Pneumocystis jiroveci Pneumonia (PJP)

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Overview of Pneumocystis jiroveci Pneumonia

Pneumocystis jiroveci pneumonia (PJP), formerly known as Pneumocystis carinii pneumonia (PCP), is the most common opportunistic infection in persons with HIV infection.

Pneumocystis first came to attention as a cause of interstitial pneumonia in severely malnourished and premature infants during World War II in Central and Eastern Europe. Before the 1980s, fewer than 100 cases of PJP were reported annually in the United States, occurring in patients who were immunosuppressed (eg, cancer patients receiving chemotherapy and solid-organ transplant recipients receiving immunosuppressants). In 1981, the Centers for Disease Control and Prevention reported PJP in 5 previously healthy homosexual men residing in the Los Angeles area.

P jiroveci is now one of several organisms known to cause life-threatening opportunistic infections in patients with advanced HIV infection worldwide. Well over 100,000 cases of PJP were reported in the first decade of the HIV epidemic in the United States in people with no other cause for immunosuppression.

While officially classified as a fungal pneumonia, PJP does not respond to antifungal treatment. Although a histopathologic demonstration of the organism is required for a definitive diagnosis (see Histologic Findings), treatment should not be delayed.[1] Treatment of PJP may be initiated before the workup is complete in severely ill high-risk patients. Treatment of PJP depends on the degree of illness at diagnosis, determined on the basis of the alveolar-arterial gradient. See the A-a Gradient calculator.

Antibiotics are primarily recommended for treatment of mild, moderate, or severe PJP. Trimethoprim-sulfamethoxazole (TMP-SMX) has been shown to be as effective as intravenous pentamidine and more effective than other alternative treatment regimens.[2] Corticosteroids are used as adjunctive initial therapy only in patients with HIV infection who have severe PJP. Preventive measures (eg, smoking cessation and chemoprophylaxis) can play an important role in disease management.

For other discussions on pneumonia,[3] see the following:

Microbiology of Pneumocystis jiroveci Pneumonia

Pneumocystis is a genus of unicellular fungi found in the respiratory tracts of many mammals and humans. Distinct genomic variability exists between host-specific members of the genus. The organism was first described in 1909 by Chagas and then a few years later by Delanöes, who ultimately named the organism in honor of Dr. Carini after isolating it from infected rats. Years later, Dr. Otto Jirovec and his group isolated the organism from humans, and the organism responsible for PJP was renamed after him.[4, 5]

The taxonomic classification of the Pneumocystis genus was debated for some time. It was initially mistaken for a trypanosome and then later for a protozoan. In the 1980s, biochemical analysis of the nucleic acid composition of Pneumocystis rRNA and mitochondrial DNA identified the organism as a unicellular fungus rather than a protozoan. Subsequent genomic sequence analysis of multiple genes including elongation factor 3, a component of fungi protein synthesis not found in protozoa, further supported this notion.

The organism is found in 3 distinct morphologic stages, as follows:

Pathophysiology and Etiology of Pneumocystis jiroveci Pneumonia

Pneumocystis organisms are commonly found in the lungs of healthy individuals. Most children are believed to have been exposed to the organism by age 3 or 4 years, and its occurrence is worldwide.[6]

Transmission of Pneumocystis

Animal studies have suggested that Pneumocystis organisms are communicable; airborne transmission has been reported. Human evidence of this is provided by molecular analysis of Pneumocystis isolates obtained from groups of patients involved in hospital outbreaks.[7, 8]

Further evidence of human transmission has been found in cases of recurrent pneumonia in which the genotype of Pneumocystis organisms in the same person differed in prior episodes. Despite this, barrier precautions are not required for patients hospitalized with P jiroveci pneumonia (PJP) except to protect other patients with depressed immunity.

Development of PJP

Disease occurs when both cellular immunity and humoral immunity are defective. Once inhaled, the trophic form of Pneumocystis organisms attach to the alveoli. Multiple host immune defects allow for uncontrolled replication of Pneumocystis organisms and development of illness. Activated alveolar macrophages without CD4+ cells are unable to eradicate Pneumocystis organisms. Increased alveolar-capillary permeability is visible on electron microscopy.

Physiologic changes include the following:

There have been reports of PJP occurring as part of the immune reconstitution syndrome.[9, 10]

Risk factors for PJP

PJP is caused by infection with P jiroveci. The following groups are at risk for PJP:[11, 12, 13]

Epidemiology of Pneumocystis jiroveci Pneumonia

Before the widespread use of prophylaxis for P jiroveci pneumonia (PJP), the frequency of Pneumocystis infection in lung transplant patients alone was as high as 88%. Now, with the routine use of prophylaxis, PJP is very rare in solid-organ transplant patients and has significantly decreased in patients infected with HIV.

