Intestinal Lavage for the Treatment of Severe C. Difficile Infections
Intestinal Lavage for the Treatment of Severe C. Difficile Infections
Clostridium Difficile infections (CDIs) are treated initially with antibiotic therapy and
 supportive care, with surgical intervention reserved for patients with significant systemic
 toxicity or perforation. Severe CDI may be refractory to medical management and require
 surgical intervention, carrying a mortality of approximately 40%.

 Mortality associated with CDI increases significantly as the severity of the infection
 increases. In patients failing medical management, earlier operation is associated with
 decreased mortality. However, the lack of validated tools to predict the necessity for
 surgical intervention, combined with the significant morbidity associated with total
 colectomy significantly reduces the likelihood of patients receiving early surgical
 intervention. The purpose of the proposed study is to assess the addition of intestinal PEG
 lavage via nasojejunal tube to usual care in the treatment of adult patients with severe CDI
 who have no immediate indication for surgical intervention.
Despite a lack of definitive evidence, total abdominal colectomy (TAC) is currently
 recommended as the surgical intervention of choice in the setting of severe-complicated CDI.
 This recommendation was based on meta-analysis of studies comparing TAC to partial colectomy
 or other surgery (such as exploratory laparotomy without colectomy, or ostomy formation) or
 no surgery, which did not find any statistical mortality difference. This recommendation is
 based on the results of sensitivity analysis and an expert panel consensus that considered
 the potential for confounding factors such as TAC occurring later in the course of the
 disease and on sicker patients, and on anticipated patient values that would pace value on a
 definitive procedure being the initial surgical intervention.

 Given the high mortality of fulminant CDI, early surgical intervention is recommended.
 However, data regarding the optimal timing for surgical intervention is lacking.
 Meta-analyses and guidelines strongly recommend early surgical management, defined as being
 before the development of shock or the requirement for vasopressors, based on very low
 quality evidence, but with the potential for significant mortality reduction.

 On the basis of CDI being a toxin mediated inflammatory process of the colonic mucosa, Neal
 et al hypothesized that surgical diversion of the fecal stream with a loop ileostomy and
 intraoperative antegrade colonic lavage may effectively treat severe CDI. Widely referred to
 as the 'Pittsburgh Protocol,' the regimen included colonic lavage with 8 litres of
 polyethylene glycol (PEG 3350) intra-operatively after formation of a loop ileostomy,
 followed by antegrade Vancomycin flushes (500mg in 500cc Ringer's Lactate TID) and IV
 Metronidazole (500mg TID) for 10 days. The study utilized a before-and-after methodology
 comparing the experimental protocol to historical controls. Forty-two patients were submitted
 to the regimen over 18 months. Three patients required reoperation for TAC. 30-day mortality
 was 19% in the intervention cohort, compared to 50% in the control. 79% of survivors went on
 to ileostomy reversal within 6 months of surgery. One of the potential benefits of this
 regimen is that given the reduced morbidity compared to TAC, practitioners may have been
 offering surgical intervention earlier in the management of CDI and not exclusively as a
 therapy of last resort. Despite the limited sample size and methodological shortcoming of
 this study, this treatment regime has been adopted in some centres for select cases. A
 randomized controlled trial to compare this less invasive surgical approach with total
 abdominal colectomy was closed prematurely given lack of meaningful patient enrolment
 (clinicaltrials.gov identifier NCT01441271).

 Given the positive results of fecal diversion and antegrade lavage and vancomycin flushed
 proposed by Neal et al, combined with the limited data regarding the benefit of intracolonic
 vancomycin, a novel treatment was instituted at London Health Sciences Centre (LHSC) to
 accomplish lavage of the colon and vancomycin flushes in an antegrade fashion using a
 nasojejunal feeding tube to facilitate delivery in select patients. The protocol allows for
 lavage and intracolonic antibiotic delivery similar to that provided by the 'Pittsburgh
 protocol' without surgical fecal diversion.

 A small preliminary cohort of patients completing this protocol at LHSC is being assessed
 retrospectively, comparing outcomes to a group undergoing the Pittsburgh protocol and initial
 total colectomy. The study was approved by the Western University Research Ethics Board (REB
 File # 104944). Interim analysis of the past 24 months includes 13 patients undergoing the
 study protocol, 9 undergoing the Pittsburgh protocol and 17 undergoing initial colectomy.
 Despite significant limitations of the study methodology, the results are encouraging and
 further study is warranted, especially given the significant mortality associated with
 fulminant CDI.
Inclusion Criteria:

 -  Adult (>= 18 years) inpatients at LHSC with symptomatic CDI (diarrhea or colonic
 ileus)

 -  CDI confirmed by standard hospital microbiology lab testing

 -  Patients must meet criteria for severe CDI, defined as either: white blood cell >
 15,000 or Serum Creatinine > 1.5 times the pre-morbid level

 -  Patients must have at least one additional risk factor for severity:

 i. Fever >38.5 (if no other source of fever suspected) ii. Vasopressor requirement
 iii. Mechanical ventilation requirement iv. Serum lactate >5 mmol/L v. Colonic
 distension (>6cm transverse colon diameter on abdominal Xray or CT) vi. Colonic wall
 thickening, on abdominal Xray or CT, as reported by radiology. vii. Calculated ATLAS
 score ≥ 4

 Exclusion Criteria:

 -  The patient is deemed to have an immediate indication for surgery related to the
 diagnosis of CDI by the on call General Surgery service.

 -  Pre-existing bowel discontinuity (e.g. ileostomy).

 -  General Surgery service or most responsible care team deem the patient to have a
 contraindication to nasojejunal tube or fecal management system

 -  Patients anticipated to be intolerant of the study regimen (e.g. severe ileus, unable
 to tolerate oral intake, etc.)