Antibiotic Resistance Oct 24, 2018 Paul Bonnar, FRCPC paule.bonnar@nshealth.ca Jason Reynolds jason.reynolds@nshealth.ca http://www.cdha.nshealth.ca/nsha-antimicrobial-stewardship
No disclosures Off-label antibiotic recommendations will be declared This speaker has been asked to disclose to the audience any involvement with industry or other organizations that may potentially influence the presentation of any education material Receiving evaluations is critical to the accreditation process. After the program, please provide feedback at https://surveys.dal.ca/opinio/s?s=44838
Learning objectives To understand the state of antibiotic resistance and local antibiotic use patterns To understand treatment of common community-acquired syndromes To become stewards of antimicrobials
MCQ Most antimicrobials are used in: a) Hospital b) Community c) Long-term Care
MCQ 2 What % of antibiotics are used unnecessarily? a) 10% b) 30% c) 60% d) 90%
pewtrusts.org 1 in 3 prescriptions unnecessary
Resistant microorganisms are expensive BSAC 2018
MCQ How common are antibiotic side-effects? a) 5% b) 20% c) 40% d) 60%
Answer 20%
Surveillance Infection prevention and control Antimicrobial Stewardship Research and innovation
ANTIBIOTIC USE PATTERNS
Medically important antimicrobials in Canada 2014 Human medicine 18% Canadian Integrated Program for Antimicrobial Resistance. Annual Report 2014. Foodproducing animals 82%
MCQ Most antibiotics are used in the community to treat: a) Urinary tract infections b) Skin infections c) Respiratory infections d) Gastrointestinal infections
Antibiotic use in the community 2014 23 million Rx dispensed 93% dispensed from community pharmacies $786M 65% Canadians received abx Most often for respiratory tract infections Canadian Antimicrobial Resistance Surveillance System Report 2016
30% NS inpatients on antimicrobials ~2/3 IV A Point Prevalence Survey of Antimicrobial Use at Hospitals in Nova Scotia Emily Black, Heather Neville, Mia Losier, Megan Harrison, Kim Abbass, Kathy Slayter, Lynn Johnston, and Ingrid Sketris Ampicillin Amoxclav Moxifloxacin Imipenem Levofloxacin Fluconazole SMX/TMP Cephalexin 2.0% 2.0% 2.1% 2.6% 3.0% 3.3% 3.6% 4.4% 30% (26/87) of orders adherent to the 2012 Capital Health - Antimicrobial handbook Vanco 5.5% Ciprofloxacin Piptazo Ceftriaxone 7.4% 8.0% 8.9% Cefazolin Metronidazole 10.9% 11.1% Black E, Neville H, Losier M, Harrison M, Abbass K, Slayter K, Johnston K, Sketris I. CPJ. 2017;150(4):S35. (abstract)
INPATIENT ANTIBIOTIC USE IN NS 16
9 8 7 2018 April-June EZ NZ WZ DOT / 100 BEDDAY 6 5 4 3 2 1 0 CTX/ CEFOTAXIME METRONIDAZOLE LEVO/MOXI PIPTAZO CEFAZOLIN CIPROFLOXACIN AMOXCLAV VANCOMYCIN CEPHALEXIN AZI/CLARI CEFUROXIME DOXYCYCLINE AMOXICILLIN TMP-SMX AMPICILLIN MEROPENEM NITROFURANTOIN 17
NZ April-June 2018 CTX/ CEFOTAXIME AZI/CLARI CIPRO METRONIDAZOLE CEFAZOLIN PIPTAZO AMOX/CLAV LEVO/MOXI CEPHALEXIN VANCOMYCIN CEFUROXIME TMP-SMX DOXYCYCLINE NITROFURANTOIN AMOXICILLIN AMPICILLIN CLINDAMYCIN CEFTAZIDIME GENT/ TOBRA MEROPENEM 8.5 4.5 4.3 4.1 3.6 3.0 2.7 2.7 2.4 2.2 2.1 2.1 1.8 1.6 1.5 0.9 0.8 0.4 0.4 0.3 18
250 NZ BY SITE 200 Apr May Jun 150 100 50 0 Colchester East Hants HC Aberdeen Lillian Fraser Memorial Cumberland Regional South Cumberland All Saints Springhill North Cumberland Memorial 19
April-June 2018 CTX/ Cefotaxime CIPRO Cefazolin Metronidazole AZI/CLARI PIPTAZO LEVO/MOXI Vancomycin AMOXCLAV Cephalexin Cefuroxime ABERDEEN 28.1 21.3 14.9 14.5 14.3 8.6 8.2 7.3 7.2 4.9 4.3 20
