Respiratory Infections

1
Respiratory Infections

• David R. Park, M.D.
• HuBio 541
• The Respiratory System

2
Respiratory Infections

• Acute Bronchitis
• Acute Exacerbations of Chronic Bronchitis
• Pneumonia
• Tuberculosis
• Nontuberculous Mycobacterial Disease

3
Importance of Respiratory Tract Infections

• Respiratory symptoms are the most common symptom
  prompting ambulatory visits
• Overall 88,827,000 visits
• 10.7 of all visits
• Antibiotic resistance rates are rising
• Respiratory tract infections are a leading cause
  of death
• Death rates from respiratory infection are
  increasing

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Continuum of Severity of Lower Respiratory Tract
Infection
Macfarlane. Semin Respir Infec 1999 14151
5
Case 1

• A 32 yo woman presents to clinic on a Friday
  afternoon with a 4 day history of an incessant
  nonproductive cough, fatigue, and intermittent
  mild subjective fevers. She has been unable to
  sleep for 2 nights and her chest aches due to the
  coughing.
• She is previously healthy, doesnt smoke, and
  traveled to New York the weekend before for a
  friends wedding. Many people were coughing on
  the plane.

6
Case 1 continued

• As you begin to examine her, she states I need
  an antibiotic for this cough. I am taking my Bar
  exam on Tuesday and I am a complete wreck. I
  cant afford to fail.
• Examination reveals normal VS and SpO2, a tired
  but not terribly ill young woman having
  occasional paroxysms of coughing, faint scattered
  expiratory wheezes but good air movement, and no
  rales or other focal chest findings.
• CXR is clear.

7
Case 1 continued

• You proudly inform her that she has Acute
  Bronchitis and that she doesnt need an
  antibiotic because it is usually caused by a
  virus.
• She looks back at you incredulously, pays her
  bill, then heads straight to a nearby walk-in
  clinic to see if she will have better luck with
  another provider.

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Acute BronchitisDefinition

• Acute cough (lt3 weeks) in a patient without
  chronic bronchitis or other explanation
• Sputum production
• Wheezing or dyspnea
• Airflow obstruction

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Causes of Acute Bronchitis

• Respiratory viruses
• (Including influenza, SARS, etc.)
• Atypical bacterial respiratory pathogens
• (Mycoplasma and Chlamydia pneumoniae)
• Typical bacterial respiratory pathogens
• (Streptococcus pneumoniae, Haemophilus
  influenzae, Moraxella catarrhalis)
• Bordetella pertussis (especially after
  known contact)

Macfarlane et al. Thorax 2001 56109-14 Macfarlan
e et al. Lancet 1993 341511-14
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Acute BronchitisDiagnosis

• History of acute unexplained cough
• Wheezing or airflow obstruction may be present
• No role for routine laboratory testing
• Top priority is to exclude pneumonia
• (CXR if pneumonia is suspected)

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Symptomsin Acute Bronchitis

• Prospective cohort study
• Acute respiratory illness presenting to Primary
  Care
• Acute Bronchitis 16 (n 1,525)
• Antibiotic for 85

Gonzales et al. JGIM 1998 13541-8
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Findings in Acute Bronchitis
Gonzales et al. JGIM 1998 13541-8
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Acute BronchitisNatural History

• Expect major interference with well-being, sleep,
  daily activities
• Resolution
• Protracted (gradual but steady)
• Return to daily activities before full symptom
  resolution
• Cough may persist for weeks

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Resolution of Acute Bronchitis
Holmes et al. AJRCCM 1998 157A168 Symptom
Diary, n 400
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Challenges of Acute Bronchitis Management

• Diagnostic uncertainty
• Continuum of severity
• Pressure to prescribe antibiotics
• the Antibiotic Expectation
• Need to limit inappropriate use of antibiotics
• Desire to avoid complications
• Imperative to relieve symptoms

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Evidence about Antibiotic Treatment of Acute
Bronchitis

• 8 Placebo-controlled RCTs
• Variable study design and quality
• Flawed by small numbers, non-consecutive
  patients, incomplete follow-up, irrelevant
  outcomes, invalid statistical methods
• 3 Meta-analyses
• No beneficial effect on duration of cough or
  illness, limitation of activities, or lost time
  from work
• Side effect symptoms considerably worse
• Suggestion of benefit in subgroups
• Cochrane review

Fahey et al. BMJ 1998316908 Smucny et al. J Fam
Pract 199847453 Bent et al. Am J Med 199910762
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Resolution of Acute Bronchitis
Williamson et al. J Fam Pract 198419481
18
Problems Associated with Inappropriate
Antibiotic Use

