C. difficile infection

The incidence of community-associated C. difficile infection (defined as occurring in patients not hospitalized in the year prior to diagnosis) is increasing.36 In addition to antibiotic use, community-associated C. difficile cases are associated with the use of gastric acid suppressive agents (e.g., proton pump inhibitors and H2-receptor antagonists). 

Leukocytosis, hypoalbuminemia, and fecal leukocytes are nonspecific but suggestive of C. difficile infection. 

Progress in defining new treatments for C. difficile infection has been hindered by the heterogeneous nature of hospital-acquired diarrhea, and in particular by whether colitis and/or pseudomembranous colitis is present in individual cases. Study groups have usually been poorly defined in this context, and given the spontaneous resolution of symptoms in a proportion of cases the true efficacy of treatment approaches often remains uncertain. Enthusiasm to explore new treatment possibilities for C. difficile has been largely fuelled by the apparently high relapse rate of conventional (metronidazole or vancomycin) treatment [138],... 

There is a consensus amongst published recommendations for the management of C. difficile infection [19-21], The most important first step in the treatment is cessation of the precipitating agent, most commonly antibiotics, if this is deemed to be medically appropriate. In mild disease, this is often sufficient for full recovery. In more... 

A randomized open trial, performed in patients with C. difficile pseudomembranous colitis, compared rifaximin (200 mg 3 times daily) to vancomycin (500 mg 2 times daily) and found the two drugs similarly effective [141]. The clearance of bacterial toxins was, however, more rapid with vancomycin. Further large double-blind clinical studies are needed to better define the role of rifaximin in the treatment of C. difficile infection. 

Dickinson et al. [27], in 1985, published a double-blind controlled trial on the use of oral vancomycin as an adjunctive therapy in acute exacerbations of idiopathic colitis. No significant difference was found between the two treatment groups with only a trend in favor of a superior efficacy of vancomycin. It is important to underline that 7 of the 40 patients enrolled had colonic CD and that none of them had C. difficile infection that could explain the action of vancomycin. Subsequently, intravenous metronidazole, in addition to steroids, was effective similar to placebo in inducing remission [28],... 

B Antibiotic-associated diarrhea due to C difficile can occur with any antibiotic, but particularly with clindamycin. With the administration of antibiotics, normal Gl flora is inhibited, which allows C. difficile to overgrow. Metronidazole is the treatment of choice for C. difficile infections. Although oral vancomycin also has activity against C. difficile, it is typically used as second-line treatment... 

C. difficile infection may cause a spectrmn of disease from mild antibiotic-associated diarrhea to pseudomembranous entercohtis. In cohtis without pseudomenbrane formation, patients present with malaise, abdominal pain, nausea, anorexia, watery diarrhea, low-grade fever, and leukocytosis. PMC is characterized by more severe illness, with severe abdominal pain, perfuse diarrhea, high fever, marked leukocytosis, and classic pseudomembrane formation evident with sigmoidoscopic examination. Symptoms can start a few days after the start of antibiotic therapy or several weeks after antibiotics have been discontinued. The onset of illness is often abrupt. 

C. difficile infection may follow, causing pseudomembranous colitis... 

C. difficile is also the cause of emerging nosocomial infections that result in abundant morbidity and mortality worldwide. The glycans Polysaccharide I (PSI) and Polysaccharide II (PSII) were recently identified on the bacterial surface, and are promising vaccine candidates to prevent C. difficile infections. PSI 41 and PSII 42 have a phosphorylated hexa- and pentasaccharide repeating unit, respectively (Scheme 14). 

In an elderly woman, who had already had a maculopapular rash after intravenous vancomycin in combination with piperacillin/tazobactam and metronidazole, a pruritic rash developed after exposure to oral vancomycin for C. difficile infection [97 ]. 

A single case report of cutaneous vasculitis in association with oral vancomycin use for the treatment of C. difficile infection in an 86-year-old man [84 ]. One report of a localised bullous eruption resembling linear IgA bullous dermatosis was documented following extravasation of vancomycin [85 ]. 

High molecular weight sodium salt of poly(styrene sulfonic acid) derivative was selected as the clinical candidate for treating C. difficile infection. This compound, under the generic name of Tolevamer, has been successful in both phase I and phase II human clinical trials. 

Lipiarmycin is a narrow-spectrum macrocyclic antibiotic discovered at Lepetit (Coronelli et al. 1975) which has been recently approved as an oral agent against C. difficile infections under the name of fidaxomicin. 

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