Pneumonia in Immunocompromised Patients 

Pneumonia in the immunocompromised host involves infection and inflammation of the lower respiratory tract. Regardless of the reason for altered immune function, pneumonia carries a high mortality rate in immunocompromised patients. Imaging results from Pneumocystis (carinii) jiroveci infection are shown below.^[1]

Immunocompromise, and, consequently, a high risk of pneumonia, is associated with the presence of the following factors:

• Malignancy
• Human immunodeficiency virus (HIV) infection
• Primary immunodeficiencies
• Transplant immunosuppression
• Pregnancy
• Alcoholism
• Cystic fibrosis
• Autoimmune disease
• Neuromuscular disease
• Cognitive dysfunction
• Spinal cord injury
• Burns
• Leukemia
• Lymphoma
• Extreme old or young age
• Solid organ malignancy chemotherapy
• Chronic steroids
• Asplenia
• Diabetes

Complications

Complications of pneumonia in immunocompromised persons can include the following:

• Pneumothorax
• Hypoglycemia (may occur with pentamidine)
• Respiratory failure/ventilatory dependence
• Acute respiratory distress syndrome
• Superinfection
• Pleural effusion
• Empyema
• Death

Many pulmonary pathogens reliably plague a host who has a dysfunctional immune system. Others are encountered more frequently with certain causes of immune suppression. Therefore, the pathophysiology can be appreciated in general and more specific contexts.^[2]

Conceptually, pneumonia susceptibility due to immunosuppression stems from neutrophil defects, immunoglobulin defects, or T-cell defects. The underlying reason for immune suppression may suggest certain pulmonary pathology.

The etiologic agents responsible for pneumonias in immunocompromised patients are often different from those found in immunocompetent patients.

Infectious causes of pneumonia in immunocompromised patients include the following:

• Bacterial organisms
• Coccidioides species
• Cytomegalovirus (CMV)
• Tuberculosis (TB)
• Histoplasma species
• Aspergillus species
• Mycobacterium avium complex (MAC)
• Pneumocystis (carinii) jiroveci (PCP)
• Influenza
• Herpes simplex virus (HSV)
• Varicella-zoster virus (VZV)
• Legionella species
• Nocardia species
• Cryptococcus neoformans
• Mucoraceae species
• Strongyloides species
• Toxoplasma species
• Capnocytophaga species

Noninfectious causes of pneumonia in immunocompromised patients include the following:

• Pulmonary hemorrhage
• Pneumonitis
• Congestive heart failure
• Pulmonary embolism
• Myocardial infarction
• Pneumothorax
• Drug-induced injury
• Radiation-induced injury

For more information, see the following:

• Mycoplasma Pneumonia
• Bacterial Pneumonia
• Viral Pneumonia
• Imaging Pneumocystis Carinii Pneumonia
• Community-Acquired Pneumonia
• Nosocomial Pneumonia
• Ventilator-Associated Pneumonia
• Pneumocystis (carinii) jiroveci Pneumonia
• Fungal Pneumonia
• Aspiration Pneumonia
• Nursing Home Acquired Pneumonia
• Chlamydial Pneumonias
• Lymphocytic Interstitial Pneumonia
• Imaging Typical Bacterial Pneumonia
• Imaging Atypical Bacterial Pneumonia
• Imaging Viral Pneumonia

Patients with human immunodeficiency virus (HIV) are at risk for a number of pulmonary infections. Pneumocystis jiroveci remains the most common opportunistic infection in this group; however, the epidemiology of pulmonary infections among patients with HIV is changing.^[2]

HIV causes dysfunction of cell-mediated, as well as humoral, immunity. CD4 T cells principally help other cells achieve their effector function. As such, at low CD4 levels, a disruption of B-cell differentiation occurs. Impaired B-cell functions, particularly of memory cells, are postulated to account for increased risk of infection.^[3] Even after the initiation of highly active antiretroviral therapy (HAART), patients with HIV have reduced marginal zone B-cell percentages.^[4]

Tuberculosis

HIV is considered to be the greatest risk factor for TB.^[5] Patients with HIV are more likely to develop active tuberculosis (TB) once infected, and they have a higher risk of death from TB. HIV is the most important recognized risk factor for progression from latent to active tuberculosis. (See the image below.)^[6]

Early diagnosis of TB can be difficult because of the lack of specific clinical findings, such as an abnormal chest radiograph or a positive purified protein derivative (PPD) skin test result.