• Antimicrobial resistance
• Costs and adverse effects
• Medicalization of self-limited problems
• Prescriptions for colds and bronchitis encourage
  reconsultation for subsequent episodes
• Reassurance, explanation, and advice about self
  care options encourage future independent
  management

Macfarlane et al. BMJ 1997 3151206 Little et
al. BMJ 1997 315350-2
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Acute Bronchitis Management

• Consider antibiotic if
• Older age
• Underlying disease
• Purulent sputum with longer duration
• or, if it really looks like pneumonia
• May give prescription to fill if not improving
  in several days
• Macfarlane et al. BMJ 20023241

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Acute Bronchitis Management

• Reassurance and explanation
• AB is a self-limited infection
• Cough is a defense mechanism
• Antibiotics just dont help, cause side effects,
  contribute to resistance, and are costly
• There are treatments that will help you feel
  better

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The Cough Box

• Information/Instruction Sheet
• Rest
• Plenty of Fluids
• Steam/Vapor
• Use of Symptomatic Treatments
• Analgesic supply
• Cough syrup supply
• ? Decongestant/antihistamine supply
• ? b-agonist bronchodilator MDI?

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Back to Case 1

• Provided diagnosis, thorough explanation, and
  reassurance
• Self-managed with fluids, acetaminophen,
  mentholatum chest rub, and steam inhalation
  before bedtime
• Given cough syrup with codeine to last one week,
  plus albuterol MDI with instructions
• Slept better, slowly improved, passed Bar
• Hasnt come back to clinic with acute bronchitis
  since (3 yrs)

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Pneumonia
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What is Pneumonia?

• Inflammation and consolidation of the lung
  parenchyma
• Due to infection and associated host inflammatory
  response

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The Changing Face of Pneumonia
Aging Population
Alcohol, Tobacco, and Drug Abuse?
New Pathogens
Chronic Diseases
New Guidelines
Salvage of Severe Illness
New Investigations
Pneumonia
Intensive Care
Foreign Travel
Immunosuppressive Drugs
New Antibiotics
Antimicrobial Drug Resistance
AIDS
Socioeconomic Hardships?
Vaccination?
Macfarlane. Semin Respir Infect 1994 9153-165
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Pneumonia Terminology

• Community-Acquired Pneumonia (CAP)
• Immunocompetent adults
• Severe CAP subgroup (ICU)
• Healthcare-Associated Pneumonia (HCAP)
• Hospital-Acquired Pneumonia (HAP)
• Ventilator-associated pneumonia (VAP)
• Opportunistic Pneumonia
• HIV
• Other

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Current Pneumonia Epidemiology

• Community-acquired
• 2-4 million cases per year, gt500,000 require
  hospitalization (20), mortality lt2-50, 10
  million physician contacts, 10-20 billion
  expenditures
• Nosocomial (HAP/HCAP)
• Complicates 0.5-5 of all admissions, 12-60 of
  ICU admissions, associated with 15 of hospital
  deaths, mortality 5-70, prolongs hospital stay
  7-9 days
• 6th leading cause of death in the USA

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Top Age-Adjusted Causes of Death
National Vital Statistics Report
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Trends in Causes of Death in USA
National Vital Statistics Report
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Community-Acquired Pneumonia

• Case Definition
• Acute illness
• Appropriate clinical features (usually 2 or more
  of fever, cough, chest pain, sputum production,
  dyspnea, rigors, sweats, confusion, abnormal
  chest exam findings, or leukocytosis)
• New radiographic infiltrate

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Causes of Pneumonia

• Respiratory viruses
• (Including influenza, SARS, etc.)
• Atypical bacterial respiratory pathogens
• (Mycoplasma and Chlamydia pneumoniae)
• Typical bacterial respiratory pathogens
• (Streptococcus pneumoniae, Haemophilus
  influenzae, Moraxella catarrhalis)
• Resistant organisms (especially HAP/HCAP)
  (Enteric GNRs, Resistant GNRs, MRSA)

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Pneumonia ( Influenza) Mortality
Mortality per 100,000 Population
Others
Sulfa
Penicillin
Reimann. AIM 1962 56144
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Prototypical Defects in Pulmonary Host Defenses
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Pneumonia Diagnosis

• History and physical examination
• Chest radiograph
• Basic laboratory evaluation
• CBC, renal function, other as indicated
• Specific diagnostic testing
• Sputum Gram stain and culture
• Blood culture
• Special tests (antigen detection, amplification
  tests, serology, etc.)

