Pneumonia, Pneumocystis Jiroveci

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Pneumonia, Pneumocystis Jiroveci

EPIDEMIOLOGY

para>No combination of symptoms, signs, blood chemistries, or radiographic findings is diagnostic of P. jiroveci pneumonia (4). ‚

Mode of transmission is unknown; likely respiratory from infected host ‚

P. jiroveci cannot be cultured. Therefore, a diagnosis relies on detection of the organism by colorimetric or immunofluorescent stains or by polymerase chain reaction (PCR) (5)[C]. ‚

The recommended duration of therapy differs in patients who are with/without AIDS: ‚

Adjunctive corticosteroid (prednisone or methylprednisolone) (4)[C],(7)[A] ‚

In patients with HIV/AIDS: Patients with previous episodes of PCP should receive lifelong secondary prophylaxis unless they respond well to highly active antiretroviral therapy (HAART) and have a CD4 count >200 cells/ Ž ¼L for at least 3 months. ‚

Serum lactate dehydrogenase levels, pulmonary function test results, and ABG measurements generally normalize with treatment. ‚

No special diet needed ‚

11 Catherinot ‚ E, Lanternier ‚ F, Bougnoux ‚ ME, et al. Pneumocystis jiroveci pneumonia. Infect Dis Clin North Am. 2010;24(1):107 " “138.22 Limper ‚ AH, Knox ‚ KS, Sarosi ‚ GA, et al. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183(1):96 " “128.33 D 'Avignon ‚ LC, Schofield ‚ CM, Hospenthal ‚ DR. Pneumocystis pneumonia. Semin Respir Crit Care Med. 2008;29(2):132 " “140.44 Krajicek ‚ BJ, Thomas ‚ CFJr, Limper ‚ AH. Pneumocystis pneumonia: current concepts in pathogenesis, diagnosis, and treatment. Clin Chest Med. 2009;30(2):265 " “278, vi.55 Kovacs ‚ JA, Masur ‚ H. Evolving health effects of Pneumocystis: one hundred years of progress in diagnosis and treatment. JAMA. 2009;301(24):2578 " “2585.66 Skelly ‚ MJ, Holzman ‚ RS, Merali ‚ S. S-adenosylmethionine levels in the diagnosis of Pneumocystis carinii pneumonia in patients with HIV infection. Clin Infect Dis. 2008;46(3):467 " “471.77 Briel ‚ M, Bucher ‚ HC, Boscacci ‚ R, et al. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection. Cochrane Database Syst Rev. 2006;(3):CD006150.88 Fei ‚ WM, Kim ‚ EJ, Sant ‚ CA, et al. Predicting mortality from HIV-associated Pneumocystis pneumonia at illness presentation: an observational cohort study. Thorax. 2009;64(12):1070 " “1076.

• P. jiroveci has a worldwide distribution, and most children have been exposed to the fungus by 2 to 4 years (5).
• The reservoir and mode of transmission for P. jiroveci is still unclear.Human studies favor an airborne transmission model, with person-to-person spread being the most likely mode of infection acquisition (4).

• Human studies favor an airborne transmission model, with person-to-person spread being the most likely mode of infection acquisition (4).

• Infants with HIV infection have a peak incidence of PCP between 2 and 6 months (5).
• HIV-infected infants have a high mortality rate, with a median survival of only 1 month.

• The prevalence of P. jiroveci colonization among healthy adults is 0 " “20% (2).
• Recent studies have demonstrated the transient nature of P. jiroveci colonization in asymptomatic, immunocompetent patients (4).
• 50% of patients with PCP are coinfected with ≥2 strains of P. jiroveci (5).
• There is evidence that distinct strains are responsible for each episode in patients who develop multiple episodes of PCP (5).

ETIOLOGY AND PATHOPHYSIOLOGY

RISK FACTORS

• Patients with HIV/AIDS infection, especially if not receiving prophylactic treatment for PCP
• Patients who are receiving high doses of glucocorticoids
• Patients who have an altered immune system not due to HIV
• Patients who are receiving chronic immunosuppressive medications
• Patients who have hematologic or solid malignancies resulting in malignancy-related immune depression

