Pneumocystis Pneumonia


Pneumocystis jiroveci pneumonia (previously called Pneumocystis carinii pneumonia, and still abbreviated PCP), is caused by an unusual fungus, P. jiroveci. Many humans appear to be infected in childhood, but clinical illness occurs only in people with advanced immunosuppression, either through new infection or reactivation of latent infection. More than 90% of PCP cases occur in patients with CD4 counts of <200 cells/µL. Cases of PCP in otherwise healthy young men who have sex with men were among the first recognized manifestations of AIDS, in 1981. The organism can affect many organ sites, but pneumonia is by far the most common form of disease. In the United States, the incidence of PCP has declined sharply since the use of prophylaxis and effective antiretroviral therapy (ART) became widespread, but PCP is still many patients' initial presenting opportunistic infection, and it is a significant cause of morbidity and mortality among HIV-infected patients.

S: Subjective

The patient reports fever, shortness of breath, particularly with exertion, nonproductive cough, night sweats, weight loss, or fatigue. Typically, the symptoms worsen over the course of days to weeks. Pleuritic pain and retrosternal pain or burning also may be present. There may be minimal symptoms early in the disease course of PCP.

Ask the patient about fever, fatigue, and weight loss, which may be present for weeks, with gradual worsening of shortness of breath. PCP may present less commonly with acute onset symptoms of fevers, chills, sweats, dyspnea, and cough.

Note: Given the possibility of HIV-associated tuberculosis (TB), patients with cough should be kept in respiratory isolation until TB is ruled out.

O: Objective

Perform a full physical examination, with particular attention to the following:

  • Vital signs, including temperature, heart rate, blood pressure, respiratory rate, oxygen saturation at rest and after exertion (there is often a sharp drop in oxygen saturation with exertion)
  • Appearance
  • Lung examination

Patients may appear relatively well, or acutely ill. Tachypnea may be pronounced, and patients may exhibit such a high respiratory rate (e.g., >30 breaths per minute) that they are unable to speak without stopping frequently to breathe. Chest examination may be normal, or reveal only minimal rales, although coughing is common on deep inspiration. Cyanosis may be present around the mouth, in the nail beds, and on mucous membranes. Cough is either unproductive, or productive of a thin layer of clear or whitish mucus.

A: Assessment

A partial differential diagnosis includes the following:

  • Pneumococcal pneumonia
  • Other bacterial pneumonias
  • TB
  • Influenza Lymphocytic interstitial pneumonitis
  • Bronchitis
  • Cytomegalovirus (CMV) pneumonitis
  • Histoplasmosis
  • Other fungal pneumonia, especially cryptococcosis
  • Pulmonary Kaposi sarcoma
  • Mycobacterium avium complex
  • Asthma, chronic obstructive pulmonary disease
  • Congestive heart failure
  • Pulmonary hypertension

