Pneumocystis pneumonia

Pneumocystis jirovecii pneumonia (PCP), previously known as Pneumocystis carinii pneumonia, is an opportunistic fungal lung infection occurring almost exclusively in immunocompromised individuals. In 50% of cases, PCP is the first manifestation of AIDS (acquired immune deficiency syndrome), but it may be caused by other immunodeficiency disorders. PCP should be suspected in patients with a history of progressive dyspnea and a dry cough with resistance to standard antibiotic treatment. Signs that support this diagnosis include a CD4 count < 200/μL, an increased beta-D-glucan level, and diffuse bilateral infiltrates on chest x-ray. Management of PCP includes high-dose trimethoprim/sulfamethoxazole (TMP/SMX), treatment of the underlying immunodeficiency disorder, and steroids in the case of severe respiratory insufficiency.

• Interstitial pneumonia caused by the yeast-like fungal organism Pneumocystis jirovecii ^[1]

• Pathogen: P. jirovecii (former P. carinii): ubiquitous, yeast-like fungus previously classified as a protozoan
• Route of transmission: airborne ^[2]
• Risk factors
  • HIV infection ^[3]
    • CD4 count: usually < 200/μL
    • Poor compliance with PCP prophylaxis or HAART
    • History of PCP infection
  • Primary immunodeficiency disorders ^[4]
    • Severe combined immunodeficiency disorder
    • Hyper IgM syndrome
  • Immunosuppressive treatment (e.g., chronic glucocorticoid therapy)
  • Malignancy (e.g., leukemia, non-Hodgkin lymphoma)
  • Malnutrition

• Usually asymptomatic
• Symptoms typically have a gradual onset (days to weeks) and include:
  • Low-grade fever and malaise
  • Dyspnea, tachypnea, and nonproductive cough
  • Fatigue, weight loss, chills
• May progress to fulminant respiratory failure

A definitive diagnosis of PCP is not always possible. The following criteria should lead to a presumptive diagnosis of PCP:

• History and clinical examination
• Oxygen saturation
• CD4 count
• Beta-D-glucan level
• Chest x-ray (if CXR is inconclusive, a CT scan should be performed)

The diagnosis should generally be confirmed via microscopic identification of P. jirovecii from respiratory secretions.

Clinical examination

• Chest auscultation
  • Bilateral crackles and rhonchi
  • Unremarkable auscultatory findings are possible in the early stages of disease.
• Pulse oximetry: oxygen saturation < 90 % at rest (worsens with exertion)

PCP is often misdiagnosed as atypical pneumonia or bronchitis because of the persistent cough and similar auscultatory findings.

Laboratory tests

• CD4 count: typically < 200/μL
• Laboratory measures
  • ↑ Beta‑D‑glucan levels ^[5]
  • ↑ LDH (typically)
• Polymerase chain reaction (PCR) ^[6]
• Confirmatory test: microscopic identification of P. jirovecii
  • Specimen from
    • Bronchoalveolar lavage
    • Induced sputum ^[7]
    • Lung tissue biopsy
  • Staining: enables visualization of disc-shaped P. jirovecii cysts with central spores ^[8]
    • Methenamine silver staining, Wright stain, or Diff-Quik stain
    • Immunofluorescence

Imaging

• Chest x‑ray
  • Typically symmetrical, diffuse interstitial infiltrates extending from the perihilar region
  • May sometimes be normal
• High-resolution CT
  • Indicated if PCP is still suspected in a patient with a normal CXR
  • High sensitivity for PCP (a negative scan thus suggests the diagnosis of PCP is unlikely)
  • Typical features
    • Ground-glass attenuation: symmetrical diffuse, interstitial infiltrates
    • Pneumatoceles: cystic air-filled spaces within the lung tissue

Acute infection ^[9]

• Treatment of choice: high‑dose TMP/SMX for up to 3 weeks
• Glucocorticoids: add in the case of severe respiratory insufficiency (either PaO₂ < 70 mmHg or alveolar-arterial oxygen gradient ≥ 35 mmHg)
• Alternatives if allergic to TMP/SMX or treatment of choice is ineffective
  • Mild/moderate disease
    • Oral trimethoprim PLUS dapsone
    • Oral atovaquone
    • Oral primaquine PLUS clindamycin
  • Moderate/severe disease
    • Oral primaquine PLUS IV clindamycin
    • Intravenous pentamidine (monotherapy) ^[10]

If a patient with suspected PCP is acutely ill then empiric treatment should be started without delay.

