(2H,5H)-dione (5FDQD)—an analog of riboflavin that was designed to bind riboswitches that naturally recognize the essential coenzyme flavin mononucleotide (FMN) and regulate FMN and riboflavin homeostasis. In vitro, 5FDQD and FMN bind to and trigger the function of an FMN riboswitch with equipotent activity. MIC and time-kill studies demonstrated that 5FDQD has potent and rapidly bactericidal activity against Clostridium difficile. In C57BL/6 mice, 5FDQD completely prevented the onset of lethal antibiotic-induced C. difficile infection (CDI). Against a panel of bacteria representative of healthy bowel flora, the antibacterial selectivity of 5FDQD was superior to currently marketed CDI therapeutics, with very little activity against representative strains from the Bacteroides, Lactobacillus, Bifidobacterium, Actinomyces, and Prevotella genera. Accordingly, a single oral dose of 5FDQD caused less alteration of culturable cecal flora in mice than the comparators. Collectively, these data suggest that 5FDQD or closely related analogs could potentially provide a high rate of CDI cure with a low likelihood of infection recurrence. Future studies will seek to assess the role of FMN riboswitch binding to the mechanism of 5FDQD antibacterial action. In aggregate, our results indicate that riboswitch-binding antibacterial compounds can be discovered and optimized to exhibit activity profiles that merit preclinical and clinical development as potential antibacterial therapeutic agents. PMID:26169403

  10. Changes in laboratory and clinical workload for Clostridium difficile infection from 2003 to 2007 in hospitals in Edinburgh.

    PubMed

    Reddy, S; Taori, S; Poxton, I R

    2010-04-01

    Clostridium difficile infection (CDI) is a growing concern with regard to increases in incidence and its associated financial burden. A retrospective analysis of patients admitted to Hospitals in Edinburgh from 2003 to 2007 and tested for C. difficile toxins was performed. A total of 45 412 faecal samples were tested and 6286 (13.8%) were positive. Overall CDI was identified in 1.7 cases/1000 in-patient occupied bed days (OBD). The incidence of CDI fell from 1.98 cases/1000 OBD in 2006 to 1.48 cases/1000 OBD in 2007. Renal Medicine, including Transplant Surgery, and Intensive Care had the highest incidence, with >6.2 cases/1000 OBD each, followed by Infectious Diseases and Gastrointestinal Medicine, with rates of 5.5 and 4.42 cases/1000 OBD, respectively. Medicine of the Elderly had an incidence of 1.69 cases/1000 OBD. Incidence increased with age, from 0.45 cases/1000 OBD in the 0-20-year-old age group to 2.02 cases/1000 OBD in the 61-80-year-old age group. Twelve percent of all toxin-positive patients were transferred through a minimum of two specialties when they remained positive for C. difficile toxins. Estimated costs over the study period for toxin testing were approximately pound126 500 and the minimal potential hospitalization costs for patients with CDI was pound20 000 000. The overall incidence of patients identified with CDI fell in 2007 compared to 2006. The incidence has increased with age; however, patients in Medicine of the Elderly had a much lower incidence than in several other specialties and therefore risk assessment of CDI should also be targeted within other specialties. Judicious application of infection control measures remains important for preventing CDI.

  11. Multicenter, Randomized Clinical Trial To Compare the Safety and Efficacy of LFF571 and Vancomycin for Clostridium difficile Infections

    PubMed Central

    Mullane, Kathleen; Lee, Christine; Bressler, Adam; Buitrago, Martha; Weiss, Karl; Dabovic, Kristina; Praestgaard, Jens; Leeds, Jennifer A.; Blais, Johanne

    2014-01-01

    Clostridium difficile infection causes serious diarrheal disease. Although several drugs are available for treatment, including vancomycin, recurrences remain a problem. LFF571 is a semisynthetic thiopeptide with potency against C. difficile in vitro. In this phase 2 exploratory study, we compared the safety and efficacy (based on a noninferiority analysis) of LFF571 to those of vancomycin used in adults with primary episodes or first recurrences of moderate C. difficile infection. Patients were randomized to receive 200 mg of LFF571 or 125 mg of vancomycin four times daily for 10 days. The primary endpoint was the proportion of clinical cures at the end of therapy in the per-protocol population. Secondary endpoints included clinical cures at the end of therapy in the modified intent-to-treat (mITT) population, the time to diarrhea resolution, and the recurrence rate. Seventy-two patients were randomized, with 46 assigned to receive LFF571. Based on the protocol-specified definition, the rate of clinical cure for LFF571 (90.6%) was noninferior to that of vancomycin (78.3%). The 30-day sustained cure rates for LFF571 and vancomycin were 56.7% and 65.0%, respectively, in the per-protocol population and 58.7% and 60.0%, respectively, in the modified intent-to-treat population. Using toxin-confirmed cases only, the recurrence rates were lower for LFF571 (19% versus 25% for vancomycin in the per-protocol population). LFF571 was generally safe and well tolerated. The incidence of adverse events (AEs) was higher for LFF571 (76.1% versus 69.2% for vancomycin), although more AEs in the vancomycin group were suspected to be related to the study drug (38.5% versus 32.6% for LFF571). One patient receiving LFF571 discontinued the study due to an AE. (This study has been registered at ClinicalTrials.gov under registration no. NCT01232595.) PMID:25534727

  12. Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection

    PubMed Central

    Gerding, D. N.; Hecht, D. W.; Louie, T.; Nord, C. E.; Talbot, G. H.; Cornely, O. A.; Buitrago, M.; Best, E.; Sambol, S.; Osmolski, J. R.; Kracker, H.; Locher, H. H.; Charef, P.; Wilcox, M.

    2016-01-01

    Objectives The aim of this study was to evaluate the susceptibilities of Clostridium difficile isolates to cadazolid, a novel antibiotic for the treatment of C. difficile infection. Methods Ribotyping and susceptibilities were determined for C. difficile isolates from a multicentre, double-blind, Phase 2 study of oral cadazolid in patients with C. difficile infection (NCT01222702, ClinicalTrials.gov; EudraCT 2010-020941-29, European Clinical Trials Database). Patients were randomized to receive 250, 500 or 1000 mg of cadazolid twice daily or 125 mg of vancomycin four times daily, for 10 days. MICs of cadazolid, vancomycin, fidaxomicin, linezolid and moxifloxacin were determined at baseline for all patients and post-baseline for patients with clinical failure or recurrence, using the agar dilution method. Results Seventy-eight of 84 patients had an evaluable toxigenic C. difficile isolate at baseline. The most frequent PCR ribotype was 027 (15.4%). Cadazolid MICs for baseline isolates (including epidemic strain 027) ranged from 0.06 to 0.25 mg/L. Baseline cadazolid MICs were similar to those of fidaxomicin and lower than those of vancomycin, linezolid and moxifloxacin. For each clinical outcome group (clinical cure, clinical failure, sustained clinical response and clinical failure or recurrence), the baseline cadazolid MIC range was 0.06–0.25 mg/L. Mean (min–max) cadazolid faecal concentration (μg/g) on day 5 was 884 (101–2710), 1706 (204–4230) and 3226 (1481–12 600) for the doses 250, 500 and 1000 mg, respectively. Conclusions For all cadazolid doses, the faecal concentration was in excess of several thousand-fold the MIC90 for C. difficile. The MIC of cadazolid for all C. difficile isolates, including epidemic strains, was low and in the same narrow range regardless of treatment outcome. PMID:26433782

  13. [Faecal transplantation as a treatment for Clostridium difficile infection, ulcerative colitis and the metabolic syndrome].

    PubMed

    Carstensen, Jeppe West; Hansen, Axel Kornerup

    2014-02-17

    Faecal transplantation as a therapeutic tool is increasingly reported in the scientific literature. Faecal transplantation is currently becoming a treatment for nosocomial, refractory infections with C. difficile. Furthermore, faecal transplantation has been suggested as a treatment for ulcerative colitis as well as for the metabolic syndrome. In the accumulated literature faecal transplantations appear to be safe, effective and superior to current treatments. Faecal transplantation remains a sparsely investigated treatment, however, especially for other diagnoses than C. difficile infection.

  14. Septicemia in Neutropenic Patients Infected with Clostridium tertium Resistant to Cefepime and Other Expanded-Spectrum Cephalosporins

    PubMed Central

    Steyaert, Sophia; Peleman, Renaat; Vaneechoutte, Mario; De Baere, Thierry; Claeys, Geert; Verschraegen, Gerda

    1999-01-01

    Clostridium tertium was isolated from two immunocompromised patients with septicemia, fever, and gastrointestinal symptoms. The strains were resistant to ceftazidime, cefepime, and clindamycin; intermediately resistant to penicillin; and susceptible to metronidazole, quinolones, and vancomycin. PMID:10523601

  15. [Experience with fecal transplantation in the treatment of Clostridium difficile infection].

    PubMed

    Vigvári, Szabolcs; Nemes, Zsuzsanna; Vincze, Aron; Solt, Jenő; Sipos, Dávid; Feiszt, Zsófia; Kappéter, Agnes; Kovács, Beáta; Péterfi, Zoltán

    2014-11-02

    Bevezetés: Az elmúlt évtizedben drámai változásokat tapasztalhattunk a Clostridium difficile-fertőzések epidemiológiájában. Célkitűzés: A szerzők arra a kérdésre kerestek választ, van-e különbség a két, felső gastrointestinalis bejuttatási módszer eredményessége között. Módszer: 100 ml szűrletet 15 esetben nasoduodenalis szondán keresztül adtak be, 15 esetben pedig nasogastricus szondán keresztül. Az elsődleges gyógyulási ráta alatt az esetek azon hányadát értették, ahol a tünetek megszűntek a széklettranszplantáció után és nem tapasztaltak recidívát sem. Másodlagos gyógyulási ráta alatt pedig a betegek azon arányát értelmezték, akiknél egy ismételt beavatkozás után szűntek meg a panaszok és nem tapasztaltak recidívát a következő hat hétben sem. Eredmények: Nasojejunalis szondát használva az elsődleges sikerráta 100%-os volt. Nasogastricus szondát használva az elsődleges sikerráta 80%-os, a másodlagos sikerráta 93,3%-os volt. Összességében a felső gastrointestinalis rendszeren keresztül végzett széklettranszplantáció elsődleges gyógyulási rátája 90,0%, a másodlagos gyógyulási ráta 96,7% volt. Következtetések: A széklettranszplantáció igen hatásos módszer, különösen a terápiarefrakter esetekben Orv. Hetil., 2014, 155(44), 1758–1762.

  16. Relative disease susceptibility and clostridial toxin antibody responses in three commercial broiler lines co-infected with Clostridium perfringens and Eimeria maxima using an experimental model of necrotic enteritis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Necrotic enteritis is an enteric disease of poultry resulting from infection by Clostridium perfringens with co-infection by Eimeria spp. constituting a major risk factor for disease pathogenesis. This study compared three commercial broiler chicken lines using an experimental model of necrotic ente...

  17. PCR detection of Clostridium chauvoei in pure cultures and in formalin-fixed, paraffin-embedded tissues.

    PubMed

    Uzal, F A; Hugenholtz, P; Blackall, L L; Petray, S; Moss, S; Assis, R A; Fernandez Miyakawa, M; Carloni, G

    2003-02-02

    The polymerase chain reaction (PCR) was used to amplify specific segments of the 16S ribosomal RNA gene of Clostridium chauvoei, a major pathogen of ruminants. Three sets of primers were used to produce amplicons of 159, 836 and 959 base pairs (bp), respectively. The PCR was evaluated by testing clinically important strains of Clostridium, including 21 strains of C. chauvoei, five strains each of Clostridium septicum and Clostridium perfringens and two strains each of Clostridium novyi, Clostridium histolyticum and Clostridium sordellii. Both purified DNA and biomass from pure cultures of each of these microorganisms were evaluated as templates in the PCR. In addition, extracts of formalin-fixed, paraffin-embedded tissues of eight sheep experimentally inoculated with C. chauvoei or C. septicum (four animals each) were also tested by the PCR using the three sets of primers. Purified DNA template of all C. chauvoei strains produced PCR amplicons of the expected size for all three primer pairs. However, when biomass from pure cultures of C. chauvoei or tissue extracts were used as templates, only the primer pair designed to produce the 159bp amplicon gave consistently positive results. No positive results were obtained with any primer pair when purified DNA or biomass from pure cultures of non-target clostridial species were used as templates. Therefore, the PCR primer sets appear to be very specific for identifying C. chauvoei in both cultures and tissues.

  18. Fatal acute spontaneous endometritis resulting from Clostridium sordelli.

    PubMed

    Hogan, S F; Ireland, K

    1989-01-01

    Intrauterine clostridial infections have historically been associated with puerperal sepsis, often subsequent to instrumented abortions. Isolated reports have been associated with a malignant neoplasm or degenerating leiomyoma, most often after instrumentation, radiation therapy, or chemotherapy. In these cases, well-known risk factors or obvious niduses for growth and causation of disease were identified. The authors report a case of fatal spontaneous endometritis resulting from Clostridum sordellii, which, to their knowledge, has not been previously reported in the literature. Characteristics of this rare virulent human pathogen are discussed.

  19. Prevalence of Clostridium difficile Infection among Solid Organ Transplant Recipients: A Meta-Analysis of Published Studies

    PubMed Central

    Paudel, Suresh; Zacharioudakis, Ioannis M.; Zervou, Fainareti N.; Ziakas, Panayiotis D.; Mylonakis, Eleftherios

    2015-01-01

    Several factors including antibiotic use, immunosuppression and frequent hospitalizations make solid organ transplant (SOT) recipients vulnerable to Clostridium difficile infection (CDI). We conducted a meta-analysis of published studies from 1991-2014 to estimate the prevalence of CDI in this patient population. We searched PubMed, EMBASE and Google Scholar databases. Among the 75,940 retrieved citations, we found 30 studies coded from 35 articles that were relevant to our study. Based on these studies, we estimated the prevalence of CDI among 21,683 patients who underwent transplantation of kidney, liver, lungs, heart, pancreas, intestine or more than one organ and stratified each study based on the type of transplanted organ, place of the study conduction, and size of patient population. The overall estimated prevalence in SOT recipients was 7.4% [95%CI, (5.6-9.5%)] and it varied based on the type of organ transplant. The prevalence was 12.7% [95%CI, (6.4%-20.9%)] among patients who underwent transplantation for more than one organ. The prevalence among other SOT recipients was: lung 10.8% [95% CI, (5.5%-17.7%)], liver 9.1 % [95%CI, (5.8%-13.2%)], intestine 8% [95% CI, (2.6%-15.9%)], heart 5.2% [95%CI, (1.8%-10.2%)], kidney 4.7% [95% CI, (2.6%-7.3%)], and pancreas 3.2% [95% CI, (0.5%-7.9%)]. Among the studies that reported relevant data, the estimated prevalence of severe CDI was 5.3% [95% CI (2.3%-9.3%)] and the overall recurrence rate was 19.7% [95% CI, (13.7%-26.6%)]. In summary, CDI is a significant complication after SOT and preventive strategies are important in order to reduce the CDI related morbidity and mortality. PMID:25886133

  20. Berberine blocks the relapse of Clostridium difficile infection in C57BL/6 mice after standard vancomycin treatment.

    PubMed

    Lv, Zhi; Peng, Guoli; Liu, Weihua; Xu, Hufeng; Su, JianRong

    2015-07-01

    Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI.

  1. Prevalence and Clinical Outcomes of Clostridium difficile Infection in the Intensive Care Unit: A Systematic Review and Meta-Analysis

    PubMed Central

    Karanika, Styliani; Paudel, Suresh; Zervou, Fainareti N.; Grigoras, Christos; Zacharioudakis, Ioannis M.; Mylonakis, Eleftherios

    2016-01-01

    Background. Intensive care unit (ICU) patients are at higher risk for Clostridium difficile infection (CDI). Methods. We performed a systematic review and meta-analysis of published studies from 1983 to 2015 using the PubMed, EMBASE, and Google Scholar databases to study the prevalence and outcomes of CDI in this patient population. Among the 9146 articles retrieved from the studies, 22 articles, which included a total of 80 835 ICU patients, were included in our final analysis. Results. The prevalence of CDI among ICU patients was 2% (95% confidence interval [CI], 1%–2%), and among diarrheic ICU patients the prevalence was 11% (95% CI, 6%–17%). Among CDI patients, 25% (95% CI, 5%–51%) were diagnosed with pseudomembranous colitis, and the estimated length of ICU stay before CDI acquisition was 10.74 days (95% CI, 5%–51%). The overall hospital mortality among ICU patients with CDI was 32% (95% CI, 26%–39%), compared with 24% (95% CI, 14%–36%) among those without CDI presenting a statistically significant difference in mortality risk (P = .030). It is worth noting that the length of ICU and hospital stay among CDI patients was significantly longer, compared with non-CDI patients (standardized mean of difference [SMD] = 0.49, 95% CI, .39%–.6%, P = .00 and SMD = 1.15, 95% CI, .44%–1.91%, P = .003, respectively). It is noteworthy that the morbidity score at ICU admission (Acute Physiology and Chronic Health Evaluation II [APACHE II]) was not statistically different between the 2 groups (P = .911), implying that the differences in outcomes can be attributed to CDI. Conclusions. The ICU setting is associated with higher prevalence of CDI. In this setting, CDI is associated with increased hospital mortality and prolonged ICU and overall hospital stay. These findings highlight the need for additional prevention and treatment studies in this setting. PMID:26788544

  2. Surveillance snapshot of Clostridium difficile infection in hospitals across Queensland detects binary toxin producing ribotype UK 244.

    PubMed

    Huber, Charlotte A; Hall, Lisa; Foster, Nikki F; Gray, Mareeka; Allen, Michelle; Richardson, Leisha J; Robson, Jennifer; Vohra, Renu; Schlebusch, Sanmarie; George, Narelle; Nimmo, Graeme R; Riley, Thomas V; Paterson, David L

    2014-12-31

    In North America and Europe, the binary toxin positive Clostridium difficile strains of the ribotypes 027 and 078 have been associated with death, toxic megacolon and other adverse outcomes. Following an increase in C. difficile infections (CDIs) in Queensland, a prevalence study involving 175 hospitals was undertaken in early 2012, identifying 168 cases of CDI over a 2 month period. Patient demographics and clinical characteristics were recorded, and C. difficile isolates were ribotyped and tested for the presence of binary toxin genes. Most patients (106/168, 63.1%) were aged over 60 years. Overall, 98 (58.3%) developed symptoms after hospitalisation; 89 cases (53.0%) developed symptoms more than 48 hours after admission. Furthermore, 27 of the 62 (67.7%) patients who developed symptoms in the community ad been hospitalised within the last 3 months. Thirteen of the 168 (7.7%) cases identified had severe disease, resulting in admission to the Intensive Care Unit or death within 30 days of the onset of symptoms. The 3 most common ribotypes isolated were UK 002 (22.9%), UK 014 (13.3%) and the binary toxin-positive ribotype UK 244 (8.4%). The only other binary toxin positive ribotype isolated was UK 078 (n = 1). Of concern was the detection of the binary toxin positive ribotype UK 244, which has recently been described in other parts of Australia and New Zealand. No isolates were of the international epidemic clone of ribotype UK 027, although ribotype UK 244 is genetically related to this clone. Further studies are required to track the epidemiology of ribotype UK 244 in Australia and New Zealand.

  3. Survey of neuraminidase production by Clostridium butyricum, Clostridium beijerinckii, and Clostridium difficile strains from clinical and nonclinical sources.

    PubMed Central

    Popoff, M R; Dodin, A

    1985-01-01

    Neuraminidase production was investigated in 57 Clostridium butyricum strains, 16 Clostridium beijerinckii strains, and 25 Clostridium difficile strains. Neuraminidase activity was found only in C. butyricum strains originating from one human newborn with neonatal necrotizing enterocolitis, two newborns with hemorrhagic colitis, one infected placenta, and one adult with peritonitis, It was concluded that neuraminidase was not a major virulence factor in C. butyricum strains. PMID:4056013

  4. The discovery of a novel antibiotic for the treatment of Clostridium difficile infections: a story of an effective academic–industrial partnership

    PubMed Central

    Mann, John; Taylor, Peter W.; Dorgan, Colin R.; Johnson, Peter D.; Wilson, Francis X.; Vickers, Richard; Dale, Aaron G

    2015-01-01

    Academic drug discovery is playing an increasingly important role in the identification of new therapies for a wide range of diseases. There is no one model that guarantees success. We describe here a drug discovery story where chance, the ability to capitalise on chance, and the assembling of a range of expertise, have all played important roles in the discovery and subsequent development of an antibiotic chemotype based on the bis-benzimidazole scaffold, with potency against a number of current therapeutically challenging diseases. One compound in this class, SMT19969, has recently entered Phase 2 human clinical trials for the treatment of Clostridium difficile infections. PMID:26949507

  5. Comparison of GenomEra C. difficile and Xpert C. difficile as confirmatory tests in a multistep algorithm for diagnosis of Clostridium difficile infection.

    PubMed

    Alcalá, Luis; Reigadas, Elena; Marín, Mercedes; Fernández-Chico, Antonia; Catalán, Pilar; Bouza, Emilio

    2015-01-01

    We compared two multistep diagnostic algorithms based on C. Diff Quik Chek Complete and, as confirmatory tests, GenomEra C. difficile and Xpert C. difficile. The sensitivity, specificity, positive predictive value, and negative predictive value were 87.2%, 99.7%, 97.1%, and 98.3%, respectively, for the GenomEra-based algorithm and 89.7%, 99.4%, 95.5%, and 98.6%, respectively, for the Xpert-based algorithm. GenomEra represents an alternative to Xpert as a confirmatory test of a multistep algorithm for Clostridium difficile infection (CDI) diagnosis.

  6. The Monoclonal Antitoxin Antibodies (Actoxumab–Bezlotoxumab) Treatment Facilitates Normalization of the Gut Microbiota of Mice with Clostridium difficile Infection

    PubMed Central

    Džunková, Mária; D'Auria, Giuseppe; Xu, Hua; Huang, Jun; Duan, Yinghua; Moya, Andrés; Kelly, Ciarán P.; Chen, Xinhua

    2016-01-01

    Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab–bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials. Although the main mechanism of protection is through direct neutralization of the toxins, the impact of MK-3415A on gut microbiota and its restoration has not been examined. Using a CDI murine model, we compared the bacterial diversity of the gut microbiome of mice under different treatments including MK-3415A, vancomycin, or vancomycin combined with MK-3415A, sampled longitudinally. Here, we showed that C. difficile infection resulted in the prevalence of Enterobacter species. Sixty percent of mice in the vehicle group died after 2 days and their microbiome was almost exclusively formed by Enterobacter. MK-3415A treatment resulted in lower Enterobacter levels and restoration of Blautia, Akkermansia, and Lactobacillus which were the core components of the original microbiota. Vancomycin treatment led to significantly lower survival rate than the combo treatment of MK-3415A and vancomycin. Vancomycin treatment decreased bacterial diversity with predominant Enterobacter and Akkermansia, while Staphylococcus expanded after vancomycin treatment was terminated. In contrast, mice treated by vancomycin combined with MK-3415A also experienced decreased bacterial diversity during vancomycin treatment. However, these animals were able to recover their initial Blautia and Lactobacillus proportions, even though episodes of Staphylococcus overgrowth were

  7. Hyperimmune bovine colostrum for treatment of GI infections: a review and update on Clostridium difficile.

    PubMed

    Steele, Jennifer; Sponseller, Jerlyn; Schmidt, Diane; Cohen, Ocean; Tzipori, Saul

    2013-07-01

    Hyperimmune bovine colostrum (HBC), produced by vaccination of a cow during gestation, is rich in targeted immunoglobulins, and can be used to treat a variety of diseases. The published history of HBC use for treating gastrointestinal infections in humans has developed over the past several decades and demonstrates the promise of this type of therapeutic for GI infectious disease. HBC, or purified derivative products, have been used successfully for treatment or prevention of cryptosporidiosis, shigellosis, rotavirus, enterotoxigenic E. coli, and C. difficile infection (CDI). Given the positive results of previous studies using HBC for treatment of CDI, we have produced HBC with antibodies against the two most important virulence factors of C. difficile, TcdA and TcdB, using a novel recombinant vaccine. Our preliminary results demonstrate efficacy of the HBC product for treatment of CDI in the gnotobiotic piglet model, and warrant more thorough investigation. HBC may provide an effective treatment alternative to antibiotics, which can spare the normal gut microflora, and reduce rates of recurrence and antibiotic resistance.

  8. Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

    PubMed Central

    McFarland, Lynne Vernice; Ozen, Metehan; Dinleyici, Ener Cagri; Goh, Shan

    2016-01-01

    Antibiotic-associated diarrhea (AAD) and Clostridum difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics. PMID:27003987

  9. Policy development for Clostridium difficile.

    PubMed

    Wilcox, Mark H

    2012-07-01

    The Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection (ARHAI) was created at the height of the incidence of Clostridium difficile infection (CDI). This article describes the role of ARHAI in the evaluation of laboratory testing for CDI, a related consultation on the legal requirements for manufacturers of in vitro diagnostic medical devices, a CDI healthcare bundle and surveillance of CDI in children.

  10. Use of a Perianal Swab Compared With a Stool Sample to Detect Symptomatic Clostridium difficile Infection.

    PubMed

    Montecalvo, Marisa A; Sisay, Emnet; McKenna, Donna; Wang, Guiqing; Visintainer, Paul; Wormser, Gary P

    2017-04-05

    OBJECTIVE To evaluate the use of a perianal swab to detect CDI. METHODS A perianal swab was collected from each inpatient with a positive stool sample for C. difficile (by polymerase chain reaction [PCR] test) and was tested for C. difficile by PCR and by culture. The variables evaluated included demographics, CDI severity, bathing before perianal swab collection, hours between stool sample and perianal swab, cycle threshold (Ct) to PCR positivity, and doses of CDI treatment before stool sample and before perianal swab. RESULTS Of 83 perianal swabs, 59 (71.1%) tested positive for C. difficile by PCR when perianal swabs were collected an average of 21 hours after the stool sample. Compared with the respective stool sample, the perianal sample was less likely to grow C. difficile (P=.005) and had a higher PCR Ct (P<.001). A direct, significant but weak correlation was detected between the Ct for a positive perianal sample and the respective stool sample (r=0.36; P=.006). An inverse dose relationship was detected between PCR positivity and CDI treatment doses before perianal swab collection (P=.27). CONCLUSION Perianal swabs are a simple method to detect C. difficile tcdB gene by PCR, with a sensitivity of 71%. These data were limited because stool samples and perianal swabs were not collected simultaneously. Compared with stool samples, the perianal Ct values and culture results were consistent with a lower bacterial load on the perianal sample due to the receipt of more CDI treatment before collection or unknown factors affecting perianal skin colonization. Infect Control Hosp Epidemiol 2017;1-5.

