A 68-year-old Caucasian male with a history of multiple myeloma on lenalidomide/dexamethasone, diabetes, and end-stage renal disease on hemodialysis was admitted to the hospital for severe diarrhea and dehydration. On physical examination, he was found to be afebrile with benign abdominal exam. His white blood cell count (WBC) was normal. Fecal leukocytes were detected. Stool ova and parasites and bacterial stool cultures were negative. A computed tomography (CT) of the abdomen and pelvis showed diffuse thickening of the colon wall involving the entire colon and rectum consistent with infectious colitis. With the high suspicion of Clostridium difficile associated colitis, metronidazole 500 mg orally every 8 hours was empirically started. The cytomegalovirus serum polymerase chain reaction (PCR), enzyme immunoassay (EIA) for C. difficile toxin A/B and C. diffile PCR were all negative. Despite metronidazole treatment, his diarrhea persisted and on the 7th hospital day, he had a temperature of 101.8°F and rifaximin 550 mg orally twice daily was added. He responded rapidly to the combination treatment and the diarrhea and fever resolved by the 14th hospital day and he was discharged on metronidazole for 14 days. However, a week later the patient was readmitted to the hospital with diarrhea, nausea and abdominal pain. On physical examination, he was afebrile and appeared to be in mild distress with right-lower quadrant and suprapubic tenderness on palpation. His leukocyte count was 6,200 cells/μL and a repeat abdominal CT showed changes of pancolitis consistent with an infectious process. Metronidazole was continued and cefepime 1 gram intravenously every 24 hours was added. Stool culture showed only normal fecal flora and blood cultures were negative, however; the EIA C. difficile toxin stool assay was positive. His therapy was changed from metronidazole and cefepime to vancomycin 250 mg orally every 6 hours, as his symptoms restarted within 5 days of receiving rifaximin and while on metronidazole. Over the following nine days, the patient showed little response to therapy, averaging six loose bowel movements a day along with persistent abdominal tenderness and distention. He had a WBC count of 5,000 cells/μL with 32% bands, and a lactate level was elevated at 4 mmol/L. An abdominal X-ray showed no bowel distention. By the 10th hospital day, the patient developed leukocytosis with a WBC count of 17,200 cells/μL and was now considered to have failed vancomycin treatment. Tigecycline 100 mg intravenously once, followed by 50 mg every 12 hours and rifaximin 550 mg orally every 12 hours, was added to the vancomycin. Though the patient's leukocyte count peaked at 19,900 cells/μL (during 2nd day of modified therapy), he responded well with a gradual decrease in leukocytosis, diarrhea, and abdominal pain. He was discharged on the 16th hospital day with resolution of symptoms after 4 days of tigecycline, rifaximin, and vancomycin treatment. He was continued on this antibiotic regimen for an additional ten days. One month after finishing antibiotics, the patient was free of symptoms.
Case 6 occurred in an 84-year-old female admitted from a nursing home with altered mental status, leukocytosis (WBC 19,300/μL), and acute kidney failure (serum creatinine increased 497% relative to baseline). The patient was admitted to the ICU with severe complicated CDI with septic shock. Intravenous metronidazole 500 mg three times daily and oral vancomycin 125 mg four times daily were started on hospital day 1. The patient’s diarrhea and leukocytosis persisted (WBC 41,200/μL) and intravenous tigecycline was added on hospital day 7 as a 100-mg loading dose followed by 50 mg twice daily. She was treated with combination tigecycline, vancomycin, and metronidazole for 3 days. The patient’s diarrhea resolved and her WBC decreased yet remained elevated (WBC 33,600/μL). Tigecycline was discontinued per the family’s decision to switch her to oral antibiotics for discharge to hospice. This patient was classified as clinical failure due to non-resolving leukocytosis and sustained response was unevaluable due to the lack of clinical cure. No side effects associated with tigecycline use were noted in the electronic medical record.