SAN FRANCISCO – If a patient with Clostridium difficile infection is not responding to single-drug treatment, it’s better to switch drugs than to add a second one, a retrospective study suggests.
The chart review encompassed 248 patients at one institution who received at least 24 hours of monotherapy or combination drug therapy for C. difficile infection from 2008 to 2010. After adjustment for confounding factors, the study showed no significant difference in the time to resolution of diarrhea in patients treated with metronidazole, vancomycin, rifaximin, or nitazoxanide alone, compared with patients who got combinations of these drugs, Jessica C. Njoku, Pharm.D., and her associates reported.
The 39 patients who got combination therapy (16%) also showed no significant differences in clinical cure rate, length of hospital stay, or mortality, compared with patients on monotherapy, Dr. Njoku said in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Diarrhea resolved in the monotherapy group in a mean of 5 days, compared with 10 days in the combination therapy group, a difference that seemed to favor monotherapy but was not statistically significant after adjustment for age, severity of C. difficile infection, immunocompetence, and whether it was a first episode or first recurrence, said Dr. Njoku, currently of Baylor University Medical Center, Dallas. She led the study while she was a fellow at the University of Nebraska Medical Center, Omaha.
The findings suggest that switching drugs instead of adding a drug is the best strategy for a patient who is not responding to initial monotherapy because adding a drug wastes resources, she said in an interview.
The study is one of the first to compare combination therapy to monotherapy for C. difficile infection, Dr. Njoku said. She and her associates conducted the study because clinicians were using drug combinations despite advice from an antimicrobial stewardship team against the practice. "We needed evidence," she said at the meeting, which was sponsored by the American Society for Microbiology.
The 2010 update to clinical practice guidelines for C. difficile infection in adults recommends oral metronidazole for mild to moderate C. difficile infections or oral vancomycin for severe infection. For C. difficile infection with severe complications, including ileus or toxic megacolon, expert opinion in the guidelines suggests treating with oral and IV vancomycin with the option of a vancomycin enema (Infect. Control Hosp. Epidemiol. 2010;31:431-55).
"In clinical practice, we don’t follow the guidelines to the letter," she noted. Her records review found that some patients in each category of severity received monotherapy and some were treated with drug combinations.
The C. difficile infection was a first episode in 90% of patients and a first recurrence in 10%. A first episode of infection was significantly more common in the monotherapy group (93%), compared with the combination therapy group (29 [74%] of 39 patients).
The monotherapy group also was significantly more likely to have mild to moderate infection (39%), compared with the combination group (3 patients [ 8%]). Patients with severe infection or severe complications were less common in the monotherapy group (55% vs. 6%, respectively) compared with patients in the combination group, 27 (69%) of whom had severe infection and 9 (23%) of whom had severe complications.
Sherry Boschert/IMNG Medical Media
Jessica C. Njoku, Pharm.D.
Cure, defined as the resolution of diarrhea (no more than two stools per day) by day 10, was achieved in 74% of patients on monotherapy and in 56% on combination therapy. The mean length of hospitalization was 16 days for monotherapy and 13 days for combination therapy. Eight percent of patients on monotherapy died, compared with 18% of patients on combination therapy. These differences between groups were not statistically significant in multivariate analyses.
Although the findings showed there was no benefit from combination therapy, this was a relatively small retrospective study at a single center, Dr. Njoku acknowledged. A larger, prospective, randomized trial comparing monotherapy with drug combinations is warranted, she said.
Patients in the study were 1 year of age or older, were positive for C. difficile toxin, and had symptoms of the infection. The study excluded patients who were pregnant or had C. difficile infection beyond a first recurrence. Exclusion criteria also cited patients with ileostomy and patients who had other enteric pathogens implicated in infectious diarrhea that were isolated in stool samples.
Dr. Njoku reported having no financial disclosures.