Chapter 353. Pneumocystis Pneumonia

Walter T. Hughes

Pneumocystis Pneumonia: Introduction

Pneumocystis pneumonia (PCP) occurs almost exclusively in the severely immunocompromised host, especially patients with congenital immunodeficiency diseases, AIDS, and cancer, and those who have had organ transplantation. Once pneumonia is apparent, the fatality rate is near 100% if untreated. Effective therapeutic and prophylactic drugs are available. The causative agent is a protozoan-like fungus known for the past century as Pneumocystis carinii. Recently, the term Pneumocystis jirovecii has been proposed for the organism found in humans,1 but acceptance has not been universal.2

Epidemiology

Pneumocystis infection is recognized among humans and lower animals worldwide. The natural habitat and mode of transmission in man are unknown, but animal studies suggest animal-to-animal transmission occurs by the airborne route.3-5 Animal-to-human transmission has not been reported, and available evidence suggests that human-to-human transmission is possible.11 Symptomatic infection occurs sporadically in immunocompromised individuals.

PCP was first recognized in humans by Van der Meer and Brug in 1942.6 During this time, epidemics of interstitial plasma cell pneumonitis were occurring in European infants. In the 1950s, several reports confirmed that Pneumocystis was the etiology of epidemics of interstitial plasma cell pneumonitis in European infants.7

With the advent of immunosuppressive therapy for cancer and methods for diagnosing congenital immunodeficiency disorders, PCP became recognized as a potentially fatal infection in such individuals.8-10

Intrauterine transmission of Pneumocystis has also been reported.12,13 Of eight pregnant women with AIDS and PCP, one infant had Pneumocystis infection.14,15 Considerable data show that at least 75% of normal children reaching 4 years of age have acquired antibody to Pneumocystis and that more than 90% of normal adults have detectable antibody.16-18,19 Furthermore, a prospective study of otherwise normal infants, ages 2 to 12 weeks, with pneumonia showed that 10 of 69 babies had detectable antibody to Pneumocystis and that one of the 10 infants had PCP.20 In serial observations of 107 normal infants, Pneumocystis DNA was detected in nasopharyngeal aspirates in 74 of the infants tested.21 In addition, Pneumocystis has been associated with sudden infant death syndrome (SIDS), but no cause and effect has been proven.22,23 The natural course of PCP can be delineated from studies done before the advent of chemoprophylaxis in 1977 in individuals at high risk for PCP. Data collected at the Centers for Disease Control (CDC) revealed 194 documented cases of PCP encountered in the United States during the 3-year period from 1967 to 1970. Twenty-five (12.9%) of these cases had primary immunodeficiency disorders; 91 (47%) had leukemia; 41 (21%) had other malignancies; 22 (11%) were organ transplant recipients, and 15 (8%) had other immunocompromising conditions.24-26From 1962 to 1971, the incidence of PCP was determined in 1251 children with malignancies and 379 patients with nonmalignant neoplasms or immunodeficiency diseases at St. Jude Children’s Research hospital; PCP was found in 4.1%, 0%, and 0% of patients, respectively.27 The incidence of PCP in cancer patients is influenced more by the extent of immunocompromise from treatment than the primary disease. In a controlled study of 160 children with acute lymphocytic leukemia without PCP prophylaxis and on intensive antileukemia therapy, 20% were found to have developed PCP.28Other at risk populations include those immunosuppressed for solid organ transplantation30, rheumatoid arthritis, lupus erythematosus, and other connective tissue diseases in adults with CD4+ T lymphocyte counts less than 250/mm3.31

A 1999 review of 4581 solid organ transplant recipients who were not receiving prophylaxis found 4.9% had PCP.30 A 2006 report showed PCP is emerging as a complication of immunosuppressive therapy for patients with rheumatoid arthritis, lupus erythematosus, and other connective tissue diseases in adults with CD4+ Tlymphocyte counts less than 250/mm3.31

Patients with HIV are ideal targets for PCP because of a profound defect in their cell-mediated immune responses. Early in the AIDS epidemic, when no antiviral therapy was available and chemoprophylaxis for PCP was not applied, some 75% of adults and 39% of infants with AIDS acquired PCP.32,33,34 In infants and children with HIV infection, PCP occurs most often in infants between 3 and 6 months of age.33-35 The use of PCP prophylaxis and highly active antiretroviral therapy (HAART) has profoundly reduced PCP in patients with AIDS. Before HAART (from 1981–1988), the incidence of PCP in 3331 HIV-infected children was 1.3 cases per 100 person-years; after the introduction of HAART (2001–2004), the incidence of PCP in 2767 HIV-infected patients decreased to less than 0.5 per 100 person-years.36 The Perinatal AIDS Collaborative Transmission Study showed a 95% decrease in PCP (cases per 100 patient-years), from 5.8 in the pre-HAART era to 0.3 in the HAART era.37,38

