Severe CDI causes volume depletion, electrolyte imbalances, and hypotension, as well as renal impairment, hemodynamic instability, leukocytosis, toxic megacolon, and death. Severe diarrhea associated with this form of CDI might include 10 or more loose stools per day. A surgical consultation should be obtained for a complete evaluation in the most severe cases, as patients may require colectomy.
Recent reports suggest oral (OP) vancomycin be considered as first-line therapy for severe CDI. Intravenous (IV) vancomycin should not be used, because it does not reach high enough stool levels to treat the infection. Vancomycin should be dosed at 500 mg four times daily for 10 to 14 days (severe CDI) and 125 mg four times daily for 10 to 14 days in cases of mild to moderate CDI; alternatively, the duration of treatment can be extended for several days after the diarrhea resolves. This usually occurs within a few days after commencing treatment.
The treatment of choice for mild to moderate CDI is metronidazole. It is dosed at either 500 mg PO three times daily or 250 mg PO four times daily. Oral metronidazole achieves higher stool concentrations than IV metronidazole, so it is the preferred route for CDI management.
Metronidazole can cause nausea and a metallic taste. It also interacts with warfarin, so the international normalized ratio (INR) must be followed. Concomitant administration of alcohol can lead to a reaction similar to that associated with use of Antabuse. The drug should not be used in pregnant women or children. Metronidazole and vancomycin usually are equally effective for treating mild to moderate CDI, but some resistance has been noted. Vancomycin PO currently is available only as a branded drug with a high cost, but this may soon change.11
Recurrence
Recurrence can occur in approximately 20% of patients within 60 days, and these patients can be treated with the same antibiotics as were previously utilized. Subsequent recurrences can be managed with pulse dosing, or by tapering the dose at the end of therapy. Due to a lack of controlled studies, the use of probiotics, such as Lactobacillus, in the prevention of CDI cannot be routinely recommended.12 However, Lactobacillus-containing products generally are considered safe in immunocompetent individuals.
The Future
Generic oral vancomycin is on the horizon and a number of agents are currently undergoing phase 3 clinical trials for CDI management. These include rifaximin, nitazoxanide, and rifampin in combination with current agents.13-16 For now, prevention is key. Utilize some of the measures noted above to prevent this potentially serious, nosocomial infection. For infected patients, current treatments are effective and new ones will be here soon. TH
Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City.
References
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2.O’Brien JA, Lahue BJ, Caro JJ, Davidson DM. The emerging infectious challenge of Clostridium difficile-associated disease in Massachusetts hospitals: clinical and economic consequences. Infect Control Hosp Epidemiol. 2007;28:1219-1227.
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6.The national healthcare safety network protocol multi-drug-resistant organism and Clostridium difficile-associated disease module version 4.1. CDC Web site. Available at: www.cdc.gov/ncidod/dhqp/ pdf/nhsn/MDRO_CDADprotocolv41Dec08final.pdf. Accessed Jan. 14, 2009.