Bacterial pneumonia

The most common bacterial pathogen causing illness in patients with HIV is Streptococcus pneumoniae. Patients infected with this organism develop pneumonia more frequently than do their non-HIV–infected counterparts, and they have a more severe clinical course when they are infected.^[7] Also see Bacterial Pneumonia.

Pneumocystis (carinii) jiroveci pneumonia

Pneumocystis (carinii) jiroveci infection remains the most common opportunistic infection among patients with HIV; however, its epidemiology is changing. Adoption of HAART has resulted in lower frequency of this infection.

Transmission of and infection from P (carinii) jiroveci is incompletely understood. Traditionally, infection in a patient with HIV has been thought to represent the reactivation latent colonization. Now, however, some evidence exists that the epidemiology of this infection is defined on a more local geographic level.^[8] As molecular analysis of P (carinii) jiroveci improves, so will the understanding of the transmission and epidemiology of this opportunistic infection. (See the images below.)

Also see Imaging Pneumocystis Carinii Pneumonia and Pneumocystis (carinii) jiroveci Pneumonia.

Histoplasmosis

For the immunocompetent host, histoplasmosis is frequently asymptomatic. In the setting of HIV, this infection is much more common and frequently progresses to disseminated disease. Immunocompromised persons living in endemic areas are at increased risk of disease.

Spores of the mold phase are inhaled and cause a localized or patchy bronchopneumonia. CD4 lymphocytes normally activate macrophages to control the infection. In patients with HIV and low CD4 counts, the likelihood of developing pulmonary and disseminated histoplasmosis is increased.^[9]

Coccidiomycosis

Coccidiomycosis also can lead to pneumonia. This fungal infection is caused by Coccidioides immitis, an organism endemic to large parts of the southwestern United States.

Spores are inhaled and then ingested by pulmonary macrophages. Impaired cell-mediated immunity in persons with HIV accounts for an increased risk of infection in these patients.^[10] Life-threatening infections have been described in patients both with HIV and impaired cellular immunity.

Cryptococcus

Cryptococcal pneumonia is more severe in patients with HIV. Patients with pulmonary disease frequently progress to disseminated disease.^[11]

Most cases are the result of the reactivation of a latent infection. Recognition and treatment are important, because pulmonary cryptococcus is thought to herald the onset of disseminated disease.

Herpes simplex virus and varicella-zoster virus

The pathophysiology of HSV and VZV infections in the setting of HIV is not well understood. Varicella pneumonia is not a common infection in patients with HIV. Few cases have been reported; these have included primary and reactivation disease.^[12]

Mycobacterium avium complex

Mycobacterium avium complex (MAC) infection refers to infection with either of two nontuberculous mycobacterial species, either M avium or M intracellulare. These infections can occur in non-HIV–infected patients; however, MAC is much more frequently encountered in the setting of HIV.

This infection is thought to represent a recent acquisition of organisms rather than the reactivation of a latent infection.

Staging of HIV-associated pneumonia

A staging system specifically for predicting mortality in HIV-associated pneumonia has been described. This model was developed by using classification tree analysis, and it relies on 3 commonly available clinical variables: neurologic symptoms, respiratory rate more than 25, and serum creatinine level. However, this study has not been subsequently validated in the era of HAART.^[13]

Malignancy

Neutrophil defects, immunoglobulin defects, and T-cell defects are all seen in patients with cancer.

Underlying malignancy itself is a risk factor for subsequent infections,^[14] while leukopenia and lymphopenia are common adverse reactions to chemotherapy.

Primary immunodeficiencies

Patients with primary immunodeficiencies are challenged by a number of pulmonary infections. The spectrum of illnesses they face is largely determined by their underlying immune dysfunction: humoral deficiencies, cellular deficiencies, or combined deficiencies.

Patients with defects of humoral immunity are unable to create functional antibodies. Their complications are characterized by severe, recurrent upper and lower respiratory tract infections.

Cellular deficiencies are rare conditions that affect T-cell development and function. Dysfunction of T cells invariably has an impact on B-cell activity; therefore, most of these conditions manifest as combined deficiencies.