  11. Using oral vancomycin prescriptions as a proxy measure for Clostridium difficile infections: a spatial and time series analysis.

    PubMed

    Polgreen, Philip M; Yang, Ming; Kuntz, Jennifer L; Laxminarayan, Ramanan; Cavanaugh, Joseph E

    2011-07-01

    Sales for a drug may be correlated with the prevalence of a condition treated by the drug. We found that state data revealed a strong spatial association and national data a strong temporal association between Clostridium difficile and oral vancomycin prescription sales, suggesting a new "signal" for detecting disease activity.

  12. An Economic Analysis of Strategies to Control Clostridium Difficile Transmission and Infection Using an Agent-Based Simulation Model

    PubMed Central

    Nelson, Richard E.; Jones, Makoto; Leecaster, Molly; Samore, Matthew H.; Ray, William; Huttner, Angela; Huttner, Benedikt; Khader, Karim; Stevens, Vanessa W.; Gerding, Dale; Schweizer, Marin L.; Rubin, Michael A.

    2016-01-01

    Background A number of strategies exist to reduce Clostridium difficile (C. difficile) transmission. We conducted an economic evaluation of “bundling” these strategies together. Methods We constructed an agent-based computer simulation of nosocomial C. difficile transmission and infection in a hospital setting. This model included the following components: interactions between patients and health care workers; room contamination via C. difficile shedding; C. difficile hand carriage and removal via hand hygiene; patient acquisition of C. difficile via contact with contaminated rooms or health care workers; and patient antimicrobial use. Six interventions were introduced alone and "bundled" together: (a) aggressive C. difficile testing; (b) empiric isolation and treatment of symptomatic patients; (c) improved adherence to hand hygiene and (d) contact precautions; (e) improved use of soap and water for hand hygiene; and (f) improved environmental cleaning. Our analysis compared these interventions using values representing 3 different scenarios: (1) base-case (BASE) values that reflect typical hospital practice, (2) intervention (INT) values that represent implementation of hospital-wide efforts to reduce C. diff transmission, and (3) optimal (OPT) values representing the highest expected results from strong adherence to the interventions. Cost parameters for each intervention were obtained from published literature. We performed our analyses assuming low, normal, and high C. difficile importation prevalence and transmissibility of C. difficile. Results INT levels of the “bundled” intervention were cost-effective at a willingness-to-pay threshold of $100,000/quality-adjusted life-year in all importation prevalence and transmissibility scenarios. OPT levels of intervention were cost-effective for normal and high importation prevalence and transmissibility scenarios. When analyzed separately, hand hygiene compliance, environmental decontamination, and empiric

  13. Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection

    PubMed Central

    Nord, Carl Erik; Talbot, George H.; Wilcox, Mark; Gerding, Dale N.; Buitrago, Martha; Kracker, Hilke; Charef, Pascal; Cornely, Oliver A.

    2015-01-01

    Cadazolid, a novel fluoroquinolone-oxazolidinone antibiotic, exhibits potent in vitro activity against Clostridium difficile, including the epidemic BI/NAP1/027 strain. This multicenter, randomized, double-blind, active reference group, phase 2 study evaluated the efficacy and safety of oral cadazolid in treatment of adult patients with C. difficile infection (CDI). Eligible patients with first occurrence/first recurrence of CDI were randomized 1:1:1:1 to 250, 500, or 1,000 mg cadazolid twice daily (BID) or oral 125 mg vancomycin four times daily (QID) for 10 days. The primary endpoint was clinical cure at test of cure (48 ± 24 h after the end of treatment; modified intent-to-treat population), defined as resolution of diarrhea with no further CDI treatment required. Secondary endpoints included recurrence rate, sustained clinical response (clinical cure without recurrence), and time to diarrhea resolution. Of 84 patients enrolled, 20, 22, 20, and 22 received 250, 500, or 1,000 mg cadazolid BID or 125 mg vancomycin QID, respectively. The primary endpoint was achieved in 76.5% (80% confidence interval [CI], 58.4, 89.3), 80.0% (63.9, 91.0), 68.4% (51.1, 82.5), and 68.2% (52.3, 81.3) of patients, respectively. There was no evidence of a cadazolid dosage-dependent response. Each dosage of cadazolid resulted in a lower recurrence rate than with vancomycin (18.2 to 25.0% versus 50%). Consequently, higher sustained clinical response rates were observed with cadazolid (46.7 to 60.0%) than with vancomycin (33.3%). The times to diarrhea resolution were similar for cadazolid and vancomycin. Cadazolid was well tolerated, with no safety signal observed. The results of this phase 2 study support further clinical development of cadazolid. (This study has been registered in the United States at ClinicalTrials.gov under registration no. NCT01222702 and in Europe with the European Medicines Agency under registration no. EUDRA-CT 2010-020941-29.) PMID:26248357

  14. Prevalence and impact of Clostridium difficile infection in elderly residents of long-term care facilities, 2011

    PubMed Central

    Ziakas, Panayiotis D.; Joyce, Nina; Zacharioudakis, Ioannis M.; Zervou, Fainareti N.; Besdine, Richard W.; Mor, Vincent; Mylonakis, Eleftherios

    2016-01-01

    Abstract The elderly population is particularly vulnerable to Clostridium difficile infection (CDI), but the epidemiology of CDI in long-term care facilities (LTCFs) is unknown. We performed a retrospective cohort study and used US 2011 LTCF resident data from the Minimum Data Set 3.0 linked to Medicare claims. We extracted CDI cases based on International Classification of Diseases-9 coding, and compared residents with the diagnosis of CDI to those who did not have a CDI diagnosis during their LTCF stay. We estimated CDI prevalence rates and calculated 3-month mortality rates. The study population consisted of 2,190,613 admissions (median age 82 years; interquartile range 76–88; female to male ratio 2:1; >80% whites), 45,500 of whom had a CDI diagnosis. The nationwide CDI prevalence rate was 1.85 per 100 LTCF admissions (95% confidence interval [CI] 1.83–1.87). The CDI rate was lower in the South (1.54%; 95% CI 1.51–1.57) and higher in the Northeast (2.29%; 95% CI 2.25–2.33). Older age, white race, presence of a feeding tube, unhealed pressure ulcers, end-stage renal disease, cirrhosis, bowel incontinence, prior tracheostomy, chemotherapy, and chronic obstructive pulmonary disease were independently related to “high risk” for CDI. Residents with a CDI diagnosis were more likely to be admitted to an acute care hospital (40% vs 31%, P < 0.001) and less likely to be discharged to the community (46% vs 54%, P < 0.001) than those not reported with CDI during stay. Importantly, CDI was associated with higher mortality (24.7% vs 18.1%, P = 0.001). CDI is common among the elderly residents of LTCFs and is associated with significant increase in 3-month mortality. The prevalence is higher in the Northeast and risk stratification can be used in CDI prevention policies. PMID:27495022

  15. The protective effect of recombinant Lactococcus lactis oral vaccine on a Clostridium difficile-infected animal model

    PubMed Central

    2013-01-01

    Background Oral immunization with vaccines may be an effective strategy for prevention of Clostridium difficile infection (CDI). However, application of previously developed vaccines for preventing CDI has been limited due to various reasons. Here, we developed a recombinant Lactococcus lactis oral vaccine and evaluated its effect on a C. difficile-infected animal model established in golden hamsters in attempt to provide an alternative strategy for CDI prevention. Methods Recombinant L. lactis vaccine was developed using the pTRKH2 plasmid, a high-copy-number Escherichia coli-L. shuttle vector: 1) L. lactis expressing secreted proteins was constructed with recombinant pTRKH2 (secreted-protein plasmid) carrying the Usp45 signal peptide (SPUsp45), nontoxic adjuvanted tetanus toxin fragment C (TETC), and 14 of the 38 C-terminal repeats (14CDTA) of nontoxic C. difficile toxin A (TcdA); and 2) L. lactis expressing secreted and membrane proteins was constructed with recombinant pTRKH2 (membrane-anchored plasmid) carrying SPUsp45, TETC, 14CDTA, and the cell wall-anchored sequence of protein M6 (cwaM6). Then, 32 male Syrian golden hamsters were randomly divided into 4 groups (n = 8 each) for gavage of normal saline (blank control) and L. lactis carrying the empty shuttle vector, secreted-protein plasmid, and membrane-anchored plasmid, respectively. After 1-week gavage of clindamycin, the animals were administered with C. difficile spore suspension. General symptoms and intestinal pathological changes of the animals were examined by naked eye and microscopy, respectively. Protein levels of anti-TcdA IgG/IgA antibodies in intestinal tissue and fluid were analyzed by enzyme-linked immunosorbent assay (ELISA). A cell culture cytotoxicity neutralization assay was done by TcdA treatment with or without anti-TcdA serum pre-incubation or treatment. Apoptosis of intestinal epithelial cells was examined by flow cytometry (FL) assay. Expression of mucosal inflammatory cytokines

  16. Clostridium difficile Infection

    MedlinePlus

    ... for someone who may have C. diff.Use chlorine bleach-based products to disinfect surfaces or items ... may be soiled with stool with detergent and chlorine bleach.If you are visiting someone in a ...

  17. Evaluation of CP Chromo Select Agar for the enumeration of Clostridium perfringens from water.

    PubMed

    Manafi, Mammad; Waldherr, Kerstin; Kundi, Michael

    2013-10-01

    The European Directive on drinking water quality has included mCP agar as the reference method for recovering Clostridium perfringens from drinking waters. In the present study, three media (mCP, TSCF and CP Chromo Select Agar) were evaluated for recovery of C. perfringens in different surface water samples. Out of 139 water samples, using a membrane filtration technique, 131 samples (94.2%) were found to be presumptively positive for C. perfringens in at least one of the culture media. Green colored colonies on CP Chromo Select Agar (CCP agar) were counted as presumptive C. perfringens isolates. Out of 483 green colonies on CCP agar, 96.3% (465 strains, indole negative) were identified as C. perfringens, and 15 strains (3.1%) were indole positive and were identified as Clostridium sordellii, Clostridium bifermentans or Clostridium tetani. Only 3 strains (0.6%) gave false positive results and were identified as Clostridium fallax, Clostridium botulinum, and Clostridium tertium. Variance analysis of the data obtained shows statistically no significant differences in the counts obtained between media employed in this work. The mCP method is very onerous for routine screening and bacterial colonies could not be used for further biochemical testing. The colonies on CCP and TSCF were easy to count and subculture for confirmation tests. TSCF detects sulfite-reducing clostridia, including species other than C. perfringens, and in some cases excessive blackening of the agar frustrated counting of the colonies. If the contamination was too high, TSCF did not consistently produce black colonies and as a consequence, the colonies were white and gave false negative results. On the other hand, the identification of typical and atypical colonies isolated from all media demonstrated that CCP agar was the most useful medium for C. perfringens recovery in water samples.

  18. Common Mesophilic Anaerobes, Including Clostridium botulinum and Clostridium tetani, in 21 Soil Specimens

    PubMed Central

    Smith, Louis Ds.

    1975-01-01

    A relatively rich medium was markedly superior to a dilute medium for the isolation of anaerobic bacteria from soil. The obligate anaerobes isolated from 21 soil samples were all clostridia and the counts ranged from 2.7 × 102 to 3.3 × 106 per g. The organisms most frequently isolated were Clostridium subterminale, C. sordellii, C. sporogenes, C. indolis, C. bifermentans, C. mangenoti, and C. perfringens. Seventeen other species were also recognized but almost one-third of the isolates could not be identified with any known species of Clostridum. C. botulinum type A was demonstrated in six soil samples, and type B in one. These soils were neutral to alkaline in reaction (average pH 7.9) and low in organic matter content (1.4%). The association of C. botulinum types A and B with neutral to alkaline soils was statistically significant (P = 0.001) as was their association with soils low in organic matter (P = 0.005). C. botulinum types E and F were found in one soil sample, pH 4.5, with organic matter 13.7%. C. tetani was isolated from two soil samples, both of intermediate pH value and higher than average organic matter content. PMID:238468

  19. Protection of mice against Clostridium chauvoei infection by anti-idiotype antibody to a monoclonal antibody to flagella.

    PubMed

    Kijima-Tanaka, M; Nakamura, M; Nagamine, N; Takahashi, T; Aoki, A; Tamura, Y

    1994-03-01

    Polyclonal rabbit anti-idiotypic antibody (anti-Id) against the protective monoclonal antibody specific to the flagella of Clostridium chauvoei was produced, purified, and characterized. Anti-Id inhibited the binding of its related monoclonal antibody to the flagellar antigen, suggesting that the anti-Id bore an internal image of the flagellar antigen. When mice were immunized with anti-Id intraperitoneally, the survival rate increased significantly, compared with mice immunized with normal rabbit IgG (P < 0.01), and specific anti-flagellar antibodies were induced.

  20. The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics

    PubMed Central

    Kujawa-Szewieczek, Agata; Adamczak, Marcin; Kwiecień, Katarzyna; Dudzicz, Sylwia; Gazda, Magdalena; Więcek, Andrzej

    2015-01-01

    Background: Lactobacillus plantarum 299v (LP299v) has been used in order to reduce gastrointestinal symptoms during antibiotic exposure. However, it remains controversial whether or not probiotics are effective in the prevention of Clostridium difficile infections (CDI) among patients receiving antibiotics. The aim of this study was to analyze the CDI among patients receiving antibiotics and hospitalized in the period before and after starting routine use of LP299v as a prevention of this infection. Methods: Among 3533 patients hospitalized in the nephrology and transplantation ward during a two-year period, 23 patients with CDI were diagnosed and enrolled in this retrospective study. Since November 2013, prevention of CDI with oral use of LP299v was performed in all patients treated with antibiotics and who were at a high risk of developing CDI. The observation period was divided into two twelve-month intervals before and after initiation of the use of LP299v as a prophylactic against CDI. Results: A significant (p = 0.0001) reduction of the number of cases of CDI was found after routinely using LP299v (n = 2; 0.11% of all hospitalized patients) compared with the previous twelve-month period of observation (n = 21; 1.21% of all hospitalized patients). Conclusions: Routine use of LP299v during treatment with antibiotics may prevent C. difficile infection in the nephrology and transplantation ward. PMID:26690209

  1. Pilin Vaccination Stimulates Weak Antibody Responses and Provides No Protection in a C57Bl/6 Murine Model of Acute Clostridium difficile Infection.

    PubMed

    Maldarelli, Grace A; Matz, Hanover; Gao, Si; Chen, Kevin; Hamza, Therwa; Yfantis, Harris G; Feng, Hanping; Donnenberg, Michael S

    Clostridium difficile is the leading cause of nosocomial infections in the United States, adding billions of dollars per year to health care costs. A vaccine targeted against the bacterium would be extremely beneficial in decreasing the morbidity and mortality caused by C. difficile-associated disease; a vaccine directed against a colonization factor would hinder the spread of the bacterium as well as prevent disease. Type IV pili (T4Ps) are extracellular appendages composed of protein monomers called pilins. They are involved in adhesion and colonization in a wide variety of bacteria and archaea, and are putative colonization factors in C. difficile. We hypothesized that vaccinating mice with pilins would lead to generation of anti-pilin antibodies, and would protect against C. difficile challenge. We found that immunizing C57Bl/6 mice with various pilins, whether combined or as individual proteins, led to low anti-pilin antibody titers and no protection upon C. difficile challenge. Passive transfer of anti-pilin antibodies led to high serum anti-pilin IgG titers, but to undetectable fecal anti-pilin IgG titers and did not protect against challenge. The low antibody titers observed in these experiments may be due to the particular strain of mice used. Further experiments, possibly with a different animal model of C. difficile infection, are needed to determine if an anti-T4P vaccine would be protective against C. difficile infection.

  2. Pilin Vaccination Stimulates Weak Antibody Responses and Provides No Protection in a C57Bl/6 Murine Model of Acute Clostridium difficile Infection

    PubMed Central

    Maldarelli, Grace A; Matz, Hanover; Gao, Si; Chen, Kevin; Hamza, Therwa; Yfantis, Harris G; Feng, Hanping; Donnenberg, Michael S

    2016-01-01

    Clostridium difficile is the leading cause of nosocomial infections in the United States, adding billions of dollars per year to health care costs. A vaccine targeted against the bacterium would be extremely beneficial in decreasing the morbidity and mortality caused by C. difficile-associated disease; a vaccine directed against a colonization factor would hinder the spread of the bacterium as well as prevent disease. Type IV pili (T4Ps) are extracellular appendages composed of protein monomers called pilins. They are involved in adhesion and colonization in a wide variety of bacteria and archaea, and are putative colonization factors in C. difficile. We hypothesized that vaccinating mice with pilins would lead to generation of anti-pilin antibodies, and would protect against C. difficile challenge. We found that immunizing C57Bl/6 mice with various pilins, whether combined or as individual proteins, led to low anti-pilin antibody titers and no protection upon C. difficile challenge. Passive transfer of anti-pilin antibodies led to high serum anti-pilin IgG titers, but to undetectable fecal anti-pilin IgG titers and did not protect against challenge. The low antibody titers observed in these experiments may be due to the particular strain of mice used. Further experiments, possibly with a different animal model of C. difficile infection, are needed to determine if an anti-T4P vaccine would be protective against C. difficile infection. PMID:27375958

  3. Soft tissue infections caused by spore-forming bacteria in injecting drug users in the United Kingdom.

    PubMed

    Brett, M M; Hood, J; Brazier, J S; Duerden, B I; Hahné, S J M

    2005-08-01

    From 2000 to May 2004 there has been a marked increase in illness resulting from spore-forming bacteria in injecting heroin users in the United Kingdom. Clostridium novyi caused 63 cases of severe illness in 2000 and seven further cases from 2001. Wound botulism first occurred in 2000 (six cases) with 51 further cases to March 2004. Tetanus occurred in 20 cases between late 2003 and March 2004. Infections with C. histolyticum (nine cases), C. sordellii (one case) and Bacillus cereus (one case) were also reported. The reasons for the increase in illness are unclear. The major risk factor was skin- or muscle-popping. The problem appears to be here to stay. This review describes the causative organisms, pathogenesis, clinical presentation, epidemiology and treatment of cases. Clinical vigilance and a high standard of anaerobic microbiology are essential. Clinicians and laboratories must report such cases (or likely cases) rapidly so that clusters can be rapidly identified, in order to control disease. Prevention relies on tetanus immunization.

  4. Soft tissue infections caused by spore-forming bacteria in injecting drug users in the United Kingdom.

    PubMed Central

    Brett, M. M.; Hood, J.; Brazier, J. S.; Duerden, B. I.; Hahné, S. J. M.

    2005-01-01

    From 2000 to May 2004 there has been a marked increase in illness resulting from spore-forming bacteria in injecting heroin users in the United Kingdom. Clostridium novyi caused 63 cases of severe illness in 2000 and seven further cases from 2001. Wound botulism first occurred in 2000 (six cases) with 51 further cases to March 2004. Tetanus occurred in 20 cases between late 2003 and March 2004. Infections with C. histolyticum (nine cases), C. sordellii (one case) and Bacillus cereus (one case) were also reported. The reasons for the increase in illness are unclear. The major risk factor was skin- or muscle-popping. The problem appears to be here to stay. This review describes the causative organisms, pathogenesis, clinical presentation, epidemiology and treatment of cases. Clinical vigilance and a high standard of anaerobic microbiology are essential. Clinicians and laboratories must report such cases (or likely cases) rapidly so that clusters can be rapidly identified, in order to control disease. Prevention relies on tetanus immunization. PMID:16050501

  5. Transient Fecal Shedding and Limited Animal-to-Animal Transmission of Clostridium difficile by Naturally Infected Finishing Feedlot Cattle ▿

    PubMed Central

    Rodriguez-Palacios, Alexander; Pickworth, Carrie; Loerch, Steve; LeJeune, Jeffrey T.

    2011-01-01

    To longitudinally assess fecal shedding and animal-to-animal transmission of Clostridium difficile among finishing feedlot cattle as a risk for beef carcass contamination, we tested 186 ± 12 steers (mean ± standard deviation; 1,369 samples) in an experimental feedlot facility during the finishing period and at harvest. Clostridium difficile was isolated from 12.9% of steers on arrival (24/186; 0 to 33% among five suppliers). Shedding decreased to undetectable levels a week later (0%; P < 0.001), and remained low (<3.6%) until immediately prior to shipment for harvest (1.2%). Antimicrobial use did not increase fecal shedding, despite treatment of 53% of animals for signs of respiratory disease. Animals shedding C. difficile on arrival, however, had 4.6 times higher odds of receiving antimicrobials for respiratory signs than nonshedders (95% confidence interval for the odds ratio, 1.4 to 14.8; P = 0.01). Neither the toxin genes nor toxin A or B was detected in most (39/42) isolates based on two complementary multiplex PCRs and enzyme-linked immunosorbent assay testing, respectively. Two linezolid- and clindamycin-resistant PCR ribotype 078 (tcdA+/tcdB+/cdtB+/39-bp-type deletion in tcdC) isolates were identified from two steers (at arrival and week 20), but these ribotypes did not become endemic. The other toxigenic isolate (tcdA+/tcdB+/cdtB+/classic tcdC; PCR ribotype 078-like) was identified in the cecum of one steer at harvest. Spatio-temporal analysis indicated transient shedding with no evidence of animal-to-animal transmission. The association between C. difficile shedding upon arrival and the subsequent need for antimicrobials for respiratory disease might indicate common predisposing factors. The isolation of toxigenic C. difficile from bovine intestines at harvest highlights the potential for food contamination in meat processing plants. PMID:21441320

  6. A Novel Multivalent, Single-Domain Antibody Targeting TcdA and TcdB Prevents Fulminant Clostridium difficile Infection in Mice

    PubMed Central

    Yang, Zhiyong; Schmidt, Diane; Liu, Weilong; Li, Shan; Shi, Lianfa; Sheng, Jinliang; Chen, Kevin; Yu, Hua; Tremblay, Jacqueline M.; Chen, Xinhua; Piepenbrink, Kurt H.; Sundberg, Eric J.; Kelly, Ciaran P.; Bai, Guang; Shoemaker, Charles B.; Feng, Hanping

    2014-01-01

    The incidence of Clostridium difficile infection (CDI) and associated mortality have increased rapidly worldwide in recent years. Therefore, it is critical to develop new therapies for CDI. In this study, we generated a novel, potently neutralizing, tetravalent, and bispecific antibody composed of 2 heavy-chain-only VH (VHH) binding domains against both TcdA and TcdB (designated “ABA”) that reverses fulminant CDI in mice infected with an epidemic 027 strain after a single injection of the antibody. We demonstrated that ABA bound to both toxins simultaneously and displayed a significantly enhanced neutralizing activity both in vitro and in vivo. Additionally, ABA was able to broadly neutralize toxins from clinical C. difficile isolates that express both TcdA and TcdB but failed to neutralize the toxin from TcdA−TcdB+ C. difficile strains. This study thus provides a rationale for the development of multivalent VHHs that target both toxins and are broadly neutralizing for treating severe CDI. PMID:24683195

  7. Utilizing Rapid Multiple-Locus Variable-Number Tandem-Repeat Analysis Typing To Aid Control of Hospital-Acquired Clostridium difficile Infection: a Multicenter Study

    PubMed Central

    Manzoor, Susan; Marriott, Claire; Parsons, Helen; Waddington, Claire; Gossain, Savita; Szczepura, Ala; Stallard, Nigel; Hawkey, Peter M.

    2012-01-01

    The early identification of outbreaks is crucial for the control of Clostridium difficile infection. This study aimed to determine if the number of hospital-acquired C. difficile infections could be reduced by rapidly typing C. difficile strains using multiple-locus variable-number tandem-repeat analysis (MLVA) compared to typing using PCR ribotyping. A total of 16 hospitals were recruited to the study, and all periods of increased incidence (PIIs) of C. difficile infection were identified. The hospitals were randomized into two study arms, the test and the control, with all isolates typed in the test using MLVA and in the control using PCR ribotyping. Following a PII, each hospital received a structured questionnaire regarding control measures implemented or stopped prior to or following the typing results. During the study period, there were a total of 1,682 hospital-apportioned C. difficile toxin-positive cases, with 868 in the control and 814 in the test, with modeling demonstrating no differences between the two arms. A total of 245 PIIs occurred, involving 785 patients. There was a significant difference in the mean turnaround time between the ribotyping and MLVA typing (13.6 and 5.3 days, respectively [P < 0.001]). The discriminatory ability of MLVA was greater than ribotyping, with 85 outbreaks being confirmed by ribotyping and 62 by MLVA. In the test arm, 40.6% of respondents strongly agreed that the typing result had aided their management of clusters, as opposed to 9.9% in the control. The study demonstrated the utility of rapidly typing C. difficile strains, demonstrating that it aided the management of clusters, enabling effective targeting of infection control resources. PMID:22837319

  8. The CpAL system regulates changes of the trans-epithelial resistance of human enterocytes during Clostridium perfringens type C infection.

    PubMed

    Nava, Porfirio; Vidal, Jorge E

    2016-06-01

    Clostridium perfringens type C strains produce severe disease in humans and animals including enterotoxaemia and hemorrhagic diarrhea. Type C disease is mediated by production of toxins that damage the site of infection inducing loss of bloody fluids. Production of type C toxins, such as CPA, PFO, and, CPB is regulated by the C. perfringens Agr-like (CpAL) quorum sensing (QS) system. The CpAL system is also required to recapitulate, in vivo, intestinal signs of C. perfringens type C-induced disease, including hemorrhagic diarrhea and accumulation of fluids. The intestinal epithelium forms a physical barrier, made up of a series of intercellular junctions including tight junctions (TJs), adherens junctions (AJs) and desmosomes (DMs). This selective barrier regulates important physiological processes, including paracellular movement of ions and solutes, which, if altered, results in loss of fluids into the intestinal lumen. In this work, the effects of C. perfringens infection on the barrier function of intestinal epithelial cells was evaluated by measuring trans-epithelial resistance (TEER). Our studies demonstrate that infection of human enterocytes with C. perfringens type C strain CN3685 induced a significant drop on TEER. Changes in TEER were mediated by the CpAL system as a CN3685ΔagrB mutant did not induce such a drop. Physical contact between bacteria and enterocytes produced more pronounced changes in TEER and this phenomenon appeared also to be mediated by the CpAL system. Finally, immunofluorescence studies demonstrate that C. perfringens type C infection redistribute TJs protein occludin, and Claudin-3, and DMs protein desmoglein-2, but did not affect the AJs protein E-cadherin.

