Pulmonary Infections

​Microbiology

• Community Acquired Pneumonia Organisms 
  • Streptococcus pneumoniae
      (often bactermic pneumonia)
  • Haemophilus influenzae
  • Moraxella catarrhalis
  • Klebsiella pneumoniae (less common)
    • (alcoholism)
    • HIGHLY resistance strains possible
• So-called "Atypical" Organisms
  • Mycoplasma
  • Chlamydophila (prev Chlamydia)
    • Intracellular anaerobe
    • Both Mycoplasma and Clamydophila termed "walking pneumonia" generally in outpatients (mild).
  • Legionella
    • In pts with severe CAP, history of travel.
    • More common in summer, often in epidemics when common-source reservoir aerosolizes bacteria (i.e. water systems, air conditioning units, such as at a hotel or cruise ship)
    • Ass'd with hyponatremia, AST/ALT elevation, GI symptoms, bradycardia.
    • Has urinary antigen test (only picks up Legionella pneumophila type 1)
      • Helpful if positive, but negative test doesn't exclude dx.
• Other pathogens: (rare)
  • Staph aureus
    • Less common cause of CAP.
    • Risk Factors: classically following influenza, cavitary pneumonia, no risk factors for aspiration, IVDU, recent history of CA-MRSA skin infection.
    • High mortality rate, cause prolongued hospitalization.
    • often ventilator associated pn.
  • Gram negatives (enteric)
    • uncommon, unless lung disease or alcoholism. (reduced gag reflex). Usually hospitals and nursing homes.
  • Pseudomonas
    • Often underlying structural lung disease
      • Risk Factors: Bronchiectasis, Cystic Fibrosis, frequent COPD Exacerbations, long term steroid therapy.
    •  
  • Anaerobes
    • Often aspiration pneumonias.
  • Viral
    • influenza, parainfluenza, respiratory syncitial virus (RSV), adenovirus (adenovirus Type 14 - severe)
• Nosocomial Infections:
  • Gram negatives (>50%)
  • Staph aureus (13-40%) (wound infections, burns, intubated, head trauma)
  • Anaerobes (5%)
        
    Risk Factors: (Intubation, >70yrs, reduced  LOC, malnutrition, metabolic acidosis)
• Aspiration Infections:
  •      (aware of pulmonary burn aspiration of gastric contents, obstructing objects)
  •       (foul-smelling spututm, lung abscesses and empyema)
  •       (OFTEN MIXED ORGANISMS)
  • Mixed Gram negative enteric aerobic rods
  • Anaerobes
  • Staph aureus
  • Rare
    • Actinomycosis (poor oral hygeine, anaerobic)
    • Nocardiosis (inhalation of soil particles)

Symptoms

• Acute Cough - purulent sputum.
  • (S. pneumon is rusty colored, red current jelly color is Klebsiella etc..)
• Fever, chills, pleuritic chest pain, dyspnea
• Rigor - classically one teeth-chattering chill is Strep. pneumo.
• Shortness of breath
• Elderly
  • Often non-specific presentation, present with confusion, exacerbation of chronic cardiopulmonary disease.
  • Tachypnea is the most sensitive finding in edlerly.
• Rule out risk factors for HAP (Healthcare Associated Pneumonia)
  • Antibiotic therapy or hospitalization in preceeding 90 days.
• Epidemiologic history for unusual pathogens.

Unusual Pathogens

• Aspiration - Gram negative enteric pathogens, organ anaerobes.
• Cough >2w with post-tussive vomiting: Bordetella pertussus.
• Cavitary infiltrates -  Community MRSA, oral anaerobes, fungal pathogens, TB
• Alcoholism - Klebsiella, Staph aureus, oral anaerobes.
• COPD/Smoking - Gram Negatives, Haemophilus, Pseudomonas, Legionella, S. aureus, Moraxella, clamodophila.
• Bat/Bird Droppings Exposure - Histoplasma capsillatum (if right geographic locale)
• Bird Expsoure - Clamydophila psittaci
• Rabbits - Tularemia
• Farm Animal / Pregnant Cats - Coxiella burnetii (Q-fever)
• Rodents Excreta - Hantavirus (recent)
• HIV Infection - Common organisms + PJP, cryptococcus, histoplasma, aspergillosis, pseudomonas, mycobacterium.
• Hotel/Cruise Ship - Legionella
• SW United States - Coccidioidomycosis species or Hantavirus. (California, desert)
• SE or E Africa - Burkholdaria pseudomallei
• Influenza - Primary influenza, secondary bacterial pneumonia (S. pneumo, S. aureus, H.influ).
• IVDU - S. aureus, TB, pneumococcus.
• Endobronchial obstruction - anaerobes, pneumococcus, H.influenzae.
• Bronchiectasis, Cystic Fibrosis - Pseudomonas or Burkholdaria cepacia
• Bioterrorism - Anthrax, Plague, Tularemia.

