diagnosis and management of acute respiratory tract infections€¦ · diagnosis and management of...
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Diagnosis and management of acute respiratory tract infections
Nathan C. Dean MD
Section Chief of Pulmonary and Critical Care Medicine Intermountain Medical Center and LDS Hospital
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Acute Respiratory Tract Infections
• Influenza and other respiratory viruses –Acute bronchitis and viral pneumonia
• Acute exacerbation of chronic bronchitis
• Community-onset pneumonia –HCAP is mostly dead!
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? Fever >37.8 CHeart rate >100VR › 24SpO2 <90%Focal rales
? Severe myalgia, fever >37.8 CAbsence of rhinorrheaDry coughInfluenza present in community
? Chronic bronchitis
Acute bronchitis
Pneumonia
Influenza
AECB
CxR
NO
NO
YES
NO
YES
YES +
-
↑ dyspnea, cough, sputum purulence
Patient with cough <2 weeks
(Asthma, CHF, Sinusitis, Tuberculosis)
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Acute Bronchitis
• Despite considerable clinician and public education, about 70% of adults with acute bronchitis get antibiotics – usually a Z-Pak
• Multiple randomized trials show no benefit from antibiotics
• Patient education yields equal satisfaction – Antibiotics have side effects, increase risk of resistance for 90 days
– Symptomatic Rx – analgesics, nasal decongestants, OTC cough syrup.
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A 65 yo woman with acute cough illness and an important engagement…
• Over 75,000 adult prescriptions for azithromycin last 12 months Select Health
• 90% Z-paks • Clinician and patient algorithms and
educational materials available through Intermountain.net – primary care – clinical programs, bronchitis CPM
• Call it a “chest cold”
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Pneumococcal resistance
• Ceftriaxone, ampicillin/amoxicillin, and levofloxacin or moxifloxacin remain highly active
• Pneumococcal macrolide resistance –Blood isolates from adults
• 19 % Salt Lake Valley
–All isolates • 49 % Salt Lake Valley
Z-Pak
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Influenza-like illness • Fever, myalgias, cough (usually dry/minimally productive), fatigue,
headache during the winter when influenza present locally – see GermWatch, also CDC website – Specificity 80 – 85 % for laboratory confirmed influenza
• but lower in older patients
– Polymerase chain reaction (PCR)-based testing is more sensitive and specific than rapid tests
• Influenza A (seasonal), influenza B, influenza A H1N1, also other respiratory viruses
• >age 60 for complications from seasonal influenza, pregnancy, but ages 20-60 and obese for H1N1 – Primary influenza pneumonia/ARDS, also bacterial superinfection
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Influenza incidence by month in North America
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Influenza
• Spread from person to person primarily through respiratory droplet transmission
• Incubation period is 1 — 4 days
• Contagious -1 to 7 days from symptom onset
http://www.cdc.gov/flu/professionals/acip/clinical.htm
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Influenza Vaccination
• Everyone over 6 months of age
• Vaccine efficacy varies between years, but “herd” immunity effect at least as important as individual efficacy
• Higher dose formulation for patients over age 65 – more immunogenic, small increase in local side effects
• Recombinant influenza vaccine available for patients with severe egg allergy
• Adjuvant flu vaccine, and a cell culture-based inactivated influenza vaccine are available, but not preferred by Advisory Committee on Immunization Practices/CDC
http://www.cdc.gov/flu/professionals/acip/clinical.htm
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Not “just” the flu!
• Influenza-associated deaths are 3,300 to 49,000 annually
• Case fatality rate from H1N1 with respiratory failure 30%
• Oseltamavir 75 mg bid for 5 days shortens duration of symptoms and decreases secondary complications
• Rx first 1-2 days of symptoms, and if still febrile or hospitalized
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Take home message
• Our patients need more oseltamavir, and many fewer Z-Paks!
