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1 Antibiotic Mindfulness - Becoming Better Stewards of a Precious Resource What Is Stewardship? Merriam-Webster: The careful and responsible management of something entrusted to one's care Paul J. Carson, MD, FACP The responsible overseeing and protection of something considered worth caring for and preserving Dept. of Public Health, Management of Infectious Diseases Because infectious diseases have been largely controlled in the United States, we can now close the book on infectious diseases. - William Stewart, MD U.S. Surgeon General, 1967 Conspicuous Consumption Antibiotics Across the Health Care Spectrum 5 out of every 6 Americans will receive a course of antibiotics annually million antibiotic Rx ( 3 million kg) / yr Avg American child will receive courses of antibiotics before age 18 Not atypical for a 2 y.o. to have spent 3 mos of their life on antibiotics Wenzel RP and Edmond MB. N Engl J Med. 2000;343: Spellberg and Bartlett. N Engl J Med. 2013; 368; Hicks and Taylor. N Engl J Med. 2013; 368; Nursing Home 1

2 A Tale of Two Countries: Rate of Outpatient Antibiotic Use, 2014 Estimated 50 million unnecessary outpt antibiotic prescriptions / yr CDC 835/ 1000 population / yr 328/ 1000 population / yr Geographic Variability in HEDIS Measures Related to Appropriate Antibiotic Use Antibiotic Prescribing Increases with Fatigue Children diagnosed with VURI not receiving an antibiotic, Adults with acute bronchitis not receiving an antibiotic, Roberts RM. Am J Manag Care. 2016;22(8): Overuse of Antibiotics in Nursing Homes Trends in Hospital Antibiotic Use from % of antbiotics will be unnecessary 70-80% will or inappropriate receive an antibiotic each year 2 million 5 will people receive will pass unnecessary through a NH each year or 1.6 inappropriate million long-term antibiotics residents in 20,000 NHs Vancomycin 43% Carbapenems 59% Piperacillin- 84% Tazobactam HeckerMT, et al. Arch Intern Med2003:163: PakyzAL, et al. Arch Intern Med. 2008;168(20):

3 Trends in Hospital Antibiotic Use from % of Antibiotic Use Unnecessary or Inappropriate HeckerMT, et al. Arch Intern Med2003:163: PakyzAL, et al. Arch Intern Med. 2008;168(20): April 2010 CDC Hazard Level for Antibiotic Resistance Threats Concerning Serious Urgent VRSA MRSA Clostridium difficile(c. diff) Ery-R GABHS VRE Carbapenem-R Enterobacteriaceae Clinda-R GBBHS MDR-Pseudomonas Drug-resistant N. gonorrhoeae ESBL-Enterobacteriaceae DR-Campylobacter DR-Salmonella Fluconazole-R Candida sp MDR-Acinetobacter MDR/XDR TB Approved Antibiotics in U.S Frequency of ADEs due to Antibiotics in Outpatient Setting # of New Abx Up to 1:4 will experience some ADE with an antibiotic 142,505 estimated emergency department visits/year due to untoward effects of antibiotics (~ 1:1000 abxprescriptions) Antibiotics account for 19.3% of drug related adverse events 78.7% for allergic events 19.2% for adverse events (e.g. diarrhea, vomiting) Approximately 50% due to penicillin & cephalosporin classes 6.1% required hospital admission NEISS-CADES project Bourgeois, et al. Pediatrics. 2009;124;e Linder. Clin Infect Dis Sep 15;47(6):744-6 Vangay, et al. Cell host & Microbe 2015;17; Shehab N et al. Clin Infect Dis. 2008;47:735 3

4 Risks with Use of the Quinolones Condition Relative Risk Achilles tendon rupture Current exposure overall Age Age > (95% CI, ) 6.4 (95% CI, ) 20.4 (95% CI, ) Serious arrhythmia 2.43, 95% (CI, ) Death 1-5 d after Levofloxacin 2.49 (95% CI, ) Aortic dissection 2.43 (95%CI, ) C. Diff infection 12.7 (95% CI, ) Risk of acquiring MRSA 3.0 (95% CI 2.5 to 3.5) (c/w 1.8 RR for other abx) Van Der Linden. JAMA Int Med 2003 Gowtham. Ann Fam Med. Apr 2014 Chien-Chang. JAMA Int Med 2015 McCusker. Emerg Infect Dis 2003 Tacconelli. JAC nd lineabxfor pneumonia and UTIs with a black box warning Over 23 million prescriptions of quinolones / yr in U.S. (most commonly prescribed class) Over 2,000 lawsuits filed for injuries in 2011 Human Microbiome Diversity of Bacteroides Species in Gut After 7 day Course of Clindamycin Human Cells Bacterial Cells Microbiology (2010), 156, Dysbiosis Do These Antibiotics Make Me Look Fat?? Obesity Auto-immune dz Metabolic syndrome Diabetes IBD Asthma Allergy Autism Mice given low dose penicillin before weaning become obese Germ free mice exposed to the microbiome of the obese mice become obese Cox et al. Cell

