Pneumonia Update 2016 Disclosure of Financial Relationships Scott A. Flanders, MD Has disclosed relationships with entities producing, Management of the Hospitalized Patient marketing, re-selling, or distributing health care goods or October, 2016 services consumed by, or used on, patients. Scott A. Flanders, M.D., MHM Consultant Advisory Boards Professor of Medicine NONE NONE Director, Hospital Medicine Program Associate Chair for Quality and Innovation Research and Grant Support Speakers Bureau CDC Foundation NONE University of Michigan AHRQ Blue Cross Blue Shield, MI Board Member NONE Pneumonia Guideline Groups * ATS / IDSA GL panel member * non-financial Key Topics to Cover Values and Preferences • Pneumonia 1. Recommend treatments shown to improve clinical outcomes – Diagnosis: CXR / Etiologies / Procalcitonin – Antibiotics – Steroids 2. Reduce unnecessary antibiotic use -Use lowest number / “spectrum” of antibiotics • “Healthcare-Associated Pneumonia” – Which pneumonia patients are at risk for resistant -De-escalate rapidly and shorten durations organisms? 1
A National Priority Clostridium difficile diagnoses: • First attempt to U.S. Hospitals 1993-2011 characterize the annual human toll of antibiotic resistance. Lessa, et al. NEJM 2015 • 450,000 US cases (2011) • 66% healthcare associated • 29,000 deaths Current Challenges Conditions Driving Antibiotic Use Antibiotic Use in U.S. Hospitals The Big Three • CDC: trend analysis over 550 hospitals; 2006-2012 • #1 Urinary Tract Infection (UTI) – 55% of patients on antibiotics • #2 Pneumonia – Overall use stable; shift to more broad spectrum use Baggs, J, et al., JAMA IM, 2016. • #3 Skin and Soft Tissue Infection • 30%-50% of use is felt to be inappropriate (UTI and pneumonia account for over half of all inpatient antibiotic use) Dellit TH, Clin Infect Dis. 2007. Fridkin S, MMWR, 2014 JAMA. 2014; 312(14): 1438-46 2
Key Topics to Cover Is CXR the Gold Standard? • Pneumonia • French study of 320 patients with suspected CAP – Diagnosis: CXR / Etiologies / Procalcitonin • Excluded very severe cases (ICU, CRB65 >3) – Antibiotics • Performed CXR in all – Steroids • Asked ED docs to assess: • “Healthcare-Associated Pneumonia” – Probability of CAP – Antibiotic plan – Which pneumonia patients are at risk for resistant organisms? – Site of care decisions • Perform Chest CT! Claessens YE, AJRCCM. 2015 • Ask docs again CT for Everyone!? Is CXR the Gold Standard? Caveats • Antibiotics after CT: 15% stopped, 45% started • 120 pts with – CXR : 30% with CT infiltrates • 190 pts with + CXR: 30% with NO CT infiltrates • CT differed often with clinical / CXR disconnect – CXR negative but high WBC, CRP, age, crackles • ED docs modified probability of CAP in 60% – CXR positive but no concerning findings – 80% in line with adjudicated diagnosis • Modify treatment, drug or site of care : 61%! • Alternate diagnoses: CHF, COPD • Takehome: CXR is one part of the assessment and Claessens YE, AJRCCM. 2015 is imperfect 3
Case #1 CAP Etiologies A 64 yo woman with CHF is admitted with 2 days of fever, non- productive cough, and shortness of breath. She has been on levofloxacin for 24 hrs per PCP. T 38.8, BP 110/75, HR • Traditional thinking: 90, sats 89% RA. WBC 11 k. CXR shows a patchy RLL infiltrate. She is started on Ceftriaxone / Azithro in the ED – S. Pneumoniae and admitted to you. Her respiratory panel is positive for adenovirus and her serum procalcitonin (x2) is 0.05mcg / L. – H. Influenzae Now what?: – Moraxella catarrhalis – Klebsiella 1) Wait for blood and sputum cultures before deciding – Atypicals (legionella, Mycoplasma, C. pneumoniae ) 2) Stop antibiotics – S. Aureus 3) Continue antibiotics for possible bacterial co-infection 4) Stop antibiotics and start Lasix for CHF exacerbation CAP Etiologies • CDC study in Chicago / Nashville (5 hospitals) • All hospitalized adults with + CXR (>2000) • Screened 18 hrs/ d, 7 d / week! • 2010-2012 • 3-10 week f/u • Control group without CAP in Nashville • 80% Ward, 20% ICU Jain S. NEJM 2015 4