  9. Preclinical Studies of Amixicile, a Systemic Therapeutic Developed for Treatment of Clostridium difficile Infections That Also Shows Efficacy against Helicobacter pylori

    PubMed Central

    Bruce, Alexandra M.; Olekhnovich, Igor; Warren, Cirle A.; Burgess, Stacey L.; Hontecillas, Raquel; Viladomiu, Monica; Bassaganya-Riera, Josep; Guerrant, Richard L.; Macdonald, Timothy L.

    2014-01-01

    Amixicile shows efficacy in the treatment of Clostridium difficile infections (CDI) in a mouse model, with no recurrence of CDI. Since amixicile selectively inhibits the action of a B vitamin (thiamine pyrophosphate) cofactor of pyruvate:ferredoxin oxidoreductase (PFOR), it may both escape mutation-based drug resistance and spare beneficial probiotic gut bacteria that do not express this enzyme. Amixicile is a water-soluble derivative of nitazoxanide (NTZ), an antiparasitic therapeutic that also shows efficacy against CDI in humans. In comparative studies, amixicile showed no toxicity to hepatocytes at 200 μM (NTZ was toxic above 10 μM); was not metabolized by human, dog, or rat liver microsomes; showed equivalence or superiority to NTZ in cytochrome P450 assays; and did not activate efflux pumps (breast cancer resistance protein, P glycoprotein). A maximum dose (300 mg/kg) of amixicile given by the oral or intraperitoneal route was well tolerated by mice and rats. Plasma exposure (rats) based on the area under the plasma concentration-time curve was 79.3 h · μg/ml (30 mg/kg dose) to 328 h · μg/ml (100 mg/kg dose), the maximum concentration of the drug in serum was 20 μg/ml, the time to the maximum concentration of the drug in serum was 0.5 to 1 h, and the half-life was 5.6 h. Amixicile did not concentrate in mouse feces or adversely affect gut populations of Bacteroides species, Firmicutes, segmented filamentous bacteria, or Lactobacillus species. Systemic bioavailability was demonstrated through eradication of Helicobacter pylori in a mouse infection model. In summary, the efficacy of amixicile in treating CDI and other infections, together with low toxicity, an absence of mutation-based drug resistance, and excellent drug metabolism and pharmacokinetic metrics, suggests a potential for broad application in the treatment of infections caused by PFOR-expressing microbial pathogens in addition to CDI. PMID:24890599

  10. Immunization with Bacillus spores expressing toxin A peptide repeats protects against infection with Clostridium difficile strains producing toxins A and B.

    PubMed

    Permpoonpattana, Patima; Hong, Huynh A; Phetcharaburanin, Jutarop; Huang, Jen-Min; Cook, Jenny; Fairweather, Neil F; Cutting, Simon M

    2011-06-01

    Clostridium difficile is a leading cause of nosocomial infection in the developed world. Two toxins, A and B, produced by most strains of C. difficile are implicated as virulence factors, yet only recently has the requirement of these for infection been investigated by genetic manipulation. Current vaccine strategies are focused mostly on parenteral delivery of toxoids. In this work, we have used bacterial spores (Bacillus subtilis) as a delivery vehicle to evaluate the carboxy-terminal repeat domains of toxins A and B as protective antigens. Our findings are important and show that oral immunization of the repeat domain of toxin A is sufficient to confer protection in a hamster model of infection designed to closely mimic the human course of infection. Importantly, neutralizing antibodies to the toxin A repeat domain were shown to be cross-reactive with the analogous domain of toxin B and, being of high avidity, provided protection against challenge with a C. difficile strain producing toxins A and B (A(+)B(+)). Thus, although many strains produce both toxins, antibodies to only toxin A can mediate protection. Animals vaccinated with recombinant spores were fully able to survive reinfection, a property that is particularly important for a disease with which patients are prone to relapse. We show that mucosal immunization, not parenteral delivery, is required to generate secretory IgA and that production of these neutralizing polymeric antibodies correlates with protection. This work demonstrates that an effective vaccine against C. difficile can be designed around two attributes, mucosal delivery and the repeat domain of toxin A.

  11. Application of Nuclear Magnetic Resonance to Detect Toxigenic Clostridium difficile from Stool Specimens: A Proof of Concept.

    PubMed

    Yang, Paul; Hash, Sara; Park, Katherine; Wong, Charlene; Doraisamy, Loganathan; Petterson, Jonas; Petti, Cathy A; Ward, Pamela M; Lee, Seung Heon; Menon, Suresh; She, Rosemary C

    2017-03-01

    We evaluated the performance of an early prototype core molecular mirroring nuclear magnetic resonance detection platform (Mentor-100) to detect toxigenic Clostridium difficile from stool. This technology uses customized nanoparticles bound to target specific oligonucleotide probes that form binaries in the presence of nucleic acid from the target microorganism. Liquid patient stool specimens were seeded with C. difficile or other Clostridium species to determine the analytical sensitivity and specificity. Samples underwent nucleic acid extraction and target amplification with probes conjugated with iron nanoparticles. Signal from nuclear magnetic resonance spin-spin relaxation time was measured to detect the presence or absence of toxigenic C. difficile. The limit of detection was <180 colony forming units per reaction of toxigenic C. difficile. No cross-reactivity was observed with nontoxigenic C. difficile, Clostridium sordellii, Clostridium perfringens, Bacillus subtilis, or Paenibacillus polymyxa at 10(8) colony forming units/mL. Correlation studies using frozen stool samples yielded a sensitivity of 88.4% (61 of 69) and a specificity of 87.0% (40 of 46) as compared with a commercial PCR assay for C. difficile. The area under the curve in the receiver operating characteristic curve analysis was 0.922. The prototype molecular mirroring platform showed promising performance for pathogen detection from clinical specimens. The platform design has the potential to offer a novel, low-cost alternative to currently available nucleic acid-based tests.

  12. [Spontaneous gas gangrene in a diabetic patient with Clostridium septicum].

    PubMed

    Mischke, A; Besier, S; Walcher, F; Waibel, H; Brade, V; Brandt, C

    2005-10-01

    Atraumatic infections due to Clostridium septicum are known to be associated with immunosuppression or even malignancy. In this case report, we present a patient with severe Clostridium septicum infection related to advanced colon cancer that had not previously been diagnosed. The case demonstrates the strong association between Clostridium septicum infections and malignancy, particularly in the presence of other predisposing diseases such as diabetes mellitus. It strongly suggests excluding malignant neoplasms, especially of the gastrointestinal tract, when severe Clostridium septicum infections occur. Moreover, if patients with known colorectal or other malignancy develop septicaemia or spontaneous gas gangrene, clinicians should be aware of Clostridium septicum as one of the main causative agents, as early diagnosis and aggressive treatment are important to improve prognosis.

  13. In Vitro and In Vivo Antibacterial Evaluation of Cadazolid, a New Antibiotic for Treatment of Clostridium difficile Infections

    PubMed Central

    Seiler, Peter; Chen, Xinhua; Schroeder, Susanne; Pfaff, Philippe; Enderlin, Michel; Klenk, Axel; Fournier, Elvire; Hubschwerlen, Christian; Ritz, Daniel; Kelly, Ciaran P.; Keck, Wolfgang

    2014-01-01

    Clostridium difficile is a leading cause of health care-associated diarrhea with significant morbidity and mortality, and new options for the treatment of C. difficile-associated diarrhea (CDAD) are needed. Cadazolid is a new oxazolidinone-type antibiotic that is currently in clinical development for treatment of CDAD. Here, we report the in vitro and in vivo antibacterial evaluation of cadazolid against C. difficile. Cadazolid showed potent in vitro activity against C. difficile with a MIC range of 0.125 to 0.5 μg/ml, including strains resistant to linezolid and fluoroquinolones. In time-kill kinetics experiments, cadazolid showed a bactericidal effect against C. difficile isolates, with >99.9% killing in 24 h, and was more bactericidal than vancomycin. In contrast to metronidazole and vancomycin, cadazolid strongly inhibited de novo toxin A and B formation in stationary-phase cultures of toxigenic C. difficile. Cadazolid also inhibited C. difficile spore formation substantially at growth-inhibitory concentrations. In the hamster and mouse models for CDAD, cadazolid was active, conferring full protection from diarrhea and death with a potency similar to that of vancomycin. These findings support further investigations of cadazolid for the treatment of CDAD. PMID:24277020

  14. In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for treatment of Clostridium difficile infections.

    PubMed

    Locher, Hans H; Seiler, Peter; Chen, Xinhua; Schroeder, Susanne; Pfaff, Philippe; Enderlin, Michel; Klenk, Axel; Fournier, Elvire; Hubschwerlen, Christian; Ritz, Daniel; Kelly, Ciaran P; Keck, Wolfgang

    2014-01-01

    Clostridium difficile is a leading cause of health care-associated diarrhea with significant morbidity and mortality, and new options for the treatment of C. difficile-associated diarrhea (CDAD) are needed. Cadazolid is a new oxazolidinone-type antibiotic that is currently in clinical development for treatment of CDAD. Here, we report the in vitro and in vivo antibacterial evaluation of cadazolid against C. difficile. Cadazolid showed potent in vitro activity against C. difficile with a MIC range of 0.125 to 0.5 μg/ml, including strains resistant to linezolid and fluoroquinolones. In time-kill kinetics experiments, cadazolid showed a bactericidal effect against C. difficile isolates, with >99.9% killing in 24 h, and was more bactericidal than vancomycin. In contrast to metronidazole and vancomycin, cadazolid strongly inhibited de novo toxin A and B formation in stationary-phase cultures of toxigenic C. difficile. Cadazolid also inhibited C. difficile spore formation substantially at growth-inhibitory concentrations. In the hamster and mouse models for CDAD, cadazolid was active, conferring full protection from diarrhea and death with a potency similar to that of vancomycin. These findings support further investigations of cadazolid for the treatment of CDAD.

  15. Host cell-induced signaling causes Clostridium perfringens to upregulate production of toxins important for intestinal infections

    PubMed Central

    Chen, Jianming; Ma, Menglin; Uzal, Francisco A; McClane, Bruce A

    2014-01-01

    Clostridium perfringens causes enteritis and enterotoxemia in humans and livestock due to prolific toxin production. In broth culture, C. perfringens uses the Agr-like quorum sensing (QS) system to regulate production of toxins important for enteritis/enterotoxemia, including beta toxin (CPB), enterotoxin, and epsilon toxin (ETX). The VirS/VirR two-component regulatory system (TCRS) also controls CPB production in broth cultures. Both the Agr-like QS and VirS/VirR systems are important when C. perfringens senses enterocyte-like Caco-2 cells and responds by upregulating CPB production; however, only the Agr-like QS system is needed for host cell-induced ETX production. These in vitro observations have pathophysiologic relevance since both the VirS/VirR and Agr-like QS signaling systems are required for C. perfringens strain CN3685 to produce CPB in vivo and to cause enteritis or enterotoxemia. Thus, apparently upon sensing its presence in the intestines, C. perfringens utilizes QS and TCRS signaling to produce toxins necessary for intestinal virulence. PMID:24061146

  16. Role of alpha-toxin in Clostridium perfringens infection determined by using recombinants of C. perfringens and Bacillus subtilis.

    PubMed Central

    Ninomiya, M; Matsushita, O; Minami, J; Sakamoto, H; Nakano, M; Okabe, A

    1994-01-01

    Clostridium perfringens type A strains which differed in alpha-toxin (phospholipase C [PLC]) productivity were inoculated intraperitoneally or intravenously into mice, and then their 50% mouse lethal doses (LD50) were determined. Strain NCTC 8237 produced ninefold higher PLC activity than strain 13. The mean LD50 for the former was 1 log unit lower than that for the latter. Two isogenic strains were constructed from strain 13: strain 13(pJIR418 alpha) (pJIR418 alpha contains the plc gene), which produced ninefold higher PLC activity than strain 13; and strain 13 PLC-, which showed no PLC productivity at all because of transformation-mediated gene disruption. The mean LD50 for strain 13(pJIR418 alpha) was 1 log unit lower than those for strain 13 PLC- and strain 13. These results indicate that PLC functions as a virulence-determining factor when it is produced in a sufficient amount. Such a difference in LD50 was also observed between Bacillus subtilis with and without the cloned plc gene. Inoculation of B. subtilis PLC+ intravenously into mice caused marked thrombocytopenia and leukocytosis. Mice inoculated with B. subtilis at 2 LD50 died because of circulatory collapse. Histological examination revealed that intravascular coagulation and vascular congestion occurred most prominently in the lungs. These results suggest that PLC plays a key role in the systemic intoxication of clostridial myonecrosis, probably by affecting the functions of platelets and phagocytes. Images PMID:7927785

  17. The alternative sigma factor σ(B) plays a crucial role in adaptive strategies of Clostridium difficile during gut infection.

    PubMed

    Kint, Nicolas; Janoir, Claire; Monot, Marc; Hoys, Sandra; Soutourina, Olga; Dupuy, Bruno; Martin-Verstraete, Isabelle

    2017-02-15

    Clostridium difficile is a major cause of diarrhoea associated with antibiotherapy. Exposed to stresses in the gut, C. difficile can survive by inducing protection, detoxification and repair systems. In several firmicutes, most of these systems are controlled by the general stress response involving σ(B) . In this work, we studied the role of σ(B) in the physiopathology of C. difficile. We showed that the survival of the sigB mutant during the stationary phase was reduced. Using a transcriptome analysis, we showed that σ(B) controls the expression of ∼25% of genes including genes involved in sporulation, metabolism, cell surface biogenesis and the management of stresses. By contrast, σ(B) does not control toxin gene expression. In agreement with the up-regulation of sporulation genes, the sporulation efficiency is higher in the sigB mutant than in the wild-type strain. sigB inactivation also led to increased sensitivity to acidification, cationic antimicrobial peptides, nitric oxide and ROS. In addition, we showed for the first time that σ(B) also plays a crucial role in oxygen tolerance in this strict anaerobe. Finally, we demonstrated that the fitness of colonisation by the sigB mutant is greatly affected in a dixenic mouse model of colonisation when compared to the wild-type strain.

  18. Fluoroquinolone and Macrolide Exposure Predict Clostridium difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. difficile Strain BI/NAP1/027

    PubMed Central

    Wieczorkiewicz, Jeffrey T.; Lopansri, Bert K.; Cheknis, Adam; Osmolski, James R.; Hecht, David W.; Gerding, Dale N.

    2015-01-01

    Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (P < 0.001; OR for macrolides, 5.2; 95% CI, 1.1 to 24.0; P = 0.04)). In contrast, clindamycin use was less frequent among the BI cases than among the controls (OR, 0.1; 95% CI, 0.03 to 0.4; P = 0.001). High-level resistance to moxifloxacin and azithromycin was more frequent among BI strains (moxifloxacin, 49/102 [48%] BI versus 0/40 non-BI, P = 0.0001; azithromycin, 100/102 [98%] BI versus 22/40 [55%] non-BI, P = 0.0001). High-level resistance to clindamycin was more frequent among non-BI strains (22/40 [55%] non-BI versus 7/102 [7%] BI, P = 0.0001). Fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain. PMID:26525793

  19. Fluoroquinolone and Macrolide Exposure Predict Clostridium difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. difficile Strain BI/NAP1/027.

    PubMed

    Wieczorkiewicz, Jeffrey T; Lopansri, Bert K; Cheknis, Adam; Osmolski, James R; Hecht, David W; Gerding, Dale N; Johnson, Stuart

    2015-11-02

    Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (P < 0.001; OR for macrolides, 5.2; 95% CI, 1.1 to 24.0; P = 0.04)). In contrast, clindamycin use was less frequent among the BI cases than among the controls (OR, 0.1; 95% CI, 0.03 to 0.4; P = 0.001). High-level resistance to moxifloxacin and azithromycin was more frequent among BI strains (moxifloxacin, 49/102 [48%] BI versus 0/40 non-BI, P = 0.0001; azithromycin, 100/102 [98%] BI versus 22/40 [55%] non-BI, P = 0.0001). High-level resistance to clindamycin was more frequent among non-BI strains (22/40 [55%] non-BI versus 7/102 [7%] BI, P = 0.0001). Fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain.

  20. Clostridium difficile extracytoplasmic function σ factor σV regulates lysozyme resistance and is necessary for pathogenesis in the hamster model of infection.

    PubMed

    Ho, Theresa D; Williams, Kyle B; Chen, Yan; Helm, Richard F; Popham, David L; Ellermeier, Craig D

    2014-06-01

    Clostridium difficile is a clinically important pathogen and the most common cause of hospital-acquired infectious diarrhea. Expression of the C. difficile gene csfV, which encodes σ(V), an extracytoplasmic function σ factor, is induced by lysozyme, which damages the peptidoglycan of bacteria. Here we show that σ(V) is required for lysozyme resistance in C. difficile. Using microarray analysis, we identified the C. difficile genes whose expression is dependent upon σ(V) and is induced by lysozyme. Although the peptidoglycan of wild-type C. difficile is intrinsically highly deacetylated, we have found that exposure to lysozyme leads to additional peptidoglycan deacetylation. This lysozyme-induced deacetylation is dependent upon σ(V). Expression of pdaV, which encodes a putative peptidoglycan deacetylase, was able to increase lysozyme resistance of a csfV mutant. The csfV mutant strain is severely attenuated compared to wild-type C. difficile in a hamster model of C. difficile-associated disease. We conclude that the σ(V) signal transduction system, which senses the host innate immune defense enzyme lysozyme, is required for lysozyme resistance and is necessary during C. difficile infection.

  1. Diagnosis of Clostridium difficile infection: comparison of four methods on specimens collected in Cary-Blair transport medium and tcdB PCR on fresh versus frozen samples.

    PubMed

    Brown, Noah A; Lebar, William D; Young, Carol L; Hankerd, Rosemary E; Newton, Duane W

    2011-03-08

    Clostridium difficile infection (CDI) caused by toxigenic strains of C. difficile is primarily a nosocomial infection with increasing prevalence. Stool specimens are typically collected in Cary-Blair transport medium to maximize culture-based detection of common stool pathogens. The goal of this study was to establish an analytically accurate and efficient algorithm for the detection of CDI in our patient population using samples collected in Cary-Blair transport medium. In addition, we wished to determine whether the sensitivity and specificity of PCR was affected by freezing samples before testing. Using 357 specimens, we compared four methods: enzyme immunoassay for the antigen glutamate dehydrogenase (Wampole™ C. DIFF CHEK-60 Assay, GDH), toxin A and B enzyme immunoassay (Remel ProSpecT™ C. difficile Toxin A/B Microplate Assay, Toxin EIA), cell culture cytotoxicity neutralization assay (Bartels™ Cytotoxicity Assay, CT), and real-time PCR targeting the toxin B gene (BD GeneOhm™ Cdiff Assay, PCR). The analytic sensitivity and specificity of each as determined using a combined gold standard were as follows: GDH, 100% and 93.2%; Toxin EIA, 82.9% and 82.9%; CT, 100% and 100%; PCR (performed on frozen specimens) 74.3% and 96.6%; respectively. However, the sensitivity and specificity of PCR improved to 100% when performed on 50 fresh stool samples collected in Cary-Blair. While CT remains a sensitive method for the detection of CDI, GDH offers an excellent initial screening method to rule out CDI. While the performance of each assay did not appear to be affected by collection in Cary-Blair medium, PCR performed better using fresh specimens.

  2. Assessment of Clostridium difficile infections by quantitative detection of tcdB toxin by use of a real-time cell analysis system.

    PubMed

    Ryder, Alex B; Huang, Ying; Li, Haijing; Zheng, Min; Wang, Xiaobo; Stratton, Charles W; Xu, Xiao; Tang, Yi-Wei

    2010-11-01

    We explored the use of a real-time cell analysis (RTCA) system for the assessment of Clostridium difficile toxins in human stool specimens by monitoring the dynamic responses of the HS27 cells to tcdB toxins. The C. difficile toxin caused cytotoxic effects on the cells, which resulted in a dose-dependent and time-dependent decrease in cell impedance. The RTCA assay possessed an analytical sensitivity of 0.2 ng/ml for C. difficile toxin B with no cross-reactions with other enterotoxins, nontoxigenic C. difficile, or other Clostridum species. Clinical validation was performed on 300 consecutively collected stool specimens from patients with suspected C. difficile infection (CDI). Each stool specimen was tested in parallel by a real-time PCR assay (PCR), a dual glutamate dehydrogenase and toxin A/B enzyme immunoassay (EIA), and the RTCA assay. In comparison to a reference standard in a combination of the three assays, the RTCA had a specificity of 99.6% and a sensitivity of 87.5% (28 of 32), which was higher than the EIA result (P = 0.005) but lower than the PCR result (P = 0.057). In addition, the RTCA assay allowed for quantification of toxin protein concentration in a given specimen. Among RTCA-positive specimens collected prior to treatment with metronidazole and/or vancomycin, a significant correlation between toxin protein concentrations and clinical CDI severities was observed (R(2) = 0.732, P = 0.0004). Toxin concentrations after treatment (0.89 ng/ml) were significantly lower than those prior to the treatment (15.68 ng/ml, Wilcoxon P = 0.01). The study demonstrates that the RTCA assay provides a functional tool for the potential assessment of C. difficile infections.

  3. Gastrointestinal localization of metronidazole by a lactobacilli-inspired tetramic acid motif improves treatment outcomes in the hamster model of Clostridium difficile infection

    PubMed Central

    Cherian, Philip T.; Wu, Xiaoqian; Yang, Lei; Scarborough, Jerrod S.; Singh, Aman P.; Alam, Zahidul A.; Lee, Richard E.; Hurdle, Julian G.

    2015-01-01

    Objectives Metronidazole, a mainstay treatment for Clostridium difficile infection (CDI), is often ineffective for severe CDI. Whilst this is thought to arise from suboptimal levels of metronidazole in the colon due to rapid absorption, empirical validation is lacking. In contrast, reutericyclin, an antibacterial tetramic acid from Lactobacillus reuteri, concentrates in the gastrointestinal tract. In this study, we modified metronidazole with reutericyclin's tetramic acid motif to obtain non-absorbed compounds, enabling assessment of the impact of pharmacokinetics on treatment outcomes. Methods A series of metronidazole-bearing tetramic acid substituents were synthesized and evaluated in terms of anti-C. difficile activities, gastric permeability, in vivo pharmacokinetics, efficacy in the hamster model of CDI and mode of action. Results Most compounds were absorbed less than metronidazole in cell-based Caco-2 permeability assays. In hamsters, lead compounds compartmentalized in the colon rather than the bloodstream with negligible levels detected in the blood, in direct contrast with metronidazole, which was rapidly absorbed into the blood and was undetectable in caecum. Accordingly, four leads were more efficacious (P < 0.05) than metronidazole in C. difficile-infected animals. Improved efficacy was not due to an alternative mode of action, as the leads retained the mode of action of metronidazole. Conclusions This study provides the clearest empirical evidence that the high absorption of metronidazole lowers treatment outcomes for CDI and suggests a role for the tetramic acid motif for colon-specific drug delivery. This approach also has the potential to lower systemic toxicity and drug interactions of nitroheterocyclic drugs for treating gastrointestine-specific diseases. PMID:26286574

  4. Diagnosis of Clostridium difficile infection: comparison of four methods on specimens collected in Cary-Blair transport medium and tcdB PCR on fresh versus frozen samples

    PubMed Central

    Brown, Noah A.; LeBar, William D.; Young, Carol L.; Hankerd, Rosemary E.; Newton, Duane W.

    2011-01-01

    Clostridium difficile infection (CDI) caused by toxigenic strains of C. difficile is primarily a nosocomial infection with increasing prevalence. Stool specimens are typically collected in Cary-Blair transport medium to maximize culture-based detection of common stool pathogens. The goal of this study was to establish an analytically accurate and efficient algorithm for the detection of CDI in our patient population using samples collected in Cary-Blair transport medium. In addition, we wished to determine whether the sensitivity and specificity of PCR was affected by freezing samples before testing. Using 357 specimens, we compared four methods: enzyme immunoassay for the antigen glutamate dehydrogenase (Wampole™ C. DIFF CHEK-60 Assay, GDH), toxin A and B enzyme immunoassay (Remel ProSpecT™ C. difficile Toxin A/B Microplate Assay, Toxin EIA), cell culture cytotoxicity neutralization assay (Bartels™ Cytotoxicity Assay, CT), and real-time PCR targeting the toxin B gene (BD GeneOhm™ Cdiff Assay, PCR). The analytic sensitivity and specificity of each as determined using a combined gold standard were as follows: GDH, 100% and 93.2%; Toxin EIA, 82.9% and 82.9%; CT, 100% and 100%; PCR (performed on frozen specimens) 74.3% and 96.6%; respectively. However, the sensitivity and specificity of PCR improved to 100% when performed on 50 fresh stool samples collected in Cary-Blair. While CT remains a sensitive method for the detection of CDI, GDH offers an excellent initial screening method to rule out CDI. While the performance of each assay did not appear to be affected by collection in Cary-Blair medium, PCR performed better using fresh specimens. PMID:24470904

  5. An in vitro culture model to study the dynamics of colonic microbiota in Syrian golden hamsters and their susceptibility to infection with Clostridium difficile.

    PubMed

    Miezeiewski, Matthew; Schnaufer, Todd; Muravsky, Michele; Wang, Su; Caro-Aguilar, Ivette; Secore, Susan; Thiriot, David S; Hsu, Charlie; Rogers, Irene; DeSantis, Todd; Kuczynski, Justin; Probst, Alexander J; Chehoud, Christel; Steger, Rachel; Warrington, Janet; Bodmer, Jean-Luc; Heinrichs, Jon H

    2015-02-01

    Clostridium difficile infections (CDI) are caused by colonization and growth of toxigenic strains of C. difficile in individuals whose intestinal microbiota has been perturbed, in most cases following antimicrobial therapy. Determination of the protective commensal gut community members could inform the development of treatments for CDI. Here, we utilized the lethal enterocolitis model in Syrian golden hamsters to analyze the microbiota disruption and recovery along a 20-day period following a single dose of clindamycin on day 0, inducing in vivo susceptibility to C. difficile infection. To determine susceptibility in vitro, spores of strain VPI 10463 were cultured with and without soluble hamster fecal filtrates and growth was quantified by quantitative PCR and toxin immunoassay. Fecal microbial population changes over time were tracked by 16S ribosomal RNA gene analysis via V4 sequencing and the PhyloChip assay. C. difficile culture growth and toxin production were inhibited by the presence of fecal extracts from untreated hamsters but not extracts collected 5 days post-administration of clindamycin. In vitro inhibition was re-established by day 15, which correlated with resistance of animals to lethal challenge. A substantial fecal microbiota shift in hamsters treated with antibiotics was observed, marked by significant changes across multiple phyla including Bacteroidetes and Proteobacteria. An incomplete return towards the baseline microbiome occurred by day 15 correlating with the inhibition of C. difficile growth in vitro and in vivo. These data suggest that soluble factors produced by the gut microbiota may be responsible for the suppression of C. difficile growth and toxin production.

