Question 17

With respect to Pneumocystis jirovecii pneumonia (PJP):    
a) List two microbiological features of the causative organism.    (1 mark)
b) List four risk factors for the development of PJP.    (2 marks)
c) List four drugs with activity against the organism.    (2 marks)
d) List the investigations used in making the diagnosis of PJP.    (5 marks)


 

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College Answer

Syllabus topic/section:

2.1.3 Sepsis and Infections – L1.

Aim:

To allow the candidate to demonstrate knowledge of a common infection in the immunosuppressed.

Discussion:

Certain sections of the question have been answered well (risk factors & investigations). This made the question easy to gain marks >5/10. However, the microbiological features & treatment drugs answers were poorly answered. In particular there were emphasis on microbiological tests that were generic. "M/C/S" for example, is not a specific method used to identify/diagnose PJ pneumonia. Candidates who are more specific about methods used will gain higher marks as they had demonstrated a knowledge of appropriate depth. For example, Tinctorial (dye based) staining e.g. Wright –Giemsa, gram-Weigert), fluorescent antibody staining, or mentioning PCR based assays.

Overall, most of the candidates have reasonable answers to succeed at the question. We suggest two 2 things for individual improvement - making note of key words & structuring the answer under headings/categories. During preparation for this examination consider these two strategies: using palm cards on topics & choosing the key words while preparing the topics + understanding their significance.

Discussion

Legionella AND Pneumocystis, in one exam paper? Colleagues, we have overdosed on atypical pneumonia. Surely this must mean that the examiners will focus on more classical biofilm-forming organisms in the next sitting. 

Microbiological features:

 

  • Unicellular spore-forming fungus
  • Intracellular pathogen
  • Obligate biotroph, cannot be cultured
  • Present in the lungs of most adults

Risk factors

  • Immunesuppression: mostly T-cell suppression:
    • Corticosteroids
    • Mycophenolate
    • Calcineurin inhibitors, eg tacrolimus, sirolimus
    • Chemotherapy agents with T cell activity:
      • Purine analogs (fludarabine, cladribine, cytarabine)
      • Idelalisib
      • Alemtuzumab
  • Immunodeficiency:
    • HIV (PJP is an AIDS-defining illness)
    • Neutropenia
    • GVHD
    • CMV

Antimicrobial options:

  • First line:
    • Trimethoprim–sulfamethoxazole
      • IV dose is 5mg/kg of trimethoprim and 25 mg/kg of sulfamethoxazole, with a maximum of  480 / 2400 mg 
      • Duration of treatment is 21 days
  • Second line agents:
    • Dapsone 100mg daily (+/- pyrimethamine 50mg weekly)
    • Pentamidine 300mg monthly
    • Clindamycin–primaquine 
    • Atovaquone 750mg bd
  • Not clear whether any additional marks would have been scored by anyone mentioning the adjunctive corticosteroids, but the college specifically asked for drugs with activity against the organism, whereas corticosteroids could be properly described as drugs with activity against the host

Investigations 

  • Microscopy with stains:
    • This organism cannot be cultured, so stained specimen microscopy is the only way.
    • Stains include:
      • Wright-Giemsa
      • Gram-Weigert
      • Grocott’s methenamine silver stain
      • modified Papanicolaou stain
      • Fluorescein-conjugated monoclonal antibody
    • Classical finding on lung biopsy is "foamy alveolar casts" 
  • PCR of respiratory samples: 
    • Sputum:  sensitivity is poor unless this is a "deep" specimen obtained with the kind of chest-wrecking cough that only hypertonic saline can produce. One could never be confident that a negative sputum sample has ruled out PJP. Gilroy & Bennett quote a 50% sensitivity even for induced sputum.
    • Bronchoalveolar lavage is the gold standard for PJP PCR. Fan et al (2013) quote sensitivity of 98.3% and specificity of 91%.
  • β-D-glucan
    • ​​​​​​​A ubiquitous component of fungal cell walls
    • Present in Candida and Aspergillus, which can lead to false positives

It is not clear whether imaging would have scored any marks, as a presumptive diagnosis on the basis of classical CT findings and suspicious history is often enough to start treatment. Judging by the examiner comments, only microbiological diagnosis was of interest.

References

Cordonnier, C., et al. "Pneumocystis jiroveci." Seminars in Respiratory and Critical Care Medicine. Vol. 41. No. 01. 333 Seventh Avenue, New York, NY 10001, USA.: Thieme Medical Publishers, 2020.

Gilroy, Shelley A., and Nicholas J. Bennett. "180 Pneumocystis jirovecii (carinii).Clinical Infectious Disease: 123.

Cushion, Melanie T. "Are members of the fungal genus pneumocystis (a) commensals;(b) opportunists;(c) pathogens; or (d) all of the above?." PLoS pathogens 6.9 (2010): e1001009.

Cushion, Melanie T., and James R. Stringer. "Stealth and opportunism: alternative lifestyles of species in the fungal genus Pneumocystis.Annual review of microbiology 64 (2010): 431-452.

Ng, Valerie L., David M. Yajko, and W. Keith Hadley. "Extrapulmonary pneumocystosis." Clinical microbiology reviews 10.3 (1997): 401-418.

Nyamande, K., and U. G. Lalloo. "Serum procalcitonin distinguishes CAP due to bacteria, Mycobacterium tuberculosis and PJP." The International Journal of Tuberculosis and Lung Disease 10.5 (2006): 510-515.

Kanne, Jeffrey P., Donald R. Yandow, and Cristopher A. Meyer. "Pneumocystis jiroveci pneumonia: high-resolution CT findings in patients with and without HIV infection." AJR-American Journal of Roentgenology 198.6 (2012): W555.

Fan, Li-Chao, et al. "Evaluation of PCR in bronchoalveolar lavage fluid for diagnosis of Pneumocystis jirovecii pneumonia: a bivariate meta-analysis and systematic review." PloS one 8.9 (2013): e73099.

Limper, Andrew H., et al. "An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients." American journal of respiratory and critical care medicine 183.1 (2011): 96-128.