Paul Bonnar, FRCPC

Transcription

1 Antibiotics Over-prescribing and New Antibiotics Sept 18, 2018 Paul Bonnar, FRCPC

2 No disclosures Off-label antibiotic recommendations will be declared Receiving evaluations is critical to the accreditation process. Please provide feedback

3 Learning objectives To understand the state of antibiotic resistance and antibiotic use patterns To be aware of new antibiotics in the pipeline To understand treatment of common community-acquired syndromes To become stewards of antimicrobials

4 MCQ Most antimicrobials are used in: a) Hospital b) Community c) Long-term Care

5 MCQ 2 What % of antibiotics are used unnecessarily? a) 10% b) 30% c) 60% d) 90%

6 pewtrusts.org Each year in Canada, >18,000 hospitalized patients acquire infections that are resistant to antimicrobials

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8 Antimicrobial resistance is an urgent global public health threat WHO: Antimicrobial Stewardship for Hospitals Training Workshop

9 Carbapenemase-producing Enterobacteriaceae Canadian Antimicrobial Resistance Surveillance System Report 2016

10 Lancet Infect Dis Dec 21 WHO priority list

11 N Engl J Med 2005;352:380-91

12 Vancomycin-resistant Enterococcus infections Canadian Antimicrobial Resistance Surveillance System Report 2016

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14 Resistant microorganisms are expensive BSAC 2018

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16 LESS REWARD Used for short duration Priced low Held in reserve LONGER DEVELOPMENT

17 IDSA Ceftazidime / Avibactam

18 Dalbavancin Tedizolid phosphate Oritavancin diphosphate Delafloxacin meglumine Lipoglycopeptide (1953) Oxazolidinone (1955) Lipoglycopeptide (1953) Indication FDA Approval date Dalvance IV SSTIs May 2014 Sivextro PO/IV SSTIs June 2014 Orbactiv IV SSTIs Aug 2014 Baxdela IV/PO SSTIs June 2017 Ceftolozane and tazobactam Ceftazidime and avibactam Meropenem and vaborbactam Isavuconazonium sulfate Ceph (1928) + BLI Ceph (1928) + BLI Zerbaxa Avycaz IV IV ciai (+metronidazole) cuti ciai (+metronidazole) cuti HAP/VAP Dec 2014 Feb 2015 Vabomere IV cuti Aug 2017 Cresemba IV/PO Invasive aspergillosis Invasive mucormycosis March 2015 Secnidazole Solosec PO Bacterial vaginosis Sept 2017 GAINS FDA report

19 Jan Ceftaroline Cephalosporin (1928) IV SSTI, CAP Fidaxomicin Macrolide (1948) PO C. diff Bedaquiline Diarylquinoline (1997) PO MDR-TB 2009 Telavancin Lipoglycopeptide IV SSTI, CAP Ann Intern Med Sep 6;165(5):

20 pewtrusts.org

21 Surveillance Infection prevention and control Antimicrobial Stewardship Research and innovation

22 ANTIBIOTIC USE PATTERNS

23 Medically important antimicrobials in Canada 2014 Human medicine 18% Canadian Integrated Program for Antimicrobial Resistance. Annual Report Foodproducing animals 82%

24 MCQ Most antibiotics are used in the community to treat: a) Urinary tract infections b) Skin infections c) Respiratory infections d) Gastrointestinal infections

25 Antibiotic use in the community 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

26 Canadian Antimicrobial Resistance Surveillance System Report 2016

27 65% Canadians filled Rx 26% amoxicillin Patterns in antimicrobial use by age group, as dispensed by Canadian Pharmacies, % azithromycin 8% ciprofloxacin Canadian Antimicrobial Resistance Surveillance System Report 2016

28 Management of UTIs Ciprofloxacin was the most commonly recommended antimicrobial agent used to treat 46% of lower UTIs in women Canadian Antimicrobial Resistance Surveillance System Report 2016

29 Canadian Antimicrobial Resistance Surveillance System Report 2016

30 Ambulatory care antibiotic use in US Overall 506 antibiotic prescriptions/1000 pop/year >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): CDC

31 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 30% NS inpatients on antimicrobials Ampicillin Amoxclav Moxifloxacin Imipenem 2.0% 2.0% 2.1% 2.6% 47% ICU ~2/3 IV Levofloxacin Fluconazole SMX/TMP Cephalexin Vanco Ciprofloxacin Piptazo Ceftriaxone 3.0% 3.3% 3.6% 4.4% 5.5% 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)

32 OPTIMIZE ANTIBIOTIC USE

33 MCQ How common are antibiotic side-effects? a) 5% b) 20% c) 40% d) 60%

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35 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