PCP prophylaxis ^[9][11]

• Indication
  • Primary prophylaxis: CD4‑cell count < 200/μl (e.g., AIDS, bone marrow suppression due to cytotoxic therapy, or primary immunosuppressive disorders)
  • Secondary prophylaxis: to prevent recurrence in patients with AIDS or other immunocompromising conditions
• Implementation
  • Low‑dose TMP/SMX
  • Alternative (e.g., if allergic to TMP/SMX): oral dapsone OR oral atovaquone ^[12][13]

• ARDS
• Bullous formation with risk of rupture → secondary pneumothorax
• Pleural effusion

We list the most important complications. The selection is not exhaustive.

• PCP was formerly the most common cause of death in HIV‑positive patients during the early years of the HIV epidemic. ^[2]
  • The introduction of HAART (highly active antiretroviral therapy) and TMP/SMX prophylaxis in patients with a CD4 count < 200/μl has significantly improved the long-term outcome of the disease.
  • Despite adequate prophylaxis, PCP infection may lead to death in patients presenting with severe symptoms (e.g., respiratory failure).

1. Stringer JR, Beard CB, Miller RF, Wakefield AE. A New Name for Pneumocystis from Humans and New Perspectives on the Host-Pathogen Relationship. Emerg Infect Dis. 2002; 8 (9): p.891–896. doi: 10.3201/eid0809.020096 . | Open in Read by QxMD
2. Morris A, Lundgren JD, Masur H, et al. Current epidemiology of Pneumocystis pneumonia. Emerg Infect Dis. 2004; 10 (10): p.1713-1720. doi: 10.3201/eid1010.030985 . | Open in Read by QxMD
3. Huang L, Crothers KA. HIV-associated Opportunistic Pneumonias. Respirology. 2009; 14 (4): p.474–485.. doi: 10.1111/j.1440-1843.2009.01534.x . | Open in Read by QxMD
4. X-linked Immunodeficiency With Hyper IgM Clinical Presentation. https://emedicine.medscape.com/article/889104-clinical. Updated: October 23, 2019. Accessed: March 9, 2020.
5. Salerno D, Mushatt D, Myers L et al. Serum and bal beta-D-glucan for the diagnosis of Pneumocystis pneumonia in HIV positive patients. Respir Med. 2014; 108 (11): p.1688-1695. doi: 10.1016/j.rmed.2014.09.017 . | Open in Read by QxMD
6. Helweg-Larsen J, Jensen JS, Benfield T, Svendsen UG, Lundgren JD, Lundgren B. Diagnostic Use of PCR for Detection of Pneumocystis carinii in Oral Wash Samples. J Clin Microbiol. 1998; 36 (7): p.2068-2072..
7. Turner D, Schwarz Y, Yust I. Induced sputum for diagnosing Pneumocystis carinii pneumonia in HIV patients: new data, new issues.. Eur Respir J. 2003; 21 (2): p.204-208.
8. Goljan EF. Rapid Review Pathology. Elsevier Saunders ; 2013
9. Maschmeyer G, Helweg-Larsen J, Pagano L, Robin C, Cordonnier C, Schellongowski P. ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients. J Antimicrob Chemother. 2016; 71 (9): p.2405-2413. doi: 10.1093/jac/dkw158 . | Open in Read by QxMD
10. Pentamidine. https://www.drugs.com/mtm/pentamidine.html. . Accessed: February 23, 2018.
11. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Updated: October 18, 2017. Accessed: February 23, 2018.
12. Quinn M, Fannin JT, Sciasci J, et al. Pentamidine for Prophylaxis against Pneumocystis jirovecii Pneumonia in Pediatric Oncology Patients Receiving Immunosuppressive Chemotherapy. Antimicrobial Agents Chemother (Bethesda). 2018; 62 (8). doi: 10.1128/aac.00173-18 . | Open in Read by QxMD
13. Awad WB, Asaad A, Al-Yasein N, Najjar R. Effectiveness and tolerability of intravenous pentamidine for Pneumocystis carinii pneumonia prophylaxis in adult hematopoietic stem cell transplant patients: a retrospective study. BMC Infect Dis. 2020; 20 (1). doi: 10.1186/s12879-020-05127-y . | Open in Read by QxMD
14. Bukhari H, Ayad M, Rosenthal A, Block M, Cortelli M. Superior vena cava syndrome secondary to thyroid cancer. J Surg Case Rep. 2011; 2011 (7): p.7. doi: 10.1093/jscr/2011.7.7 . | Open in Read by QxMD
15. Bennett NJ, Gilroy SA. Pneumocystis jiroveci Pneumonia. Pneumocystis jiroveci Pneumonia. New York, NY: WebMD. http://emedicine.medscape.com/article/225976-overview#a1. Updated: October 19, 2016. Accessed: March 20, 2017.