In combined deficiencies, T-cell and B-cell function is disturbed. These patients present not only with recurrent episodes of respiratory syncytial virus (RSV), HSV, VZV, influenza, and other viral respiratory infections, but also with chronic diarrhea and chronic mucocutaneous candidiasis.

Transplant immunosuppression

Solid-organ and bone-marrow transplant patients have a heightened risk of pulmonary infection. Timing since transplantation, use of immunosuppressive medications, and the type of transplant are all important in predicting these complications.

For solid-organ and bone-marrow transplant patients, the time since transplant is a major predictor of infectious complications. Induction regimens are used in the early posttransplant period, while maintenance therapies are later, long-term medication strategies.

In addition, the depth and duration of neutropenia are risk factors for infection in transplant patients.^[15] Risk factors for pulmonary nocardial disease reportedly include the receipt of high-dose steroids, CMV disease in the previous 6 months, and high median calcineurin inhibitor level.^[16]

A variety of antilymphoproliferative agents are used commonly in solid-organ transplantation patients, including cyclosporine, azathioprine, and tacrolimus. Additionally, monoclonal and polyclonal antibodies to hematopoietic antigens are increasingly being used. The full medication history should be available through the patient’s transplant coordinator.

Like solid-organ transplant patients, various antilymphoproliferative agents are used commonly in bone-marrow transplantation patients. Distinguishing between CMV, idiopathic pneumonia syndrome, and graft-versus-host disease is challenging.^[17]

PCP can occur even in patients who are on prophylactic treatment with trimethoprim-sulfamethoxazole.^[18]

Pregnancy

Pregnancy results in immunologic changes, including a decrease in helper-T-cell numbers, a reduction in the activity of natural killer cells, and a decrease in cell-mediated immune function, that predispose patients to infections.^[19] In addition, the elevated serum concentrations of progesterone and 17beta-estradiol observed in the latter half of pregnancy can stimulate the growth and maturation of Coccidioides immitis.^{[20, 21]}

Cardiopulmonary changes that occur as a part of normal pregnancy may result in a diminished capacity to compensate for the effects of respiratory disease.^[22]

Further, a reluctance to perform imaging studies in pregnant patients may lead to delayed detection of pneumonias.

The etiologic agent is not identified in approximately half of cases of community-acquired pneumonia in pregnancy. S pneumoniae and Haemophilus influenzae are the most frequently identified bacterial agents.^[22]

Alcohol consumption

Alcohol consumption affects systemic and pulmonary immune function. Current alcohol use is an independent risk factor for severe community-acquired pneumonia. Additionally, patients who are alcoholics are frequently also smokers. The negative effect of these risk factors for pulmonary infections are additive. Chronic alcohol drinkers also have decreased saliva production, an important component of mucosal defense.^[23]

Patients who are receiving treatment with corticosteroids for alcoholic hepatitis are at increased risk of developing Pneumocystis pneumonia.^[24]

Cystic fibrosis

Patients with cystic fibrosis experience progressive lung disease, which leads to respiratory insufficiency and failure.

In cystic fibrosis, abnormal chloride and sodium transport in the respiratory epithelium results in the development of thick, viscous secretions. Chronic airway obstruction leads to colonization by pathogenic bacteria, including Pseudomonas aeruginosa.^[25]

Autoimmune diseases

Patients with autoimmune diseases, either primary ones or those resulting from immunosuppressive therapies, are at higher risk of infectious pulmonary complications.

In systemic lupus erythematosus (SLE), distinguishing infection from an autoimmune flare is important. Treatment with steroids in the setting of infection could be deleterious. Susceptibility to infections derives from therapeutic and disease-related factors.

Complement deficiencies and elevated Fc gamma III and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels may contribute to increased susceptibility to infection in patients with SLE.^[26] Deficiencies of functional mannose-binding lectin do not appear to be the reason for increased infection burden.^[27]

Low complement, the use of more than 20 mg prednisone daily, and the use of cyclophosphamide in patients with SLE were important risk factors in multivariate analyses.^[28]

Severe manifestations of disease are treated with immunosuppressive therapies.^[26]

In connective tissue diseases, the primary condition and the use of immunosuppressive medications place patients at increased risk. Of 5,411 cases reviewed, 29% of patients developed a serious infection; 24% died from this infection—most reported as bacteremia or pneumonia.^[29]

Neuromuscular disease

Poorly managed secretions and frequent aspiration are risk factors for pneumonitis and pneumonias. Reasons for a breakdown in this component of pulmonary defense can be functional, resulting in an overwhelmed immune system.

