> Table of Contents > Pneumonia, Pneumocystis Jiroveci
Pneumonia, Pneumocystis Jiroveci
Cameron M. Shawver, DO
Marvin H. Sineath Jr., MD, CAQSM
image BASICS
DESCRIPTION
  • Pneumocystis jiroveci causes pneumonia primarily in immunocompromised patients.
  • The fungus that causes this pneumonia in humans was previously called Pneumocystis carinii.
  • The name was formally changed to Pneumocystis jiroveci in 2001, following the discovery that the fungus that infects humans is unique and distinctive from the fungus that infects animals (1).
  • P. jiroveci is extremely resistant to traditional antifungal agents, including both amphotericin and azole agents (2).
  • To prevent confusion, the term PCP, which used to represent P. carinii pneumonia, now represents Pneumocystis pneumonia (3).
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/&mgr;L 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/&mgr;L.
      • 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/&mgr;L 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
image DIAGNOSIS
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/&mgr;L 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].
P.815

image 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]
image 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/&mgr;L 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
1. Catherinot E, Lanternier F, Bougnoux ME, et al. Pneumocystis jiroveci pneumonia. Infect Dis Clin North Am. 2010;24(1):107-138.
2. 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.
3. D'Avignon LC, Schofield CM, Hospenthal DR. Pneumocystis pneumonia. Semin Respir Crit Care Med. 2008;29(2):132-140.
4. Krajicek BJ, Thomas CF Jr, Limper AH. Pneumocystis pneumonia: current concepts in pathogenesis, diagnosis, and treatment. Clin Chest Med. 2009;30(2):265-278, vi.
5. Kovacs JA, Masur H. Evolving health effects of Pneumocystis: one hundred years of progress in diagnosis and treatment. JAMA. 2009;301(24): 2578-2585.
6. 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.
7. 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.
8. 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
&NA;
  • 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
&NA;
HIV/AIDS
Codes
&NA;
ICD10
B59 Pneumocystosis
Clinical Pearls
&NA;
  • 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/&mgr;L. 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/&mgr;L 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.