In The News:
Report of New Antibiotic Specific for C. Difficile

     



       Clostridium difficile, (C-diff or CDF), is surpassing the widely feared Methicillin-resistant Staphylococcus aureus, commonly known as MRSA, in the number of cases reported, according to the national Centers for Disease Control. C-diff is a bacterial illness that can cause symptoms ranging from severe diarrhea to life-threatening inflammation of the colon. The number one cause of the infection is antibiotic use, but it can also be spread from person to person. Illness from C. difficile most commonly affects older adults in hospitals or in long term care facilities.

      The best way to prevent the infection is careful hand washing and good sanitation, plus the cautionary use of antibiotics. The intestinal tract has millions of good bacteria that keep diseases like C-diff in check. However, when an antibiotic is taken, the amount of good bacteria is reduced. If the antibiotic isn't strong enough to keep the C-diff in check, C-diff overpopulates inside the colon and causes illness. C-diff can also survive for weeks or months on hard surfaces including bed rails, call buttons, faucets, privacy curtains, even nurses uniforms. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. Relapses of C. difficile diarrhea have been reported in approximately 20% of cases.

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      C. difficile was first isolated in 1935, when Hall and O'Toole first described its toxigenic characteristics (1). Toxin-producing strains of C. difficile produce two toxins: toxin A, an enterotoxin, and toxin B, a cytotoxin. It is the production of these toxins by C. difficile in the gut which ultimately leads to the disease. As a result, much effort has been made to develop detection methods for these toxins and to learn how they act.

     The most common clinical diagnostic procedures for C. difficile antibiotic-associated colitis are cell culture cytotoxicity and latex agglutination assays.  The cell culture cytotoxicity assay (CTA) detects the presence of toxin B by the observation of cytopathic effect on cell culture.  The assay is very sensitive (50pg/ml toxin B) (5), but requires a minimum of two days to complete.  Latex agglutination is a common stool screening method for detection of proteins associated with C. difficile, though cross- reactivity and detection of nontoxigenic C. difficile has been reported (6-12). C. difficile EIA methods have been researched by a number of investigators, with a reported sensitivity to either toxin A or toxin B of 1-10 ng/ml.

     Widespread use of antibiotics, coupled with the emergence of the hypervirulent (B1/NAP1/027) strain of C-diff, has altered the epidemiology of CDF. Even with effective treatment regimens, there is an escalation in severity, treatment failures, and recurrences. For patients with Clostridium difficile infection, the addition of monoclonal antibodies against C. difficile to antibiotic treatment reduces the risk of recurrent infection (7% trial group vs. 25% control placebo group).  

     A new type of antibiotic that is effective against the hospital-acquired superbug C. difficile has just been reported by a group from University College Cork, Teagasc (the Irish Agriculture and Food Development Authority) and the University of Alberta (14).  These authors screened more than 30,000 bacteria isolated from the human gut and discovered that the new antibiotic consists of two distinct peptides that act together to kill a wide range of clinical C. difficile. The specificity of thuricin towards Clostridium difficile is a key advantage that it has over other antibiotic treatments; that tests have shown it doesn't have an impact on other bacteria in the gut (14).

Picture at top of article: C. difficile colonies on a blood agar plate
(Lyras D et al. Nature 2009;458:1176-1179).

References:

 

1.    Hall, I.C. and E. O'Toole, Intestinal flora in newborn infants.  A.J. Dis. Child.  (1935)  49:390:402. 

2.    Bartlett, J.G., et al.,  N. Eng. J. Med. (1978)  298:531- 534. 

3.    Bartlett, J.G., et al., Rev. Infect. Dis. (1979)  1:370-378. 

4.    Borriello, S.P., et al., J. Clin Path.  (1987)  40: 573-580. 

5.    Lyerly, D.M., et al.,  Clostridium difficile: Its disease and toxins.  Clinical Microbiology Review.  (1988) 1:1-18. 

6.    Kelly, M.T., et al., Journal of Clinical Microbiology, (1987) 25:1244-1247.

7.    Oadri, S.M. et al., High incidence of false positives by a latex agglutination test for the diagnosis of Clostridium difficile- associated colitis in compromised patients.

8.    Bennett, R.G., et al., Journal of Clinical Microbiology (1989) 27: 889-893. 

9.    Lyerly, D.M., and Wilkins, T.D.,  Commercial latex test for Clostridium difficile toxin A does not detect Toxin A. Journal of Clinical Microbiology (1986)  23: 662-623

10.   Lyerly, D. M., et al., Journal of Clinical Microbiology (1988) 26: 397-400. 

11.   Miles, B.L., et al., Journal of Clinical Microbiology (1988) 26: 2452-2455. 

12.   Woods, G.L. and Iwen, P.C., Comparison of a Dot Immunobinding Assay, Latex Agglutination, and Cytotoxin Assay For laboratory Diagnosis of Clostridium difficile-Associated Diarrhea.  Journal of Clinical Microbiology. (1990) 28: 855-857.

13.   Lowry, I. et al., Treatment with Monoclonal Antibodies against Clostridium difficile Toxins, N Engl J Med. (2010) 362:197-205.

14.   Rea, M.C. et al., Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon, PNAS (2010) 10.1073/pnas.1001224107