Saturday, March 24, 2012

Drinking Stool

Motivation: Pouring mashed up liquid stool down NG tube? Sounds disgusting.  Imagine the smell from the next burp.  I heard about his idea from a friend last night post-dinner, and I almost could not believe that it works.  But, "fecal transplant" or fecal bacteriotherapy exists and, in some niche corners of the country, is considered the salvage therapy of choice for severe C. diff infections.  What about the data?  There have not been RCTs but plenty of convincing case series. Reviewed is one of the larger case series.

Paper: Aas, J., Gessert, C.E., and Bakken, J.S.  Recurrent Clostridium difficile Colitis: Case Series Involving 18 Patients Treated with Donor Stool Administered via a Nasogastric Tube. CID (2003) 36: 580-585.

Methods: Study was conducted in a single centre in Minnesota.  Inclusion criteria for stool receipients were documented C. difficile infections and two or more relapses despite adequate treatment.  Stool donors were usually spouses or other close family members or donors if family members were not present.  Collected stool was screened by culture and O+P screen to rule out pathogenic infection.  Collected stool was mixed with 50-70 mL of normal saline and then homogenized using a household blender.  The blended mixture was filtered through a paper coffee filter.  For four days prior to transfer, receipients were treated with oral vancomycin and then treated with omeprazole on the day of transplantation.  An NG tube was placed with instillation of 25 mL of liquid stool followed by 25 mLof NS through the tube.  Then, the NG tube was removed, and patients were discharged or returned to their wards.

Results:
Cohort: The study recruited 18 participants.  Mean age was 73 years (range, 51-88) with 72% female (13/18 patients).  Five were inpatients while 13 were treated at GI clinic.  Patients in general had received a mean of 3.6 courses of anti-microbial therapy (metronidazole/vancomycin) prior to consideration for stool transplant.

Follow-up Results:  Of the 18 patients treated, 15 experienced complete resolution defined as cessation of diarrhea and negative C. diff stool testing at ninety day follow-up! Two inpatients treated with stool transplant died (one had ESRD undergoing peritoneal dialysis who developed peritonitis and died, other patient had COPD complicated by pneumonia 14 days after stool transplant).  There was one treatment failure in the protocol who developed recurrent C. diff that was successfully treated after one additional course of oral vancomycin.

Discussion: I am amazed that the procedure works.  The cure rate was 83% in patients with refractory C. difficile infection.  I think that this therapy points out the important fact that C. diff flourishes because of the lack of normal bowel flora, and continuous rounds of metronidazole/vancomycin do little to fix that problem.  The authors chose close family members for donors because presumably their bowel flora is similar to the patient's bowel flora.  A cautionary note for the article are the two deaths.  While both patients were sick prior to the transplantation, it is possible that introducing stool to a very sick patient at risk for aspiration could be dangerous (one patient died of PNA after stool transplantation).  This procedure is probably best suited to the outpatient setting.  On the other hand, there have been reports of C. diff induced ICU level colitis being treated with stool transplantation introduced by colonoscopy, which bypasses the risk of aspiration and ileus in sick patients.  While this theory needs confirmation with a RCT, the stool transplant is cheap and probably effective!

PS: Sorry for the far between posts.  I will write more regularly.

Sunday, March 11, 2012

PCP and Steroids

Motivation: For prevention of PCP in patients taking steroids, I have heard a variety of rumors on the needs of Pneumocystis pneumonia prophylaxis.  After what dose of steroid and what duration do patients need prophylaxis?  Some doctors prescribe Bactrim for more than 20 mg of prednisone use for more than a month to some GI doctors who do not prescribe prophylaxis even on higher doses of prednisone.  Recently, our medicine team wondered where the data came from.  One of the major studies addressing this question came from Mayo Clinic in 1996.

Paper: Yale, S.H. and Limper, A.H. "Pneumocystis carinii Pneumonia in Patients Without Acquired Immunodeficiency Syndrome: Associated Illnesses and Prior Corticosteroid Therapy." Mayo Clinical Proc.(1996) 71: 5-13.

Methods: Between 1985-1991, data on patients presenting to Mayo Clinic with Pneumocystis pneumonia but without HIV were retrospectively analyzed.  PCP was proven by bronchoalveolar lavage, lung biopsy, or autopsy.  Patients were excluded from analyses if clinical syndrome was suggestive of AIDS.

Results:
Cohort: Between 1985-1991, there were 116 patients with PCP pneumonia without AIDS.  These patients commonly had associated conditions of hematologic malignancy (30.2%), organ transplantation (25%), inflammatory diseases (22.4%), solid tumors (12.9%), and other diseases.

Steroid Use: Of the 116 patients, 105 (90.5%) had used steroid therapy within one month of diagnosis of PCP.  98 (84.5%) were using steroids at time of diagnosis.  Prednisone use dose and duration are depicted as below:
  • Median dose: 30 mg of prednisone (25th percentile was 16 mg meaning 25% were using less than 16 mg)
  • Median duration: 12 weeks (25th percentile was at 8 weeks)
Concurrent Infections: In 57.8% of patients, additional infectious agents were detected.  No significant differences in incidence of concurrent infections were noted among different underlying illnesses (such as malignancy vs inflammatory diseases).  The most common concurrent infection was CML (35.3%) followed by Candida infection (18.1%).

Outcome: Overall, in-hospital mortality was 34%.  Respiratory failure occurred in 43% of patients and was associated with 66% mortality.  Of note, PCP infection was associated with a 100% mortality in patients with solid malignancies.  Finally, survival to discharge from hospital was linked to lower dose of corticosteroid at the time of diagnosis.

Discussion: Overall, this paper provides a rough guide to the dose of steroid (median 30 mg) and duration (median 12 weeks) associated with PCP.  However, I think that this paper also shows that there is no absolute threshold effect beyond which the risk clearly skyrockets.  The 25th and 75th percentiles were very  wide.  Another interesting and cautionary outcome is that in the immunosuppressed, there is often co-infection of multiple pathogens, and the process of diagnosis should not stop after detecting PCP.  Also, 11 patients got PCP without using steroids.  PCP should remain on the differential for any immunosuppressed individual.

This paper also has some significant limitations.  First, patients who were selected in this analyses had received at least BAL or lung biopsy.  Currently, many patients are diagnosed by stains of sputum and may be less sick than those getting BAL.  Also, the paper does not address properly the more interesting question of what is a safe dose of prednisone to use without prophylaxis.  Perhaps if the authors picked a population with medium to low dose prednisone use, then a "safe" dose could be described.