IDSA/SHEA Guidelines on C difficile Infection in Adults and Children
In 2021, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) published a focused update to their 2018 clinical practice guidelines on treatment of Clostridioides (Clostridium) difficile infection (CDI). [14, 15] Recommendations included the following:
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In patients with a first C difficile infection (CDI) episode, fidaxomicin is recommended instead of a standard course of vancomycin
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In those with recurrent CDI episodes, fidaxomicin (standard or extended-pulsed regimen), rather than a standard course of vancomycin, is recommended
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In patients who experience a recurrent CDI episode within the preceding 6 months, it is recommended to use bezlotoxumab as a co-intervention in combination with standard-of-care (SOC) antibiotics, rather than SOC antibiotics only
ASCRS Guidelines on C difficile Infection
In 2021, the American Society of Colon and Rectal Surgeons (ASCRS) published clinical practice guidelines on the management of CDI. [16] Recommendations included the following:
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Oral vancomycin or fidaxomicin is first-line treatment for an initial CDI
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Metronidazole alone is no longer considered appropriate first-line treatment for CDI
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Surgery for C difficile colitis should be reserved for patients with colonic perforation or severe colitis who do not improve with medical therapy
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Subtotal colectomy with end ileostomy is recommended for severe-complicated or fulminant C difficile colitis
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A diverting loop ileostomy with antegrade colonic lavage may be an alternative to subtotal colectomy for the treatment of severe-complicated or fulminant CDI
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A prolonged course of vancomycin, adding bezlotoxumab or using fidaxomicin, is an acceptable therapy for recurrent or refractory CDI in stable patients
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Patients with recurrent or refractory CDI should be considered for fecal bacteriotherapy if conventional measures have failed
WSES Guidelines on C difficile Infection in Surgical Patients
In February 2019, the World Society of Emergency Surgery (WSES) published the following guidelines on diagnosis and treatment of CDI in surgical patients. [17]
Diagnosis
Diagnosis of CDI should be based on clinical signs and symptoms in combination with laboratory tests. Stool testing should only be performed on diarrheal stools from at-risk patients with clinically significant diarrhea (≥3 loose stools in 24 hours) with no obvious alternative explanation.
For patients with ileus who may be unable to produce stool specimens, polymerase chain reaction (PCR) testing of perirectal swabs is an acceptable alternative to stool specimen analysis.
Nucleic acid amplification testing (NAAT) for C difficile toxin genes appears to be sensitive and specific and may be used as a standard diagnostic test for CDI. NAAT may be performed as a single-step algorithm or included in a two-step algorithm starting with toxin enzyme immunoassay (EIA).
Glutamate dehydrogenase (GDH) testing is sensitive but does not differentiate between toxigenic and nontoxigenic strains. It may be used in association with toxin A/B EIA testing. Algorithms including screening with EIA for GDH followed by toxin assay may be suggested.
EIA for toxin A/B is fast, inexpensive, and highly specific but is relatively insensitive and is not recommended alone.
C difficile culture is relatively slow but sensitive and is rarely performed as a routine diagnostic test. It is recommended for subsequent epidemiologic typing and characterization of strains.
Repeat testing after a first negative sample during the same diarrheal episode may be useful only in selected cases with (a) ongoing clinical suspicion during an epidemic situation or (b) high clinical suspicion during endemic situations.
Computed tomography (CT) is suggested for patients with clinical manifestations of severe-to-complicated C difficile colitis; however, it is not sensitive enough for screening.
Ultrasonography (US) may be useful in critically ill patients suspected of having pseudomembranous colitis who cannot be transported to the CT suite.
Flexible sigmoidoscopy may be helpful in diagnosing C difficile colitis when there is a high level of clinical suspicion for CDI.
Antibiotic therapy
Unnecessary antibiotics should be discontinued if CDI is suspected. Unnecessary proton pump inhibitors (PPIs) should be discontinued in patients at high risk for CDI.
