Pneumocystis pneumonia

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

Introduction

 

pulmonary pneumocystosis due to Pneumocystis carinii (CDC)

Pneumocystis pneumonia (PCP) is caused by the fungal pathogen, Pneumocystis jirovecii (formerly Pneumocystis carinii). PCP is a life-threatening pneumonia (infection of the lungs) that predominantly affects persons with medical conditions that compromise the immune system, especially persons who are infected with human immunodeficiency virus (HIV) and who have the acquired immune deficiency syndrome (AIDS). PCP also affects persons who have primary immunodeficiency (children) and those receiving chemotherapy for cancer or hematologic malignancy (e.g., leukemia, lymphoma), immunosuppressive medications after organ or bone marrow transplantation, and corticosteroids or immunomodulating medications for a variety of medical conditions. Despite significant advances in our understanding of Pneumocystis and PCP, major gaps in our knowledge remain. This article provides a brief history of Pneumocystis and PCP and discusses the ongoing controversy surrounding its nomenclature. The article describes the epidemiology of PCP, its risk factors, presenting symptoms and signs, and the appearance on chest X-rays. It also describes the tests used to diagnose PCP and outlines recommended treatment and prevention regimens.

 

History of Pneumocystis and PCP before the HIV/AIDS epidemic

 

In 1909, Carlos Chagas, a Brazilian physician, discovered that a new protozoan, which he named Trypanosoma cruzi in honor of his mentor, Oswaldo Cruz, was the cause of the severe, life-threatening disease American trypanosomiasis (also referred to as Chagas disease). Chagas described cyst-like organisms in the lungs of the rats and guinea pigs that he had infected with T. cruzi. He mistakenly concluded that these cysts were part of the T. cruzi life cycle when, in fact, the cysts were Pneumocystis. One year later, Antonio Carini, an Italian physician and microbiologist, noted that these cysts were present in some rats infected with T. cruzi, but were absent in others, and therefore he correctly suggested that the cysts were unrelated to trypanosomiasis. Subsequently, Pierre and Marie Delanoë observed the cysts in rats without T. cruzi infection. These observations led the Delanoës to the conclusion that the cyst-like organisms described by Chagas and Carini actually belonged to a new species, which they named Pneumocystis carinii, in honor of Carini. The Delanoës also made the important observations that Pneumocystis infection was limited to the lungs and that infection could be transmitted from mother to newborn rat. Since P. carinii appeared to only infect rodents, it held little scientific interest and faded into temporary obscurity.

 

During and after World War II, P. carinii was discovered to cause pneumonia in humans, and it was identified as the cause of epidemics of interstitial plasma cell pneumonitis affecting premature and malnourished infants. Joseph Vanek and Otto Jirovec were among the European investigators who established the connection between P. carinii and infant pneumonia. Subsequently, Pneumocystis carinii pneumonia (PCP) was also described in the U.S. as an unusual cause of severe pneumonia in infants with primary immune deficiency diseases and in children and adults, virtually all of whom had immunodeficiency due to underlying malignancy, organ transplantation, or immunosuppressive medications. Nevertheless, PCP remained an uncommon cause of pneumonia. Before the HIV/AIDS epidemic, there were fewer than 100 histologically (the diseased tissue viewed under a microscope) confirmed cases of PCP per year reported in the U.S.

 

History of PCP during the HIV/AIDS epidemic

 

In 1981, the description of PCP in 15 previously healthy men who either had sex with other men (MSM) and/or who were injection drug users (IDU) was the precursor to an explosion of cases that signaled the HIV/AIDS epidemic that currently affects an estimated 33-34 million people worldwide. Throughout the epidemic, PCP has been the leading AIDS-defining opportunistic infection in the U.S. PCP was the AIDS-defining diagnosis for 58% of the first 1,000 AIDS cases, either on its own or accompanied by concurrent Kaposi’s sarcoma (an HIV-associated cancer). At its peak, from 1990 to 1993, there were greater than 20,000 cases per year of PCP reported to the Centers for Disease Control and Prevention (CDC) as AIDS-defining diagnoses – and countless more cases occurred in individuals after their diagnosis of AIDS. Among cohorts of persons with HIV infection, PCP was the most frequent serious opportunistic infection seen, and it was estimated that greater than 75% of persons with AIDS developed PCP at least once during their lifetime.

In association with the uses of antiretroviral medications to treat underlying HIV infection and preventative therapy (prophylaxis) against Pneumocystis, the incidence of PCP has decreased. In 1997, the last year that the CDC’s annual HIV/AIDS Surveillance Report included data on specific AIDS-defining diagnoses, there were fewer than 9,500 cases of PCP reported to the CDC. Since PCP was never a reportable disease unless it was an AIDS-defining diagnosis, there are no current national data on PCP in persons with HIV infection http://www.cdc.gov/MMWR/preview/MMWRhtml/00018871.htm).

 

PCP in the present

 

Today, the incidence of HIV-associated PCP has declined dramatically in the U.S., Western Europe, and areas of the world where combination antiretroviral therapy is widely available. However, PCP is increasingly described in Africa, Asia, and Latin America, areas of the world where greater than 90% of the estimated people living with HIV/AIDS reside and where access to combination antiretroviral therapy and even PCP prophylaxis are limited. In these areas, the general absence of specialized medical personnel and equipment to diagnose and manage PCP and the more limited PCP treatment options lead to the extremely high mortality rates reported in many published studies.

 

As new therapies and approaches are developed to treat the spectrum of human disease, new populations of individuals are found to be at risk for PCP. As stated previously, persons without underlying HIV infection but with primary immunodeficiency or persons receiving chemotherapy for cancer or hematologic malignancy (e.g., leukemia, lymphoma), immunosuppressive medications after organ or bone marrow transplantation, and corticosteroids are at increased risk for PCP. To this list can be added persons who receive tumor necrosis factor-α antagonists (medications that block the action of tumor necrosis factor-α) for treatment of an increasing list of medical conditions including psoriasis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and Crohn’s disease. Precise data on the magnitude of the risk for PCP is less clear in these populations and await further study. However, since the numbers of persons in these non-HIV, at-risk populations are growing, this information is urgently needed.

 

What is Pneumocystis?

 

Pneumocystis is a fungus. Originally, it was classified as a protozoan based on its morphologic (structural) features, similarities in host pathology with other protozoa, and the effectiveness of “antiprotozoan” drugs such as trimethoprim-sulfamethoxazole and pentamidine. Subsequently, it has been re-classified as a fungus after molecular studies demonstrated that the organism is genetically more closely related to ascomycetous fungi, such as Saccharomyces cerevisiae, than to protozoa.

 

Pneumocystis is host species-specific. Originally, Pneumocystis was thought to be a single species capable of infecting a wide range of mammalian hosts. Subsequently, laboratory experiments suggest that Pneumocystis isolated from one mammalian species cannot infect a different mammalian species. Thus, humans cannot develop disease after exposure to Pneumocystis from infected animals (e.g., pets).

 

Pneumocystis has been found in every continent except for Antarctica, and it is only found in mammals. Pneumocystis has been found in disparate zoological orders from more than 30 different mammalian hosts. It is believed that every mammalian species has at least one species of Pneumocystis that infects it.

 

Nomenclature. The nomenclature for Pneumocystis is surrounded by controversy, with researchers in the Pneumocystis community in disagreement. This has resulted in inconsistency within the medical literature, with the names P. carinii, P. jiroveci (with one “i”), and P. jirovecii (with two “i”s) all being used to describe the Pneumocystis that infects humans. In recognition of the species-specificity of Pneumocystis, many but not all authorities refer to the Pneumocystis that infects humans as P. jirovecii, in honor of Otto Jirovec, one of the first to describe Pneumocystis in humans. P. carinii now refers to the organism that infects most rodents while P. jiroveci is an incorrect spelling that dates to 1976 when Pneumocystis was still believed to be a protozoan and therefore the International Code of Zoological Nomenclature was used, instead of the International Code of Botanical Nomenclature, which is used for fungi.

 

Where does Pneumocystis jirovecii reside and how is it transmitted?

 

The definitive answers to these questions remain unanswered but data are emerging. As stated previously, Pneumocystis is host species-specific and thus humans cannot develop disease after exposure to infected animals. In the laboratory, lab animals have been shown to be a reservoir for the specific Pneumocystis that infects them and animal-to-animal transmission has been demonstrated to occur via an airborne route. Furthermore, both animals with PCP and animals who are colonized with Pneumocystis (defined as the presence of Pneumocystis in the absence of pneumonia) have been shown to be capable of transmitting the infection to other animals.