Prior to the widespread use of highly active antiretroviral therapy (HAART), PJP occurred in 70%-80% of patients with HIV infection. The frequency of PJP is decreasing with the use of PJP prophylaxis and HAART. PJP is still the most common opportunistic infection in patients with HIV infection. Patients with HIV infection are more prone to PJP recurrence than patients not infected with HIV.

In developing regions of the world, the prevalence of PJP was once thought to be much lower,[18] but studies have shown that the lower reported incidence is likely a failure to accurately diagnose PJP. An accurate diagnosis requires access to modern medical care, which is not available worldwide.

Currently, the frequency of documented Pneumocystis infection is increasing in Africa, with Pneumocystis organisms found in up to 80% of infants with pneumonia who have HIV infection. In sub-Saharan Africa, tuberculosis is a common co-infection in persons with PJP.[19]

Prognosis of Pneumocystis jiroveci Pneumonia

In patients with HIV infection, PJP once carried a mortality rate of 20%-40%, depending on disease severity at presentation. Currently, mortality rates of 10%-20% are reported. PJP is still a major cause of death in patients with AIDS in the United States.

In persons without HIV infection, PJP carries a worse prognosis[20] ; this has not changed significantly in the past 20 years. Mortality rates of 30%-50% have been documented in several large studies.

The prognosis of PJP is worse in patients who present with concurrent pulmonary disease, in patients who develop pneumothorax, and in patients who require mechanical ventilation. The higher mortality rate is likely a result of delayed diagnosis and delayed initiation of appropriate treatment.

Clinical Presentation of Pneumocystis jiroveci Pneumonia

Patient history

The symptoms of P jiroveci pneumonia (PJP) are nonspecific. PJP in patients with HIV infection tends to run a more subacute indolent course and tends to present much later, often after several weeks of symptoms, compared with PJP associated with other immunocompromising conditions.[21] Symptoms of PJP include the following:

Physical examination

The physical examination findings of PJP are nonspecific and include the following:

Additional findings in children with severe disease include cyanosis, nasal flaring, and intercostal retractions.

Extrapulmonary manifestations

Although Pneumocystis infection rarely causes extrapulmonary manifestations, such findings may be present in patients receiving aerosolized pentamidine for prophylaxis or in patients with advanced HIV infection who are not taking any prophylaxis. They may also occur in the absence of lung involvement.

Based on most well-documented findings, Pneumocystis infection may present in almost any organ system, as follows:

Complications

A pathophysiologic process similar to acute respiratory distress syndrome (ARDS) may occur in patients with severe PJP.[22] These patients may require intubation. This greatly diminishes the prognosis.

Differential Diagnosis of Pneumocystis jiroveci Pneumonia

The differential diagnoses of P jiroveci pneumonia (PJP) include the following conditions:[23]

Laboratory Studies

A lactic dehydrogenase (LDH) study is performed as part of the initial workup.[24] LDH levels are usually elevated (>220 U/L) in patients with P jiroveci pneumonia (PJP). They are elevated in 90% of patients with PJP who are infected with HIV. The study has a high sensitivity (78%-100%); its specificity is much lower because other disease processes can result in an elevated LDH level.

LDH levels appear to reflect the degree of lung injury. They should decline with successful treatment. Consistently elevated LDH levels during treatment may indicate therapy failure and a worse prognosis.

Quantitative PCR for pneumocystis may be useful in distinguishing between colonization and active infection.[25]

Sputum P jirovecii PCR testing may be a viable alternative to invasive testing. This could be a more timely method for sample collection and would provide a safer alternative to bronchoscopic evaluation in patients who already have respiratory failure. Further studies comparing the sensitivity, specificity, and positive and negative predictive values for each sample type are needed.[26]

β-D-Glucan (BDG) is a cell-wall component of many fungi, including Candida, Aspergillus, and Pneumocystis (but not the Zygomycetes). It has been shown to be a sensitive test to detect PJP in a meta-analysis of 13 studies assessing the sensitivity, specificity, and overall accuracy of the test. A negative serum BDG result is sufficient for excluding PJP only in patients with HIV infection. In non-HIV cases, the results should be interpreted in parallel with clinical and radiologic findings.[27]

Chest Radiography

Chest radiography should be obtained in any immunocompromised patient with fever and/or respiratory signs or symptoms.[28] The chest radiographic findings may be normal in patients with early mild disease. Diffuse bilateral infiltrates extending from the perihilar region are visible in most patients with P jiroveci pneumonia (PJP). Less-common findings include patchy asymmetric infiltrates, pneumothorax, and pneumatoceles. A radiographically normal chest radiograph has also been described. Pleural effusions and intrathoracic adenopathy are rare.

Pneumothorax may also develop in patients using aerosolized pentamidine. Apical disease may also be found in patients using aerosolized pentamidine for prophylaxis, as shown in the image below.



