CLINICAL TREATMENT GUIDELINES FOR CLOSTRIDIUM DIFFICILE
Transcription
CLINICAL TREATMENT GUIDELINES FOR CLOSTRIDIUM DIFFICILE
CLINICAL TREATMENT GUIDELINES FOR CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS Index: Indications for CDI testing……………………………. Bristol Stool Chart…………………………………….. Diagnostic and Treatment Algorithm…………………. Assay Results and Interpretation……………………… Infection Prevention Measures………………………... Tables of Disease Severity and Treatment.…………… Chemoprophylaxis for Recurrent CDI………………... Outpatient Oral Vancomycin Therapy Guide………… Page 1 Page 2 Page 3 Page 4 Page 4 Page 5 Page 6 Page 7 INDICATIONS FOR TESTING: On admission: Patients with diarrhea whose differential diagnosis includes: o Community-onset CDI o Healthcare-facility associated CDI in recently hospitalized patients, nursing home residents, frequent outpatient exposure to healthcare settings such as dialysis, appointments, etc. Hospitalized patients: New onset of clinically significant diarrhea o Defined as 3 or more diarrheal bowel movements (Type 6 or 7 on Bristol Stool Chart, see page 2) in 24 hours OR a patient self-report of new onset of loose stools and abdominal pain o Significant deviation from baseline stooling pattern in patients with ostomy, tube feeds, or other causes of chronically loose/high output stools Additional factors to consider: new unexplained fever/leukocytosis in a hospitalized patient age > 60 years recent history of antibiotic exposure history of gastrointestinal surgery or irritable bowel disease (IBD) co-existing immunodeficiency (i.e. HIV/AIDS, recent chemotherapy) multiple comorbidities indicators of potential disease severity o age > 60 years, temperature > 38.3°C, albumin < 2.5 mg/dL, peripheral WBC count ≥ 15,000 cells/mm3, acute renal failure (> 1.5 x baseline) a high clinical suspicion for CDI and high clinical acuity should prompt testing as soon as possible Situations when testing is not advised: negative C. difficile stool assay in the last 72 hours diarrhea in the setting of a laxative or a bowel stimulant in the previous 48 hours test of cure Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D. Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention 1 CLINICAL TREATMENT GUIDELINES FOR CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D. Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention 2 CLINICAL TREATMENT GUIDELINES FOR CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS Clinical Suspicion of CDI Order one C. difficile stool assay Discontinue antidiarrheals, antiperistaltics, and unnecessary antibiotics Reevaluate necessity of acid suppressive medications Maintain hydration and electrolyte replacement Consider empiric C. difficile treatment Implement empiric contact isolation if expected testing turnaround time > 4hours GDH antigen (+); toxin A/B (+) GDH antigen (-); toxin A/B (+) GDH antigen (+); toxin A/B (-) PCR testing done PCR (+) PCR (-) No Clostridium difficile Infection: Clostridium difficile Infection: Confirm that patient is in contact isolation Continue contact isolation until resolution of symptoms and end of therapy (see page 4) Begin CDI treatment (see page 5) Consult Infectious Diseases and/or G.I. for diagnostic uncertainty Consult Surgery for Severe CDI Signs and symptoms improve in 4-6 days: Complete course of therapy Further stool testing is not advised Room is terminally cleaned GDH antigen (-); toxin A/B (-) Discontinue CDI treatment if initiated Discontinue empiric contact precautions for CDI if initiated Evaluate other causes of diarrhea if appropriate May repeat C difficile stool assay after 72 hours in patients with persistent diarrhea No improvement of diarrhea within 4-6 days and patient receiving oral metronidazole: Start oral vancomycin Consider IV metronidazole (see page 5) Progressive signs and symptoms (toxic megacolon, fulminant colitis): Obtain abdominal/pelvic CT scan Begin therapy for severe or fulminant disease (page 5) Consult Surgery Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D. Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention 3 CLINICAL TREATMENT GUIDELINES FOR CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS . CLOSTRIDIUM DIFFICILE ASSAY RESULTS AND INTERPRETATION GDH Result Toxin Assay Result Interpretation Recommendations Negative Negative No CDI present No further action. Repeat testing is discouraged. Discontinue contact isolation as appropriate. Discrepant GDH and Toxin results Reflex to PCR by Microbiology Lab Positive Positive If PCR is Negative: No CDI present If PCR is Positive: CDI is present CDI is present Continue contact isolation and begin therapy. Repeat testing is discouraged. C. difficile GDH/Toxin EIA Performance Characteristics Sensitivity 90.5%, Specificity 93.1%, PPV 76.4%, NPV 97.6% C. difficile PCR Assay Performance Characteristics Sensitivity 98.8%, Specificity 90.9%, PPV 56%, NPV 99.8% INFECTION PREVENTION MEASURES All patient care units will use the same procedures for testing, treatment, and isolation. All patients with presumed or suspected C. difficile should be isolated if CDI testing is expected to take > 4 hours to result back to provider. Isolation procedures include: use of dedicated patient equipment, universal glove and gown use, hand hygiene with alcohol based sanitizer before and after entry and exit of patient room, followed by hand washing with soap and water after room exit if a sink is readily available. o The patient is cleared of the need for isolation once treatment is completed and the patient is asymptomatic (stools back to baseline consistency), and if the flag is removed by the Infection Prevention Program. o Terminal cleaning of rooms of all patients with C. difficile infection must occur once the isolation status is discontinued or the patient is discharged. Rooms that housed patients with C. difficile must be cleared with the ATP Bioluminescence assay by Environmental Services, and may require terminal disinfection with UV. Contact Infection Prevention and Environmental Services for assistance. o Please refer to the RGHS Infection Prevention Manual for further guidance on isolation precautions in CDI. http://rghsportal/Policies/2012r5%20IP%20Manual%20REVISED%20(8).pdf Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D. Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention 4 CLINICAL TREATMENT GUIDELINES FOR CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS DISEASE SEVERITY AND TREATMENT RECOMMENDATIONS: General note: for CDI patients requiring continued broad-spectrum antimicrobial therapy, consideration should be given to continuing CDI treatment for the duration of concomitant antimicrobials, or evaluating for secondary CDI prophylaxis (page 6) Mild to Moderate CDI: minimal evidence of toxicity Assessment Drug of choice Initial episode Metronidazole 500 mg PO q8 for 10-14 days Recurrent episode Metronidazole 500 mg PO q8 for 10 – 14 days OR Vancomycin 125mg PO q6 for 10 – 14 days Consider an oral vancomycin taper after completion of therapy in patients with multiple recurrences: • Week 1: Vancomycin 125 mg PO q12h • Week 2: Vancomycin 125 mg PO q24h • Week 3: Vancomycin 125 mg PO q48h • Week 4: Vancomycin 125 mg PO q72h Comment If no clinical improvement in 4-6 days, consider changing to oral vancomycin for severe CDI. 1st recurrence: Retreatment with metronidazole is preferable for mild-moderate CDI. > 1 recurrence: Treatment requires oral vancomycin. If recurrence is severe or fulminant, see below. Severe CDI: any of the following criteria endoscopic evidence of pseudomembranous colitis ● requires treatment for C. difficile in the ICU at least 2 of the following not attributable to other causes: age > 60 years, temperature > 38.3°C, albumin < 2.5 mg/dL, peripheral WBC count ≥ 15,000 cells/mm3, acute renal failure (> 1.5 x baseline) Assessment Initial episode Severe CDI developing despite therapy for mild to moderate CDI Drug of choice Vancomycin 125 mg PO q6 for 10-14 days Severe, complicated CDI Vancomycin 500 mg PO q6 for 10-14 days Vancomycin 125 mg PO q6 for 10-14 days ± Metronidazole 500 mg IV q8 Comment Please Note: There is no literature suggesting combination oral metronidazole and oral vancomycin offers clinical benefit over oral vancomycin alone. Evaluate for fulminant CDI and treat accordingly. Consider adding Metronidazole 500 mg IV q8* if Encourage Surgical/Infectious ileus or otherwise unable to ascertain adequate Diseases and/or GI consult. bioavailability of oral agents Fulminant CDI: evidence of ileus, toxic megacolon, hypotension or shock, or colonic perforation Assessment Drug of choice Comment Urgent Surgery consult Initial CDI episode Vancomycin 500 mg PO q6 for 10 – 14 days or worsening PLUS Strongly encourage Infectious despite therapy Metronidazole 500 mg IV q8* for 10 – 14 days Ileus present Consider adding per rectum Vancomycin 500 mg Diseases and/or GI consult in 500 mL of 0.9% NaCl q4-12 hours * Note: IV metronidazole may be discontinued when clinically stable and ileus resolved . Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D. Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention 5 CLINICAL TREATMENT GUIDELINES FOR CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS CHEMOPROPHYLAXIS OF RECURRENT CDI Primary Prophylaxis: o Current literature does not support primary prophylaxis for high risk patients who have never had CDI Secondary Prophylaxis: o Patients with recent or prior CDI requiring antimicrobial therapy for another indication may be at risk of CDI recurrence. o Routine use of secondary CDI prophylaxis in such cases has not been evaluated in the literature, may place the patient at risk for unnecessary drug related toxicities, and may promote emergence of drug-resistant organisms such as vancomycin-resistant enterococci (VRE). o The risks and benefits of CDI prophylaxis should be considered for each clinical scenario. The following is an effort to provide guidance to prescribing physicians who choose to implement CDI secondary prophylaxis for certain high risk patients on a case-by-case basis. Contact ASP for guidance if secondary prophylaxis of CDI is initiated for any patient. o Patients who may benefit from CDI secondary prophylaxis: A history of documented recurrent CDI (> 2 episodes), most recent episode treated with symptom resolution within the preceding 3 months A history of severe, life-threatening CDI at any time in the past o Recommended therapy Vancomycin 125 mg PO q24h o Duration of prophylaxis Prophylaxis can be given for the duration of concomitant antimicrobial therapy, plus 7 days beyond completion of the other antimicrobials. Alternatively, consideration may be given to tapering doses of oral vancomycin (q24h, q48, q72h) over 2-3 weeks upon completion of other antimicrobials. References: Cohen S et al. Infection Control and Hospital Epidemiology 2010; 31:5 Zar F et al. Clinical Infectious Diseases 2007; 45: 302 Katz, DA et al Americal Journal of Medicine 1996; 100 Patterson LR et al Annals of Internal Medicine 2009; 151 Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D. Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention 6 CLINICAL TREATMENT GUIDELINES FOR CLOSTRIDIUM DIFFICILE INFECTIONS (CDI) IN ADULTS OUTPATIENT ORAL VANCOMYCIN THERAPY Pharmacotherapy with oral vancomycin products for the treatment of Clostridium difficile infections in adults is extremely costly (see table below). In an attempt to help reduce medication expenses, some retail pharmacies readily compound oral vancomycin solution from the commercially available vancomycin powder for injection. Please consider providing this information to your patients if oral vancomycin therapy is warranted. Other neighborhood pharmacies may be capable of compounding oral vancomycin solution; however, it is recommended to call in advance if the below pharmacies are not a feasible option. Product Drug Acquisition Costs* Vancomycin Oral Capsule – 125 mg Vancomycin Oral Capsule – 250 mg Vancomycin Oral Capsule – 500 mg Vancomycin Powder for Injection – 1 gram (powder used to compound solution) Vancomycin Powder for Injection – 5 grams (powder used to compound solution) Vancomycin Powder for Injection – 10 grams (powder used to compound solution) $23.54/capsule $43.40/capsule $86.80/2 capsules $4.25/vial $24.28/vial $35.79/vial Total Cost of Therapy* (14 Days) $1318.24 $2430.40 $4860.80 $119 (maximum recommended dose) $ 135.97 (maximum recommended dose) $107.37 (maximum recommended dose) * Total Cost of Therapy based on 2010 drug acquisition costs at RGH Oral Vancomycin Solution Concentration: 250 mg/5 mL Readily Available Compounding Pharmacies in Rochester, NY and Surrounding Areas: The General Apothecary Rochester General Hospital 1415 Portland Ave, Suite 125 Rochester, NY 14621 (585) 922-3970 RMH Retail Pharmacy LLC 1500 N James St Rome, NY 13440 (315) 338-7690 Twelve Corners Apothecary 1832 Monroe Avenue Rochester, NY 14618 (585) 244-8600 Pine Pharmacy 5110 Main St, Suite 101 Williamsville, NY 14221 (716) 332-2288 R Drugs Etc 222 Alexander Street, #2700 Rochester, NY 14607 (5850 262-3760 Version Date: October 2012 Author: Maryrose Laguio-Vila, M.D. Reviewed and Approved by RGH Infectious Diseases Unit, RGH Infection Prevention 7