Care Process Model APRIL 2014

DIAGNOSIS AND MANAGEMENT OF Clostridium difficile (C. diff) Infection

This care process model (CPM) was developed jointly by Intermountain Healthcare’s Antibiotic Stewardship Committee, Division of Infectious Diseases, Multiple-Drug Resistant Organism (MDRO) subcommittee, Central Laboratory, and experts in gastroenterology. Based on expert opinion, Society for Healthcare of America/Infectious Disease Society of America IDSA Clinical Practice Guidelines, and American College of Gastroenterology AJG Guidelines, this CPM provides best-practice recommendations for diagnosis and management of Clostridium difficile (C. diff)infections in adults, including guidance for when and which antibiotics should be used.

KEY POINTS • C. diff is common and preventable. C. diffaccounts for 20% to 30% of cases of antibiotic-associated diarrhea and is the most commonly recognized cause of infectious diarrhea in healthcare settings. IDSA Cases often appear in clusters GOALS and outbreaks within institutions. Healthcare workers’ hands are the main means of spread during non-outbreak periods, indicating that handwashing is critical. Other appropriate infection-control measures (gowns, gloves, room cleaning with • Prevent C. diffby ensuring bleach, etc.) are essential to the control of spread within hospitals (see back page for prevention tips). appropriate antibiotic use with the • Several studies have demonstrated that C. diff is usually induced by antibiotics. Olson et al reported that 96% of help of Intermountain’s Antibiotic patients with symptomatic C. difftook antibiotics within 14 days of diarrhea onset, and all patients received antibiotics Stewardship Programs. within the previous 3 months. OLS Both length of antibiotic exposure and exposure to multiple antibiotics increase the • Prevent the spread of C. diffby risk for infection. IDSA optimizing infection-control • Antibiotics are overprescribed. Up to 50% of antibiotic prescriptions are either inappropriate (wrong drug) or measures. unnecessary (not needed).CDC Reducing this number could decrease the incidence of C. diff. • C. diff is a serious illness that requires coordinated treatment. C. diffcan range from a mild, irritating illness to a • Treat C. diffappropriately by prolonged, life-threatening infection. Appropriate treatment of C. diff,and the management of complications, is complex and determining severity of infection and may require a coordinated effort from Infectious Diseases, Gastroenterology, and Internal Medicine. prescribing appropriate antibiotics based on severity. Why Focus on C. diff? • • C. diff is a serious public health threat. In the United States, C. diffcauses 250,000 infections and 14,000 deaths per Manage recurrent C. diffin a year, and it costs at least $1 billion in excess medical costs per year. CDC coordinated, cost-effective way. • The Centers for Disease Control and Prevention (CDC) has raised C. diff to a threat level of urgent. Because C. diffspreads rapidly and is naturally resistant to many drugs used to treat other infections, the CDC called C. diffan “immediate public health threat that requires urgent and aggressive action” in its 2013 Threats Report. CDC • A more virulent strain resistant to fluoroquinolones has emerged. Deaths related to C. diff increased 400% between 2000 and 2007, in part due to this more virulent strain. CDC A 2005 study of 8 healthcare facilities showed that this resistant strain accounted for 50% or more of the isolates from 5 of the 8 facilities included in the study. NEJM The inside pages of this tool provide an algorithm and associated notes, and can be folded open and posted in your office or clinic. The back page provides prevention tips, references, and resources. DIAGNOSIS C. diff diff C. DIAGNOSIS AND MANAGEMENT OF symptom only the as diarrhea with Presents MILD Infection complicated) severe- or severe of definition the meet that symptoms and signs not (but symptoms additional and diarrhea with Presents MODERATE Signs Symptoms of and • • • • Avoid testing for 48 hours after laxative administration. laxative after hours 48 for testing Avoid container). the of shape the takes that stool loose or (liquid stools diarrheal test Only TEST stool sample (2-step GDH/toxin A/B test) (2-stepTEST A/B stool sample GDH/toxin DIAGNOSE DIAGNOSE (+) (+) acid suppressive therapy if possible if therapy suppressive acid STOP any inducing antibiotics (d) or antibiotics STOP inducing any Toxin GDH • • • • • • • • of disease: during the course following the of ≥2 develops or has and diarrhea with Presents • • • • • • • • Age ≥65 years ≥65 Age level preinfection the creatinineSerum level ≥1.5 times to due findings imaging CT abdominal Abnormal ileus of diagnosis Clinical to due Hg mm <100 pressure blood Systolic ≥38.0°C Fever >20% neutrophils of bandemia ≥15,000 or WBC cells/µL <2.5 mg/mL Hypoalbuminemia

ALGORITHM: C. diff C. SEVERE EDUCATE patient (e) patient EDUCATE C. diff C. C. diff diff C. ordered reflexively ASSESS severity infection; amplification test Nucleic acid infection (-) (+) Toxin (+) GDH C. diff diff C.