  6. Surveillance of Clostridium difficile Infections: Results from a Six-Year Retrospective Study in Nine Hospitals of a North Italian Local Health Authority

    PubMed Central

    Roncarati, Greta; Dallolio, Laura; Leoni, Erica; Panico, Manuela; Zanni, Angela; Farruggia, Patrizia

    2017-01-01

    Clostridium difficile is an emerging cause of healthcare associated infections. In nine hospitals of an Italian Local Health Authority the episodes of C. difficile infection (CDI) were identified using the data registered by the centralized Laboratory Information System, from 2010 to 2015. CDI incidence (positive patients for A and/or B toxins per patients-days) was analysed per year, hospital, and ward. A number of cases approximately equivalent to the mean of identified cases per year were studied retrospectively to highlight the risk factors associated to CDI and their severity. Nine hundred and forty-two patients affected by CDI were identified. The overall incidence was 3.7/10,000 patients-days, with a stable trend across the six years and the highest rates observed in smaller and outlying hospitals (up to 17.8/10,000), where the admitted patients were older and the wards with the highest incidences (long-term-care: 7.6/10,000, general medicine: 5.7/10,000) were more represented. The mean age of patients in each hospital was correlated with CDI rates. Of the 101 cases selected for the retrospective study, 86.1% were healthcare associated, 10.9% community acquired; 9.1% met the criteria for recurrent case and 23.8% for severe case of CDI. The overall mortality rate was 28.7%. Comorbidity conditions occurred in 91.1%, previous exposure to antibiotics in 76.2%, and proton pump inhibitors in 77.2%. Recurrent and severe cases were significantly associated with renal insufficiency and creatinine levels ≥2 mg/dL. The survey based on the centralized laboratory data was useful to study CDI epidemiology in the different centres in order to identify possible weaknesses and plan control strategies, in particular the reinforcement of staff training, mainly targeted at compliance with contact precautions and hand hygiene. PMID:28075419

  7. An Increase in Healthcare-Associated Clostridium difficile Infection Associated with Use of a Defective Peracetic Acid-Based Surface Disinfectant.

    PubMed

    Cadnum, Jennifer L; Jencson, Annette L; O'Donnell, Marguerite C; Flannery, Elizabeth R; Nerandzic, Michelle M; Donskey, Curtis J

    2017-03-01

    BACKGROUND We investigated an increase in the incidence of healthcare-associated Clostridium difficile infection (CDI) that occurred following a change from a bleach disinfectant to a peracetic acid-based disinfectant. OBJECTIVE To evaluate the efficacy of the peracetic acid-based disinfectant. DESIGN Laboratory-based product evaluation. METHODS The commercial peracetic acid-based product is activated on site by mixing a small volume of concentrated hydrogen peroxide and peracetic acid present in a "SmartCap" reservoir with the remaining contents of the container. We measured concentrations of peracetic acid in newly activated and in-use product and determined the stability of nonactivated and activated product. We tested the efficacy of the product against C. difficile spores using the American Society for Testing and Materials standard quantitative carrier disk test method. RESULTS Measured concentrations of peracetic acid (50-800 parts per million [ppm]) were significantly lower than the level stated on the product label (1,500 ppm), and similar results were obtained for containers from multiple lot numbers and from another hospital. Product with peracetic acid levels below 600 ppm had significantly reduced activity against C. difficile spores. Peracetic acid concentrations were reduced markedly after storage of either activated or nonactivated product for several weeks. The Environmental Protection Agency confirmed the finding of low disinfectant levels and ordered discontinuation of sale of the product. CONCLUSION Use of a defective peracetic acid-based surface disinfectant may have contributed to an increase in healthcare-associated CDI. Our findings highlight the importance of evaluating the efficacy of liquid disinfectants in healthcare settings. Infect Control Hosp Epidemiol 2017;38:300-305.

  8. Evidence for antibiotic induced Clostridium perfringens diarrhoea

    PubMed Central

    Modi, N; Wilcox, M

    2001-01-01

    Clostridium difficile is a well documented cause of antibiotic associated diarrhoea in hospitalised patients, but may account for only approximately 20% of all cases. This leader reviews the current knowledge and understanding of the pathogenesis, epidemiology, and diagnosis of non-food borne Clostridium perfringens diarrhoea. Although enterotoxigenic C perfringens has been implicated in some C difficile negative cases of antibiotic associated diarrhoea, C perfringens enterotoxin detection methods are not part of the routine laboratory investigation of such cases. Testing for C perfringens enterotoxin in faecal samples from patients with antibiotic associated diarrhoea and sporadic diarrhoea on a routine basis would have considerable resource implications. Therefore, criteria for initiating investigations and optimum laboratory tests need to be established. In addition, establishing the true burden of C perfringens antibiotic associated diarrhoea is important before optimum control and treatment measures can be defined. Key Words: Clostridium perfringens • Clostridium difficile • hospital acquired infective diarrhoea PMID:11577119

  9. Evaluating the Use of the Case Mix Index for Risk Adjustment of Healthcare-Associated Infection Data: An Illustration using Clostridium difficile Infection Data from the National Healthcare Safety Network.

    PubMed

    Thompson, Nicola D; Edwards, Jonathan R; Dudeck, Margaret A; Fridkin, Scott K; Magill, Shelley S

    2016-01-01

    BACKGROUND Case mix index (CMI) has been used as a facility-level indicator of patient disease severity. We sought to evaluate the potential for CMI to be used for risk adjustment of National Healthcare Safety Network (NHSN) healthcare-associated infection (HAI) data. METHODS NHSN facility-wide laboratory-identified Clostridium difficile infection event data from 2012 were merged with the fiscal year 2012 Inpatient Prospective Payment System (IPPS) Impact file by CMS certification number (CCN) to obtain a CMI value for hospitals reporting to NHSN. Negative binomial regression was used to evaluate whether CMI was significantly associated with healthcare facility-onset (HO) CDI in univariate and multivariate analysis. RESULTS Among 1,468 acute care hospitals reporting CDI data to NHSN in 2012, 1,429 matched by CCN to a CMI value in the Impact file. CMI (median, 1.49; interquartile range, 1.36-1.66) was a significant predictor of HO CDI in univariate analysis (P<.0001). After controlling for community onset CDI prevalence rate, medical school affiliation, hospital size, and CDI test type use, CMI remained highly significant (P<.0001), with an increase of 0.1 point in CMI associated with a 3.4% increase in the HO CDI incidence rate. CONCLUSIONS CMI was a significant predictor of NHSN HO CDI incidence. Additional work to explore the feasibility of using CMI for risk adjustment of NHSN data is necessary. Infect. Control Hosp. Epidemiol. 2015;37(1):19-25.

  10. Fecal Microbiota Transplantation for Clostridium difficile-Associated Diarrhea.

    PubMed

    Cohen, Nathaniel A; Ben Ami, Ronen; Guzner-Gur, Hanan; Santo, Moshe E; Halpern, Zamir; Maharshak, Nitsan

    2015-08-01

    Clostridium difficile-associated diarrhea is a problem most hospital-based physicians will face in their career. This review aims to refresh current knowledge with regard to Clostridium difficile infection and bring physicians up to date with the latest developments in the growing field of fecal microbiota transplantation, the benefits it offers, and the promise this and other developments hold for the future.

  11. Vaccines against Clostridium difficile.

    PubMed

    Leuzzi, Rosanna; Adamo, Roberto; Scarselli, Maria

    2014-01-01

    Clostridium difficile infection (CDI) is recognized as a major cause of nosocomial diseases ranging from antibiotic related diarrhea to fulminant colitis. Emergence during the last 2 decades of C. difficile strains associated with high incidence, severity and lethal outcomes has increased the challenges for CDI treatment. A limited number of drugs have proven to be effective against CDI and concerns about antibiotic resistance as well as recurring disease solicited the search for novel therapeutic strategies. Active vaccination provides the attractive opportunity to prevent CDI, and intense research in recent years led to development of experimental vaccines, 3 of which are currently under clinical evaluation. This review summarizes recent achievements and remaining challenges in the field of C. difficile vaccines, and discusses future perspectives in view of newly-identified candidate antigens.

  12. New approach to the management of Clostridium difficile infection: colonisation with non-toxigenic C. difficile during daily ampicillin or ceftriaxone administration.

    PubMed

    Merrigan, Michelle M; Sambol, Susan P; Johnson, Stuart; Gerding, Dale N

    2009-03-01

    Non-toxigenic strains of Clostridium difficile are highly effective in preventing toxigenic C. difficile infection in hamsters when given following a single dose of an antimicrobial agent. The goal of this study was to determine the ability of non-toxigenic C. difficile to colonise hamsters during administration of an antibiotic to which the organisms are resistant - ceftriaxone - and an antibiotic to which they are susceptible - ampicillin - and to determine if non-toxigenic colonisation is protective against toxigenic strain challenge. Groups of four or five hamsters were administered daily ceftriaxone 60 mg/kg/d intraperitoneally or ampicillin 60 mg/kg/d orally for 5 days. Three non-toxigenic strains of C. difficile, M3, M23, and T7 (MICs 96-128 mg/L) were each given orally at a dose of 1 x 10(6) spores to groups of five animals 3h after the first dose of ceftriaxone. All animals were colonised successfully by day 3 of the study and when challenged with 1 x 10(6) spores of toxigenic strain J9 (MIC >256 mg/L) on day 3 all animals survived, whereas the control animal given ceftriaxone, but not non-toxigenic C. difficile, died within 48h of challenge. When groups of four hamsters were given ampicillin, administration of non-toxigenic strain M3 (MIC 2 mg/L) or toxigenic strain J9 (MIC 0.75 mg/L) at 1 x 10(6) spores did not result in any colonisation or infection of the animals until day 8, 3 days after the last ampicillin dose. A protection study was designed by giving M3 spores to groups of five animals daily for 5 days beginning on day 1, 3, or 5 of ampicillin. Toxigenic challenge was given with J9 spores on day 3 of each M3 regimen. M3 colonised all animals by day 8 and none became infected with J9. Colonisation by non-toxigenic C. difficile is an effective prevention strategy during antibiotic administration of ceftriaxone or ampicillin, but multiple-day administration is required for ampicillin and colonisation does not occur until several days after the drug

  13. Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of a Microbiota-Based Drug Targeted at Recurrent Clostridium difficile Infection

    PubMed Central

    Dubberke, Erik R.; Mullane, Kathleen M.; Gerding, Dale N.; Lee, Christine H.; Louie, Thomas J.; Guthertz, Harriet; Jones, Courtney

    2016-01-01

    Background. Vancomycin-resistant Enterococcus (VRE) is a major healthcare-associated pathogen and a well known complication among transplant and immunocompromised patients. We report on stool VRE clearance in a post hoc analysis of the Phase 2 PUNCH CD study assessing a microbiota-based drug for recurrent Clostridium difficile infection (CDI). Methods. A total of 34 patients enrolled in the PUNCH CD study received 1 or 2 doses of RBX2660 (microbiota suspension). Patients were requested to voluntarily submit stool samples at baseline and at 7, 30, and 60 days and 6 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and Gram staining. Vancomycin resistance was confirmed by Etest. Results. VRE status (at least 1 test result) was available for 30 patients. All stool samples for 19 patients (63.3%, mean age 61.7 years, 68% female) tested VRE negative. Eleven patients (36.7%, mean age 75.5 years, 64% female) were VRE positive at the first test (baseline or 7-day follow-up). Of these patients, 72.7%, n = 8 converted to negative as of the last available follow-up (30 or 60 days or 6 months). Of the other 3: 1 died (follow-up data not available); 1 patient remained positive at all follow-ups; 1 patient retested positive at 6 months with negative tests during the interim. Conclusions. Although based on a small sample size, this secondary analysis demonstrated the possibility of successfully converting a high percentage of VRE-positive patients to negative in a recurrent CDI population with RBX2660. PMID:27703995

  14. Cost-Effectiveness Analysis of Five Competing Strategies for the Management of Multiple Recurrent Community-Onset Clostridium difficile Infection in France

    PubMed Central

    Galperine, Tatiana; Denies, Fanette; Lannoy, Damien; Lenne, Xavier; Odou, Pascal; Guery, Benoit; Dervaux, Benoit

    2017-01-01

    Background Clostridium difficile infection (CDI) is characterized by high rates of recurrence, resulting in substantial health care costs. The aim of this study was to analyze the cost-effectiveness of treatments for the management of second recurrence of community-onset CDI in France. Methods We developed a decision-analytic simulation model to compare 5 treatments for the management of second recurrence of community-onset CDI: pulsed-tapered vancomycin, fidaxomicin, fecal microbiota transplantation (FMT) via colonoscopy, FMT via duodenal infusion, and FMT via enema. The model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) among the 5 treatments. ICERs were interpreted using a willingness-to-pay threshold of €32,000/QALY. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses. Results Three strategies were on the efficiency frontier: pulsed-tapered vancomycin, FMT via enema, and FMT via colonoscopy, in order of increasing effectiveness. FMT via duodenal infusion and fidaxomicin were dominated (i.e. less effective and costlier) by FMT via colonoscopy and FMT via enema. FMT via enema compared with pulsed-tapered vancomycin had an ICER of €18,092/QALY. The ICER for FMT via colonoscopy versus FMT via enema was €73,653/QALY. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations showed that FMT via enema was the most cost-effective strategy in 58% of simulations and FMT via colonoscopy was favored in 19% at a willingness-to-pay threshold of €32,000/QALY. Conclusions FMT via enema is the most cost-effective initial strategy for the management of second recurrence of community-onset CDI at a willingness-to-pay threshold of €32,000/QALY. PMID:28103289

  15. Hospital discharge abstracts have limited accuracy in identifying occurrence of Clostridium difficile infections among hospitalized individuals with inflammatory bowel disease: A population-based study

    PubMed Central

    Singh, Harminder; Nugent, Zoann; Yu, B. Nancy; Lix, Lisa M.; Targownik, Laura; Bernstein, Charles

    2017-01-01

    Background Hospital discharge databases are used to study the epidemiology of Clostridium difficile infections (CDI) among hospitalized patients with inflammatory bowel disease (IBD). CDI in IBD is increasingly important and accurately estimating its occurrence is critical in understanding its comorbidity. There are limited data on the reliability of the International Classification of Diseases 10th revision (ICD-10) (now widely used in North America) CDI code in determining occurrence of CDI among hospitalized patients. We compared the performance of ICD-10 CDI coding to laboratory confirmed CDI diagnoses. Methods The University of Manitoba IBD Epidemiology Database was used to identify individuals with and without IBD discharged with CDI diagnoses between 07/01/2005 and 3/31/2014. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ICD-10 CDI code was compared to laboratory CDI diagnoses recorded in a province wide CDI dataset. Multivariable logistic regression models were performed to test the predictors of diagnostic inaccuracy of ICD-10 CDI code. Results There were 273 episodes of laboratory confirmed CDI (hospitalized and non-hospitalized) among 7396 individuals with IBD and 536 among 66,297 matched controls. The sensitivity, specificity, PPV and NPV of ICD-10 CDI code in discharge abstracts was 72.8%, 99.6%, 64.1% and 99.7% among those with IBD and 70.8%, 99.9%, 79.0% and 99.9% among those without IBD. Predictors of diagnostic inaccuracy included IBD, older age, increased co-morbidity and earlier years of hospitalization. Conclusions Identification of CDI using ICD-10 CDI code in hospital discharge abstracts may not identify up to 30% of CDI cases, with worse performance among those with IBD. PMID:28199401

  16. Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.

    PubMed

    Peer, Xavier; An, Gary

    2014-10-01

    Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the C. difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, fecal microbial transplant. The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of

  17. Hydrogen peroxide vapor room disinfection and hand hygiene improvements reduce Clostridium difficile infection, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and extended-spectrum β-lactamase.

    PubMed

    Horn, Kim; Otter, Jonathan A

    2015-12-01

    We report a statistically significant reduction in Clostridium difficile infection (from 1.38 to 0.90 cases per 1,000 patient days), vancomycin-resistant enterococci (from 0.21 to 0.01 cases per 1,000 patient days), and extended-spectrum β-lactamase-producing gram-negative bacteria (from 0.16 to 0.01 cases per 1,000 patient days) associated with the introduction of hydrogen peroxide vapor for terminal decontamination of patient rooms and improvements in hand hygiene compliance.

  18. Purification of Clostridium toxoids.

    PubMed

    Buchowicz, I; Hay, M; Schiller, B; Korbecki, M; Sochańska, R

    1977-01-01

    A two-step fractionation procedure was applied for purification and concentration of the individual Clostridium toxoids. The toxoids were precipitated with hydrochloric acid in the presence of sodium sextametaphosphate, then antigenic fractions were separated from inactive contaminants by Sephadex G-75 filtration. Specific activity of the preparations thus obtained, as determined by Mancini radial immunodiffusion, was 150--565 binding units per mg of protein nitrogen for Clostridium perfringens toxoid, 204--352 binding units for Clostridium oedematiens toxoid and 26.6 -- 51.2 binding units for Clostridium septicum toxoid.

  19. The Association between GABA-Modulators and Clostridium difficile Infection – A Matched Retrospective Case-Control Study

    PubMed Central

    Ström, Jonathan; Tham, Johan; Månsson, Fredrik; Ahl, Jonas; Savidge, Tor C.; Dann, Sara M.

    2017-01-01

    Objective Recently, metabolomics studies have suggested that the neurotransmitter γ-amino butyric acid (GABA) may modulate C. difficile infection (CDI) pathogenesis. In the present study, we investigated the association between GABA-modulating pharmaceuticals and CDI development. Methods In July-December 2013, we performed a matched, retrospective case-control study in Skåne county, Sweden, to assess the association between the use of GABA-modulators (defined as regular use of at least one of the following: zolpidem, zopiclone, benzodiazepines, gabapentin, pregabalin or baclofen) and CDI. Multivariate regression models, adjusted for known risk factors for CDI, were fitted to assess the associations and a propensity score-adjusted analysis was performed. Results The study included 292 cases and 292 matched controls. In a multivariate regression model only recent antibiotic use (clindamycin, cephalosporins and fluoroquinolones) and nursing home residency was significantly associated with CDI. The regular use of any GABA-modulator was not associated with CDI (OR = 1.07, 95%CI 0.69–1.66, p = 0.76). The association between regular use of the selective GABA-agonist zolpidem and CDI trended towards significance (OR = 2.31, 95%CI 0.91–5.86, p = 0.078). These associations remained when only cases treated with antibiotics were included. Corresponding findings for zolpidem was observed in a propensity-score adjusted analysis (OR = 2.52, 95% CI 0.91–6.97, p = 0.075). Severe initial CDI was significantly associated with CDI recurrence (OR = 3.77, 95% CU 1.20–11.86, p = 0.023). Conclusion This study did not identify a general association between GABA-modulators and CDI. A trend towards a significant association between zolpidem and CDI was observed, an association that should be re-assessed in a study appropriately powered for this particular hypothesis. PMID:28060888

  20. Healthcare-associated infections studies project: an American Journal of Infection Control and National Healthcare Safety Network data quality collaboration-LabID Clostridium Difficile event 2013.

    PubMed

    Hebden, Joan N; Anttila, Angela; Allen-Bridson, Kathy; Morrell, Gloria C; Wright, Marc-Oliver; Horan, Teresa

    2013-10-01

    This is the first in a series of case studies that will be published in American Journal of Infection Control following the Centers for Disease Control and Prevention/National Healthcare Safety Network (NHSN) surveillance definition update of 2013. These cases reflect some of the complex patient scenarios infection professionals encounter during daily surveillance of health care-associated infections using NHSN definitions. Answers to the questions posed and immediate feedback in the form of answers and explanations are available at: http://www.surveymonkey.com/s/AJIC-NHSN-LbId2013. All individual participant answers will remain confidential, although it is the authors' hope to share a summary of the findings at a later date. Cases, answers, and explanations have been reviewed and approved by NHSN staff. Active participation is encouraged and recommended. Review/reference Chapter 12-Multidrug-resistant organism &C difficile infection module protocol, of the NHSN Patient Safety Component Manual (http://www.cdc.gov/nhsn/PDFs/pscManual/12pscMDRO_CDADcurrent.pdf), for information you may need to answer the case study questions.

  1. Multi-institution case–control and cohort study of risk factors for the development and mortality of Clostridium difficile infections in Japan

    PubMed Central

    Takahashi, Masahiko; Mori, Nobuaki; Bito, Seiji

    2014-01-01

    Objective To examine risk factors for Clostridium difficile infection (CDI) morbidity and mortality in Japan. Design Multimethod investigation including a case–control study and cohort study. Setting 47 participating facilities of the National Hospital Organization (NHO). Participants 1026 patients with CDI and 878 patients in the control group over the age of 18 years admitted to the subject NHO facilities from November 2010 to October 2011. Main outcome measures In a case–control study, we identify risk factors for CDI development. Next, in a cohort study, we identify risk factors for all-cause mortality within 30 days following CDI onset. Results A total of 1026 cases of CDI meeting the definitions of this investigation were identified, encompassing 878 patients at 42 of the 47 subject facilities. In the case–control study, we identified, compared with no antibiotics use, use of first-generation and second-generation cephem antibiotics (OR 1.44; 95% CI 1.10 to 1.87), use of third-generation and fourth-generation cephem antibiotics (OR 1.86; 95% CI 1.48 to 2.33) and use of carbapenem antibiotics (OR 1.87; 95% CI 1.44 to 2.42) the risk factors for CDI development. However, use of penicillin was not identified as a risk factor. In the cohort study, sufficient data for analysis was available for 924 CDI cases; 102 of them (11.0%) resulted in death within 30 days of CDI onset. Compared with no anti-CDI drug use, use of vancomycin was associated with reduced risk of mortality (OR 0.43; 95% CI 0.25 to 0.75) whereas metronidazole was not. Conclusions The findings mirror those of previous studies from Europe and North America, identifying the administration of broad-spectrum antibiotics as a risk factor for CDI development. The use of vancomycin is associated with a decreased risk of mortality. PMID:25186155

  2. Clostridium difficile and the microbiota

    PubMed Central

    Seekatz, Anna M.; Young, Vincent B.

    2014-01-01

    Clostridium difficile infection (CDI) is the leading health care–associated illness. Both human and animal models have demonstrated the importance of the gut microbiota’s capability of providing colonization resistance against C. difficile. Risk factors for disease development include antibiotic use, which disrupts the gut microbiota, leading to the loss of colonization resistance and subsequent CDI. Identification of the specific microbes capable of restoring this function remains elusive. Future studies directed at how microbial communities influence the metabolic environment may help elucidate the role of the microbiota in disease development. These findings will improve current biotherapeutics for patients with CDI, particularly those with recurrent disease. PMID:25036699

  3. Autism and Clostridium tetani.

    PubMed

    Bolte, E R

    1998-08-01

    Autism is a severe developmental disability believed to have multiple etiologies. This paper outlines the possibility of a subacute, chronic tetanus infection of the intestinal tract as the underlying cause for symptoms of autism observed in some individuals. A significant percentage of individuals with autism have a history of extensive antibiotic use. Oral antibiotics significantly disrupt protective intestinal microbiota, creating a favorable environment for colonization by opportunistic pathogens. Clostridium tetani is an ubiquitous anaerobic bacillus that produces a potent neurotoxin. Intestinal colonization by C. tetani, and subsequent neurotoxin release, have been demonstrated in laboratory animals which were fed vegetative cells. The vagus nerve is capable of transporting tetanus neurotoxin (TeNT) and provides a route of ascent from the intestinal tract to the CNS. This route bypasses TeNT's normal preferential binding sites in the spinal cord, and therefore the symptoms of a typical tetanus infection are not evident. Once in the brain, TeNT disrupts the release of neurotransmitters by the proteolytic cleavage of synaptobrevin, a synaptic vesicle membrane protein. This inhibition of neurotransmitter release would explain a wide variety of behavioral deficits apparent in autism. Lab animals injected in the brain with TeNT have exhibited many of these behaviors. Some children with autism have also shown a significant reduction in stereotyped behaviors when treated with antimicrobials effective against intestinal clostridia. When viewed as sequelae to a subacute, chronic tetanus infection, many of the puzzling abnormalities of autism have a logical basis. A review of atypical tetanus cases, and strategies to test the validity of this paper's hypothesis, are included.

  4. The effect of probiotics on Clostridium difficile diarrhea.

    PubMed

    Pochapin, M

    2000-01-01

    Clostridium difficile is the leading cause of nosocomially acquired intestinal infection in the United States, affecting virtually all cases of pseudomembranous colitis and up to 20% of cases of antibiotic-associated diarrhea. Even after receiving antibiotic treatment with either metronidazole or vancomycin, 20% of patients will have recurrent Clostridium difficile diarrhea. An innovative approach to the problem involves the introduction of competing, nonpathogenic (probiotic) organisms into the intestinal tract to restore microbial balance. The theoretical premise behind this approach is that the protective intestinal microflora is damaged by antibiotic treatment; the initial antibiotic exposure thus leaves the host susceptible to colonization and subsequent infection by Clostridium difficile. A so-called "second-hit" to the intestinal microflora occurs when the infected host is treated with flagyl or vancomycin, further destroying susceptible bacterial flora. Probiotic agents, such as Lactobacillus GG and Saccharomyces boulardii, have been studied for the treatment of Clostridium difficile. We are currently running a prospective, randomized, placebo-controlled trial of Lactobacillus GG in combination with standard antibiotics for the treatment of Clostridium difficile infection. Although it is too early to draw statistically significant conclusions, two patterns seem to be emerging: Lactobacillus GG is effective in reducing the 3-wk recurrence rate of Clostridium difficile, and patients feel better when taking Lactobacillus GG, as compared with the placebo, with early disappearance of abdominal cramps and diarrhea. In conclusion, the use of probiotics for the treatment of primary and recurrent Clostridium difficile diarrhea looks promising. Patients seem to have less recurrent Clostridium difficile diarrhea and early symptomatic improvement when using the probiotic Lactobacillus GG.

  5. A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity against Clostridium difficile infection in mice and hamsters.