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Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis jiroveci pneumonia.

Go to Imaging Pneumocystis Carinii Pneumonia for complete information on this topic.

Computed Tomography

High-resolution computed tomography (HRCT) scanning of chest is helpful when the chest radiography findings are equivocal. HRCT yields a high sensitivity for P jiroveci pneumonia (PJP) in patients with HIV infection.

The typical appearance is patchy areas of ground-glass attenuation with a background of interlobular septal thickening. Negative (normal or unchanged) CT scan findings alone do not rule out PJP (see the image below).



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CT scan of chest, with classic patchy areas of ground-glass attenuation.

Go to Imaging Pneumocystis Carinii Pneumonia for complete information on this topic.

Other Noninvasive Tests

Pulmonary function tests

Pulmonary function tests should be obtained as part of the initial noninvasive workup in patients with suspected P jiroveci pneumonia (PJP). Results may demonstrate a decreased diffusion capacity of carbon monoxide (DLCO) of less than 75% predicted. Decreased DLCO has a high sensitivity (89%-100%) but poor specificity (53%). PJP is unlikely if DLCO is normal.

When combined with normal or unchanged HRCT findings, pulmonary function tests may be used to identify patients unlikely to have PJP; such patients may be managed with observation alone.

Pulse oximetry

Pulse oximetry on room air should be measured in all patients. The oxygen saturation should be measured both at rest and with exertion. If any hypoxemia is found (O2 saturation < 90%), then an arterial blood gas (ABG) level should be obtained to evaluate the need for possible adjunctive corticosteroids.

HIV testing

The diagnosis of PJP should prompt consideration for HIV testing and other immune evaluations of lymphocytes and antibodies. If HIV testing is performed, appropriate pretest and posttest counseling guidelines must be followed.

Laboratory testing

Serum LDH may be elevated in patients with PJP.

Sputum Induction

If P jiroveci pneumonia (PJP) is strongly suspected, obtain a sputum sample by sputum induction for histopathologic testing. Pneumocystis organisms are frequently found in sputum induced by inhalation of a hypertonic saline solution. Sputum induction is the quickest and least-invasive method for definitively diagnosing PJP.[29] Expectorated sputum has a very low sensitivity and should not be submitted for diagnosis. Pneumocystis antigen detection assays on sputum may also be helpful but may have a low sensitivity.

The sensitivity of sputum induction varies widely (< 50% to >90%) and depends on proficiency in using the technique and the experience of the laboratory. Specificity is high (99%-100%). This study may be less sensitive in patients without HIV infection, as the immunodeficiency caused by HIV infection typically leads to a greater alveolar load of Pneumocystis organisms. It may also be less sensitive in patients receiving aerosolized pentamidine for prophylaxis.

Invasive Procedures

Bronchoalveolar lavage

Bronchoalveolar lavage (BAL) is the most common invasive procedure used to diagnose P jiroveci pneumonia (PJP). It has a diagnostic yield that exceeds 90% (and may be higher if multiple lobes are sampled).[30] BAL yields a lower sensitivity in patients receiving aerosolized pentamidine, in which case a transbronchial biopsy may be performed in conjunction with BAL.[31]

Obtain BAL if PJP is strongly suspected and the induced sputum sample findings are negative. BAL may be used in patients who are unable to cooperate with an induced sputum sample (eg, because of altered mental status). BAL may be less useful in cases of suspected PJP relapse. Consultation with a pulmonologist is required for BAL.

Lung biopsy

Open lung biopsy is the most invasive procedure and yields 100% sensitivity and specificity because it provides the greatest amount of tissue for diagnosis. However, this procedure is reserved for rare cases when bronchoscopy findings are nondiagnostic.

Histologic Findings

Because clinical and radiologic findings are not specific for PJP and because P jiroveci cannot be grown in vitro, histopathologic demonstration is necessary before a definitive diagnosis is established. The following are the staining techniques available for respiratory tract secretions.

Crystal violet, Giemsa, Diff-Quik, and Wright stain are used to detect both the trophozoite and cyst forms but not the cyst wall. Diff-Quik stain demonstrating P jiroveci is seen in the image below.



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Diff-Quik stain demonstrating Pneumocystis jiroveci.

Methenamine silver, toluidine blue, and Gram-Weigert selectively stain the wall of Pneumocystis cysts. Silver Gram stain showing P jiroveci is seen in the image below .



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Silver Gram stain showing Pneumocystis jiroveci.

Papanicolaou smear may demonstrate a foamy-appearing eosinophilic material surrounding Pneumocystis organisms (as seen in the image below).



View Image

Papanicolaou smear of Pneumocystis jiroveci.

Some facilities prefer to use direct immunofluorescence using monoclonal antibodies to detect Pneumocystis organisms because it may be more sensitive than histologic staining.