While the incidence of PCP has declined in children with AIDS in the United States, the incidence has increased in Africa. From 1992 to 1993, 16% of children dying with AIDS had PCP39; 29% of those dying from 1997 to 200040 and 44% of those dying between 2000 and 2001 had PCP.41

As with other immunosuppressed states, highly significant risk factor for PCP in HIV-infected patients is a marked reduction in the CD4+ T lymphocyte count.

Pathophysiology

The portal of entry for Pneumocystis is believed to be the respiratory tract via the airborne route. In the infected lung, the organism is found in both cystic and extracystic forms. The cyst is a round, oval, or cup-shaped structure approximately 4 to 6 microns in diameter (Fig. 353-1). Within the mature cyst are as many as eight daughter cells, referred to as sporozoites, that are pleomorphic and often crescent shaped. These cells eventually excyst through breaks in the cyst wall. Outside the cyst, the daughter cell, now termed a trophozoite, varies from 2 to 5 microns in diameter. These thin-walled trophozoites tend to cluster in masses.

Figure 353-1.

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Cyst forms of Pneumocystis as seen in bronchoalveolar lavage specimen stained with Gomori methenamine silver nitrate method.

In the normal, healthy individual, Pneumocystis may lie dormant in the alveoli, eliciting no tissue response and leaving the host asymptomatic.42 In the severely immunocompromised host, organisms replicate to large numbers and an extensive diffuse alveolar disease and interstitial infiltration may progress to death.

Pneumocystis attaches to the alveolar epithelial cells, and alveolar macrophages ingest and degrade the organisms; this provokes neutrophil, lymphocyte, and monocyte infiltration and cytokine release. Alveolar disruption impedes gas exchange and leads to respiratory failure.43,44 The CD4+ T lymphocyte serves to recruit and activate other immune effector cells.45,46There is an increase in CD8+ lymphocytes in the lungs.47 Surfactant phospholipids are reduced in PCP, further impairing pulmonary function.48-51 Although using surfactant in clinical application in humans has not been adequately studied, a case report describes immediate improvement in an infant with respirator-dependent PCP upon administration of synthetic surfactant via endotracheal tube.52

Clinical Features

The clinical manifestations of PCP may present abruptly as an acute febrile episode with respiratory symptoms or a more subtle subacute illness with little or no fever. In all cases, tachypnea, cough, dyspnea, and oxygen desaturation occur. Typically, the chest radiograph shows bilateral, diffuse alveolar disease with symmetric reticular (interstitial) or granular opacites (eFig. 353.1). However, by the time pneumonitis is discernible by radiograph, tachypnea, flaring of nasal alae, intercostal retractions, and even cyanosis may be evident on examination. Even with diffuse pneumonitis, rales may not be heard. Once pneumonitis is evident, the infection progresses to a fatal outcome in nearly 100% of cases if untreated.

eFigure 353.1.

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Chest radiograph of Pneumocystis pneumonia showing bilateral diffuse alveolar disease.

Atypically, lobar, nodular, or miliary lesions are found. The type of clinical presentation is generally related to the patient’s age and the underlying primary disease and its treatment. Infants tend to have the slower subacute course, and older children have the acute onset. Studies have found that HIV-infected patients present with a higher arterial oxygen tension and a lower alveolar-arterial oxygen gradient than other immunocompromised hosts.42

In children with severe protein-calorie malnutrition the onset is often subtle, with chronic diarrhea and weight loss preceding the onset of cough, tachypnea, and dyspnea. Fever is often absent, and symptoms may persist for several days before evidence of pneumonitis is seen on the chest radiograph.53 By the time pneumonitis is discernible by radiograph, tachypnea, flaring of nasal alae, intercostal retractions, and even cyanosis may be evident on examination. Even with diffuse pneumonitis, rales may not be heard.

It is important to note that both the acute and subacute presentation for PCP may occur in any immunosuppressive disease and in any age group. Hypoxia, as revealed by decreased arterial oxygen tension, is found in essentially all cases of PCP.

