Antibiotic Update Choosing Wisely with Academic Detailing Conference. Paul Bonnar MD, FRCPC. Oct 21,

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Antibiotic Update 2017 Choosing Wisely with Academic Detailing Conference Paul Bonnar MD, FRCPC Oct 21, 2017 Paule.bonnar@nshealth.ca

No disclosures Off-label antibiotic use will be declared

Objectives Utilize an antimicrobial stewardship approach for prescribing antibiotics. Appreciate the risks and potential harms of antibiotic use. Review the treatment recommendations for common infectious syndromes.

Outline Intro to AMS & why we care about AMR Antibiotic use in the community How to reduce antibiotic use Syndromes

Is there an infection? Likely pathogens? Is it bacterial? Resistance issues? Approach to infections Urgency to treat? Non-pharm options? Assessment plan How long should I treat? Goal of therapy

What is Antimicrobial Stewardship? Coordinated interventions designed to improve and measure the appropriate use of antimicrobials Right drug Right dose Right duration Right route Barlam. Clin Infect Dis. 2016;62(10):e51 e77 Tamma CID 2017;64(5):537 43

TEAM MEMBERS Andrea Kent Paul Bonnar Ian Davis

TEAM MEMBERS Jason Reynolds Kim Abbass Stephen Smith Valerie Murphy

VISION Safe and effective use of antimicrobial agents in patients cared for in NSHA

Pharmacy Nursing Microbiology Clinicians Public IT

WHY WE CARE 27% patients received antibiotics 1 in 5 had antibioticassociated ADE n= 1488 Tamma. JAMA Intern Med. 2017 Jun 12

1 in 5 had antibioticassociated ADE Tamma. JAMA Intern Med. 2017 Jun 12

The primary reason a particular antibiotic is given is I like it Kim. American Journal of Medicine 1989(87):201

Drugs of fear Fear, Uncertainty, Doubt +/- faulty thinking (Crislip) Our job is to adjust this fear and uncertainty (McIntyre) Emotions, underlying beliefs/attitudes, social norms Hulscher Lancet Infect Dis 2010;10: 167 75 Livorsi ICHE. 2015;36(9):1065 1072

the potential adverse effects of antibiotics have a limited influence on physician decision making prescribing decisions of other physicians are questioned, but there is reluctance to provide critique, feedback, or advice. 4 themes culture of antibiotic prescribing Trainees are strongly influenced by the prescribing behavior of their supervising staff physicians abx overuse is recognize d but generally accepted Livorsi Infect. Control Hosp. Epidemiol. 2015;36(9):1065 1072

Prophylaxis Observation Crislip

Sick source bug treatment duration outcome

www.antimicrobialstewardship.com RESOURCES

http://www.cdha.nshealth.ca/nsha-antimicrobial-stewardship

ANTIBIOTIC USE IN THE COMMUNITY Dr. Emily Black, Dalhousie Pharmacy

Antibiotic use in the community In 2014, 23 million antimicrobials were dispensed 93% dispensed from community pharmacies Most often used to treat respiratory tract infections Total antimicrobials dispensed through community pharmacies within provinces or territories in Canada, 2014 Canadian Antimicrobial Resistance Surveillance System Report, 2016 Available at: https://www.canada.ca/en/public-health/services/publications/drugs- health-products/canadian-antimicrobial-resistance-surveillance-system-report- 2016.html#a3-2-2 Dr. Emily Black, Dalhousie Pharmacy

Antibiotic use in the community 65% of Canadians filled a prescription for an antimicrobial to treat a bacterial infection in 2014 26% amoxicillin 9% azithromycin 8% ciprofloxacin Patterns in antimicrobial use by age group, as dispensed by Canadian Pharmacies, 2010-2014 Canadian Antimicrobial Resistance Surveillance System Report, 2016 Available at: https://www.canada.ca/en/public-health/services/publications/drugs-healthproducts/canadian-antimicrobial-resistance-surveillance-system-report-2016.html#a3-2-2 Dr. Emily Black, Dalhousie Pharmacy

Antibiotic use in the community Management of UTIs Ciprofloxacin was the most commonly recommended antimicrobial agent used to treat 46% of lower UTIs in women Dr. Emily Black, Dalhousie Pharmacy Canadian Antimicrobial Resistance Surveillance System Report, 2016 Available at: https://www.canada.ca/en/publichealth/services/publications/drugs-health-products/canadianantimicrobial-resistance-surveillance-system-report-2016.html#a3-2-2

