Clostridium difficile Colitis

Transcription

1 1 Clostridium difficile Colitis William R. Sonnenberg, MD 2 Disclosure Dr. Sonnenberg has no conflict of interest, financial agreement, or working affiliation with any group or organization. 3 Learning Objectives Learn to identify the symptoms of Clostridium Difficile; Identify patients at risk for developing Clostridium Difficile; Learn treatment and prevention option for Clostridium Difficile. 1

2 4 Case Presentation 60 year old male CAD with stents Morbidly obese Admitted to tertiary hospital for cellulitis and sepsis Vancomycin, Zosyn, clindamycin Discharged on Zyvox Changed to SXT/TMP due to availability Developed diarrhea after discharge 5 Physical Examination Afebrile, HR 106, RR 20 Acutely ill in appearance LLQ tenderness 3 cm ulcer left lower leg Positive stool for C. diff. WBC 39,000 Cultures from previous hospitalization all negative 6 Its Important Prime nosocomial pathogen Only nosocomial pathogen 453,000 cases/year in ,000 deaths/year ¼ community acquired Quadruples cost of hospitalizations Daniel A. Leffler, M.D., and J. Thomas Lamont, M.D. N Engl J Med 2015; 372:

3 7 Its Getting Worse 84 cases/100,000 in 2005, doubled that of 1996 Mortality from 0.5 deaths in 1999 to 2.0 deaths/100,000 in x increase BI/NAP1/027 strain Higher toxins More fluoroquinolone resistance Triple mortality 8 Incidence of Nosocomial Clostridium difficile Leffler DA, Lamont JT. N Engl J Med 2015;372: Incidence and Mortality Increasing in USA # of CDI Cases per 100,000 Discharges Principal Diagnosis All Diagnoses Mortality Annual Mortality Rate per Million Population Elixhauser A, et al. Healthcare Cost and Utilization Project: Statistical Brief #50. April Available at: Accessed March 10, Redelings MD, et al. Emerg Infect Dis. 2007;13:

4 10 C. Difficile Burden by Location Lessa FC et al. N Engl J Med 2015;372: Death and Money Hospital-acquired, hospital-onset: 165,000 cases $1.3 billion in excess costs 9,000 deaths annually Hospital-acquired, post-discharge (up to 4 weeks) 50,000 cases $0.3 billion in excess costs 3,000 deaths annually Nursing home-onset: 263,000 cases $2.2 billion in excess costs 16,500 deaths annually Campbell et al. Infect Control Hosp Epidemiol. 2009:30: Dubberke et al. Emerg Infect Dis. 2008;14: Dubberke et al. Clin Infect Dis. 2008;46: Risk Factors Antibiotics Recent hospitalization Environmental contamination Age increases risk and severity 10 times greater over age 65 Acid suppression?? Inflammatory bowel disease 4

5 13 Antibiotic Misuse Up to 85% of patients with C. dif. colitis have antibiotic exposure 28 days earlier More than 8 in 10 Americans received antibiotic in 2011 Chang HT et al. Infect Control Hosp Epidemiol 2007; 28: Unnecessary Antibiotic Prescriptions Graphic: Erik Dunham, NPR/U.S. Food and Drug Administration 15 PPI and C. Diff 5

6 16 Depression? Major depression associated with 36% increase of CDI Mirtazapine + fluoxetine doubled positive test Lowry F. Antidepressants Linked to Doubling of C difficile Risk. Medscape Medical News 17 Definition Three unformed stools in 24 hours Positive stool test Or Endoscopic pseudomembranous colitis Infect Control Hosp Epidemiol. 2010;31(5): Symptoms Significant diarrhea Recent antibiotic exposure Abdominal pain Fever Foul odor resembling horse manure 6