    PubMed

    Wang, Yuan-Kai; Yan, Ya-Xian; Kim, Hyeun Bum; Ju, Xianghong; Zhao, Song; Zhang, Keshan; Tzipori, Saul; Sun, Xingmin

    2015-01-01

    Clostridium difficile is the major cause of hospital-acquired infectious diarrhea and colitis in developed countries. The pathogenicity of C. difficile is mainly mediated by the release of 2 large potent exotoxins, toxin A (TcdA) and toxin B (TcdB), both of which require neutralization to prevent disease occurrence. We have generated a novel chimeric protein, designated mTcd138, comprised of the glucosyltransferase and cysteine proteinase domains of TcdB and the receptor binding domain of TcdA and expressed it in Bacillus megaterium. To ensure that mTcd138 is atoxic, 2 point mutations were introduced to the glucosyltransferase domain of TcdB, which essentially eliminates toxicity of mTcd138. Parenteral immunizations of mice and hamsters with mTcd138 induced protective antibodies to both toxins and provided protection against infection with the hyper-virulent C. difficile strain UK6.

  6. Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+): Characterization, Manufacture, Mechanisms of Action, and Quality Control of a Specific Probiotic Combination for Primary Prevention of Clostridium difficile Infection.

    PubMed

    Auclair, Julie; Frappier, Martin; Millette, Mathieu

    2015-05-15

    A specific probiotic formulation composed of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+) has been marketed in North America since 1996. The strains and the commercial products have been evaluated for safety, identity, gastrointestinal survival, and stability throughout shelf life. The capacity of both the fermented beverages and the capsules to reduce incidences of antibiotic-associated diarrhea and Clostridium difficile infection (CDI) has been demonstrated in human clinical trials. Individual strains and the finished products have shown antimicrobial activity against C. difficile and toxin A/B neutralization capacity in vitro. The use of this specific probiotic formulation as part of a bundle of preventive measures to control CDI in healthcare settings is discussed.

  7. Collagenase Clostridium Histolyticum Injection

    MedlinePlus

    ... disease (a thickening of tissue [plaque] inside the penis that causes the penis to curve). Collagenase Clostridium histolyticum injection is in ... the plaque of thickened tissue and allows the penis to be straightened.

  8. Clostridium difficile colitis: pathogenesis and host defence.

    PubMed

    Abt, Michael C; McKenney, Peter T; Pamer, Eric G

    2016-10-01

    Clostridium difficile is a major cause of intestinal infection and diarrhoea in individuals following antibiotic treatment. Recent studies have begun to elucidate the mechanisms that induce spore formation and germination and have determined the roles of C. difficile toxins in disease pathogenesis. Exciting progress has also been made in defining the role of the microbiome, specific commensal bacterial species and host immunity in defence against infection with C. difficile. This Review will summarize the recent discoveries and developments in our understanding of C. difficile infection and pathogenesis.

  9. Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection.

    PubMed

    Kaleko, Michael; Bristol, J Andrew; Hubert, Steven; Parsley, Todd; Widmer, Giovanni; Tzipori, Saul; Subramanian, Poorani; Hasan, Nur; Koski, Perrti; Kokai-Kun, John; Sliman, Joseph; Jones, Annie; Connelly, Sheila

    2016-10-01

    The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta-lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. Here we present the preclinical development and early clinical studies of the beta-lactamase enzymes, P3A, currently referred to as SYN-004, and its precursor, P1A. Both P1A and SYN-004 were designed as orally-delivered, non-systemically available therapeutics for use with intravenous beta-lactam antibiotics. SYN-004 was engineered from P1A, a beta-lactamase isolated from Bacillus licheniformis, to broaden its antibiotic degradation profile. SYN-004 efficiently hydrolyses penicillins and cephalosporins, the most widely used IV beta-lactam antibiotics. In animal studies, SYN-004 degraded ceftriaxone in the GI tract of dogs and protected the microbiome of pigs from ceftriaxone-induced changes. Phase I clinical studies demonstrated SYN-004 safety and tolerability. Phase 2 studies are in progress to assess the utility of SYN-004 for the prevention of antibiotic-associated diarrhea and Clostridium difficile disease.

  10. Evaluating the Effectiveness of an Antimicrobial Stewardship Program on Reducing the Incidence Rate of Healthcare-Associated Clostridium difficile Infection: A Non-Randomized, Stepped Wedge, Single-Site, Observational Study

    PubMed Central

    McArthur, Leslie

    2016-01-01

    Background The incidence rate of healthcare-associated Clostridium difficile infection (HA-CDI) is estimated at 1 in 100 patients. Antibiotic exposure is the most consistently reported risk factor for HA-CDI. Strategies to reduce the risk of HA-CDI have focused on reducing antibiotic utilization. Prospective audit and feedback is a commonly used antimicrobial stewardship intervention (ASi). The impact of this ASi on risk of HA-CDI is equivocal. This study examines the effectiveness of a prospective audit and feedback ASi on reducing the risk of HA-CDI. Methods Single-site, 339 bed community-hospital in Barrie, Ontario, Canada. Primary outcome is HA-CDI incidence rate. Daily prospective and audit ASi is the exposure variable. ASi implemented across 6 wards in a non-randomized, stepped wedge design. Criteria for ASi; any intravenous antibiotic use for ≥ 48 hrs, any oral fluoroquinolone or oral second generation cephalosporin use for ≥ 48 hrs, or any antimicrobial use for ≥ 5 days. HA-CDI cases and model covariates were aggregated by ward, year and month starting September 2008 and ending February 2016. Multi-level mixed effect negative binomial regression analysis was used to model the primary outcome, with intercept and slope coefficients for ward-level random effects estimated. Other covariates tested for inclusion in the final model were derived from previously published risk factors. Deviance residuals were used to assess the model’s goodness-of-fit. Findings The dataset included 486 observation periods, of which 350 were control periods and 136 were intervention periods. After accounting for all other model covariates, the estimated overall ASi incidence rate ratio (IRR) was 0.48 (95% 0.30, 0.79). The ASi effect was independent of antimicrobial utilization. The ASi did not seem to reduce the risk of Clostridium difficile infection on the surgery wards (IRR 0.87, 95% CI 0.45, 1.69) compared to the medicine wards (IRR 0.42, 95% CI 0.28, 0.63). The ward

  11. Clostridium septicum gas gangrene in a previously healthy 8-year-old female with survival.

    PubMed

    Pinzon-Guzman, Carolina; Bashir, Dalia; McSherry, George; Beck, Michael J; Rocourt, Dorothy V

    2013-04-01

    We present the only reported case of an immunocompetent pediatric patient in the literature to have fulminate gas gangrene of the lower extremity and concomitant gastrointestinal tract infection due to Clostridium septicum coinfected with Clostridium difficile colitis respectively. The patient survived with aggressive medical and surgical treatment.

  12. Discrimination of clostridium species using a magnetic bead based hybridization assay

    NASA Astrophysics Data System (ADS)

    Pahlow, Susanne; Seise, Barbara; Pollok, Sibyll; Seyboldt, Christian; Weber, Karina; Popp, Jürgen

    2014-05-01

    Clostridium chauvoei is the causative agent of blackleg, which is an endogenous bacterial infection. Mainly cattle and other ruminants are affected. The symptoms of blackleg are very similar to those of malignant edema, an infection caused by Clostridium septicum. [1, 2] Therefore a reliable differentiation of Clostridium chauvoei from other Clostridium species is required. Traditional microbiological detection methods are time consuming and laborious. Additionally, the unique identification is hindered by the overgrowing tendency of swarming Clostridium septicum colonies when both species are present. [1, 3, 4] Thus, there is a crucial need to improve and simplify the specific detection of Clostridium chauvoei and Clostridium septicum. Here we present an easy and fast Clostridium species discrimination method combining magnetic beads and fluorescence spectroscopy. Functionalized magnetic particles exhibit plentiful advantages, like their simple manipulation in combination with a large binding capacity of biomolecules. A specific region of the pathogenic DNA is amplified and labelled with biotin by polymerase chain reaction (PCR). These PCR products were then immobilized on magnetic beads exploiting the strong biotin-streptavidin interaction. The specific detection of different Clostridium species is achieved by using fluorescence dye labeled probe DNA for the hybridization with the immobilized PCR products. Finally, the samples were investigated by fluorescence spectroscopy. [5

  13. Antimicrobial stewardship and Clostridium difficile-associated diarrhea.

    PubMed

    Piacenti, Frank J; Leuthner, Kimberly D

    2013-10-01

    Antimicrobial stewardship programs are essential to health care institutions to promote the appropriate use of antibiotics not only to decrease antimicrobial resistance but to prevent the spread and infection of Clostridium difficile. Clostridium difficile-associated diarrhea is increasing rapidly in the United States and is now considered a major public health problem that poses an immediate threat to the health of patients prescribed antibiotics, more so than antimicrobial resistance. Clostridium difficile-associated disease is the result of collateral damage to the normal bacterial flora of the human body, which is an inevitable consequence of any antibiotic use. Antimicrobial stewardship programs such as audit with feedback and antibiotic restriction are designed to help limit Clostridium difficile infections and other hospital-associated organisms by optimizing antimicrobial selection, dosing, de-escalation, and duration of therapy. These programs also incorporate implementation of hospital-wide guidelines, staff education, enforcement of infection-control policies, and the use of electronic medical records when possible to help control antibiotic use. This article reviews the literature on how antimicrobial stewardship programs impact Clostridium difficile rates and discusses experiences in designing, implementing, monitoring, and follow-through of such programs.

  14. Bacteriophages of Clostridium perfringens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The specific aims of the book chapter are to: (1) Briefly review the nomenclature of bacteriophages and how these agents are classified. (2) Discuss the problems associated with addition/removal of antibiotics in commercial animal feeds. (3) Provide a brief overview of Clostridium perfringens biolog...

  15. Clostridium tetani bacteraemia.

    PubMed

    Hallit, Rabih Riad; Afridi, Muhammad; Sison, Raymund; Salem, Elie; Boghossian, Jack; Slim, Jihad

    2013-01-01

    Tetanus is a neuromuscular disease in which Clostridium tetani exotoxin (tetanospasmin) produces muscle spasms, incapacitating its host. To our knowledge, C. tetani bacteraemia has never been reported in the literature. The ideal management of this entity remains unresolved given that there is no literature to guide the therapy.

  16. John G. Bartlett: Contributions to the discovery of Clostridium difficile antibiotic-associated diarrhea.

    PubMed

    Gorbach, Sherwood L

    2014-09-15

    In 1975 John Bartlett began trials investigating the problem of antibiotic-associated diarrhea and pseudomembranous colitis. His work led the discovery of Clostridium difficile and he identified it as the leading cause of hospital-associated infections.

  17. Development of a real time PCR Taqman assay based on the TPI gene for simultaneous identification of Clostridium chauvoei and Clostridium septicum.

    PubMed

    Garofolo, G; Galante, D; Serrecchia, L; Buonavoglia, D; Fasanella, A

    2011-02-01

    In the present study, a Taqman allelic discrimination assay based on three SNPs of the TPI gene is described. It was used as a differential diagnostic tool to detect blackleg and malignant edema. Sudden deaths of grazing ruminants, such as cattle, sheep and goats, which show clinical signs related to hyperacute infective processes, encouraged the development of a rapid and precise diagnostic molecular method. Specific primers and probes for Clostridium septicum and Clostridium chauvoei were designed on the basis of the TPI gene sequence. The multiplex PCR was tested on the DNA of a total of 57 strains, including 24 Clostridium chauvoei, 20 Clostridium septicum, 1 Bacillus anthracis and 12 other Clostridium spp. The DNA samples from Clostridium chauvoei and Clostridium septicum strains were amplified. Amplification of other DNA samples was not observed, with the exception of Clostridium tertium, which showed a weak positive signal. To avoid misdiagnosis, a confirmatory assay based on a Sybr green real time PCR was proposed. The authors confirmed the efficacy and the specificity of the test used in this study, which proved to be a useful tool for the diagnosis of clostridiosis that are often diagnosed using only traditional tools.

  18. Evaluation of the national Cleanyourhands campaign to reduce Staphylococcus aureus bacteraemia and Clostridium difficile infection in hospitals in England and Wales by improved hand hygiene: four year, prospective, ecological, interrupted time series study

    PubMed Central

    Fuller, Christopher; Savage, Joan; Cookson, Barry; Hayward, Andrew; Cooper, Ben; Duckworth, Georgia; Michie, Susan; Murray, Miranda; Jeanes, Annette; Roberts, J; Teare, Louise; Charlett, Andre

    2012-01-01

    Objective To evaluate the impact of the Cleanyourhands campaign on rates of hospital procurement of alcohol hand rub and soap, report trends in selected healthcare associated infections, and investigate the association between infections and procurement. Design Prospective, ecological, interrupted time series study from 1 July 2004 to 30 June 2008. Setting 187 acute trusts in England and Wales. Intervention Installation of bedside alcohol hand rub, materials promoting hand hygiene and institutional engagement, regular hand hygiene audits, rolled out nationally from 1 December 2004. Main outcome measures Quarterly (that is, every three months) rates for each trust of hospital procurement of alcohol hand rub and liquid soap; Staphylococcus aureus bacteraemia (meticillin resistant (MRSA) and meticillin sensitive (MSSA)) and Clostridium difficile infection for each trust. Associations between procurement and infection rates assessed by mixed effect Poisson regression model (which also accounted for effect of bed occupancy, hospital type, and timing of other national interventions targeting these infections). Results Combined procurement of soap and alcohol hand rub tripled from 21.8 to 59.8 mL per patient bed day; procurement rose in association with each phase of the campaign. Rates fell for MRSA bacteraemia (1.88 to 0.91 cases per 10 000 bed days) and C difficile infection (16.75 to 9.49 cases). MSSA bacteraemia rates did not fall. Increased procurement of soap was independently associated with reduced C difficile infection throughout the study (adjusted incidence rate ratio for 1 mL increase per patient bed day 0.993, 95% confidence interval 0.990 to 0.996; P<0.0001). Increased procurement of alcohol hand rub was independently associated with reduced MRSA bacteraemia, but only in the last four quarters of the study (0.990, 0.985 to 0.995; P<0.0001). Publication of the Health Act 2006 was strongly associated with reduced MRSA bacteraemia (0.86, 0.75 to 0.98; P=0

  19. Fecal Microbiota Transplantation Using Upper Gastrointestinal Tract for the Treatment of Refractory or Severe Complicated Clostridium difficile Infection in Elderly Patients in Poor Medical Condition: The First Study in an Asian Country

    PubMed Central

    Gweon, Tae-Geun; Kim, Jinsu; Lim, Chul-Hyun; Park, Jae Myung; Lee, Dong-Gun; Lee, In Seok; Cho, Young-Seok; Kim, Sang Woo; Choi, Myung-Gyu

    2016-01-01

    Background and Aims. Fecal microbiota transplantation (FMT) is a highly effective treatment option for refractory Clostridium difficile infection (CDI). FMT may be challenging in patients with a low performance status, because of their poor medical condition. The aims of this study were to describe our experience treating patients in poor medical condition with refractory or severe complicated CDI using FMT via the upper GI tract route. Methods. This study was a retrospective review of seven elderly patients with refractory or severe complicated CDI and a poor medical condition who were treated with FMT through the upper GI tract route from May 2012 through August 2013. The outcomes studied included the cure rate of CDI and adverse events. Results. Of these seven patients who received FMT via the upper GI tract route, all patients were cured. During the 11-month follow-up period, CDI recurrence was observed in two patients; rescue FMT was performed in these patients, which led to a full cure. Vomiting was observed in two patients. Conclusions. FMT via the upper gastrointestinal tract route may be effective for the treatment of refractory or severe complicated CDI in patients with a low performance status. Physicians should be aware of adverse events, especially vomiting. PMID:27127501

  20. A Decade of Experience in Primary Prevention of Clostridium difficile Infection at a Community Hospital Using the Probiotic Combination Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+).

    PubMed

    Maziade, Pierre-Jean; Pereira, Pascale; Goldstein, Ellie J C

    2015-05-15

    In August 2003, the 284-bed community hospital Pierre-Le Gardeur (PLGH) in Quebec experienced a major outbreak associated with the Clostridium difficile NAP1/027/BI strain. Augmented standard preventive measures (SPMs) were not able to control this outbreak. It was decided in February 2004 to give to every adult inpatient on antibiotics, without any exclusion, a probiotic (Bio-K+: Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2) within 12 hours of the antibiotic prescription. Augmented SPMs were continued. The use of the probiotic in addition to SPMs was associated with a marked reduction of C. difficile infection (CDI). During the 10 years of observation, 44 835 inpatients received Bio-K+, and the CDI rate at PLGH declined from 18.0 cases per 10,000 patient-days and remained at low mean levels of 2.3 cases per 10,000 patient-days. Additionally, 10-year data collected by the Ministry of Health in Quebec comparing the CDI rate between Quebec hospitals showed that CDI rates at PLGH were consistently and continuously lower compared with those at similar hospitals. Blood cultures were monitored at PLGH for Lactobacillus bacteremia through the 10 years' experience, and no Lactobacillus bacteremias were detected. Despite the limitation of an observational study, we concluded that the probiotic Bio-K+ was safe and effective in decreasing our primary CDI rate.

  1. Comparison of Simplexa universal direct PCR with cytotoxicity assay for diagnosis of Clostridium difficile infection: performance, cost, and correlation with disease.

    PubMed

    Landry, Marie L; Ferguson, David; Topal, Jeffrey

    2014-01-01

    Simplexa Clostridium difficile universal direct PCR, a real-time PCR assay for the detection of the C. difficile toxin B (tcdB) gene using the 3M integrated cycler, was compared with a two-step algorithm which includes the C. Diff Chek-60 glutamate dehydrogenase (GDH) antigen assay followed by cytotoxin neutralization. Three hundred forty-two liquid or semisolid stools submitted for diagnostic C. difficile testing, 171 GDH antigen positive and 171 GDH antigen negative, were selected for the study. All samples were tested by the C. Diff Chek-60 GDH antigen assay, cytotoxin neutralization, and Simplexa direct PCR. Of 171 GDH-positive samples, 4 were excluded (from patients on therapy or from whom duplicate samples were obtained) and 88 were determined to be true positives for toxigenic C. difficile. Of the 88, 67 (76.1%) were positive by the two-step method and 86 (97.7%) were positive by PCR. Seventy-nine were positive by the GDH antigen assay only. Of 171 GDH antigen-negative samples, none were positive by PCR. One antigen-negative sample positive by the cytotoxin assay only was deemed a false positive based on chart review. Simplexa C. difficile universal direct PCR was significantly more sensitive for detecting toxigenic C. difficile bacteria than cytotoxin neutralization (P = 0.0002). However, most PCR-positive/cytotoxin-negative patients did not have clear C. difficile disease. The estimated cost avoidance provided by a more rapid molecular diagnosis was outweighed by the cost of isolating and treating PCR-positive/cytotoxin-negative patients. The costs, clinical consequences, and impact on nosocomial transmission of treating and/or isolating patients positive for toxigenic C. difficile by PCR but negative for in vivo toxin production merit further study.

  2. Clostridium septicum Aortitis of the Infrarenal Abdominal Aorta

    PubMed Central

    Shah, Aditya; Yousuf, Tariq; Rachid, Mohammed; Ali, Naureen; Tabriz, Muhammad; Loughry, Kevin

    2016-01-01

    Clostridium septicum aortitis is a rare infection that has a strong association with occult colonic malignancy. There is also emerging evidence to support the combination of medical and surgical management over medical management alone. To the best of our knowledge, we report the 40th known case of C. septicum aortitis. PMID:26767087

  3. Clostridium glycolicum isolated from a patient with otogenic brain abscesses.

    PubMed

    Van Leer, C; Wensing, A M J; van Leeuwen, J P; Zandbergen, E G J; Swanink, C M A

    2009-02-01

    We describe a case of brain abscesses with gas formation following otitis media, for which the patient treated himself by placing clay in his ear. Several microorganisms, including Clostridium glycolicum, were cultured from material obtained from the patient. This is the first report of an infection in an immunocompetent patient associated with this microorganism.

  4. Prevention of Healthcare-Associated Clostridium difficile: What Works?

    PubMed Central

    Dubberke, Erik R.

    2013-01-01

    Prevention of Clostridium difficile infection (CDI) has become extremely important because of increases in CDI incidence and severity. Unfortunately CDI prevention efforts are hampered by lack of data to support optimal prevention methods, especially for endemic CDI. Studies are needed to define optimal prevention practices and to investigate novel prevention methods. PMID:20929366

  5. A case of Clostridium septicum spontaneous gas gangrene.

    PubMed

    Dylewski, Joe; Drummond, Robert; Rowen, John

    2007-03-01

    Severe skin and soft tissue infections (SSTIs) are often life-threatening emergencies that require a rapid diagnosis. Gas gangrene is one of the most fulminant types of SSTI and is usually caused by Clostridium perfringens' contamination of an open wound. Although gas gangrene is usually associated with fecally contaminated wounds, "spontaneous" cases occur and are most commonly caused by Clostridium (C.) septicum. We report a case of spontaneous gas gangrene caused by C. septicum that only became manifest while the patient was being monitored in the emergency department. We also review the diagnosis and treatment aspects of this entity.

  6. A population-based matched cohort study examining the mortality and costs of patients with community-onset Clostridium difficile infection identified using emergency department visits and hospital admissions

    PubMed Central

    Nanwa, Natasha; Sander, Beate; Krahn, Murray; Daneman, Nick; Lu, Hong; Austin, Peter C.; Govindarajan, Anand; Rosella, Laura C.; Cadarette, Suzanne M.; Kwong, Jeffrey C.

    2017-01-01

    Few studies have evaluated the mortality or quantified the economic burden of community-onset Clostridium difficile infection (CDI). We estimated the attributable mortality and costs of community-onset CDI. We conducted a population-based matched cohort study. We identified incident subjects with community-onset CDI using health administrative data (emergency department visits and hospital admissions) in Ontario, Canada between January 1, 2003 and December 31, 2010. We propensity-score matched each infected subject to one uninfected subject and followed subjects in the cohort until December 31, 2011. We evaluated all-cause mortality and costs (unadjusted and adjusted for survival) from the healthcare payer perspective (2014 Canadian dollars). During our study period, we identified 7,950 infected subjects. The mean age was 63.5 years (standard deviation = 22.0), 62.7% were female, and 45.0% were very high users of the healthcare system. The relative risk for 30-day, 180-day, and 1-year mortality were 7.32 (95% confidence interval [CI], 5.94–9.02), 3.55 (95%CI, 3.17–3.97), and 2.59 (95%CI, 2.37–2.83), respectively. Mean attributable cumulative 30-day, 180-day, and 1-year costs (unadjusted for survival) were $7,434 (95%CI, $7,122-$7,762), $12,517 (95%CI, $11,687-$13,366), and $13,217 (95%CI, $12,062-$14,388). Mean attributable cumulative 1-, 2-, and 3-year costs (adjusted for survival) were $10,700 (95%CI, $9,811-$11,645), $13,312 (95%CI, $12,024-$14,682), and $15,812 (95%CI, $14,159-$17,571). Infected subjects had considerably higher risk of all-cause mortality and costs compared with uninfected subjects. This study provides insight on an understudied patient group. Our study findings will facilitate assessment of interventions to prevent community-onset CDI. PMID:28257438

  7. Clostridium difficile: from obscurity to superbug.

    PubMed

    Brazier, J S

    2008-01-01

    According to the UK media and popular press, Clostridium difficile is now a fully fledged member of that notorious but ill-defined group of microorganisms portrayed to the general public as superbugs. Following the trail blazed by methicillin-resistant Staphylococcus aureus (MRSA), C. difficile has made the transition from being an obscure anaerobic bacterium, mainly of interest to specialist anaerobic microbiologists, to that of an infamous superbug responsible for outbreaks of hospital-acquired infection that commonly result in serious disease and death. This review tracks the rise in scientific knowledge and public awareness of this organism.

  8. Toxin Plasmids of Clostridium perfringens

    PubMed Central

    Li, Jihong; Adams, Vicki; Bannam, Trudi L.; Miyamoto, Kazuaki; Garcia, Jorge P.; Uzal, Francisco A.; Rood, Julian I.

    2013-01-01

    SUMMARY In both humans and animals, Clostridium perfringens is an important cause of histotoxic infections and diseases originating in the intestines, such as enteritis and enterotoxemia. The virulence of this Gram-positive, anaerobic bacterium is heavily dependent upon its prolific toxin-producing ability. Many of the ∼16 toxins produced by C. perfringens are encoded by large plasmids that range in size from ∼45 kb to ∼140 kb. These plasmid-encoded toxins are often closely associated with mobile elements. A C. perfringens strain can carry up to three different toxin plasmids, with a single plasmid carrying up to three distinct toxin genes. Molecular Koch's postulate analyses have established the importance of several plasmid-encoded toxins when C. perfringens disease strains cause enteritis or enterotoxemias. Many toxin plasmids are closely related, suggesting a common evolutionary origin. In particular, most toxin plasmids and some antibiotic resistance plasmids of C. perfringens share an ∼35-kb region containing a Tn916-related conjugation locus named tcp (transfer of clostridial plasmids). This tcp locus can mediate highly efficient conjugative transfer of these toxin or resistance plasmids. For example, conjugative transfer of a toxin plasmid from an infecting strain to C. perfringens normal intestinal flora strains may help to amplify and prolong an infection. Therefore, the presence of toxin genes on conjugative plasmids, particularly in association with insertion sequences that may mobilize these toxin genes, likely provides C. perfringens with considerable virulence plasticity and adaptability when it causes diseases originating in the gastrointestinal tract. PMID:23699255

  9. Clostridium difficile outbreaks: prevention and treatment strategies

    PubMed Central

    Martinez, Fernando J; Leffler, Daniel A; Kelly, Ciaran P

    2012-01-01

    The incidence and severity of Clostridium difficile infection (CDI) have increased dramatically over the past decade. Its treatment, however, has largely remained the same with the exception of oral vancomycin use as a first-line agent in severe disease. From 1999 to 2004, 20,642 deaths were attributed to CDI in the United States, almost 7 times the rate of all other intestinal infections combined. Worldwide, several major CDI outbreaks have occurred, and many of these were associated with the NAP1 strain. This ‘epidemic’ strain has contributed to the rising incidence and mortality of CDI. The purpose of this article is to review the current management, treatment, infection control, and prevention strategies that are needed to combat this increasingly morbid disease. PMID:22826646

  10. The Role of Glutamate Dehydrogenase (GDH) Testing Assay in the Diagnosis of Clostridium difficile Infections: A High Sensitive Screening Test and an Essential Step in the Proposed Laboratory Diagnosis Workflow for Developing Countries like China.