Treatment of PJP - General Considerations

While officially classified as a fungal pneumonia, P jiroveci pneumonia (PJP) does not respond to antifungal treatment. The treatment of choice is TMP-SMX, with second-line agents including pentamidine, dapsone (often in combination with pyrimethamine), or atovaquone. However, there are a few reports of successful caspofungin administration in PJP. Echinocandins such as caspofungin may be active against Pneumocystis based on their activity against the inclusion of (1-3)beta-D glucan into the fungal cell wall, but clinical data are lacking. Case reports suggest it may be worthy of consideration as a salvage treatment option in nonresponsive cases, and further research is clearly warranted.[32]

Although a histopathologic demonstration of the organism is required for a definitive diagnosis (see Histologic Findings), treatment should not be delayed. Treatment of PJP may be initiated before the workup is complete in severely ill high-risk patients.

Appropriate histopathologic testing may still be used to confirm a diagnosis of PJP after treatment is initiated. Endotracheal tube aspirates from severely ill patients on mechanical ventilation may be submitted for diagnosis. Pneumocystis organisms persist in the host for days to weeks after therapy is started, allowing time for completion of the appropriate workup.

Treatment of PJP depends on the degree of illness at diagnosis. Degree of illness is determined based on the alveolar-arterial gradient: mild (< 35 mm Hg), moderate/severe (35-45 mm Hg), or severe (>45 mm Hg). Severe disease is also indicated by a room air partial pressure of oxygen lower than 70 mm Hg. Treatment of extrapulmonary manifestations of PJP is the same as that for other pneumonias.

In patients without HIV infection, response to treatment should begin within 4-5 days. In patients infected with HIV, the treatment response typically takes longer but should occur within the first 8 days. If no response occurs within the expected time, an appropriate alternative regimen should be used. Adding additional PJP medications to a current regimen only increases the risk of adverse drug reactions without improving the likelihood of a good outcome. Up to 10% of mild-to-moderate PJP cases fail to respond to antibiotic treatment because of lack of drug efficacy.

All patients who require corticosteroids should be admitted to the hospital because of the risk of progressive respiratory compromise.

Because of increasing evidence of possible human transmission (see Pathophysiology and Etiology of PJP),[33] the CDC Hospital Infection Control Practice Advisory Committee has recommended that patients with PJP not have direct contact with other immunocompromised patients.

Antibiotic Therapy

Antibiotics are primarily recommended for treatment of mild, moderate, or severe P jiroveci pneumonia (PJP). TMP-SMX has been shown to be as effective as intravenous pentamidine and more effective than other alternative treatment regimens.[2, 34] The parenteral route may be considered in patients who present with serious illness or in those with gastrointestinal side effects.

Thomas et al have reported that a lower dose of TMP-SMX (10 mg/kg/d) is effective for PJP associated with HIV infection and carries fewer side effects,[35] but this should not yet be taken as a recommendation. Recent guidelines have been published.[36]

TMP-SMX is the preferred initial therapy during pregnancy according to consensus guidelines. The patient’s neonatologist should be informed if the medication is used near delivery because of potential for hyperbilirubinemia and kernicterus. For the treatment of infections that are resistant to TMP-SMX, the combination of clindamycin and primaquine is likely to be more effective than intravenous pentamidine.[37, 38]

The recommended duration of treatment for PJP is 21 days in patients with HIV infection and 14 days in all other patients. Patients infected with HIV tend to have a higher organism burden and respond to treatment slower than patients without HIV infection and therefore require a longer duration of therapy.

Adjunctive Corticosteroid Therapy

Corticosteroids are used as adjunctive initial therapy only in patients with HIV infection who have severe P jiroveci pneumonia (PJP) as defined by a room air arterial oxygen pressure of less than 70 mm Hg or an arterial-alveolar O2 gradient that exceeds 35 mm Hg. Adjunctive steroids are not recommended in patients without HIV infection.

Microbial degradation and clearance may trigger further inflammation, which can provoke a severe inflammatory response in the lungs that often worsens after therapy is begun. Adjunctive corticosteroid therapy can blunt this inflammatory response, reduce deterioration of oxygenation, and reduce the incidence of respiratory failure.[39, 40]

Further Outpatient Care

Arranging close medical follow-up with a primary care provider upon hospital discharge is essential to monitor resolution of disease and to initiate prophylactic medication (see Prevention of PJP).

Oral therapy with TMP-SMX has been shown to be very effective in the outpatient setting. However, oral therapy should be considered only in patients with mild-to-moderate P jiroveci pneumonia (PJP) who have reliable outpatient follow-up care.