DIAGNOSIS • • • • Radiographic: • • • • Clinical: diff C. following the of any develops or with presents AND disease severe for criteria Meets • • • • • • • •

or megacolon Colonic dilation Pancolitis Ileus Ascites change status Mental distention abdominal Significant medications and/or vasoactive Sustained hypotension requiring volume repletion ICU the to Admission (c) infection Infection (a)(b)Infection (-) (-) SEVERE-COMPLICATED (-) GDH Toxin

: IDSA,AJG (c) • • Laboratory: • • • Any evidence of evidence endAny organ failure >2.2 mmol/L lactate Serum cells/ <2,000 >35,000 or WBC IDSA the clinicalstatusof is notnecessaryunless µ as a result of the the of aresult as END. L patient changes.

Repeat testing

accessing this sheet.) this accessing patient education. Infection support difficile Clostridium (e) education. Patient and the duration ofrecurrence symptoms. antibiotics (d) Inducing • • test acid nucleic amplification Direct • • Center) Medical Valley Regional Utah and Children’s Hospital Primary antigenCombined test GDH/toxin A/B strategies: testing 2 different mind. in context clinical the with interpreted be always should and infection of suspicion (c) Testing. • • of symptoms and (b) Signs feeding). tube (including tract GI the of manipulation and HIV, surgery, GI chemotherapy, cancer age, duration include of advanced hospitalization, risk factors Other of reports precedes usually use Antimicrobial of risk the increase antimicrobials multiple to (a) factors. Risk ALGORITHM NOTES: DIAGNOSIS sites for for sites Center Medical Regional Utah Valley and Children’sHospital Primary at test first-line as Used possible: Results possible: Results result. indeterminate an yields test first the if reflexively done is (PCR-based) test second A first. is done test A/B (GDH)/Toxin dehydrogenase glutamate Acombined algorithm. is a2-step This patients). the half than fewer in (found leukocytosis aperipheral and discomfort, abdominal Fever, cramping, use). (e.g., cause laxative another to attributed in (≥3 diarrhea unexplained onset, New – – – – – – – – – – Negative for toxigenic toxigenic for Negative toxigenic for Positive Toxin =INDETERMINATE Negative and GDH Positive Toxin =NEGATIVE Negative and GDH Negative Toxin =POSITIVE Positive and GDH Positive – – patient does not requirepatient does treatment. is negative, test second If is positive, test second If result. final for reflexively) (done test PCR-based to Refer C. diff diff C. INDETERMINATE Laboratory testing should be used to confirm clinical clinical confirm to used be should testing Laboratory without antimicrobial use. without Longer exposure to antimicrobials and exposure exposure and antimicrobials to exposure Longer

Intermountain microbiology laboratories use use laboratories microbiology Intermountain C. diff C. Use the Krames Krames the Use (See back for directions for for directions for back (See C. diff C. AND tests. may influence the risk of risk the influence may IDSA

HealthSheet to to HealthSheet as a reflex second-line test at all other other all at test second-line areflex as C. diff diff C. C. diff diff C. C. diff diff C. C. diff C. diagnosis is confirmed. is confirmed. diagnosis test is negative, and the the and is negative, test , but there are occasional occasional are there , but infection infection ≤

IDSA 24 consecutive hours) not not hours) 24 consecutive C. diff diff C. (at all sites except except (at sites all infection. infection. include: IDSA C. diff C.

TREATMENT for 10for days daily 3times orally mg Metronidazole recurrence Third recurrence Second recurrence First daily for 10 for daily days 125 4times orally mg to Switch MILD-MODERATE improvement in 5–7 days vancomycin If no • • 2weeks for 3days 2or 125THEN every mg Vancomycin ( infection for first antibiotic used Same metronidazole • • , 500 500 , Consult Infectious Diseases and/or Gastroenterology for evaluation of emerging therapies (e.g., FMT, fidaxomicin, etc.) (e.g., FMT, fidaxomicin, therapies emerging of evaluation for Gastroenterology and/or Diseases Infectious Consult criteriameets under first infection, SEVERE-COMPLICATED above) with Stabilize C. diff C. , MILD-MODERATE Suspicion Recurrent of 10 days for daily 4times orally Vancomycin (h) [FMT] therapy microbiota (e.g., fecal therapies for evaluation of emerging Gastroenterology and/or Diseases Consult Infectious ,

