Probiotics are not without risk, and several cases of bacteremia have been reported.18,19 Immunocompromised patients appear to be at comparably higher risk, and probiotics should be avoided in this group. Numerous adjunctive agents, including intraluminal toxin binders, biotherapeutic agents, monoclonal antibodies, and a C difficile vaccine, are in various stages of development.2
How to handle recurrences
Relapse rates for CDI range from 6% to 25%,2 and affect patients who receive either vancomycin or metronidazole for the initial treatment. The mechanism relates to either relapse of the original infection or reinfection of susceptible patients with a new strain of C difficile.
Risk of relapse. Elderly patients treated with metronidazole seem to be particularly susceptible to CDI relapse.20 Other risk factors include the administration of non-C difficile antibiotics during or after treatment of CDI, a defective immune response against toxin A, glucocorticoid use, prior stroke, and concurrent use of a proton-pump inhibitor.21-25
TABLE 2 lists tapering and/or pulsed dosing of oral vancomycin as treatment for patients with a second recurrence. We often prescribe the following 6-week regimen, telling patients to take 125 mg vancomycin:
- 4 times a day for one week,
- then 2 times a day for one week,
- then once a day for one week,
- then every other day for one week, and
- finally, every 72 hours for 2 weeks.
Oral metronidazole should not be used beyond the first recurrence or for long-term therapy because of cumulative neurotoxicity, which can be irreversible.2
Management of patients whose CDI recurs after a long course of vancomycin is challenging. Oral rifaximin therapy (400 mg twice a day for 14 days), started immediately at the end of the oral vancomycin course, was shown to cure 7 of 8 patients with multiple relapses.26 Other potential treatment options are oral nitazoxanide, IV tigecycline, or IV immunoglobulin.
CASE You explain to Mary S that diagnostic tests are needed before you can determine whether she can safely take loperamide. When she comes in later that day, you collect a stool sample for C difficile antigen and toxin testing, and order a complete blood count and electrolyte panel.
The patient’s C difficile tests come back positive, her white blood cell count is <15,000 cells/mcL, and her creatinine level is ≤1.5 times her baseline, so you start her on oral metronidazole 500 mg every 8 hours for 14 days. (If the antigen assay had been positive and the toxin negative, you would have either repeated the test or treated Mary S empirically with metronidazole. If the initial antigen assay had been negative, you would have advised her to take the loperamide.)
You schedule a follow-up visit a day or 2 after starting therapy. If the patient is dehydrated or her symptoms have not improved by then, hospitalization may be required.
TABLE 2
Treatment recommendations for C difficile infection
| Clinical description | Clinical evidence | Recommended treatment |
|---|---|---|
| Initial episode (mild or moderate) | Leukocytosis with a white cell count <15,000 cells/mcL and creatinine <1.5 times premorbid level | Metronidazole (oral) 500 mg TID for 10-14 d |
| Initial episode (severe) | Leukocytosis with a white cell count ≥15,000 cells/mcL or creatinine ≥1.5 times premorbid level | Vancomycin (oral) 125 mg QID for 10-14 d |
| Initial episode (severe, complicated) | Hypotension or shock, ileus, megacolon | Vancomycin 500 mg QID (oral or by NG tube) plus metronidazole 500 mg (IV). If complete ileus, consider adding rectal instillation of vancomycin |
| First recurrence | Same as initial episode | |
| Second recurrence | Vancomycin in a tapered and/or pulsed regimen | |
| NG, nasogastric. Adapted from: Cohen SH, et al. Infect Control Hosp Epidemiol. 2010.2 | ||
CORRESPONDENCE
Richard R. Watkins, MD, MS, Division of Infectious Diseases, Akron General Medical Center, 224 West Exchange Street, Suite 290, Akron, OH 44302; rwatkins@agmc.org