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Acute exacerbation of chronic bronchitis
• In a patient previously diagnosed with COPD: –Cough increases in frequency and severity –Sputum production increases in volume and/or
changes character –Dyspnea increases
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Acute exacerbation of chronic bronchitis
• 70% are infectious in cause, either viral or bacterial
• 30% air pollution, change in medications, pulmonary embolism, cardiac disease, other
• Single best predictor is prior history of exacerbations
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Acute exacerbation of chronic bronchitis Treatment
• Exclude specific, treatable causes such as pneumothorax,
heart failure
• Begin or increase albuterol/ipratropium
• Corticosteroids
– 40 mg PO for 5 days
• Antibiotics for inpatients, but for outpatients only with moderate to severe exacerbations and sputum purulence
– Doxycycline, Amox-Clav, Fluoroquinolone
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Intermountain Pneumonia Care Process Model
• Dates back to 1995, updated for 2016
• Intended for immunocompetent patients ≥ 18 years, excluding….
– solid organ, bone marrow or stem cell transplant recipients
– patients receiving cancer chemotherapy or chronic (> 30 days) “high dose” corticosteroids
– patients with congenital or acquired immunodeficiency or HIV infected with CD4 count < 350/mm3
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Why Pneumonia Care Process Model?
• 7th leading cause of death in the Unites States
• $10 billion per year in treatment costs
• Evidence that well designed and implemented local treatment guidelines decrease mortality and improve other clinical outcomes
https://www.cdc.gov/pneumonia/ 2007 ATS/IDSA Clin Infect Dis 44:Suppl 2, S27
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Diagnosis/Definition
• “In addition to a constellation of suggestive clinical features, the diagnosis of pneumonia requires a demonstrable infiltrate by chest radiograph or CT, with or without supporting microbiological data”
• 2014 Utah Instacare data: 40% of patients diagnosed and treated for pneumonia did not have chest radiography.
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Constellation of suggestive clinical features
Metlay Arch Intern Med 1997;157:1453–1459.
0
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30
40
50
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80
90
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1 8 -4 46 5 -7 4³7 5
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Under-diagnosis of Pneumonia
• Atypical presentations - chest pain, abdominal pain, confusion, without prominent cough or sputum production
• In patients with suggestive symptoms, abnormal vital signs and/or abnormal chest exam predict pneumonia and indicate need for CXR
Heckerling Ann Intern Med 1990 113:664 Bushyhead Med Care 1983; 21:661-673
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Benefits of a Chest X-ray
• May obtain information on etiology, prognosis, or alternative diagnosis1
• May indicate the presence of complications, such as pleural effusion, multilobar disease2
• Absence of infiltrates rules out CAP in most cases. Acute bronchitis is not an indication for antibiotics3
1. Mandell LA et al. Clin Infect Dis. 2000;31:383–421. 2. American Thoracic Society. Am J Resp Crit Care Med. 2001;163:1730–1754. 3. Gonzales R. A 65 yo woman with acute cough illness and an important engagement JAMA 2003 289:2701-8..
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Community-acquired Pneumonia Accuracy of Clinical Diagnosis
• 236 cases of pneumonia diagnosed and treated by general practitioners without chest radiographs
• All patients had chest radiographs after discharge home or hospital admission
• 93/236 (38%) had initial radiographic infiltrate
Woodhead Lancet 1987 1: 671-674
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Does chest radiograph negative pneumonia exist?
• Subsequent radiograph occasionally shows an infiltrate not seen initially
• Only 2 additional patients (1%) in Woodhead study had radiographic infiltrate at 7-10 days not seen initially
• ? Role of dehydration – 1 case report – Increased BUN and 1 liter greater fluid intake 24
hours retrospectively associated with radiographic worsening
Hash J Fam Pract 2000; 49:833
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Over-diagnosis of Pneumonia • Pneumonia a clinical syndrome….
