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
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. 3rd Edition.
Peter Walzer and Melanie T. Cushion. Pneumocystis Pneumonia. 3rd Edition.
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