1887

Abstract

Purpose. This study aimed to describe the correlation between Clostridium difficile spore and toxin levels within the human host. In addition, we assessed whether overgrowth of Candida albicans modified this association.

Methodology. We measured toxin, spore and Candida albicans levels among 200 successively collected stool samples that tested positive for C. difficile, and PCR ribotyped these C. difficile isolates. Analysis of variance and linear regression were used to test the association between spore and toxin levels. Kruskal–Wallis tests and t-tests were used to compare the association between spore or toxin levels and host, specimen, or pathogen characteristics.

Results. C. difficile toxin and spore levels were positively associated (P<0.001); this association did not vary significantly with C. albicans overgrowth [≥5 logs of C. albicans colony-forming units (c.f.u.) g]. However, ribotypes 027 and 078–126 were significantly associated with higher levels of toxin and spores, and C. albicans overgrowth.

Conclusion. The strong positive association observed between in vivo levels of C. difficile toxin and spores suggests that patients with more severe C. difficile infections may have increased spore production, enhancing C. difficile transmission. Although, on average, spore levels were higher in toxin-positive samples than in toxin-negative/PCR-positive samples, spores were found in almost all toxin-negative samples. The ubiquity of spore production among toxin-negative and formed stool samples emphasizes the importance of following infection prevention and control measures for all C. difficile-positive patients during their entire hospital stay.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000719
2018-03-13
2019-10-15
Loading full text...

Full text loading...

/deliver/fulltext/jmm/67/5/631.html?itemId=/content/journal/jmm/10.1099/jmm.0.000719&mimeType=html&fmt=ahah