• Pulmonary emboli, interstitial lung disease, heart failure, atelectasis, lung cancer, TB have overlapping signs and symptoms
• Patients who fail to respond to antibiotics within 3 to 5 days should be re-evaluated
• Patients with recurrent “pneumonia” should be evaluated for alternative diagnoses, e.g. chronic aspiration, hypersensitivity pneumonitis
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To Admit or Not to Admit? An important question…
• Costs are 20 times higher in hospitalized patients1
• Less ill patients return to work and usual activities faster if treated at home2
• Patients hospitalized after initial outpatient treatment have higher mortality3
• Severely ill patients not initially admitted to ICU have higher mortality4
1) Niederman Clinical Therapeutics 20:820-837, 1998 2) Labarere Chest 131:480 2007 3) Minogue Ann Emerg Med 31:376 1998 4) Neill Thorax 51:1010 1996
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% Pneumonia patients admitted to hospital by individual emergency physicians over 11 years
Dean Ann of Emerg Med 2012 59:35
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Lim Thorax 2003; 58:377–382.
CURB-65
• Scoring 0-1 Home treatment OK
2 Ward admission or observation
3+ Hospital admission ?Assess for ICU
• Score 1 point each for: – Confusion – BUN > 20 – Respiratory rate ≥ 30/min – BP (systolic BP ≤ 90 mmHg or diastolic BP ≤ 60 mmHg) – Age ≥ 65 years
1.5
9.2
22
0
5
10
15
20
25
0-1 2 3+
Mortality, %
CURB-65 SCORE
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Additional Severity Assessment
• Sp02 < 90 %
• Pleural effusion → >1 cm on decubitus CXR, > 5 cm on lateral CXR, visible on AP upright
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Algorithm for Outpatient Pneumonia: Diagnosis and Triage
No infiltrateLook for alternative diagnosis
Evaluate for admissionusing prediction rule
Diagnostic tests optional
Outpatient
Diagnostic tests for patientswith specific conditions
Hospitalize
Infiltrate and clinicalsigns & symptoms
History, physical, chest x-ray
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Outpatient Antibiotic Therapy No antibiotic last 3 months, no comorbidities
• Doxycycline 100 mg bid for 7 days – Sun sensitivity, Epigastric pain/Nausea, Category D pregnancy
• Ceftriaxone 1 gm IV/IM and/or amoxicillin 1000 mg tid plus oral azithromycin 500 mg daily for 3 days
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Outpatient Antibiotic Therapy COPD, CHF, diabetes, malignancy, or renal failure
OR antimicrobial use within last 3 months
• Ceftriaxone 1 gm IV qd or Amoxicillin 1000 mg tid – plus oral azithromycin or doxycycline
• Fluoroquinolone (oral unless nauseated/NPO) moxifloxacin 400 mg qd for 7 days or levofloxacin 750 mg for 5 days
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Timing of First Antibiotic Dose
• “For patients admitted through the emergency room, the first antibiotic dose should be administered while still in the emergency department”
– OR for mortality 0.83 (p = 0.01) when antibiotics administered within 4 hours of hospitalization1
Houck Arch Intern Med 2004; 164:637
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Empiric non-ICU Inpatient Therapy
• Ceftriaxone 1 gm IV qd plus azithromycin or oral doxycycline – Change to amoxicillin 1000 mg when clinically stable to
complete 7 days
–Levofloxacin 750 mg for 5 days
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Empiric ICU Therapy
• Ceftriaxone 1 gm IV q 12 plus intravenous azithromycin (levofloxacin 750 mg if macrolide allergic)
• For patients with history of hives/anaphylaxis to penicillins or cephalosporins: – intravenous clindamycin or carbapenem plus
levofloxacin 750 mg
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5-year Trends in Initial Antibiotic Use for Hospitalized Pneumonia Patients, 2006-2010 (N=95,511)
39%
36% 36% 36% 36% 34% 33%
29%
33% 34% 34%
32%
16%
20% 24%
28%
31%
16% 19%
21%
24%
27%
4.1% 4.5% 4.9% 5.0% 5.3%
0.5% 0.6% 0.7% 0.9% 0.7% 0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
2006 2007 2008 2009 2010
Azithromycin %Ceftriaxone %Resp Fluoroquinolones %Vancomycin %Pip/Tazo %Cefepime %Linezolid %
Jones BE Clin Infect Dis 2015 61(9):1403
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Concept of HealthCare Associated Pneumonia (HCAP)
is (mostly) dead • Intended to identify patients with community-
acquired pneumonia at increased risk for pathogens resistant to ceftriaxone or Ampicillin -sulbactam plus macrolide empiric antibiotics
• 2005 IDSA/ATS pneumonia guideline definition: – Hospitalization for more than 2 days within 3 months – Nursing home residents – Chronic dialysis, wound care, IV center
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HCAP is (mostly) dead • Outcomes in patients with HCAP worse when
treated with HCAP guideline–concordant regimes compared to CAP therapy – OR for mortality 2.18, 95% CI 1.86-2.551
– Survival to 28 days 65% in the compliance group and 79% in the non-compliance group (p=0.004)2
1) Attridge Eur Respir J 2011, 38:878
2) Kett Lancet Infect Dis 2011 11(3):181
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Odds ratios for mortality associated with implementation of ePneumonia
Dean Annals Emerg Med 2015 66:511
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Why did following HCAP guidelines not improve outcomes?
