Elsevier

Surgery

Volume 162, Issue 2, August 2017, Pages 325-348
Surgery

Colon/Rectum
Clostridium difficile disease: Diagnosis, pathogenesis, and treatment update

https://doi.org/10.1016/j.surg.2017.01.018Get rights and content

Clostridium difficile infections are the leading cause of health care–associated infectious diarrhea, posing a significant risk for both medical and surgical patients. Because of the significant morbidity and mortality associated with C difficile infections, knowledge of the epidemiology of C difficile in combination with a high index of suspicion and susceptible patient populations (including surgical, postcolectomy, and inflammatory bowel disease patients) is warranted. C difficile infections present with a wide spectrum of disease, ranging from mild diarrhea to fulminant colitis or small bowel enteritis and recurrent C difficile infections. Early implementation of medical and operative treatment strategies for C difficile infections is imperative for optimal patient outcomes. National and international guidelines recommend early operative consultation and total abdominal colectomy with end ileostomy and preservation of rectum. Diverting loop ileostomy and colonic lavage followed by intravenous metronidazole and intracolonic vancomycin administered via the efferent limb of the ileostomy should be considered as an alternative to total colectomy in selected patients. New and emerging strategies for C difficile infection treatment include monoclonal antibodies, vaccines, probiotics, biotherapeutics, and new antibiotics. A successful C difficile prevention and eradication program requires a multidisciplinary approach that includes early disease recognition, implementation of guidelines for monitoring adherence to environmental control, judicious hand hygiene, evidence-based treatment and management strategies, and a focused antibiotic stewardship program. Surgeons are an important part of the clinical team in the management of C difficile infection prevention and treatment.

Section snippets

Epidemiology

It has been conservatively estimated that CDI is responsible for over 500,000 enteric infections, the majority of which are hospital acquired.3 Over the past decade, there has been a significant increase in both the incidence and economic burden associated with CDI. Estimates of the annual economic burden ranges from $436 million to $3 billion dollars in the United States.4, 5, 6, 7 The morbidity associated with this disease process is significant, with more than 9% of hospital admissions for

History

The first description of a C difficile–associated disease (CDAD)-like process was recorded in a surgical patient at Johns Hopkins University in 1892.23 The patient was a 22-year-old woman who underwent operative care by Dr William Osler for resection of a tumor in the gastric pylorus. Early in the postoperative period, she developed severe diarrhea and died on the 15th postoperative day. The postmortem revealed a pseudomembranous “diphtheritic membrane” in the small bowel which upon cytological

Risk factors for CDI

Clinicians must be aware of the risk factors for CDI (Table I), because this will assist them in having a high index of suspicion in making an early diagnosis. Antibiotic use is the most common risk factor for initial and recurrent CDI.32 Although all antibiotics are associated with increased CDI risk, clindamycin, fluoroquinolones, and second-generation and higher cephalosporins are associated with the highest CDI risk. Proton pump inhibitors were identified as risk factors in some studies but

Pathogenesis

The gastrointestinal tract is a complex ecosystem exposed to a constant flow of microbial populations, many of which transit through the length of the bowel without establishing residency or causing disease. This microbial population of the gastrointestinal tract represents great genetic and ecologic diversity with an estimated 15,000 to 36,000 different species of bacteria residing within the lumen and on the mucosal surfaces.42

Clostridia are a heterogeneous group of organisms that exist in

Diagnosis and laboratory testing

The diagnosis of CDI requires rapid and accurate technologies for individual patient management and prevention of nosocomial transmission. Accurate diagnosis of CDI relies on a combination of clinical history and laboratory tests.55 Anaerobic culture of C difficile from stool remains a sensitive method for diagnosis, but acquisition of C difficile alone does not diagnose CDI because 4% of healthy adults may carry this organism in their normal intestinal flora and 20% to 25% of C difficile

Radiologic diagnostic imaging

Diagnostic imaging can assist in making an early diagnosis of CDI. Plain radiography of the abdomen can demonstrate polypoid mucosal thickening, “thumbprinting” (wide transverse bands associated with haustral fold thickening), or gaseous distention of the colon (ileus). CT scan imaging is most commonly used to evaluate patients with CDI to determine the severity of disease. Common CT findings include wall thickening, low-attenuation mural thickening corresponding to mucosal and submucosal

Clinical presentation

Acquisition of C difficile, like most enteric pathogens, results in a wide spectrum of clinical manifestations including intracolonic and extracolonic. The clinical features can vary from asymptomatic presentation to fulminant colitis and peritonitis due to perforation of the colon.

Medical treatment strategies

Initial management of CDI should always be discontinuation of antimicrobial agents that may have led to CDI. Antibiotic treatment of CDI is the mainstay of therapy, and specific antibiotic treatment guideline recommendations are based on the severity of CDI disease. Although initial systematic reviews documented that no antimicrobial agent was clearly superior for the initial cure of CDI,91 additional analyses stratified by disease severity identified that vancomycin provided improved initial

New and emerging medical treatment strategies

New approaches to CDI prevention and treatment are needed (Fig 4). Antibiotics under development include cadazolid and ridinilazole. Surotomycin has had disappointing phase 3 results. Multiple live biotherapeutics are being developed, including freeze thawed and encapsulated versions of fecal microbiota transplantation to improve the practicality of treating patients with recurrent CDI. Alternatives to fecal microbiota transplantation that aim to improve safety, including a microbial suspension

Operative treatment strategies

Operative consultation should be considered early in the course of severe and complicated CDI (Fig 5), as operative consultation may be beneficial.116, 117 High mortality rates have been reported with operative treatment for CDI, likely related to significant delay in operative intervention,118 but operative therapy for severe CDI can indeed be lifesaving. A systematic review of 510 patients with fulminant C difficile colitis reported decreased mortality comparing operative treatment with

Small bowel CDI

Small bowel involvement in CDI (enteritis) is uncommon; however, increasing case reports and series have been published, some leading to fatal outcome. Small bowel CDI is more commonly associated with abdominal operations and particularly among patients with IBD and with total abdominal colectomy.85 CT imaging features of CDI of the small bowel include mesenteric or retroperitoneal fat stranding, ascites, small bowel distention and mural thickening with the terminal ileum being the most

Recurrent CDI treatment

Recurrent CDI affects 15% to 35% of patients with primary CDI, and additional patients go on to develop chronic relapsing CDI. Prolonged vancomycin oral taper is the initial treatment strategy for recurrent CDI. For the first recurrence, use of the same regimen used in the first episode is recommended, unless the severity of disease dictates a switch from metronidazole to vancomycin. For the second recurrence and all subsequent recurrences, vancomycin is typically recommended in tapering and

Infection control strategies and prevention

The challenges posed by CDI represent one of the most difficult patient care issues confronting health care workers and infection control personnel. All efforts to prevent and control CDI should be implemented (Table V). Early recognition of patients who are suspected of having or who are diagnosed with CDI is the primary step in preventing the spread of this epidemiologically significant organism.49 C difficile can spread by direct or indirect contact with the patient or his/her environment.

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