Pneumocystis Jirovecii (Carinii) Pneumonia

Synonyms: Pneumocystis jirovecii, pneumocystosis

Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality among immunocompromised people. It remains a leading AIDS-defining opportunistic infection in HIV-infected individuals.¹ Pneumocystis is primarily a pulmonary pathogen but extrapulmonary disease occurs in about 1% of cases.

Pneumocystis organisms from different host species have very different DNA sequences, indicating multiple species. Because of the genetic and functional distinctness, the organism that causes human PCP (formerly known as Pneumocystis carinii) is now named Pneumocystis jirovecii.²
P. jirovecii is a unicellular eukaryote which shares characteristics with both protozoa and fungi.

• The background rate of infection in the general population is extremely low at less than 1 case per million population per year.
• When HIV was first characterised, PCP affected up to 75% of HIV-infected individuals. Current rates of infection in the HIV-positive population in the developed world are about 10–20%.
• The incidence of PCP in HIV-positive patients has been significantly reduced by prophylactic medication and highly active antiretroviral therapy (HAART).³
• In the developing world, rates of PCP are lower, possibly due to poor survival with HIV, underdiagnosis and prior pulmonary infection with TB and other organisms.

Risk factors

• PCP tends to affect HIV positive patients who have a CD4 count below 200 cells/mm³
• HIV patients with oral thrush or fever, or AIDS-defining diagnosis
• Patients taking steroids or other immunosuppressants
• Patients with haematological malignancy
• Organ-transplant recipients
• Congenital immune deficiency, e.g. thymic aplasia, Severe Combined Immune Deficiency (SCID), hypogammaglobulinaemia
• Severe malnutrition (poor nutrition in HIV-positive individuals increases risk)

• Cough is usually non-productive but productive cough may occur in up to a third of patients
• Exertional dyspnoea
• Fever
• Tachypnoea
• Chest pain
• There may be signs of AIDS such as thrush, oral hairy leukoplakia or Kaposi's sarcoma.
• Respiratory examination is highly variable and often normal. Scattered crackles and wheeze may be present, or rarely signs of focal consolidation.
• Pulse oximetry may show low SaO₂ at rest
• Extrapulmonary disease may manifest as hepatosplenomegaly, lymphadenopathy or ocular disease

• Bacterial or viral pneumonia
• Mycobacterium avium intracellulare complex infection
• Atypical pneumonia
• Pulmonary Kaposi's sarcoma
• Tuberculosis
• Influenza
• CMV infection
• Aspergillosis
• Measles
• Varicella (chickenpox) pneumonitis
• Coxiella burnetii (Q fever)
• Thoracic actinomycosis
• Pulmonary nocardiosis
• Lymphocytic interstitial pneumonia (associated with autoimmune disease)
• Pulmonary embolism

• Bloods:
  • Elevated LDH is indicative of the diagnosis but not highly specific or sensitive.
  • Arterial blood gases may show hypoxia and hypocarbia due to hyperventilation.
  • The alveolar-arterial oxygen tension gradient may be increased.
• Radiology:
  • CXR can be normal or show perihilar fluffy shadows or pneumothorax.
  • CT imaging shows ground glass infiltrates but has low sensitivity and specificity.
  • Gallium scanning is highly sensitive but with low and variable specificity.
• Microbiology:
  • The organism cannot be routinely cultured and is detected by staining of the cyst wall or trophozoite, usually with silver-based stains.
  • Sputum may be collected following inhalation of nebulised saline and/or chest physiotherapy, and should be sent for routine and mycobacterial culture. Repeated samples may need to be taken to confirm the diagnosis.
  • If sputum is negative but PCP is still suspected, then bronchoscopy with bronchoalveolar lavage or transbronchial biopsy may detect the organism.
  • Open lung biopsy may occasionally be employed.
• Pulmonary function tests:
  • May show a modest reduction in the vital capacity (VC) and the total lung capacity (TLC).
  • Most consistent abnormality is a decrease in the single-breath diffusing capacity for carbon monoxide (DLCO), which has a sensitivity of 89%.

• Mild:
  • Breathlessness on mild exercise, which may be associated with cough and sweats
  • Arterial blood gases and oxygen saturation at rest, on air: PaO₂ >11 kPa; SaO₂ >96%
  • Chest X-Ray: normal or minor perihilar infiltrates
• Moderate:
  • Breathlessness on minimal exercise, fever (with or without sweats)
  • Arterial blood gases and oxygen saturation at rest, on air: PaO₂ 8–11 kPa; SaO₂ 91-96%
  • Chest X-Ray: diffuse interstitial shadowing
• Severe:
  • Breathlessness at rest, persistent fever and cough
  • Arterial blood gases and oxygen saturation at rest, on air: PaO₂ <8 kPa; SaO₂ <91%
  • Chest X-Ray: extensive interstitial shadowing, with or without alveolar shadowing

See Drug Treatment for Pneumocystis Pneumonia for more detail.

• Early diagnosis greatly aids successful therapy.
• Mild cases may be treated with oral medication as outpatients. Moderate to severe cases usually require hospitalisation and intravenous therapy.
• Treating empirically without confirmation of the diagnosis may be necessary, but is best avoided if possible, due to the danger of missing other causes for the symptoms.
• Patients often deteriorate 3–5 days after starting treatment. This is thought to be due to inflammation caused by dead pneumocystis organisms.
• Treatment is usually given for 2–3 weeks.

Mild to moderate disease

• High dose co-trimoxazole (trimethoprim-sulphamethoxazole) is the drug of choice.
• Alternatives if the patient is unable to tolerate co-trimoxazole are:
  • Atovaquone (less effective but less toxic than co-trimoxazole or pentamidine)
  • Dapsone with trimethoprim
  • Clindamycin with primaquine
  • Inhaled pentamidine isetionate may also be used for mild disease

Severe disease

• Intravenous high-dose co-trimoxazole is first line treatment but toxic effects mean it may not be tolerated.
• Pentamidine isetionate:
  • Given by intravenous infusion is used for patients who either cannot tolerate co-trimoxazole or who have not responded to it.
  • Can cause severe hypotension during or immediately after infusion; blood pressure and glucose should be carefully monitored.
• Oral prednisolone or parenteral hydrocortisone:
  • Steroids are an important adjunctive therapy for patients with moderate to severe infections associated with HIV infection.
  • Steroids are usually given in high dosage for 5-7 days and then the dose is reduced and continued for a further 2 weeks.
  • Steroid treatment should be started at the same time as the antimicrobial therapy and withdrawn before antimicrobial treatment is complete.

• Prophylaxis against pneumocystis pneumonia should be considered for:
  • All patients with a history of the pneumocystis infection.
  • Severely immunocompromised patients.
• Prophylaxis should continue until immunity recovers sufficiently.
• Oral co-trimoxazole by mouth is the drug of choice.
• Intermittent inhalation of pentamidine isetionate is used for patients unable to tolerate co-trimoxazole but it doesn't suppress extrapulmonary pneumocystosis.
• Dapsone and atovaquone have also been used for prophylaxis.
• Patients (particularly children) who start highly active antiretroviral therapy (HAART) and attain low HIV viral load and improved CD4 counts may have prophylactic therapy safely discontinued.^5,6

• Respiratory failure
• Acute respiratory distress syndrome
• Worsening of condition after starting therapy
• Pulmonary cyst formation
• Pneumothorax
• Haematogenous spread
• Extrapulmonary infection (typically affects bone marrow, liver, spleen, lymph nodes, gut and eyes)

Mortality is about 10–20% in mild to moderate cases, rising to 40–50% in patients who require artificial ventilation.