P: Plan

Diagnostic Evaluation

  • CD4 cell count: Check records for a recent CD4 count (CD4 is <200 cells/µL in >90% of PCP cases). Note that a CD4 count obtained in the setting of acute illness (e.g., when the patient presents with pneumonia) may be substantially lower than the usual baseline, and may be difficult to interpret.
  • Pulse oximetry at rest and after exercise: Oxygen desaturation with exercise suggests an abnormal alveolar-arterial O2 gradient (A-a gradient).
  • Arterial blood gas (ABG): Hypoxemia is common, as is elevation in A-a gradient. Generally, PO2 levels and A-a gradient are associated with disease severity. Poorer outcomes are seen with PO2 <70 mm Hg and A-a gradient >35 mm Hg.
  • Lactate dehydrogenase (LDH): Elevated serum LDH (>300-500 IU/L) is common.
  • Chest X-ray: Typically shows bilateral interstitial infiltrates, but atypical patterns with cavitation, lobar infiltrates, nodules, or pneumothorax may occur, and chest X-ray findings may be normal in some cases. Upper-lobe predominance is common if the patient is receiving aerosolized pentamidine for PCP prophylaxis.
  • Thin-section chest computed tomography (CT) scan: May show patchy ground-glass opacities; in a patient with clinical signs or symptoms of PCP, these are suggestive but not diagnostic of PCP.
  • Sputum induction: The patient inhales saline mist to mobilize sputum from the lungs. The respiratory therapist collects expectorated sputum, which is stained and examined for P. jiroveci organisms. This technique is useful because of its noninvasive approach, but it requires an experienced technician, and is not available at all centers. Sensitivity varies widely (10-95%), depending on the expertise level of the staff at a particular center. (If there is any chance that the patient has TB, sputum induction should be performed in a confined space in a negative pressure area or near an exhaust fan vented safely outside, and samples should be sent for acid-fast bacilli [AFB] smear and culture.)
  • Bronchoscopy with bronchoalveolar lavage (BAL): Definitive diagnosis usually can be made through detection of organisms in BAL fluid obtained during bronchoscopy. Sensitivity is >95% at centers with an experienced staff. BAL fluid can be evaluated for bacteria, mycobacteria, and fungi, as well as for P. jiroveci. Polymerase chain reaction (PCR) testing increasingly is used; its specificity has not been well established.
  • Transbronchial biopsy: May be performed if BAL is not diagnostic and if lung disease is progressive despite treatment, to look for diagnoses other than PCP. Open lung biopsy rarely is performed.


Presumptive treatment often is initiated on the basis of clinical presentation, chest X-ray findings, and ABG results, while definitive diagnostic tests are pending. The standard and alternative treatment regimens are shown below. Duration of treatment is 21 days for all regimens.

Trimethoprim-sulfamethoxazole (TMP-SMX, Bactrim, Septra, cotrimoxazole) is the drug of choice, administered IV or PO for 21 days (a typical PO dose is 2 double-strength tablets taken TID). Adverse effects of TMP-SMX (e.g., rash, fever, leukopenia, anemia, gastrointestinal intolerance, hepatotoxicity, hyperkalemia) are common, mostly mild, and usually "treated through" successfully. Patients who have had previous reactions to sulfa drugs also may be desensitized successfully (see chapter Sulfa Desensitization). TMP-SMX requires dosage adjustment for patients with renal insufficiency.

Pentamidine has similar efficacy to TMP-SMX but greater toxicity (nephrotoxicity, pancreatitis, glucose dysregulation, cardiac arrhythmias). It usually is reserved for patients with severe disease who require IV therapy.

Adjunctive corticosteroids

Adjunctive corticosteroids should be given if the patient's PO2 is <70 mm Hg (breathing room air) or the A-a gradient is ≥35 mm Hg. Corticosteroids should be given as early as possible (preferably before or with the first dose of antibiotic therapy) and within 36-72 hours of the start of anti-PCP therapy:

  • Prednisone 40 mg BID days 1-5; 40 mg QD on days 6-10; 20 mg QD on days 11-21. Alternatively, IV methylprednisolone can be given, at 75% of the prednisone dosage.

Moderate to Severe PCP

Preferred therapy

  • TMP-SMX (TMP 15-20 mg/kg/day + SMX 75- 100 mg/kg/day) IV in divided doses Q6H or Q8H (switch to PO after clinical improvement)

Alternative therapy

  • Pentamidine 4 mg/kg IV QD (dosage reduction to 3 mg/kg QD may be needed if toxicities develop)
  • Clindamycin 600 mg IV or 900 mg IV Q8H (or 300 mg PO Q6H or 450 mg PO Q8H) + primaquine* base 30 mg PO QD

Mild to Moderate PCP

Preferred therapy

  • TMP-SMX (TMP 15-20 mg/kg/day + SMX 75- 100 mg/kg/day) PO, in divided doses TID
  • TMP-SMX double-strength (DS), 2 tablets TID

Alternative therapy

  • Dapsone* 100 mg PO QD + TMP 15 mg/kg/day PO in 3 divided doses
  • Clindamycin (300 mg PO Q6H or 450 mg PO Q8H) + primaquine* base 30 mg PO QD
  • Atovaquone 750 mg PO BID with food

* Test for G6PD deficiency before use (most common among patients of African or Mediterranean descent); caution with use in patients with GCPD deficiency.