36 Dose / frequency Choice Optimal use Duration / timing Route

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38 Empiric vs targeted therapy Empiric therapy Treating an infection without knowing the causative pathogen Relying on experience and precedent Prophylaxis Prevention of disease Both rely on - Knowledge of location of disease in the body - Local epidemiology Classes of infective agents Targeted therapy Antibiotic regimen determined by identity and antibiotic sensitivities More refined and specific compared to empiric therapy WHO: Antimicrobial Stewardship for Hospitals Training Workshop Commensal an organism in a co-operative relationship in which the person derives some benefit while remaining unaffected by its presence do not cause disease when in their usual location Staphylococcus epidermidis on skin, Escherichia coli in gastrointestinal tract Pathogen an organism that causes disease some organisms are always regarded as pathogenic Mycobacterium tuberculosis, Salmonella typhi, influenza virus - some sites are normally sterile e.g. blood, cerebrospinal fluid (CSF), bladder any organisms in these sites are usually thought of as pathogenic WHO: Antimicrobial Stewardship for Hospitals Training Workshop

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40 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

41 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

42 Don t prescribe antibiotics in adults with bronchitis/asthma in adults and children with uncomplicated sore throats for upper respiratory infections that are likely viral in origin, such as influenza-like illness, or self-limiting, such as sinus infections of less than 7 days of duration adult cough with antibiotics even if it lasts more than 1 week, unless bacterial pneumonia is suspected (mean viral cough duration is 18 days) asymptomatic bacteriuria (ASB) in non-pregnant patients Don t routinely prescribe IV forms of highly bioavailable antimicrobial agents Don t prescribe alternate 2 nd line antimicrobials to patients reporting nonsevere reactions to penicillin when beta-lactams are the recommended 1 st therapy

43 Clinical question Do you you use delayed prescriptions? a) Yes b) No

44 Barriers in community stewardship Knowledge gaps best practices and clinical practice guidelines Clinician perception of patient expectations 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

45 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):

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47 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

48 DELAYED PRESCRIPTIONS DELAYED STRATEGIES Patient-led prescription strategy Prescription collection strategy Immediate abx No abx 32% 23% 91% 12% P<.001 Abad. JAMA Intern Med. 2016;176(1):21-29

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50 Duration

51 Inappropriate use in hospitals Common problems Antimicrobial not indicated 30-50% inpatient use inappropriate or suboptimal 1 Spectrum to broad Incorrect duration Incorrect dose Microbiology mismatch Spectrum too narrow 0.00% 5.00% 10.00% 15.00% 20.00% 25.00% 30.00% 1. CDC Get Smart for Healthcare in Hospitals and Long Term Care 2. Antimicrobial prescribing practice in Australian hospitals. December 2016

52 Spellberg. JAMA Intern Med Sep 1;176(9):

53 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

54 Antibiotic time outs

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56 Followup on sensitivity results Drug-Bug mismatch

57 73% of interventions were narrowing antimicrobial therapy

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59 Handbook S. aureus Candidemia Meningitis ASB/cystitis Vancomycin

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62 LOS Cost Beta-lactam allergy Tx failure MDRO C diff

63 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

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65 SYNDROMES

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

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68 Practice Points Asymptomatic bacteriuria is a colonization state NOT an infection Antibiotics are NOT indicated Bacteriuria and pyuria are expected findings in the elderly Symptomatic UTI is much less common than asymptomatic bacteriuria Nicolle LE. Infect Dis Clin North Am 1997;11(3): Nicolle LE. Infect Control Hosp Epidemiol 2001;22(3):

69 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 69

70 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 Nov;63(11):

71 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

72 Management of UTIs Ciprofloxacin was the most commonly recommended antimicrobial agent used to treat 46% of lower UTIs in women Canadian Antimicrobial Resistance Surveillance System Report 2016

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75 Respiratory infections

76 Acute bronchitis Respiratory syndromes Pneumonia

77 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

78 Case: LK with cough ID: CC: HPI: PMHx: Meds: All: Social Hx: Vitals Phx 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 120/70 mmhg, 90bpm, RR 20, afebrile Normal

79 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

80 Antibiotics for bronchitis Endpoint Clinical improvement at follow-up Adverse effects in the antibiotic group RR (95% CI) 1.07 ( ) NNT for an additional beneficial outcome (NNTB)= (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.: CD DOI: / CD000245

81 Canadian Antimicrobial Resistance Surveillance System Report 2016

82 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

83 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

84 CAP requiring hospitalization among US adults NEJM 2015; 373:415-27

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87 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

88 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):

89 Minimizing collateral damage Acute bronchitis is usually VIRAL 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

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

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

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

93 Rhinosinusitis - management Amoxicillin* Amox-clav recommended by IDSA: (weak, low) Allergy Doxycycline or fluoroquinolone Duration 5-7 days (weak, low-moderate) Chow. Clin Infect Dis Apr;54(8):e72-e112 Kaplan. Can Fam Physician Mar; 60(3):

94 Rhinosinusitis - management Amoxicillin* Amox-clav recommended by IDSA Allergy Doxycycline or fluoroquinolone Duration 5-7 days Kaplan. Can Fam Physician Mar; 60(3):

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

96 Canadian Antimicrobial Resistance Surveillance System Report 2016

97 Skin and soft tissue infections

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99 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

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101 Improvement takes time Bruun. CID. 2016;63(8):

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

103 C. difficile CDC

104 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

105 Summary Antibiotics are widely used in outpatients, resistance is a major concern Techniques to optimize antibiotic usage Approach to common syndromes sick source bug treatment duration outcome