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Antibiotic-Associated Diarrhea (AAD)

Author: Dr. Geethu Thomas - Gastro Health  

The consequences of long-term antibiotic administration are diarrhea, antibiotic resistance, impaired immunity, increased cost of treatment, organ failures and deaths and reduction in beneficial phytoestrogens.

Antibiotic-associated diarrhea (AAD) is unexplained diarrhea associated with the use of an antibiotic. AAD may occur up to two to three weeks following the cessation of antibiotic therapy rather than during the treatment. Antibiotics cause diarrhea due to infection by antibiotic-resistant pathogens such as Staphylococcus aureus, Clostridium difficile, Candida albicans, Clostridium perfringens type A, Klebsiella oxytoca, etc.

Clostridium difficile-associated disease (CDAD) is one among the most important causes of antibiotic-associated diarrhea. It is responsible for 15 to 25 % of cases of AAD.CDAD is a serious condition with a mortality of up to 25 % in frail elderly.The average age of those with Clostridium difficile infection is nearly 20 years older than the average age of those in hospitalization for other reasons.

CDAD is defined as unexplained diarrhea occurring after two hours to within two months after antibiotic usage and is often accompanied by fever, abdominal pain, and cramps. CDAD is established when a toxin is identified in the stool, regardless of C.difficile isolation from the stool.

The laboratory diagnosis is based on culture and toxin detection in fecal specimens. Culture is very sensitive, but if carried out without toxin testing, it may lead to misdiagnosis of CDAD as it detects even asymptomatic cases. C. Diff Quik Chek Complete® test is a rapid cassette assay that simultaneously detects both glutamate dehydrogenase (GDH) antigen and toxins A and B of C. difficile in fecal specimens.

C. difficile is a spore-bearing, gram-positive bacterium, present in ample amounts in the environment. Spores of C.difficile are hard to eradicate as they are resistant to drying and heating, and also resistant to most of the antiseptic disinfectants. The ability to produce spores explains how the organism being fastidiously anaerobic, can be acquired from the environment. Broad-spectrum antibiotics such as Clindamycin, Fluoroquinolones, Cephalosporins, etc. most often cause CDAD.

C.difficile is acquired from the hospital environment. It causes increased burden in terms of cost and health. The risk factors involved in the acquisition of CDAD are patient age above 65 years, treatment with broad-spectrum antibiotics, exposure to an infant carrier or infected adult, tracheostomy, immunodeficiency, Ryle’s tube feeding, antacids, intestinal surgeries, chemotherapy, and chronic kidney disease.

C.difficile produces toxins that attack the lining of the intestine. Toxins A and B are the primary virulence factors contributing to the pathogenesis of CDAD, and the genes responsible for these toxins are TcdA and TcdB. The toxin expression is increased by antibiotic concentration. TcdA is a potent enterotoxin. TcdB is cytotoxic and is more potent (~1000 fold) than TcdA. Another toxin is the binary toxin encoded by genes ctdA and ctdB. CDAD may progress to a fatal condition known as pseudomembranous colitis (PMC) with rapidly fatal fulminating colitis and megacolon, resulting in death.

The cultivation of the organism, though difficult, is considered gold standard. Although stool culture has high sensitivity, as the rate of asymptomatic carriage of C.difficile among hospitalized patients is high, the specificity for CDAD is low. The disadvantages of the cell cytotoxicity neutralization assay (CCNA) is that it is technically demanding and has a relatively long turn around time (24 to 48 hours). Although endoscopy is required for the specific diagnosis of PMC, it is an invasive test and not sufficient to diagnose all the cases of CDAD. Newer methods like toxin detection by immunochromatography have a rapid turn around time and are inexpensive.

The most crucial aspect in the management of CDAD is an early identification of the disease and the discontinuation of the inciting agent, as it has the potential to emerge as an epidemic strain causing large hospital outbreaks. The treatment and isolation of infected cases decrease not only the treatment cost incurred by the patient but also reduces the morbidity and halts the spread of the disease in the community.

For more information consult a diarrhea specialist online --> https://www.icliniq.com/ask-a-doctor-online/medical-gastroenterologist/diarrhea

Image: Antibiotic-Associated Diarrhea (AAD) Last reviewed at: 07.Sep.2018

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