5 Prevalence of colorectal adenomas on screening colonoscopy in the Nurses Health Study based on > 2mos of antibiotic exposure at a younger age 36% increased risk if received age % increased risk if received age JAMA Pediatr. 2014;168(11): Are doctors just being stupid? Or Evil? Risks of not recognizing and treating early sepsis Risks of overdiagnosis and treatment Call for Antimicrobial Stewardship - Preserve a Precious Resource We must come to the belief that casually writing for an antibiotic is not a benign act! 5

6 What Is Antimicrobial Stewardship? Right Drug, Right Dose, Right Duration, Right Time, Every Time Antibiotic Expenditures in U.S. by Treatment Setting, 2009 Total Cost $10.7 billion) Antibiotic Risks ADEs C diff Abx resistance Antibiotic Benefits Resolution of Infxn Morbidity & mortality 34% 5% 61% Community Hospital Nursing Home Antibiotic Time-Out 1. Does my patient really need an antibiotic? 2. If I am going to give an antibiotic, what is the most appropriate choice? 3. Can I revisit the situation in a couple days to assess clinical progress, cultures, and ability to adjust my antibiotics? 4. Have I set an appropriate duration of therapy? Antibiotic Time-Out 1. Does my patient really need an antibiotic? 2. If I am going to give an antibiotic, what is the most appropriate choice? 3. Can I revisit the situation in a couple days to assess clinical progress, cultures, and ability to adjust my antibiotics? 4. Have I set an appropriate duration of therapy? Respiratory Infections are the # 1 Reason for Office Visits Nearly Two-thirds of all Oral Solid Antibiotic Prescriptions are for Sinusitis and Bronchitis Number of common office visits (millions) Percent oral solid antibiotic use Respiratory infections Hypertension Disorders of lipid metabolism Diabetes mellitus Depressive disorder 0 Sinusitis Bronchitis Pharyngitis Pneumonia Otitis media Telithromycin (Ketek ) is indicated for acute exacerbations of chronic bronchitis, acute bacterial sinusitis and mild-to-moderate community-acquired pneumonia Source: Verispan PDDA 2004 Source: SDI, FANDxRx. Based on all tablets/capsule antibiotics for the 52 weeks ending April 6,

7 Acute Uncomplicated Rhinosinusitis Antibiotics Only If: Symptoms lasting > 10 days, or How Do You Clinically Distinguish Bacterial Sinusitis From a VURI?? 3-4 days of severe symptoms or high fever, or Double-sickening start worsening after initial improvement Guidelines from the AAO-Head and Neck Surgery million Antibiotic Prescriptions Annually in U.S. Acute Bronchitis: Meta-Analysis of Abx v. Placebo 95% of patients at Sanford with acute uncomplicated sinusitis N = 875 Cochrane Review 2012 AAP Recommendations for Watchful Waiting in AOM Child >6 mosold Non-severe AOM Unilateral disease Mild pain < 48 hrs Temp < degrees F Acute SuppartiveOtitis Media Otitis Media with Effusion Consideration with parent for watchful waiting for hrs 7

8 Pharyngitis Appropriate Antibiotic Grp A Strep Only in: 37% of children 18% of adults No antibiotics without a positive test Condition 1 st Line Antibiotic 2 nd Line Antibiotic Acute Otitis Media Amoxicillin Cefdinir, Cefprozil Acute Bacterial Sinusitis Amoxicillin Amoxicillin clavulanate Pharyngitis Penicilliin V Benzathine Penicillin Doxycycline Cephalexin Clindamycin Urinary Tract Infection What is It? Asymptomatic Bacteriuria = UTI Common, esp. elderly women and compromised pts 20-50% of treated UTI is actually Asx Bacteriuria Ratio of asxbacteriuria to symptomatic UTI in LTC is > 100:1 Good evidence that Rx gives no benefit and causes harm (ADEs, resistance, more UTI) UTI is #1 reason for Abx in LTCFs Do UTIs Cause That? - Myths, Legends, and Reality: Problem: What constitutes symptoms in an elderly, incontinent, and demented patient with limited ability to communicate? ASB is common as are atypical presentations for infection. Unexplained falls Weakness Evidence for this is overall poor quality Delirium Change in mental status Change in urine character Kallin K, et al. J Family Practice 2004:53;41 52 Campbell AJ. BMJ2008;337:a2320 Juthani Mehta M. J Am Geriatr Soc 2009;57: Nicolle, L. J Amer Geri Soc 2009;57: Rituparna, D. Infect Control and Hosp Epid 2011;32:84 6 Gupta K. JAMA 2014;311: SundvallPD.BMC Family Practice 2011, 12:36 Juthan Mehta M. JAMA2014;312:

