CC
A 65-year-old male, status post incision and drainage (I&D) of a severe facial infection, who was previously admitted to the hospital for treatment of an odontogenic infection, complains of the new onset of severe “watery diarrhea.”
HPI
The patient was admitted 6 days earlier and was taken to the operating room on that day, where I&D of the right submandibular–medial masticator and submental spaces, with extraction of a grossly carious right mandibular first molar, was performed. He remained intubated for 3 days and was maintained on intravenous (IV) clindamycin (900 mg every 8 hours). A previously placed nasogastric tube was also removed. The patient continued to do well and was transferred to the ward from the intensive care unit on the fourth postoperative day, with continuation of the IV clindamycin therapy.
On hospital day 6, the patient reported lower abdominal pain and cramping of over 12 hours’ duration. He also reported experiencing nausea, malaise, fever, and chills. He had several episodes of profuse, watery diarrhea, which were documented by the nursing staff. There was no evidence of blood in his stool, but he has had minimal oral intake since the symptoms began.
PMHX/PDHX/medications/allergies/SH/FH
Allergies. The patient has a penicillin allergy (history of rash).
Current medications. He is receiving clindamycin 900 mg intravenously every 8 hours and morphine sulfate 2 mg every 4 hours as needed for pain.
Examination
General. The patient is an obese male in mild distress who is resting in bed.
Vital signs. His blood pressure is 110/68 mm Hg, heart rate is 118 bpm (tachycardia secondary to elevated temperature and gastrointestinal [GI] fluid losses), respirations are 18 breaths per minute, and temperature is 38.8°C (fever secondary to release of inflammatory mediators in the GI tract).
Maxillofacial. With decreasing facial edema, drains in the submandibular and submental spaces are nonproductive; removal is pending.
Abdominal. The abdomen is soft, nontender, and nondistended, with hyperactive bowel sounds in all four quadrants. There is no guarding or rebound tenderness (these would be indicative of peritonitis).
Imaging
Plain radiographic imaging studies of the abdomen (e.g., kidney–ureter–bladder) can be used to assist in the diagnosis of Clostridioides difficile –associated diarrhea. ( Clostridium difficle was reclassified in 2016 to Clostridioides difficle , this necessary change allowed the continued use of the familiar abbreviation C. difficle or C. diff ). Plain radiographs may reveal a dilated colon suggestive of ileus. (Patients with severe disease may develop colonic ileus or toxic dilatation with abdominal pain and distension with minimal or no diarrhea.) A diffusely thickened or edematous colonic mucosa is often better visualized on an abdominal computed tomography scan. Thickening can sometimes be seen on abdominal plain films.
Colonoscopy or sigmoidoscopy is a more invasive diagnostic modality that is reserved for cases in which rapid diagnosis is necessary or stool samples cannot be obtained secondary to ileus. The finding of pseudomembranes is pathognomonic for C. difficile colitis. Because of the increased risk for intestinal perforation, endoscopy should be used sparingly in patients with suspected C. difficile –associated diarrhea.
Because this patient is relatively stable, abdominal imaging and endoscopy are not indicated.
Labs
A basic metabolic panel demonstrated an elevated sodium level (148 mEq/L) and elevated blood urea nitrogen and creatinine (secondary to dehydration). Serial complete blood counts demonstrated elevation of the white blood cell (WBC) count, from 12,000 to 20,000 cells/μL, with bandemia.
The result of the patient’s stool guaiac test was negative for blood. The enzyme-linked immunosorbent assay (ELISA) result for C. difficile toxin was positive.
The current Infectious Diseases Society of America (IDSA) guidelines for testing for C. difficile infection (CDI) outline limiting testing to patients (who are not taking laxatives) with an unexplained onset of three or more unformed stools in 24 hours. There is a high prevalence of asymptomatic C. difficile colonization in infants, and it is not recommended to test children younger than 1 year of age. Repeat testing within 7 days of onset of diarrhea is not recommended because there is a high rate of false-positive results.