Classification

• Classified as:
  • Typical Pneumonia
    • Rapid onset, severe symptoms, productive cough, dense CXR consolidation.
  • Atypical Pneumonia
    • Slower onset, less severe symptoms, less severe cough, minimal sputum, CXR (patchy/interstitial pattern)
  • Community Acquired (<14d in hospital)
  • Hospital Acquired (>14d)
• Can sometimes narrow down to organism by symptoms and radiologic findings.
• 

• Chest Xray findings:
  • 1. Lobar Pneumonia
    • Distinct anatomic segment of the lung.  Respects anatomic boundaries (no proteases/hyaloronidases to break down tissue).
    • S. pneumoniae, H. influenzae, Legionella
      • 
  • 2. Bronchopneumonia
    • Originates in small ariways and spreads to adjacent ones.  "Patchy infiltrates" that involve multiple areas of the lung and extend down bronchi. 
    • S.aureus, Gram negatives, Mycoplasma, Chlamydia, viruses
      • 
  • 3. Intersitial pneumonia
    • Lung interstitium inflamed: fine diffuse grandular infiltrate.
    • Influenza, CMV, Pneumocystis jirovecii, Miliary TB (micronodular infiltrates).
      • (Can look like CHF)
      • 
  • 4. Lung abscess
    • Tissue necrosis, cavities with inflammatory fluid
    • Do CT
    • Anaerobics and S.aureus.
  • 5. Nodular Lesions
    • Yeasts: (cryptococcus) Moulds (Histoplasmosis, coccidiomycosis) - nodular
    • Do CT
    • "Cannonball lesions" from hematogenous spread of endocarditis.

Investigations

• Diagnosis:
  • Clinical findings are often not sufficient to diagnose pneumonia
  • CXR is mandatory, but initial normal CXR does not exclude if has focal resp physical exam findings + symptoms.
    • Repeat CXR in 24-48hrs may show airspace disease.
• Workup:
  • CBC + differential, O2 sat, arterial gasses (pH <7.35 = bad, or O2 < 60mmHg = bad)
  • BUN > 10.7 mmol/L (kidney hypoperfusion or dehydration)
  • Serum Na < 130 (increased ADH from depleted volume).
  • Glucose > 13.9 (bad prognostic factor)
  • Consider: Blood cultures, sputum gram stain + culture, pneumococcal + legionella urine antigen testing (all required for ICU)
  • Blood cultures x2
    • Draw before first dose of abx, esp in ICU, on hospitalized pts it's unclear.  I.e. is a quality medicare indicator in all hospitalized admissions, but most guidelines for ICU only.
    • Positive in 5-14% of hospitalized CAP pts. --> obtain before abx (quality care indicator for medicare)
    • Initially studies indicated lack of benefit of cultures in non-severe CAP, but now optional. 
    • See table on UpToDate (recreated below)
  • Sputum Gram Stain and Culture
    • Controversial:  Guidelines by Infections Disease Society of America and American Thoracic Society:
      • Optional for outpatients.
      • In hospitalized pts (not in ICU) recommended for:  (optional in the rest)
        • Outpatient therapy ineffective
        • Cavitary infiltrates
        • Alcoholism
        • Chronic Liver Disease
        • Functional or Anatomic Asplenia
        • Severe Obstructive or Structural Lung Disease
        • Leukopenia
    • Lots of pharynx contamination (need to cough deeply to bring up sputum).. may represent colonization. (Check for squamous cells (>10 is poor sample) and PMNs + bronchial epithelial cells (good sample))
    • Sputum for : Gram stain, cultures, sensitivity, PCR
    • PMNs  --> bacterial, Mononuclear cells --> Mycoplasma, Chlamydia, viral
    • Difficult to culture Legionella, mycoplasma, chlamydia, Pneumocystis jirovecii, likely need PCR
      • Can also do urinary antigens.
  • Bronchoalveolar lavage - useful for PJP
  • Legionella urine antigen Indicated for recent travel pts, but often done by specialists on high risk patients.
    • (only picks up Legionella pneumophila type 1).  70-90% Sn, 99% Sp.
  • Pneumococcal urine atigen: 70% Sn, 96% SP, rapid test.
  • NOTE: Severe CAP requiring ICU admission should have blood cultures, Legionella, and pneumococcus urinary antigens, and sputum culture (expectorated or endotrachial aspirate).

