Thinking Beyond Antibiotics
Risk Factors, Diagnosis, and Management of Clostridium Difficile in the Emergency Department
By Sarah Hill
CASE
· L.P. is a 65 y.o. male with a pertinent PMHx of pre-diabetes, HTN presenting for diarrhea.
· Endorses profuse, watery diarrhea with crampy abdominal pain for one week. Has 5-6 episodes of diarrhea per day which are non-bloody and non-oily. He also endorses mild headache, fatigue, and dizziness with exertion. His diarrhea occurs 1 hour after eating or drinking and does not change with type of food.
· Notably, L.P. had a sinus infection two weeks prior for which he was prescribed Augmentin. His antibiotic course ended last week.
· Denies fever/chills, nausea/vomiting, chest pain, shortness of breath, or loss of consciousness. Denies any sick contacts or recent travel (including camping trips). No history of HIV, nor any risk factors for HIV.
· VS: were unremarkable (BP: 112/66, Temp: 36.6 °C (97.9 °F), Heart Rate: 78, Resp: 18, SpO2: 98 % on RA).
· PE: notable for mild, generalized abdominal tenderness to palpation without rebound or guarding. Bowel sounds were present, and his abdomen was soft and non-distended.
· Labs: notable for a lactate of 2.0 (0.4-1.6), and white blood cell count, lipase, creatinine, and chemistries all within normal limits.
ED Management
· He had an abdominal CT scan with IV contrast (see below) which was read as, “Mild colonic wall thickening and mucosal hyperenhancement in the sigmoid colon and rectum without significant pericolonic stranding, favoring colitis.”
· He received 1L bolus NS. Repeat lactate was 1.2.
· L.P. was unable to provide a stool sample for further analysis. With shared decision making, he was discharged and advised to follow up with his primary care doctor within the next few days to arrange for further testing and treatment.
Clinical Question: What is the role of testing and treating Clostridium difficile in the emergency department?
Summary of Evidence
Clostridium difficile is an anaerobic, Gram-positive bacteria which can produce significant morbidity in many patients. It is typically presents with profuse, watery diarrhea, though it can sometimes cause bloody diarrhea, fever, abdominal pain, nausea, decreased appetite, vomiting or constipation.8 The Infectious Diseases Society of America (IDSA) recommends that C. difficile infection be considered in patients with three or more unexplained diarrhea episodes in 24 hours.9 This is a relatively broad definition and allows a low threshold for testing.
Risk factors for C. difficile infection are classically taught as recent antibiotic use and hospitalization; however, patient age, malnutrition, recent surgery, medical comorbidities (e.g. cancer, liver disease, IBD), use of immunosuppressive medications, and use of proton-pump inhibitors have also been associated with increased risk of C. difficile infection.10 There have been attempts to create a prediction model based on these risk factors; however, these have not been validated and are not generally recommended to risk stratify patients at this point. 8 Although having an elevated white blood cell count is a significant prognostic indicator for patients with C. difficile infection, there is still some debate over whether or not leukocytosis is predictive of the initial diagnosis.12
Testing for C. difficile in the emergency department depends on the types of stool sample tests available, as there is no universally accepted clinical laboratory diagnosis. Some of these tests are controversial because of their lack of ability to distinguish between carriage status and pathology, and each test has different degrees of sensitivity and specificity. The IDSA has proposed two models for testing: a one step or multi-step.3 The one step method is a PCR method that tests for C. difficile toxin nucleic acid (NAAT). The multi-step process includes a glutamate dehydrogenase (GDH), which is highly sensitive but not specific, followed by an enzyme immunoassay (EIA) test, which is more specific. Though NAAT testing is quicker than the multistep process, it is a newer, more expensive method, and clinical efficacy has been less well studied than the multistep process.1
In the emergency department setting, it may be beneficial to employ a method of testing which displays rapid results while sacrificing some specificity, as opposed to more traditional methods that require >24 hours to result. As was the case with the patient described above, he was ultimately discharged, though he was not able to provide a stool sample for analysis. Had he been able to provide a sample, it would have been beneficial to get these results quicker in order to facilitate rapid discharge with the appropriate antibiotics treatment.
Once a patient has received a positive C. difficile test, treatment will be necessary. It is important to discontinue any ongoing antibiotics in these patients who have C. difficile infection and diarrhea symptoms.8 In addition, it is also recommended to initiate either oral vancomycin or fidaxomicin, which is a newer method of treatment. Patients may be given the option between vancomycin and fidaxomicin, as both have been shown to be equally effective against C. difficile infection in two randomized clinical trials.6,7 While vancomycin is significantly cheaper than fidaxomicin ($20-40 vs. $380), oral vancomycin is dosed 4 times per day, which may be less optimal for patients compared to fidaxomicin BID dosing.4 Though metronidazole is second-line for treatment, it has been shown to be less effective than oral vancomycin in two randomized clinical trials.5
Recommendations
- Presentation of C. difficile can vary; it includes watery diarrhea, bloody diarrhea, vomiting or constipation.
- Risk factors are not limited to recent antibiotic use and hospitalization; there may be an association with age, malnutrition, recent surgery, certain medical comorbidities, immunosuppressive medications, and PPIs
- Test patients with more than three diarrhea episodes in a 24-hour period (without a known cause) for C. difficile infection, especially with risk factors of antibiotic use, hospitalization, or other risk factors listed above.
- Testing method will vary based on institution, as there is no universally accepted clinical laboratory diagnosis. In the ED setting, recommend employing testing methods which result quickly to prioritize rapid diagnosis, treatment planning, and discharge.
- Vancomycin and fidaxomicin are the drugs of choice for C. difficile infection
References
1. Humphries RM, Uslan DZ, Rubin Z. Performance of Clostridium difficile toxin enzyme immunoassay and nucleic acid amplification tests stratified by patient disease severity. J Clin Microbiol. 2013 Mar;51(3):869-73. doi: 10.1128/JCM.02970-12. Epub 2012 Dec 26. PMID: 23269736; PMCID: PMC3592059.
2. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH. 2010. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).
3. Centers for Disease Control and Prevention (CDC): FAQs for Clinicians about C. diff. October 25, 2022
4. Johns Hopkins POCT-IT Guides, Antibiotics, Clostridioides (previously Clostridium) difficile Infections. October 19, 2022
5. Johnson S, Samore MH, Farrow KA, et al. Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. N Engl J Med. 1999;341(22):1645-51.
6. Cornely OA, Crook DW, Esposito R, et al; OPT-80-004 Clinical Study Group. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;55(Suppl 2):S93-103.
7. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection.N Engl J Med. 2011;364(5):422-31.
8. Carius, Brandon M., et al. "Clostridioides difficile infection evaluation and management in the emergency department." The American Journal of Emergency Medicine 38.10 (2020): 2203-2208.
9. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48.
10. Cunningham R, Dale B, Undy B, Gaunt N. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhea. J Hosp Infect. 2003;54(3):243-5
11. Gourdazi M, Seyedjavadi SS, Goudarzi H, et al. Clostridium difficile infection: epidemiology, pathogenesis, risk factors, and therapeutic options. Scientifica (Cairo). 2014;2014:916826.
12. Bosch, D. E., Mathias, P. C., Krumm, N., Bryan, A., Fang, F. C., & Greninger, A. L. (2021). Elevated White Blood Cell Count Does Not Predict Clostridium difficile Nucleic Acid Testing Results. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73(4), 699–705. https://doi.org/10.1093/cid/ciab10
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