cessation of the inciting antibiotic as soon as possible.

Treatment with concomitant

antibiotics (ie, antibiotics other than those given to treat C. difficile infection) is
associated both with significant prolongation of diarrhea and with increased risk of
recurrent C. difficile infection If ongoing antibiotics are essential try to o select
antibiotic therapy that is less frequently implicated in antibiotic-associated CDI, such as
parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline.

antimotility agents such as loperamide and opiates have traditionally been avoided in
CDI, but the evidence that they cause harm is equivocal

Patients with typical manifestations of C. difficile infection (eg, diarrhea, abdominal

pain, or nausea and vomiting) and a positive diagnostic assay should receive antibiotics
for treatment for C. difficile infection. Empiric therapy is appropriate pending results of
diagnostic testing if the clinical suspicion is high Treatment is not indicated in patients
who have a positive toxin assay but are asymptomatic.

C. difficile infection (CDI) may develop signs of systemic toxicity with or without
profuse diarrhea . Severe CDI include white blood cell count of >15,000, serum
albumin <3 g/dL, and/or a serum creatinine level 1.5 times the premorbid level

One point each was given for age >60 years, temperature >38.3C, serum albumin <2.5
g/dL (25 g/L), or peripheral white blood cell count >15,000 cells/microL . Two points
were given for endoscopic evidence of pseudomembranous colitis or treatment in the
intensive care unit. Patients with two or more points were considered to have severe
disease.

Mild or moderate disease oral metronidazole, oral vancomycin, and oral fidaxomicin
metr and vanco produced similar rates of clinical cure (90 versus 98 percent) of
metronidazole can cause dose-dependent peripheral neuropathy and side effects of
nausea and metallic taste. Use of oral vancomycin is appropriate for initial therapy of
nonsevere disease in pregnant, breastfeeding, or intolerant/allergic to metro
Duration for nonsevere C. difficile diarrhea is 10 to 14 days If pt are on antibiotics for
underelying infection, continue CDI treatment throughout the antibiotic course plus an
additional week after its completion. Repeat stool assays are NOT warranted during or
following treatment in patients who are recovering or are symptom free. Up to 50
percent of patients have positive stool assays for as long as six weeks after the
completion of therapy .Risk factors associated with metronidazole failure include recent
cephalosporin use, C. difficile on admission, and transfer from another hospital .Failure
to respond to metroe within five to seven days should prompt change to vancomycin
(125 mg q 6 h .

severe CDI Toxic megacolon should be suspected if the patient develops abdominal
distention with diminution of diarrhea; this may reflect paralytic ileus resulting from
loss of colonic muscular tone .

tx oral vancomycin (125 mg four times daily) . If no clinical improvement within

24 to 48 hours or who develop complications (such as renal failure, ileus), do oral
vancomycin to 500 mg four times daily. Some experts start with high dose in severely ill
pt . Fidaxomicin 200 mgq 12h may be considered in patients who cannot tolerate
vancomycin or are not improving on it . In the setting of ileus, add iv metronidazole
(500 mg every eight hours).. Intracolonic vancomycin may be considered in patients
with profound ileus. Duration of antibiotic 10 to 14 days .If antib are needed for
underlying infection continue CDI treatment throughout the antibiotic course plus one
additional week after its completion. If no vanco or fidaxomicin are available consider
oral metronidazole 500 q 8h but is less efective . Intravenous tigecycline has been used
in a small number of patients with severe CDI that was refractory to standard therapy.

Intracolonic vancomycin (vancomycin enema) may be an effective adjunctive therapy

for patients who cannot tolerate the oral preparation or for patients who have a condition
preventing oral vancomycin from reaching the colon such as ileus, megacolon,
Hartman's pouch, ileostomy, or colonic diversion Rectal vancomycin is often given as a
retention enema containing 500 mg in 100 mL of normal saline every six hours. One
report suggests that patients with megacolon may benefit from colonoscopic
decompression and placement of a tube in the right colon, which can be perfused with a
1 mg/mL solution of vancomycin in normal saline to deliver a total dose of 1 to 2 g per
day . Dose adjustments may be required depending on individual circumstances,
including extent of colonic disease and patient weight. It is important to note that
vancomycin can be absorbed through inflamed colonic mucosa and cause toxicity

Surgery toxic megacolon, perforation or impending perforation, necrotizing colitis,

or rapidly progressive and/or refractory disease with systemic inflammatory response
syndrome leading to multiorgan system failure .Surgery may be needed if unresponsive
to medical therapy within 48 hours .However, in the setting of CDI due to the
hypervirulent strain, some patients progressed from severe disease to death in less than
48 hours .In one study colectomy was most beneficial for immunocompetent patients
aged 65 years with a white blood cell count 20,000 cells/microL and/or a plasma
lactate between 2.2 and 4.9 mEq/L . Two surgical approaches have been described:
subtotal colectomy (removal of the entire colon with ileostomy without removal of the
rectum) and diverting loop ileostomy with colonic lavage .Primary anastomosis is not
feasible acutely due to the pancolitis associated with severe disease. However, after
colonic inflammation has subsided, closure of the ileostomy and ileorectal anastomosis
can be created.