Procalcitonin: The Algorithm Procalcitonin • Microbial toxins and bacterial-specific pro- inflammatory mediators stimulate release • Levels are higher with bacterial infections vs. other • Rapid rise / fall correlates with clinical response • Correlates with severity of illness / prognosis • Not affected by steroids • Rapid testing available CHEST 2012 Procalcitonin and Antibiotic Use Procalcitonin and Outcomes RCT/Year Patients with Setting Antibiotic Respiratory Use 14 Trials, 4221 Patients with Respiratory Infections Infection OR=0.82 (0.71-0.97) 25 Christ-Crain, 2004 243 ED 22% Christ-Crain, 2006 302 ED/Inpt. 20 19% Stolz, 2007 208 ED/Inpt. Briel, 2008 458 Multicenter 15 Nobre, 2008 53 ICU PCT OR=0.94 (0.71-1.23) Kristoffeger, 2009 210 ED/Inpt 10 Control Schuetz, 2009 1359 Multicenter 6.3% 5.7% 5 Stolz, 2009 101 Multicenter, ICU Long, 2009 127 ED 0 Burkhardt, 2010 550 ICU Mortality Treatment Failure Bouadma, 2010 397 ED CID 2012 Cochrane 2012 Long, 2011 156 ED 5
Procalcitonin: Caution Warranted Procalcitonin: Use in Practice • 260 CAP pts: Extensive diagnostic testing • 200,000 COPD patients; 5% with PCT testing – (blood, sputum, urine antigens, PCT, PCR for viral) • Weak association with fewer abx starts • 23% bacterial, 16% viral (+/- bacterial), 46% ? • No association with duration of therapy Lindenauer, In Press, 2016 • Bacterial: 23% with PCT < 0.1 mcg / L (many PSI IV) • Viral: 23% with PCT > 0.25 mcg / L • 85% did not get more than 1 PCT test Lindenauer, In Press, 2016 Vaughn, Submitted, 2016 • “A low PCT cannot RELIABLY exclude serious bacterial infection” Musher, et al. J. Infection 2013 Key Topics to Cover Procalcitonin: Bottom Line • It is another less than perfect, but potentially useful • Pneumonia diagnostic test – Diagnosis: CXR / Etiologies / Procalcitonin • Should not be sole variable used to decide whether – Antibiotics to use antibiotics or not – Steroids • Most useful when on the fence re giving / stopping • “Healthcare-Associated Pneumonia” antibiotics – Which pneumonia patients are at risk for resistant – e.g., infiltrate, positive viral panel AND low PCT organisms? • It can reduce antimicrobial use if protocols for de- escalation are followed 6
Key Issues in Antibiotic Management Macrolides and Outcomes Meta-analysis; 23 studies with138,000 patients • Are macrolides (atypical coverage) necessary? • What regimens are effective for aspiration Macrolides vs. Nonmacrolides pneumonia? Mortality: RR=0.78 (0.64-0.95) • What duration of treatment is ideal? Asadi, CID, 2012 Macrolides: Antibiotic Therapy Immunomodulatory Properties? IDSA / ATS 2007 Guidelines + Modifications • b -lactam* + macrolide (or doxycycline) (*Ceftriaxone, Cefotaxime, Amp / Sul, Ertapenem, Ceftaroline) – Or, Respiratory fluoroquinolone • ICU: ß-lactam+macrolide – Or ß-lactam+fluoroquinolone – Anti-pseudomonal (many options) or CA-MRSA Rx (Vanco or Linezolid) if risk factors: independent of ICU status Corrales-Medina, Jo Infection, 2011 7
Macrolides and Outcomes Macrolides and Pneumonia Meta-analysis; 23 studies with138,000 patients RCT: Beta Lactam + Macrolide vs. Beta Lactam Beta-lactam + macro vs. Fluoroquinolone • RCT of 580 CAP pts; 6 Swiss hospitals Mortality RR = 1.17 (0.91-1.50) • Excluded: Severe Pneumonia, HCAP risk factors • Legionella urine antigen performed in all Macrolide vs. Nonmacrolide (RCTs only) • Day7 Stability: HR < 100, SBP > 90, T < 38, RR < 24, Oxygen Sat > 90% RA by day 7 Mortality RR = 1.13 (0.65-1.98) RR=1 • Macrolide: 67% No Macrolide: 59% Garin, et al. JAMA IM, 2014 Asadi, CID, 2012 Macrolides and Pneumonia Macrolides and Pneumonia RCT: Beta Lactam + Macrolide vs. Beta Lactam Pragmatic, Cluster, Randomized,Non-Inferiority Trial Beta-lactam Beta-lactam + macro Fluoro Hazard Ratio for Instability Patients 656 739 888 Adherence 93% 88% 93% Atypical pathogens 0.33 (0.13-0.85) PSI Class IV 0.81 (0.59-1.10) 90 d Mort. 9% 11% 8.8% Days to oral 4 4 3 No atypical pathogens 0.99 (0.80-1.22) LOS 6 6 6 PSI Class I-III 1.06 (0.82-1.36) Beta-lactam monotherapy: Non-inferior! (No diff at 90 days: mortality, ICU admits, LOS, complications, recurrence) (for non-ICU patients without legionella) Garin, et al. JAMA IM, 2014 Postma DF, et al. NEJM, 2015 8
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