Primary care antibiotic use Overall 506 antibiotic prescriptions/1000 pop >30% are unnecessary 50% if include selection, dosing, duration Top 3: sinusitis, otitis media, pharyngitis Acute respiratory conditions 221 antibiotic prescriptions/1000 pop annually 50% unnecessary Fleming-Dutra. JAMA. 2016;315(17):1864-1873 CDC

STRATEGIES for COMMUNITY PRESCRIBERS The behaviour of prescribing antibiotics is complex

Barriers in community stewardship Knowledge gaps best practices and clinical practice guidelines Clinician perception of patient expectations Perceived pressure to see patients quickly Clinician concerns about decreased patient satisfaction with clinical visits when antibiotics are not prescribed Sanchez. MMWR Recomm Rep 2016;65(No. RR-6):1 12

IV TO PO Fluoroquinolones Metronidazole Fluconazole Trimethoprimsulfamethoxazole Clindamycin Linezolid

LOS Cost Beta-lactam allergy Tx failure MDRO C diff

Beta-lactam allergy http://en.horizonnb.ca/home/careers-and-education/learning/antimicrobial-use.aspx

A point on bone scans Diagnostic method Sensitivity Specificity Probe to bone 0.60 (0.46-0.73) 0.91 (0.86-0.94) Plain radiography 0.54 (0.44-0.63) *chronicity 0.68 (0.53-0.80) MRI 0.90 (0.82-0.95) 0.79 (0.62-0.91) Bone Scan 0.81 (0.73-0.87) 0.28 (0.17-0.42) Dinh. Clin Infect Dis. 2008 Aug 15;47(4):519-27

Symptom free pee 82 year old female admitted for nausea & vomiting Cloudy urine, foul smelling Urine culture: Pseudomonas aeruginosa

Dipstick: leuk esterase + E. coli What if Candida Pregnant

https://www.ammi.ca/?id=127

ASYMPTOMATIC BACTERIURIA COMMON Dipstick NOT helpful MOST receive antibiotics Mental status changes alone Can rehydrate and r/a 24 hours Nicolle LE. CMAJ 2000;163:285 6. Nicolle LE. ICHE 2001;22(3):167-75

Nudge, nudge RCT 5 primary care clinics Acute respiratory infections Poster: signed commitment letter Posted in exam rooms for 12 weeks 20% absolute reduction in inappropriate abx (p=.02) Meeker. JAMA Intern Med. 2014;174(3):425-431

DELAYED PRESCRIPTIONS UK > 50% of ARI prescriptions are delayed RCT, multicenter in Spain acute pharyngitis, rhinosinusitis, acute bronchitis, or AECOPD 4 groups Patient-led prescription strategy Prescription collection strategy Immediate abx No abx Abad. JAMA Intern Med. 2016;176(1):21-29

DELAYED PRESCRIPTIONS DELAYED STRATEGIES Patient-led prescription strategy Prescription collection strategy Immediate abx No abx 32% 23% 91% 12% Abad. JAMA Intern Med. 2016;176(1):21-29

https://nccid.ca/antibiotic-awareness/

Acute bronchitis Pneumonia Respiratory infections AECOPD

Case: LK with cough ID: CC: HPI: PMHx: Meds: Allergies: Social Hx: LK, 65 yo female, weight 90kg Cough with productive sputum LK presents with 3 days of cough productive for green sputum. Started after runny nose and sore throat. No dyspnea, sweats, or chills. She did not measure temperature. Hypertension, coronary artery disease ASA, Perindopril, metoprolol, atorvastatin Penicillin allergy Lives with husband. Nonsmoker Vitals Phx 120/70 mmhg, 90bpm, RR 20, afebrile Normal

Case: LK with cough ID: CC: HPI: PMHx: Meds: All: Social Hx: Vitals Phx LK, 65 yo female, weight 90kg Cough with productive sputum LK presents with 3 days of cough productive for green sputum. Started after runny nose and sore throat. No dyspnea, sweats, or chills. She did not measure temperature. Hypertension, coronary artery disease ASA, Perindopril, metoprolol, atorvastatin Penicillin allergy Lives with husband. Nonsmoker 120/70 mmhg, 90bpm, RR 20, afebrile Normal

