Pneumocystis jirovecii

Pneumocystis jirovecii pneumonia is encountered by the intensivist a lot more than it is encountered by the respiratory physician, but perhaps less than it is encountered by the transplant haematologist or HIV specialist. And when the encounter occurs, much of the microbiology is subsumed into the need to make and confirm the diagnosis, which is then followed by some completely unrelated core ICU business like mechanical ventilation. Perhaps in recognition of this fact, PJP has appeared only once in the exams, as Question 17 from the second paper of 2023, where the focus of the examiners was on listing facts rather than deep analysis, suggesting that the standard for a safe intensivist would be a passing familiarity with how to competently identify this organism.

To develop this level of familiarity, the reader is redirected to better resources; as the author acknowledges himself to be less an authority and more a fascinated amateur. Cordonnier et al (2020) was excellent, and seems to be available for free, but was seventeen pages long, and if long articles are called for then the well-resourced first-world reader may already have access to the four UpToDate chapters that deal with this organism, and perhaps even the expansive entry by Gilroy & Bennett in Clinical Infectious Disease. More often the time-poor exam candidate will instead demand a brief summary, which is unfortunately not to be found anywhere. The closest thing was probably this entry from eTG, which is paywalled for most readers.

Microbiology of Pneumocystis jirovecii

Microbiological features was the specific wording used by the college examiners, which was only a "list" question, and only for one mark of the total ten, but which still implies that some candidates would have been rewarded for their knowledge of this fascinating beast. Those features, in the briefest detail, as the author struggles not to shamelessly geek all over this topic: 

  • Unicellular spore-forming fungus
  • Intracellular pathogen (obligate biotroph, i.e. dependent on the host for its nutrient supply, and without any environmental reservoir), which means it cannot be easily cultured from samples.
  • Ubiquitous among the lungs of mammals, for which each host species has its own Pneumocystis parasite (ours is P.jirovecii, whereas for example P.murina infects exclusively mice)
  • They are apparently present in basically all human lungs, and appear to  cause no disease in the immunocompetent host.

Its usually referred to as a "unicellular fungus", which is a weird thing for a fungus to be. Unicellular fungi are most commonly referred to as yeasts, whereas whenever one hears "fungus" in the medical vernacular the speaker will usually be referring to organisms like Aspergillus which form hyphae and which are more properly described as molds.  But Pneumocystis escapes these nomenclature norms mostly owing to the joys of molecular analysis. It belongs to the Ascomycota group, which contains other pathogenic yeasts like Candida, but its cell wall contains cholesterol instead of ergosterol, making it distinct from the more common yeasts. Moreover it has unusual reproductive behaviours: for example it does not relicate by budding, as all good godfearing yeasts are supposed to do,  but instead has a weird lifecycle where it has an option of asexual binary fission or sexual reproduction resulting in formation of an ascus (cyst) containing eight ascospores. In case the reader is interested in even more weird terminology, an ascospore is a propagule of a spore-forming fungus, i.e. a seed particle which can give rise to new individual organism, and a major vector for airborne Pneumocystis transmission, which according to Cushion (2010) occurs for all humans almost immediately after birth.  Anyway:  "yeast-like fungus" is how it is sometimes referred to in the literature, as an understanding nod to these eccentricities. Strangely, the same literature also often refers to its tortuous course through biological classification systems as an "identity crisis", which of course could not be further from the truth. Pneumocystis was never in a crisis, it was confident in its  acceptance of its healthy authentic self, and the various historical attempts to shoehorn it into protozoa were just expressions of confused microbiological bigotry.

Assessment of suspected Pneumocystis jirovecii pneumonia

The CICM exams tend to focus on structured answers, and the most likely question about PJP would be an "outline your assessment" question, which typically requires a "history, examination, investigations" sort of structure.

History would usually include some risk factors:

  • Immunesuppression: mostly T-cell suppression:
    • Corticosteroids: more than 15 mg of prednisone per day for 6–12 weeks is enough to put you at risk, according to Cordonnier
    • Mycophenolate
    • Calcineurin inhibitors, eg tacrolimus, sirolimus
    • Chemotherapy agents with T cell activity:
      • Purine analogs (fludarabine, cladribine, cytarabine)
      • Idelalisib
      • Alemtuzumab
    • Patient groups taking these drugs regularly would have to include:
      • Haematological malignancy patients
      • Bone marrow and solid organ transplant recipients
      • Autoimmune disease sufferers
  • Immunodeficiency:
    • HIV (PJP is an AIDS-defining illness)
    • Neutropenia
    • GVHD
    • CMV


  • Nonspecific, and completely out of proportion to the examination findings:
    • Fever
    • Dry cough
    • Chest pain
    • Dyspnoea, respiratory failure
  • Subacute progression, can be up to 2-5 weeks

Examination findings

  • Tachypnea, tachycardia
  • Creps on auscultation
  • Hypoxia, especially with exertion
  • Limited to the lungs: "extrapulmonary pneumocystosis" is an extremely rare condition, reserved for historical descriptions of severely ill HIV patients prior to the availability of antiretroviral therapy. Sites commonly affected in those patients included liver, spleen, bone marrow, and lymph nodes.

Classical biochemistry

  • Pneumocystis infection often has a raised LDH level (over 460 IU/L),  but this is not a part of any sort of diagnostic workup. These patients often have elevated LDH anyway, because cancer.
  • Procalcitonin is usually only modestly elevated (Nyamande & Lalloo, 2006)

Classical radiological findings

  • Ground glass appearance, rather than consolidation
  • Interstitial perihilar and apical infiltrates
  • Sparing of the peripheries
  • Invasion along interlobular septae
  • Cystic lesions (hence Pneumocystis)
  • Generally CT findings can be supportive, but the spectrum of radiological appearance is so variable that one would never be able to fully commit to a diagnosis just on the basis of CT. 

Diagnosis of Pneumocystis infection

This section of Question 17 from the second paper of 2023 attracted half the marks from the whole question, which probably reflects the real world importance of correctly interpreting the investigations that confirm this diagnosis. The result will be to embark on a long course of relatively toxic therapy, which may harm the already damaged bone marrow and exacerbate whatever immunocompromise has led to this position in the first place. 

  • 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: Problem is, we all have it.  
    • 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

Antimicrobial options

Most fungi have ergosterol in their walls, and are susceptible to drugs which target the synthesis of ergosterol, such as the azoles polyenes and allylamines (eg. terbinafine). Fortunately, this fungus has a dihydropteroate synthase eznyme susceptible to sulfamethoxazole, and dihydrofolate reductase enzyme susceptible to trimethoprim, and it is possible to impair its folate synthesis using this combination of sulfonamide agents. Thus:

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

Adjunctive steroids: recommended for patients with severe PJP, i.e. those with ICU-level hypoxia. ATS guidelines recommend 21 days:

  • Prednisone 40 mg twice daily for 5 days
  • 40 mg daily on Days 6 through 11
  • then 20 mg daily through Day 21

Theoretically, echinocandins can also be used to treat PJP, as they target β-D-glucan synthesis.


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.