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Pneumonia TreatmentExpert Guidelines (ATS, IDSA,
others)

• CAP
• Outpatient (oral macrolide or doxycycline)
• Inpatient or comorbidities (fluoroquinolone or
  b-lactam and macrolide combination )
• Severe (b-lactam and macrolide, consider others)
• HAP/HCAP/VAP
• Early (similar to CAP)
• Late or prior antibiotic (cover
  multidrug-resistant pathogens such as resistant
  GNRs and MRSA)

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Pneumonia Case Studies
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Case 2

• 37 year old woman
• 3d malaise, fever, cough
• s/p meningioma rsxn
• T38.3, P100, R24, BP130/70
• poor dentition
• decreased BS right upper chest
• WBC 12K

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Case 2 -- continued
Gram stain of sputum smear
Sputum Sample
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Case 2 -- continued

• Mixed aerobic/anaerobic aspiration pneumonia
• Due to aspiration of oropharyngeal secretions
  during generalized seizure
• During post-operative period following meningioma
  resection

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Case 4

• 43 year old man
• 2 days fever, chills, cough, and chest pain
• s/p failed cadaveric renal transplantation on
  prednisone/immuran
• T39, P140, R32, BP150/70
• Dyspneic, confused, consolidation of R chest
• WBC 22K, BUN/Cr 80/4.4, Glucose 68, CPK 541

41
Case 4 -- continued
Sputum Gram stain purulent without organisms
42
Case 4 -- continued

• Legionella pneumonia (Legionnaires disease)
• Due to depressed cell-mediated immunity caused by
  combination immunosuppressive therapy and renal
  failure

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Case 5

• 48 year old man with T6 paraplegia due to GSW
• 10 days ago myalgias, dry cough, sore throat
• 2 days fever, chills, phlegm, and chest pain
• T38.8, P130, R30, BP110/60
• Tachypneic, confused with rattling cough
• WBC 20K

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Case 5 -- continued
Sputum Gram stain
45
Case 5 -- continued

• Pneumococcal pneumonia
• Resulting from poor cough effectiveness (due to
  paraplegia) plus altered mucociliary escalator
  function (due to recent influenza virus infection)

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Tuberculosis
47
TuberculosisGlobal Health Importance

• TB is the single leading infectious killer
  worldwide
• Half the worlds population harbors latent TB
  infection (3,000,000,000)
• 15 million new cases of active TB occur each year
• 3 million deaths are attributable to TB each
  year--mostly in young men, women, and children

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Transmission and Pathogenesis of Tuberculosis
Maintained -- TB Remains Dormant
No Infection
Adequacy of Innate Defenses
Exposure
Contained -- Latent Infection
Maintenance of Acquired Defenses
Primary Infection (Silent Dissemination)
Development of Acquired Defenses
Not Maintained -- Late Reactivation
Not Contained -- Progressive Primary Disease
Transmission
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Tuberculosis Infectiousness in Different
Settings

• Setting
• TB Wards (chronic)
• TB Ward (newly treated)
• Cavitary TB Contacts
• Laryngeal TB
• Bronchoscopy
• Autopsy (with bone saw)

• Dissemination Rate
• (Infectious quanta/hour)
• 0.6
• 1.3
• 13
• 60
• 250
• 5000

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Tuberculosis Diagnosis

• Clinical suspicion is key
• Sputum examination (AFB smear)
• Helpful if positive
• Positive in only half of TB patients
• Sputum AFB culture
• Gold standard for pulmonary TB diagnosis
• Takes 3-6 weeks to grow
• Amplification tests (role being defined)

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Standard TB Treatment Regimen

• Initiation phase - 4 drugs
• isoniazid (INH)
• rifampin (RIF)
• pyrazinamide (PZA)
• ethambutol (EMB) or streptomycin (SM)
• Stop EMB based on susceptibility results but
  always use PZA with INH/RIF for initial 2 months
• Continuation phase use INH/RIF for 4-7 additional
  months (6-9 months total)

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Institutional TB Infection Control the Industrial
Hygiene Paradigm

• Administrative controls
• Surveillance and triage protocols
• Early identification of possible cases
• Strict isolation policies
• Environmental controls
• Negative pressure isolation rooms
• Enhanced air disinfection
• ventilation
• air filtration (HEPA filters)
• UV germicidal irradiation (UVGI)
• Personal protective devices

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Case 6

• 56 year old homeless native Alaskan woman
• 5 weeks fever, malaise, weight loss, productive
  cough, and chest pain
• T37.8, P100, R28, BP105/65
• Emaciated with ronchorous breath sounds
• WBC 12K, Na 130

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Case 6 -- continued
CT Scan shows cavitary and nodular disease
Sputum Smear AFB Positive
55
Case 6 -- continued

• Reactivation Tuberculosis with cavitary, smear
  positive disease (highly contagious).
• Needs respiratory isolation in addition to
  medical therapy for TB.