    PubMed

    Cheng, Jing-Wei; Xiao, Meng; Kudinha, Timothy; Xu, Zhi-Peng; Sun, Lin-Ying; Hou, Xin; Zhang, Li; Fan, Xin; Kong, Fanrong; Xu, Ying-Chun

    2015-01-01

    The incidence and severity of Clostridium difficile infection (CDI) in North America and Europe has increased significantly since the 2000s. However, CDI is not widely recognized in China and other developing countries due to limited laboratory diagnostic capacity and low awareness. Most published studies on laboratory workflows for CDI diagnosis are from developed countries, and thus may not be suitable for most developing countries. Therefore, an alternative strategy for developing countries is needed. In this study, we evaluated the performance of the Glutamate Dehydrogenase (GDH) test and its associated workflow on 416 fecal specimens from suspected CDI cases. The assay exhibited excellent sensitivity (100.0%) and specificity (92.8%), compared to culture based method, and thus could be a good screening marker for C. difficile but not for indication of toxin production. The VIDAS CDAB assay, which can detect toxin A/B directly from fecal specimens, showed good specificity (99.7%) and positive predictive value (97.2%), but low sensitivity (45.0%) and negative predictive value (88.3%), compared with PCR-based toxin gene detection. Therefore, we propose a practical and efficient GDH test based workflow strategy for the laboratory diagnosis of CDI in developing countries like China. By applying this new workflow, the CDI laboratory diagnosis rate was notably improved in our center, yet the increasing cost was kept at a minimum level. Furthermore, to gain some insights into the genetic population structure of C. difficile isolates from our hospital, we performed MLST and PCR toxin gene typing.

  11. Clostridiolysin S, a Post-translationally Modified Biotoxin from Clostridium botulinum*

    PubMed Central

    Gonzalez, David J.; Lee, Shaun W.; Hensler, Mary E.; Markley, Andrew L.; Dahesh, Samira; Mitchell, Douglas A.; Bandeira, Nuno; Nizet, Victor; Dixon, Jack E.; Dorrestein, Pieter C.

    2010-01-01

    Through elaboration of its botulinum toxins, Clostridium botulinum produces clinical syndromes of infant botulism, wound botulism, and other invasive infections. Using comparative genomic analysis, an orphan nine-gene cluster was identified in C. botulinum and the related foodborne pathogen Clostridium sporogenes that resembled the biosynthetic machinery for streptolysin S, a key virulence factor from group A Streptococcus responsible for its hallmark β-hemolytic phenotype. Genetic complementation, in vitro reconstitution, mass spectral analysis, and plasmid intergrational mutagenesis demonstrate that the streptolysin S-like gene cluster from Clostridium sp. is responsible for the biogenesis of a novel post-translationally modified hemolytic toxin, clostridiolysin S. PMID:20581111

  12. Clostridium difficile phages: still difficult?

    PubMed Central

    Hargreaves, Katherine R.; Clokie, Martha R. J.

    2014-01-01

    Phages that infect Clostridium difficile were first isolated for typing purposes in the 1980s, but their use was short lived. However, the rise of C. difficile epidemics over the last decade has triggered a resurgence of interest in using phages to combat this pathogen. Phage therapy is an attractive treatment option for C. difficile infection, however, developing suitable phages is challenging. In this review we summarize the difficulties faced by researchers in this field, and we discuss the solutions and strategies used for the development of C. difficile phages for use as novel therapeutics. Epidemiological data has highlighted the diversity and distribution of C. difficile, and shown that novel strains continue to emerge in clinical settings. In parallel with epidemiological studies, advances in molecular biology have bolstered our understanding of C. difficile biology, and our knowledge of phage–host interactions in other bacterial species. These three fields of biology have therefore paved the way for future work on C. difficile phages to progress and develop. Benefits of using C. difficile phages as therapeutic agents include the fact that they have highly specific interactions with their bacterial hosts. Studies also show that they can reduce bacterial numbers in both in vitro and in vivo systems. Genetic analysis has revealed the genomic diversity among these phages and provided an insight into their taxonomy and evolution. No strictly virulent C. difficile phages have been reported and this contributes to the difficulties with their therapeutic exploitation. Although treatment approaches using the phage-encoded endolysin protein have been explored, the benefits of using “whole-phages” are such that they remain a major research focus. Whilst we don’t envisage working with C. difficile phages will be problem-free, sufficient study should inform future strategies to facilitate their development to combat this problematic pathogen. PMID:24808893

  13. Physical Characterization of Clostridium Botulinum Neurotoxin Genes

    DTIC Science & Technology

    1992-02-17

    type A toxin of Clostridium difficile ; Von Eichel-Streiber, 1989) or total failure (eg., the bacteriocir, of the Clostridium perf•ingens plasmid... CLOSTRIDIUM BOTULINUM NEUROTOXIN GENES PRINCIPAL INVESTIGATIR: NIGEL P. MINTON PI ADDRESS: Public Health Laboratory Service Center for Applied...NUMBERS Physical Characterization of Clostridium botulinum DAMDl7-90-Z-0033 Neurotoxin Genes 61102A 6. AUTHOR(S) 3Ml61102BSI2 AA Nigel P. Minton DA335530

  14. Fatal Spontaneous Clostridium bifermentans Necrotizing Endometritis: A Case Report and Literature Review of the Pathogen

    PubMed Central

    Hale, Andrew; Kirby, James E.; Albrecht, Mary

    2016-01-01

    Clostridium bifermentans is a rare pathogen in humans. A fatal case of fulminant endometritis with toxic shock and capillary leak secondary to C bifermentans infection in a young woman is described, and this is compared to all 13 previously described cases of C bifermentans infection. PMID:27419167

  15. Clostridium chauvoei-associated meningoencephalitis in a calf.

    PubMed

    2016-01-16

    ·Meningoencephalitis in a calf associated with Clostridium chauvoei infection. ·Bovine papular stomatitis in calves. ·Otitis media due to Mycoplasma bovis in calves. ·Sporadic porcine abortion due to Nocardia species. ·Spotty liver disease in hens. These are among matters discussed in the disease surveillance report for September 2015 from SAC Consulting: Veterinary Services (SAC C VS).

  16. A Quantitative Electrochemiluminescence Assay for Clostridium perfringens alpha toxin

    DTIC Science & Technology

    2006-08-10

    is the predominant etiolog- ical agent responsible for gas gangrene [1], although other Clostridium species including C. novyi, C. bifermentans, and...great reduction of the inci- dence of gangrene [1]. Gas gangrene remains a potential problematic disease after traumatic injury such as burns and...is a bacterium associated with three disease syndromes: classic gas gangrene (a muscle tis- sue infection resulting in muscle necrosis), enteritis

  17. An ultrasensitive rapid immunocytotoxicity assay for detecting Clostridium difficile toxins

    PubMed Central

    He, Xiangyun; Wang, Jufang; Steele, Jennifer; Sun, Xingmin; Nie, Weijia; Tzipori, Saul; Feng, Hanping

    2009-01-01

    We describe a novel ultrasensitive cell-based immunocytotoxicity assay for detecting less then 1 pg/ml of Clostridium difficile toxins in porcine clinical samples. The assay is simple to perform with a turnaround time of approximately 3 hours and capable of detecting less then 1 pg/ml of toxin A. Using this assay, we were able to detect the presence of C. difficile toxins in the fecal and serum specimens of experimentally infected piglets. PMID:19393695

  18. Clostridium defficiel in the urogenital tract of males and females.

    PubMed

    Hafiz, S; McEntegart, M G; Morton, R S; Waitkins, S A

    1975-02-22

    A study of the occurrence of Clostridium difficile in the urogenital tract of males and females revealed higher isolation-rates in patients attending the special (venereal-disease) clinic than in patients attending family-planning and urological clinics. The presence of Cl. difficile in patients with venereal diseases is being investigated to see if the organism is simply an opportunist infecting a urethra disturbed by some antecedent disease, or if it is perhaps a primary cuase of disease.

  19. Development and validation of a multiplex real-time PCR for detection of Clostridium chauvoei and Clostridium septicum.

    PubMed

    Lange, Martin; Neubauer, Heinrich; Seyboldt, Christian

    2010-08-01

    Clostridium chauvoei is the causative agent of blackleg in cattle and sheep. The clinical symptoms of this severe disease are very similar to that of malignant edema (Clostridium septicum), infections of other Clostridium species belonging to the gas edema complex, and anthrax (Bacillus anthracis). C. chauvoei and C. septicum are closely related taxa and share many phenotypic properties hampering diagnosis by using traditional microbiological methods. Thus, there is a need for a fast and reliable identification method for specific detection of both species in clinical samples. The multiplex real-time PCR assay presented here is based on the detection of the spo0A gene and enables the simultaneous identification of C. chauvoei and C. septicum. The assay design includes an amplification control DNA template for the recognition of PCR-inhibitors. Assay validation was performed using a collection of 29 C. chauvoei, 38 C. septicum strains and 26 strains of other Clostridium species. Furthermore, the real-time PCR assay was successfully tested on tissue samples from 19 clinical blackleg cases. The assay allowed the reliable detection of one picogram DNA which represents approximate 239 genome equivalents.

  20. Genomics of Clostridium tetani.

    PubMed

    Brüggemann, Holger; Brzuszkiewicz, Elzbieta; Chapeton-Montes, Diana; Plourde, Lucile; Speck, Denis; Popoff, Michel R

    2015-05-01

    Genomic information about Clostridium tetani, the causative agent of the tetanus disease, is scarce. The genome of strain E88, a strain used in vaccine production, was sequenced about 10 years ago. One additional genome (strain 12124569) has recently been released. Here we report three new genomes of C. tetani and describe major differences among all five C. tetani genomes. They all harbor tetanus-toxin-encoding plasmids that contain highly conserved genes for TeNT (tetanus toxin), TetR (transcriptional regulator of TeNT) and ColT (collagenase), but substantially differ in other plasmid regions. The chromosomes share a large core genome that contains about 85% of all genes of a given chromosome. The non-core chromosome comprises mainly prophage-like genomic regions and genes encoding environmental interaction and defense functions (e.g. surface proteins, restriction-modification systems, toxin-antitoxin systems, CRISPR/Cas systems) and other fitness functions (e.g. transport systems, metabolic activities). This new genome information will help to assess the level of genome plasticity of the species C. tetani and provide the basis for detailed comparative studies.

  1. Clostridium perfringens type A-E toxin plasmids.

    PubMed

    Freedman, John C; Theoret, James R; Wisniewski, Jessica A; Uzal, Francisco A; Rood, Julian I; McClane, Bruce A

    2015-05-01

    Clostridium perfringens relies upon plasmid-encoded toxin genes to cause intestinal infections. These toxin genes are associated with insertion sequences that may facilitate their mobilization and transfer, giving rise to new toxin plasmids with common backbones. Most toxin plasmids carry a transfer of clostridial plasmids locus mediating conjugation, which likely explains the presence of similar toxin plasmids in otherwise unrelated C. perfringens strains. The association of many toxin genes with insertion sequences and conjugative plasmids provides virulence flexibility when causing intestinal infections. However, incompatibility issues apparently limit the number of toxin plasmids maintained by a single cell.

  2. [Characteristics of Clostridium tetani and laboratory diagnosis of tetanus].

    PubMed

    Smietańska, Karolina; Rokosz-Chudziak, Natalia; Rastawicki, Waldemar

    2013-01-01

    The causative agent of tetanus is the obligate anaerobic bacterium--Clostridium tetani. These bacteria form endospores that are able to survive long periods of exposure to air and other adverse environmental conditions. Infection generally occurs through wound contamination. We can distinguish several forms of tetanus: generalized, local and neonatal. Diagnosis of tetanus is based primarily on the patient's clinical symptoms (muscle cramps, painful back muscle spasms, generalized contractions of the arcuate curvature of the body) as well as on microbiological diagnosis. This article is a brief review of C. tetani and diagnosis of infections caused by these organisms in humans.

  3. Clostridium perfringens type A–E toxin plasmids

    PubMed Central

    Freedman, John C.; Theoret, James R.; Wisniewski, Jessica A.; Uzal, Francisco A.; Rood, Julian I.; McClane, Bruce A.

    2014-01-01

    Clostridium perfringens relies upon plasmid-encoded toxin genes to cause intestinal infections. These toxin genes are associated with insertion sequences that may facilitate their mobilization and transfer, giving rise to new toxin plasmids with common backbones. Most toxin plasmids carry a transfer of clostridial plasmids locus mediating conjugation, which likely explains the presence of similar toxin plasmids in otherwise unrelated C. perfringens strains. The association of many toxin genes with insertion sequences and conjugative plasmids provides virulence flexibility when causing intestinal infections. However, incompatibility issues apparently limit the number of toxin plasmids maintained by a single cell. PMID:25283728

  4. Necrotizing gastritis associated with Clostridium septicum in a rabbit.

    PubMed

    Garcia, Jorge P; Moore, Janet; Loukopoulos, Panayiotis; Diab, Santiago S; Uzal, Francisco A

    2014-09-01

    Clostridium septicum is the causative agent of histotoxic infections, including malignant edema and braxy (necrotizing abomasitis) in several animal species. The carcass of a 2-year-old, female New Zealand white rabbit with a history of acute depression and obtundation followed by death was received at the California Animal Health and Food Safety Laboratory System (San Bernardino, California) for necropsy and diagnostic workup. No gross lesions were detected at necropsy. Microscopically, there was moderate to severe, multifocal fibrinonecrotizing, transmural gastritis with numerous intralesional Gram-positive, sporulated rods, and disseminated thrombosis of the brain, lungs, heart, and liver, with occasional intravascular rods. The rods observed within the gastric wall and thrombi in the stomach and lung were positive for C. septicum by immunohistochemical staining. However, this microorganism was not isolated from stomach content. Clostridium septicum should be included in the list of possible etiologies of gastritis in rabbits.

  5. [Clostridium difficile infecion--diagnostics, prevention and treatment].

    PubMed

    Piekarska, Marta; Wandałowicz, Alicja D; Miigoć, Henryka

    2014-04-01

    Clostridium difficile is the most common cause of an antibiotic-associated diarrhoea. Frequency of Clostridium difficile infections (CDI) increased in the last decade. This study presents current preventive measure i.e. hand washing, disposable gloves. Additionally, the article presents diagnostic methods: detection glutamine dehydrogenase (GDH), toxins A and B, cytotoxicity neutralization test, polymerase chain reaction methods (PCR) i.e. nucleic acid amplification test (NAAT) and stool culture. Moreover available methods of treatment were presented depending on severity of CDI e.i. metronidazole, vancomycin, fidaxomicin, rifaximin. Furthermore, the review provides information about alternative methods of treatment in view of new hypervirulent strains of C. difficile and increasing resistance to commonly used antibiotics, including: fuscid acid, bacitracin, probiotics, non-toxigenic strains, immunoglobulins, monoclonal antibodies, vaccines, toxins binders and fecal transplant.

  6. ClosTron-mediated engineering of Clostridium.

    PubMed

    Kuehne, Sarah A; Heap, John T; Cooksley, Clare M; Cartman, Stephen T; Minton, Nigel P

    2011-01-01

    The genus Clostridium is a diverse assemblage of Gram positive, anaerobic, endospore-forming bacteria. Whilst certain species have achieved notoriety as important animal and human pathogens (e.g. Clostridium difficile, Clostridium botulinum, Clostridium tetani, and Clostridium perfringens), the vast majority of the genus are entirely benign, and are able to undertake all manner of useful biotransformations. Prominent amongst them are those species able to produce the biofuels, butanol and ethanol from biomass-derived residues, such as Clostridium acetobutylicum, Clostridium beijerinkii, Clostridium thermocellum, and Clostridium phytofermentans. The prominence of the genus in disease and biotechnology has led to the need for more effective means of genetic modification. The historical absence of methods based on conventional strategies for "knock-in" and "knock-out" in Clostridium has led to the adoption of recombination-independent procedures, typified by ClosTron technology. The ClosTron uses a retargeted group II intron and a retro-transposition-activated marker to selectively insert DNA into defined sites within the genome, to bring about gene inactivation and/or cargo DNA delivery. The procedure is extremely efficient, rapid, and requires minimal effort by the operator.

  7. Intracellular survival of Clostridium chauvoei in bovine macrophages.

    PubMed

    Pires, Prhiscylla Sadanã; Santos, Renato Lima; da Paixão, Tatiane Alves; de Oliveira Bernardes, Laura Cristina; de Macêdo, Auricélio Alves; Gonçalves, Luciana Aramuni; de Oliveira Júnior, Carlos Augusto; Silva, Rodrigo Otávio Silveira; Lobato, Francisco Carlos Faria

    2017-02-01

    Clostridium chauvoei is the etiological agent of blackleg, a severe disease of domestic ruminants, causing myonecrosis and serious toxemia with high mortality. Despite the known importance of this agent, studies evaluating its pathogenesis of blackleg are scarce, and many are based on an unproven hypothesis that states that macrophages are responsible for carrying C. chauvoei spores from the intestines to muscles in the early stages of blackleg. Therefore, the present study aimed to investigate the survival of C. chauvoei vegetative cells or spores after phagocytosis by a murine macrophage cell line (RAW 264.7) and bovine monocyte-derived macrophages and to profile inflammatory and anti-inflammatory cytokine transcripts of bovine macrophages infected with C. chauvoei vegetative cells or spores. Both vegetative cells and spores of C. chauvoei remain viable after internalization by murine and bovine macrophages. Bovine macrophages infected with vegetative cells showed a pro-inflammatory profile, while those infected with spores displayed an anti-inflammatory profile. Together, these results corroborate the classical hypothesis that macrophages may play a role in the early pathogenesis of blackleg. Moreover, this is the first study to evaluate the infection kinetics and cytokine profile of bovine monocyte-derived macrophages infected with a Clostridium species.

  8. Physical Characterization of Clostridium Botulinum Neurotoxin Genes

    DTIC Science & Technology

    1993-10-01

    jacewoburylicwn was obtained. 14. SUBJECT TERMS 115. NUMBER OF PAGES Foreign, BD, Clostridium , Cloning, Vaccines , BL3, ________ DNAotrahnsfery, Gn...met with either very limited success (eg., type A toxin of Clostridium difficile ; von Eichel-Streiber, 1989) or total failure (eg., the bacteriocin of...AD-A27 2 939 GRANT NO: DAMDl7-90-Z-0033 TITLE: PHYSICAL CHARACTERIZATION OF CLOSTRIDIUM BOTULINUM NEUROTOXIN GENES PRINCIPAL INVESTIGATOR: Nigel P

  9. Infection

    DTIC Science & Technology

    2010-09-01

    standing, diagnosis, and treatment of musculoskeletal infections. Key Words: musculoskeletal infection, biofilm , bacteria, biomaterial (J Orthop Trauma...form a biofilm , or slime layer.1 The recurrence of infections is often the result of microbial biofilm formation on the implant, enabling the persistence...Klebsiella pneumoniae). Staphylococcus species is by far the most studied pathogen in musculoskeletal infections and can produce a multilayered biofilm

  10. A case of reactive arthritis due to Clostridium difficile colitis

    PubMed Central

    Essenmacher, Alex C.; Khurram, Nazish; Bismack, Gregory T.

    2016-01-01

    Reactive arthritis is an acute, aseptic, inflammatory arthropathy following an infectious process but removed from the site of primary infection. It is often attributed to genitourinary and enteric pathogens, such as Chlamydia, Salmonella, Shigella, Campylobacter, and Yersinia, in susceptible individuals. An uncommon and less recognized cause of this disease is preceding colonic infection with Clostridium difficile, an organism associated with pseudomembranous colitis and diarrhea in hospitalized patients and those recently exposed to antibiotics. Recognition of this association may be complicated by non-specific presentation of diarrhea, the interval between gastrointestinal and arthritic symptoms, and the wide differential in mono- and oligoarthritis. We present the case of a 61-year-old, hospitalized patient recently treated for C. difficile colitis who developed sudden, non-traumatic, right knee pain and swelling. Physical examination and radiographs disclosed joint effusion, and sterile aspiration produced cloudy fluid with predominant neutrophils and no growth on cultures. Diagnostic accuracy is enhanced by contemporaneous laboratory investigations excluding other entities such as gout and rheumatoid arthritis and other infections that typically precede reactive arthritis. Contribution of Clostridium infection to reactive arthritis is an obscure association frequently difficult to prove, but this organism is warranted inclusion in the differential of reactive arthritis. PMID:26908381

  11. Low Prevalence of Clostridium septicum Fecal Carriage in an Adult Population

    PubMed Central

    Kopliku, Fatos; Schubert, Alyxandria M.; Mogle, Jill; Schloss, Patrick D.; Young, Vincent B.; Aronoff, David M.

    2014-01-01

    Clostridium septicum is an uncommon cause of severe infection. Real-time PCR against the C. septicum-specific alpha-toxin gene (csa) was used to estimate the prevalence of this microbe in human stool from 161 asymptomatic community-dwelling adults and 192 hospitalized patients with diarrhea. All samples were negative, suggesting a low prevalence. PMID:25481351

  12. Draft Genome Sequence of Clostridium difficile Belonging to Ribotype 018 and Sequence Type 17

    PubMed Central

    Riccobono, E.; Di Pilato, V.; Della Malva, N.; Meini, S.; Ciraolo, F.; Torricelli, F.

    2016-01-01

    Clostridium difficile, belonging to ribotype 018 (RT018), is one of the most prevalent genotypes circulating in hospital settings in Italy. Here, we report the draft genome of C. difficile CD8-15 belonging to RT018, isolated from a patient with fatal C. difficile-associated infection. PMID:27587821

  13. Glycan arrays containing synthetic Clostridium difficile lipoteichoic acid oligomers as tools toward a carbohydrate vaccine.

    PubMed

    Martin, Christopher E; Broecker, Felix; Eller, Steffen; Oberli, Matthias A; Anish, Chakkumkal; Pereira, Claney L; Seeberger, Peter H

    2013-08-18

    Clostridium difficile is a leading cause of severe nosocomial infections. Cell-surface carbohydrate antigens are promising vaccine candidates. Here we report the first total synthesis of oligomers of the lipoteichoic acid antigen repeating unit. Synthetic glycan microarrays revealed anti-glycan antibodies in the blood of patients that help to define epitopes for vaccine development.

  14. [Toxins of Clostridium perfringens as a natural and bioterroristic threats].

    PubMed

    Omernik, Andrzej; Płusa, Tadeusz

    2015-09-01

    Clostridium perfringens is absolutely anaerobic rod-shaped, sporeforming bacterium. The morbidity is connected with producing toxins. Depending on the type of toxin produced Clostridium perfringens can be divided into five serotypes:A-E. Under natural conditions, this bacterium is responsible for local outbreaks of food poisoning associated with eating contaminated food which which was improperly heat treated. Some countries with lower economic level are endemic foci of necrotizing enteritis caused by Clostridium perfringens. The bacterium is also a major cause of gas gangrene. It is a disease, associated with wound infection, with potentially fatal prognosis in the case of treatment's delays. In the absence of early radical surgery, antibiotic therapy and (if available) hyperbaric treatment leads to the spread of toxins in the body causing shock, coma and death. Due to the force of produced toxins is a pathogen that poses a substrate for the production of biological weapons. It could potentially be used to induce outbreaks of food poisoning and by missiles contamination by spore lead to increased morbidity of gas gangrene in injured soldiers. C. perfringens types B and D produce epsilon toxin considered to be the third most powerful bacterial toxin. Because of the ability to disperse the toxin as an aerosol and a lack of methods of treatment and prevention of poisoning possible factors it is a potential tool for bioterrorism It is advisable to continue research into vaccines and treatments for poisoning toxins of C. perfringens.

  15. Electrophoretic study of Clostridium species.

    PubMed Central

    Cato, E P; Hash, D E; Holdeman, L V; Moore, W E

    1982-01-01

    Polyacrylamide gel electrophoretic analysis of soluble cellular proteins (without sodium dodecyl sulfate) of 70 Clostridium species indicated that the procedure was readily applicable to the differentiation of species in the genus. The protein patterns correlated well with the available DNA homology data and with most accepted differential tests. Results indicated that several earlier names for species were synonyms of those of accepted species and that two accepted species may be synonymous. Images PMID:6175658

  16. Action of nitroheterocyclic drugs against Clostridium difficile

    PubMed Central

    Kumar, Manish; Adhikari, Sudip; Hurdle, Julian G.

    2014-01-01

    The nitroheterocyclic classes of drugs have a long history of use in treating anaerobic infections, as exemplified by metronidazole as a first-line treatment for mild-to-moderate Clostridium difficile infection (CDI). Since direct comparisons of the three major classes of nitroheterocyclic drugs (i.e. nitroimidazole, nitazoxanide and nitrofurans) and nitrosating agents against C. difficile are under-examined, in this study their actions against C. difficile were compared. Results show that whilst transient resistance occurs to metronidazole and nitazoxanide, stable resistance arises to nitrofurans upon serial passage. All compounds killed C. difficile at high concentrations in addition to the host defence nitrosating agent S-nitrosoglutathione (GSNO). This suggests that GSNO killing of C. difficile contributes to its efficacy in murine CDI. Although nitric oxide production could not be detected for the nitroheterocyclic drugs, the cellular response to metronidazole and nitrofurans has some overlap with the response to GSNO, causing significant upregulation of the hybrid-cluster protein Hcp that responds to nitrosative stress. These findings provide new insights into the action of nitroheterocyclic drugs against C. difficile. PMID:25129314

  17. Characterization of Clostridium spp. isolated from spoiled processed cheese products.

    PubMed

    Lycken, Lena; Borch, Elisabeth

    2006-08-01

    Of 42 spoiled cheese spread products, 35 were found to harbor Clostridium spp. Typical signs of spoilage were gas production and off-odor. The identity was determined for about half of the isolates (n = 124) by Analytab Products (API), Biolog, the RiboPrinter System, 16S rDNA sequencing, cellular fatty acid analysis, or some combination of these. The majority of isolates were identified as Clostridium sporogenes (in 33% of products), but Clostridium cochlearium (in 12% of products) and Clostridium tyrobutyricum (in 2% of products) were also retrieved. Similarity analysis of the riboprint patterns for 21 isolates resulted in the identification of 10 ribogroups. A high degree of relatedness was observed between isolates of C. sporogenes originating from products produced 3 years apart, indicating a common and, over time, persistent source of infection. The spoilage potential of 11 well-characterized isolates and two culture collection strains was analyzed by inoculating shrimp cheese spread with single cultures and then storing them at 37 degrees C. Tubes inoculated with C. tyrobutyricum did not show any visible signs of growth (e.g., coagulation, discoloration, gas formation) in the cheese spread. After 2 weeks of incubation, tubes inoculated with C. cochlearium or C. sporogenes showed gas-holes, syneresis with separation of coagulated casein and liquid, and a change in color of the cheese. The amount of CO2 produced by C. cochlearium strains was approximately one-third that produced by the majority of C. sporogenes strains. To our knowledge, this is the first study to isolate and identify C. cochlearium as a spoilage organism in cheese spread.

