Antibiotic Associated Diarrhea

ANTIBIOTIC ASSOCIATED DIARRHEA

Erwin Astha Triyono
Usman Hadi

ABSTRACT
Antibiotic-associated diarrhea (AAD) is the most common cause of diarrhea in
hospitalized patients, representing an important source of morbidity, mortality, and
cost. Although no infectious agent is found in most cases of AAD, Clostridium difficile
is frequently identified in patients with signs and symptoms of colitis. All types of
antimicrobial agents have been implicated, leading to a wide range of clinical
manifestations, from asymptomatic carrier state to severe pseudomembranous colitis.
Most cases of AAD respond to supportive measures and withdrawal of antibiotics. In
patients with severe and persistent symptoms effective antibiotic therapy is available,
but relapses are common.

INTRODUCTION
Antibiotic-associated diarrhea (AAD) is defined as otherwise unexplained diarrhea
that occurs in association with the administration of antibiotics. AAD can occurs in
patients who are treated with ampicillin (5-10 %), amoxillin-clavulanate (10-25 %),
cefixime (15-20 %), cephalosporins, fluoroquinolones, azithromycin, chlarithromycin,
erythromycin, and tetracycline (2-5 %). The rates of AAD associated with parenterally
administered antibiotics are similar with orally administered agents. Infection with
Clostridium difficile accounts for only 10-20 percent of the cases of AAD but it accounts
for the majority of cases of colitis associated with antibiotic therapy

Diarrhea Associated with C. difficile Infection

Infection with C. difficile causes a toxin-mediated enteric disease the characteristic
clinical and pathological features of which have been reproduced in hamsters. It has
a characteristic endoscopic appearance in people. Recent studies suggest that
immunologic susceptibility has a role in C. difficile infection. The presence of IgG
antibody toxin A protecs againts the clinical expression of C. difficile infection and
against relapse.
Major risk factors for C. difficile include

Advanced age. A population-based study in Sweden showed that, in people

who were older than 60 years of age, the incidence of positive assays for C.
difficile toxin was to 20-100 times as high as the incidence in people who
were 10-20 years of age.
Hospitalization. Hospitalized adults have rate of colonization of 20-30 %, as
compared with a rate of 3 % in outpatients.

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Erwin Astha Triyono, Usman Hadi

Exposure to antibiotics. Penicillins, clindamycin, and cephalosporins are

antibiotics most f requently a ssociated with C. difi cille diar rhea tha t is
unrelated to superinfection with this organism.

Mechanism Other Than C. difficile Infection

AAD may also be caused by other enteric pathogens, by the direct effects of antimicrobial
agents on the intestinal mucosa, and by the metabolic consequences of reduced
concentrations of fecal flora. Infection with either subtype causes a self-limited diarrhea
that generally resolves within 24 hours. There is no specific treatment, and few laboratories
offer the diagnostic tests necessary to identify this pathogen. Other enteric pathogens
that can cause diarrhea include

Salmonella may also cause pseudomembranous colitis.

C. perfringens type A produces an enterotoxin known to cause food poisoning;
more recently, a different genotype has been implicated in AAD.
S. aureus can causes colitis so the distinction is important because
metronidazole is effective for C. difficile infection, not for S. aureus.
and possibly C. albicans. The finding of candida species in the stool at a
concentration of more than 100,000 org per gram stool and in some patients
whose condition has improved after nystatin therapy has sug gested that
candida species may cause AAD.

PATOPHYSIOLOGY
Anti bi oti cs ~ speci fi c bacteri a

W hen an anti bi oti c ki l l s one type of bacteri a (i ncl ude fecal anaerobes that are norm al l y present),
other bacteri a i n the gut are present i n greater num bers

Upset the natural bal ance of

bacteri a i n the i ntesti ne

The m etabol i sm of carbohydrates m ay decrease,

w hi ch causes osm oti c di arrhea, and the rate of
breakdow n of pri m ary bi l e aci ds, w hi ch are potent
col oni c secretory agents, m ay be reduced

Too m any harm ful bacteri a i n the i ntesti nes can cause di arrhea
(Havi ng too m any of the bacteri a cal l ed Cl ostri di um di ffi ci l e/
e/ other causes severe di arrhea /
pseudom em branous col i ti s)

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Antibiotic Associated Diarrhea

Multiple effects of Drugs on Gastrointestinal Tract

Erythromycin acts as a motilin-receptor agonist and accelerates the rate of gastric
emptying. The clavulanate in amoxillin-clavulanate appears to stimulate small-bowel
motility. Penicillins may cause segmental colitis. In many suspected cases, nonantibiotic
drugs are the cause of diarrhea attributed to antibiotics; these include laxatives, antacids,
contrast agent, products containing lactose or sorbitol, NSAID, antiarrhytmic drugs,
and cholinergic agents