Diverting loop ileostomy and colonic lavage may be a potential alternative procedure
to colectomy in the treatment of severe complicated CDI .The surgical approach
involved creation of a loop ileostomy, intraoperative colonic lavage with warmed
polyethylene glycol solution via the ileostomy, and postoperative antegrade instillation
of vancomycin flushes via the ileostomy. Preservation of the colon was achieved in 93
percent of patients.

RECURRENT DISEASE

Initial recurrence The signs and symptoms of recurrence are similar to those in the
initial episode, usually without progression in severity . Because a positive stool toxin
assay does not exclude asymptomatic carriage, other causes for diarrhea should be
considered, including other infections, inflammatory bowel disease, or irritable bowel
syndrome. Colonoscopy should be considered in atypical cases . For treatment of an
initial episode of CDI, fidaxomicin has been associated with a lower incidence of
recurrent CDI than vancomycin Patients with mild symptoms of recurrence who are
otherwise well may be managed conservatively without further antibiotic therapy.
Nonsevere initial recurrence following therapy for CDI can be treated with
metronidazole. The decision to administer vancomycin as treatment for a first
recurrence should be based upon the presence of markers of severe disease at the time
of first recurrence rather than on previous drug exposure.

Subsequent recurrences Patients with one recurrence have a substantial risk of

subsequent CDI episodes after the second course of antibiotic therapy is discontinued.
Patients with multiple recurrences may benefit from vancomycin (administered in a
pulse-tapered fashion), fidaxomicin, or rifaximin, with or without the use of probiotics

Fidaxomicin may be an appropriate therapy in patients with recurrent CDI or perhaps as

initial therapy in patients at high risk of developing recurrent disease

Use of secondary prophylaxis during concomitant antibiotic use may be useful for
prevention of recurrent infections

Other therapeutic options Fecal microbiota transplant Monoclonal antibodies

against C. difficile toxin appears to reduce the recurrence rate of C. difficile infection.
Bezlotoxumab (a monoclonal antibody that binds to C. difficile toxin B) is approved for
secondary prevention of C. difficile infection in patients at high risk for recurrence
(including patients >65 years of age and those with a prior history of CDI).
Intravenous immune globulin (IVIG) in relapsing or severe C. difficile colitis in
addition to antibiotic therapy anion-binding resins colestipol and cholestyramine are
not effective as primary therapy for C. difficile colitis, although they may be beneficial
as adjunctive therapy for relapsing infection. In a series of 11 patients with relapsing
CDImAnion-exchange resins bind vancomycin as well as toxins; thus, the resin must be
taken at least two or three hours apart from the vancomycin .Suggested regimens are
colestipol (5 g every 12 hours) or cholestyramine (4 g three or four times daily) for one
to two weeks, usually with vancomycin.
Tolevamer is a C. difficile toxin-binding resin developed specifically for CDI . but it is
inferior to both vancomycin and metronidazole as primary therapy for CDI

Initial episode
Metronidazole 500 mg orally three times daily or 250 mg four times daily for 10 to 14
days
Vancomycin 125 mg orally four times daily for 10 to 14 days
First relapse
Confirm diagnosis (refer to text)
If symptoms are mild, conservative management may be appropriate
If antibiotics are needed, repeat treatment as in initial episode above. Alternative:
fidaxomicin 200 mg orally twice daily for 10 days.[1,2]
Second relapse[3,4]
Confirm diagnosis (refer to text)
Tapering and pulsed oral vancomycin (below), with or without probiotics (for example,
Saccharomyces boulardii 500 mg orally twice daily). The probiotics may be overlapped
with the final week of the taper and continued for two additional weeks in the absence
of antibiotics.
125 mg orally four times daily for 7 to 14 days
125 mg orally twice daily for 7 days
125 mg orally once daily for 7 days
125 mg orally every other day for 7 days
125 mg orally every 3 days for 14 days
Alternative: fidaxomicin 200 mg orally twice daily for 10 days[1,2]
Subsequent relapse[1,2,5]
Confirm diagnosis (refer to text)
Fidaxomicin 200 mg orally twice daily for 10 days if not used previously
Fecal bacteriotherapy (fecal microbiota transplant)