Pneumonia in Immunocompromised Patients
(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. 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 infection, such as pulmonary hemorrhage, pulmonary edema, radiation injury, pulmonary toxicity due to cytotoxic drugs, and tumor infiltrates.
Pneumonia in Immunocompromised Patients
|
Immune System Defect |
Disorders Or Therapy Associated With Defect* |
Likely Pathogens |
Defective PMNs |
||
|
Neutropenia |
Acute leukemia, aplastic anemia, cancer chemotherapy |
Gram-negative bacteria Staphylococcus aureus Aspergillus Candida |
|
Defective chemotaxis |
S. aureus Gram-negative aerobes |
|
|
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 |
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. Many disorders cause multiple defects. |
||
|
PMN = polymorphonuclear leukocytes. |
||
Symptoms and Signs
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.
Diagnosis
Chest x-ray and assessment of oxygenation (usually by pulse oximetry) are done in immunocompromised patients with respiratory symptoms, 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.
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, PCR for cytomegalovirus in a transplant patient or in a patient with AIDS). If signs, symptoms, or risk factors for Aspergillus infection are present, serum galactomannan assay should be done.
Optimally, a firm diagnosis is made with induced sputum, bronchoscopy, or both, especially in patients with mild pneumonia, severe defects in immune function, or failure to respond to broad-spectrum antibiotics.
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, tumor, a cytotoxic drug reaction, or radiation injury.
X-rays showing localized consolidation usually indicate an infection involving bacteria, mycobacteria, fungi, or Nocardia species. 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, and > 80% of AIDS patients have this infection at some time if prophylaxis is not given. Patients with HIV infection become vulnerable to P. jirovecii pneumonia when the CD4+ T cell count is <200/microL.
Treatment
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
Therapies to enhance immune system function are indicated for the prevention of pneumonia in immunocompromised patients. For example, patients with chemotherapy-induced neutropenia should receive granulocyte-colony stimulating factor (G-CSF, or filgrastim), and patients with hypogammaglobulinemia due to an inherited or acquired disease (eg, multiple myeloma, leukemia) should receive IV immune globulin.
Patients with HIV and CD4+ T lymphocyte count < 200/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 sputum testing, ideally with induced or bronchoscopically obtained sample.
-
Begin with broad-spectrum antimicrobial therapy.
