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Pneumonia in Immunocompromised Patients


Sanjay Sethi

, MD, University at Buffalo SUNY

Last full review/revision Dec 2020| Content last modified Dec 2020
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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 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. 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 drugs, and tumor infiltrates.


Pneumonia in Immunocompromised Patients

Immune System Defect

Disorders Or Therapy Associated With Defect*

Likely Pathogens

Defective PMNs


Acute leukemia, aplastic anemia, cancer chemotherapy

Gram-negative bacteria

Staphylococcus aureus



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


Viruses (eg, herpes simplex virus, cytomegalovirus)

Strongyloides species

Opportunistic fungi (eg, Aspergillus, Mucor, Cryptococcus species

Nocardia species

Toxoplasma species

Pneumocystis jirovecii

Toxoplasma species


Herpes simplex virus

Opportunistic fungi (eg, Aspergillus, Mucor, Cryptococcus species)


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


P. jirovecii


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.

Pearls & Pitfalls

  • Have a high index of suspicion for pneumonia in immunocompromised patients because symptoms can be atypical or muted.


  • 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, 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 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, 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.


  • 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.


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 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.

Drugs Mentioned In This Article

Drug Name Select Trade
Gammagard S/D
No US brand name
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