recommended before serum lactate >5 (54). Total colectomy with end ileostomy is the
procedure of choice. Select patients with disease clearly limited to the ascending colon have
been treated successfully with right hemicolectomy, but intraoperative colonoscopy should be
performed to rule out left-sided disease (40).
A retrospective review with patients infected with the epidemicC. difficilestrain B1/NAP1
showed that colectomy was most beneficial for immunocompetent patients aged>65 years with
a WBC>20,000 cells/mL and/or a plasma lactate between 2.2 and 4.9 meq/L (56).
Among patients requiring surgery, mortality rates after colectomy have ranged from 38%
to 80% in small series (40). In a study of patients with fulminant colitis requiring colectomy, the
need for preoperative vasopressor support significantly predicted postoperative mortality (40).
Other Medications
Alternate agents for the treatment of CDI include teicoplanin, fusidic acid, and bacitracin (34).
Teicoplanin may be at least as effective as oral vancomycin or metronidazole but is expensive
and not available in the United States. Both fusidic acid, also not available in the United States,
and bacitracin have been shown to be less effective than vancomycin (54).
Anion exchange resins, such as colestiol and cholestyramine, assert their effect onC. difficile
toxin by binding toxin in the colon. The anion exchange resins are not as effective as oral
vancomycin and metronidazole and should not be used as the single agents. Currently, there is
no indication for use of these resins. Resins must be taken at least two hours apart from oral
vancomycin since it binds vancomycin as well as toxins.
Tolevamer, a new toxin-binding resin developed for use in CDI demonstrated
noninferiority to vancomycin in a phase 2 study by Louie et al. (48). However, in the first of
two subsequent phase 3 trials, tolevamer demonstrated significantly worse outcomes
compared with standard therapy with oral vancomycin and metronidazole (57).
Rifaximinis a nonabsorbed, semisynthetic analogue of rifampin, which is FDA approved for
treatment of travelers’ diarrhea and is useful in managing hepatic encephalopathy. It has wide
antibacterial activity and poor absorption, leading tohigh intraluminal concentrations. In vitro,
rifaximin has demonstrated a highdegree of activity against mostC. difficilestrains with MIC
values similar to rifampin; however, high-level resistance has been demonstrated in 3% or more of
C. difficilestrains and recent reports suggest that resistance is even more widespread (21).
Rifaximin should be avoided until it is approved for use by the FDA.
Other investigational agents include nitazoxanide, tinidazole, OPT-80/PAR-101, ramo-
planin, human monoclonal antibodies, and toxoid A and B vaccines (58).
TREATMENT OF RECURRENT CDI
Recurrent CDI occurs in approximately 20% of the cases. Although it usually develops within
15 days after discontinuing the antibiotic, it can develop after as much as two months.
Approximately 50% of the recurrences represent reinfection (59).
Risk factors for recurrence include advanced age, marked elevation of WBC count during
initial episode, chronic renal insufficiency, CA-CDI, and antimicrobial use between initial
treatment and recurrence. The most important risk factor is previous recurrence (8). Patients
with at least one recurrence have 50% to 65% risk of experiencing an additional episode.
Failure of the immune system to mount antitoxin IgG titers in response to the first episode of
CDI may play a role in recurrent CDI. The frequency of relapse is nearly equal for vancomycin
and metronidazole (1).
The ultimate goal of treatment of recurrent CDI is to discontinue all antibiotics. It is
important to note that not all patients who has recurrent diarrhea after discontinuing
metronidazole or vancomycin have recurrent CDI. It is not recommended to repeat stool
assays after therapy unless the patients has moderate to severe diarrhea. In cases with minimal
symptoms therapy is not warranted (60).
Patients with first recurrence can be treated with the same drug as initial therapy (unless
severe CDI in which case oral vancomycin is preferred). Metronidazole should not be used
beyond the first recurrence and duration should not be longer than 14 days.
Current recommendations (IDSA, 2007) suggest oral vancomycin taperpulse dosing
beyond the first recurrence (Table 3). Tapered or pulsed dosing of vancomycin allows resistant
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