A recent study of HIV-infected children with pneumonia showed four clinical factors were independently associated with PCP: respiratory rate greater than 59 respirations per minute, arterial hemoglobin saturation (SaO2) less than or equal to 92%, less than 6 months of age, and the absence of vomiting.54

In patients with PCP, the disease and the organisms remain localized to the lungs, even in fatal cases, with rare exception. Rarely Pneumocystis has been found in extrapulmonary sites, including meninges, spleen, liver, pancreas, thyroid, brain, kidneys, bone marrow, heart, lymph nodes, ears, eyes, stomach, intestinal tract, ureter, muscles, adrenal glands, and peritoneum. Usually no clinical manifestations are associated with these infected sites.

In a recent study of 56 cancer patients with PCP, the clinical manifestations included fever in 86%, dyspnea in 79%, and cough in 57% of the cases. The pneumonitis presented with severe hypoxemia (PaO2 = 50–70 mm Hg) and bilateral interstitial infiltrates (80%) and bilateral ground-glass appearance (89%) by computed tomography. Sixteen (29%) patients required assisted mechanical ventilation and 11 (19.6%) died.55

Diagnosis

A definitive diagnosis requires the demonstration of Pneumocystis in infected lung tissue or in material from the lung that is obtained by bronchoalveolar lavage (BAL); induced sputum; or open lung, transbronchial, percutaneous, or endobronchial brush biopsies. BAL is usually the preferred procedure for children, although the lung biopsy remains the “gold standard,” because it provides histology of the disease. The specimen is stained with Gomori, toluidine blue O, calcofluor white, or Giemsa stains (see Fig. 353-1 and eFigs. 353.2, 353.3, and 353.4). A fluorescence-conjugated monoclonal antibody (Meriflour, Meridian Bioscience, Cincinnati) is highly sensitive and specific (eFig. 353.5). Serum antibody titers to Pneumocystis are of no diagnostic value.

eFigure 353.2.

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Cyst forms of Pneumocystis as seen in bronchoalveolar lavage specimen stained with toluidine blue O method.

eFigure 353.3.

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Pneumocystis sporozoites as seen in bronchoalveolar lavage specimen stained with Giemsa method. Eight crescent-shaped sporozoites (arrow) are clustered within the confines of a cyst wall. Giemsa does not stain the cyst wall. Compare organism with background red blood cells for estimation of size.

eFigure 353.4.

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Lung biopsy specimen stained with hematoxylin and eosin. This shows alveoli filled with the typical “frothy proteinaceous” material and reactive alveolar macrophages. Pneumocystis does not stain with hematoxylin and eosin.

eFigure 353.5.

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Lung biopsy specimen stained with Gomori methenamine silver nitrate method. This shows the dark-staining cyst forms of Pneumocystis filling the alveoli.

Pneumocystis DNA/RNA has been detected in lung tissue, in sputum, and in oral and nasal secretions by polymerase chain reaction (PCR), but this approach has not been adequately standardized and studied to adopt for diagnosis. While lung biopsy is the most sensitive and specific procedure and provides histopathology on the extent of disease process (eFigs. 353.4 and 353.5), BAL is usually the procedure initially used because of the possible complications from general anesthesia, pneumothorax, hemorrhage, and pneumomediastinum with biopsy. The reported diagnostic sensitivity of BAL ranges from 89% to greater than 98%.56,57

Due to the dearth of data on induced sputum in infants and children, the sensitivity of the procedure for diagnosis is not known. However, if microscopic methods find Pneumocystis in the sputum of a patient of any age who has clinical evidence of pneumonitis, it can be dependably accepted as diagnostic of PCP. If the first induced sputum sample is negative, a BAL is warranted.58

Because Pneumocystis is highly resistant to acid and because PCP is associated with a massive number of organisms in the lungs, gastric lavage might provide a means to obtain diagnostic specimens (as with acid-fast mycobacteria). The early study of Chan and colleagues59 found Pneumocystis in gastric aspirates of 23% of children with PCP, and none of the uninfected controls yielded the organism. More recently, a study60found that 48.6% of 35 children with HIV and respiratory symptoms suggestive of PCP had microscopically detectable Pneumocystis in nasogastric aspirates. Also, studies of 105 gastric aspirates from 52 infants and children in Bangkok showed Pneumocystis in 11 (10%) of the samples done by immunofluorescence antibody test and showed Pneumocystis DNA in 13% of the samples done by single-step PCR and 62% done by nested PCR (eFig. 353.6). There was moderate agreement with single-step PCR but none with nested PCR.61

eFigure 353.6.

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Pneumocystis cysts and trophozoites in a cluster stained with fluorescein-labeled antibody.

Treatment

Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred drug for treating Pneumocystis pneumonia (Table 353-1). The dosage is based on 20 mg of TMP and 100 mg SMX per kg per day orally, or three fourths of this dose given IV in 3 or 4 doses. A 2-week course is usually adequate for patients without AIDS, but at least 3 weeks of treatment is needed for patients with AIDS.

Table 353-1. Drugs for the Treatment of Pneumocystis Pneumonia.

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Table 353-1. Drugs for the Treatment of Pneumocystis Pneumonia.

Drug

Administration

Notations

Trimethoprim-sulfamethoxazole (TMP-SMX)

15–20 mg TMP + 75–100 mg SMX kg/day, IV, in 3–4 divided doses. May change to PO as pneumonitis subsides.

Drug of first choice

Total daily dose not to exceed 960 mg TMP/4800 mg SMX

Pentamidine isethionate

4 mg/kg IV once daily

Drug of second choice

Total daily dose not to exceed 300 mg

High toxicity

Infuse over 1–11/2 hr period

Atovaquone

Ages < 3 mo and > 24 mo = 30–40 mg/kg per day in two divided doses PO.

Food increases absorption 2–3 times

Ages 3 mo to 24 mo = 45 mg/kg per day in two divided doses.

Few adverse effects

Approved for mild and moderate PCP

Dapsone-trimethoprim

Dapsone 2 mg/kg once daily, PO

Do not use dapsone or TMP alone for treatment.

AND TMP 15 mg/kg per day, PO in three divided doses

Total dose of dapsone not to exceed 100 mg/day

Studied in mild and moderate cases of PCP

Clindamycin-primaquine

Clindamycin 40 mg/kg per day IV in four divided doses

Not studied in children with PCP

AND Primaquine 0.3 mg/kg per day PO

Doses estimated from use in other infections in children

Exclude G6PD deficient patients

Prednisone

Days 1–5 = 1.0 mg/kg twice daily

Consider use in patients with PaO2 < 70 mm Hg or with alveolar-arterial gradient of > 35 mm Hg

Days 6–10 = 0.5 mg/kg twice daily.

Days 11–21 = 0.5 mg/kg once daily

TMP-SMX is usually administered intravenously at first. When there is evidence of clinical improvement and the patient can take and tolerate oral therapy, the drug combination can be given orally, using either tablets or suspension. The recommended doses provide an effective therapeutic serum concentration of 5 to 10 mcg/mL of TMP.62 Because patients who have one episode of PCP and recover are at high risk for a recurrent episode, all individuals treated for PCP should be maintained on TMP-SMX at prophylactic doses indefinitely or until the immunocompromised state is resolved.63 TMP-SMX is generally well tolerated, but HIV-infected patients have an exceptionally high rate of adverse reactions.64 These include rash, fever, anorexia, nausea, vomiting, diarrhea, leukopenia, thrombocytopenia, anemia, renal toxicity, and exfoliative skin disorders (Stevens-Johnson syndrome). Unless the reaction is mild and insignificant, TMP-SMX should be discontinued and therapy continued with another drug, usually pentamidine. About 15% of HIV-infected children have substantial adverse reactions to TMP-SMX.65

Pentamidine is recommended for patients who cannot tolerate or who do not respond to TMP-SMX. The drug must be administered parenterally and is frequently associated with nephrotoxicity, hypoglycemia, and other adverse effects. Pentamidine is given as a single IV dose at 4 mg/kg. Pentamidine isethionate is available only by the intravenous, intramuscular, and aerosol routes. Aerosolized pentamidine is only minimally effective for therapy and should not be used. The intravenous route is preferred to avoid the severe cutaneous reactions encountered from intramuscular administration. Pentamidine is highly toxic, causing nephrotoxicity, hypokalemia, hypo- and hyperglycemia, pancreatitis, leukopenia, cardiac arrhythmias, and cutaneous sterile abscess and necrosis. Adverse reactions occur in up to 80% of patients receiving pentamidine, and the drug must be discontinued in half the cases.66-70