  18. Clostridium perfringens type A enteritis in blue and yellow macaw (Ara ararauna).

    PubMed

    Guimarães, Marta Brito; Torres, Luciana Neves; Mesquita, Ramon Gomes; Ampuero, Fernanda; Cunha, Marcos Paulo Vieira; Ferreira, Thais Sebastiana Porfida; Ferreira, Antonio José Piantino; Catão-Dias, José Luiz; Moreno, Andrea Micke; Knöbl, Terezinha

    2014-12-01

    This study describes an outbreak of necrotic enteritis caused by Clostridium perfringens type A in captive macaws (Ara ararauna). Two psittacine birds presented a history of prostration and died 18 hr after manifestation of clinical signs. The necropsy findings and histopathologic lesions were indicative of necrotic enteritis. Microbiologic assays resulted in the growth of large gram-positive bacilli that were identified as C. perfringens. PCR was used to identify clostridium toxinotypes and confirmed the identification of isolated strains as C pefringens type A, positive to gene codifying beta 2 toxin. The infection source and predisposing factors could not be ascertained.

  19. Phylogenetic analysis and PCR detection of Clostridium chauvoei, Clostridium haemolyticum, Clostridium novyi types A and B, and Clostridium septicum based on the flagellin gene.

    PubMed

    Sasaki, Yoshimasa; Kojima, Akemi; Aoki, Hiroshi; Ogikubo, Yasuaki; Takikawa, Noriyasu; Tamura, Yutaka

    2002-05-01

    The flagellin genes (fliC) of Clostridium chauvoei, Clostridium haemolyticum, Clostridium novyi types A and B, and Clostridium septicum were analysed by PCR amplification and DNA sequencing. The five Clostridium species have at least two copies of the flagellin gene (fliC) arranged in tandem on the chromosome. The deduced N- and C-terminal aminoacid sequences of the flagellin proteins (FliCs) of these clostridia are well conserved but their central region aminoacid sequences are not. Phylogenic analysis based on the N-terminal aminoacid sequence of the FliC protein revealed that these clostridia, which belong to Clostridium 16S rDNA phylogenic cluster I (), are more closely related to Bacillus subtilis than to Clostridium difficile, which belongs to the cluster XI. Moreover, a multiplex polymerase reaction (PCR) system based on the fliC sequence was developed to rapidly identify C. chauvoei, C. haemolyticum, C. novyi types A and B, and C. septicum. PCR of each Clostridium amplified a species-specific band. The multiplex PCR system may be useful for rapid identification of pathogenic clostridia.

  20. Fulminant massive gas gangrene caused by Clostridium perfringens.

    PubMed

    Kuroda, Shoji; Okada, Yumi; Mita, Masaki; Okamoto, Yasuo; Kato, Hirotaka; Ueyama, Shigemitsu; Fujii, Ikuzo; Morita, Sumiharu; Yoshida, Yasuaki

    2005-05-01

    Clostridium perfringens (C.P) gas gangrene is one of the most fulminant infectious diseases. We encountered fulminant massive gas gangrene in a 56- year-old man with alcoholic liver cirrhosis. The patient died 14 hours after diagnosis of gas gangrene (54 hours after admission). Dramatic changes in abdominal CT imaging revealed development of a massive volume of gas in the intra-portal vein, retroperitoneum and abdominal subcutaneous tissue within 24 hours. We also proved C.P infection by immunohistological staining, leading to a diagnosis of C.P gas gangrene.

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

    PubMed

    Fejes, I; Dégi, R; Végh, M

    2013-02-01

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

  2. Novel approaches to treating Clostridium difficile-associated colitis.

    PubMed

    Padua, David; Pothoulakis, Charalabos

    2016-01-01

    Clostridium difficile is being recognized as a growing threat to many health-care systems. Epidemiology data shows that infection rates are soaring and the disease burden is increasing. Despite the efficacy of standard treatments, it is becoming evident that novel therapeutics will be required to tackle this disease. These new treatments aim to enhance the intestinal microbial barrier, activate the immune system and neutralize the toxins that mediate this disease. Many of these therapies are still in the beginning stages of investigation, however, in the next few years, more clinical data will become available to help implement many of these exciting new therapeutic approaches.

  3. Quantitative real-time PCR assay for Clostridium septicum in poultry gangrenous dermatitis associated samples.

    PubMed

    Neumann, A P; Dunham, S M; Rehberger, T G; Siragusa, G R

    2010-08-01

    Clostridium septicum is a spore-forming anaerobe frequently implicated in cases of gangrenous dermatitis (GD) and other spontaneously occurring myonecrotic infections of poultry. Although C. septicum is readily cultured from diseased tissues it can be difficult to enumerate due to its tendency to swarm over the surface of agar plates. In this study a quantitative real-time PCR assay was developed in order to more accurately measure the levels of C. septicum in healthy as well as GD associated poultry samples. The assay was specifically designed to target the C. septicum alpha toxin gene, csa, which is, to our knowledge, carried by all strains of C. septicum and has been shown to be essential for virulence. Genomic DNAs from a diverse collection of bacterial species, including closely related Clostridium chauvoei, Clostridium carnis, Clostridium tertium as well as several strains of Clostridium perfringens, all failed to produce a positive reaction. An approximate reproducible limit of detection in spiked extracts of at least 10(3) cfu/g of C. septicum was observed for a variety of different sample types. C. septicum levels in broiler chicken field samples estimated from the results of qPCR were statistically correlated to culture based enumerations obtained from those same tissues.

  4. Clostridium botulinum type E occurs and grows in the alga Cladophora glomerata

    USGS Publications Warehouse

    Byappanahalli, M.N.; Whitman, R.L.

    2009-01-01

    In recent years, massive avian die-offs from Clostridium botulinum type E infection have occurred in the Sleeping Bear Dunes National Lakeshore (SLBE) area of Lake Michigan. These outbreaks have been coincidental with massive blooms of the green algae Cladophora, mostly Cladophora glomerata. We tested the hypothesis that Clostridium botulinum type E can grow under suitable conditions in these algal mats. In a lab mesocosm study, Cladophora from four outbreak-impacted beaches from SLBE were compared with four unimpacted beaches in the Milwaukee–Racine area for bontE gene of Clostridium botulinum. Frequency of the bontE gene was higher after incubation (25 °C for up to 6 weeks) of Cladophora from impacted vs. the unimpacted area. Since no type E gene was detected initially in Cladophora from any of the eight locations, we infer that the increased occurrence of type E gene arose from spore germination or vegetative Clostridium growth within the existing algal mats of SLBE. Moreover, we found that the congener Clostridium perfringens readily grows in mesocosms containing Cladophora.

  5. [Clostridium tetani isolated from patients with systemic tetanus].

    PubMed

    Onuki, Tomoyo; Nihonyanagi, Shin; Nakamura, Masaki; Ide, Toshimitsu; Hattori, Jun; Kanoh, Yuhsaku; Soma, Kazui

    2013-01-01

    Clostridium tetani is widely distributed in ground or mud, especially in field and pond-shore surface layers. C. tetani is rarely isolated from specimens of patients with tetanus, and is generally diagnosed based on clinical symptoms such as trismus or general tonic spasms. This means that positive C. tetani infection is rarely diagnosed bacterially. Using gram straing, we identified C. tetani in specimens from patients suspected of C. tetani infection brought to the Kitasato University Hospital emergency center. Rapid gram staining information in the bacteriology laboratory is expected to improve recovery from C. tetani infection. It is therefore necessary to ensure clinical specimen quality control, and to keep standard strains of rare bacteria for isolation and identification.

  6. Regulation of toxin synthesis in Clostridium botulinum and Clostridium tetani.

    PubMed

    Connan, Chloé; Denève, Cécile; Mazuet, Christelle; Popoff, Michel R

    2013-12-01

    Botulinum and tetanus neurotoxins are structurally and functionally related proteins that are potent inhibitors of neuroexocytosis. Botulinum neurotoxin (BoNT) associates with non-toxic proteins (ANTPs) to form complexes of various sizes, whereas tetanus toxin (TeNT) does not form any complex. The BoNT and ANTP genes are clustered in a DNA segment called the botulinum locus, which has different genomic localization (chromosome, plasmid, phage) in the various Clostridium botulinum types and subtypes. The botulinum locus genes are organized in two polycistronic operons (ntnh-bont and ha/orfX operons) transcribed in opposite orientations. A gene called botR lying between the two operons in C. botulinum type A encodes an alternative sigma factor which regulates positively the synthesis of BoNT and ANTPs at the late exponential growth phase and beginning of the stationary phase. In Clostridium tetani, the gene located immediately upstream of tent encodes a positive regulatory protein, TetR, which is related to BotR. C. botulinum and C. tetani genomes contain several two-component systems and predicted regulatory orphan genes. In C. botulinum type A, four two-component systems have been found that positively or negatively regulate the synthesis of BoNT and ANTPs independently of BotR/A. The synthesis of neurotoxin in Clostridia seems to be under the control of complex network of regulation.

  7. Molecular genetics and pathogenesis of Clostridium perfringens.

    PubMed Central

    Rood, J I; Cole, S T

    1991-01-01

    Clostridium perfringens is the causative agent of a number of human diseases, such as gas gangrene and food poisoning, and many diseases of animals. Recently significant advances have been made in the development of C. perfringens genetics. Studies on bacteriocin plasmids and conjugative R plasmids have led to the cloning and analysis of many C. perfringens genes and the construction of shuttle plasmids. The relationship of antibiotic resistance genes to similar genes from other bacteria has been elucidated. A detailed physical map of the C. perfringens chromosome has been prepared, and numerous genes have been located on that map. Reproducible transformation methods for the introduction of plasmids into C. perfringens have been developed, and several genes coding for the production of extracellular toxins and enzymes have been cloned. Now that it is possible to freely move genetic information back and forth between C. perfringens and Escherichia coli, it will be possible to apply modern molecular methods to studies on the pathogenesis of C. perfringens infections. PMID:1779929

  8. Crystal structure of Clostridium difficile toxin A

    PubMed Central

    Chumbler, Nicole M.; Rutherford, Stacey A.; Zhang, Zhifen; Farrow, Melissa A.; Lisher, John P.; Farquhar, Erik; Giedroc, David P.; Spiller, Benjamin W.; Melnyk, Roman A.; Lacy, D. Borden

    2016-01-01

    Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Disease is mediated by the actions of two toxins, TcdA and TcdB, which cause the diarrhoea, as well as inflammation and necrosis within the colon1,2. The toxins are large (308 and 270 kDa, respectively), homologous (47% amino acid identity) glucosyltransferases that target small GTPases within the host3,4. The multidomain toxins enter cells by receptor-mediated endocytosis and, upon exposure to the low pH of the endosome, insert into and deliver two enzymatic domains across the membrane. Eukaryotic inositol-hexakisphosphate (InsP6) binds an autoprocessing domain to activate a proteolysis event that releases the N-terminal glucosyltransferase domain into the cytosol. Here, we report the crystal structure of a 1,832-amino-acid fragment of TcdA (TcdA1832), which reveals a requirement for zinc in the mechanism of toxin autoprocessing and an extended delivery domain that serves as a scaffold for the hydrophobic α-helices involved in pH-dependent pore formation. A surface loop of the delivery domain whose sequence is strictly conserved among all large clostridial toxins is shown to be functionally important, and is highlighted for future efforts in the development of vaccines and novel therapeutics. PMID:27571750

  9. Secretome analysis of Clostridium difficile strains.

    PubMed

    Boetzkes, Alexander; Felkel, Katharina Wiebke; Zeiser, Johannes; Jochim, Nelli; Just, Ingo; Pich, Andreas

    2012-08-01

    Clostridium difficile causes infections ranging from mild C. difficile-associated diarrhea to severe pseudomembranous colitis. Since 2003 new hypervirulent C. difficile strains (PCR ribotype 027) emerged characterized by a dramatically increased mortality. The secretomes of the three C. difficile strains CDR20291, CD196, and CD630 were analyzed and compared. Proteins were separated and analyzed by means of SDS--PAGE and LC-MS. MS data were analyzed using Mascot and proteins were checked for export signals with SecretomeP and SignalP. LC-MS analysis revealed 158 different proteins in the supernatant of C. difficile. Most of the identified proteins originate from the cytoplasm. Thirty-two proteins in CDR20291, 36 in CD196 and 26 in CD630 were identified to be secreted by C. difficile strains. Those were mainly S-layer proteins, substrate-binding proteins of ABC-transporters, cell wall hydrolases, pilin and unknown hypothetical proteins. Toxin A and toxin B were identified after growth in brain heart infusion medium using immunological techniques. The ADP-ribosyltransferase-binding component protein, which is a part of the binary toxin CDT, was only identified in the hypervirulent ribotype 027 strains. Further proteins that are secreted specifically by hypervirulent strains were identified.

  10. Multilocus Sequence Typing of Clostridium difficile▿

    PubMed Central

    Griffiths, David; Fawley, Warren; Kachrimanidou, Melina; Bowden, Rory; Crook, Derrick W.; Fung, Rowena; Golubchik, Tanya; Harding, Rosalind M.; Jeffery, Katie J. M.; Jolley, Keith A.; Kirton, Richard; Peto, Tim E.; Rees, Gareth; Stoesser, Nicole; Vaughan, Alison; Walker, A. Sarah; Young, Bernadette C.; Wilcox, Mark; Dingle, Kate E.

    2010-01-01

    A robust high-throughput multilocus sequence typing (MLST) scheme for Clostridium difficile was developed and validated using a diverse collection of 50 reference isolates representing 45 different PCR ribotypes and 102 isolates from recent clinical samples. A total of 49 PCR ribotypes were represented overall. All isolates were typed by MLST and yielded 40 sequence types (STs). A web-accessible database was set up (http://pubmlst.org/cdifficile/) to facilitate the dissemination and comparison of C. difficile MLST genotyping data among laboratories. MLST and PCR ribotyping were similar in discriminatory abilities, having indices of discrimination of 0.90 and 0.92, respectively. Some STs corresponded to a single PCR ribotype (32/40), other STs corresponded to multiple PCR ribotypes (8/40), and, conversely, the PCR ribotype was not always predictive of the ST. The total number of variable nucleotide sites in the concatenated MLST sequences was 103/3,501 (2.9%). Concatenated MLST sequences were used to construct a neighbor-joining tree which identified four phylogenetic groups of STs and one outlier (ST-11; PCR ribotype 078). These groups apparently correlate with clades identified previously by comparative genomics. The MLST scheme was sufficiently robust to allow direct genotyping of C. difficile in total stool DNA extracts without isolate culture. The direct (nonculture) MLST approach may prove useful as a rapid genotyping method, potentially benefiting individual patients and informing hospital infection control. PMID:20042623

  11. Genomics of Clostridium botulinum group III strains.

    PubMed

    Sakaguchi, Yoshihiko; Suzuki, Tomonori; Yamamoto, Yumiko; Nishikawa, Atsushi; Oguma, Keiji

    2015-05-01

    In Clostridium botulinum, the characteristics of type C and D strains are quite different from other types, and they are classified as group III. They produce C2 binary toxin and C3 exoenzyme in addition to type C and D neurotoxins. Two different phages and many plasmids are identified in the organisms. The genes of neurotoxin and C3 exoenzyme are converted from toxigenic strains to non-toxigenic strains by the specific bacteriophages (phages), whereas, the C2 toxin gene is carried by large or small plasmids. Classification of type C and D strains has been in confusion because 1) antigenicity of type C and D neurotoxins is complex, 2) the cells produce two types of toxins, neurotoxin and C2 toxin, and 3) some non-toxigenic strains can be converted to produce C or D neurotoxin by the infection with phages. Until now, entire nucleotide sequences of cell chromosomes, phages, and plasmids have been determined. Since both genetic and protein-chemical analyses have been clarifying the above confusions, these data are reviewed historically.

  12. Clostridium difficile and Clostridium perfringens from wild carnivore species in Brazil.

    PubMed

    Silva, Rodrigo Otávio Silveira; D'Elia, Mirella Lauria; Tostes Teixeira, Erika Procópio; Pereira, Pedro Lúcio Lithg; de Magalhães Soares, Danielle Ferreira; Cavalcanti, Álvaro Roberto; Kocuvan, Aleksander; Rupnik, Maja; Santos, André Luiz Quagliatto; Junior, Carlos Augusto Oliveira; Lobato, Francisco Carlos Faria

    2014-08-01

    Despite some case reports, the importance of Clostridium perfringens and Clostridium difficile for wild carnivores remains unclear. Thus, the objective of this study was to identify C. perfringens and C. difficile strains in stool samples from wild carnivore species in Brazil. A total of 34 stool samples were collected and subjected to C. perfringens and C. difficile isolation. Suggestive colonies of C. perfringens were then analyzed for genes encoding the major C. perfringens toxins (alpha, beta, epsilon and iota) and the beta-2 toxin (cpb2), enterotoxin (cpe) and NetB (netb) genes. C. difficile strains were analyzed by multiplex-PCR for toxins A (tcdA) and B (tcdB) and a binary toxin gene (cdtB) and also submitted to a PCR ribotyping. Unthawed aliquots of samples positive for C. difficile isolation were subjected to the detection of A/B toxins by a cytotoxicity assay (CTA). C. perfringens was isolated from 26 samples (76.5%), all of which were genotyped as type A. The netb gene was not detected, whereas the cpb2 and cpe genes were found in nine and three C. perfringens strains, respectively. C. difficile was isolated from two (5.9%) samples. A non-toxigenic strain was recovered from a non-diarrheic maned wolf (Chrysocyon brachyurus). Conversely, a toxigenic strain was found in the sample of a diarrheic ocelot (Leopardus pardallis); an unthawed stool sample was also positive for A/B toxins by CTA, indicating a diagnosis of C. difficile-associated diarrhea in this animal. The present work suggests that wild carnivore species could carry C. difficile strains and that they could be susceptible to C. difficile infection.

  13. Infection

    MedlinePlus

    ... 23(4):251-69. Association for Professionals in Infection Control and Epidemiology (APIC) guideline. Back to Top Administration ... : Hospital Scope | Glossary | References | Site Map | Credits Freedom of ...

  14. Effective Sequestration of Clostridium difficile Protein Toxins by Calcium Aluminosilicate

    PubMed Central

    Pokusaeva, Karina; Carpenter, Robert

    2015-01-01

    Clostridium difficile is a leading cause of antibiotic-associated diarrhea and the etiologic agent responsible for C. difficile infection. Toxin A (TcdA) and toxin B (TcdB) are nearly indispensable virulence factors for Clostridium difficile pathogenesis. Given the toxin-centric mechanism by which C. difficile pathogenesis occurs, the selective sequestration with neutralization of TcdA and TcdB by nonantibiotic agents represents a novel mode of action to prevent or treat C. difficile-associated disease. In this preclinical study, we used quantitative enzyme immunoassays to determine the extent by which a novel drug, calcium aluminosilicate uniform particle size nonswelling M-1 (CAS UPSN M-1), is capable of sequestering TcdA and TcdB in vitro. The following major findings were derived from the present study. First, we show that CAS UPSN M-1 efficiently sequestered both TcdA and TcdB to undetectable levels. Second, we show that CAS UPSN M-1's affinity for TcdA is greater than its affinity for TcdB. Last, we show that CAS UPSN M-1 exhibited limited binding affinity for nontarget proteins. Taken together, these results suggest that ingestion of calcium aluminosilicate might protect gastrointestinal tissues from antibiotic- or chemotherapy-induced C. difficile infection by neutralizing the cytotoxic and proinflammatory effects of luminal TcdA and TcdB. PMID:26149988

  15. Clostridium difficile disease: Diagnosis, pathogenesis, and treatment update.

    PubMed

    Napolitano, Lena M; Edmiston, Charles E

    2017-03-03

    Clostridium difficile infections are the leading cause of health care-associated infectious diarrhea, posing a significant risk for both medical and surgical patients. Because of the significant morbidity and mortality associated with C difficile infections, knowledge of the epidemiology of C difficile in combination with a high index of suspicion and susceptible patient populations (including surgical, postcolectomy, and inflammatory bowel disease patients) is warranted. C difficile infections present with a wide spectrum of disease, ranging from mild diarrhea to fulminant colitis or small bowel enteritis and recurrent C difficile infections. Early implementation of medical and operative treatment strategies for C difficile infections is imperative for optimal patient outcomes. National and international guidelines recommend early operative consultation and total abdominal colectomy with end ileostomy and preservation of rectum. Diverting loop ileostomy and colonic lavage followed by intravenous metronidazole and intracolonic vancomycin administered via the efferent limb of the ileostomy should be considered as an alternative to total colectomy in selected patients. New and emerging strategies for C difficile infection treatment include monoclonal antibodies, vaccines, probiotics, biotherapeutics, and new antibiotics. A successful C difficile prevention and eradication program requires a multidisciplinary approach that includes early disease recognition, implementation of guidelines for monitoring adherence to environmental control, judicious hand hygiene, evidence-based treatment and management strategies, and a focused antibiotic stewardship program. Surgeons are an important part of the clinical team in the management of C difficile infection prevention and treatment.

  16. Lytic Clostridium perfringens Bacteriophage 39-O Genomic

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Screening for bacteriophages lytic for Clostridium perfringens was completed utilizing filtered samples obtained from poultry (intestinal material), soil, sewage and poultry processing drainage water. Following limit dilution cloning and three rounds of plaque purification lytic phage preparations ...

  17. Clostridium difficile and C. difficile Toxin Testing

    MedlinePlus

    ... C diff antigen; GDH Formal name: Clostridium difficile Culture; C. difficile Toxin, A and B; C. difficile Cytotoxin Assay; Glutamate Dehydrogenase Test Related tests: Stool Culture ; O&P At a Glance Test Sample The ...

  18. Clostridium septicum: An Unusual Link to a Lower Gastrointestinal Bleed

    PubMed Central

    Jessamy, Kegan; Ojevwe, Fidelis O.; Ubagharaji, Ezinnaya; Sharma, Anuj; Anozie, Obiajulu; Gilman, Christy Ann; Rawlins, Sekou

    2016-01-01

    Clostridium septicum is a highly virulent pathogen which is associated with colorectal malignancy, hematological malignancy, immunosuppression, diabetes mellitus and cyclical neutropenia. Presentation may include disseminated clostridial infection in the form of septicemia, gas gangrene, and mycotic aortic aneurysms. We report the case of a 62-year-old female presenting with necrotizing fasciitis of her left thigh and subsequently developing rectal bleeding. While she was being treated with empiric antibiotics, her blood culture was found to be positive for C. septicum. We would like to highlight the importance of early colorectal cancer screening in minimizing the occurrence of undetected tumors which provide an optimal growth environment for C. septicum, leading to localized and/or remote infection. PMID:27721737

  19. Blowhole Colostomy for Clostridium difficile-Associated Toxic Megacolon

    PubMed Central

    Kerstens, Jeroen; de Gheldere, Charles; Vanclooster, Patrick

    2016-01-01

    We present the case of a 58-year-old man who underwent urgent blowhole colostomy for toxic megacolon (TM) secondary to Clostridium difficile infection (CDI). This infection occurred under antibiotic coverage with amoxicillin-clavulanic acid, four days after laparoscopic sigmoidectomy in our hospital. Although prospective clinical research regarding the surgical management of TM is lacking, decompressive procedures like blowhole colostomy are reported to carry a high risk of postoperative morbidity and mortality and are widely regarded as obsolete. Subtotal or total colectomy with end ileostomy is currently considered the procedure of choice. After presenting our case, we discuss the literature available on the subject to argue that the scarce evidence on the optimal surgical treatment for TM is primarily based on TM associated with inflammatory bowel diseases (IBD) and that there might be a rationale for considering minimally invasive procedures like blowhole colostomy for CDI-associated TM. PMID:28097034

  20. The Design of a Clostridium difficile Carbohydrate-Based Vaccine.

    PubMed

    Monteiro, Mario A

    2016-01-01

    Clostridium difficile vaccines composed of surface polysaccharides (PSs) have the potential to simultaneously control infection and colonization levels in humans. Hot water-phenol treatment of C. difficile biomass can extricate water-soluble PS-I and PS-II; and water- and phenol-soluble PS-III. C. difficile vaccines based on PS-II have attracted the most attention due its facile purification and ubiquitous expression by C. difficile ribotypes. Anti PS-II antibodies recognize both C. difficile vegetative cell and sporulating preparations and confer protection against C. difficile infection in a mouse model. The design of such an efficacious C. difficile PS-II conjugate vaccine is described here.

  1. Clostridium difficile: development of a novel candidate vaccine.

    PubMed

    Foglia, Ginamarie; Shah, Siddhi; Luxemburger, Christine; Pietrobon, Patricia J Freda

    2012-06-19

    Clostridium difficile has become the most frequent hospital-acquired infection in North America and the EU. C. difficile infection (CDI) is present worldwide and disease awareness is increasing. In the US, EU, and Canada, in addition to hospital diagnosed disease, CDI has also been reported with increasing frequency in the community. Hypervirulent strains have increased the morbidity and mortality associated with CDI. Current treatment options are suboptimal. Of all patients treated for CDI, 20% relapse and 65% of those experiencing a second relapse become chronic cases. An association between increased serum levels of IgG antibody against toxin A and asymptomatic carriage of C. difficile provides a rationale for vaccine development. Sanofi Pasteur's C. difficile candidate vaccine is being developed for the prevention of primary disease. The target population is adults at risk of CDI, those with planned hospitalization, long-term care/nursing home residents, and adults with co-morbidities requiring frequent/prolonged antibiotic use.

  2. Predisposing factors and prevention of Clostridium perfringens-associated enteritis.

    PubMed

    Allaart, Janneke G; van Asten, Alphons J A M; Gröne, Andrea

    2013-09-01

    Clostridium perfringens is one of the major causes of intestinal disease in humans and animals. Its pathogenicity is contributed to by the production of a variety of toxins. In addition, predisposing environmental factors are important for the induction of C. perfringens-associated enteritis as shown by infection models. Environmental contamination, gastric and intestinal pH, intestinal microflora, nutrition, concurrent infections, and medical interventions may influence the intestinal colonization, growth, and toxin production by C. perfringens. Prevention of C. perfringens-associated enteritis may be mediated by the use of feed additives like probiotics, prebiotics, organic acids, essential oils, bacteriophages, lysozymes, bacteriocins, and antimicrobial peptides. Here we summarize and discuss published data on the influence of different environmental predisposing factors and preventive measures. Further research should focus on feed composition and feed additives in order to prevent C. perfringens-associated enteritis.

