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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.
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
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 jiroveci 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 on the basis of 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, Pneumocystis jiroveci 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. jiroveci 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. jiroveci pneumonia. About 30% of patients with HIV infection have P.
jiroveci 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.
jiroveci pneumonia when the CD4+ helper cell count is < 200/μL.
Treatment
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
jiroveci pneumonia
P.
jiroveci 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.
jiroveci 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 malignancies, and patients taking corticosteroids are at risk of developing P.
jiroveci 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
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).
Confirmation of diagnosis requires histopathologic demonstration of the organism with methenamine 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.
Prognosis
Overall mortality for P.
jiroveci pneumonia in hospitalized patients is 15 to 20%. Risk factors for death may include previous history of P.
jiroveci pneumonia, older age, and, in HIV-infected patients, CD4+ cell count < 50/μL.
Treatment
Treatment is with trimethoprim-sulfamethoxazole (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. jiroveci cysts persist in the lungs for weeks. Adverse effects of treatment are more common in patients with AIDS and include rash, neutropenia, hepatitis, and fever. Alternative regimens are pentamidine 4 mg/kg IV once/day; atovaquone 750 mg po bid; TMP 5 mg/kg po qid with dapsone 100 mg po once/day; or clindamycin 300 to 900 mg IV q 6 to 8 h with primaquine base 15 to 30 mg/day po, also for 21 days. The major limitation of pentamidine 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 prednisone 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. jiroveci 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, dapsone 100 mg po once/day or aerosolized pentamidine 300 mg once/month can be used. These prophylactic regimens are also probably indicated for non–HIV-infected patients at risk of P. jiroveci pneumonia.
Last full review/revision May 2008 by John G. Bartlett, MD
Content last modified May 2008
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