Empirical antibiotic therapy should be avoided unless CDI is strongly suspected. In such cases, empirical therapy for CDI should be considered while test results are awaited.
Oral metronidazole should be limited to treatment of an initial episode of mild-to-moderate CDI. Oral vancomycin is recommended for treatment of mild-to-moderate disease unresponsive to metronidazole. Repeated or prolonged courses of metronidazole should be avoided. Oral vancomycin and fidaxomicin are both recommended for treatment of severe CDI.
When oral antibiotics cannot reach the colon, vancomycin may be administered as a retention enema via a large rectal tube or catheter.
Fidaxomicin may be used to treat CDI, especially in patients at higher risk for recurrence (eg, elderly patients or those receiving concomitant antibiotics).
Surgical management
Patients with severe CDI who progress to systemic toxicity should undergo early surgical consultation and should be evaluated for potential surgical intervention.
For patients with fulminant colitis, total colectomy should be considered. However, diverting loop ileostomy with colonic lavage is a useful alternative.
Fulminant colitis should be treated with high-dose vancomycin (500 mg q6hr), orally or via enema or both, in combination with intravenous (IV) metronidazole (500 mg q8hr).
Supportive care
Early detection of shock and aggressive management of organ dysfunction are essential for improved outcomes in fulminant colitis. Supportive measures (eg, IV fluid resuscitation, albumin supplementation, and electrolyte replacement) should be provided to all patients with severe CDI.
Recurrent CDI
The first recurrence of CDI may be treated with vancomycin (particularly if metronidazole was used for the initial episode) or fidaxomicin. Antibiotic options for further recurrences include oral vancomycin in a tapered and pulsed regimen.
Probiotics
Limited direct evidence supports the use of probiotics in managing a first episode of CDI as an adjunct to antibiotics for immunocompetent patients.
Prophylactic probiotics may be considered for inpatients receiving antibiotics during a high-risk period before the disease develops. Probiotics should be not used in immunocompromised patients.
Probiotics for prevention of recurrent CDI may be an effective adjunct to standard antibiotic treatment (vancomycin) in patients with at least one prior episode of CDI.
Fecal microbiota transplantation
Fecal microbiota transplantation (FMT) may be an effective option for patients with multiple recurrences of CDI in whom appropriate antibiotic treatments have failed.
Monoclonal antibodies
Coadjuvant monoclonal antibody (bezlotoxumab) therapy may prevent CDI recurrences, particularly in patients who have CDI due to the 027 epidemic strain, are immunocompromised, or have severe CDI.
Intravenous immunoglobulin
IV immunoglobulin (IVIG) should be used only as adjunctive therapy in patients with multiple recurrences or fulminant CDI.
Enteral nutrition
Tube feeding patients should be clinically assessed due to their risk for developing CDI.
Antimotility agents
The use of antiperistaltic agents to treat CDI is discouraged. If such agents are used to control persistent symptoms, they must always be accompanied by medical therapy.
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Colonic pseudomembranes of pseudomembranous colitis. Photographs courtesy of Eric M. Osgard, MD.
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Endoscopic visualization of pseudomembranous colitis, a characteristic manifestation of full-blown Clostridium difficile colitis. Classic pseudomembranes are visible as raised yellow plaques, which range from 2-10 mm in diameter and are scattered over the colorectal mucosa. Courtesy of Gregory Ginsberg, MD, University of Pennsylvania.
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Gross pathology specimen from a case of pseudomembranous colitis revealing characteristic yellowish plaques.
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Gross pathology specimen from a case of pseudomembranous colitis, again demonstrating characteristic yellowish plaques.
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Frontal abdominal radiograph in a patient with proved pseudomembranous colitis. Note the nodular haustral thickening, most pronounced in the transverse colon.
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Barium enema demonstrating typical serrated appearance of the barium column (resulting from trapped barium between the edematous mucosal folds and the plaquelike membranes of pseudomembranous colitis).