GENERAL PREVENTION

• Indications for prophylaxisHIV-infected adults (5)Should start when CD4 count is <200 cells/ Ž ¼L or if the patient develops oropharyngeal candidiasisHIV-infected children (5)Prophylaxis should be provided for children ≥6 years based on adult guidelines.For children aged 1 to 5 years, start when CD4 count is <500 cells/ Ž ¼L.For infants <12 months, start when the CD4 percentage is <15%.Non " “HIV-infected adults receiving immunosuppressive medications or with underlying immune system deficits should receive PCP prophylaxis, but currently there are no specific guidelines on when to start this.
• MedicationTrimethoprim-sulfamethoxazole (TMP-SMX)Adults: 1 double-strength tablet daily or 1 double-strength tablet 3 times per weekChildren >2 months: 150 mg TMP/m2/day in divided doses q12h for 3 days per weekAtovaquone suspensionAdults: 1,500 mg PO once daily with foodChildren: not to exceed 1,500 mg/day1 to 3 months: 30 mg/kg/day PO once daily4 to 24 months: 45 mg/kg/day PO once daily>24 months: 30 mg/kg/day PO once dailyAdolescents ≥13 years: Refer to adult dosing.DapsoneAdults only: 50 mg BID or 100 mg once dailyPentamidineAdults only: 300 mg aerosolized every 4 weeks
• Discontinuation of prophylaxisWhen CD4+ cell counts are >200 cells/ Ž ¼L for a period of 3 months in the adult population (2)[C]There are no clear guidelines for discontinuation of prophylaxis in children.

• HIV-infected adults (5)Should start when CD4 count is <200 cells/ Ž ¼L or if the patient develops oropharyngeal candidiasis
• HIV-infected children (5)Prophylaxis should be provided for children ≥6 years based on adult guidelines.For children aged 1 to 5 years, start when CD4 count is <500 cells/ Ž ¼L.For infants <12 months, start when the CD4 percentage is <15%.
• Non " “HIV-infected adults receiving immunosuppressive medications or with underlying immune system deficits should receive PCP prophylaxis, but currently there are no specific guidelines on when to start this.

• Should start when CD4 count is <200 cells/ Ž ¼L or if the patient develops oropharyngeal candidiasis

• Prophylaxis should be provided for children ≥6 years based on adult guidelines.
• For children aged 1 to 5 years, start when CD4 count is <500 cells/ Ž ¼L.
• For infants <12 months, start when the CD4 percentage is <15%.

• Trimethoprim-sulfamethoxazole (TMP-SMX)Adults: 1 double-strength tablet daily or 1 double-strength tablet 3 times per weekChildren >2 months: 150 mg TMP/m2/day in divided doses q12h for 3 days per week
• Atovaquone suspensionAdults: 1,500 mg PO once daily with foodChildren: not to exceed 1,500 mg/day1 to 3 months: 30 mg/kg/day PO once daily4 to 24 months: 45 mg/kg/day PO once daily>24 months: 30 mg/kg/day PO once dailyAdolescents ≥13 years: Refer to adult dosing.
• DapsoneAdults only: 50 mg BID or 100 mg once daily
• PentamidineAdults only: 300 mg aerosolized every 4 weeks

• Adults: 1 double-strength tablet daily or 1 double-strength tablet 3 times per week
• Children >2 months: 150 mg TMP/m2/day in divided doses q12h for 3 days per week

• Adults: 1,500 mg PO once daily with food
• Children: not to exceed 1,500 mg/day1 to 3 months: 30 mg/kg/day PO once daily4 to 24 months: 45 mg/kg/day PO once daily>24 months: 30 mg/kg/day PO once dailyAdolescents ≥13 years: Refer to adult dosing.

• 1 to 3 months: 30 mg/kg/day PO once daily
• 4 to 24 months: 45 mg/kg/day PO once daily
• >24 months: 30 mg/kg/day PO once daily
• Adolescents ≥13 years: Refer to adult dosing.

• Adults only: 50 mg BID or 100 mg once daily

• Adults only: 300 mg aerosolized every 4 weeks

• When CD4+ cell counts are >200 cells/ Ž ¼L for a period of 3 months in the adult population (2)[C]
• There are no clear guidelines for discontinuation of prophylaxis in children.

