Author : Laurence Huang, M.D. Professor of Medicine University of California San Francisco Chief, HIV/AIDS Chest Clinic San Francisco General Hospital

2008-07-28

HIV/AIDS-Associated Pneumonias

Bacterial pneumonia, Pneumocystis pneumonia (PCP), and Tuberculosis (TB)

Pneumonia is a frequent complication of human immunodeficiency virus (HIV) infection and may be a sign of acquired immune deficiency syndrome (AIDS) in persons with HIV. This article describes the principal pneumonias that are associated with HIV/AIDS. The article describes risk factors for the main pneumonias, their presenting symptoms and signs, typical laboratory abnormalities, and chest X-ray findings. It provides a description of common laboratory tests and diagnostic procedures that are used to evaluate a person with suspected HIV-associated pneumonia, as well as recommended treatment and prevention regimens.

Introduction

Pneumonia is an inflammatory process in the lungs. Usually, pneumonia is caused by infectious micro-organisms such as bacteria, mycobacteria, fungi, viruses, and protozoa, but it also can result from non-infectious processes such as chemical or physical injury to the lungs (aspiration pneumonia). In this article, “pneumonia” will refer specifically to infectious causes of pneumonia. Persons with HIV infection are at greater risk for developing most infectious pneumonias than persons without HIV. Thus, these pneumonias are considered to be HIV/AIDS-associated.

What are the principal HIV/AIDS-associated pneumonias?

The principal HIV/AIDS-associated pneumonias are bacterial pneumonia, Pneumocystis pneumonia (PCP), tuberculosis (TB) and, in certain geographic regions, pneumonias due to endemic fungi (fungi that are found exclusively in a particular geographic region) (Table 1). Occasionally, viruses and protozoa cause pneumonia. In most studies of pneumonia in persons with HIV/AIDS, bacterial pneumonia, PCP, and TB account for the majority of pneumonias.  

Bacterial pneumonia: While bacterial pneumonia does occur in people with a healthy immune system (immunocompetent), the incidence of bacterial pneumonia is significantly higher among persons with HIV infection. (1) In the United States, bacterial pneumonia is the most frequent HIV-associated pneumonia. In fact, bacterial pneumonia may be the first perceptible sign of underlying HIV infection and can occur at any stage of HIV disease and at any CD4 cell count (a CD4 cell is a type of white blood cell that is important in the immune system). Recurrent bacterial pneumonia (defined as two or more episodes within a 12-month period) is an AIDS-defining condition http://www.cdc.gov/MMWR/preview/MMWRhtml/00018871.htm). (2)

As is the case for immunocompetent persons, Streptococcus pneumoniae and Haemophilus species are the major causes of bacterial pneumonias in persons with HIV infection. Two other pathogens – Pseudomonas aeruginosa and Staphylococcus aureus – appear with an increased frequency in persons with HIV infection than they do in immunocompetent persons. In addition, the increasing prevalence of drug-resistant bacteria, including drug-resistant Streptococcus pneumoniae (DRSP) and methicillin-resistant Staphylococcus aureus (MRSA) are important concerns in persons with HIV infection.

Pneumocystis pneumonia (PCP): Prior to the HIV/AIDS epidemic, PCP was a rare cause of pneumonia, occurring primarily in persons whose immune systems were compromised (immunocompromised) from hematologic malignancy (e.g., leukemia, lymphoma), primary immunodeficiency (children), organ transplantation, and chemotherapy for cancer. In 1981, PCP was one of the diseases that signaled the onset of the HIV/AIDS epidemic in the United States. Throughout much of the epidemic, PCP was the leading AIDS-defining opportunistic infection and the most frequent opportunistic infection among persons with HIV/AIDS. In association with the use of antiretroviral medications to treat underlying HIV infection and of preventative therapy (prophylaxis) against Pneumocystis, the incidence of PCP has decreased. However, PCP remains an important cause of disease and death in persons with HIV infection and our understanding of it is incomplete. In addition, there are unanswered questions regarding potential drug resistance to the first-line recommended PCP treatment and prophylaxis medication, trimethoprim-sulfamethoxazole.

 

PCP in humans is caused by the fungal organism, Pneumocystis jirovecii (formerly P. carinii). In approximately 20-25% of cases in the U.S., PCP is the first perceptible sign of underlying HIV infection. PCP is an AIDS-defining condition and, prior to the 1993 U.S. Centers for Disease Control and Prevention (CDC) Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS among Adolescents and Adults, PCP was the AIDS-defining condition for over 40% of new AIDS cases annually.

 

Tuberculosis (TB): TB is caused predominantly by Mycobacterium tuberculosis and, less frequently, by other members of the M. tuberculosis complex. Worldwide, TB is the dominant HIV/AIDS-associated pneumonia. It is estimated that one-third of the world’s population is infected with M. tuberculosis and that the regions of the world that have the highest numbers of persons living with HIV/AIDS are also the regions with the greatest numbers of persons infected with M. tuberculosis. In the United States, the annual number of TB cases has declined, but the proportion of cases among foreign-born persons has increased.

 

Mycobacterium Tuberculosis electron micrograph. CDC

While TB occurs in immunocompetent persons, the incidence of TB is significantly higher among persons with HIV infection. TB may be the first perceptible sign of underlying HIV infection and can occur at any stage of HIV disease and at any CD4 cell count. The presence of HIV infection increases the probability that a person who is latently infected with M. tuberculosis will progress to active TB and thus TB is an AIDS-defining condition http://www.cdc.gov/MMWR/preview/MMWRhtml/00018871.htm). (2)

TB is transmitted from person to person via airborne droplets that contain M. tuberculosis. In a person with TB, these droplets are typically generated through coughing and a number of factors influence whether an individual who is exposed to a person with TB will become infected with M. tuberculosis. Once infected, a person’s risk of progressing to active TB (e.g., pneumonia) depends in part on their underlying immune status. Among immunocompetent persons, infection with M. tuberculosis is asymptomatic in an estimated 90% of cases, resulting in latent tuberculosis infection (LTBI), a state in which dormant mycobacteria with the potential to cause future disease persist in the body for life. In these people, the lifetime risk of progressing from LTBI to active TB is approximately 10%. In contrast, people with HIV infection are at an increased risk of progressing from LTBI to active TB at an estimated rate of approximately 5%–10% per year.

 

What are the risk factors for pneumonia?

In general, the CD4 cell count is an excellent indicator of the risk of opportunistic infection, including pneumonia, in an individual with HIV infection (Table 2). (3) As described previously, persons with HIV infection can develop bacterial pneumonia and TB at any CD4 cell count. However, the incidence of both pneumonias increases progressively as the CD4 cell count decreases. PCP and pneumonia caused by the fungus Cryptococcus neoformans typically occur in persons with a CD4 cell count below 200 cells/μL (or a CD4% below 14%). When the CD4 cell count is below 200 cells/μL, persons with bacterial pneumonia often have accompanying bacteremia (presence of bacteria in the bloodstream) and those with TB often have disseminated disease (disease that has spread throughout the body). Bacterial pneumonia due to Pseudomonas aeruginosa usually occurs in persons with a CD4 cell count below 100 cells/μL. Lastly, diseases caused by endemic fungi (Histoplasma capsulatum, Coccidioides immitis), non endemic fungi (Aspergillus fumigatus and other Aspergillus species), Cytomegalovirus (CMV), and nontuberculous mycobacteria (Mycobacterium avium complex, MAC) occur at CD4 cell counts below 50 cells/μL. These latter diseases are less common in the current era but when they do occur they are often disseminated throughout the body and are still associated with a high mortality.

Injection drug use and cigarette smoking are both associated with an increased risk for bacterial pneumonia. (1) Exposure to another person with TB is a risk factor for infection with Mycobacterium tuberculosis and persons with HIV infection are at greater risk of progressing from latent tuberculosis infection (LTBI) to active TB. (3) Environmental exposure to H. capsulatum or C. immitis, typically through activities in an endemic area that disturb soil containing the fungus, is a risk factor for these infections. (3)

Prior bacterial pneumonia and prior PCP are risk factors for recurrent disease. (3) Persons with oral candidiasis (a fungal infection in the mouth) are also at an increased risk for PCP. (3) Persons with neutropenia (a low number of neutrophils, cells that help the body defend itself against certain infections) are at increased risk for bacterial infections and fungal infections such as those caused by Aspergillus species.

What are the symptoms of pneumonia?

In general, the cardinal symptoms of pneumonia are fever, cough, and breathlessness or shortness of breath (dyspnea). The duration and characteristics of these symptoms differ among the major pneumonias and can be used to rank the probability of these pneumonias in a given person.
For example, persons with bacterial pneumonia typically present with a short duration of symptoms (three to five days) and a cough that is productive of pus-containing (purulent) sputum (matter coughed up from the lungs). These persons may also present with chills or rigors and pleurisy (chest pain during breathing). In contrast, persons with PCP usually present with a longer duration of symptoms (two to four weeks) and a dry, non-productive cough. Similarly, persons with TB present with a longer duration of symptoms, but also frequently report constitutional complaints such as night sweats, anorexia (loss of appetite), and weight loss. Thus, bacterial pneumonia would be the most likely diagnosis in a person with 3 days of fever, cough productive of purulent sputum, dyspnea, and pleurisy and a compatible chest radiograph. Persons who present with a mixture of these symptoms or persons whose symptoms change characteristics (for example, an initially non-productive cough that subsequently becomes productive of purulent sputum) may have pneumonia from more than one cause. Persons with HIV infection, perhaps more than any other underlying disease, appear to present with more than one concurrent illness. Although precise data on the frequency of dual pneumonias in persons with HIV infection are scarce, these data and clinical experience indicate that this occurs in approximately 10% of cases.  

What are the clinical signs of pneumonia?

Persons with pneumonia typically have a fever (oral temperature greater than 37.5°C or 99.5°F). They may have tachycardia (heart rate greater than 100 beats per minute) and tachypnea (respiratory rate greater than 20 breaths per minute). Persons with bacterial pneumonia and accompanying septicemia (infection that has spread into the bloodstream) may have hypotension (abnormally low blood pressure). Pulse oximetry (a non-invasive method for measuring the level of oxygen in the arteries [arterial oxygen saturation] or percentage of hemoglobin molecules bound with oxygen molecules) provides an estimate of the severity of pneumonia. Although persons with mild pneumonia may have a normal arterial oxygen saturation (greater than 94%), most persons with pneumonia will have a low arterial oxygen saturation at rest that frequently decreases further upon exertion. In particular, persons with PCP characteristically have a decrease in their arterial oxygen saturation by 3-5% upon exertion. Persons with severe pneumonia will generally appear ill and in respiratory distress (labored breathing, inability to speak using full sentences). They may have cyanosis (a bluish or purplish discoloration of the skin that is due to insufficient oxygenation of the blood). The lung examination is usually abnormal in persons with pneumonia. One exception to this rule is PCP where up to 50% of persons with PCP may have lung examinations that fail to reveal any abnormalities.  

What laboratory tests might my doctor order?

Depending on a host of factors that include CD4 cell count, symptoms and signs, and an assessment of the probability of pneumonia and its severity, clinicians may order a variety of laboratory tests (tests that may help suggest a particular pneumonia).

Chest radiograph (X-ray)

The X-ray or chest radiograph is the cornerstone of the evaluation of suspected pneumonia. In most cases, clinicians will obtain frontal (PA or posteroanterior) and lateral views of the chest. If abnormalities are seen, ideally the chest radiograph will be compared with any prior radiographs to determine whether the noted abnormalities are new or old and, if old, whether they have changed or are stable (unchanged).

Persons with bacterial pneumonia will present with an abnormal chest radiograph. Usually, the abnormality is on one side; abnormalities on both sides suggest a more severe pneumonia. Most often, the chest radiograph reveals an abnormality that is consolidated on one-side, in a specific area of the lung (Figure 1). Occasionally, the radiograph also reveals a pleural effusion (excessive fluid in the space that surrounds the lung).

Persons with mild PCP occasionally may present with a normal chest radiograph. Characteristically, however, the radiograph reveals abnormalities on both sides. Most often, abnormalities contain symmetric, fine reticular or granular opacities (Figure 2). Occasionally, cysts or pneumatoceles (thin-walled, air-filled spaces that are located within the lung) are seen. Pleural effusions are rarely due to PCP.

Persons with disseminated TB may present with a normal chest radiograph. Pulmonary TB in persons with HIV infection can present with a variety of radiographic abnormalities, depending in part on the person’s CD4 cell count. In persons with a high CD4 cell count (i.e., CD4 greater than 400 cells/μL), the characteristic radiograph reveals upper lung zone abnormalities and frequently, cavitation (the presence of thick-walled, irregularly margined, air-filled spaces that are located within the lung) (Figure 3). In contrast, in persons with a low CD4 cell count (i.e., CD4 less than 200 cells/μL), middle and/or lower lung zone abnormalities (Figure 4) or diffuse abnormalities are as frequent as upper lung zone abnormalities and cavitation is less frequent. In addition, a miliary pattern (innumerable tiny, 1-5 mm sized nodules throughout the chest radiograph) (Figure 5) and intrathoracic lymphadenopathy (enlargement of the lymph nodes within the lung or thorax) are more common in persons with a low CD4 cell count. The chest radiograph may also reveal a pleural effusion.

White blood cell (WBC) count
The white blood cell (WBC) count measures the number of leukocytes in the blood. Leukocytes are cells that help the body defend itself against many infections. Thus, in persons with pneumonia,                       especially bacterial pneumonia, the WBC count may be elevated. Arterial oxygen saturation and arterial

Blood gas analysis

Persons with mild pneumonia may have a normal arterial oxygen saturation (greater than 94%), but most will have a low arterial oxygen saturation at rest that frequently decreases further upon exertion. People who have a low arterial oxygen saturation may undergo additional testing with an arterial blood gas (ABG).

An ABG is an invasive procedure whereby blood is obtained from an artery, most often the radial   artery, located at the wrist. The resulting arterial blood is sent for analysis of a person’s pH and partial pressures of carbon dioxide (PaCO2) and oxygen (PaO2). Most persons with pneumonia will have a low PaO2 and will be short of breath. These people typically require supplemental oxygen to raise their PaO2 and relieve their symptoms.  

What diagnostic tests might my doctor order?

There are a variety of diagnostic procedures and microbiologic tests that might be obtained in the evaluation of suspected pneumonia in a person with HIV infection. Which procedures might be obtained and which tests might be performed depend on the specific pneumonia being evaluated and the severity of that pneumonia.                     Sputum examination and culture                  Persons with bacterial pneumonia typically have a productive cough. When they spontaneously                         cough up sputum, it may be collected and sent to the laboratory for Gram’s stain (a method for                         staining specimens and then examining the stained specimen under a microscope to identify                                 possible bacterial causes of infection) and bacterial culture. If bacteria are identified, testing will be                  done to determine which antibiotics the bacteria are susceptible to and to which ones they may                         be resistant.  

Similarly, persons with TB often have a productive cough; occasionally the cough produces sputum that is blood-tinged or has highly visible bright, red blood. In the case of suspected TB, sputum specimens will be collected over two or three days, preferably the first morning specimen each day, and sent to the laboratory for acid-fast bacillus (AFB) stain and mycobacterial culture. If M. tuberculosis is identified in culture (often requiring a few weeks), testing will be done to determine which anti-tuberculous medications the mycobacteria are susceptible to and to which ones they may be resistant.

 

M. tuberculosis nucleic acid amplification tests or direct amplification tests can be performed directly on clinical specimens such as sputum. Typically, these tests are performed on persons whose AFB smear was positive. A positive nucleic acid amplification test in a person who is AFB smear-positive indicates TB.

 

In contrast to bacterial pneumonia and TB, persons with PCP typically have a non-productive cough. In these persons, clinicians may induce sputum production by having the person inhale hypertonic saline solution that has been reduced to a fine, aerosol spray.

 

Fungal pneumonias can occasionally be diagnosed by sputum examination and culture, including those due to Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. Pneumonia due to Toxoplasma gondii and Strongyloides stercoralis can also occasionally be diagnosed by sputum examination. However, the diagnosis of invasive pulmonary aspergillosis typically requires demonstration of the fungus in lung tissue specimens obtained from biopsy. Similarly, the diagnosis of CMV pneumonia typically requires demonstration of the viral inclusions in lung tissue specimens obtained from a biopsy.

Blood cultures

Streptococcus pneumoniae is the most frequent cause of bacterial pneumonia and pneumococcal pneumonia is often accompanied by bacteremia. Bacteremia occurs especially when the CD4 cell count is below 200 cells/μL. Thus, blood cultures may be collected in cases of suspected bacterial pneumonia. If bacteria are identified in culture, antibiotic susceptibility testing can be done.

Similarly, TB is often accompanied by mycobacteremia, especially when the CD4 cell count is below 200 cells/μL. The probability of disseminated TB is also increased when the CD4 cell count is below 200 cells/μL. Thus, mycobacterial blood cultures may be collected in these cases. If M. tuberculosis is identified in culture, susceptibility testing can be done.

At present, Pneumocystis jirovecii cannot be cultured. However, other fungi such as Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis can be cultured. Thus, fungal blood cultures may be collected when these pneumonias are suspected.

                 Serology                 The serum cryptococcal antigen (sCrAg) is an extremely sensitive and specific test for                   cryptococcemia (the presence of cryptococcus in the bloodstream) and cryptococcal meningitis.The sCrAg assay (test) should be performed on all persons with pneumonia where cryptococcus is a possibility. Persons with a positive sCrAg assay should have an evaluation to determine the extent of disease (e.g., lumbar puncture or “spinal tap” for possible meningitis). However, the sCrAg assay may be negative in HIV-infected patients who have isolated cryptococcal pneumonia (pneumonia that is limited to the lungs). Persons with a negative sCrAg assay but with respiratory complaints or chest radiograph findings should undergo further pulmonary evaluation for possible isolated cryptococcal pneumonia.

The Histoplasma capsulatum polysaccharide antigen test is a sensitive and specific test for the presence of the fungus that causes histoplasmosis. The antigen can be measured in urine, blood and other fluids, including BAL fluid, which is a procedure where saline is squirted into the lungs through a bronchoscope (see below) and then recollected, so it can be tested. At present, the urine test is the most widely used.

The galactomannan assay has been used for the diagnosis of invasive aspergillosis. Galactomannan is a major constituent of Aspergillus cell walls and can be measured in urine, blood and other fluids, including BAL fluid. The precise use of this assay in persons with HIV infection requires additional study.

Bronchoscopy

Bronchoscopy is an invasive procedure performed by a specialist in pulmonary medicine. After administration of topical anesthetic, a bronchoscope is inserted through the mouth (or occasionally the nose) and passed into the trachea and the bronchi. During bronchoscopy, lung samples may be taken, most often by bronchoalveolar lavage (BAL, a procedure where saline is instilled into the lung, then suctioned back into a specimen container) or biopsy (a procedure where forceps are used to remove a small piece of lung tissue). These specimens can then be sent for microscopic examination and culture as described for sputum specimens.

Bronchoscopy with BAL is the gold standard procedure to diagnose PCP. Less commonly, it is used to diagnose bacterial pneumonia or TB. Bronchoscopy with biopsies is a means of obtaining lung tissue to diagnose invasive pulmonary aspergillosis and CMV pneumonia.

Thoracentesis and pleural biopsy

Persons who have evidence of a pleural effusion on their chest radiograph may undergo additional radiographic testing to determine whether the effusion is free-flowing. In such cases, a thoracentesis may be performed. Thoracentesis is an invasive procedure where a small needle is inserted into the pleural space and pleural fluid is removed. The fluid can then be sent for microscopic examination and culture as described for sputum specimens. Pleural biopsy (an invasive procedure to obtain a small piece of pleural tissue) may also be performed in persons with a free-flowing pleural effusion.

What are the treatments for HIV-AIDS-associated pneumonia?

The treatment of HIV/AIDS-associated pneumonia depends on the specific pneumonia that is either diagnosed by one of the procedures described above or is based on the person’s clinical presentation (empirical treatment). In general, the treatment of pneumonia in persons with HIV infection is similar or identical to that in persons without HIV. Table 3 provides a list of typical empiric treatment regimens for bacterial pneumonia, TB, and PCP. In the case of bacterial pneumonia, the initial antibiotic regimen may be altered if a specific bacteria is identified and its antibiotic susceptibility is determined.
It is important to note that the duration of treatment also differs for these three pneumonias. Persons with bacterial pneumonia are typically treated for 10-14 days and those with PCP are usually treated for 21 days. Persons with TB are treated for a minimum of six months if the M. tuberculosis is sensitive to the first-line anti-tuberculous medications and longer if the organism is resistant to one or more of these medications. For further details, please refer to the current Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), and HIV Medicine Association (HIVMA)/Infectious Diseases Society of America (IDSA) guidelines, Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents (http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=14&ClassID=4) and the same organizations’ Treating Opportunistic Infections Among HIV-Exposed and Infected Children. (4) (5)  

What can I do to prevent pneumonia?

There are several steps that a person with HIV infection can take to decrease their risk of pneumonia.
First, persons who smoke cigarettes and those who use injection drugs should strongly consider quitting as these behaviors are associated with an increased risk for bacterial pneumonia.
Second, screening for LTBI should be performed annually and after any exposure to a person with TB. Persons who are found to be latently infected with M. tuberculosis should be evaluated for active TB. If no evidence of TB is found, these persons should receive treatment for LTBI, usually the drug isoniazid for 9 months. Third, persons who have a CD4 cell count less than 200 cells/μL (or a CD4% less than 14%) and those with oral candidiasis regardless of their CD4 cell count should receive primary PCP prophylaxis (preventative therapy to prevent a first occurrence), usually with trimethoprim-sulfamethoxazole. Persons who have had PCP should receive secondary PCP prophylaxis (preventative therapy to prevent a recurrence), usually with trimethoprim-sulfamethoxazole as well. Finally, persons with HIV infection can receive vaccines and/or preventive therapy to prevent certain HIV/AIDS-associated pneumonias. (3) For example, the U.S. Public Health Service and Infectious Diseases Society of America (IDSA) guidelines recommend that persons with HIV infection whose CD4 cell count is greater than 200 cells/μL receive the 23-valent pneumococcal polysaccharide vaccine. This vaccine offers protection against 23 types of pneumococcal bacteria (http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-ppv.pdf). The pneumococcal vaccine may also be given to persons with HIV infection whose CD4 cell count is less than 200 cells/μL, but the effectiveness of the pneumococcal vaccine may be diminished. In addition, the guidelines recommend that persons with HIV infection receive an annual flu vaccine. For further details, please refer to the current U.S. Public Health Service and Infectious Diseases Society of America (IDSA) guidelines, Guidelines for the Prevention of Opportunistic Infections Among HIV-Infected Persons (http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=13&ClassID=4). (3)  

Conclusion

Persons with HIV infection are at greater risk for developing most infectious pneumonias than persons without HIV. If indicated by the person’s immune  (i.e., CD4 cell count) and virologic (i.e., plasma HIV RNA or “viral load”) status, strict adherence to antiretroviral medications and PCP prophylaxis, receipt of the 23-valent pneumococcal vaccine, and regular screening for LTBI offer the best hope for prevention of the most common HIV/AIDS-associated pneumonias. Those persons who develop symptoms that may indicate possible pneumonia should seek prompt medical attention so that the appropriate laboratory tests and diagnostic procedures may be performed and the appropriate treatment may be initiated.  

More Information

Web Resources Department of Health and Human Services AIDS Info: http://aidsinfo.nih.gov/
Department of Health and Human Services Centers for Disease Control and Prevention (HIV/AIDS): http://www.cdc.gov/hiv/
Department of Health and Human Services Centers for Disease Control and Prevention (Global HIV/AIDS): http://www.cdc.gov/nchstp/od/gap/default.html
The National Institutes of Health Office of AIDS Research (OAR): http://www.oar.nih.gov/
University of California San Francisco HIV InSite: http://hivinsite.ucsf.edu/
Books
Raphael Dolin, Henry Masur, and Michael Saag. AIDS Therapy. 3^rd Edition.
Peter Walzer and Melanie T. Cushion. Pneumocystis Pneumonia. 3^rd Edition.
Mario C. Raviglione. Reichman and Hershfield’s Tuberculosis: A Comprehensive, International Approach. 3^rd Edition.
 

