Pneumocystis carinii Pneumonia

Aka: Pneumocystis carinii Pneumonia, Pneumocystis jiroveci Pneumonia, Pneumocystis jiroveci, Pneumocystis carinii, PCP Pneumonia, Pneumocystis carinii infection

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II. Epidemiology

  1. United States Incidence: 20,000 to 60,000 cases/year
  2. HIV without prophylaxis develops PCP sometime
    1. Lifetime Incidence before 2008 (before HAART): 75-90%
    2. Incidence after 2008-2010 (after HAART): 0.5 per 100 person-years

III. Risk Factors

  1. HIV with CD4 Count related risk of Pneumocystis
    1. CD4 Count >200: Risk <1% over 6 months
    2. CD4 Count <200 (Accounts for 85-95% of cases)
      1. Risk 6% over 6 months
      2. Risk 18% at 1 year
  2. Immunosuppression in non-HIV conditions
    1. Solid organ or Hematopoietic Stem Cell Transplant recipients
    2. High dose Corticosteroids (Prednisone 20 mg or higher)
      1. Cancer Chemotherapy patients
      2. Rheumatologic Disease
    3. References
      1. Fillatre (2014) Am J Med 127(12): e11-7 +PMID: 25058862 [PubMed]

IV. Pathophysiology

  1. Pneumocystis defies classification
    1. Both Protozoan and Fungal Characteristics
  2. Recently renamed as Pneumocystis jiroveci
  3. Ubiquitous organism
    1. Most humans and mammals exposed early in life
    2. Clinically Significant infection occurs in AIDS with CD4 Count <250 cell/ul
  4. Clinical infection may represent reactivation

V. Symptoms

  1. Symptoms usually develop over 1-2 weeks
    1. Typical Bacterial Pneumonia develops over 3-5 days
  2. Initial Symptoms (occur in 66%, often subtle)
    1. Fever
    2. Malaise
    3. Non-productive Cough
    4. Exertional Dyspnea
  3. Pronounced Symptoms
    1. Sputum production
    2. Chest Pain
    3. Chills
    4. Exertional Dyspnea
      1. Profound Hypoxia occurs with even just a few steps taken

VI. Labs

  1. White Blood Cell Count Normal
    1. Elevated WBC Count in typical Bacterial Pneumonia
  2. Lactate Dehydrogenase (LDH) > 350 units/L associated with PCP
    1. Test Sensitivity: 78 to 100%
      1. Normal LDH may decrease the likelihood of PCP
    2. Test Specificity: 35 to 78%
      1. Elevated LDL also seen with Bacterial Pneumonia and Tuberculosis
  3. Sputum induction
    1. Methods
      1. Sputum PCR (preferred)
      2. Sputum DFA
    2. Efficacy
      1. Test Sensitivity 80-90% for Pneumocystis (induced Sputum with PCR)
        1. However expectorated Sputum has low Test Sensitivity
      2. Negative Predictive Value only 50-60%
    3. Examination stains
      1. Methenamine silver
      2. Giemsa stains
  4. Serum Beta D-Glucan
    1. High False Positive Rate
    2. Negative Predictive Value >95%
    3. Efficacy in AIDS for Beta D-Glucan >80 pg/ml
      1. Test Sensitivity: 92%
      2. Test Specificity: 65% (75% if respiratory symptoms)
    4. References
      1. Karageorgopoulos (2013) Clin Microbiol 19(1): 39-49 +PMID: 22329494 [PubMed]

VII. Imaging: Chest XRay

  1. Diffuse bilateral Interstitial Infiltrates (80-95%)
    1. Seen in Tuberculosis
    2. Seen in Bacterial Pneumonia
    3. Bat winging appearance
  2. Focal infiltrates rarely seen with Pneumocystis
  3. Images
    1. RadPneumocystisPneumoniaMedPix1121.jpgFrom MedPix with permission.
    2. RadPneumocystisPneumoniaMedPix6563.jpgFrom MedPix with permission.