Prevention of PJP

Smoking cessation

Smoking cessation is strongly recommended in patients with HIV infection, as studies have shown that, in addition to the common deleterious effects of tobacco use, smokers are at an increased risk of P jiroveci pneumonia (PJP) and have a more complicated treatment course.[41]

Chemoprophylaxis in patients with HIV Infection

Two types of outpatient chemoprophylactic therapies exist. Primary prophylaxis is used in immunocompromised patients without a history of PJP. Secondary prophylaxis is used in patients with a prior bout of PJP.

An expert panel overseen by the US Public Health Service and Infectious Disease Society of America has published guidelines on prophylaxis against P jiroveci pneumonia (PJP) in adult and pediatric patients with HIV infection. Chemoprophylaxis is recommended for the following groups:

One study suggests that discontinuation of prophylaxis may be safe in patients with HIV and CD4 counts of 101-200 cells/μL and suppressed viral load.[42]

Chemoprophylaxis in patients without HIV infection

Unlike in patients with HIV infection, no specific PJP prophylaxis guidelines exist for immunocompromised patients without HIV infection. In general, chemoprophylaxis should be considered in any of the following patients:

Chemoprophylactic regimens

TMP-SMX is the agent of choice for PJP prophylaxis in the absence of a contraindication. In patients who cannot tolerate TMP-SMX, other options include dapsone, dapsone plus pyrimethamine, atovaquone, and aerosolized pentamidine. Commonly used prophylactic regimens are discussed below.

For TMP-SMX, the normal dosage is one double-strength tablet (160 mg TMP to 800 mg SMX) daily. One single-strength tablet (80 mg TMP to 400 mg SMX) daily is also effective. Another alternative is one double-strength tablet 3 times per week. However, a daily-dosing regimen provides an additional benefit of cross protection against Toxoplasma gondii infection and other bacterial infections.

The use of TMP-SMX for long-term PJP prophylaxis does not seem to affect the rates of infection by drug-resistant organisms such as pneumococcus or Staphylococcus aureus. TMP-SMX resistance has been reported among some isolates of Pneumocystis.[43]

For dapsone, the dosage is 100 mg daily by mouth if it is administered alone. If dapsone is given with pyrimethamine (plus leucovorin), the dosage is 50 mg of dapsone daily by mouth with 50 mg of pyrimethamine weekly and 25 mg of leucovorin weekly. Dapsone with pyrimethamine (plus leucovorin) provides protection against T gondii infection, but not other bacterial infections.

For atovaquone, the dosage is 1500 mg by mouth once daily given with food. This agent has a low toxicity profile and is an alternative if the patient cannot tolerate TMP-SMX or dapsone. However, atovaquone is very expensive.

For aerosolized pentamidine, the normal dosage is 300 mg in 6 mL sterile water via Respirgard nebulizer every 4 weeks. This agent is better tolerated than dapsone or TMP-SMX. However, it is much more expensive and less effective than other prophylactic agents. Side effects include cough and bronchospasm. The potential for extrapulmonary Pneumocystis manifestations and apical lung disease exists. In addition, aerosolized pentamidine may diminish the diagnostic sensitivity of sputum induction and bronchoalveolar lavage.

What is Pneumocystis jiroveci pneumonia (PJP)?When was Pneumocystis jiroveci pneumonia (PJP) first identified?What is the role of Pneumocystis jiroveci pneumonia (PJP) in HIV infection?How is Pneumocystis jiroveci pneumonia (PJP) diagnosed and when should treatment be initiated?What is the treatment for Pneumocystis jiroveci pneumonia (PJP)?What is the microbiology of the Pneumocystis genus?Where are Pneumocystis organisms commonly found?How is Pneumocystis organisms transmitted?What is the pathogenesis of Pneumocystis jiroveci pneumonia (PJP)?What are risk factors for Pneumocystis jiroveci pneumonia (PJP)?How prevalent is Pneumocystis jiroveci pneumonia (PJP)?What is the mortality rate for Pneumocystis jiroveci pneumonia (PJP)?What are the signs and symptoms of Pneumocystis jiroveci pneumonia (PJP)?What are the physical findings suggestive of Pneumocystis jiroveci pneumonia (PJP)?What extrapulmonary symptoms of Pneumocystis jiroveci pneumonia (PJP)?What are possible complications of Pneumocystis jiroveci pneumonia (PJP)?Which conditions should be included in the differential diagnosis of Pneumocystis jiroveci pneumonia (PJP)?What is the role of lab testing in the diagnosis of Pneumocystis jiroveci pneumonia (PJP)?What is the role of radiography in the diagnosis of Pneumocystis jiroveci pneumonia (PJP)?What is the role of CT scanning in the diagnosis of Pneumocystis jiroveci pneumonia (PJP)?What is the role of pulmonary function testing in the diagnosis of Pneumocystis jiroveci pneumonia (PJP)?What is the role of pulse oximetry in the diagnosis of Pneumocystis jiroveci pneumonia (PJP)?When is HIV testing indicated in the workup of Pneumocystis jiroveci pneumonia (PJP)?What serum LDH findings suggest Pneumocystis jiroveci pneumonia (PJP)?When should a sputum sample be obtained in the workup of Pneumocystis jiroveci pneumonia (PJP)?What is the specificity and sensitivity of sputum induction in the workup of Pneumocystis jiroveci pneumonia (PJP)?What is the role of bronchoalveolar lavage (BAL) in the diagnosis of Pneumocystis jiroveci pneumonia (PJP)?When is open lung biopsy indicated in the workup of Pneumocystis jiroveci pneumonia (PJP)?Which staining techniques are used for histologic evaluation of Pneumocystis jiroveci pneumonia (PJP)?What is the treatment of choice for Pneumocystis jiroveci pneumonia (PJP)?When should treatment be initiated for Pneumocystis jiroveci pneumonia (PJP)?How is degree of illness determined in Pneumocystis jiroveci pneumonia (PJP)?When is treatment response expected in Pneumocystis jiroveci pneumonia (PJP)?When is inpatient treatment indicated for Pneumocystis jiroveci pneumonia (PJP)?What are CDC hospital infection control recommendations for Pneumocystis jiroveci pneumonia (PJP)?What antibiotic regimen are effective for treatment of Pneumocystis jiroveci pneumonia (PJP)?What is the indication for adjunctive corticosteroid therapy for Pneumocystis jiroveci pneumonia (PJP)?What follow-up care is necessary for Pneumocystis jiroveci pneumonia (PJP)?How does smoking affect the disease course of Pneumocystis jiroveci pneumonia (PJP)?What are the US Public Health Service-IDSA guidelines for chemoprophylaxis guidelines prophylaxis against Pneumocystis jiroveci pneumonia (PJP)?Which patients should consider chemoprophylaxis against Pneumocystis jiroveci pneumonia (PJP)?What is the regimen for TMP-SMX prophylaxis against Pneumocystis jiroveci pneumonia (PJP)?What is the chemoprophylactic regimen for dapsone in reference to Pneumocystis jiroveci pneumonia (PJP)?What is the chemoprophylactic regimen for atovaquone in reference to Pneumocystis jiroveci pneumonia (PJP)?What is the chemoprophylactic regimen for aerosolized pentamidine in reference to Pneumocystis jiroveci pneumonia (PJP)?

Author

Shelley A Gilroy, MD, FIDSA, Associate Professor of Medicine, Infectious Disease and HIV Medicine, Albany Medical College; Lead Physician, HIV Medicine, Division of Infectious Diseases, Samuel S Stratton VA Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Harold L Manning, MD, Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School

Disclosure: Nothing to disclose.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD, Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Klaus-Dieter Lessnau, MD, FCCP, Former Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Disclosure: Nothing to disclose.

Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP, Assistant Professor of Pediatrics, Co-Director of Antimicrobial Stewardship, Medical Director, Division of Pediatric Infectious Diseases and Immunology, Connecticut Children's Medical Center

Disclosure: Received research grant from: Cubist<br/>Received income in an amount equal to or greater than $250 from: Horizon Pharmaceuticals, Shire<br/>Medico legal consulting for: Various.

Acknowledgements

Frederick Burton Rose, MD, FACP Professor, Department of Medicine, University Hospital Epidemiologist, State University of New York Upstate Medical University