  • Indication	Blood Culture	Sputum Culture	Legionella UAT	Pneumococcal UAT	Other
    ICU Admission	X	X	X	X	- Endotracheal Aspirate or Bronch or BAL
    Failure of Outpt Abx Therapy		X	X	X
    Cavitary Infiltrates	X	X			- Fungal + TB cultures
    Leukipenia	X			X
    Alcohol Abuse	X	X	X	X
    Chronic Severe Liver Disease	X			X
    Severe Obstructive/Structural Lung Disease		X
    Asplenia (anatomic or functional)	X			X
    Recent Travel (within past 2 weeks)			X		- Complex (see "Unusual Pathogens")
    Positive Legionella UAT Result		X	---
    Positive Pneumococcal UAT Result	X	X		---
    Pleural Effusion	X	X	X	X	- Thoracentesis and pleural fluid cultures

Management

• Admit or Not Admit

  • Outpatient management is preferrable, several scoring systems help guide hospitalization need.
  • CURB65 is very common (because it's easy compared to PSI)

    • CURB65 Score: Confusion Blood Urea Nitrogen  >20 mg/dL (7.14 mmol/L) Respiratory Rate  ≥ 30 bpm Blood Pressure sBP < 90 or dBP < 60 Age ≥ 65   NEW: CRB65 Score - Can drop Urea

      -  0 or 1 --> Outpatient                    Treatment (Low Mort) -  ≥ 2 --> Hospitalization -  ≥ 3 --> Consider ICU

    • 

  • Pneumonia Severity Index (PSI) Complicated calcuation (20 different variables), use online calculator. Assigns to 5 mortality risk groups (I - V) Groups 1-2 => Outpatient Management (Low Mortality Risk Groups) Group 3 => Brief hospitalization for observation Groups 4-5 => Require hospitalization

  • PORT score is also around, but not as common.
  • CURB65 and PSI scoring systems most popular.
    • Studies show that both are effective for predicting mortality.
    • Negative predictive value is greater than positive. 
    • Also predict the time to clinical stability. 
  • However, they are part of the decision.  Pts with poor social supports and underlying chronic disease etc.. require admission that aren't in scoring systems.
  • CAP considered severe if requires early ICU care.
  • Patients admitted to ICU have lower mortality than those transferred to the ICU.  Hence early ICU admission reduces mortality for severe CAP.
    • 50% of ICU deaths due to CAP occurs in patients who were initially admitted to the medical ward

• Admission to ICU decision criteria:

  • Proposed to the Infectious Diseases Society of America (IDSA) and American Thoracic Society proposed guidelines for ICU admission (major + minor criteria)

  • Major Criteria	Minor Criteria
    Need for mechanical vent and vasopressor support	Clinical Confusion (new-onset disorientation to person, place, or time) Hypothermia (core temperature <36.0 °C [96.8 °F]) Respiration rate ≥30/min Hypotension necessitating aggressive fluid resuscitation Multilobar pulmonary infiltrates Laboratory Arterial PO2/FIO2 ratio ≤250 or requiring NIPP Leukopenia (<4000 cells/µL [4.0 × 109/L]) Thrombocytopenia (<100,000 /µL [10 × 109/L]) Blood urea nitrogen >20 mg/dL (7.1 mmol/L)
    Major Criteria => Admit to ICU ≥ 3 Mintor Criteria => Admit to ICU This has not undergone extensive validation, but recent investigation has shown that the negative predictive value of the severe CAP minor criteria is greater than 90%.

Complications

• If not improvement consider:
  • BOOP
  • Vasulitis
  • PE
  • Resistant Pathogen
  • Parapnemonic effusion or empyema (esp if initially improve then relapse).
    • 1/3 develop effusion.
    • Thoracentesis if ≥50% of hemithorax (large pleural effusion) or fail to respond clinically.
      • (If stable, improving, but small-to-moderate effusion, can just observe)
• Follow-up
  • Chest imaging not indicated in most patients.
  • F/U CXR - consider to document clearance and r/o malignancy (9.2% had pulmonary malignancy)
    • 6-8 weeks for smokers, and >40yo. 
  • Counsel smokers
  • F/U office visit 10-14 days post-therapy.

