Clostridium difficile and the disease it causes.
Clostridium difficile is a spore-forming, toxin-producing, anaerobic bacterium abundant in soils and water. Frequent and early colonization of the human intestinal flora is common and often asymptomatic. Antimicrobials given commonly disrupt the intestinal microflora and through proliferation in colon and production of toxin A and B it precipitates C. difficile infection (CDI). The enterocytic detachment and bowel inflammation provoke C. difficile-associated diarrhoea (CDAD) sometimes developing into severe pseudomembranous colitis (PMC) and paralytic ileus. Infection is acquired from an endogenous source or from spores in the environment, most easily facilitated during hospital stay. In the elderly, comorbidity, hospitalization and antimicrobial treatment present as major risk factors and the slow recolonization of the normal flora likely responsible for single or multiple recurrences of CDI (25-50%) post therapy. The key procedure for diagnosis is toxin detection from stool specimens and sometimes in combination with culture to increase sensitivity. In mild cases stopping the offending antimicrobial will lead to resolution (25%) but standard therapy still consist of either oral metronidazole or vancomycin. Alternative agents are presently being developed and fidaxomicin, as well as nitrothiazolide are promising. Furthermore, host factors like low antitoxin A levels in serum relates to increased risk of recurrence and small numbers of patients have received immunoglobulin with good results. An immunogenic toxoid vaccine has been developed and human colostrum rich in specific secretory Ig A also support the future use of immunotherapy. Today we experience a tenfold increase of CDI incidence in the western world and both epidemics and therapeutic failure of metronidazole is contributing to morbidity and mortality. The current epidemic of the C. difficile strain NAP1/027 emerging in 2002 in Canada and the USA has now spread to most parts of Europe and virulence factors like high toxin production and sporulation challenge the therapeutic situation and cause great concern among infection control workers. Excessive use of modern fluoroquinolones is thought to play an important role in facilitating this epidemic since NAP1/027 was shown to have acquired moxifloxacin resistance compared to historical strains of the same genotype. Both the current epidemic like this and other local outbreaks from resistant or virulent strains warrant culture to be routinely performed enabling susceptibility testing and typing of the pathogen. Genotyping is most commonly done today by pulse-field gel electrophoresis (PFGE) or PCR ribotyping but multilocus variable-number tandem-repeat analysis (MLVA) seems promising. Epidemiological surveillance using all these tools will help us to better understand the global spread of C. difficile.
Norén
Torbjörn
T
Department of Infectious Diseases, Orebro University Hospital and Orebro University, Orebro, Sweden. torbjorn.noren@orebroll.se
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism; D016360:Clostridioides difficile / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003015:Clostridium Infections / Q000188:drug therapy / Q000382:microbiology / Q000628:therapy; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D004768:Enterotoxins / Q000378:metabolism; D006801:Humans
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile