Pneumonia in immunocompromised patients is often caused by unusual pathogens that otherwise have limited virulence; it may also be caused by the same pathogens that cause pneumonia in immunocompetent patients, but manifests as more severe infection. Symptoms and signs depend on the pathogen and on the conditions compromising the immune system. Diagnosis is based on blood cultures and bronchoscopic sampling of respiratory secretions, sometimes with quantitative cultures. Molecular diagnostics are being increasingly used. Because of the variety of possible pathogens, identifying an etiology early is important. Treatment depends on the immune system defect and the pathogen.
(See also Overview of Pneumonia.)
The potential pathogens in patients with compromised immune system defenses are legion; they include those that cause community-acquired pneumonia as well as unusual pathogens. More than one pathogen may be involved. Likely pathogens depend on the type of defect in immune system defenses (see table Pneumonia in Immunocompromised Patients). However, respiratory symptoms and changes on chest x-rays in immunocompromised patients may be due to various processes other than (or in addition to) infection, such as pulmonary hemorrhage, pulmonary edema, radiation injury, pulmonary toxicity due to cytotoxic or immunotherapy drugs, and tumor infiltrates.
Pneumonia in Immunocompromised Patients
Immune System Defect | Examples of Disorders Or Therapy With Defect* | Likely Pathogens |
|---|---|---|
Defective polymorphonuclear leukocytes | ||
Neutropenia | Acute leukemia, aplastic anemia, cancer chemotherapy | Gram-negative bacteria Staphylococcus aureus Aspergillus Candida |
Defective chemotaxis | S. aureus Gram-negative aerobic bacteria | |
Defective intracellular killing | Chronic granulomatous disease | S. aureus |
Defective alternative pathway | Streptococcus pneumoniae Haemophilus influenzae | |
C5 deficiency | Congenital disorder | S. pneumoniae S. aureus Gram-negative bacteria |
Cell-mediated immunity | ||
T-cell deficiency or dysfunction | Hodgkin lymphoma, cancer chemotherapy, corticosteroid therapy | Mycobacteria Viruses (eg, herpes simplex virus, cytomegalovirus) Strongyloides species Opportunistic fungi (eg, Aspergillus, Mucor, Cryptococcus species Nocardia species Toxoplasma species |
Pneumocystis jirovecii Toxoplasma species Cytomegalovirus Herpes simplex virus Opportunistic fungi (eg, Aspergillus, Mucor, Cryptococcus species) Mycobacteria | ||
Humoral immunodeficiency | ||
B-cell deficiency or dysfunction | Agammaglobulinemia, hematologic malignancies, HIV infection, nephrotic syndrome, impaired splenic function, congenital disorders such as common variable immune deficiency Chemotherapy, biologic therapy, or chimeric antigen receptor-modified T (CAR-T) cell therapy, organ transplantation | S. pneumoniae H. influenzae Neisseria meningitidis |
Selective deficiency: IgA, IgG, IgM | S. pneumoniae H. influenzae | |
Hypogammaglobulinemia | P. jirovecii Cytomegalovirus S. pneumoniae H. influenzae | |
* Examples. Many disorders cause multiple defects. | ||
Symptoms and Signs of Pneumonia in Immunocompromised Patients
Symptoms and signs may be the same as those that occur with community-acquired pneumonia in immunocompetent patients. Symptoms may include malaise, chills, fever, rigor, cough, dyspnea, and chest pain. However, 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.
Pearls & Pitfalls
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Diagnosis of Pneumonia in Immunocompromised Patients
Chest x-ray
Assessment of oxygenation
Sputum induction or bronchoscopy to obtain lower respiratory samples
Blood cultures
Pathogens predicted based on symptoms, x-ray changes, and type of immunodeficiency
Chest x-ray and assessment of oxygenation (usually by pulse oximetry) are done in immunocompromised patients with respiratory symptoms or signs, or fever. If an infiltrate or hypoxemia is present, diagnostic studies should be done. Chest x-ray may be normal in Pneumocystis jirovecii pneumonia, but hypoxia or an increased alveolar-arterial oxygen gradient is usually present. If clinical suspicion of pneumonia is high and the chest x-ray is unrevealing, a chest CT scan should be done.
