BOSTON – Single-dose intravenous immunoglobulin may be an effective adjunctive therapy for patients with severe, recurrent Clostridium difficile colitis that is refractory to standard treatment, according to data presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy.
In a retrospective review of 15 patients whose C. difficile colitis was unresponsive to standard therapy with metronidazole, vancomycin, and/or other agents, adjunctive treatment with a single dose of intravenous immunoglobulin (IVIG) led to clinical improvement in 87% of the cases, reported lead investigator Dr. Bienvenido G. Yangco of the Infectious Disease Research Institute in Tampa.
“Thirteen of the 15 patients had improvement or resolution of diarrhea, fever, and leukocytosis and were eventually discharged from the hospital,” he said. “One patient who demonstrated initial improvement was readmitted to the hospital 1 month later for recurrent C. difficile colitis [CDC], while 10 of the remaining 11 patients who had a repeat C. difficile toxin test remained negative after IVIG and have maintained clinical improvement to date.”
The patients included in this review were treated between January 2009 and July 2010 and were C. difficile cytotoxin positive with diarrhea, abdominal pain, distention, fever, leukocytosis, radiographic or colonoscopic evidence of colitis, and persistent or recurrent clinical manifestations despite receiving standard therapies, which included metronidazole (12 patients), vancomycin (13 patients), nitazoxanide (13 patients), and probiotics (9 patients), Dr. Yangco explained. The patients ranged in age from 61 to 92 years, with a mean age of 77, and had the following risk factors for CDC: advanced age, recent antibiotic exposure, and hospitalization, he said.
Of the 15 patients, 2 received a single IVIG dose of 200 mg/kg and 13 received a single 400-mg/kg dose. Among the patients receiving the higher dose, two underwent colectomy. One of these patients, whose colectomy was related to colorectal cancer, had resolution of CDC, and the other patient died, Dr. Yangco said. None of the patients had adverse effects from the IVIG treatment.
The findings are clinically relevant given the dramatic increases in the incidence and severity of C. difficile colitis in recent years and the suboptimal clinical outcomes observed with standard therapies, despite the relative nonexistence of C. difficile resistance to these drugs in vitro, said Dr. Yangco. He attributed the clinical/microbiological discrepancy to “low or waning antitoxin antibody levels in patients with C. difficile colitis.”
Although passive immunotherapy with IVIG in patients who don’t respond to standard treatment has been used since 1991, and its efficacy has been reported in small case series and observational studies, no controlled trials of IVIG in CDC have been performed to date, said Dr. Yangco. “It should be noted that the IVIG doses in the published studies vary from 200 to 1,250 mg/kg for 1-5 consecutive days or once every 3 weeks for 2-3 doses, and in those reports there have been definite benefits and possible efficacy observed with IVIG,” he said. “None of the published studies” has discouraged its use.
Although the findings of the current study are limited by the small number of patients and the retrospective design, the apparent efficacy of single-dose IVIG for the treatment of severe, recurrent CDC “warrants further investigation in prospective, controlled studies,” Dr. Yangco stressed.
“It is very likely that [the] high cost of IVIG – often cited as an obstacle to its use – might be offset in these patients by the benefits associated with sustained clinical improvement, including shorter hospital stays and fewer readmissions.” Furthermore, he said, “changing patterns of C. difficile colitis are compelling reasons for us to reexamine and change our current approach to managing the disease.”
Dr. Yangco disclosed financial relationships with Sanofi Pasteur, Gilead Sciences, Pfizer, Tibotec, Merck, and J.G. Johnson. He noted that this study was not funded by a pharmaceutical company.