ABERDEEN CTX/ Cefotaxime CIPRO Cefazolin Metronidazole AZI/CLARI PIPTAZO LEVO/MOXI High: Vancomycin Ceftriaxone AMOXCLAV Ciprofloxacin Cephalexin Macrolides Cefuroxime 28.1 21.3 14.9 14.5 14.3 8.6 8.2 7.3 7.2 4.9 4.3 Low: Carbapenems 21
OPTIMIZE ANTIBIOTIC USE
Misuse of antibiotics Underuse An antibiotic is not used when it could improve health Unnecessary use An antibiotic is not indicated e.g. non bacterial infections Inappropriate use Incorrect timing, choice, dose, route, or duration
Inappropriate use in hospitals Common indications where prescribing is inappropriate or suboptimal Surgical prophylaxis Respiratory infections (CAP, bronchitis, AECOPD) Urinary tract infections Skin and soft tissue infections GI Antimicrobial prescribing practice in Australian hospitals. December 2016
Dose / frequency Choice Optimal use Duration / timing Route
Pr ophylaxis Observat ion Therapeut ic t rial Specif ic t herapy Em piric
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 Leah Day
TEAM MEMBERS Jason Reynolds Kim Abbass Stephen Smith Valerie Murphy
SUMMARY OF ACTIVITIES Prospective audit and feedback IV to PO policy Obtaining antimicrobial use data Presentations / education Handbook & guidelines Research / QI projects Point Prevalence Surveys Redundant therapy policy Public engagement: Antibiotic Awareness Week Website Cascading sensitivities Antibiograms Beta-lactam allergy algorithm Formulary review Outpatient Academic Detailing
FORMULARY INFO Caspofungin replacing micafungin Better evidence for pediatric patients 70mg IV x 1, then 50mg IV q24h Same spectrum of activity Levofloxacin replacing moxifloxacin Oral levofloxacin is less expensive Levofloxacin is narrower- spectrum & moxifloxacin has poor anaerobic activity Levofloxacin is the respiratory fluoroquinolone when require broader coverage than betalactam Protect antimicrobials Green: No special instructions Stoplight system Optimize safe antimicrobial use Yellow: Clinical guideline Red: AMS reviews within 48-72h Therapeutic interchange for cefazolin Cefazolin 2g dose will replace 1g dose
STRATEGIES Duration Antibiotic time outs Followup sensitivity results Drug-Bug mismatch
Duration
Incorrect duration common cause of unnecessary use
Patients on abx Abx in the IV PO Conversion Policy given IV Orders with an indication Orders with duration or reassessment date TOTAL 34% 41% 77% 44% Central 34% 30% 83% 34% Western 29% 30% 87% 53% Northern 37% 44% 79% 47% Eastern 42% 55% 58% 39% Sept 2017
Median total LOT was 9.5 days for CAP in US Spellberg. JAMA Intern Med. 2016 Sep 1;176(9):1254-5. Yi et al. CID 2018:66 (1 May)
Antibiotic time outs
IV TO PO FQNs Clindamycin Linezolid Metronidazole Fluconazole TMP-SMX
Followup on sensitivity results Drug-Bug mismatch
73% of interventions were narrowing antimicrobial therapy
CULTURE OF CULTURING Effect of positive lab result Indiscriminate culturing / PANculturing Standing orders Reflex testing PPOs Positive Cx drive Rx
Handbook S. aureus Candidemia Meningitis ASB/cystitis Vancomycin
LOS Cost Beta-lactam allergy Tx failure MDRO C diff