 

In clinical studies, emerging data suggests that humans are a reservoir for P. jirovecii. Early serologic studies demonstrated that exposure to Pneumocystis occurs early in life and that the majority of young children have developed antibodies against Pneumocystis by an early age. These studies support the traditional theory that PCP results from reactivation of a latent infection that is acquired early in childhood. Accordingly, there is little reason to implement measures to avoid or minimize exposure to P. jirovecii among at-risk adult populations because such exposure will undoubtedly have occurred already. However, outbreaks of PCP have been described among different populations of immunosuppressed persons and are consistent with person-to-person transmission and a recent exposure causing PCP. Thus, an argument can be made that persons with medical conditions that place them at risk for PCP should avoid close contact with individuals with PCP. However, P. jirovecii can be detected in persons without PCP, suggesting that these persons are colonized with P. jirovecii and may be another reservoir of the organism, capable of transmitting the infection to others. Since there is no current means of detecting which people may be colonized with P. jirovecii, efforts at avoiding close contact with these individuals is likely impossible.

 

What are the risk factors for PCP?

 

Persons with medical conditions that compromise the immune system are at risk for PCP. In most but not all of these persons, the primary immunologic deficiency is in the number or function of T cells (a type of white blood cell that is involved in defending the body against certain infections). Persons with congenital or acquired immunodeficiency and those who require life-long immunosuppressive medications (e.g., after organ transplantation) remain at risk for PCP for life, while those who receive chemotherapy or immunosuppressive medications are at risk for PCP during the period of immunosuppression.

 

Risk factors among persons with HIV infection. PCP is the HIV-identifying diagnosis in a significant proportion of persons with undiagnosed HIV infection. Thus, persons with risk factors for HIV infection (e.g., unprotected sex, injection drug use) should present promptly for medical attention if they develop any symptoms or signs suggestive of PCP (see below). Clinicians should obtain a detailed history of HIV risk behaviors in persons with a clinical and radiographic presentation suggestive of PCP.

 

Among persons with HIV infection, several risk factors for PCP have been defined while other potential risk factors remain speculative. The main risk factors are a CD4 cell count below 200 cells/μL and a history of oropharyngeal candidiasis (thrush) or prior PCP, regardless of CD4 cell count. The CD4 cell count is a strong predictor of a person’s risk for PCP and PCP was perhaps the first disease to document the role of the CD4 count as a tool to assess the risk for the development of opportunistic infection. The U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) guidelines for preventing opportunistic infections recommend that adults or adolescents who are infected with HIV and who have a CD4 cell count less than 200 cells/μL or a history of oropharyngeal candidiasis receive primary Pneumocystis prophylaxis (to prevent a first episode of PCP) (http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=13&ClassID=4). The guidelines also recommend that persons with prior PCP receive secondary prophylaxis (to prevent a second or subsequent episode of PCP). Persons without these specific criteria but who have a CD4 lymphocyte percentage less than14% or a prior AIDS-defining illness should be considered for Pneumocystis prophylaxis. These recommendations also apply to pregnant women who are infected with HIV. Once started, persons should remain on prophylaxis for life, unless their CD4 cell counts increase from less than 200 cells/μL to greater than 200 cells/μL for at least three months as a result of combination antiretroviral therapy.

 

What are the symptoms of PCP?

 

The clinical presentation of PCP in persons with HIV infection differs from the presentation in other immunocompromised persons. In general, persons with HIV infection present with a sub-acute onset and a longer symptom duration than other immunocompromised persons. Studies comparing the clinical presentation of PCP in these two groups have found that persons with HIV infection present with a higher arterial oxygen tension (PaO₂) and a lower alveolar-arterial (A-a) oxygen gradient (two measures of the oxygen in arterial blood) than non-HIV, immunocompromised persons. In addition, persons with HIV infection have significantly greater numbers of Pneumocystis organisms and also significantly fewer neutrophils (a type of white blood cell that is involved in defending the body against certain infections) recovered on bronchoscopy with bronchoalveolar lavage (BAL, which is an invasive procedure used to diagnose PCP).

 

Classically, PCP presents with fever, cough, and shortness of breath on exertion. In persons with HIV/AIDS, symptoms are often subtle at the onset but are gradually progressive and may be present for weeks and occasionally months before diagnosis. The cough is usually dry and non-productive unless a concurrent bacterial infection is present, in which case the cough may be productive of purulent (pus-containing) sputum. The cough may be brought on or worsened by deep breathing and may be accompanied by “chest tightness” that results in a short, rapid breathing pattern. Initially, the shortness of breath is mild and may be downplayed or dismissed by the individual. If undiagnosed and untreated, the shortness of breath will progress until it is present at rest. Fatigue is a frequent complaint whereas chest pain, chills, and night sweats are less frequent complaints. The presence of pleurisy (chest pain that is brought on or worsened by deep breathing or coughing) may be a sign of a pneumothorax (collapse of the lung) and should prompt the person to seek immediate medical attention.

 

What are the clinical signs of PCP?

 

Persons with PCP 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).

 

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 PCP. Although persons with mild PCP may have a normal arterial oxygen saturation (greater than 94%), most persons with PCP 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 PCP 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 may be normal in 50% of persons with PCP. The most characteristic abnormal finding on lung examination is inspiratory crackles.

 

What are the chest x-ray findings of PCP?

 

Classically, PCP presents with bilateral (on both sides), diffuse, and symmetric reticular (interstitial) or granular opacities (Figure 1). Typically, PCP begins with central or perihilar opacities and a middle-lower lung zone predominance. As with the classic radiographic presentation, these opacities are bilateral and symmetric and can progress to diffuse involvement if undiagnosed and untreated. However, PCP can also present with unilateral (on one side), focal, or asymmetric opacities. These chest x-ray appearances are more typical of other pneumonias and may lead to delays in the diagnosis and initiation of appropriate PCP treatment. Occasionally, cysts or pneumatoceles (thin-walled, air-filled spaces that are located within the lung) are seen. These pneumatoceles are associated with an increased risk for pneumothorax (collapse of the lung).

 

PCP can present with a normal chest x-ray. The frequency of a normal chest x-ray in PCP depends in part on when the person presented for medical attention. In persons with suspected PCP who have a normal chest x-ray, a chest high resolution computed tomography (HRCT) may be useful. PCP presents with ground glass opacities on chest HRCT (Figure 2) and the absence of these opacities strongly argues against the presence of PCP.

 

How is PCP diagnosed?

 

At present, there are no blood tests that are specific for PCP. In addition, Pneumocystis cannot be cultured, so the diagnosis of PCP relies on microscopic visualization of the characteristic Pneumocystis cysts and/or trophic forms on stained specimens typically obtained from one of the following diagnostic procedures.

 

Sputum induction. Most persons with PCP have a non-productive cough and thus they may need to have sputum induced in order to diagnose PCP. Sputum induction is a procedure where sputum is induced by the inhalation of a hypertonic saline mist that has been generated by an ultrasonic nebulizer. Sputum induction may be the initial procedure performed in persons with suspected PCP; those with a negative sputum induction may need to undergo a second diagnostic procedure, bronchoscopy.

 

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 (the major breathing passages). 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). Bronchoscopy with BAL is the gold standard procedure to diagnose PCP.

 

What are the treatments for PCP?

 

The standard duration of PCP therapy in persons without HIV infection is 14 days. In persons with HIV infection, the standard duration of PCP therapy is 21 days. The treatment duration was lengthened for persons with HIV infection based upon early relapses seen after 14 days of treatment. These recommended treatment durations are appropriate for most patients. However, patients with severe PCP may require more than 14-21 days of therapy while patients with mild disease may respond to a shorter course of treatment.

 

There are three principles of fundamental importance related to PCP treatment: (1) Prompt initiation of therapy can improve prognosis; (2) Trimethoprim-sulfamethoxazole is the drug of choice for mild, moderate, or severe PCP; (3) Adjunctive corticosteroid therapy improves survival for patients with moderate or severe PCP. The severity of PCP at the time of presentation and initiation of therapy is one of the strongest predictors of outcome. PCP severity is classified by the partial pressure of oxygen (PaO2) and the alveolar-arterial (A-a) oxygen gradient and is measured by arterial blood gas analysis (an invasive procedure whereby blood is obtained from an artery, most often the radial artery, located at the wrist). In general, the greater the severity of PCP at the time that PCP therapy is initiated, the higher the mortality. Thus, persons at risk of PCP should seek medical attention if they develop suggestive symptoms of PCP, even if the symptoms are mild, and clinicians caring for these patients should begin empiric therapy promptly.

 

Trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole is the recommended first-line regimen to treat PCP unless there is a history of a life-threatening adverse reaction to this medication. Trimethoprim-sulfamethoxazole is a fixed-dose combination of two medications, trimethoprim and sulfamethoxazole, and the medication can be given by mouth (via tablet or an oral suspension) or through an intravenous catheter. Trimethoprim-sulfamethoxazole is associated with well recognized toxicities, including fever, rash, pruritus (itching), and gastrointestinal complaints (nausea, vomiting). Rarely, trimethoprim-sulfamethoxazole causes life-threatening reactions, including severe dermatologic reactions, hepatitis (inflammation of the liver), and bone marrow suppression, manifested by anemia (low red blood cell count), neutropenia (low white blood cell count), and/or thrombocytopenia (low platelet count). Persons who develop peeling or blistering of their skin (as in severe sunburn) or right-sided abdominal pain with or without accompanying jaundice (yellowish discoloration of the skin) should seek immediate medical attention.

 

In addition to PCP, trimethoprim-sulfamethoxazole is also used to treat certain infections caused by bacteria. Many of these bacteria have developed resistance to this medication that can be demonstrated using laboratory methods. Although Pneumocystis cannot be cultured and therefore the standard laboratory methods used to detect trimethoprim-sulfamethoxazole resistance cannot be employed, there is some suggestive evidence that Pneumocystis can develop resistance to sulfamethoxazole (the more active of the two drugs) as well as dapsone, another drug used to treat PCP (see below). Sulfa drug (sulfamethoxazole and dapsone) resistance is suggested by the presence of non-synonymous point mutations in the Pneumocystis dihydropteroate synthase (DHPS) gene. DHPS mutations are found especially in patients who have been exposed to sulfa drugs, but it remains unclear whether the reported mutations are clinically important. Published studies are contradictory, with some studies finding a significant association between the present of DHPS mutations and increased mortality or PCP treatment failure and others failing to find an association. The majority of persons with PCP and DHPS mutations who are treated with trimethoprim-sulfamethoxazole respond to this therapy, so this regimen should remain as the first-line therapy, regardless of the presence of DHPS mutations. At present DHPS sequencing to determine whether DHPS mutations are present is an investigational research tool.

 

Pentamidine. Pentamidine has comparable efficacy to trimethoprim-sulfamethoxazole and is an alternative to this medication in persons with moderate to severe PCP. However, this medication must be given through an intravenous catheter for PCP treatment and its use is accompanied by a high frequency of side effects. {Note: Pentamidine can also be given via a nebulizer but this should only be used for prevention and should rarely, if ever, be used for treatment.} The main side effects of intravenous pentamidine include nephrotoxicity (inpairment of kidney function), pancreatitis (inflammation of the pancreas), and hypo (low) or hyper (high) glycemia (levels of glucose). Rarely, intravenous pentamidine causes life-threatening cardiac arrhythmias (abnormal heart rhythm).

Clindamycin plus primaquine. Clindamycin and primaquine are two medications that, when used together, are an effective regimen to treat PCP (if used alone neither medication is effective). Clindamycin can be given by mouth (via capsule or an oral suspension) or through an intravenous catheter; primaquine is available only by mouth (as a tablet). Although the regimen is inconvenient in that two drugs are involved, it is an important alternative for persons with PCP. The main side effects of clindamycin include rash, diarrhea, and gastrointestinal complaints (nausea, vomiting). Persons taking clindamycin who develop abdominal pain, nausea, anorexia (loss of appetite), and profuse watery diarrhea may have a rare but life-threatening complication of clindamycin – pseudomembranous colitis (inflammation of the colon or large intestine) – that can also be seen with other antibiotics and should seek immediate medical attention. The main concern in using primaquine is hemolytic anemia (low red blood cell count due to hemolysis or destruction of red blood cells) in persons who are deficient in glucose-6-phosphate dehydrogenase (G-6-PD) (an inherited disorder with resultant low levels of this enzyme, which is involved in red blood cell metabolism).

