para>No combination of symptoms, signs, blood chemistries, or radiographic findings is diagnostic of P. jiroveci pneumonia (4). ‚
EPIDEMIOLOGY
- 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).
Incidence
- 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.
Prevalence
- 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
Mode of transmission is unknown; likely respiratory from infected host ‚
RISK FACTORS
Individuals at risk (4) ‚
- 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 prophylaxis
- 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.
- Medication
- Trimethoprim-sulfamethoxazole (TMP-SMX)
- 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
- Atovaquone suspension
- Adults: 1,500 mg PO once daily with food
- Children: not to exceed 1,500 mg/day
- 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.
- Dapsone
- Adults only: 50 mg BID or 100 mg once daily
- Pentamidine
- Adults only: 300 mg aerosolized every 4 weeks
- Discontinuation of prophylaxis
- 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 patients
- Subacute onset over several weeks
- Progressively worsening dyspnea
- Tachypnea
- Cough: nonproductive or productive of clear sputum
- Low-grade fever, chills
- Weakness, fatigue, malaise
- Non " “HIV-infected immunocompromised patients
- More acute onset with fulminant respiratory failure
- 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
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]. ‚
- 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 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]
- High-resolution CT is more sensitive than CXR.
Diagnostic Procedures/Other
- 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].
TREATMENT
The recommended duration of therapy differs in patients who are with/without AIDS: ‚
- 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 dosing
- TMP: 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]
- Precautions
- History of sulfa allergy
- There is an emergence of drug-resistant PCP, especially against TMP-SMX.
Second Line
- 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, plus
- Trimethoprim 5 mg/kg PO TID
- Check 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, plus
- Primaquine 30 mg PO once daily
- Atovaquone
- Adults: 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].
ADDITIONAL THERAPIES
Adjunctive corticosteroid (prednisone or methylprednisolone) (4)[C],(7)[A] ‚
- 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 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
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. ‚
Patient Monitoring
Serum lactate dehydrogenase levels, pulmonary function test results, and ABG measurements generally normalize with treatment. ‚
DIET
No special diet needed ‚
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
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.
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
HIV/AIDS ‚
CODES
ICD10
B59 Pneumocystosis ‚
ICD9
136.3 Pneumocystosis ‚
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.