This patient has severe Clostridium difficile infection (CDI) and should be treated with oral vancomycin. Consensus guidelines for the treatment of CDI indicate that the specific antibiotic and route of administration should be guided by the severity of disease. Severe CDI is defined by the Infectious Diseases Society of America as a leukocyte count of 15,000/µL (15 × 109/L) or greater and a serum creatinine level greater than 1.5 times the baseline level. Although more recent guidelines (see citation) use slightly different measures for defining severity, infectious disease and gastroenterology specialties concur that the preferred treatment for severe CDI is oral vancomycin. This is based on lower cure rates with oral metronidazole compared with vancomycin for patients with severe disease.
Oral metronidazole is the recommended initial therapy for patients with mild to moderate CDI (leukocyte count <15,000/µL [15 × 109/L] and serum creatinine level <1.5 times baseline) based on cure rates similar to those of vancomycin and lower cost. A newer antimicrobial agent, fidaxomicin, showed noninferiority to vancomycin in the treatment of patients with mild to moderate CDI and, in a subset of patients, was associated with fewer relapses. However, the cost difference is substantial. A 10-day course of fidaxomicin approaches $3000, whereas metronidazole costs less than $30 and oral vancomycin costs less than $700. The indications for fidaxomicin will likely evolve, but as of publication it is not recommended as initial therapy for mild to moderate CDI.
Complicated CDI is defined as severe disease with the additional findings of hypotension, ileus, or megacolon. Patients with ileus may have limited transit of oral antibiotics to distal sites of infection in the colon. Therefore, in this critically ill group, the recommendation is to give vancomycin orally or through a rectal tube in addition to intravenous metronidazole. Parenteral metronidazole has variable penetration but provides some delivery to the distal colon in the setting of ileus. In contrast, intravenous vancomycin does not achieve appreciable levels intraluminally, and this route of administration is not indicated for treatment of CDI.
No treatment benefit results from combination therapy with oral metronidazole and oral vancomycin for CDI regardless of severity of infection.