Pneumonia is a leading cause of death in persons with neuromuscular disease. Impairment of cough and swallowing mechanisms contributes to an increased risk of pneumonia.^[30] Gastroesophageal reflux is more common, persistent, and severe in patients with cerebral palsy. Kyphoscoliosis secondary to unequal muscle tone leads to restrictive lung function and predisposes to atelectasis.^[31]

Cognitive dysfunction

Drooling, feeding problems, and aspiration place patients with cognitive dysfunction at higher risk of pulmonary infections.^[31]

Spinal cord injury

Muscular weakness from spinal cord injury may contribute to a dysfunctional cough reflex.^[31]

Extremes of age

Older patients may complain of fewer symptoms than younger patients, making the diagnosis more challenging.^{[32, 33]}

Children and infants at risk of RSV infection include those younger than 24 months with chronic lung disease who have required medical therapy within 6 months of RSV season onset, preterm infants born prior to 32 weeks’ gestation, preterm infants born at 32-35 weeks’ gestation with at least 2 additional risk factors, and those with hemodynamically significant heart disease.^[34]

Burn

Complications arise from direct lung injury and from indirect pulmonary effects (eg, decreased lung expansion secondary to circumferential burns).

Bacterial clearance is impaired in patients with inhalational injury. This can result from a variety of causes, including impaired cough, impaired mucociliary action, airway plugging, and impaired alveolar macrophage function.^[35]

Selective oral decontamination in burn patients has been advocated in some burn centers. Reduced oral carriage of organisms responsible for pulmonary infections is speculated to account for a lower frequency of pneumonias in these patients.^[36]

Leukemia

Leukemia itself (primarily chronic lymphocytic leukemia) is characterized by frequent infectious episodes. Patients who are undergoing chemotherapy are additionally at risk for severe neutropenia and subsequent pulmonary infections.^[37]

Lymphoma

When lymphoma compromises airway lumen, secondary postobstructive pneumonias can develop. Patients with lymphoma are often taking steroids, which increase their risk of pulmonary infections.

Solid-organ malignancy chemotherapy

Patients who are undergoing chemotherapy for solid-organ tumors are at increased risk of infections. Pulmonary infections are common.

Steroids

Patients who are taking steroids long term are at higher risk for pulmonary infections.^[38] This includes patients who are taking steroids long term for sarcoidosis; they have the same risk for pulmonary infections as do other chronic steroid users, and they are also at risk for complications from postobstructive infections secondary to compressive granulomas.

The dose and duration of use are predictive of increased risk of pneumonia. Low-dose and short-term use carry minimal additional risk of pneumonia; dosages more than 10 mg/d or cumulatively 700 mg of prednisone increased patients' risk of pulmonary infection.^[39]

Asplenic patients

These patients are at particularly high risk for acquiring infections from encapsulated organisms.^[40] They also have a higher rate of infection from pneumonias overall.^[41]

Hyperglycemia and diabetes

Hyperglycemia and diabetes cause neutrophil dysfunction and are independent predictors of poor outcomes in patients with pneumonia.

HIV

In patients with HIV who are infected with S pneumoniae, the risk of pneumonia is 10-100 times greater than non-HIV infected persons.^[40]

In patients with PCP, risk of infection is strongly correlated with CD4 count. In patients with a CD4 count between 201 and 350, the incidence was 0.5%.^[42]

Transplant immunosuppression

In renal transplant patients with pneumonia, the sources of pneumonia occur at the following rates: bacterial (23%), tuberculosis (20%), fungal (9%), PCP (4%), Nocardia (4%), and viral (2%).^[18]

Bacterial infection is the leading cause of death in single and double lung transplant patients in the first 3 months after transplantation.^[43] CMV is the most common viral cause of morbidity and mortality and usually occurs 1-4 months after transplantation.^[43] Approximately 50% will have infection or disease.^[43] Nocardia has the highest frequency in lung transplant patients.^[16] The incidence of PCP declined with the routine use of prophylaxis.

In heart transplant patients, the overall rate of infections in one 2-year period was 70%, with pneumonia listed as the second most common infection (19%). The etiology of the pneumonias was not described by the authors.^[44] Another study of 34 patients had 28% with pneumonias during the follow-up period: 16% had community-acquired pneumonia, 9% with a fungal etiology, and 3% with hospital-acquired pneumonia. These infections also tended to occur during the first 6 months after transplantation.^[45]

In liver transplant patients, the sources of pneumonia occur at the following rates: bacterial (26%), viral (15%), PCP (11%), and fungal (6%).^[46]

Bone-marrow transplant

Infectious and noninfectious pulmonary complications occur in bone-marrow transplant recipients. Autopsy findings among 63 patients included 96 pulmonary complications. Twenty-eight percent were infectious: bacterial pneumonia (48%), pulmonary aspergillosis (41%), CMV (7%), and Candida bronchopneumonia (4%).^[47] Fungal infections were difficult to diagnose antemortem.^[48]

Extremes of age

Adults older than 85 years were 16 times more likely to die from influenza than were those aged 65-69 year.^[49] Hospitalization rates for influenza are substantially increased in patients older than 65 years.^[50]

Elderly patients have a significantly higher rate of community-acquired pneumonia than do younger patients.^[51] One study found that moxifloxacin was associated with faster clinical recovery from community-acquired pneumonia in elderly patients than was levofloxacin.^[33]

Alcoholism

The frequencies of severe pneumonia (as defined by American Thoracic Society [ATS] criteria), bilateral pneumonia, and multilobar pneumonia are more common among alcoholic patients.^[52]

Asplenia

In asplenic patients, the overall incidence of invasive pneumococcal disease is 500 cases per 100,000 per year.^[40]

Autoimmune diseases

In patients with SLE, the most frequent infection is bacterial community-acquired pneumonia.^[53] Intravenous steroids and immunosuppressants are independent risk factors for infection.^[53]

In one series of patients with SLE, pneumonia was, over the course of 3 years, the third most common infection, behind urinary tract infection and skin/soft-tissue infection. Risk factors for infection were low CH₅₀ levels and the use of more than 20 mg prednisone daily.^[28] The frequency of pulmonary infections has been higher in other published SLE cohorts.^[27]

Sex predilection in pneumococcal disease

An increased male-to-female ratio for pneumococcal disease has been described. This is thought to be related to underlying conditions, such as alcoholism and smoking, which are more common in males.^[40]

Community-acquired pneumonia

A Canadian study found a 13.7% mortality rate in immunocompromised patients with community-acquired pneumonia. Mortality correlated with the etiology of immunosuppression.^[54]

HIV-associated pneumonia

From 1999-2000, the leading cause of death was from PCP.^[55] More than 50% of patients who died were not on or were not adherent to HAART.^[55]

The case-fatality rate in patients with TB is higher in patients co-infected with HIV.^[56]

For community-acquired pneumonia, the in-patient mortality rate is 9.1%.^[13] The clinical staging system predicts mortality: neurologic symptoms, elevated respiratory rate, and elevated creatinine.^[13]

Age-associated pneumonia

Pneumonia is the leading cause of infection-related death in elderly persons.^[51] Patients older than 90 years have twice the pneumonia mortality rate of patients aged 65-69 years.^[57] Elderly persons have a disproportionate rate of intensive care unit (ICU) admission and mechanical ventilation.^[51]

Mortality from influenza and RSV disproportionately affects elderly persons.^[49]

The traditional pneumonia severity index (PSI) may not be applicable to elderly patients; a modified PSI that incorporates performance status has been described.^[58]

Patient history

The underlying cause of immunosuppression is a crucial aspect of the history.

Nonspecific findings may include the following:

• Fever
• Exertional dyspnea, followed by dyspnea at rest with progression of disease
• Cough, most often nonproductive in patients with acquired immunodeficiency disease (AIDS)
• Pleuritic chest pain
• Anorexia and weight loss
• Abdominal pain

Physical examination

Pulmonary findings may be nonspecific or nonexistent in immunocompromised patients.