SYMPTOMS
Symptoms usually start between 4 and 9 days after you start to take the medicine.
The main symptoms are loose bowel movements or more bowel movements than
normal. Most often the loose bowel movements are mild and go away when stop
ta kin g the an ti bio tic . Som eti me s a ve ry se rio us ty pe of di arr hea c all ed
psudomembranous colitis happens. Symptoms of pseudomembranous colitis are
more severe and may include

A lot of watery diarrhea (sometimes bloody)

Abdominal pain and cramping
Nausea
Dehydration
Fever
Leucocytosis, fecal leucocytes, hypoalbuminemia
Colonic thickening on CT Scan
Characteristic changes apparent on endoscopic inspection or biopsy

DIAGNOSTIC TEST

Laboratory findings

Non specific
Leucocytosis
Hypoalbuminemia (reflecting a protein-losing enteropathy)
Fecal leucocytes

Histologic findings in the colon range from normal to psudomembranous colitis.

Abdominal radiography, CT scan, and Endoscopy may faciliate the detection of
C. difficile infection but non specific, relatively insensitive, and often expensive,
and they have been almost completely supplanted by assays for C. difficile toxin.

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Erwin Astha Triyono, Usman Hadi

Cytotoxin assay that uses tissue

culture has been the gold standard for diagnosis.

It is the most sensitive test, detecting as little as 10 pg of toxin B. However, most
laboratories do not offer tissue-culture assays, and the result of the assay are not
available for 24-48 hours.
Alternatives include enzyme immunoassays and toxin culture assays (the result
of this test should be available within hours or one day)
The diagnosis can also be made by culturing stool on selective medium, including
the toxin-culture assay, with broth cultures of isolates to identify toxigenic strains.

DIAGNOSIS

Ask about the medicines they are taking.

If symptoms are mild, They may not need any lab tests.
If more severe symptoms, check a sample of bowel movement and examine the
lining of rectum and lower bowel.

THERAPY

If

symptoms are more severe

o
Bed rest
o
Intravenous (IV) fluid
o
Another antibiotic to treat bacteria causing the severe symptoms
Indication for treatment with metronidazole or vancomycin include positive assays
for C. difficile toxin with evidence of colitis, severe diarrhea, persistent diarrhea despite
the discontinuation of the implicated agent; or the need to continue treating the
original infection.
Metronidazole is preferred because it is less expensive than vancomycin and avoid
the potential risk of promoting vancomycin-resistant enterococci in nosocomial
cases.
Indication for oral vancomycin, as opposed to metronidazol, are pregnancy, lactation,
intolerance of metronidazole, or failure to respond to metronidazole after three to
five days of treatment.
Oral metronidazole (500 mg three times daily or 250 mg four times daily -10 days)
and oral vancomycin (125 mg four times daily -10 days)
If intravenous treatment required, only metronidazole (and not vancomycin) is
effective.
The anticipated response to treatment is resolution of fever within one day and
resolution of diarrhea in four to five days.
Severely ill patients who have no response to metronidazole or vancomycin may
require colectomy (in rare instances)

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Antibiotic Associated Diarrhea

If symptoms are mild

o
Stop taking the antibiotic
o
Change the diet for a few days
In addition, taking concentrated supplements of benefecial bacteria (probiotics)
or eating yogurt may relieve symptoms or help prevent antibiotic-associated diarrhea
in the first place

PROGNOSIS

In Mild case : Diarrhea may last up to 14 days after stop taking the antibiotic
In more severe cases : The symptoms may not go away until several weeks after
we begin treatment, and the symptoms may return after treatment because some
antibiotics have an effect on bacteria for a long time

PREVENTION

Take antibiotics only when they are necessary

Take antibiotics exactly
When possible, avoid taking antibiotics that cause you have these symptoms

REFERENCES
1.

Barlett JG (2002). Antibiotics-associated diarrhea. N Engl J Med; 346 (5): 334-339.

2.

Greb C, Kalem T, Kalble T (2003). Antibiotic induced diarrhea and pseudomembranous colitis.
Urologe A; 42(1): 82-89.

3.

Guerrant RL, et al (2001). Practice guidelines for the management of infections diarrhea. Clin
Infect Dis; 32: 331-348

4.

Horne JS, Swanson LN (1996). Diarrhea. The Center for Disease Control (CDC); Available at
www.cdc.gov/mcidod/disease.htm

5.

Ticehurts JR, Aird DZ, Dam LM, et al (2006). Effective detection of toxigenic clostridium difficile
by algorithm including test for antigen and cytotoxin. J Clin Microbiol 2006; 44(3): 1145-1149.

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