Intravenous tigecycline in the treatment of severe recurrent Clostridium difficile colitis

To the Editor: Interest in alternative therapies for Clostridium difficile infections (CDIs) is increasing as these infections become important causes of patient morbidity and mortality. Recurrent CDIs can be severe and difficult to treat. In-vitro data,1 followed by reports of the efficacy of tigecycline in the treatment of severe refractory cases of CDI,2 suggest that tigecycline should be considered as an alternative or adjunctive antimicrobial agent in these situations. To date, it has been used mostly as a “salvage” strategy in combination with other antibiotics in the face of clinical deterioration.2,3 We report the successful use of tigecycline monotherapy in the treatment of a patient with recurrent C. difficile colitis.

An 83-year-old woman was admitted to hospital in July 2009 with acute diverticulitis. She was treated with intravenous cefotaxime (1 g three times daily for 6 days): her presenting fever and abdominal pain resolved but she developed watery diarrhoea. Despite positive stool cultures for toxigenic C. difficile, initial toxin testing by enzyme immunoassay (EIA [TechLab C. Difficile Tox A/B II]) of stool specimens was negative. After a 7-day course of oral metronidazole 200 mg three times daily, the diarrhoea abated.

One month after discharge, our patient re-presented with anorexia, severe abdominal pain and diarrhoea. Six days of oral metronidazole, prescribed by her local doctor, had little effect. A computed tomography scan of the abdomen revealed diffuse thickening of the colon from the ileocaecal junction to the rectum, consistent with a pancolitis. Sigmoidoscopy showed grossly abnormal mucosa with pseudomembranes present. A diagnosis of C. difficile pseudomembranous colitis was made. After 10 days of oral vancomycin 250 mg, four times daily, her symptoms had resolved, and repeat sigmoidoscopy showed reversal of the mucosal changes. Six days later, the pseudomembranous colitis recurred. She rapidly responded to the recommencement of oral vancomycin, given as a tapering course over 6 weeks.

Twelve days after completing the 6-week course of vancomycin, the patient presented with her third episode of colitis. Most reported strategies for recurrent CDI, such as faecal transplantation, probiotics or novel antimicrobials,4 were not practicable or available for timely use for our patient. Tigecycline, a broad-spectrum glycylcycline antibiotic, is available as part of the hospital formulary for the treatment of complicated skin and soft-tissue infections and complicated intra-abdominal infections. Encouraged by recent reports of success using tigecycline as adjunctive therapy for severe cases of CDI,2 we prescribed, as monotherapy, intravenous tigecycline 50 mg twice daily for 2 weeks. Our patient’s condition improved over 1 week. At 3-month follow-up, she remained asymptomatic, with repeat stool cultures and polymerase chain reaction (PCR) testing for C. difficile toxin negative at Days 75 and 107 following the last episode of colitis.

Our case also highlights a diagnostic matter. In general, use of EIA to detect C. difficile toxin A or B is highly specific. However, in clinical settings where the prevalence of CDI is low, the positive predictive values for these assays are inadequate to rule in the diagnosis of CDI. Confirmatory laboratory testing using an alternative method (in this case, PCR) proved more reliable in the diagnosis of our patient’s recurrent CDI. Typing showed that our patient’s isolate was not PCR ribotype 027, a hypervirulent strain in Europe and North America associated with high mortality.5

We recommend consideration of tigecycline as a useful antimicrobial agent in the management of both recurrent and severe CDI.