9/18/2018. Clostridium Difficile: Updates on Diagnosis and Treatment. Clostridium difficile Infection (CDI) Clostridium difficile Infection (CDI)

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1 Clostridium Difficile: Updates on Diagnosis and Treatment Elizabeth Hudson, DO, MPH 9/25/18 Antibiotic-associated diarrhea and colitis were well established soon after widespread use of antibiotics In 1978, C. difficile was identified as the causative pathogen in the majority of cases of antibiotic-associated colitis many early cases were attributed to clindamycin Between 1989 and 1992, a strain of C. difficile highly resistant to clindamycin was implicated in large outbreaks of diarrhea in four hospitals in the United States From 2003 to 2006, CDI was observed to be more frequent, severe, refractory to standard therapy, and more likely to relapse than previously described These observations have been attributed to the emergence of a new strain designated BI, NAP1, or ribotype 027 This strain appears to be more virulent than other strains: attributable to increased toxin production compared with previous strains Fluoroquinolone use has strongly correlated with the emergence of this strain 1

2 In 2011, an estimated 453,000 initial cases of CDI occurred in the United States An estimated 159,700 cases were community associated and 293,000 were health care associated, with 107,600 of them hospital acquired The BI/NAP1/027 strain was identified more often in health care-associated cases than in community-associated cases Seeing more colonization with C diff C. difficile carriage occurs in 8 to 10 % of adults residing in hospitals or long-term care facilities (the carrier rate among healthy adults is about 3 percent) Asymptomatic C. difficile carriers are capable of shedding C. difficile spores and serve as a reservoir for environmental contamination to other hospitalized patients New exposure and colonization by C. difficile are more likely to lead to CDI, while patients previously colonized with C. difficile are more likely to remain asymptomatic during their hospitalization Antibiotic exposure Age > 65 Risk Factors for First Episode of CDI Immunocompromised patients (CA, Chemo, IBD) PPI use: risk of CDI ranges from 1.4 to 2.75 times higher among patients with PPI exposure compared with those without PPI exposure causal association has not been established and the relationship between the risk of CDI and PPI dose and duration of use is uncertain d/c unnecessary PPIs is reasonable although there is insufficient evidence for discontinuation of PPIs as a measure for preventing CDI Hospitalization (exposure to colonized patients) 2

3 Risk Factors for Recurrent Episode of CDI The same as for initial infection AND Need for ongoing therapy with concomitant antibiotics during treatment for CDI Patient with a UTI or PNA and C diff Serum creatinine 1.2 mg/dl Clinical Manifestations of CDI For most with CDI, symptoms occur in the setting of recent (within the past 8 weeks) or current antibiotic use Most often see 2 weeks after receipt of antibiotics Fluoroquinolones, Clinda, Cephalosporins and Penicillins are most likely to predispose to CDI Any antibiotic can predispose to CDI 5-10 % have not been exposed to antibiotics? Exposed to a shedding asymptomatic carrier Carrier state : reservoir Clinical Manifestations of CDI Nonsevere CDI: Watery diarrhea (>or= 3 stools in 24 hours) with lower abdominal pain and cramping, Low grade fever, and Leukocytosis of >or= 15K and Creatinine of <1.5 Severe CDI: Diarrhea, diffuse abdominal pain, lactic acidosis, elevated creatinine and marked leukocytosis (up to 40K) Occasionally, severe CDI presents as ileus with little to no diarrhea: colon atonic Fulminant colitis: CDI with severe sepsis Patient should have CT A/P done and Surgical evaluation 3

4 Copyrights apply Diagnosis of CDI Clinical diagnosis: don t wait for lab confirmation to treat in right clinical scenario! Kaiser So Cal changed testing algorithm for C diff ~ 3 years ago Two step test Initial test for C diff Ag and toxin A and B test and reflex to NAAT PCR if these results are indeterminate Checks for NAP1 toxin, too Treatment of Nonsevere CDI Please note that Flagyl is no longer the initial treatment of choice for nonsevere CDI Many Flagyl failures in nonsevere CDI 4

5 Treatment of C diff: Severe Disease There is no consensus definition for severe CDI, nor is there agreement as to the most important clinical indicators that should be used to differentiate severity Patients with acute CDI may develop signs of systemic toxicity with or without profuse diarrhea warranting admission to an intensive care unit or emergency surgery Treatment of CDI: Severe Disease Severe CDI can quickly progress to fulminant CDI Some cases of severe CDI require surgical intervention Treatment of CDI: Fulminant Disease Surgery is sometimes required, especially with megacolon Many of these patients are on other antibiotics for other infections If so, treatment for CDI should be extended to one additional week after other s completion 5

6 Treatment of Recurrent CDI Recurrent C. difficile infection is defined by resolution of CDI symptoms while on appropriate therapy, followed by reappearance of symptoms within two to eight weeks after treatment has been stopped Fecal Microbiota Transplantation (FMT) For patients with multiple recurrences who have received appropriate antibiotic treatment for at least three CDI episodes (initial episode plus two recurrences), recommendation is for fecal microbiota transplantation (FMT) Instillation of processed stool collected from a healthy donor into the intestinal tract of a patient with recurrent CDI Efficacy of FMT has been evaluated in randomized trials; cure rates 70-90% Alteration of the colonic microbiota appears to be FMT appears to be safe; mild to moderate adverse events (such as abdominal discomfort) are generally self-limited Questions? 6

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