Empiric Therapy:

• Step 1:  Risk Factors for MDR?

  • Use of antibiotics within the preceding 90 days

  • Current hospitalization of ≥5 days

  •  

    High frequency of antibiotic resistance in the community or in the specific hospital unit

  • Immunosuppressive disease and/or therapy

  • (Severe septic shock)

  • HCAP risk factor

•  

  If Risk Factors for MDR: (ONE of)

  • Antipseudomonal cephalosporin (ceftazidime 2g q8h, cefepime 2g q8h)

  • Antipseudomonal carbepenem (meropenem 1g q8h, imipenem 500mg-1g q6h)

  • Pip-tazo 4.5g q6h

  • If penicillin allergic --> (if mild, rash etc..) can trial cephalosporin or aztreonam (even less cross-reactivity)

  • If penicillin anaphylaxis --> consult allergy specialist

• Add-on therapies

  • Ciprofloxacin

  • Levofloxacin

  • Gentamycin

  • Tobramycin

• PLUS ONE of the following (if MRSA is suspected, there are MRSA risk factors, or there is a high incidence of MRSA locally):

  • Linezolid

  • Vancomycin (15-20mg/kg + dose interval by renal function)

  • Telavancin

Source; IDSA Guidelines / UpToDate.com

Histoplasmosis

• Histoplasma capsulatum
• Primarily in Midwest and Southeast USA.
• Grows in moist soil in temperate climate --
  • Ohio River and Mississippi River Valleys (CLASSIC)
• Exposure from soil excavation, construction, and also from Caves/buildings with bats.
• Exists as mycelia in environment, and yeast in the body.
  • Converts to yeast, upregulates calcium binding protein... frequently see calcifications.
  • Macrophages present histo antigens to T-cells in lymph nodes, and become activated inseveral weeks.
• Symptoms:
  • Astymptomatic/mild flu-like-illness + clear in healty
  • Young,  Elderly, Immunocompromised:
    • 14 days post-exposure
      • high fever, headache, cough (no sputum), dull CP.
      • CXR- patchy infiltrates, then later to "buckshot" calcifications.
      • Mediastinal lymphadenopathy (like lymphoma and sarcoid).
  • If disseminated disease (10%)
    • Meningitis, lymphocytosis, low glucose.
    • Reticularnodular pattern on CXR. (CXR normal in 1/3)
• Diagnosis:
  • Culture: needs selective media, lab needs to know. Takes 7 days (Not routine).
  • Lysis-centrifugation.
  • Bronchoscopic lavage fluid -- should test. (90% yield in HIV pts)
  • Urine antigen test.  (90% if disseminated, 40% if cavitary, and 20% pulmonary)
  • Histopathology good too.  Silver stain.
  • Bottom line: Difficult to detect.  
    • If disseminated --> do bone marrow culture
• Treatment:
  • Itraconazole is good agent.  Recommended for:
    • Acute pulmonary illness that fails to imrpove in 7 days.
    • Extensive mediastinal involvement.
    • Progressive cavitary disease.
  • Amphotericin B if more severe disease.
    • or if no improvement with Itraconazole

Coccidiomycosis

• Coccidioides immitis
• Grows in soil; prefers dry, alkaline soil, hot summers, and winters with few freezes.
  • These conditions exist in California's San Joaquin Valley in southern Arizona, New mexico, and texas
• Also in Mexico, Central America, and South America.
• Contracted in summer (dust storms, excavation, earthquakes).
• Cell-mediated immunity (Endospores).
• Sx:
  • non-productive cough, fever, pleuritic chest pain, SOB, headache, fatigue.
  • skin manifestations: erythema nodosum, erythema multiforme, nonpruritic papular rash.
  • Eosinophilia.
• Disseminates in AIDS/HIV.
• Chronic Lung Infection: fibrosis, nodules, cavities.
• Chronic pleural effusions in young healthy athletic males.
• Dx:
  • Sputum examination (or gathered by bronchoscopy)
  • Easy to culture on mycology plates.
  • Serology: IgG, IgM
• Tx:
  • Only if disseminated disease.
  • Amphotericin B
  • Fluconazole or itraconazole if less severe.