Acute Bronchitis Nasal congestion, rhinitis, sore throat, malaise Acute cough +/- sputum 10d to >3weeks Inflammation large and mid airways No signs of pneumonia Most commonly viruses Rhinovirus Influenza RSV Metapneumovirus Coronaviruses Adenovirus <10% M. pneumoniae, C. pneumoniae, B. pertussis No antibiotics 60-80% of patients receive abx Principles and Practice of Infectious Diseases 2014 Pt reassurance, Vaccinations, smoking cessation

Suspecting pneumonia/obtaining imaging: Abnormal vital signs (pulse >100/min, respiratory rate >24 breaths/min, or temperature >38 C) NLR = 0.18 Signs of consolidation on chest examination (rales, egophony, or tactile fremitus) Metlay. JAMA. 1997 Nov 5;278(17):1440-5.

Antibiotics for bronchitis Endpoint Clinical improvement at follow-up adverse effects in the antibiotic group RR (95% CI) 1.07 (0.99 1.15) 1.20 (1.05 to 1.36) Smith SM, Fahey T, Smucny J, Becker LA. Antibiotics for acute bronchitis. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD000245. DOI: 10.1002/14651858.CD000245

Bordetella pertussis All adults should receive one dose of Tdap vaccine All pregnant women 26 weeks who have not received a dose of a pertussis-containing vaccine in adulthood Canadian Immunization Guide

Case: LK with cough ID: CC: HPI: PMHx: Meds: Allergies: Social Hx: Vitals Phx Invest. LK, 89 yo female, weight 90kg Cough with productive sputum LK presents with 3 days of cough productive for green sputum. Also increasing dyspnea. Some sweats and mild chills. She did not measure temperature. Hypertension, coronary artery disease ASA, Perindopril, metoprolol, atorvastatin Penicillin allergy Lives with husband. Nonsmoker 120/70 mmhg, 100bpm, afebrile Crackles left lower base Chest Xray: Left lower lobe opacity

MANAGEMENT OF OUTPATIENT PNEUMONIA Controversial Doxycycline: less pneumo resistance than macrolides S. pneumoniae most common bacterial pathogen Macrolides: increasing pneumococcal resistance Amoxicillin best oral betalactam against S. pneumoniae Role of atypical pathogens debatable Clinical Infectious Diseases ; 2007 ; 44 : S27 -S72

Toronto CAP guidelines http://www.antimicrobialstewardship.com/

Outpatient therapy Infectious Diseases Society of America and the American Thoracic Society 2007 1. Previously healthy and no use of antimicrobials within the previous three months 2. Presence of comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; or use of antimicrobials within the previous 3 months (in which case an alternative from a different class should be selected): Macrolide or doxycycline Respiratory fluoroquinolone Or Beta-lactam (high-dose amoxicillin, amoxicillin-clavulanate; alternative agents: ceftriaxone, or cefuroxime) PLUS a macrolide

BTS / NICE CAP treated in community: amoxicillin 500mg po TID x 5days Alternative: doxycycline or clarithromycin

Duration Admitted patients, moderate to severe Amoxicillin 3 days vs 8 days Clinical success at d10: 93% in both groups Adverse events: 11% placebo; 21% treatment group p=0.1 el Moussaoui. BMJ. 2006 Jun 10;332(7554):1355.

afebrile for 48 hours no more than one clinical instability factor defined as HR >100 beats/min RR >24 breaths/min SBP 90 mmhg Sats < 90% on room air Success at 30 days was 92.6% (long) and 94.4% (short) Uranga et al. JAMA Intern Med. 2016;176(9):1257-1265

Minimizing collateral damage Make sure the patient has an infection Use as narrow a spectrum agent as possible Evidence supports amoxicillin for mild CAP Use as short a course as necessary Evidence supports azithromycin for 3 days Evidence supports levofloxacin 750 mg for 5 days

Sinusitis 38 year old with a history of asthma Facial congestion x 5days Fever x 24hours, now resolved Rhinorrhea: yellow