Other drugs with demonstrated efficacy for treating PCP are atovaquone, dapsone plus trimethoprim, fansidar, and clindamycin plus primaquine (Table 353-1). Atovaquone offers a safe alternative to TMP-SMX and is available only as an oral suspension (750 mg per 5 ml). It has been evaluated for treatment of PCP in adults with AIDS and was found to have therapeutic efficacy related directly to the plasma concentration of the drug.71 At a mean steady-state concentration of at least 15 mcg/mL, therapeutic success was achieved in more than 95% of cases; at levels of 5 to 10 mcg/mL, only 69% had successful outcome. Thus, it is essential to emphasize the administration of this medication with food (preferably fatty meals), which will provide a two- to threefold greater plasma concentration than when administered in a fasting state. Adverse events with atovaquone therapy include nausea, vomiting, diarrhea, and rash. No fatal adverse reactions have been reported.72,73

The combination of dapsone and trimethoprim has proven effective in treating PCP in adults with AIDS. Trimethoprim alone has little, if any, effect on PCP but is synergistic to enhance therapeutic efficacy of dapsone. Dapsone alone is effective in only about 61% of cases, while dapsone plus trimethoprim is effective in 100% of cases.74,75 Reversible neutropenia is a common adverse effect of dapsone. Other side effects to dapsone are rash, methemoglobinemia, anemia, thrombocytopenia, and elevated transaminases.76

Lack of data on the use of clindamycin plus primaquine to treat PCP in children relegates this regimen to cases where the aforementioned regimens cannot be used.

Trimetrexate, a folate antagonist that was once used to treat PCP in adults, has been removed from the market by the manufacturers and is no longer available.

Supportive measures are important in managing PCP. Administering oxygen and using assisted mechanical ventilation are indicated with severe hypoxia. Evidence suggests that using a corticosteroid may enhance survival in patients with moderate and severe PCP.77-79 With PaO2 values less than 70 mm Hg or an alveolar-arterial gradient of greater than 35 mm Hg, the administration of a corticosteroid such as prednisone is recommended (see Table 353-1 for doses).

Once pneumonitis is evident on chest radiograph, PCP is fatal in approximately 100% of cases if untreated. When defervescence reveals signs of clinical improvement from treatment, a decrease in respiratory rate and an increase in PaO2 may be seen at a mean of 4.5 Â±2.5 days and improvement in chest radiograph may be seen at 7.7 Â±4.5 days after treatment begins.80

Prevention

Pneumocystis pneumonitis can be prevented by the prophylactic use of TMP-SMX in a dosage of 5 mg of TMP and 25 mg of SMX per kg per day orally (daily or 3 days a week) in equally divided doses. For patients who cannot tolerate TMP-SMX, atovaquone, dapsone, and aerosolized pentamidine are effective alternatives (Table 353-2).76,81-83,84 The host is protected for only as long as the drug is administered. Updated CDC and NIH guidelines established for prophylaxis in infants and children with HIV infection recommend the following individuals receive PCP prophylaxis: all HIV-infected and indeterminate infants ages 1 to 12 months; children ages 1 through 5 years with CD4+ T lymphocyte counts of less than 500/mm3 (or < 15%); and children age 6 years and older with CD4+ T lymphocyte counts of less than 200/mm3 (or < 15%).38 Other patients at high risk for PCP and who warrant prophylaxis are those who have received organ transplants, those who have certain malignancies and congenital immunodeficiency syndromes, and those who require prolonged immunosuppressive therapy.

Table 353-2 Pneumocystis Pneumonia Prophylaxis Regimens.

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Table 353-2 Pneumocystis Pneumonia Prophylaxis Regimens.

Drug

Administration

Notations

Trimethoprim-sulfamethoxazole (TMP-SMX)

5 mg TMP + 25 mg SMX kg/day or 3 times per week on consecutive days

Drug of choice

If adverse events, stop drug and consider restarting at desensitizing doses

Total dose not to exceed 320 mg TMP/1600 mg SMX daily

Also has broad-spectrum antibiotic activity

Atovaquone

Ages < 3 mo and > 24 mo = 30 mg/kg once daily

Drug of second choice

Ages 4 to 24 mo = 45 mg/kg once daily

Administer with meal (high fat preferred)

Strong safety record

No antibacterial effect

Total daily dose not to exceed 1500 mg/day

Dapsone

Ages ⩾ 1 mo = 2 mg/kg per day PO or 4 mg/kg per week

Drug of second choice

Monitor for anemia and methemoglobinemia

Marketed in tablet form only but syrup may be obtained through compassionate IND

Total daily dose not to exceed 100 mg daily or 200 mg weekly doses

Aerosolized pentamidine

Ages ⩾ 5 yr = 300 mg once per month

Drug of third choice

Administer with Respirgard II nebulizer (Marquest, Englewood, CO)

