Clostridium difficile: new and old treatment options

Abstract number: S234

Bouza E.

A high percentage of C. difficile strains are resistant to antimicrobials such as cephalosporins, clindamycin, macrolides, aminoglycosides, tetracyclines, cotrimoxazole, ertapenem, imipenem, and chloramphenicol. On the contrary, the microorganism shows "in vitro" susceptibility to ampicillin, meropenem, metronidazole, penicillin, piperacillin, teicoplanin and vancomycin. Until recently, the activity of both first-line drugs for the therapy of CDAD, vancomycin and metronidazole, was not argued and susceptibility testing was not even routinely recommended. At present, metronidazole resistance, uncommon but present, is an heterogeneous resistance with clinical consequences that have yet to be elucidated.

Metronidazole and vancomycin remain the drugs of choice for the treatment of CDAD but, both have important limitations and adverse effects. Metronidazole has been linked to a high rate of non-responses and relapses mainly in patients infected with the 027 epidemic strain. Patients with severe or recurrent disease require Vancomycin in higher doses and during longer periods of time.

New antimicrobial agents active "in vitro" against C. difficile include: teicoplanin, ramoplanin, daptomycin, telavancin, linezolid, nitazoxanide, tiacumicins B and C and rifaximin. Their role as alternative antimicrobial agents against C. difficile is still being defined.

Nitazoxanide is an antihelminthic and antiprotozoal agent that is at least as effective as metronidazole in treating C. difficile colitis.

Intravenous immunoglobulins have been used in patients with severe disease or multiple recurrences but there is not any prospective and comparative study to establish their role in the treatment of this disease.

A hyperimmune bovine gammaglobulin that neutralizes the effects of C. difficile toxins is under development

Data regarding the role of oligofructose in the prevention of relapses of CDAD are still conflicting. Tolevamer (GT160–246) is a polyanionic polymer chain with a high molecular weight that has clinical cure rates similar to oral Vancomycin when administered to humans at 6 g/day but failed to achieve non-inferiority when used at 9g/day in a recent clinical trial.

Local bacteriotherapy is the name for the lavage of the lumen of the colon or for the administration of enemas prepared with fresh faeces from healthy volunteers. Reports are almost always of isolated cases or short series and there is no relevant study that allows for giving any recommendations on this method, with obvious drawbacks. This therapy has the additional risk of the transmission of other infectious agents.

Exchange resins such as colestipol or colestyramine that are able to bind to C. difficile toxin, may also bind to antimicrobials used to treat CDAD; therefore, their clinical use is not recommended..

Surgery is a last resource for the treatment of unmanageable CDAD with toxic megacolon or colon perforations.

Finally, the perspective for a C. difficile vaccine look very promising at the present time.