Clinical Manifestations Viral - 5-10 days -peak d3-6 -nasal d/c and congestion are prominent -mild fever 1 st 48 hrs Bacterial 1) Persistent symptoms 2) Onset of severe symptoms 3) Double sickening Chow. Clin Infect Dis. 2012 Apr;54(8):e72-e112

Bacterial Rhinosinusitis Symptoms 10 days without improvement Severe symptoms: fever >39 C + purulent nasal discharge or facial pain for at least 3-4 days Initial viral infection that improved with subsequent worsening: new fever, headache, nasal discharge Chow. Clin Infect Dis. 2012 Apr;54(8):e72-e112

Rhinosinusitis - management 1 2 3 Amoxicillin* Amox-clav recommended by IDSA Allergy Doxycycline (off label) or fluoroquinolone Duration 5-7 days Chow. Clin Infect Dis. 2012 Apr;54(8):e72-e112 Kaplan. Can Fam Physician. 2014 Mar; 60(3): 227-234.

Sinusitis is over treated 10% 90% 70% resolve spontaneously Bacterial Viral Chow. Clin Infect Dis. 2012 Apr;54(8):e72-e112

Cellulitis Cellulitis Gp A streptococcus Gp C/G streptococcus Gp B streptococcus S. aureus Adding clindamycin Does Not improve outcomes Doubles the risk of diarrhea Brindle R, et al. BMJ Open 2017;7:e013260

Erysipelas Gp A streptococcus Gp C or G streptococcus Gp B streptococcus S. aureus Beta-hemolytic strep: Predictably penicillin susceptible Streptococcus pyogenes Penicillin, amoxicillin, 1 st generation cephalosporin

Predisposing factors Lymphedema, venous stasis, obesity, diabetes mellitus Tinea pedis Management of cellulitis and erysipelas should include elevation of the affected area and treatment of underlying conditions. The skin should be sufficiently hydrated to avoid dryness and cracking without interdigital maceration.

No evidence for routine systemic antibiotics Commonly colonized Gram positive and Gram negatives Consider dermatitis Monitor for signs of cellulitis Local heat and tenderness Increasing erythema of the surrounding skin Lymphangitis (red streaks traversing up the limb) Rapid increase in the size of the ulcer Fever Venous Stasis Cochrane Database Syst Rev. 2014 Jan 10;(1):CD003557

Improvement takes time Antibiotic escalation in 34%, usually within 2 days of initiation Bruun. CID. 2016;63(8):1034 41

Mimickers of infection Unilateral inflammation DVT Contact dermatitis Drug reaction Gout Erythema migrans Pyoderma gangrenosum Polyarteritis nodosa Miscellaneous Bullous pemphigoid

Mimickers of infection Bilateral inflammation Usually not infection Venous stasis Contact dermatitis Lymphedema with chronic inflammation Neuropathic arthropathy (Charcot joint) Peripheral vascular disease

Duration Levofloxacin, RCT 5days vs 10days Outcome: resolution at 14 days, with absence of relapse by 28 days 98% resolution in both groups Hepburn. Arch Intern Med. 2004;164:1669-1674

Duration Levofloxacin 5days vs 10days outcome measure was resolution at 14 days, with absence of relapse by 28 days 98% resolution in both groups A case was considered a clinical success even with mild residual erythema, hyperpigmentation or edema Hepburn. Arch Intern Med. 2004;164:1669-1674

Nail punctures Pseudomonas: rubber-soled shoe Debridement Tetanus Foreign bodies

C. difficile infection Diarrhea: 3 or more unformed stools in 24 hours + A. Pseudomembranous colitis Or B. Stool testing for toxigenic C. difficile Cohen. Infection Control and Hospital Epidemiology ; 2010 ; 31 : 431-455

Unrelenting diarrhea 38 yo female Clindamycin for tooth infection Diarrhea: 8 times /day, liquid, abdominal pain Received metronidazole for 14 days for + C diff: symptoms better Persistent soft bowel movements 3 times per day Repeat C. diff positive

Recurrence 30% of patients after 1 st episode Differentiate post infectious IBS vs relapse Test of cure not recommended (nor in asymptomatic patients) False positives Persistent positive Cohen. Infection Control and Hospital Epidemiology ; 2010 ; 31 : 431-455

Summary Antibiotics are widely used Techniques to optimize antibiotic usage Approach to common syndromes sick source bug treatment duration outcome