Findings at physical examination may include the following:

• Fever
• Tachypnea
• Tachycardia or bradycardia
• Rales or crackles
• Rhonchi
• Decreased breath sounds
• Dullness to percussion
• Egophony

The differential diagnosis for pneumonia in immunocompromised patients includes the following:

• Asthma
• Bronchitis
• Chronic Obstructive Pulmonary Disease and Emphysema
• Congestive Heart Failure and Pulmonary Edema
• Pneumonia, Aspiration
• Pneumonia, Bacterial
• Pneumonia, Empyema and Abscess
• Pneumonia, Mycoplasma
• Pneumothorax, Iatrogenic, Spontaneous and Pneumomediastinum
• Tuberculosis

Other disorders to consider include endocarditis and pulmonary embolism.

Laboratory studies that should be obtained include the patient’s white blood cell (WBC) count, arterial blood gas (ABG) level, and lactate dehydrogenase (LDH) level.

Sputum culture, sputum Gram stain, acid-fast bacillus (AFB) smear, and AFB culture should be collected with caution in the emergency department. If there is even a remote suspicion of tuberculosis, these specimens should be obtained after the patient has been placed in isolation.

Blood cultures, despite their low yield and infrequent impact on care, are considered standard of care.^{[59, 60]}

In severe community-acquired pneumonia, urinary antigen testing for Legionella pneumophila and Streptococcus species should be performed early.

Other routine laboratory studies as are clinically indicated.

Chest radiography, shown below, is the initial imaging study. Chest radiographic findings may be normal, or they may show infiltrates with consolidation, peribronchovascular, or nodular lesions. As many as 14% of chest radiographic findings are normal in AIDS patients with pulmonary TB.^[61]

A chest computed tomography (CT) scan, seen below, identifies pneumonic infiltrates not seen on chest radiographs and may facilitate diagnosis days sooner.^[1]

The diagnostic yield from bronchoalveolar lavage (BAL) is high in immunocompromised patients with respiratory complaints.^{[2, 62]}

BAL is rarely performed in the emergency department; CT scanning can facilitate more efficient in-patient evaluation.

The frequent need for invasive diagnostic testing in immunocompromised patients should support early pulmonary consultation on these patients from the emergency department (particularly in transplant recipients).^[1]

CMV immunostaining of BAL specimens is useful in the diagnosis of CMV pneumonitis in immunocompromised patients.^[63]

Some authors have supported obtaining a diffusing capacity of lung for carbon monoxide (DLCO) measurement in HIV-infected patients who have normal findings on chest radiographs, as an algorithm for the evaluation of PCP.^[64]

Diagnostic thoracentesis should be performed on parapneumonic effusions to identify empyema. When the pH of the effusion is less than 7.2, this supports tube thoracostomy for drainage.^{[65, 66]}

Selective use of the polymerase chain reaction (PCR) in suspected TB may be indicated.

PCR testing for Pneumocystis pneumonia in non-HIV–immunocompromised patients shows promise. In patients with a negative result, withdrawal of anti-PCP therapy may be considered.^[67]

PCR or VZV-IgM (immunoglobulin M) testing for VZV pneumonia may be performed.

Selective testing for coccidioidomycosis, with direct examination and culture of respiratory secretions or cerebrospinal fluid (CSF), or by biopsy of suspicious pulmonary or cutaneous lesions (which may reveal characteristic double-contoured spherules with endospores and without budding), may be indicated.

Aspergillus galactomannan antigen testing improves diagnostic yield of invasive pulmonary aspergillosis.^[1]

If feasible, sputum culture in the emergency department could help tailor inpatient antibiotic therapy.^[25]

Lung ultrasonography is an emerging diagnostic modality that aides in the identification of pneumonias and effusions.^{[68, 69, 70]}

Prehospital and emergency department care

Prehospital care consists of the following:

• Oxygen administration
• Establishment of intravenous access
• Oxygen saturation and cardiac monitoring

Emergency department care consists of the following:

• Oxygen administration
• Oxygen saturation and cardiac monitoring
• Empiric antimicrobial therapy
• Chest physiotherapy

A Canadian study that proposed stratifying these patients into “high-risk” and “low-risk” groups based on the etiology of their immunosuppression found that patients in the low-risk group could then be stratified according to the pneumonia severity index (PSI). This application of the PSI has not been validated outside of this study.^[54]

The following specialists may be consulted:

• Pulmonologist and/or critical care specialist
• Infectious disease specialist
• Immunologist in cases of known or suspected primary immunodeficiency

If outpatient management is possible, arrange for follow-up with a primary care practitioner within 24 hours.

