Fidaxomycin shows promise in managing recurrent clostridioides difficile infections.
C. diff recently got an extreme makeover. It has a new name, new severity criteria, and new first line treatment agents. However, it remains a nasty player in the world of nosocomial infections and antibiotic-associated diarrhea.
Clostridoides (previously Clostridium) difficile infection (CDI) is a common diarrheal infection that occurs most often in hospitalized patients or following antibiotic use. While antibiotics are essential for treating many infections and meeting sepsis core measures, they have the untoward effect of allowing C diff to get its foot in the door. Antibiotics kill the quiet, unobtrusive tenants of the colon, namely the billions of commensal bacteria that were minding their own business. C diff then seizes the opportunity, filling the now vacant GI mucosa, replicating, and sometimes causing symptomatic CDI. The antibiotic classes most often associated with CDI are fluoroquinolones, clindamycin, and broad spectrum cephalosporins/penicillins. Macrolides and trimethoprim-sulfamethoxazole are occasionally associated with CDI, and other classes such as metronidazole, vancomycin, tetracycline, and aminoglycosides are rarely associated with CDI. In addition to antibiotic use, higher risk patients include those who are older, immunocompromised, reside in a nursing home, or those who have been recently hospitalized or had surgery. CDI racks up a health-care bill of $1.1 billion in the US annually.
Diagnosis and Severity
To make the diagnosis, patients should have at least three watery stools in 24 hours and a positive stool study. Patients with signs of fulminant colitis or severe infection can be treated empirically even before the stool study is back. The Infectious Disease Society of America (IDSA) has published criteria for assessing severity of CDI. The infection is considered non-severe if the white blood count is ≤ 15,000cells/mL and the serum creatinine is <1.5mg/dL. Patients are designated as having severe CDI if the WBC is over 15,000cells/mL and the serum creatinine is ≥ 1.5mg/dL. Patients who have hypotension, signs of shock, toxic megacolon, or ileus are diagnosed as fulminant colitis, which previously was called severe, complicated CDI.
Treatment of Initial Infection
When managing a patient with CDI, first provide supportive care for patients who are dehydrated or have electrolyte abnormalities. Next, stop the offending antibiotic if possible, or switch to one of the antibiotics that are more rarely associated with CDI. Then consider your C diff treatment options. Prior to the latest IDSA guidelines, metronidazole was the preferred first-line agent for treating CDI.
Now, for an initial, non-severe or severe episode in adults, the recommendations are for either oral vancomycin 125mg, four times daily for 10 days or oral fidaxomicin 200mg BID for 10 days. If neither of those is available, then metronidazole, 500mg TID for 10 days can be used instead. For patients with an initial fulminant episode, vancomycin 500mg, four times daily by mouth or nasogastric tube is recommended. For patients who have an ileus and may not be able to absorb the oral vancomycin, rectal vancomycin can be considered as well, though absorption is erratic. The dosing of rectal vancomycin is 500mg in 100mL of saline administered via rectal tube Q6 hours. For patients with fulminant disease, particularly those with an ileus, IV metronidazole 500mg Q8 hours should also be used in addition to the oral vancomycin. There is no role for IV vancomycin.
Treatment of recurrent disease essentially ratchets up the treatment ladder from the prior treatment used. If metronidazole was used in the initial treatment, then vancomycin should be used for the recurrence. If vancomycin was used for the initial treatment, then fidaxomicin is recommended for the recurrence. Another option is for an extended vancomycin taper. The evidence behind the recommendations for treatment of recurrent disease is weaker than for the initial treatment. For patients who have a second recurrence, treatment options can also include fecal transplantation. The latter is clearly outside the scope of ED practice, and would require a referral.
How it works:
Fidaxomicin is a great option for CDI because it is bactericidal and is narrow spectrum. It selectively kills the C diff bacteria, while leaving the rest of the gut flora unharmed. Fidaxomicin is a macrocyclic antibiotic, has minimal absorption systemically when taken orally, and has been associated with lower rates of recurrent CDI compared with vancomycin. In addition, fidaxomicin is given BID, enhancing compliance potential over vancomycin. Vancomycin and metronidazole are both bacteriostatic against C. diff.
Cost and availability are the big downsides of the new recommendations. A course of fidaxomicin costs around $3,500, insurance coverage is inconsistent, and it is not on formulary at all institutions. A course of oral vancomycin is around $1,200, while a metronidazole is only $22.
Dosing Summary for Initial Episodes of CDI in Adults
|Non-severe||WBC ≤ 15k, SCr < 1.5mg/dL||Vancomycin 125mg PO QID x 10 days or
Fidaxomicin 200mg PO BID x 10 days
If these are unavailable, consider metronidazole 500mg PO TID x 10 days
|Severe||WBC > 15k, SCr ≥ 1.5mg/dL||Vancomycin 125mg PO QID x 10 days or
Fidaxomicin 200mg PO BID x 10 days
|Fulminant colitis||Hypotension, shock, ileus, or megacolon||Vancomycin 500mg PO QID.
(if ileus consider rectal vancomycin 500mg in 100mL normal saline via rectal tube Q6hrs) and metronidazole IV 500mg Q8hrs
McDonald 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 and Epidemiology of America (SHEA), Clin Infect. Dis. 2018 19;66(7):e1-e48