Pneumonia in immunocompromised patients is often caused by unusual pathogens. Symptoms and signs depend on the pathogen. Diagnosis is based on blood cultures and bronchoscopic sampling of respiratory secretions, sometimes with quantitative cultures. Treatment depends on the host defect and pathogen.

The potential pathogens in patients with compromised defenses are legion. Likely pathogens based on the type of defect in host defenses are listed in Table 7: Pneumonia: Pneumonia in Immunocompromised Patients. However, respiratory symptoms and changes on chest x-rays in immunocompromised patients may be due to various processes other than infection, such as pulmonary hemorrhage, pulmonary edema, radiation injury, pulmonary toxicity due to cytotoxic drugs, and tumor infiltrates.

Table 7
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Pneumonia in Immunocompromised Patients Host Defect Disorders Or Therapy Associated With Defect* Likely Pathogens Defective PMNs Neutropenia Acute leukemia, aplastic anemia, cancer chemotherapy Gram-negative bacteria, Staphylococcus aureus, Aspergillus sp, Candida sp Defective chemotaxis Diabetes mellitus S. aureus, gram-negative aerobes Defective intracellular killing Chronic granulomatous disease S. aureus Defective alternative pathway Sickle cell disease Streptococcus pneumoniae, Haemophilus influenzae C5 deficiency Congenital disorder S. pneumoniae, S. aureus, gram-negative bacteria Cell-mediated immunodeficiency (T-cell deficiency or dysfunction) Hodgkin lymphoma, cancer chemotherapy, corticosteroid therapy Mycobacteria, viruses (herpes simplex virus, cytomegalovirus), Strongyloides sp, opportunistic fungi (Aspergillus, Mucor, Cryptococcus spp), Nocardia sp, Toxoplasma sp AIDS Pneumocystis jirovecii, Toxoplasma sp, cytomegalovirus, herpes simplex virus, opportunistic fungi (Aspergillus, Mucor, Cryptococcus spp), mycobacteria Humoral immunodeficiency (B-cell deficiency or dysfunction) Multiple myeloma, agammaglobulinemia S. pneumoniae, H. influenzae, Neisseria meningitidis Selective deficiency: IgA, IgG, IgM S. pneumoniae, H. influenzae Hypogammaglobulinemia P. jirovecii, cytomegalovirus, S. pneumoniae, H. influenzae *Examples. Pneumonia in Immunocompromised Patients Host Defect Disorders Or Therapy Associated With Defect* Likely Pathogens Defective PMNs Neutropenia Acute leukemia, aplastic anemia, cancer chemotherapy Gram-negative bacteria, Staphylococcus aureus, Aspergillus sp, Candida sp Defective chemotaxis Diabetes mellitus S. aureus, gram-negative aerobes Defective intracellular killing Chronic granulomatous disease S. aureus Defective alternative pathway Sickle cell disease Streptococcus pneumoniae, Haemophilus influenzae C5 deficiency Congenital disorder S. pneumoniae, S. aureus, gram-negative bacteria Cell-mediated immunodeficiency (T-cell deficiency or dysfunction) Hodgkin lymphoma, cancer chemotherapy, corticosteroid therapy Mycobacteria, viruses (herpes simplex virus, cytomegalovirus), Strongyloides sp, opportunistic fungi (Aspergillus, Mucor, Cryptococcus spp), Nocardia sp, Toxoplasma sp AIDS Pneumocystis jirovecii, Toxoplasma sp, cytomegalovirus, herpes simplex virus, opportunistic fungi (Aspergillus, Mucor, Cryptococcus spp), mycobacteria Humoral immunodeficiency (B-cell deficiency or dysfunction) Multiple myeloma, agammaglobulinemia S. pneumoniae, H. influenzae, Neisseria meningitidis Selective deficiency: IgA, IgG, IgM S. pneumoniae, H. influenzae Hypogammaglobulinemia P. jirovecii, cytomegalovirus, S. pneumoniae, H. influenzae *Examples.