The 2 goals of pharmacologic therapy are the eradication of infections and prophylaxis against common pathogens in high-risk patients.^[60]

Inpatient non-ICU treatment

Inpatient, non-ICU treatment consists of a respiratory fluoroquinolone and a beta lactam plus a macrolide

Inpatient ICU treatment

Inpatient ICU treatment consists of a beta lactam plus either azithromycin or fluoroquinolone.

For Pseudomonas infection, use an antipneumococcal, antipseudomonal beta-lactam plus either ciprofloxacin or levofloxacin (750-mg dose) or beta lactam plus an aminoglycoside and azithromycin or a beta lactam plus an aminoglycoside and an antipneumococcal fluoroquinolone.

For community-acquired, methicillin-resistant Staphylococcus aureus infection, add vancomycin or linezolid.

The FDA warns against the concurrent use of linezolid with serotonergic psychiatric drugs, unless indicated for life-threatening or urgent conditions. Linezolid may increase serotonin CNS levels as a result of MAO-A inhibition, increasing the risk of serotonin syndrome.^[71]

General influenza vaccination recommendations for immunocompromised persons

The following groups should receive influenza vaccination^[50] :

• All persons aged 50 years old or older
• Women who will be pregnant during influenza season
• Adults and children who have any condition that can compromise respiratory function or handling of secretions
• Residents of nursing homes or other long-term care facilities
• Adults and children who have immunosuppression from medications or from HIV
• All children aged 6 months to 4 years

Persons in close contact to immunocompromised persons should also be vaccinated, as the immunocompromised person may not have a good response to the flu vaccine.^[50]

MAC in HIV

Treatment consists of weekly azithromycin or daily clarithromycin for patients with CD4 count less than 50.^[72]

Histoplasmosis in HIV

Persons at high risk because of occupational exposure or those who live in a community with a hyperendemic rate are recommended to consider prophylaxis with itraconazole for CD4 counts less than 100.^[73]

Pneumocystis(carinii)jiroveci pneumonia in HIV

Prophylaxis recommendations are different for children younger than 1 year who have HIV; these recommendations are not based on CD4 count.^{[74, 75, 76]} In HIV-infected patients on HAART, PCP prophylaxis can be safely discontinued after the CD4 count has increased to more than 200 for more than 3 months.^[77]

Cystic fibrosis

Research indicates that therapy with azithromycin can be used for persons aged 6 years or older with cystic fibrosis who are chronically infected with P aeruginosa.^[78]

Systemic lupus erythematosus

Pneumococcal and influenza vaccines are recommended.

High-risk infants and children

Children and infants at risk of RSV infection include those younger than 24 months with chronic lung disease who have required medical therapy within 6 months of RSV season onset, preterm infants born prior to 32 weeks’ gestation, preterm infants born at 32-35 weeks’ gestation with at least 2 additional risk factors, and those with hemodynamically significant heart disease. These patients should be considered for immune prophylaxis.^[34]

Chemotherapy

American Society of Clinical Oncology has guidelines on the use of hematopoietic colony-stimulating factors. These chemotherapy regimens have decreased the incidence of febrile neutropenia by more than 40%; however, the guidelines are still controversial. The use of colony-stimulating factors should be made in collaboration with the patient’s treating oncologist and will rarely be indicated in the emergency department. The Infectious Disease Society of America has guidelines on use of antimicrobial medications in neutropenic patients with cancer.

Pneumococcal vaccination

A Cochrane Database of Systematic Reviews article indicates the pneumococcal vaccination does not reduce deaths or hospitalizations from streptococcus; however, there could be a benefit for persons at greatest risk of serious infection.^[79]

PCP prophylaxis in non-HIV immunocompromised patients

A Cochrane Database of Systematic Reviews article states that prophylaxis against PCP could be considered in all patients with hematologic malignancies or who have undergone bone-marrow or solid-organ transplantation.^[80]