Watch for cough, sneezing, and bronchospasm

Good safety record

When deciding which patients should receive chemoprophylaxis, the following high-risk factors should be considered: all HIV-infected patients as defined above; lymphoproliferative malignancies; prolonged corticosteroid therapy; extensive impairment of cell-mediated immunity (eg, severe combined immunodeficiency syndrome, S-linked CD 40 ligand deficiency); CD4+ T lymphocyte counts less than 200/mm3 (15%); severe malnutrition; bone marrow transplant recipients; certain solid organ transplant recipients; previous episode of PCP; brain tumor; and Wegener’s granulomatosis.

Trimethoprim-sulfamethoxazole has been the preferred drug for PCP prophylaxis for 3 decades and has been thoroughly evaluated in children with AIDS and in those with non-AIDS immunosuppressive diseases. In a recent randomized, placebo-controlled study of 534 HIV-infected children in Zambia, patients received TMP-SMX or placebo for prophylaxis along with antiretroviral therapy (ART). The mortality rate was 14 deaths per 100 child-years in the TMP-SMX group and 23 deaths per 100 child-years in the placebo group, showing prophylaxis reduced fatalities and prevented PCP.85 Generally what is observed with PCP in AIDS patients is somewhat similar to what occurs in non-AIDS patients, except adverse reactions to TMP-SMX are more frequent in HIV-infected patients than in those without HIV.When non-life-threatening adverse effects occur, TMP-SMX can be discontinued; when the reaction has resolved, the drug combination can be restarted with a desensitizing scheme.86 If the initial adverse reaction is life-threatening, stop TMP-SMX and use an alternative drug. Usually atovaquone or dapsone is the drug of second choice.

Atovaquone is effective and safe for PCP prophylaxis. A major disadvantage of atovaquone is its cost. A month of prophylaxis with atovaquone costs about 40 times that of TMP-SMX. Unlike TMP-SMX, atovaquone has no antibacterial activity but is effective against Toxoplasma gondii, Babesia species, and malaria. A prospective controlled study compared atovaquone plus azithromycin with TMP-SMX in 366 HIV-infected children at high risk for PCP.81 Results showed the regimens were equally effective in preventing PCP and bacterial infections. In a recent study, 86 children with leukemia who were intolerant to TMP-SMX received atovaquone prophylaxis over a period of 172 patient-years. No cases of PCP occurred, and no significant adverse effects were found.87 Daily atovaquone prophylaxis has been shown to be as effective as dapsone82 and aerosolized pentamidine.88 Dapsone is as effective as atovaquone or aerosolized pentamidine for prophylaxis but is possibly less effective than TMP-SMX.76,82 Similarly, no cases of PCP were encountered in peripheral blood stem cell transplant recipients receiving either TMP-SMX or atovaquone, while treatment-limiting adverse reactions occurred in 40% of those on TMP-SMX and none of those given atovaquone.89

Dapsone is a sulfone with several known adverse effects; however, it has been proven relatively safe for PCP prophylaxis. The long plasma half-life of dapsone allows its use as a once-a-day or once-a-week dosage administration.90 This drug is as effective as atovaquone or aerosolized pentamidine for prophylaxis but is possibly less effective than TMP-SMX.76,82

The pediatric dosage for aerosolized pentamidine is 300 mg once a month; the same dose is recommended for adults.91 This drug is somewhat more cumbersome to administer than dapsone or atovaquone but has the advantage of compliance through direct observational therapy once a month.92 During and following administration with the Respirgard II nebulizer, patients should be observed for cough and bronchospasm.84

Once PCP prophylaxis has been started, it should be continued as long as the susceptible immunocompromised state exists. Usually within 3 to 6 months after completion of chemotherapy, the prophylaxis can be stopped. Recent studies in both adults and children with AIDS show that those on HAART who achieve immune reconstitution of CD4+ T lymphocyte to greater than 15% may have PCP prophylaxis discontinued if monitoring with CD4+ T lymphocyte count is continued.38,65,93,95-97

References

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Chapter 353. Pneumocystis Pneumonia

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Pneumocystis Pneumonia: Introduction

Epidemiology

Pathophysiology

Figure 353-1.

Clinical Features

eFigure 353.1.

Diagnosis

eFigure 353.2.

eFigure 353.3.

eFigure 353.4.

eFigure 353.5.

eFigure 353.6.

Treatment

Prevention

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