Clostridium difficile antibiotic-associated

Clostridium difficile Antibiotic-associated colitis Metronidazole Vancomycin... 

Important members of this toxin family are Clostridium difficile toxins A and B, which are implicated in antibiotics-associated diarrhea and pseudomembranous colitis. The large clostridial cytotoxins are single-chain toxins with molecular masses of 250-308 kDa. The enzyme domain is located at the N terminus. The toxins are taken up from an acidic endosomal compartment. They glucosylate RhoA at Thr37 also, Rac and Cdc42 are substrates. Other members of this toxin family such as Clostridium sordellii lethal toxin possess a different substrate specificity and modify Rac but not Rho. In addition, Ras subfamily proteins (e.g., Ras, Ral, and Rap) are modified. As for C3, they are widely used as tools to study Rho functions [2] [4]. 

Nosocomial Clostridium difficile-associated diarrhea (CDAD) is almost always associated with antimicrobial use therefore, we should avoid unnecessary and inappropriate antibiotic therapy. Almost all antibiotics except aminoglycosides have been associated with CDAD. 

Antibiotic-associated diarrhea Pseudomembranous colitis Clostridium difficile Rifaximin Clostridium difficile-assodated diarrhea... 

Diarrhea is a well-known complication of antibiotic therapy. Rates of antibiotic-associated diarrhea (AAD) vary from 5 to 25%. Some antibiotics are more likely to cause diarrhea than others, specifically, those that are broad spectrum and those that target anaerobic flora. This paper reviews the effects of antibiotics on the fecal flora as well as host factors which contribute to AAD. Clinical features and treatment of AAD are also described. Prevention of AAD rests on wise antibiotic policies, the use of probiotics and prevention of acquisition in the hospital setting. Data from clinical trials suggest that poorly absorbed antimicrobials might have a decreased risk of causing AAD and Clostridium difficile-associated disease, as concluded from studies of antibiotics used for preoperative bowel decontamination and poorly absorbed antibiotics used for traveler s diarrhea. Controlled trials would prove this but are not yet available. Probiotics may be a good adjunct to poorly absorbed antibiotics to minimize the risk of diarrhea associated with antibiotics. 

Rnobel H, Salvado M, Plass E, Orfila A, Llo-rach I, Diez A Nosocomial epidemic outbreak of diarrhea from Clostridium difficile. Comparative study of diarrhea associated with the use of antibiotics (in Spanish). Med Clin (Bare) 1994 102 165-168. 

Crabtree TD, Pelletier SJ, Gleason TG, Pruett TL, Sawyer RG Clinical characteristics and antibiotic utilization in surgical patients with Clostridium difficile-associated diarrhea. Am Surg 1999 65 507-511. 

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of Clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of antibiotic-associated colitis. ... 

Vancomycin is not absorbed after oral administration and must be given intravenously. Oral administrations are used for intraluminal gastrointestinal infections such as antibiotic-associated pseudomembranous colitis produced by Clostridium difficile. Vancomycin is widely distributed in the body but does not cross the blood brain barrier and does not penetrate into bone. It is excreted mainly via the urine, resulting in accumulation in patients with renal insufficiency. Its elimination half-life is 4-11 hours but can increase to 6-10 days in renal failure. 

The spectrum of gastrointestinal tract infections (GTI) cover a wide spectrum from asymptomatic Helicobacter pylori gastritis to self-limiting viral gastroenteritis to food poisoning to bacterial enterocolitis to antibiotic-associated Clostridium difficile colitis to typhoid fever with sepsis and multi-organ failure. 

Vancomycin is poorly absorbed from the intestinal tract and is administered orally only for the treatment of antibiotic-associated enterocolitis caused by Clostridium difficile. Parenteral doses must be administered intravenously. A 1 hour intravenous infusion of 1 g produces blood levels of 15-30 jig/mL for 1-2 hours. The drug is widely distributed in the body. Cerebrospinal fluid levels 7-30% of simultaneous serum concentrations are achieved if there is meningeal inflammation. Ninety percent of the drug is excreted by glomerular filtration. In the presence of renal insufficiency, striking accumulation may occur (Table 43-2). In functionally anephric patients, the... 

Oral vancomycin, 0.125-0.25 g every 6 hours, is used to treat antibiotic-associated enterocolitis caused by Clostridium difficile. However, because of the emergence of vancomycin-resistant enterococci and the strong selective pressure of oral vancomycin for these resistant organisms, metronidazole is strongly preferred as initial therapy and vancomycin should be reserved for treatment of refractory cases. 

Clostridium difficile is a commensal Gram-positive anaerobic bacterium of the human intestine, found in about 2-5% of the population. C. difficile is the most serious cause of antibiotic-associated diarrhoea and can lead to pseudomembranous colitis, a severe infection of the colon, often resulting from eradication of the normal gut flora by antibiotics. Discontinuation of causative antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. The bacterium produces several known toxins, including enterotoxin (toxin A) and cytotoxin (toxin B), both of which are responsible for the diarrhoea and inflammation seen in infected patients another toxin, binary toxin, has also been described. 

Adverse effects. Ampicillin may cause diarrhoea but the incidence (12%) is less with amoxicillin. Ampicillin and amoxicillin are the commonest antibiotics to be associated with Clostridium difficile diarrhoea, although this is related to the frequency... 