125 mg orally 4 times daily for 14 days, THEN 125 mg twice daily for 7 days, THEN 125 mg once daily for 7 days, 7days, 125 for daily THEN once mg 7days, for daily 125 THEN 14 for twice mg days, daily 125 4times orally mg , fidaxomicin, etc.) vancomycin improvement in or or Infection Diagnosis Infection (first infection) SEVERE (g) vancomycin 7 days If no PRESCRIBE antibiotics for first infection (f) infection first for antibiotics PRESCRIBE

, 125 mg ALGORITHM: , 125 mg orally 4 times daily (plus IV IV (plus daily , 125 4times orally mg ) MANAGE recurrent (j) TEST stool sample (c) sample TEST stool • • • • • • • • primary infection primary as treatment Same severe metronidazole distention: abdominal no If evaluation of emerging therapies (e.g., FMT management and for further Gastroenterology and/or Diseases Consult Infectious µL per cells >50,000 of WBC peripheral a and >5 of mmol/L lactate serum and shock refractory with ill patients Vancomycin distention: abdominal significant and/or megacolon, toxic ileus, If Consult Colorectal Surgery for consideration of colectomy Surgery Consult Colorectal response) clinical on depends (duration saline) normal mL AND daily times (+)

TREATMENT C. diff diff C. SEVERE , 500 mg orally 4 times daily AND AND daily 4times orally mg , 500 vancomycin , IV 500 mg 3 times daily (duration depends on clinical response) clinical on depends (duration daily 3times mg 500 , IV C. diff C. metronidazole SEVERE-COMPLICATED If noimprovementin Infection (i) Infection , rectally 4 times daily (500 mg vancomycin in 500 500 in vancomycin mg (500 daily 4times , rectally 48–72 hours Vancomycin (-) and and primary infection primary as treatment Same severe-complicated vancomycin (h) SEVERE-COMPLICATED NOTE: NOTE: symptoms resolve unlesstheclinical symptoms resolveunlesstheclinical END. Evaluatefor , fidaxomicin, etc.) , 125 mg orally 4 times daily AND AND daily , 125 4times orally mg other diagnoses. metronidazole status ofthepatient changes. status ofthepatientchanges.

Test ofcureisunnecessaryif Test ofcureisunnecessaryif retention enema if

for severely severely for ,

IV 500 mg 3 3 mg 500 IV

• (h) Fecal microbiota therapy (FMT). tablets. vancomycin than effective cost more and (g) Intravenous vancomycin toxic megacolon. with Antiperistaltics. (f) ALGORITHM NOTES: TREATMENT therapy because of potential neurotoxicity. cumulative for because therapy Metronidazole.(j) retreatment. prompt not should symptoms no or minimal recurrent have a after diarrhea recurrent with patients all Not of completing therapy.weeks (i) • • • Indications fact sheets to educate the patient: to educate sheets fact FMT education. etc. requirements, screening indications, Protocol Therapy Microbiota FMT protocol. conditions that increases risk of perforation. and bleeding, spontaneous immunosuppression, significant Contraindications to FMT: – – – – – C. diff C. – – – – – Recurrent or relapsing relapsing or Recurrent Information for Donors for Information Therapy: Microbiota Fecal Recipients for Information Therapy: Microbiota Fecal hours 48 therapystandard after fulminant or Severe aweek least at for Moderate morbidity) significant with associated and hospitalization OR antibiotic alternative an without or with vancomycin of taper week a6–8 of failure and infection moderate to mild of C. diff C. b. At least 2 episodes of severe infection resulting in in resulting infection severe of 2episodes At least • • • • • recurrence. Intermountain measures: Intermountain . Antiperistaltics may obscure symptoms and precipitate precipitate and symptoms obscure may . Antiperistaltics Mortality recurrence of Rate use antimicrobial Total therapy onset) antibiotic Initial community and (hospital-acquired healthcare-associated infection of Incidence C. diff diff C. for FMT: for C. diff C.