• HCAP patients are a sorry lot at high risk for mortality from multiple causes
• The HCAP criteria have poor positive and negative predictive value for the presence of resistant pathogens
• Overly broad antibiotic therapy without macrolides may worsen outcome in patients without resistant pathogens
• ?More C-diff colitis, more renal toxicity, no immune-modulating benefit from macrolide combination therapy?
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HCAP
Ignores important epidemiologic risk factors for resistant pathogens
–Prior antibiotic exposure –Co-morbid illness – chronic respiratory
disease, heart failure, diabetes –Prior culture results –Use of proton pump inhibitors –Functional status (ambulatory or not) –Need for enteral feeding
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Drug Resistance in Pneumonia Score
Points
Antibiotic use < 60 days 2 Long term care 2 Tube feeding 2 Prior drug resistant community-acquired pneumonia 2 Hospitalization < 60 days 1 Chronic pulmonary disease 1 Poor functional status 1 Gastric acid suppression 1 Wound care 1 MRSA colonization (1 year) 1
Webb BJ, Antimicrobial Agents and Chemotherapy 2016 22;60(5):2652
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Recommended empiric antibiotics for patients with DRIP score 4 or greater
• Vancomycin 25 mg/kg IV • Cefepime or Piperacillin-Tazo • Azithromycin 500 mg IV
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DRIP score 4 or greater and all ICU admitted community-acquired pneumonia patients
• Blood, sputum, tracheal aspirate, pleural fluid cultures
• Urinary antigens for pneumococcus and legionella
• Nasal swab for MRSA
• Change from Vancomycin and Cefepime to Ceftriaxone within 48 hours for patients without a resistant organism identified
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DRIP implementation study
Salt Lake Valley Hospitals 11/2014 to 10/2015
B Webb, European Respiratory Society London 2016
DRIP versus Usual Care DRIP, % Usual Care, % p value
Inadequate Spectrum
0.67 0.93 NS
Overtreatment 20.6 27.8 0.008
Appropriate Spectrum
78.6 71.0 0.005
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DRIP implementation study
Salt Lake Valley Emergency Departments – 11 months
• Odds of in-hospital mortality
– ePneumonia with DRIP (odds ratio 0.64; upper 95% confidence interval 1.04; p = 0.06)
• Decreased length of hospital stay
– ePneumonia with DRIP (coeff – 0.147; upper 95% CI – 0.137; p < 0.001).
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Prevention • Smoking cessation – current smoking doubles the risk of
pneumococcal and legionella pneumonia
• Consider dysphagia, esophageal dysmotility, structural parenchymal/airway disease in patients with recurrent pneumonia
• PCV 13 (Prevnar) for persons ≥ 65 years and for those with selected high-risk concurrent diseases - current ACIP guidelines
• Pneumococcal polysaccharide vaccine (Pneumovax) recommended 1-2 years after PCV 13
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(Asthma, CHF, Sinusitis, TB)
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Summary • Accurate diagnosis of respiratory tract infections • Fewer Zpaks, more oseltamavir, amoxicillin,
doxycycline • Objective severity measures to determine site of
care • Antibiotics given at the site of diagnosis, directed
at common pathogens • Decision support to reliably deliver care elements
is linked with better clinical outcomes