Intestinal microbiota transplantation, a simple and effective treatment for severe and refractory Clostridium difficile infection. Zainah H, Hassan M, Shiekh-Sroujieh L, Hassan S, Alangaden G, Ramesh M. Dig Dis Sci. 2015 Jan;60(1):181-5.
This is a retrospective single-center study that evaluated patients with severe refractory Clostridium difficile colitis who received intestinal microbiota transplant (IMT). Severe Clostridium difficile was defined as patients having ≥ 2 of the following: age > 60 years, albumin < 2.5 mg/dL, temperature > 38.3° C, WBC > 15 within 48 hr of Clostridium diagnosis OR endoscopic evidence of pseudomembranous colitis OR treatment in the intensive care unit for Clostridium difficile infection. Refractory was defined as non-resolution after 7 days of oral vancomycin +/- IV metronidazole. Intestinal microbiota transplant was performed via nasogastric tube or colonoscope after donor stool screening. Antibiotics for Clostridium difficile were stopped 24 hours beforehand.
49 patients received IMT over the 2 year study period, 14 of which were identified as severe and refractory. Of the 14 patients, 6 patients (43%) had primary Clostridium difficile and 8 patients (57%) had recurrent disease. Overall cure was achieved in 11 patients (79%). 3 patients were nonresponders. There were four deaths (29%), all of which were due to progression of underlying cancer. There were no morbidities related to the intestinal microbiota transplant.
The majority of literature regarding intestinal microbiota transplants addresses recurrent, outpatient Clostridium difficile infections. This paper applies to the acute care surgeon, who is often faced with a high-risk operative candidate, and offers a therapy that would obviate the need for surgery. Discussion between acute care surgeons and infectious disease physicians to further incorporate this treatment in Clostridium difficile management is warranted.
Clostridium Difficile Infection from a Surgical Perspective. Kaiser AM, Hogen R, Bordeianou L, Alavi K, Wise PE, Sudan R. J Gastrointest Surg. 2015 Jul;19(7):1363-77.
This review summarizes the risk factors, treatment options and factors affecting surgical outcomes for Clostridium difficile infection (CDI) based on the current literature. The incidence and severity of CDI has increased substantially over the past ten years, with mortality approaching 80% for fulminant disease. Acute Care surgeons must identify and minimize the risk of CDI, and determine which patients will benefit from surgery. Earlier identification of patients that might fail non-operative management is essential for improving surgical outcomes.
Surgery is required for only a small percentage of patients but should not be delayed in the setting of severe or fulminant disease. The authors’ findings that early surgical treatment (i.e. before the development of shock, vasopressor requirement, multi-organ failure and mental status changes) is associated with better outcomes supports the EAST practice management guidelines for the surgical treatment of Clostridium difficile-associated disease published in 2014. Open total abdominal colectomy with end ileostomy is their preferred surgical approach for patients with severe or fulminant colitis. The focus should be on early devascularization of the colon to limit the systemic inflammatory response. Even though the rectal stump may harbor disease, the authors suggest that the risks associated with a procto-colectomy outweigh the benefits. They also do not recommend a segmental colectomy as it leaves inflamed tissue behind, and up to 15.9 % of patients will require reoperation.
While new treatment strategies for mild or recurrent disease are emerging, including loop ileostomy with colonic lavage, fecal microbiota transfer and C. difficile vaccinations, there is insufficient data to make any conclusions about their safety and efficacy. They conclude that the most severe forms of CDI benefit from involvement of a surgical team but further research is needed to determine the optimal timing and indications for surgical intervention.
Diagnosis and treatment of Clostridium difficile in adults: a systematic review. Bagdasarian N, Rao K, Malani PN. JAMA. 2015 Jan 27;313(4):398-408.
This review discusses the current best practices for the diagnosis and treatment of C difficile Infections (CDI) in adults. The authors searched Ovid MEDLINE and Cochrane databases for relevant articles from January 1978 to October 2014. Out of 4682 articles, 116 were included in this review.
The authors stress that the diagnosis of CDI cannot be made on laboratory tests alone but requires the presence of diarrhea (≥ 3 unformed stools/24 hrs) or radiologic evidence of ileus or toxic megacolon; and a positive stool test for toxigenic C difficile (tCD) or its toxins or colonoscopic or pathologic findings of pseudomembranes. The gold standard for detecting tCD is toxigenic culture, while the gold standard for detecting toxins A/B is cell cytotoxicity assay (CCA). Rapid testing for tCD includes glutamate dehydrogenase (GDH) testing and nucleic acid amplification testing (NAAT). However, GDH is present in nontoxigenic strains of C Diff, and NAAT testing’s high sensitivity can identify tCD in asymptomatic patients. This underscores the importance of testing only symptomatic patients.
Treatment of CDI should be based on severity and risk of recurrence or complications. One clinical practice guideline categorizes mild CDI as WBC of < 15 and serum creatinine (crt) < 1.5 times premorbid level, severe as WBC ≥15 or crt ≥ 1.5 times premorbid levels, and severe, complicated (fulminant) CDI as having hypotension, shock, ileus or megacolon. Older patients, those with co-morbidities, and those with severe disease are some factors that put patients at a greater risk.
In general, oral metronidazole (MTZ) has higher failure and higher recurrence rates when compared to oral vancomycin (VNC). Intravenous MTZ has failure rates with mild and severe disease, and its use as monotherapy is discouraged. The authors state in severe or complicated cases, a combination of oral and rectal VNC may be useful; however, there is little data to support this practice. Early surgical evaluation for fulminant CDI is warranted as early intervention can reduce mortality. Recurrent CDI should be treated with oral VNC or fidaxomicin (FID), which also has better response rates when concomitant antibiotics cannot be stopped. Higher cost prohibits FID as first line therapy. Other treatments discussed include probiotics, which may prevent initial infections and recurrences, C Difficile vaccines which are in development, and fecal microbiota transplantation which has very promising clinical response rates in recurrent disease.