VIII. Diagnosis

  1. Clinical diagnosis
  2. Definitive diagnosis is typically by bronchoalveolar lavage
  3. Factors suggestive of PCP
    1. Interstitial Infiltrates AND Thrush (Odds Ratio 11.8)
    2. Exertional Dyspnea
    3. Inspiratory crackles
    4. Subacute disease course

IX. Management: General

  1. Treatment Duration for 21 days (followed by PCP Prophylaxis)
  2. Treatment protocols are based on level of illness (esp if PaO2 <70 mmHg)
  3. Initiate Antiretroviral therapy within 2 weeks of PCP diagnosis (HIV patients)

X. Management: First-line agents

  1. Duration: 21 days of treatment and then prophylaxis
  2. Not critically ill (PaO2 >70 mmHg) and able to take oral medications
    1. No Corticosteroids indicated
    2. Trimethoprim-Sulfamethoxazole (Bactrim, Septra) DS 2 tabs orally every 8 hours (15 mg/kg of trimethoprim/day)
      1. Adverse reactions occur in 40-60% within 3 weeks
    3. Alternative (Fewer dose limiting adverse reactions, but risk of Methemoglobinemia)
      1. Dapsone 100 mg orally every 24 hours AND Trimethoprim 5 mg/kg orally every 8 hours
  3. Critically ill with Hypoxia (PaO2 <70 mmHg or A-a Gradient >35) or unable to take oral medications
    1. Start Corticosteroids 15-30 min before Antibiotics (see dosing below)
    2. Trimethoprim-Sulfamethoxazole (Bactrim, Septra) 15-20 mg/kg of trimethoprim/day IV divided every 6-8 hours

XI. Management: Alternative Regimen

  1. Duration: 21 days of treatment and then prophylaxis
  2. Not critically ill (PaO2 >70 mmHg) and able to take oral medications
    1. No Corticosteroids indicated
    2. Clindamycin 600 mg IV or 300-400 mg PO every 6 hours AND
    3. Primquine 15-30 mg of based every 24 hours or Atovaquone 750 mg po bid
  3. Critically ill (PaO2 <70 mmHg or A-a Gradient >35) or unable to take oral medications
    1. Start Corticosteroids 15-30 min before Antibiotics (see dosing below)
    2. Clindamycin 600 mg IV every 8 hours AND Primquine 15-30 mg of based every 24 hours OR
    3. Pentamidine 4 mg/kg/day IV (or IM)

XII. Management: Corticosteroids

  1. Efficacy
    1. Prevents alveolar inflammation and exudation
    2. Results from the killing of Pneumocystis organisms
    3. Reduces the risk of intubation and death by 50%
  2. Indications (based on Arterial Blood Gas)
    1. Arterial pO2 < 70 mmHg
    2. A-a Gradient > 35 mmHg on room air
  3. Dosing: Prednisone
    1. Start: 40 mg twice daily for 5 days
    2. Next: 40 mg every 24 hours for 5 days
    3. Taper: 20 mg every 24 hours for 11 days

XIII. Prevention: Pneumocystis Prophylaxis

  1. Indications
    1. CD4 Count <200 cells
    2. HIV patients with respiratory symptoms
  2. Duration
    1. Continue prophylaxis until CD4 Count >200 for at least 3 months
  3. First-Line Protocol
    1. Trimethoprim-Sulfamethoxazole (Bactrim, Septra)
      1. One DS or SS tab orally daily OR
      2. One DS 3 times weekly OR
  4. Alternative Protocols
    1. Pentamidine 300 mg in 6 ml sterile water aerosolized every 4 weeks OR
    2. Atovaquone 1500 mg orally every 24 hours with food OR
    3. Dapsone 200 mg and Pyrimethamine 75 mg AND Folinic Acid 25 mg once each week

XIV. Prognosis

  1. Treated appropriately: 10 to 20% mortality
    1. Higher mortality with severe infections
  2. Untreated: Uniformly fatal

XV. References

  1. Parker and Bond (2023) Crit Dec Emerg Med 37(10): 4-9
  2. Gilbert (2017) