Treatment and prevention of antibiotic associated diarrhea
Introduction
Antibiotic associated diarrhea (AAD) is a common complication of antibiotic therapy, occurring in approximately 5 to 25% of patients receiving antibiotics [1], [2], [3], [4]. The incidence of AAD varies with the class of antibiotic used and with risk factors in patients treated: AAD has been observed in a wide variety of patient populations including orthopedic, obstetric/gynecologic, intensive-care-unit patients and even ambulatory patients [5]. This type of diarrhea has been recognized since 1950 with the development of broad spectrum antibiotics; this complication was initially considered as mild, until the emergence of pseudomembranous colitis (PMC) occurring in patients treated with clindamycin. Clostridium difficile has been identified as the agent of PMC in 1978 [1]. Since then, research on epidemiology and pathogenesis of this severe infection has been widely carried out and the mechanisms of AAD have been better understood. The antibiotic treatment disrupts the equilibrium of the normal gut flora. The pathogenesis of AAD includes alteration of the numerous physiological functions of the normal microflora which contributes normally to fermentation processes and to the phenomenon termed ‘resistance to colonization’ [6]. Disruption of the ecologic equilibrium of the normal intestinal flora may result in diarrhea associated with alteration of fermentation processes, reduction of short chain fatty acids production and emergence of pathogenic organisms such as C. difficile. The objectives of this review comprise, after a summary of pathogenic mechanisms and epidemiologic factors of AAD, a review of the current methods of treatment and prevention of AAD, including an analysis of the place and experience of bio therapeutic agents.
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Pathogenesis of AAD
During the last ten years pathogenic mechanisms of AAD have given rise to experimental studies in animal models, and in in vivo and ex vivo studies (ileal loops from rats and CACO2 enterocyte cultures). This resulted in a better understanding of the mechanisms of the antibiotic mode of action on the enteric flora, and established the basis of appropriate treatment and prevention of AAD and of PMC. During most antibiotic therapy courses, alteration of the normal flora of the bowel leads to loss
Clinical presentation
A wide spectrum of AAD clinical presentations is observed. Uncomplicated diarrhoea has the highest incidence and can occur early during antibiotic therapy (62% of cases) or with a delayed onset (2–6 weeks after the end of the treatment). Diarrhea can be associated with colitis characterized by fever, abdominal pain, hypoalbuminemia and leukocytosis [2]. Many intermediate presentations have been described; from simple diarrhea and fulminant PMC, which expresses as watery diarrhea (90–95%), fever
Epidemiology and risk factors
Two main types of predisposing factors have been recognized in AAD: the antibiotic class and the host factors (age and underlying pathologies) (Table 1). Other environmental circumstances may also contribute to the spread of PMC.
Mild or moderate cases of AAD
Treatments of AAD comprise conventional measures such as rehydration and discontinuation of the inciting agent or replacement of the latter if necessary by a more appropriate antibiotic, such as quinolones, metronidazole, co-trimoxazole, parenteral aminoglycosides or tetracyclines. These antibiotics have less risk of induction of diarrhea.
Antibiotic therapy in severe AAD: treatment of PMC
Severe cases of AAD particularly those related to C. difficile require a suitably adapted oral antibiotic therapy. The recommended antibacterial agents are
Discussion
Several living microorganisms have been used in the treatment and prevention of antibiotic-associated-diarrhea. They are bacteria such as L. casei GG, Bifidobacterium bifidum or yeasts such as S. boulardii. The mode of action of S. boulardii against C. difficile has been carefully evaluated in experimental studies in animal models [24]. It was demonstrated that S. boulardii serine protease inhibits the pathogenic effects of toxins A and B in human colonic mucosa. In C. difficile induced
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