Penicillin Amoxicillin Ampicillin Cloxacillin Piperacillin Cephalexin Cefazolin Cefadroxil Cefoxitin Cefuroxime Cefprozil Cefaclor Cefotaxime Ceftriaxone Cefixime Ceftazidime Ceftolozane Penicillin X X X X X Amoxicillin X X X X X X X X Ampicillin X X X X X X X X Cloxacillin X X X X Piperacillin X X X X Cephalexin X X X X X Cefazolin Cefadroxil X X X X X Cefoxitin X X Cefuroxime X X X X Cefprozil X X X X X Cefaclor X X X X X Cefotaxime X X Ceftriaxone X X Cefixime Ceftazidime X Ceftolozane X=Risk of cross reaction due to identical or similar side chains
http://www.cdha.nshealth.ca/nsha-antimicrobial-stewardship
Discharge antibiotics Only 21% appropriate for duration Chavada et al. BMC Infectious Diseases (2018) 18:225
SYNDROMES
Symptom free pee 82 year old female admitted for nausea & vomiting Cloudy urine, foul smelling Urine culture: Pseudomonas aeruginosa
SYMPTOM FREE PEE: LET IT BE https://www.ammi.ca/?id=127
NITROFURANTOIN 1 st line by IDSA Beers: previously high severity risk potential for renal impairment safer alternatives available NOT nephrotoxic Excreted by kidneys Low egfr: less drug in urinary tract; risk of non-renal toxicities 51
Beers - update Avoid if ClCr <30mL/min Avoid long term use (also should avoid if interstitial lung disease) Low quality of evidence Strong strength of recommendation J Am Geriatr Soc. 2015 Nov;63(11):2227-46
Cystitis: Nitrofurantoin 5 days (A-I) Fosfomycin 3g 1 dose (A-1) TMP/SMX 1DS po BID 3 days (A-I) (off label) Amoxclav 875/125mg BID 5-7days (B-I) (MOXIFLOXACIN does not get into urine) CID, Volume 52, Issue 5, 1 March 2011, Pages e103 e120
Respiratory infections
Acute bronchitis Respiratory syndromes Pneumonia
Case: LK with cough ID: CC: HPI: PMHx: Meds: Allergies: Social Hx: LK, 45 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
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 (but 60-80% of patients receive abx) Principles and Practice of Infectious Diseases 2014 Pt reassurance, Vaccinations, smoking cessation
Antibiotics for bronchitis Endpoint Clinical improvement at follow-up Adverse effects in the antibiotic group RR (95% CI) 1.07 (0.99 1.15) NNT for an additional beneficial outcome (NNTB)= 22 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
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 chills. She did not measure temperature. Hypertension, coronary artery disease ASA, Perindopril, metoprolol, atorvastatin Penicillin allergy Lives with husband. Nonsmoker 120/70 mmhg, 100bpm, febrile Crackles left lower base Chest Xray: Left lower lobe opacity
MANAGEMENT of COMMUNITY ACQUIRED 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
http://www.antimicrobialstewardship.com/
BTS / NICE CAP treated in community: amoxicillin 500mg po TID x 5days [1a] Alternative: doxycycline [4b] or clarithromycin [1b] Thorax 2009; 64 (Suppl III):iii1 iii55
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); p=.54 Uranga et al. JAMA Intern Med. 2016;176(9):1257-1265
Skin and soft tissue infections
Improvement takes time Antibiotic escalation in 34%, usually within 2 days of initiation Bruun. CID. 2016;63(8):1034 41
TIPS Not all lab results are relevant Fever is not always infection Watch for sensitivity results Allergy assessments, allergy is harmful Side effects are common A complete prescription requires an INDICATION Use resources: Academic detailing, NSHA ASP
Summary Antibiotics are widely used, resistance is a major concern Techniques to optimize antibiotic usage Approach to common syndromes sick source bug treatment duration outcome
paule.bonnar@nshealth.ca jason.reynolds@nshealth.ca