Sputum testing and blood cultures are done. Sputum testing should include Gram stain, mycobacterial and fungal stains and cultures, and sometimes testing for viruses (eg, polymerase chain reaction for cytomegalovirus in a patient who has had a transplant or in a patient with HIV). If signs, symptoms, or risk factors for Aspergillus infection are present, serum galactomannan assay should be done.
It is important to aggressively pursue a microbiological diagnosis with induced sputum, bronchoscopy, or both, especially in patients with severe defects in immune function or failure to respond to broad-spectrum antibiotics.
Molecular testing that detects pathogen-specific nucleic acids or antigens is being increasingly used to determine the microbial cause.
Pathogen identification
Likely pathogens can often be predicted based on symptoms, x-ray changes, and the type of immunodeficiency. In patients with acute symptoms, the differential diagnosis includes bacterial infection, hemorrhage, pulmonary edema, a leukocyte agglutinin reaction to transfusion of blood products, and pulmonary emboli. An indolent time course is more suggestive of a fungal or mycobacterial infection, an opportunistic viral infection, P. jirovecii pneumonia, a tumor, a cytotoxic drug reaction, or radiation injury.
X-rays showing localized consolidation usually indicate an infection involving bacteria (including Nocardia), mycobacteria, or fungi.
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 species, fungi, or tumor.
Cavitary disease suggests mycobacteria, Nocardia species, fungi, or bacteria, particularly S. aureus.
In organ or bone marrow transplantation recipients with bilateral interstitial pneumonia, the usual cause is cytomegalovirus, or the disease is idiopathic.
A pleural-based consolidation is usually Aspergillus infection.
In patients with acquired immunodeficiency syndrome (AIDS), bilateral pneumonia is usually P. jirovecii pneumonia. About 30% of patients with human immunodeficiency virus (HIV) infection have P. jirovecii pneumonia as the initial AIDS-defining diagnosis. Patients with HIV infection who are not on antiretroviral therapy are at high risk for developing this pneumonia if prophylaxis is not given. Patients with HIV infection become vulnerable to P. jirovecii pneumonia when the CD4+ T cell count is < 200 cells/microL.
Treatment of Pneumonia in Immunocompromised Patients
Broad-spectrum antimicrobial therapy
The antimicrobial therapy depends on the immune system defect and the risk factors for specific pathogens. Consultation with an infectious diseases specialist is usually indicated. In patients with neutropenia, empiric treatment depends on the immune system defect, x-ray findings, and severity of illness. Generally, broad-spectrum antibiotics that are effective against gram-negative bacilli, Staphylococcus aureus, and anaerobes are needed, as for hospital-acquired pneumonia. If patients with conditions other than HIV infection do not improve with 5 days of antibiotic therapy, antifungal therapy is frequently added empirically.
Therapies to enhance immune system function are an important adjunct for the treatment of pneumonia in immunocompromised patients.
Prevention of Pneumonia in Immunocompromised Patients
Patients with HIV and CD4+ T cell count < 200 cells/microL should receive daily prophylactic therapy with trimethoprim/sulfamethoxazole or other appropriate therapy.
Vaccination is also important in these patients. For example, patients at risk of pneumonia with encapsulated bacteria (eg, hypogammaglobulinemia, asplenia) should receive vaccinations against pneumococcus and H. influenzae.
Key Points
Consider typical as well as unusual pathogens in immunocompromised patients who have pneumonia.
If patients have hypoxemia or an abnormal chest x-ray, do further testing, including obtaining lower respiratory samples, either induced or bronchoscopically.
Begin with broad-spectrum antimicrobial therapy.