Frederick Burton Rose, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

References

  1. Benson C, Kaplan J, Masur H. 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. Clin Infect Dis. 2005. 40:S131.
  2. Safrin S, Finkelstein DM, Feinberg J, et al. Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group. Ann Intern Med. 1996 May 1. 124(9):792-802. [View Abstract]
  3. Cunha BA. Pneumonia Essentials. 2nd ed. Royal Oak, Mich: Physicians Press; 2007.
  4. Cushion MT, Stringer JR. Has the name really been changed? It has for most researchers. Clin Infect Dis. 2005 Dec 15. 41(12):1756-8. [View Abstract]
  5. Gigliotti F. Pneumocystis carinii: has the name really been changed?. Clin Infect Dis. 2005 Dec 15. 41(12):1752-5. [View Abstract]
  6. Slogrove AL, Cotton MF, Esser MM. Severe Infections in HIV-Exposed Uninfected Infants: Clinical Evidence of Immunodeficiency. J Trop Pediatr. 2009 Jul 14. [View Abstract]
  7. Schmoldt S, Schuhegger R, Wendler T, et al. Molecular evidence of nosocomial Pneumocystis jirovecii transmission among 16 patients after kidney transplantation. J Clin Microbiol. 2008 Mar. 46(3):966-71. [View Abstract]
  8. de Boer MG, Bruijnesteijn van Coppenraet LE, Gaasbeek A, et al. An outbreak of Pneumocystis jiroveci pneumonia with 1 predominant genotype among renal transplant recipients: interhuman transmission or a common environmental source?. Clin Infect Dis. 2007 May 1. 44(9):1143-9. [View Abstract]
  9. Mori S, Polatino S, Estrada-Y-Martin RM. Pneumocystis-associated organizing pneumonia as a manifestation of immune reconstitution inflammatory syndrome in an HIV-infected individual with a normal CD4+ T-cell count following antiretroviral therapy. Int J STD AIDS. 2009 Sep. 20(9):662-5. [View Abstract]
  10. Kolditz M, Halank M, Bandt D, Spornraft-Ragaller P, Höffken G. Early recurrence of Pneumocystis jiroveci pneumonia in two HIV-infected patients: linking infection relapse and immune reconstitution syndrome. Respirology. 2009 Aug. 14(6):910-2. [View Abstract]
  11. Hui M, Kwok WT. Pneumocystis carinii pneumonia in Hong Kong: a 10 year retrospective study. J Med Microbiol. 2006 Jan. 55:85-8. [View Abstract]
  12. Mori S, Cho I, Sugimoto M. A followup study of asymptomatic carriers of Pneumocystis jiroveci during immunosuppressive therapy for rheumatoid arthritis. J Rheumatol. 2009 Aug. 36(8):1600-5. [View Abstract]
  13. Resnick IB, Averbuch D, Aker M, et al. Is Pneumocystis carinii pneumonia after stem cell transplantations a contagious disease?. Clin Transplant. 2005 Jun. 19(3):427-31. [View Abstract]
  14. Byers DK, Decker CF. Unusual case of Pneumocystis jiroveci pneumonia during primary HIV infection. AIDS Read. 2008 Jun. 18(6):313-7. [View Abstract]
  15. Sax P. HIV Essentials. Royal Oak, Mich: Physicians Press; 2007.
  16. Ritter ML, Pirofski L. Mycophenolate mofetil: effects on cellular immune subsets, infectious complications, and antimicrobial activity. Transpl Infect Dis. 2009 Aug. 11(4):290-7. [View Abstract]
  17. Barbounis V, Aperis G, Gambletsas E, et al. Pneumocystis carinii pneumonia in patients with solid tumors and lymphomas: predisposing factors and outcome. Anticancer Res. 2005 Jan-Feb. 25(1B):651-5. [View Abstract]
  18. Abouya YL, Beaumel A, Lucas S, et al. Pneumocystis carinii pneumonia. An uncommon cause of death in African patients with acquired immunodeficiency syndrome. Am Rev Respir Dis. 1992 Mar. 145(3):617-20. [View Abstract]
  19. Murray JF. Pulmonary complications of HIV-1 infection among adults living in Sub-Saharan Africa. Int J Tuberc Lung Dis. 2005 Aug. 9(8):826-35. [View Abstract]
  20. Su YS, Lu JJ, Perng CL, Chang FY. Pneumocystis jirovecii pneumonia in patients with and without human immunodeficiency virus infection. J Microbiol Immunol Infect. 2008 Dec. 41(6):478-82. [View Abstract]
  21. Fujii T, Nakamura T, Iwamoto A. Pneumocystis pneumonia in patients with HIV infection: clinical manifestations, laboratory findings, and radiological features. J Infect Chemother. 2007 Feb. 13(1):1-7. [View Abstract]
  22. Festic E, Gajic O, Limper AH, et al. Acute respiratory failure due to pneumocystis pneumonia in patients without human immunodeficiency virus infection: outcome and associated features. Chest. 2005 Aug. 128(2):573-9. [View Abstract]
  23. Cunha BA, Schoch PE, Berbari N. Cryptococcal vs Pneumocystis (carinii) jiroveci pneumonia (PCP): Clinical & Microbiology differential diagnsotic considerations. Infect Dis Pract. 2006. 30:514-517.
  24. Grover SA, Coupal L, Suissa S, et al. The clinical utility of serum lactate dehydrogenase in diagnosing pneumocystis carinii pneumonia among hospitalized AIDS patients. Clin Invest Med. 1992 Aug. 15(4):309-17. [View Abstract]