COMMONLY ASSOCIATED CONDITIONS

• HIV/AIDS
• Chronic obstructive pulmonary disease (COPD)
• Interstitial lung disease
• Connective tissue diseases treated with corticosteroids
• Cancer and organ transplant patients on immunosuppressive medication

DIAGNOSIS

HISTORY

• HIV-infected patientsSubacute onset over several weeksProgressively worsening dyspneaTachypneaCough: nonproductive or productive of clear sputumLow-grade fever, chillsWeakness, fatigue, malaise
• Non " “HIV-infected immunocompromised patientsMore acute onset with fulminant respiratory failureAbrupt tachypnea, dyspneaFeverDry cough

• Subacute onset over several weeksProgressively worsening dyspneaTachypneaCough: nonproductive or productive of clear sputumLow-grade fever, chillsWeakness, fatigue, malaise

• Progressively worsening dyspnea
• Tachypnea
• Cough: nonproductive or productive of clear sputum
• Low-grade fever, chills
• Weakness, fatigue, malaise

• More acute onset with fulminant respiratory failureAbrupt tachypnea, dyspneaFeverDry cough

• Abrupt tachypnea, dyspnea
• Fever
• Dry cough

PHYSICAL EXAM

• Fever
• Tachypnea
• Tachycardia
• Lung exam is normal or near normal.

DIFFERENTIAL DIAGNOSIS

• Tuberculosis
• Bacterial pneumonia
• Fungal pneumonia
• Viral pneumonia

DIAGNOSTIC TESTS & INTERPRETATION

• ABG: reveals hypoxemia and increased alveolar " “arterial gradient that varies with severity of disease
• LDH: Serum lactate dehydrogenase is frequently increased (nonspecific; likely due to underlying lung inflammation and injury).
• CD4 cell count is generally <200 cells/ Ž ¼L in HIV-infected patients with PCP.
• S-adenosylmethionine levels are significantly lower in a patient with PCP. The levels increase with successful treatment (6)[B].
• Comprehensive metabolic profile
• Chest x-ray (CXR) (4)[C]Bilateral, symmetric, fine, reticular interstitial infiltrates involving perihilar areas; becomes more homogeneous and diffuse as severity of infection progressesLess common patterns include upper lobe involvement in patients receiving aerosolized pentamidine, solitary or multiple nodular opacities, lobar infiltrates, pneumatoceles, and pneumothoraces.May be normal in up to 30% of patients with PCP (3)[C]
• High-resolution CT is more sensitive than CXR.

• Bilateral, symmetric, fine, reticular interstitial infiltrates involving perihilar areas; becomes more homogeneous and diffuse as severity of infection progresses
• Less common patterns include upper lobe involvement in patients receiving aerosolized pentamidine, solitary or multiple nodular opacities, lobar infiltrates, pneumatoceles, and pneumothoraces.
• May be normal in up to 30% of patients with PCP (3)[C]

• Fiber-optic bronchoscopy with bronchoalveolar lavage (BAL) is the preferred diagnostic procedure to obtain samples for direct fluorescent antibody staining.Sensitivities range from 89% to >98%.
• Pneumocystis trophic forms or cysts obtained from induced sputum, BAL fluid, or lung tissue, which can be visualized using conventional stains
• PCR can detect Pneumocystis from respiratory sources, but the potential remains for false positives (4)[C].

• Sensitivities range from 89% to >98%.

TREATMENT

• In patients with PCP who do not have AIDS, the typical duration of therapy is 14 days.
• Treatment of PCP in patients who have AIDS was increased to 21 days due to the risk for relapse after only 14 days of treatment (4)[C].

MEDICATION

• TMP-SMX (2,4)[C]
• Adult dosingTMP: 15 to 20 mg/kg/day, PO or IV, divided into 4 doses
• Pediatric dosing (>2 months) (4)[C]TMP: 15 to 20 mg/kg/day in divided doses q6 " “8h
• Reduce doses of TMP-SMX in patients with renal failure.
• Treatment response to Pneumocystis therapy often requires at least 7 to 10 days before clinical improvement is documented (2)[C].
• Pregnancy risk factor: Category C (4)[C]
• PrecautionsHistory of sulfa allergyThere is an emergence of drug-resistant PCP, especially against TMP-SMX.

• TMP: 15 to 20 mg/kg/day, PO or IV, divided into 4 doses

• TMP: 15 to 20 mg/kg/day in divided doses q6 " “8h

• History of sulfa allergy
• There is an emergence of drug-resistant PCP, especially against TMP-SMX.

• Pentamidine (for moderate to severe cases)Adults and children: 4 mg/kg IV or IM once daily
• Dapsone + trimethoprim (adults only)Dapsone 100 mg PO once daily, plusTrimethoprim 5 mg/kg PO TIDCheck the glucose-6-phosphate dehydrogenase level before beginning dapsone, as hemolysis may result.
• Clindamycin + primaquine (adults only)Clindamycin 600 to 900 mg IV q8h or 300 to 450 mg PO QID, plusPrimaquine 30 mg PO once daily
• AtovaquoneAdults: 750 mg PO BID (>13 years of age)Children: 40 mg/kg/day PO divided BID (max 1,500 mg)
• Note: Pentamidine has greater toxicity than TMP-SMX: hypotension, hypoglycemia, pancreatitis (4)[C].

