After 14 days in ICU with a diagnosis of community-acquired pneumonia, a patient's signs and symptoms have not improved despite antimicrobial therapy.

a) List the factors that might be responsible for the slow resolution. (60% marks) 

b) Outline your assessment to identify the cause of the slow resolution. (40% marks)

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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)

References

References

Li, Meiling, et al. "Risk factors for slowly resolving pneumonia in the intensive care unit." Journal of Microbiology, Immunology and Infection (2014).

Sialer, Salvador, Adamantia Liapikou, and Antoni Torres. "What is the best approach to the nonresponding patient with community-acquired pneumonia?." Infectious disease clinics of North America 27.1 (2013): 189-203.

COJOCARU, Manole, et al.  "Pulmonary manifestations of systemic autoimmune diseases." Maedica 6.3 (2011): 224.

Kuru, Tünay, and Joseph P. Lynch. "Nonresolving or slowly resolving pneumonia." Clinics in chest medicine 20.3 (1999): 623-651.

Kyprianou, Andreas, et al. "The challenge of non resolving pneumonia." Postgrad Med 113.1 (2003): 79-92.

Rome, Lauren, Ganesan Murali, and Michael Lippmann. "Nonresolving pneumonia and mimics of pneumonia." Medical clinics of North America 85.6 (2001): 1511-1530.

Menéndez, Rosario, and A. Torres. "Evaluation of non-resolving and progressive pneumonia." Intensive Care Medicine. Springer New York, 2003. 175-187.

Oster, Gerry, et al. "Initial treatment failure in non-ICU community-acquired pneumonia: risk factors and association with length of stay, total hospital charges, and mortality." Journal of medical economics 16.6 (2013): 809-819.

Pareja, Jaime G., Robert Garland, and Henry Koziel. "Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia." CHEST Journal 113.5 (1998): 1215-1224.

Rodrigo, Chamira, et al. "Effect of corticosteroid therapy on influenza-related mortality: a systematic review and meta-analysis." Journal of Infectious Diseases 212.2 (2015): 183-194.

Parody, Rocio, et al. "Predicting survival in adults with invasive aspergillosis during therapy for hematological malignancies or after hematopoietic stem cell transplantation: single‐center analysis and validation of the seattle, french, and strasbourg prognostic indexes." American journal of hematology 84.9 (2009): 571-578.

Bradley, B., et al. "Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society (vol 63, Suppl V, pg v1, 2008)." Thorax 63.11 (2008): 1029-1029.

Davis, William B., Henry E. Wilson, and Robert L. Wall. "Eosinophilic alveolitis in acute respiratory failure. A clinical marker for a non-infectious etiology." CHEST Journal 90.1 (1986): 7-10.

Steinberg, Kenneth P., et al. "Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome." New England Journal of Medicine 354.16 (2006): 1671-1684.