 

Trimethoprim plus dapsone. Trimethoprim and dapsone are two medications that, when used together, are an effective regimen to treat PCP (if used alone neither medication is an effective treatment). Trimethoprim and dapsone are an alternative to trimethoprim-sulfamethoxazole in persons with mild to moderate PCP. The efficacy of trimethoprim plus dapsone for mild to moderate PCP is comparable to that of trimethoprim-sulfamethoxazole, and the former may be somewhat better tolerated than the latter. However, a history of life-threatening side effects from trimethoprim-sulfamethoxazole should preclude the use of trimethoprim and dapsone. This regimen is also less convenient than trimethoprim-sulfamethoxazole in that two drugs are involved (trimethoprim is taken three times daily and dapsone is taken once daily). The main concern in using dapsone is hemolytic anemia (low red blood cell count due to hemolysis or destruction of red blood cells) in persons who are deficient in glucose-6-phosphate dehydrogenase (G-6-PD) (an inherited disorder with resultant low levels of this enzyme, which is involved in red blood cell metabolism).

 

Atovaquone. Atovaquone is a potential alternative to trimethoprim-sulfamethoxazole in persons with mild to moderate PCP. Atovaquone is given by mouth as an oral suspension (no intravenous formulation is available). Atovaquone absorption is improved by ingestion with a high-fat meal and decreased in persons with diarrhea. Similar to DHPS mutations and trimethoprim-sulfamethoxazole, mutations in cytochrome b, the target for atovaquone, have been described. Their clinical importance is similarly unknown.

 

Adjunctive corticosteroids. Adjunctive corticosteroids, either with oral prednisone or intravenous solumedrol, are recommended for patients with moderate to severe PCP whose initial room air PO₂ is less than 70 mm Hg or whose alveolar-arterial oxygen gradient is greater than 35 mm Hg. When combined with standard PCP treatment within 72 hours of initial therapy, several studies demonstrated a significant decrease in mortality among persons with HIV infection and moderate to severe PCP. There may be benefit in persons with mild PCP, however, the mortality in this population is low even without prednisone therapy.

There is often considerable concern about the safety of prednisone in persons with PCP and underlying immune deficiency. There is no definitive evidence that a 21-day course increases the likelihood that another opportunistic infection, Kaposi’s sarcoma, or tuberculosis will appear or, if present, will be exacerbated.

 

What can I do to prevent PCP?

 

Persons with HIV infection. Persons with HIV infection 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. Many of the same medications used to treat PCP are also used to prophylaxis against the disease (http://www.cdc.gov/hiv/resources/brochures/pcpb.htm). As noted above, for persons with HIV, once they begin prophylaxis, they should remain on it for life, unless their CD4 cell counts increase from less than 200 cells/μL to greater than 200 cells/μL for at least three months as a result of combination antiretroviral therapy. For those without underlying HIV infection, the precise criteria depend on the cause of immunosuppression and whether the immunosuppression is temporary (i.e., related to medications or therapy that are only given for a defined period) or permanent.

 

Trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole is the recommended first-line preventive regimen against PCP unless there is a history of a life-threatening adverse reaction to this medication. A single tablet (either double strength, DS, or single strength) is usually taken by mouth either daily or thrice weekly (DS only).

 

Dapsone. Dapsone is considered the best alternative prophylaxis regimen for patients who cannot tolerate trimethoprim-sulfamethoxazole. The usual dose is 100 mg by mouth daily.

 

Atovaquone. Atovaquone is an alternative to trimethoprim-sulfamethoxazole and dapsone. The usual dose is 1500 mg (liquid suspension) by mouth daily.

 

Aerosolized pentamidine. Aerosolized pentamidine is an effective PCP prophylaxis regimen, especially in persons with HIV infection with a CD4 cell count of more than 100 cells/μL. However, it is less effective than trimethoprim-sulfamethoxazole or dapsone. Aerosolized pentamidine is administered once a month.

 

Conclusion

 

PCP is a life-threatening pneumonia that predominantly affects persons with medical conditions that compromise the immune system, especially persons who are infected with HIV. Classically, PCP presents with fever, cough, and shortness of breath on exertion and with bilateral, diffuse, and symmetric reticular (interstitial) or granular opacities on chest x-ray. Sputum induction and bronchoscopy with BAL are the two procedures used to diagnose PCP. Trimethoprim-sulfamethoxazole is the recommended first-line regimen to treat PCP unless there is a history of a life-threatening adverse reaction to this medication. It is also the recommended first-line regimen to prevent PCP.

 

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 (HIV/AIDS): http://www.cdc.gov/hiv/resources/brochures/pcpb.htm

 

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.

 

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