• Adults and children: 4 mg/kg IV or IM once daily

• Dapsone 100 mg PO once daily, plus
• Trimethoprim 5 mg/kg PO TIDCheck the glucose-6-phosphate dehydrogenase level before beginning dapsone, as hemolysis may result.

• Check the glucose-6-phosphate dehydrogenase level before beginning dapsone, as hemolysis may result.

• Clindamycin 600 to 900 mg IV q8h or 300 to 450 mg PO QID, plus
• Primaquine 30 mg PO once daily

• Adults: 750 mg PO BID (>13 years of age)
• Children: 40 mg/kg/day PO divided BID (max 1,500 mg)

ADDITIONAL THERAPIES

• Adjunctive corticosteroids are shown to provide benefits in patients who have AIDS and symptoms of moderate to severe PCP.
• Corticosteroids provide the greatest benefit to HIV patients who have hypoxemia manifested as a partial pressure of arterial oxygen <70 mm Hg or an alveolar " “arterial gradient >35 mm Hg on room air.
• Adults and children >13 years of age: prednisone, 40 mg PO BID on days 1 to 5; 40 mg daily on days 6 to 11; 20 mg daily on days 12 to 21

INPATIENT CONSIDERATIONS

• No set criteria for hospital admission
• Five predictors of mortality in HIV-associated Pneumocystis pneumonia (8)Increased age of the patientRecent IV drug useTotal bilirubin >0.6 mg/dLSerum albumin <3 g/dLAlveolar " “arterial oxygen gradient ≥50 mm Hg (8)[C]

• Increased age of the patient
• Recent IV drug use
• Total bilirubin >0.6 mg/dL
• Serum albumin <3 g/dL
• Alveolar " “arterial oxygen gradient ≥50 mm Hg (8)[C]

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

DIET

PATIENT EDUCATION

• Centers for Disease Control and Prevention: www.cdc.gov/ncidod/dpd/parasites/pneumocystis/default.htm
• FamilyDoctor.org: http://familydoctor.org/familydoctor/en/diseases-conditions/hiv-and-aids/complications/pneumocystis-pneumonia-pcp-and-hiv.html

REFERENCES

ADDITIONAL READING

• Benson ‚ CA, Kaplan ‚ JE, Masur ‚ H, et al. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Disease Society of America. MMWR Recomm Rep. 2004;53(RR-15):1 " “112.
• Green ‚ H, Paul ‚ M, Vidal ‚ L, et al. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev. 2007;(3):CD005590.
• Kaplan ‚ JE, Masur ‚ H, Holmes ‚ KK. Guidelines for preventing opportunistic infections among HIV-infected persons " ”2002. Recommendations of the U.S. Public Health Service and the Infectious Disease Society of America. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5108a1.htm.
• Shankar ‚ SM, Nania ‚ JJ. Management of Pneumocystis jiroveci pneumonia in children receiving chemotherapy. Paediatr Drugs. 2007;9(5):301 " “309.
• Stringer ‚ JR, Beard ‚ CB, Miller ‚ RF, et al. A new name (Pneumocystis jiroveci) for Pneumocystis from humans. Emerg Infect Dis. 2002;8(9):891 " “896.

SEE ALSO

CODES

ICD10

ICD9

SNOMED

• 415125002 Pneumocystosis jiroveci pneumonia (disorder)
• 420403001 Pneumocystosis associated with AIDS

CLINICAL PEARLS

• Colonization with P. jiroveci is common in the pediatric population.
• PCP only occurs in immunocompromised patients.
• Patients with HIV are at risk once their CD4 count is <200 cells/ Ž ¼L. At that time, TMP-SMX should be initiated as prophylaxis. Prophylaxis may end after HAART has been initiated and the CD4 count is >200 cells/ Ž ¼L for 3 months.
• Patients who are immunocompromised are also at risk. Currently, no clear clinical guidelines are available as to when to initiate or end prophylaxis.
• The first-line treatment is TMP-SMX. The typical duration of therapy is 14 days in non " “AIDS-infected patients and 21 days in AIDS-infected patients.