Symptoms and Signs

Symptoms and signs may be the same as those found with community-acquired or hospital-acquired pneumonia in immunocompetent patients, though immunocompromised patients may have no fever or respiratory signs and are less likely to have purulent sputum if they are neutropenic. In some patients, the only sign is fever.

Diagnosis

• Chest x-ray
• Assessment of oxygenation
• Induction or bronchoscopy to obtain sputum
• Blood cultures
• Pathogens predicted based on symptoms, x-ray changes, and type of immunodeficiency

An immunocompromised patient with respiratory symptoms, signs, or fever should undergo chest x-ray and assessment of oxygenation (usually by pulse oximetry). If an infiltrate is present, diagnostic studies should include sputum Gram stain and culture and blood cultures. Chest x-ray may be normal in Pneumocystis jirovecii pneumonia, but hypoxia is usually present. Optimally, a firm diagnosis is made with induced sputum, bronchoscopy, or both, especially in patients with chronic pneumonia, atypical presentation, severe defects in immune function, or failure to respond to broad-spectrum antibiotics.

Likely pathogens can often be predicted based on symptoms, x-ray changes, and the type of immunodeficiency. In patients with acute symptoms, likely diagnoses are bacterial infection, hemorrhage, pulmonary edema, a leukocyte agglutinin reaction, and pulmonary emboli. A subacute or chronic presentation is more suggestive of a fungal or mycobacterial infection, an opportunistic viral infection, P. jirovecii pneumonia, tumor, a cytotoxic drug reaction, or radiation injury.

X-rays showing localized consolidation usually indicate an infection involving bacteria, mycobacteria, fungi, or Nocardia sp. A diffuse interstitial pattern is more likely to represent a viral infection, P. jirovecii pneumonia, drug or radiation injury, or pulmonary edema. Diffuse nodular lesions suggest mycobacteria, Nocardia sp, fungi, or tumor. Cavitary disease suggests mycobacteria, Nocardia sp, fungi, or bacteria.

In organ or marrow transplantation recipients with bilateral interstitial pneumonia, the usual cause is cytomegalovirus, or the disease is idiopathic. A pleural-based consolidation is usually aspergillosis. In AIDS patients, bilateral pneumonia is usually P. jirovecii pneumonia. About 30% of patients with HIV infection have P. jirovecii pneumonia as the initial AIDS-defining diagnosis, and > 80% of AIDS patients have this infection at some time if prophylaxis is not given (see Human Immunodeficiency Virus (HIV): Prevention of opportunistic infections). Patients with HIV infection become vulnerable to P. jirovecii pneumonia when the CD4⁺ helper cell count is < 200/μL.

Treatment

• Broad-spectrum antimicrobial therapy

In neutropenic patients, empiric treatment depends on the host defect, x-ray, and severity of illness. Generally, broad-spectrum drugs are needed to cover gram-negative bacilli, Staphylococcus aureus, and anaerobes, as for hospital-acquired pneumonia (see Pneumonia: Treatment). If patients with conditions other than HIV do not improve with 5 days of antibiotic therapy, antifungal therapy is frequently added empirically.

Pneumocystis jirovecii Pneumonia

P. jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with HIV and in those receiving systemic corticosteroids. Symptoms include fever, dyspnea, and dry cough. Diagnosis requires demonstration of the organism in an induced sputum specimen or bronchoscopic brushing. Treatment is with antibiotics, usually trimethoprim/sulfamethoxazole or dapsone/trimethoprim, clindamycin/primaquine, atovaquone, or pentamidine. Patients with Pao₂ < 70 mm Hg receive systemic corticosteroids. Prognosis is generally good with timely treatment.

