Page 979 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

710 PART 5: Infectious Disorders

Endoscopy can be helpful in the diagnosis of C difficile colitis, but its reasons previously outlined. However, for cases of severe CDI, which is
widespread application for this purpose is limited. The characteristic defined as leukocytosis >15,000 and elevation of serum creatinine >1.5
finding of pseudomembranes comprised of necrotic epithelial tissue premorbid level, oral vancomycin is the treatment of choice. 28
and inflammatory cells all but confirms the diagnosis of C difficile colitis When oral therapy is not feasible or in cases of severe complicated
in the appropriate clinical setting. However, this finding is not always CDI, intravenous metronidazole achieves adequate intraluminal con-
encountered, even in severe episodes of C difficile colitis. Moreover, to centrations to eradicate C difficile colitis. The recommended dosage
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perform colonoscopy or even flexible sigmoidoscopy in the setting of is 500 mg every 8 hours. Intravenous vancomycin should never be used
C difficile infection is to expose the patient to the risk of unnecessary to treat C difficile infection. After parenteral vancomycin administra-
trauma that could result in the accidental perforation of an already tion, drug levels within the intestinal lumen are not sufficient to ensure
inflamed and friable GI tract. eradication. The role of vancomycin in treating C difficile infection in
■ TREATMENT the critically ill patient instead focuses on intraluminal therapy. When
administered via a rectal tube or in the form of an enema, vancomy-
Whenever feasible, the first and most important step in the treat- cin can serve as a useful adjunct to intravenous metronidazole for the
ment of the patient with C difficile colitis is the discontinuation of the severely ill patient. Such methods are particularly useful in the setting
pharmacologic agent that precipitated the infection. In most cases, this of toxic megacolon caused by C difficile, when GI motility has all but
means that ongoing antimicrobial therapy for other indications should halted, and reliable delivery of drug administered orally or by a feeding
be withdrawn as soon as it is safe to do so. However, this is a particular tube cannot be assumed. However, caution is advised when employing
challenge when dealing with the critically ill patient. Broad-spectrum these techniques. The GI mucosa is exceedingly friable in the setting of
antimicrobial therapy, even when given empirically, may be essential to C difficile infection, particularly when toxic megacolon has developed.
the survival of the septic patients commonly encountered in this setting. Such patients are at high risk for GI perforation. When the patient is
For them, the discontinuation of therapy is not advisable, and an agent critically ill as a consequence of C difficile colitis (rather than critically ill
with activity against C difficile (discussed below) must instead be added and also having C difficile colitis), combined therapy with metronidazole
to the antimicrobial regimen. (500 to 750 mg) IV every 6 to 8 hours plus vancomycin 500 mg enterally
The most appropriate antimicrobial strategy to treat C difficile colitis every 6 hours has been advised. 46
can be the source of some controversy and confusion for even experi- Relapse of CDI occurs in approximately 20% to 25% of cases.
enced caregivers in the ICU. Both metronidazole and vancomycin, when A relapse if suggested by recurrence of symptoms 3 to 21 days after treat-
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administered orally, have been shown to be effective in the treatment of ment is stopped. Retreatment of patients with either recurrent C dif-
C difficile colitis. Several clinical trials have pointed to the equivalence ficile colitis or those who fail to respond to initial metronidazole therapy
of vancomycin and metronidazole therapy. One study by Zar et al is controversial and bears special attention. Clinicians should avoid the
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stratified patients based on severity of disease and randomized to receive practice of routine laboratory testing to detect C difficile toxin at the end
metronidazole or oral vancomycin. Severity of disease was based on a of a course of therapy in an effort to confirm clearance. Infected patients
point system, with one point given for age >60, temperature >38.3, may continue to shed detectable toxin after therapy is complete. Some
albumin <2.5 mg/dL, or peripheral WBC count >15,000. Patients were individuals may do so intermittently for years. In these cases, additional
considered to have severe CDI with a score of 2 or greater. The study therapy is not warranted. However, when diarrhea continues despite
found patients with mild disease had similar clinical cure rates with initial therapy or recurs soon thereafter, additional treatment is advised.
metronidazole (90%) or oral vancomycin (98%), respectively (p = 0.36). In these circumstances, a switch to vancomycin or a more prolonged
However, patients with severe disease had better rates of cure with oral course of metronidazole has been advocated. However, in most cases,
vancomycin (97%) versus metronidazole (76%) in this study (p = .02). simple retreatment with metronidazole appears to be just as efficacious.
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ment of CDI should be based on severity of disease and patient tolerance ■ PREVENTION
In the absence of other rigorous trials to test this observation, manage-
of the medications (Table 76-5). Prevention of CDI is one of the most important aspects of control-
For patients with C difficile colitis who can tolerate oral therapy and are ling and managing the disease. Prevention can be divided into two
considered to have mild to moderated disease, treatment should be initi- categories: preventing horizontal transmission to minimize exposure
ated with metronidazole, 500 mg every 8 hours. While many clinicians and decreasing risk factors for patients to develop CDI. The risk of
elect to treat for longer periods, the duration of metronidazole therapy horizontal transmission in the hospital increases as the length of hospital
necessary to treat C difficile need not extend beyond 10 to 14 days. For stay increases. Optimal infection control strategy takes a multifactorial
patients who cannot tolerate metronidazole, enteral vancomycin is an approach to decrease the risk of transmission and should be put into
effective alternative, but should not be used as first-line therapy for the practice in the intensive care unit to help combat spread. Health care

TABLE 76-5 Recommendations for Treatment of CDI
Initial episode: mild- Leukocyte count of 15,000 or lower Metronidazole 500 mg oral three times a day Duration—10-14 days
moderate disease Serum creatinine level less than 1.5 times
premorbid level
Initial episode: severe Leukocyte count of 15,000 or higher Vancomycin 125 mg oral four times a day Duration—10-14 days
Serum creatinine level greater than or
equal to 1.5 times premorbid level
Initial episode: severe, Hypotension, shock, ileus, megacolon Vancomycin 500 mg oral or via nasogastric tube four times a day plus Duration will vary
complicated metronidazole 500 mg intravenous every 8 hours, if complete ileus con-
sider rectal instillation of vancomycin, surgical consultation for colectomy
First recurrence NA Same as for initial episode depending on severity Duration—10-14 days
Second recurrence NA Vancomycin in a tapered or pulsed regimen Duration will vary depending on response
to treatment anywhere from 4 to 8 weeks

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