References

1.         Hirschtick RE, Glassroth J, Jordan MC, Wilcosky TC, Wallace JM, Kvale PA, Markowitz N, Rosen MJ, Mangura BT, Hopewell PC. Bacterial pneumonia in persons infected with the human immunodeficiency virus. Pulmonary Complications of HIV Infection Study Group. N Engl J Med 1995;333(13):845-51.
2.         Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992;41(RR-17):1-19.
3.         Kaplan JE, Masur H, Holmes KK. Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep 2002;51(RR-8):1-52.
4.         Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep 2004;53(RR-15):1-112.
5.         Mofenson LM, Oleske J, Serchuck L, Van Dyke R, Wilfert C. Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Recomm Rep 2004;53(RR-14):1-92.

Table 1. HIV/AIDS-associated Pneumonias

Bacteria

Streptococcus pneumoniae

Haemophilus influenzae and other Haemophilus

Staphylococcus aureus

Pseudomonas aeruginosa

Klebsiella pneumoniae

Rhodococcus equi

Mycobacteria

Mycobacterium tuberculosis

Mycobacterium kansasii

Mycobacterium avium complex (MAC)a

Other nontuberculous mycobacteria

Fungi

Pneumocystis jirovecii (formerly carinii)

Cryptococcus neoformans

Histoplasma capsulatum

Coccidioides immitis

Penicillium marneffei

Aspergillus fumigatus and other Aspergillus species

Viruses

Cytomegalovirus (CMV)a

Protozoa

Toxoplasma gondii

Strongyloides stercoralis

aCytomegalovirus (CMV) and Mycobacterium avium complex (MAC) are rarely the cause of pulmonary dysfunction in patients with HIV infection regardless of their CD4 cell count.

 
 

Table 2. CD4 Cell Count Ranges for HIV/AIDS-associated Pneumonias

Any CD4 Cell Count

Upper respiratory tract infection

Acute bronchitis/sinusitis

Bacterial pneumonia (most often Streptococcus pneumoniae, Haemophilus spp.)

Mycobacterium tuberculosis pneumonia

CD4 Cell Count < 200 cells/uL

Pneumocystis jirovecii pneumonia (PCP)

Cryptococcus neoformans pneumonia

Bacterial pneumonia accompanied by bacteremia or septicemia

Extrapulmonary or disseminated M. tuberculosis

CD4 Cell Count < 100 cells/uL

Bacterial pneumonia due to Pseudomonas aeruginosa

Toxoplasma gondii pneumonia

CD4 Cell Count < 50 cells/uL

Histoplasma capsulatum: usually associated with disseminated disease

Coccidioides immitis: usually associated with disseminated disease

Aspergillus species (most often A. fumigatus) pneumonia

Cytomegalovirus pneumonia: usually associated with disseminated disease

Mycobacterium avium complex: usually associated with disseminated disease

 
 

Table 3. Selected Empiric Treatment Regimens for Bacterial Pneumonia, Tuberculosis, and Pneumocystis Pneumonia

Bacterial Pneumonia

Outpatient

            Beta-lactam (oral) plus macrolide (oral) antibiotic OR

            Beta-lactam (oral) plus doxycycline (oral) OR

            Respiratory fluoroquinolone (oral)

 

Inpatient

            Beta-lactam (intravenous) plus macrolide (oral) antibiotic OR

            Beta-lactam (intravenous) plus doxycycline (oral) OR

            Respiratory fluoroquinolone (intravenous)

 

Tuberculosis (standard initial therapy consists of 4 drugs plus vitamin B6)

            INH (isoniazid) AND

            Rifampin AND

            Ethambutol AND

            Pyrazinamide

 

Pneumocystis Pneumonia*

Outpatient

            Trimethoprim-sulfamethoxazole (oral) OR

            Trimethoprim (oral) plus dapsone (oral) OR

            Clindamycin (oral) plus primaquine (oral) OR

            Atovaquone (liquid suspension)

 

Inpatient

            Trimethoprim-sulfamethoxazole (intravenous) OR

            Pentamidine (intravenous) OR

            Clindamycin (intravenous) plus primaquine (oral)

* Persons with PCP who have moderate to severe disease should also receive adjunctive corticosteroids (e.g., prednisone)