IDSA Intermountain’s Use Intermountain’s Intermountain’s Use . A repeat positive test in a patient with with apatient in test positive . Arepeat infection not responding to standard therapy therapy standard to responding not infection Do not prescribe metronidazole for long for metronidazole prescribe not Do Avoid antiperistaltic agents for patients patients for agents Avoid antiperistaltic C. diff diff C. Recurrences generally occur within 4 within occur generally Recurrences C. diff C. infection with no response to to response no with infection provides provides Toxic megacolon, sepsis, sepsis, Toxic megacolon,

(defined as (defined taken orally is equally efficacious efficacious is equally orally taken Fecal Fecal a. a. C. diff C. At least 3 episodes 3episodes At least infection infection

IDSA term ‑term References PREVENTION: GENERAL AJG Surawicz, CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J To reduce C. diffinfections, follow these prevention tips: Gastroenterol. 2013;108(4):478-498. • CDC Centers for Disease Control and Prevention. Antibiotic resistance Minimize unnecessary antimicrobial use by: threats in the United States, 2013. http://www.cdc.gov/ –– Treating infection, not colonization or contamination. Not every bacterial culture requires antibiotic drugresistance/threat-report-2013. Accessed November 18, 2013. IDSA Cohen SH, Gerding DN, Johnson S, et al. Clinical practice therapy. Ensure that a true infection is present before prescribing an antibiotic. guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and –– Reviewing all antimicrobial medications and microbiology results after 48 hours of use to determine if the Infectious Diseases Society of America (IDSA). Infect Control modifications can be made. Hosp Epidemiol. 2010;31(5):431-455. NEJM McDonald LC, Killgore GE, Thompson A, et al. An epidemic, –– Using the narrowest spectrum antimicrobial to treat suspected or proven infections. toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005;353:2433-2441. –– Providing indications with every antimicrobial order. OLS Olson MM, Shanholtzer CJ, Lee JT Jr, Gerding DN. Ten years of • prospective Clostridium difficile-associated disease surveillance Recommending routine use of probiotics for the prevention of C. diffis not recommended. There are and treatment at the Minneapolis VA Medical Center, 1982–1991. limited data to support the use of probiotics, and there is a potential risk of bloodstream infection. IDSA Infect Control Hosp Epidemiol. 1994;15:371–381. • Only use acid-suppressing medications (H2B/PPI) when clinically indicated. Intermountain patient tools To order copies, go to i-printstore.com. PREVENTION: IN THE HOSPITAL • Fecal Microbiota Therapy: Information for Recipients • Fecal Microbiota Therapy: Information for Donors • Initiate contact isolation for patients with: Krames patient tools –– Any diarrhea suspected to be infectious To find and print theClostridium difficile Infection Krames –– Suspected or known C. diff infection HealthSheet at your desktop: –– Recurrent diarrhea and a history of recent C. diff infection 1. Open the Patient Education Library page by typing PEN in your address bar (within the firewall). –– Confirmed case ofC. diff infection (contact isolation required for the duration of hospitalization) 2. Click the KRAMES On-Demand button. • Adhere to good hand hygiene practices with use of SOAP AND WATER following glove removal if C. diff 3. Type “Clostridium difficile” in the search bar. The Clostridium infection is suspected or confirmed. difficile Infection HealthSheet appears at the top of the list. This HealthSheet will also appear in the Cerner EMR as a suggested • Disinfect personal equipment used for patients with C. diffinfection with sodium hypochlorite containing patient education item. disinfectant (bleach). When using disinfectants, follow recommendations regarding appropriate kill time and Intermountain provider tools always wear appropriate personal protective equipment (gown and gloves). Available from intermountain.net and intermountainphysician.org: • Antibiotic Best Practices web page • Fecal Microbiota Therapy Protocol • Clostridium difficile (C. diff) Flash Card This CPM presents a model of best care based on the best available scientific evidence at the time of publication. It is not a prescription for every physician or every patient, nor does it replace clinical judgment. All statements, protocols, and recommendations herein are viewed Development Team as transitory and iterative. Although physicians are encouraged to follow the CPM to help focus on and measure quality, deviations are a means for discovering improvements in patient care and expanding the knowledge base. Send feedback to Eddie Stenehjem, MD, MSc, • Whitney Buckel, PharmD • Russ Miller, MD Intermountain Healthcare, Infectious Diseases, [email protected]). • Kristin Dascomb, MD • Doug Smith, MD • Chad Gonzales, MD • Eddie Stenehjem, MD • Bert Lopansri, MD ©2014 Intermountain Healthcare. All rights reserved. Patient and Provider Publications 801-442-2963 CPM070 - 04/14 Not intended to replace physician judgment with respect to individual variations and needs.