  3. Infection,

    DTIC Science & Technology

    1980-10-16

    inapparent infection. A refeeding program may thus become complicated by the sudden appearance of a life-threatening infectious illness (3). (3) The...Beisel, W. R. 23 Unusually low serum concentrations of inorganic phosphate have been reported in patients with gram-negative sepsis and in Reye’s syndrome ...infection should be corrected by a well-managed program of convalescent-period refeeding . This aspect of nutritional support is too often ignored. On the

  4. [Clostridium-difficile-associated diarrhea].

    PubMed

    Bujanda, Luis; Cosme, Angel

    2009-01-01

    Clostridium difficile is the most frequent cause of nosocomial diarrhea and is a significant cause of morbidity among hospitalized patients. The inflammation is produced as a result of a non-specific response to toxins. In the last few years, a hypervirulent strain, NAP1/BI/027, has been reported. Symptoms usually consist of abdominal pain and diarrhea. The diagnosis should be suspected in any patient who develops diarrhea during antibiotic therapy or 6-8 weeks after treatment. Diagnosis should be confirmed by the detection of CD toxin in stool and by colonoscopy in special situations. The treatment of choice is metronidazole or vancomycin. In some patients who do not respond to this therapy or who have complications, subtotal colectomy may be required. Relapse is frequent and must be distinguished from reinfection. Prevention and control in healthcare settings requires careful attention.

  5. Identification of Clostridium Species and DNA Fingerprinting of Clostridium perfringens by Amplified Fragment Length Polymorphism Analysis▿

    PubMed Central

    Keto-Timonen, Riikka; Heikinheimo, Annamari; Eerola, Erkki; Korkeala, Hannu

    2006-01-01

    An amplified fragment length polymorphism (AFLP) method was applied to 129 strains representing 24 different Clostridium species, with special emphasis on pathogenic clostridia of medical or veterinary interest, to assess the potential of AFLP for identification of clostridia. In addition, the ability of the same AFLP protocol to type clostridia at the strain level was assessed by focusing on Clostridium perfringens strains. All strains were typeable by AFLP, so the method seemed to overcome the problem of extracellular DNase production. AFLP differentiated all Clostridium species tested, except for Clostridium ramosum and Clostridium limosum, which clustered together with a 45% similarity level. Other Clostridium species were divided into species-specific clusters or occupied separate positions. Wide genetic diversity was observed among Clostridium botulinum strains, which were divided into seven species-specific clusters. The same AFLP protocol was also suitable for typing C. perfringens at the strain level. A total of 29 different AFLP types were identified for 37 strains of C. perfringens; strains initially originating from the same isolate showed identical fingerprinting patterns and were distinguished from unrelated strains. AFLP proved to be a highly reproducible, easy-to-perform, and relatively fast method which enables high throughput of samples and can serve in the generation of identification libraries. These results indicate that the AFLP method provides a promising tool for the identification and characterization of Clostridium species. PMID:16971642

  6. Physiology and Sporulation in Clostridium.

    PubMed

    Dürre, Peter

    2014-08-01

    Clostridia are Gram-positive, anaerobic, endospore-forming bacteria, incapable of dissimilatory sulfate reduction. Comprising approximately 180 species, the genus Clostridium is one of the largest bacterial genera. Physiology is mostly devoted to acid production. Numerous pathways are known, such as the homoacetate fermentation by acetogens, the propionate fermentation by Clostridium propionicum, and the butyrate/butanol fermentation by C. acetobutylicum, a well-known solvent producer. Clostridia degrade sugars, alcohols, amino acids, purines, pyrimidines, and polymers such as starch and cellulose. Energy conservation can be performed by substrate-level phosphorylation as well as by the generation of ion gradients. Endospore formation resembles the mechanism elucidated in Bacillus. Morphology, contents, and properties of spores are very similar to bacilli endospores. Sporulating clostridia usually form swollen mother cells and accumulate the storage substance granulose. However, clostridial sporulation differs by not employing the so-called phosphorelay. Initiation starts by direct phosphorylation of the master regulator Spo0A. The cascade of sporulation-specific sigma factors is again identical to what is known from Bacillus. The onset of sporulation is coupled in some species to either solvent (acetone, butanol) or toxin (e.g., C. perfringens enterotoxin) formation. The germination of spores is often induced by various amino acids, often in combination with phosphate and sodium ions. In medical applications, C. butyricum spores are used as a C. difficile prophylaxis and as treatment against diarrhea. Recombinant spores are currently under investigation and testing as antitumor agents, because they germinate only in hypoxic tissues (i.e., tumor tissue), allowing precise targeting and direct killing of tumor cells.

  7. Clostridium difficile from food and surface samples in a Belgian nursing home: an unlikely source of contamination.

    PubMed

    Rodriguez, C; Korsak, N; Taminiau, B; Avesani, V; Van Broeck, J; Brach, P; Delmée, M; Daube, G

    2015-04-01

    This study investigates the contamination of foods and surfaces with Clostridium difficile in a single nursing home. C. difficile PCR-ribotype 078 was found in one food sample and in none of the tested surfaces. These results indicate that food and surfaces are an unlikely source of C. difficile infection in this setting.

  8. Clinical impact of switching conventional enzyme immunoassay with nucleic acid amplification test for suspected Clostridium difficile-associated diarrhea.

    PubMed

    Johnson, Steven W; Kanatani, Meganne; Humphries, Romney M; Uslan, Daniel Z

    2013-04-01

    The impact of a new Clostridium difficile nucleic acid amplification test (NAAT) on antibiotic utilization in patients with suspected C difficile infection was assessed. This single-center, cross-sectional study of 270 patients demonstrated that the use of NAAT decreased antibiotic expenditure by reducing prolonged empiric days of therapy in these patients.

  9. Comparison of antimicrobial susceptibility among Clostridium difficile isolated from an integrated human and swine population in Texas

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clostridium difficile can be a major problem in hospitals because the bacterium primarily affects individuals with an altered gut flora, which largely occurs through prolonged antibiotic use. Proposed sources of increased community-acquired infections are food animals and retail meats. The objecti...

  10. Usefulness of Adjunctive Fecal Calprotectin and Serum Procalcitonin in Individuals Positive for Clostridium difficile Toxin Gene by PCR Assay

    PubMed Central

    Gheorghe, Romina; Eastmond, Jennifer; Miller, Mark A.

    2015-01-01

    In 54/64 subjects with nosocomial diarrhea, fecal calprotectin levels correlated with the results of stool samples tested for Clostridium difficile toxin gene by PCR. Fecal calprotectin levels can be used as an adjunctive measure to PCR to support the diagnosis of C. difficile infection. PMID:26354814

  11. Coinfection with Clostridium piliforme and Felid herpesvirus 1 in a kitten.

    PubMed

    Neto, Rachel T; Uzal, Francisco A; Hodzic, Emir; Persiani, Michele; Jolissaint, Shazia; Alcaraz, Ana; Carvallo, Francisco R

    2015-07-01

    A 1-month-old Domestic Shorthair kitten was submitted for autopsy, with a history of upper respiratory tract infection and diarrhea. This was the third kitten from the same litter that had died with similar clinical findings within a period of 1 month. Severe conjunctivitis, rhinitis, tracheitis, and bronchointerstitial pneumonia were present, together with lymphohistiocytic colitis. Respiratory lesions were caused by infection with Felid herpesvirus 1. Colonic lesions were associated with the presence of long filamentous bacteria, identified as Clostridium piliforme, in the cytoplasm of epithelial cells. Our report describes a case of concurrent C. piliforme infection (Tyzzer's disease) and feline rhinotracheitis in a kitten.

  12. A rare case intractable diarrhea secondary to Clostridium difficile and cytomegalovirus coinfection

    PubMed Central

    John, Santhosh Gheevarghese; Dominguez, Cristian; Chandiramani, Vijay; Vemulappalli, Tejo

    2013-01-01

    Patient: Male, 63 Final Diagnosis: Cytomegalo virus (CMV) infection Symptoms: Diarrhea Medication:— Clinical Procedure:— Specialty: Infectious Diseases Objective: Unusual clinical course Background: Coinfection with cytomegalovirus in a patient with Clostridium difficile persistent diarrhea and colitis can lead to a delay in diagnosis and treatment. Case Report: A 63-year-old man with squamous cell carcinoma of the lower lip, status post surgical resection and currently on chemoradiation presented with intractable diarrhea and abdominal pain. Initial workup showed Clostridium difficile diarrhea with pancolitis. Diarrhea persisted despite being on antibiotics and bacteriological cure for C. difficile. Further noninvasive work up revealed associated cytomegalovirus infection, and patient had a dramatic response to ganciclovir without any relapse. Conclusions: Physicians should be cognizant about other causes of diarrhea and colitis in immunocompromised patient when treatment for primary diagnosis fails to resolve their symptoms. PMID:24298304

  13. Manganese superoxide dismutase from human pathogen Clostridium difficile.

    PubMed

    Li, Wei; Wang, Hongfei; Lei, Cheng; Ying, Tianlei; Tan, Xiangshi

    2015-05-01

    Clostridium difficile is a human pathogen that causes severe antibiotic-associated Clostridium difficile infection (CDI). Herein the MnSODcd from C. difficile was cloned, expressed in Escherichia Coli,and characterized by X-ray crystallography, UV/Vis and EPR spectroscopy, and activity assay, et al. The crystal structure of MnSODcd (2.32 Å) reveals a manganese coordination geometry of distorted trigonal bipyramidal, with His111, His197 and Asp193 providing the equatorial ligands and with His56 and a hydroxide or water forming the axial ligands. The catalytic activity of MnSODcd (8,600 U/mg) can be effectively inhibited by 2-methoxyestradiol with an IC50 of 75 μM. The affinity investigation between 2-methoxyestradiol and MnSODcd by ITC indicated a binding constant of 8.6 μM with enthalpy changes (ΔH = -4.08 ± 0.03 kcal/mol, ΔS = 9.53 ± 0.02 cal/mol/deg). An inhibitory mechanism of MnSODcd by 2-methoxyestradiol was probed and proposed based on molecular docking models and gel filtration analysis. The 2-methoxyestradiol may bind MnSODcd to interfere with the cross-linking between the two active sites of the dimer enzyme, compromising the SOD activity. These results provide valuable insight into the rational design of MnSODcd inhibitors for potential therapeutics for CDI.

  14. The role of Clostridium difficile in the paediatric and neonatal gut - a narrative review.

    PubMed

    Lees, E A; Miyajima, F; Pirmohamed, M; Carrol, E D

    2016-07-01

    Clostridium difficile is an important nosocomial pathogen in adults. Its significance in children is less well defined, but cases of C. difficile infection (CDI) appear to be increasingly prevalent in paediatric patients. This review aims to summarize reported Clostridium difficile carriage rates across children of different age groups, appraise the relationship between CDI and factors such as method of delivery, type of infant feed, antibiotic use, and co-morbidities, and review factors affecting the gut microbiome in children and the host immune response to C. difficile. Searches of PubMed and Google Scholar using the terms 'Clostridium difficile neonates' and 'Clostridium difficile children' were completed, and reference lists of retrieved publications screened for further papers. In total, 88 papers containing relevant data were included. There was large inter-study variation in reported C. difficile carriage rates. There was an association between CDI and recent antibiotic use, and co-morbidities such as immunosuppression and inflammatory bowel disease. C. difficile was also found in stools of children with diarrhoea attributed to other pathogens (e.g. rotavirus). The role of C. difficile in the paediatric gut remains unclear; is it an innocent bystander in diarrhoeal disease caused by other organisms, or a pathogen causing subclinical to severe symptoms? Further investigation of the development of serological and local host response to C. difficile carriage may shed new light on disease mechanisms. Work is underway on defining a framework for diagnosis and management of paediatric CDI.

  15. Amplification of the 16S-23S rDNA spacer region for rapid detection of Clostridium chauvoei and Clostridium septicum.

    PubMed

    Sasaki, Y; Yamamoto, K; Amimoto, K; Kojima, A; Ogikubo, Y; Norimatsu, M; Ogata, H; Tamura, Y

    2001-12-01

    Amplification of the 16S-23S rDNA spacer region by polymerase chain reaction (PCR) was used for the rapid detection of Clostridium chauvoei and C septicum. To assess its specificity, PCR was performed with total DNA from 42 strains of clostridia and three strains of other genera. PCR products specific to C chauvoei or to C septicum were generated from homologous cultures only. Clostridium chauvoer-specific or C septicum-specific amplicons were also generated from tissues of cows experimentally infected with C chauvoei or C septicum and in DNA samples from cows clinically diagnosed as having blackleg or malignant oedema. These results suggest that a species-specific PCR may be useful for the rapid and direct detection of C chauvoei and C septicum in clinical specimens.

  16. In Vitro Activities of MCB3681 and Eight Comparators against Clostridium difficile Isolates with Known Ribotypes and Diverse Geographical Spread

    PubMed Central

    Pilling, Sally; Vernon, Jonathan; Wilcox, Mark H.

    2016-01-01

    ABSTRACT Treatments for Clostridium difficile infection remain limited, despite the introduction of fidaxomicin, and development of new agents is necessary. We determined the in vitro susceptibilities of 199 prevalent or emerging Clostridium difficile PCR ribotypes to MCB3681, a novel investigational quinolonyl-oxazolidinone, and 8 comparators (metronidazole, vancomycin, fidaxomicin, moxifloxacin, ciprofloxacin, clindamycin, tigecycline, and linezolid). MCB3681 showed good activity against C. difficile with no evidence of MCB3681 resistance in isolates showing either moxifloxacin or linezolid resistance or both moxifloxacin and linezolid resistance. PMID:27993853

  17. Adjuvants for Clostridium tetani and Clostridium diphtheriae vaccines updating.

    PubMed

    Alshanqiti, Fatimah M; Al-Masaudi, Saad B; Al-Hejin, Ahmed M; Redwan, Elrashdy M

    2017-01-01

    It's known that diphtheria and tetanus are a contagious lethal diseases over the years, they caused by pathogenic microbes corynebacterium diphtheria and Clostridium tetani, respectively. The diseases result from the production of bacterial toxin. Vaccination with bacterial toxoid vaccines adsorbed on particulates adjuvants still are the best way to prevent this epidemic diseases from spread. The particulate vaccines have been shown to be more efficient than soluble one for the induction of the immune responses. Nanoparticles can be engineered to enhance the immune responses. As well known the immune response to inactivate killed and subunit vaccine enhances by alum adjuvants. The adjuvants examined and tested after reducing its size to particle size, thus mimic size of viruses which is considered smallest units can derive the immune system. The major issue is minimizing the adjuvant particles, to gain insight of resulting immunity types and impact on immune response. The adjuvant effect of micro/nanoparticles appears to largely be a consequence of their uptake into antigen presenting cells.

  18. Traditional Chinese Medicine QPYF as Preventive Treatment for Clostridium difficile Associated Diarrhea in a Mouse Model

    PubMed Central

    Ya-Nan, Guo; Hao-Jun, Zhang; Hong-Bing, Jia; Ping, Li; Xin-Zhu, Liu

    2016-01-01

    Traditional Chinese medicine QPYF has a good effect for treating antibiotic-associated diarrhea in clinical practice. The aim of this study is to test its efficacy to prevent Clostridium difficile associated diarrhea (CDAD) in a mouse model. C57BL/6 mice were infected with Clostridium difficile VPI 10463 after exposure to antimicrobial mixture. QPYF was administered from 7 days prior to Clostridium difficile infection to 20 days after infection, and its effect was compared with no treatment and receiving placebo. The mice were monitored for 20 days and the percent survival, disease activity index, weight loss, colon histopathology, and the levels of toxins in the feces were measured. The expressions of TNF α, MCP-1, NF-κB p65, and phospho-NF-κB p65 in the colon were presented by immunohistochemistry. The survival rate of QPYF group (93.75%) was higher than that of model control group (65%). The mice treated with QPYF had a lower weight loss and disease activity index, compared to the mice with placebo. A significantly lower level of histopathology scores, toxins in the feces, and TNF α, MCP-1, NF-κB p65, and phospho-NF-κB p65 were detected for QPYF-treated mice. Traditional Chinese medicine QPYF showed a good preventive effect for CDAD in a mouse model. PMID:27999606

  19. Fatal case of hemolytic-uremic syndrome in an adult due to a rare serogroup O91 Entero hemorrhagic Escherichia coli associated with a Clostridium difficile infection. More than meets the eye.

    PubMed

    Guillard, Thomas; Limelette, Anne; Le Magrex-Debar, Elisabeth; Wynckel, Alain; Gouali, Malika; Mariani-Kurkdjian, Patricia; Guyot-Colosio, Charlotte; de Champs, Christophe

    2015-08-01

    Hemolytic-uremic syndrome due to enterohemorrhagic Escherichia coli, belonging to serogroup O91 has rarely been described. We report here a case of post-diarrheal HUS due to EHEC O91 in an elderly patient for whom diagnosis was delayed given a previously diagnosed C. difficile infection. This case highlights the usefulness of Shiga-toxin detection.

  20. Thermostable chaperonin from Clostridium thermocellum.

    PubMed

    Cross, S J; Ciruela, A; Poomputsa, K; Romaniec, M P; Freedman, R B

    1996-06-01

    Homologues of the chaperonins Cpn60 and Cpn10 have been purified from the Gram-positive cellulolytic thermophile Clostridium thermocellum. The Cpn60 protein was purified by ATP-affinity chromatography and the Cpn10 protein was purified by gel-filtration, ion-exchange and hydrophobic interaction chromatographies. The identities of the proteins were confirmed by N-terminal sequence analysis and antigenic cross-reactivity. The Cpn60 homologue is a weak, thermostable ATPase (t1/2 at 70 decrees C more than 90 min) with optimum activity (Kcat 0.07 S-1) between 60 degrees C and 70 degrees C. The ATPase activity of the authentic Cpn60 was inhibited by Escherichia coli GroES. The catalytic properties of a recombinant C. thermocellum Cpn60 purified from a GST-Cpn60 fusion protein expressed in E. coli [Ciruela (1995) Ph.D. Thesis, University of Kent] were identical with those of the authentic C. thermocellum Cpn60. Gel-filtration studies show that at room temperature the Cpn60 migrates mainly as a heptamer. Electron microscopy confirms the presence of complexes showing 7-fold rotational symmetry and also reveals a small number of particles that seem to be tetradecamers with a similar structure to E. coli GroEL complexes.

  1. Cellulolytic Activity of Clostridium acetobutylicum.

    PubMed

    Lee, S F; Forsberg, C W; Gibbins, L N

    1985-08-01

    Clostridium acetobutylicum NRRL B527 and ATCC 824 exhibited extracellular and cell-bound endoglucanase and cellobiase activities during growth in a chemically defined medium with cellobiose as the sole source of carbohydrate. For both strains, the endoglucanase was found to be mainly extracellular (70 to 90%) during growth in continuous or batch cultures with the pH maintained at 5.2, whereas the cellobiase was mainly cell associated (60 to 90%). During continuous cultivation of strain B527 with cellobiose as the limiting nutrient, maximum production of the endoglucanase and cellobiase occurred at pH values of 5.2 and 4.8, respectively. In the carbon-limited continuous cultures, strain 824 produced similar levels of endoglucanase, cellobiosidase, and cellobiase activities regardless of the carbon source used. However, in ammonium- or phosphate-limited cultures, with an excess of glucose, only 1/10 of the endoglucanase was produced, and neither cellobiosidase nor cellobiase activities were detectable. A crude extracellular enzyme preparation from strain B527 hydrolyzed carboxymethylcellulose and phosphoric acid-swollen cellulose readily and microcrystalline cellulose (A vicel) to a lesser extent. Glucose accounted for more than 90% of the reducing sugar produced by the hydrolysis of acid-swollen cellulose and Avicel. Strain B527 did not grow in medium with acid-swollen cellulose as the sole source of carbohydrate, although it grew readily on the products obtained by hydrolyzing the cellulose in vitro with a preparation of extracellular cellulase derived from the same organism.

  2. [Diarrhea associated with Clostridium difficile in the elderly: new perspectives].

    PubMed

    Pareja-Sierra, Teresa

    2014-01-01

    Infection due to Clostridium difficile is currently the main cause of hospital acquired gastrointestinal disease. Its prevalence in the elderly population is higher due to there being many associated risk factors in this age group, such as comorbidity, frequent exposure to the healthcare or residential home setting, immunosenescence, greater consumption of antibiotics, and antiacids. The diagnostic techniques have notably improved in the last few years, which could also account for an increase in its diagnosis. The new expert consensus recommendations propose stratifying the clinical situation of the patient in order to choose the treatment option. Therapeutic options have recently been included in the new Clinical Guidelines, such as flidaxomicin or fecal transplants, with encouraging results, particularly for the control of frequent recurrences.

  3. Recent Insights into Clostridium perfringens Beta-Toxin

    PubMed Central

    Nagahama, Masahiro; Ochi, Sadayuki; Oda, Masataka; Miyamoto, Kazuaki; Takehara, Masaya; Kobayashi, Keiko

    2015-01-01

    Clostridium perfringens beta-toxin is a key mediator of necrotizing enterocolitis and enterotoxemia. It is a pore-forming toxin (PFT) that exerts cytotoxic effect. Experimental investigation using piglet and rabbit intestinal loop models and a mouse infection model apparently showed that beta-toxin is the important pathogenic factor of the organisms. The toxin caused the swelling and disruption of HL-60 cells and formed a functional pore in the lipid raft microdomains of sensitive cells. These findings represent significant progress in the characterization of the toxin with knowledge on its biological features, mechanism of action and structure-function having been accumulated. Our aims here are to review the current progresses in our comprehension of the virulence of C. perfringens type C and the character, biological feature and structure-function of beta-toxin. PMID:25654787

  4. Persisting variation in testing and reporting Clostridium difficile cases

    PubMed Central

    Parekh, Sejal; Dabrowski, Hannah; Petkar, Hawabibee

    2015-01-01

    Previous evidence suggested a significant variation in the testing algorithms used across the United Kingdom for the diagnosis of Clostridium difficile infection (CDI) and new national guidelines were issued in 2012. The main aim of this paper was to explore if such variation in testing and reporting is still present, to compare the management of CDI cases, and to investigate if there is any significant variation in the antibiotic policies among different hospitals. Using London hospitals as a sample, results show that there is still a wide variation of testing methods and reporting used, making comparisons difficult. It is likely that the overall variability in practices would be greater at a national and, even more, at international level. The relationship between broad-spectrum antibiotics and C. difficile incidence and alternative approaches in antibiotic guidelines may require further studies. PMID:26877769

  5. Lipoprotein CD0873 is a novel adhesin of Clostridium difficile.

    PubMed

    Kovacs-Simon, Andrea; Leuzzi, Rosanna; Kasendra, Magdalena; Minton, Nigel; Titball, Richard W; Michell, Stephen L

    2014-07-15

    Clostridium difficile is a cause of antibiotic-associated diarrhea and colitis, a healthcare-associated intestinal disease. Colonization of the gut is a critical step in the course of infection. The C. difficile lipoprotein CD0873 was identified as a putative adhesin through a bioinformatics approach. Surface exposure of CD0873 was confirmed and a CD0873 mutant was generated. The CD0873 mutant showed a significant reduction in adherence to Caco-2 cells and wild-type bacteria preincubated with anti-CD0873 antibodies showed significantly decreased adherence to Caco-2 cells. In addition, we demonstrated that purified recombinant CD0873 protein alone associates with Caco-2 cells. This is the first definitive identification of a C. difficile adhesin, which now allows work to devise improved measures for preventing and treating disease.

  6. RNA-based control mechanisms of Clostridium difficile.

    PubMed

    Soutourina, Olga

    2017-02-16

    Clostridium difficile (CD)-associated diarrhoea is currently the most prevalent nosocomial diarrhoea worldwide. Many characteristics of CD pathogenicity remain poorly understood. Recent data strongly indicate the importance of an RNA network for the control of gene expression in CD. More than 200 regulatory RNAs have been identified by deep sequencing and targeted approaches, including Hfq-dependent trans riboregulators, cis-antisense RNAs, CRISPR RNAs, and c-di-GMP-responsive riboswitches. These regulatory RNAs are involved in the control of major processes in the CD infection cycle, for example motility, biofilm formation, adhesion, sporulation, stress response, and defence against bacteriophages. We will discuss recent advances in elucidation of the original features of RNA-based mechanisms in this important enteropathogen. This knowledge may pave the way for further discoveries in this emergent field.

  7. The Regulatory Networks That Control Clostridium difficile Toxin Synthesis

    PubMed Central

    Martin-Verstraete, Isabelle; Peltier, Johann; Dupuy, Bruno

    2016-01-01

    The pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. Among the enterotoxic clostridia, Clostridium difficile is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. The symptoms of C. difficile infection are essentially caused by the production of two exotoxins: TcdA and TcdB. Moreover, for severe forms of disease, the spectrum of diseases caused by C. difficile has also been correlated to the levels of toxins that are produced during host infection. This observation strengthened the idea that the regulation of toxin synthesis is an important part of C. difficile pathogenesis. This review summarizes our current knowledge about the regulators and sigma factors that have been reported to control toxin gene expression in response to several environmental signals and stresses, including the availability of certain carbon sources and amino acids, or to signaling molecules, such as the autoinducing peptides of quorum sensing systems. The overlapping regulation of key metabolic pathways and toxin synthesis strongly suggests that toxin production is a complex response that is triggered by bacteria in response to particular states of nutrient availability during infection. PMID:27187475

  8. ISOLATION OF CLOSTRIDIUM TETANI FROM SOIL.

    PubMed

    SANADA, I; NISHIDA, S

    1965-03-01

    Sanada, Ichiro (Kanazawa University, Kanazawa, Japan), and Shoki Nishida. Isolation of Clostridium tetani from soil. J. Bacteriol. 89:626-629. 1965.-The higher the temperatures applied to soil specimens, the weaker the toxigenicity of Clostridium tetani strains isolated from them. The glucose- and maltose-fermenting ability of these isolates was inversely proportional to their toxigenicity. The biological properties of atoxic strains were indistinguishable from those of C. tetanomorphum. Since a considerable number of toxic strains fermented glucose and maltose, these criteria are of doubtful value for differentiating C. tetani from C. tetanomorphum.

  9. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

    PubMed

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger

    2016-04-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins.

  10. Identification of Clostridium botulinum, Clostridium argentinense, and related organisms by cellular fatty acid analysis.