7 19 Clostridium difficile Fecal-oral transmission Anaerobic, grampositive, spore-forming Noninvasive Spores resistant to heat, acid, and antibiotics Can survive 70 days 2 endotoxins (TcdA and TcdB) 20 NAP1 Hypervirulent Strain Severe, fulminant colitis Leukocytosis Renal failure Toxic megacolon Fluoroquinolones may have role Toxin A and B 21 Poorer Prognosis Albumin < 3 Hgb < 9 Creatinine > 1.5 Ulcerative colitis Ananthakrishnan AN, et al. Aliment Pharmacol Ther Apr. 35(7):

8 22 Fulminant Colitis Toxic megacolon, colonic perforation, death 3% of CDI 34.7% in-hospital mortality 23 Toxic Megacolon 24 Pseudomembrane 8

9 25 Endoscopic Pseudomembrane 26 Pseudomembrane 27 Colonization 7% to 26% colonization in acute care facilities 2% in community ½ are asymptomatic Colonization risk increases daily during hospitalization Symptoms begin within 3 days of colonization Infect Control Hosp Epidemiol. 2010;31(5):

10 28 Bedside Commode vs. BP Cuff?? 11.5% 10.0% Manian FA, et al. Infect Control Hosp Epidemiol Mar;17(3): Antibiotic Class and C. dif. Very Common Clindamycin Ampicillin Amoxicillin Cephalosporins Fluoroquinolones Somewhat Common Other penicillins Sulfonamides Trimethoprim Macrolides 30 Testing for C. difficile Enzyme assay for toxins Rapid, easy DNA-tests Higher sensitivity and specificity Detect BI/NA1/027 strain May detect low levels of uncertain significance Cultures not wildly available, anaerobic 10

11 Pathogenesis of C. difficile Infection. Leffler DA, Lamont JT. N Engl J Med 2015;372: Stool Testing Confine testing to patients with diarrhea Not post treatment testing to confirm eradication Successfully treated will test positive for weeks or months after resolution of symptoms Sethi AK, Al-Nassir WN, Nerandzic MM, Bobulsky GS, Donskey CJ. Persistence of skin contamination and environmental shedding of Clostridium difficile during and after treatment of C. difficile infection. Infect Control Hosp Epidemiol 2010;31: Prevention of C. difficile 11

12 34 Prevention Methods Antibiotic stewardship Hygiene Isolation Probiotics mixed results 35 No antibiotics for apparent viral URIs (AAP) Don t treat bacteriuria in elderly without symptoms (Am Ger Soc.) Don t obtain a C. difficile toxin test to confirm cure if symptoms have resolved 36 ABX Stewardship Antibiotics are a shared resource, (and becoming a scarce resource). Using antibiotics properly is analogous to developing and maintaining good roads. Bringing new antibiotics into our current environment is akin to buying a new car because you hit a pot hole, but doing nothing to fix the road 12

13 37 Less New Models 38 Antibiotics for Bronchitis 90% are viral, 10%-30% multiple viruses Viral shedding is often decreasing at presentation 2/3 are treated with antibiotics 55% of our patients believe they help for URI s 25% use left over antibiotics 39 Do Antibiotics Help Bronchitis? NNT 5.6 for cough reduction at follow-up Number needed to harm 16.7 Smucny JJ, Becker LA, Glazier RH, McIsaac W. Are antibiotics effective treatment for acute bronchitis? A meta-analysis. J Fam Pract. 1998;47(6):

14 40 Rate of ABX Use for Acute Bronchitis 3000 visits for acute bronchitis, Extended macrolides increased from 25% to 40% Other broad spectrums prescribed 1/3 of the time Education is not working Michael L. Barnett, MD 1 ; Jeffrey A. Linder, MD, MPH ;311(19): JAMA. 41 ABX for Adults With Acute Bronchitis in USA, JAMA. 2014;311(19): Effect of Stewardship 450 bed hospital in Scotland Antibiotic use monitored Ceftriaxone 95% Ciprofloxacin 72.5% C. diff 77% MRSA 25% Dancer SJ, et al. Int J Antimicrob Agents 2013;41:

15 43 Green Mucous Bacterial Infection 44 Do Antibiotics Prevent Pneumonia? 814,000 pts, 1.5 million visits 65% Dx with bronchitis Significant minor adverse side effects in treated group Less hospitalizations for pneumonia in antibiotic group NNT is 12,225 Meropol SB et al. Ann Fam Med March/April 2013 vol. 11 no Managing Antibiotic Expectations Call it a chest cold Set realistic expectations, about 3 weeks Explain antibiotics don t help; create resistance and side effects Doesn t prevent pneumonia Consider pocket script 15

16 46 Sinusitis AAO Guidelines 86% placebo v. 91% of ABX get better in 1-2 weeks 90% get antibiotics Watchful waiting for 7 days after 10 days of symptoms Amoxicillin +/- clavulanate 5-10 days Otolarynol Head Neck Surg, April Vol 152:2 Suppl S IDSA Guidelines for Sinusitis Don t use antibiotics unless absolutely necessary Symptoms more than 10 days with worsening Use amoxicillin-clavulanate for adults Tice A et al: IDSA. Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect Dis Asymptomatic Bacteriuria Nursing home 50% of women 40% of men Cause of mental status change? Only if fever, abnormal WBC s Needs cytokines for mental status change 16

17 49 Pharyngitis and Antibiotics 60% receive antibiotic, 10% should 15% get azithromycin Penicillin is drug of choice, prescribed 9% of time No PCN resistance, but more common in new, broad spectrum antibiotics Barnett ML, Linder JA. Antibiotic prescribing to adults with sore throat in the United States, (Research letter) JAMA Intern Med Hygiene Spores everywhere in health care facilities Alcohol based hand wash ineffective Need soap and water 51 Isolation for Infected Patients Single room Gloves and gowns Soap and water Post discharge disinfection of room Muto CA, et al. Clin Infect Dis 2007;45:

18 52 Treatment 53 Antibiotics Metronidazole + Vancomycin No clinically reported resistance Vancomycin better for severe infection Metronidazole failures increasing with BI/NAP1/ strain 54 Fidaxomicin Poorly absorbed, bactericidal Less recurrences than Vancomycin 15% v. 25% No differences BI/NAP1/027 High cost Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011;364:

19 55 Recurrences 20% after initial infection 60% after multiple infections Reexposure or reactivation of spores Impaired immunity and weakened barrier function 56 Antibiotics for Recurrences Repeating metronidazole or Vancomycin 50% effective Fidaxomicin may be more effective Tapered or pulsed dose Vancomycin 57 Cholestyramine Binds Vancomycin and metronidazole Don t use 19

20 58 Antidiarrheal Agents Don t use agents like Lomotil or Imodium Increase severity of symptoms 59 Surgery Emergency colectomy 80% mortality Diverting ileostomy and colonic lavage with Vancomycin 60 Bacterial Flora Adult flora tend to be stable over time Quadrillion cells 1,000 species Depletion and reduced diversity Firmicutes Bacteriodetes 20

21 61 Fecal Transplantation Fecal microbial diversity, may last months after antibiotic 90% effective with simultaneous cessation of antibiotics Cure Rate Fecal Transplantation for Recurrent C. difficile Infection Leffler DA, Lamont JT. N Engl J Med 2015;372: Changes to the Microbiota after Fecal Microbial Transplantation for Recurrent C. difficile Infection. Leffler DA, Lamont JT. N Engl J Med 2015;372:

22 64 Additional Measures Stop unnecessary antibiotics Fluids and lytes Avoid antimotility agents Review use of PPIs 65 Nicer C. diff Spores? Non-toxigenic C. diff spores or placebo given to 168 patients Fecal colonization occurred in 69% Odds ratio of recurrence 0.28 of those colonized Diarrhea + abd pain in 46% of treated v. 33% of placebo Gerding, DN et al. JAMA 2015;313(17): Every antibiotic expected by a patient, every unnecessary prescription written by a doctor, every uncompleted course of antibiotics is potentially signing a death warrant for a future patient Dryden, et al