  25. Fauchier T, Hasseine L, Gari-Toussaint M, Casanova V, Marty PM, Pomares C. Detection of Pneumocystis jirovecii by Quantitative PCR to Differentiate Colonization and Pneumonia in Immunocompromised HIV-Positive and HIV-Negative Patients. Journal of Clinical Microbiology. 2016 Jun. 54(6):1487-1494. [View Abstract]
  26. Pennington K,Wilson J, Limper AH, Escalante P. Positive Pneumocystis jirovecii Sputum PCR Results with Negative Bronchoscopic PCR Results in Suspected Pneumocystis Pneumonia. Canadian Respiratory Journal. 2018 April. 2018:1-5. [View Abstract]
  27. Li WJ, Guo YL, Liu TJ, Wang K, Kong JL. Diagnosis of pneumocystis pneumonia using serum 1-3 -B-D Glucan:a bivariate mets-analysis and systematic review. J Thorac Dis. 2015 Dec. 7(12):2214-2225.
  28. DeLorenzo LJ, Huang CT, Maguire GP, et al. Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS. Chest. 1987 Mar. 91(3):323-7. [View Abstract]
  29. Bigby TD, Margolskee D, Curtis JL, et al. The usefulness of induced sputum in the diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Am Rev Respir Dis. 1986 Apr. 133(4):515-8. [View Abstract]
  30. Bigby TD. Diagnosis of Pneumocystis carinii pneumonia. How invasive?. Chest. 1994 Mar. 105(3):650-2. [View Abstract]
  31. Broaddus C, Dake MD, Stulbarg MS, et al. Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Jun. 102(6):747-52. [View Abstract]
  32. Ceballos ME, Ortega M, Andresen M, Wozniak A, García P, Balcells ME. Successful treatment with echinocandin in an HIV-infected individual failing first-line therapy for Pneumocystis jirovecii pneumonia. AIDS. 2011 Nov 13. 25(17):2192-3. [View Abstract]
  33. Gianella S, Haeberli L, Joos B, Ledergerber B, Wüthrich RP, Weber R, et al. Molecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients. Transpl Infect Dis. 2009 Sep 9. [View Abstract]
  34. Estrada S, García-Campos F, Calderón R, Delgado E, Bengoa R, Enciso C. Pneumocystis jiroveci (carinii) pneumonia following a second infusion of infliximab in a patient with ulcerative colitis. Inflamm Bowel Dis. 2009 Feb. 15(2):315-6. [View Abstract]
  35. Thomas M, Rupali P, Woodhouse A, Ellis-Pegler R. Good outcome with trimethoprim 10 mg/kg/day-sulfamethoxazole 50 mg/kg/day for Pneumocystis jirovecii pneumonia in HIV infected patients. Scand J Infect Dis. 2009 Aug 17. 1-7. [View Abstract]
  36. [Guideline] Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. AIDSinfo. Available at https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportunistic-infection/0. March 28, 2019; Accessed: April 24, 2019.
  37. Smego RA Jr, Nagar S, Maloba B, et al. A meta-analysis of salvage therapy for Pneumocystis carinii pneumonia. Arch Intern Med. 2001 Jun 25. 161(12):1529-33. [View Abstract]
  38. Benfield T, Atzori C, Miller RF, et al. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review. J Acquir Immune Defic Syndr. 2008 May 1. 48(1):63-7. [View Abstract]
  39. Bozzette SA. The use of corticosteroids in Pneumocystis carinii pneumonia. J Infect Dis. 1990 Dec. 162(6):1365-9. [View Abstract]
  40. Bozzette SA, Sattler FR, Chiu J, et al. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med. 1990 Nov 22. 323(21):1451-7. [View Abstract]
  41. Miguez-Burbano MJ, Ashkin D, Rodriguez A, et al. Increased risk of Pneumocystis carinii and community-acquired pneumonia with tobacco use in HIV disease. Int J Infect Dis. 2005 Jul. 9(4):208-17. [View Abstract]
  42. Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research. Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count Clin Infect Dis</i>. 2010 Sep 1. 51(5):611-9. [View Abstract]
  43. Sibanda EL, Weller IV, Hakim JG, Cowan FM. Does trimethoprim-sulfamethoxazole prophylaxis for HIV induce bacterial resistance to other antibiotic classes? Results of a systematic review. Clin Infect Dis. 2011 May. 52(9):1184-94. [View Abstract]
  44. Coleman DL, Hattner RS, Luce JM, et al. Correlation between gallium lung scans and fiberoptic bronchoscopy in patients with suspected Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome. Am Rev Respir Dis. 1984 Dec. 130(6):1166-9. [View Abstract]
  45. Ewald H, Raatz H, Boscacci R, Furrer H, Bucher HC, Briel M. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection. Cochrane Database Syst Rev. 2015 Apr 2. 4:CD006150. [View Abstract]

Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis jiroveci pneumonia.

CT scan of chest, with classic patchy areas of ground-glass attenuation.

Diff-Quik stain demonstrating Pneumocystis jiroveci.

Silver Gram stain showing Pneumocystis jiroveci.

Papanicolaou smear of Pneumocystis jiroveci.

Diff-Quik stain demonstrating Pneumocystis jiroveci.

Silver Gram stain showing Pneumocystis jiroveci.

Papanicolaou smear of Pneumocystis jiroveci.

Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis jiroveci pneumonia.

CT scan of chest, with classic patchy areas of ground-glass attenuation.