Other therapy notes

  • Patients started on IV therapy can be switched to a PO treatment regimen to complete the 3-week course when they are afebrile, have improved oxygenation, and are able to take oral medications.
  • For patients not already on ART, ART generally should be started within 2 weeks of initiating treatment for PCP.
  • Paradoxical worsening of PCP resulting from presumed immune reconstitution inflammatory syndrome (see chapter Immune Reconstitution Inflammatory Syndrome) has been reported; monitor patients for worsening symptoms after ART initiation.
  • Consultation with HIV experts is advisable when initiating of ART in the setting of PCP.

Treatment failures

The average time to clinical improvement for hospitalized patients is 4-8 days, so premature change in therapy should be avoided. For patients who fail to improve on appropriate therapy, it is important to exclude other diagnoses, rule out fluid overload, and consult an infectious disease specialist.

Secondary Prophylaxis

Anti-PCP prophylaxis (chronic maintenance therapy) should be given to all patients who have had an episode of PCP. Prophylaxis should be continued for life, unless immune reconstitution occurs as a result of ART and the CD4 count has been >200 cells/µL for more than 3 months.

In patients with stable CD4 count of >200 cells/µL on effective ART, it is recommended that PCP prophylaxis be discontinued because it offers little clinical benefit but may cause drug toxicity, drug interactions, and selection of drug-resistant pathogens, plus it adds to the cost of care and to the patient's pill burden.

If PCP occurred at a CD4 count of >200 cells/µL, it is recommended to continue prophylaxis for life despite immune reconstitution; however, data to support this approach are limited.

Prophylactic therapy


  • TMP-SMX DS, 1 tablet PO QD, or 1 single-strength tablet PO QD


  • TMP-SMX DS: 1 tablet PO TIW (e.g., Monday, Wednesday, Friday)
  • Dapsone* 100 mg PO QD, or 50 mg PO BID
  • Dapsone* 50 mg PO QD + pyrimethamine 50 mg PO once weekly + leucovorin 25 mg PO once weekly
  • Dapsone* 200 mg PO + pyrimethamine 75 mg + leucovorin 25 mg, all once weekly
  • Aerosolized pentamidine 300 mg once monthly, via Respirgard II nebulizer (note: does not prevent toxoplasmosis) (Warning: May increase the risk of extrapulmonary pneumocystosis, pneumothorax, and bronchospasm.)
  • Atovaquone 1,500 mg PO QD (with or without pyrimethamine 25 mg PO QD + leucovorin 10 mg PO QD)

* Use with caution in G6PD deficiency.

Primary Prophylaxis

  • Primary prophylaxis against PCP should be given to all HIV-infected patients with a CD4 count of <200 cells/µL, CD4 percentage of <14%, or a history of oral candidiasis; see chapter Opportunistic Infection Prophylaxis.

Patient Education

  • Patients should be instructed to take all medications exactly as prescribed.
  • Patients should call their health care provider if symptoms worsen.
  • Patients being treated with TMP-SMX or dapsone who develop rash, fever, or other new symptoms should call their provider to be evaluated for a drug reaction.
  • Patients should understand that taking anti-PCP prophylaxis is extremely important for preventing repeat episodes of illness. Patients should not stop taking these medicines without talking with their health care provider, and should not let their supply of medications run out.
  • Patients should be counselled about the importance of ART in restoring immune system function to reduce the likelihood of illness and death from PCP and other OIs.