P. jirovecii is a ubiquitous organism transmitted by aerosol route and causes no disease in immunocompetent patients. Patients with HIV infection and CD4+ counts < 200/μL, organ transplant recipients, patients who have hematologic cancers, and patients taking corticosteroids are at risk of developing P. jirovecii pneumonia. Most have fever, dyspnea, and a dry, nonproductive cough that evolves subacutely over several weeks (HIV infection) or acutely over several days (other causes of compromised cell-mediated immunity).

Diagnosis

• Chest x-ray
• Pulse oximetry
• Histopathologic confirmation

Patients should have chest x-ray and assessment of oxygenation by pulse oximetry. The chest x-ray characteristically shows diffuse, bilateral perihilar infiltrates, but 20 to 30% of patients have normal x-rays. However, hypoxemia is often present even when chest x-ray shows no infiltrate; this finding can be an important clue to diagnosis. When pulse oximetry is abnormal, ABGs are often obtained to show severity of hypoxemia (including an increase in the alveolar-arterial O₂ gradient). If obtained, pulmonary function tests show altered diffusing capacity (although this is rarely done as a diagnostic test).

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Confirmation of diagnosis requires histopathologic demonstration of the organism with methenamineSome Trade Names
HIPREX
MANDELAMINE
UREX
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silver, Giemsa, Wright-Giemsa, modified Grocott, Weigert-Gram, or monoclonal antibody stain. Sputum specimens are usually obtained by induced sputum or bronchoscopy. Sensitivity ranges from 30 to 80% for induced sputum and is > 95% for bronchoscopy with bronchoalveolar lavage.

Pneumocystis Pneumonia

Prognosis

Overall mortality for P. jirovecii pneumonia in hospitalized patients is 15 to 20%. Risk factors for death may include previous history of P. jirovecii pneumonia, older age, and, in HIV-infected patients, CD4+ cell count < 50/μL.

Treatment

• Trimethoprim/sulfamethoxazoleSome Trade Names
  BACTRIM
  SEPTRA
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• Corticosteroids if Pao₂ < 70 mm Hg

Treatment is with trimethoprim/sulfamethoxazoleSome Trade Names
BACTRIM
SEPTRA
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(TMP/SMX) 4 to 5 mg/kg IV or po tid for 14 to 21 days. Treatment can be started before diagnosis is confirmed because P. jirovecii cysts persist in the lungs for weeks. Adverse effects of treatment are more common among patients with AIDS and include rash, neutropenia, hepatitis, and fever. Alternative regimens are pentamidineSome Trade Names
NEBUPENT
PENTAM 300
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4 mg/kg IV once/day; atovaquoneSome Trade Names
MEPRON
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750 mg po bid; TMP 5 mg/kg po qid with dapsoneSome Trade Names
ACZONE
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100 mg po once/day; or clindamycinSome Trade Names
CLEOCIN
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300 to 900 mg IV q 6 to 8 h with primaquineSome Trade Names
No US trade name
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base 15 to 30 mg/day po, also for 21 days. The major limitation of pentamidineSome Trade Names
NEBUPENT
PENTAM 300
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is the high frequency of toxic adverse effects, including renal failure, hypotension, and hypoglycemia. Adjunctive therapy with corticosteroids is recommended for patients with a Pao₂ < 70 mm Hg. The suggested regimen is prednisoneSome Trade Names
DELTASONE
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40 mg bid (or its equivalent) for the first 5 days, 40 mg once/day for the next 5 days (or 20 mg bid), and then 20 mg once/day for the duration of treatment.

Prevention

HIV-infected patients who have had P. jirovecii pneumonia or who have a CD4+ count < 200/μL should receive prophylaxis with TMP/SMX 80/400 mg once/day; if this regimen is not tolerated, dapsoneSome Trade Names
ACZONE
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100 mg po once/day or aerosolized pentamidineSome Trade Names
NEBUPENT
PENTAM 300
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300 mg once/month can be used. These prophylactic regimens are also probably indicated for non–HIV-infected patients at risk of P. jirovecii pneumonia.

Last full review/revision May 2008 by John G. Bartlett, MD

Content last modified July 2012