References

  1. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014; 370: 1198– 1208 [CrossRef] [PubMed]
    [Google Scholar]
  2. Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015; 372: 825– 834 [CrossRef] [PubMed]
    [Google Scholar]
  3. CDC 2015; Healthcare-associated infections (HAIs), Clostridium difficile infection. Available from www.cdc.gov/HAI/organisms/cdiff/Cdiff_infect.html
  4. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis 2012; 55: S88– S92 [CrossRef] [PubMed]
    [Google Scholar]
  5. Martin JS, Monaghan TM, Wilcox MH. Clostridium difficile infection: advances in epidemiology, diagnosis and transmission. Nature Rev Gastroenterol Hepatol 2016; 13: [Crossref]
    [Google Scholar]
  6. Akerlund T, Svenungsson B, Lagergren A, Burman LG. Correlation of disease severity with fecal toxin levels in patients with Clostridium difficile-associated diarrhea and distribution of PCR ribotypes and toxin yields in vitro of corresponding isolates. J Clin Microbiol 2006; 44: 353– 358 [CrossRef] [PubMed]
    [Google Scholar]
  7. Carlson PE, Walk ST, Bourgis AE, Liu MW, Kopliku F et al. The relationship between phenotype, ribotype, and clinical disease in human Clostridium difficile isolates. Anaerobe 2013; 24: 109– 116 [CrossRef] [PubMed]
    [Google Scholar]
  8. Underwood S, Guan S, Vijayasubhash V, Baines SD, Graham L et al. Characterization of the sporulation initiation pathway of Clostridium difficile and its role in toxin production. J Bacteriol 2009; 191: 7296– 7305 [CrossRef] [PubMed]
    [Google Scholar]
  9. Koenigsknecht MJ, Theriot CM, Bergin IL, Schumacher CA, Schloss PD et al. Dynamics and establishment of Clostridium difficile infection in the murine gastrointestinal tract. Infect Immun 2015; 83: 934– 941 [CrossRef] [PubMed]
    [Google Scholar]
  10. Mackin KE, Carter GP, Howarth P, Rood JI, Lyras D. Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile. PLoS One 2013; 8: e79666 [CrossRef] [PubMed]
    [Google Scholar]
  11. Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med 2000; 342: 390– 397 [CrossRef] [PubMed]
    [Google Scholar]
  12. van Leeuwen PT, van der Peet JM, Bikker FJ, Hoogenkamp MA, Oliveira Paiva AM et al. Interspecies interactions between Clostridium difficile and Candida albicans. mSphere 2016; 1: e00187-16 [CrossRef] [PubMed]
    [Google Scholar]
  13. Raponi G, Visconti V, Brunetti G, Ghezzi MC. Clostridium difficile infection and Candida colonization of the gut: is there a correlation?. Clin Infect Dis 2014; 59: 1648– 1649 [CrossRef] [PubMed]
    [Google Scholar]
  14. Manian FA, Bryant A. Does Candida species overgrowth protect against Clostridium difficile infection?. Clin Infect Dis 2013; 56: 464– 465 [CrossRef] [PubMed]
    [Google Scholar]
  15. Zimmaro Bliss D, Larson SJ, Burr JK, Savik K. Reliability of a stool consistency classification system. J Wound Ostomy Continence Nurs 2001; 28: 305– 313 [PubMed]
    [Google Scholar]
  16. Techlab 2008; C. difficile Tox A/B II Insert Blacksburg, VA 24060 www.techlab.com/wp-content/uploads/2013/06/t5015insert_rev_0308.pdf
  17. Rosenthal M, Aiello A, Larson E, Chenoweth C, Foxman B. Healthcare workers' hand microbiome may mediate carriage of hospital pathogens. Pathogens 2013; 3: 1– 13 [CrossRef] [PubMed]
    [Google Scholar]
  18. Walk ST, Micic D, Jain R, Lo ES, Trivedi I et al. Clostridium difficile ribotype does not predict severe infection. Clin Infect Dis 2012; 55: 1661– 1668 [CrossRef] [PubMed]
    [Google Scholar]
  19. Goorhuis A, Bakker D, Corver J, Debast SB, Harmanus C et al. Emergence of Clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin Infect Dis 2008; 47: 1162– 1170 [CrossRef] [PubMed]
    [Google Scholar]
  20. Merrigan M, Venugopal A, Mallozzi M, Roxas B, Viswanathan VK et al. Human hypervirulent Clostridium difficile strains exhibit increased sporulation as well as robust toxin production. J Bacteriol 2010; 192: 4904– 4911 [CrossRef] [PubMed]
    [Google Scholar]
  21. Baker I, Leeming JP, Reynolds R, Ibrahim I, Darley E. Clinical relevance of a positive molecular test in the diagnosis of Clostridium difficile infection. J Hosp Infect 2013; 84: 311– 315 [CrossRef] [PubMed]
    [Google Scholar]
  22. Heeg D, Burns DA, Cartman ST, Minton NP. Spores of Clostridium difficile clinical isolates display a diverse germination response to bile salts. PLoS One 2012; 7: e32381 [CrossRef] [PubMed]
    [Google Scholar]
  23. Burns DA, Heeg D, Cartman ST, Minton NP. Reconsidering the sporulation characteristics of hypervirulent Clostridium difficile BI/NAP1/027. PLoS One 2011; 6: e24894 [CrossRef] [PubMed]
    [Google Scholar]
  24. Burns DA, Heap JT, Minton NP. The diverse sporulation characteristics of Clostridium difficile clinical isolates are not associated with type. Anaerobe 2010; 16: 618– 622 [CrossRef] [PubMed]
    [Google Scholar]
  25. Saujet L, Monot M, Dupuy B, Soutourina O, Martin-Verstraete I. The key sigma factor of transition phase, SigH, controls sporulation, metabolism, and virulence factor expression in Clostridium difficile. J Bacteriol 2011; 193: 3186– 3196 [CrossRef] [PubMed]
    [Google Scholar]
  26. Bouillaut L, Dubois T, Sonenshein AL, Dupuy B. Integration of metabolism and virulence in Clostridium difficile. Res Microbiol 2015; 166: 375– 383 [CrossRef] [PubMed]
    [Google Scholar]
  27. Paredes-Sabja D, Sarker MR. Clostridium perfringens sporulation and its relevance to pathogenesis. Future Microbiol 2009; 4: 519– 525 [CrossRef] [PubMed]
    [Google Scholar]
  28. Robinson CD, Auchtung JM, Collins J, Britton RA. Epidemic Clostridium difficile strains demonstrate increased competitive fitness compared to nonepidemic isolates. Infect Immun 2014; 82: 2815– 2825 [CrossRef] [PubMed]
    [Google Scholar]
  29. Rao K, Micic D, Natarajan M, Winters S, Kiel MJ et al. Clostridium difficile ribotype 027: relationship to age, detectability of toxins A or B in stool with rapid testing, severe infection, and mortality. Clin Infect Dis 2015; 61: 233– 241 [CrossRef] [PubMed]
    [Google Scholar]
  30. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010; 31: 431– 455 [CrossRef] [PubMed]
    [Google Scholar]
  31. Lawley TD, Clare S, Walker AW, Goulding D, Stabler RA et al. Antibiotic treatment of Clostridium difficile carrier mice triggers a supershedder state, spore-mediated transmission, and severe disease in immunocompromised hosts. Infect Immun 2009; 77: 3661– 3669 [CrossRef] [PubMed]
    [Google Scholar]
  32. Johnson S et al. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. Ann Intern Med 1992; 117: 297– 302 [CrossRef]
    [Google Scholar]
  33. Gilligan PH. Contemporary approaches for the laboratory diagnosis of Clostridium difficile infections. Semin Colon Rectal Surg 2014; 25: 137– 142 [CrossRef]
    [Google Scholar]
  34. Polage CR, Chin DL, Leslie JL, Tang J, Cohen SH et al. Outcomes in patients tested for Clostridium difficile toxins. Diagn Microbiol Infect Dis 2012; 74: 369– 373 [CrossRef] [PubMed]
    [Google Scholar]
  35. Polage CR, Gyorke CE, Kennedy MA, Leslie JL, Chin DL et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med 2015; 175: 1792– 1801 [CrossRef] [PubMed]
    [Google Scholar]
  36. Nerandzic MM, Mullane K, Miller MA, Babakhani F, Donskey CJ. Reduced acquisition and overgrowth of vancomycin-resistant enterococci and Candida species in patients treated with fidaxomicin versus vancomycin for Clostridium difficile infection. Clin Infect Dis 2012; 55: S121– S126 [CrossRef] [PubMed]
    [Google Scholar]
  37. Edwards AN, Karim ST, Pascual RA, Jowhar LM, Anderson SE et al. Chemical and stress resistances of Clostridium difficile spores and vegetative cells. Front Microbiol 2016; 7: 1698 [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000719
Loading
/content/journal/jmm/10.1099/jmm.0.000719
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error