The most serious adverse effect is antibiotic-associated (pseudomembranous) colitis (see p. 210) usually due to opportunistic infection of the bowel with Clostridium difficile which produces an entero-toxin clindamycin should be stopped if any diarrhoea occurs. 

Antibiotic-associated pseudomembraneous colitis (caused by Clostridium difficile)... 

Antimicrobials are the commonest drugs that cause diarrhoea, probably due to alteration of bowel flora. It may range from a mild inconvenience to life-threatening antibiotic-associated (pseudomembranous colitis), due to colonisation of the bowel with Clostridium difficile. The condition particularly affects... 

Clostridium difficile has been isolated in 11-33% of patients with antibiotic-associated diarrhea, 60-75% of patients with antibiotic-associated colitis, and 96-100% of patients with pseudomembranous colitis (117,134,135). However, about 2% of the adult population are asymptomatic carriers (127). Primary symptomless colonization with C. difficile reduces the risk of antibiotic-associated diarrhea (136). Infants up to 2 years seem to be refractory to pseudomembranous colitis, although a high percentage may be carriers of C. difficile (135,137). The reasons for this are unknown. It has been speculated that infants lack receptors for the toxin. 

Aronsson B, Mollby R, Nord CE. Clostridium difficile and antibiotic associated diarrhoea in Sweden. Scand J Infect Dis Suppl 1982 35 53-8. 

In a retrospective cohort study of patients hospitalized in a Canadian teaching hospital during January 2003 to June 2004 there were 7421 episodes of care in 5619 patients, who were observed until they developed Clostridium difficile-s s,ocmt d diarrhea, or died, or for 60 days after discharge (107). Fluoroquinolones were the antibiotics that were most strongly associated with Clostridium di aJe-associated diarrhea (adjusted hazard ratio = 3.44 95% Cl = 2.65, 4.47). Almost one-quarter of all in-patients received quinolones, for which the population-attributable fraction of Clostridium difficile-as,s,odsAed diarrhea was 36%. All three generations of cephalosporins, macrolides, clindamycin, and intravenous beta-lactam/beta-lactamase inhibitors were intermediate-risk antibiotics, with similar hazard ratios (1.56-1.89). 

Gorenek L, Dizer U, Besirbellioglu B, Eyigun CP, Hacibektasoglu A, Van Thiel DH. The diagnosis and treatment of Clostridium difficile in antibiotic-associated diarrhea. Hepatogastroenterology 1999 46(25) 343-8. 

Antibiotic-associated diarrhea can develop with any antibacterial agent. Vancomycin has been implicated as a rare cause of diarrhea associated with Clostridium difficile (56), despite the fact that vancomycin is often used to treat it. 

The most notable adverse effect associated with clindamycin is antibiotic-associated colitis secondary to toxigenic Clostridium difficile. This organism usually overgrows in the Gl tract in the presence of antibiotics due to the inhibition of normal Gl flora. Ironically, the drug of choice for the treatment of antibiotic-associated colitis is metronidazole. Clindamycin also can cause diarrhea that is not related to C. difficile. 

Banno Y, Kobayashi T, Watanabe K, et al. (1981) Two toxins (D-1 and D-2) of Clostridium difficile causing antibiotic-associated colitis purification and some characterization. In Biochem. Int. 2 629-635. 

Libby JM, Jortner BS, Wilkins TD (1982) Effects of the two toxins of Clostridium difficile in antibiotic-associated cecitis in hamsters. In Infect. Immun. 36 822-829. 

Vancomycin is an antibiotic used to treat Staphylococcus and Clostridium difficile.These bacteria infect bones and joints and cause endocarditis and enterocolitis. Vancomycin is commonly prescribed to patients who are susceptible to endocarditis to prevent this infection from occurring. Vancomycin is particularly successful in treating methicillin-resistant strains of bacteria. However, parenteral vancomycin is not used to treat antibiotic-associated pseudomembranous colitis. 

Baverud, V., Gustafsson, A., Franklin, A., Lindholm, A. Gunnarsson, A. (1997) Clostridium difficile associated with acute colitis in mature horses treated with antibiotics. Equine Veterinary Journal, 29, 279-284. 

Vancomycin is also used for the treatment of Clostridium difficile and staphylococcal enterocolitis, which are treated orally or parenterally. However, parenteral vancomycin is not recommended for treating antibiotic-associated pseudomenbranous coMtis. 

Clostridium difficile is a Gram-positive bacteria, spore-forming, responsible for 15-20% of the antibiotic-associated diarrhoeas (Hamrick et al. 1989 Eckel et al. 2002). The gold-standard technique for the detection of Clostridium difficile is the stool cytotoxin assay. The microbiological mechanism is related to the production of two toxins (toxins A and B) by Clostridium difficile (Kyne et al. 2000). Disturbance of the normal bacterial flora in the colonic lumen is an important factor for the development of PMC (Ros et al. 1996). Children younger than 1 year develop symptomatic disease probably because of immature enterocytic membrane receptors for the toxin (Ros et al. 1996). 

Walk, S.T. and Young, V.B. 2008. Emerging insights into antibiotic-associated diarrhea and Clostridium difficile infection through the lens of microbial ecology. Interdiscip Perspect Infect Dis. Article ID 125081. doi 10.1155/2008/125081. 

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