Question 21

College answer

Factors contributing to non-resolution or delayed resolution of pneumonia

1. Host factors: 
2. Agent (organism factors)
3. Extent of disease
4. Due to Complication of Pneumonia
5. Incorrect Diagnosis: Diseases mimicking pneumonia

Host factors:

• Age > 60
• H/o Smoking
• Comorbidities: COPD, CCF, DM, CRF, alcoholism
• Malnutrition
• Immunosuppressed host 
• Underlying lung disease

Agent or Organism factors

• Resistant organism: especially in patients treated with beta lactams in the recent past, hospitalised in last 3 months, pneumonia in the last 1 year.
• Nosocomial pneumonia: MRSA in a hospitalised patient, with indwelling IV catheters, dialysis patients etc. Pseudomonas aerogenosa infection,  
• Unusual pathogen: TB, atypical mycobacterium, nocardia, actinomyceces, Pneumocystis jiroveci,
• Fungal: Aspergillus, Cryptococcus, and Histoplasma etc

Extent of disease

• Bilateral multi-lobar pneumonia
• Associated with bacteraemia

As a result of Complications of pneumonia.

• Empyema
• Abscess
• Metastatic infection such as infective endocarditis
• ARDS/fibrotic lung disease

Diseases mimicking pneumonia

• Malignancy
• Systemic vasculitis
• Collagen vascular disorder
• Pulmonary oedema, CCF, heart failure with preserved EF, mitral regurgitation
• Drug induced pneumonitis
• Radiation pneumonitis
• Hypersensitivity Pneumonitis.

b)                                                                                                                                             

Assessment will involve history, examination and investigations to delineate which of the causes from the above list may be contributing.

 History: 

• Detailed history of travel, pets, occupation, medication, addiction and family history
• Past medical history; e.g. radiation for lymphoma or breast cancer, systemic disease e.g., RA
• Allergies
• Medications

Examination: 

• Looking for signs of complication and signs suggestive of other systemic illness such as collagen vascular disorders.
• Assess for other sources of sepsis e.g. abscess, infectious endocarditis, catheter-related

Investigation:

Will depend upon the findings of the history and examination. Specific respiratory investigations may include: 

• Repeat Tracheal aspirates- Send for fungal and cultures for unusual organisms
• Bronchoscopic aspirates both for infectious causes and cytology
• US guided pleural tap If fluid present
• CT Chest: High resolution chest CT to detect parenchymal abnormalities, including emphysema, airspace disease, interstitial disease, and nodules o Chest CT also detects sequestered foci of infection, such as lung abscess and empyema, and helps direct biopsy procedures.
• Thoracoscopic or open Lung biopsy: If bronchoscopy is non diagnostic and failure to improve and large specimens are required then open lung biopsy can be resorted to.

Other investigations may include:

• Echocardiography
• Vasculitis screen
• EPG, IEPG, immunology screen, HIV serology

Discussion

Factors Associated with Treatment Failure
in Community-Acquired Pneumonia

Wrong disease Abscess Empyema Vasculitis (eg. Wegeners) Malignancy (eg. lung primary, mets or lymphoma) Alveolar haemorrhage BOOP Alveolar proteinosis SLE Heart failure PE Sarcoidosis Eosinophilic pneumonia

Wrong antimicrobial agents Underdosing Inappropriate dose interval Poor penetration into lung tissue Viral pneumonia Atypical pneumonia, or a resistant organism: Mycobacterium tuberculosis Nocardia Actinomyces israelii Aspergillus Coxiella burnetii (Q fever) Chlamydia psittaci (psittacosis) Leptospira interrogans (leptospirosis) Pseudomonas pseudomallei (melioidosis)

Predictors of poor response to antibiotics: Elderly patient Multiple comorbidities Alcoholism Smoking (and COPD) Multilobar pneumonia Bacteraemia Empyema and lung abscess Legionella pneumonia Polymicrobial pneumonia

A brilliant article on this topic is offered from Clinics in Chest Medicine (Kuru and Lynch, 1999), but unfortunately it is behind a paywall.  The next best source is probably the UpToDate page on nonresolving pneumonia. Again, access to the latter requires the exchange of money. This LITFL article, however, is free.

• Culture again! You have selected some sort of Horrendomonas with your empirical therapy, and it will require a different antibiotic cocktail.
• TTE: the contribution of cardiogenic pulmonary oedema to the respiratory failure needs to be considered.
• CT chest; particularly high-resolution CT: it will reveal the full extent of the pneumonia, and it will unveil new cavitating lesions, loculated collections and bronchial masses.
• Sputum eosinophils: eosinophilic pneumonitis may be to blame.
• Acid-fast bacilli: it would be embarrassing to miss tuberculosis
• Aspergillus investigations as well as the other fungi
• CMV, VZV, HSV - PCR on sputum (though inlikely in an immunocompetent host)
• Autoimmune screen; perhaps this "pneumonia" is in fact a pulmonary manifestation of a systemic autoimmune disease, eg. SLE, RA, Sjögren's syndrome, mixed connective tissue disease, Wegener's granulomatosis, Churg-Strauss syndrome, Goodpasture's syndrome,  ankylosing spondylitis, and so on and so forth.
• Bronchoscopy: it will reveal any bronchial obstruction, and it may allow the lavage of a lobe, thereby collecting valuable specimens.
• Lung biopsy: Even though this is invasive, it may be indicated in situations where the diagnosis is uncertain and the potential treatments are aggressive and mutually incompatible (eg. high dose steroids vs. high dose antibiotics)