Abstract
Clostridium difficile is a gram-positive bacterium that is recognized as a causative organism of pseudomembranous enterocolitis. This infection has become a major public health challenge and is a source of considerable morbidity and mortality in those infected. We present a 62-year-old African American female with a long history of HIV infection, who presented with abdominal pain and continuous diarrhea due to pseudomembranous colitis. After failing multiple episodes of conventional therapy, it was decided to treat her with fecal microbiota transplantation. Fecal microbiota transplantation was given on 3 separate occasions from a biological-related donor without success. It was only after a fourth transplant was done with a nonrelated donor that the patient resolved her diarrhea within 48 hours. We suggest that fecal samples from different donors have different abilities to cure Clostridium difficile colitis in at least this immunosuppressed patient.
Introduction
Clostridium difficile is a gram-positive bacterium responsible for pseudomembranous colitis which is a leading cause of both community- and hospital-acquired pseudomembranous colitis it has become a major health challenge and a cause of considerable morbidity. Risk factors associated with the development of C. difficile pseudomembranous colitis includes prolonged use of antibiotics, advanced age, and immunosuppression. 1 Immunocompromised patients are at particular risk of C. difficile infection and is a common cause of bacterial diarrhea in persons with HIV infection (incidence ratio 1.3-9 cases per 1000 person-years). 2 Approved treatment includes oral vancomycin, fidaxomycin, and metronidazole. Recently there has been accumulating evidence that fecal transplantation benefits patients, especially with refractory C. difficile colitis. 3 The fecal microbiota transplantation (FMT) has been safe and well tolerated, with few serious adverse events, even though it is often administered to patients with significant comorbid conditions. 4 Fecal microbiota transplantation has been shown to be efficacious and safe in several case series and a recently published clinical trial. However no study has investigated the safety and efficacy of fecal transplant in a larger cohort of immunocompromised patients. 5 While protocols vary, it is unclear whether or not the donor may have an effect on clinical outcome in the recipient patient. Our case presentation suggests that the donor selection may be important.
Case Presentation
We present the case of a 62-year-old African American female infected with HIV for over 10 years period of time who had prolonged CD4 count of less than 200 cells/mm3 mostly due to noncompliance of HIV medications. She presented to our institution with diarrhea over the past 10- to 14-day period of time, with 8 to 15 loose stools a day after prolonged course of antibiotics prescribed by her nursing home. Concomitant illnesses include hypertension, diabetes mellitus, congestive heart failure, end-stage renal disease on hemodialysis, and cytomegalovirus retinitis (for which she was on valganciclovir therapy). At the time of admission to the hospital, the patient was dehydrated because of 8 to 15 loose stools a day over the past 2 weeks and the associated abdominal pain. Her temperature was 100°F and blood pressure 110/70 mm Hg. Examination revealed diffuse abdominal tenderness without rebound or rigidity. Basic laboratory data were normal except for an elevated creatinine due to renal failure. Stool analysis was positive for C. difficile toxin and negative for Cryptosporidium, Giardia, [ova and parasite], or any bacteria pathogens. Diagnostic colonoscopy confirmed pseudomembranous colitis. Table 1 shows the treatment and regimen.
Course of Therapy.a
aPatient follow-up 6 months posttreatment showed no evidence of diarrhea or recurrent disease.
Discussion
It is not uncommon for clinicians to experience failure of the standard treatment for C difficile colitis in both immune-intact and immunosuppressed patients. The literature is now growing, suggesting that FMT may benefit a significant percentage of these patients who have failed other therapies. Protocols vary on how the stool is evaluated and how it should be administered. In our particular patient who failed multiple therapies, we gave stool from a blood relative (son) in three different fashions (via colonoscopy, NG tube and rectal enema), and all three FMTs failed. However, when a nonrelative was used as the donor and utilizing the same protocol, the patients diarrhea was controlled within 48 hours, despite the prior documented failures. This is the first publication that we are aware of to suggest that the donor of the stool may be important in the clinical response of the patient, and may suggest that stool from a nonrelated donor may be therapeutic when FMT fails and when the donor is a family member.
Footnotes
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JG and CM have been consultants or speakers in conferences supported by AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, ViiV Healthcare, Janssen, Merck, and Gilead and are members of institutions that received research grants from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, ViiV Healthcare, Boehringer Ingelheim, Pfizer, Janssen, Merck Frost, Gilead and Tibotec (Janssen) Therapeutics; has served an investigator for Abbott, Avexa Ltd, Boehringer Ingelheim Pharmaceuticals (BI), Inc, Gilead Sciences, GlaxoSmithKline, Merck & Co, Inc, Pfizer Inc, Roche Laboratories, Parexel, Hiesped and Tibotec Therapeutics; and his institution has received honoraria for speaking or chairing engagements from Abbvie, Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Merck & Co, Inc, Pfizer Inc, and Tibotec Therapeutics.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.