The reference tests for diagnosis of C. difficile –mediated disease is a cytotoxin assay. Although this test is highly sensitive and specific, it is difficult to perform, and the results are not available for 24 to 48 hours. In addition, the testing facility must be equipped with tissue culture capabilities. Instead, it is recommended to use enzyme ELISA can be used to detect C. difficile toxin (A and/or B) in stool. This test has a sensitivity of 63% to 99% and a specificity of 93% to 100%. ELISA can be quickly performed (2–6 hours) and is the laboratory test most frequently used to diagnose CDI. Bacterial culture, nucleic acid amplification testing, and antigen glutamate dehydrogenase detection methods have high sensitivity but low specificity for accurately detecting C. difficile.
The average range for peripheral WBCs in patients with C. difficile –associated diarrhea is 12,000 to 20,000 cells/μL, but occasionally, the count is higher. An important indicator of impending fulminant colitis is a sudden rise in peripheral WBCs to 30,000 to 50,000 cells/μL. Because progression to shock can occur even in patients who have had benign symptoms for weeks, early warning signs, such as leukocytosis, can be invaluable.
Assessment
Resolving odontogenic infection now complicated by C. difficile–associated diarrhea.
Treatment
In otherwise healthy adults, the first steps are to discontinue the precipitating antibiotic and to administer fluids and electrolytes to maintain hydration. For many patients, antibiotic-associated diarrhea is a mild and self-limited illness that responds to the discontinuation of antibiotics, supportive care, and fluid and electrolyte replacement. Specific pharmacotherapy for C. difficile –associated diarrhea should be initiated after the diagnosis of C. difficile has been confirmed or in highly suggestive cases of severely ill patients.
The IDSA recently updated its guidelines for the management of CDI in 2021, which are outlined in Table 8.1 . Fidaxomicin, a macrocyclic antibiotic and the newest US Food and Drug Administration–approved treatment for CDI, is the recommended first-line treatment for initial and recurrent CDI. Fidaxomicin is orally delivered, similar to vancomycin, with minimal systemic absorption, targeted activity against C. difficile, and a low risk of resistance. Four randomized clinical trials have shown that patients treated with 200 mg of fidaxomicin given twice daily for 10 days have a lower risk of CDI recurrence than those treated with vancomycin.
| Clinical Presentation | Recommended and Alternative Treatments | Comments |
|---|---|---|
| Initial CDI episode | Preferred: fidaxomicin 200 mg given twice daily for 10 days | Implementation depends on available resources |
| Alternative: vancomycin 125 mg given four times daily PO for 10 days | Vancomycin remains an acceptable alternative | |
| Alternative for nonsevere CDI, if above agents are unavailable: metronidazole, 500 mg three times daily PO for 10–14 days | Definition of nonsevere CDI is supported by the following laboratory parameters: WBC count of ≤15,000 cells/μL and a serum creatinine level <1.5 mg/dL | |
| First CDI recurrence | Preferred: fidaxomicin 200 mg given twice daily for 10 days OR twice daily for 5 days followed by once every other day for 20 days | — |
| Alternative: vancomycin PO in a tapered and pulsed regimen | Tapered or pulsed vancomycin regimen example: 125 mg four times daily for 10–14 days, two times daily for 7 days, once daily for 7 days, and then every 2–3 days for 2–8 weeks | |
| Alternative: vancomycin 125 mg given four times daily PO for 10 days | Consider a standard course of vancomycin if metronidazole was used for treatment of the first episode | |
| Adjunctive treatment: bezlotoxumab 10 mg/kg given intravenously once during administration of SOC antibiotics b | Data when combined with fidaxomicin are limited; caution for use in patients with CHF c | |
| Second or subsequent CDI recurrence | Fidaxomicin 200 mg given twice daily for 10 days OR twice daily for 5 days followed by once every other day for 20 days | — |
| Vancomycin PO in a tapered and pulsed regimen | … | |
| Vancomycin 125 mg four times daily PO for 10 days followed by rifaximin 400 mg three times daily for 20 days | … | |
| Fecal microbiota transplantation | The opinion of the panel is that appropriate antibiotic treatments for at least two recurrences (i.e., three CDI episodes) should be tried before offering fecal microbiota transplantation | |
| Adjunctive treatment: bezlotoxumab 10 mg/kg given intravenously once during administration of SOC antibiotics b | Data when combined with fidaxomicin are limited; caution for use in patients with CHF b | |
| Fulminant CDI |
|
Definition of fulminant CDI is supported by hypotension or shock, ileus, and megacolon |
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