(See also Overview of Pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more .)
The potential pathogens in patients with compromised immune system defenses are legion; they include those that cause community-acquired pneumonia Etiology Community-acquired pneumonia is defined as pneumonia that is acquired outside the hospital. The most commonly identified pathogens are Streptococcus pneumoniae, Haemophilus influenzae... read more 
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 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 Diffuse Alveolar Hemorrhage Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage. There are numerous causes, but autoimmune disorders are most common. Most patients present with dyspnea, cough, hemoptysis... read more 
, pulmonary edema Pulmonary Edema Pulmonary edema is acute, severe left ventricular failure with pulmonary venous hypertension and alveolar flooding. Findings are severe dyspnea, diaphoresis, wheezing, and sometimes blood-tinged... read more 
, radiation injury Focal radiation injury Ionizing radiation injures tissues variably, depending on factors such as radiation dose, rate of exposure, type of radiation, and part of the body exposed. Symptoms may be local (eg, burns)... read more 
, pulmonary toxicity due to cytotoxic or immunotherapy drugs, and tumor infiltrates.
Symptoms and Signs of Pneumonia in Immunocompromised Patients
Symptoms and signs may be the same as those that occur with community-acquired pneumonia Symptoms and Signs Community-acquired pneumonia is defined as pneumonia that is acquired outside the hospital. The most commonly identified pathogens are Streptococcus pneumoniae, Haemophilus influenzae... read more 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 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, 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 Pneumocystis jirovecii Pneumonia Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic... read more 
, but hypoxia or an increased alveolar-arterial oxygen gradient is usually present. If clinical suspicion of pneumonia is high and the chest x-ray shows no or minor abnormalities, 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 transplant patient or in a patient with AIDS). If signs, symptoms, or risk factors for Aspergillus infection Pathophysiology Aspergillosis is an opportunistic infection that usually affects the lower respiratory tract and is caused by inhaling spores of the filamentous fungus Aspergillus, commonly present in... read more 
are present, serum galactomannan assay Diagnosis 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 Pneumocystis jirovecii Pneumonia Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic... read more , 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 Pneumocystis jirovecii Pneumonia Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic... read more . 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 Postexposure prophylaxis (PEP) Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more 
is not given. Patients with HIV infection become vulnerable to P. jirovecii pneumonia when the CD4+ T cell count is < 200/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 Treatment Hospital-acquired pneumonia (HAP) develops at least 48 hours after hospital admission. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant... read more . 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 Prevention Pneumonia in immunocompromised patients is often caused by unusual pathogens but may also be caused by the same pathogens that cause community-acquired pneumonia. Symptoms and signs depend on... read more are an important adjunct for the treatment of pneumonia in immunocompromised patients.
Prevention of Pneumonia in Immunocompromised Patients
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 cell 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 Pneumococcal Vaccine Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more and H. influenzae Haemophilus influenzae Type b (Hib) Vaccine Haemophilus influenzae type b (Hib) vaccines help prevent Haemophilus infections but not infections caused by other strains of H. influenzae bacteria. H. influenzae causes... read more .
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.