9 UTI Pathway to Assist with Antibiotic Use for Sub-Acute Care, LTC & Nursing Home Facilities START: Suspected UTI. What are the patient s symptoms? Empiric Antimicrobial Management of UTI STOP WAIT GO Mental Status Changes (resident seems off ), Foul Smelling Urine, OR Urine Color Changes (dark or cloudy) Antibiotics and Urine Culture NOT INDICATED, further eval n and monitoring required Seek alternative causes changes (e.g. dehydration, medications, environmental changes, metabolic problems, bleeding, cardiovascular, stroke, etc.) PLACE RESIDENT ON CLOSE MONITORING PROTOCOL Increased fluid intake (unless contraindicated) Monitor & document I/Osand VS every shift for next 24h New or Changing Urinary Symptoms (Urgency, frequency, suprapubic pain, gross hematuria, CV angle tenderness, incontinence, persistent foul urine) OR Signs of Sepsis ( ) THENtake a clean catch urine (per protocol) and send for UA and/or C&S Syndrome Antibiotic Duration Comments Uncomplicated Cystitis Pyelonephritis - Outpatient - Inpatient Complicated Cystitis Pyelonephritis Nitrofurantoin 100 mg bid TMP-SMX DS bid Fosfomycin 3 gm Cipro or Levo 250 mg bid - Cipro 500 mg bid - IV FQ, CP or ES-PCN - Cipro 500 mg bid - IV CP, ES-PCN, FQ 5 days 3 days Single dose 3 days 7 days 5-10 days 5-14 days First choice, low resistance, Avoid if GFR < 30 Avoid if regional resistance > 20% or recent use Minimal resistance, avoid if any suspicion of pyelo 2 nd line agents, should be reserved if can t take above Definitive therapy should be based on C&S data. Consider carbapenem if ESBL risk is high Need to empirically cover for pseudomonas and consider ESBL. Definitive rx based on C&S data Antibiotic Resistance Trends in E. coli Urinary Isolates 51 SSTI - Infection not Really Present n = 12,253,679 No documentation other than skin changes -no fever, no WBC, no pain Dependent Rubor Sanchez GV. Antimicrob Agents Chemother 2012 SSTI - Infection not Really Present No documentation other than skin changes -no fever, no WBC, no pain SSTI - Infection not Really Present No documentation other than skin changes -no fever, no WBC, no pain Acute Edema / Expansion Syndrome Stasis dermatitis and Stasis ulceration Lipodermatosclerosis 9

10 Empiric Rx of Cellulitis 55 Empiric Antibiotic Choices for SSI Purulent or Wound Usually staphylococcal MRSA will account for ~ 50% depending on your community Non-purulent usually due to beta-hemolytic strep If Strep likely IV start with cefazolin(2gm IV q 8 hrs) or ceftriaxone (1gm IV) Continue with p.o. cephalexin or dicloxacillin Don t shortchange the dose... Minimum 500 mg qid, can give up to 1gm qidin the obese If S. aureus likely IV start with vancomycin Continue with p.o. Zyvox or cephalexin + TMP-SMX or Minocycline Antibiotic Time-Out 1. Does my patient really need an antibiotic? 2. If I am going to give an antibiotic, what is the most appropriate choice? 3. Can I revisit the situation in a couple days to assess clinical progress, cultures, and ability to adjust my antibiotics? 4. Have I set an appropriate duration of therapy? Disease Duration of Therapy It May Be Shorter Than You Think! Duration of Treatment (days) Short Long Pharyngitis Acute Sinusitis 5 10 COPD exacerbation < 5 > 7 CAP HCAP, HAP < Cellulitis UTI Cystitis 5 days (macrodantin) 3 days (TMP-SMX, quinolones) UTI Pyelonephritis 5 days (quinolones) 14 days (TMP-SMX, or Beta lactam) Peritonitis 4-7 days after source control 10 7 Altimimi S. Cochrane Database 2012 Spellberg B. JAMA Int Med 2016 The art of medicine is to amuse the patient while nature cures the disease Voltaire A desire to take medicine is, perhaps, the greatest feature which distinguishes man from animals One of the first duties of the physician is to educate the masses not to take medicines Sir William Osler 10

11 Patient Education Resources CDC s Get Smart Patient Education (office posters, fact sheets, viral prescription pads ABIM/Consumer Reports Choosing Wisely patient education handouts (excellent!) 11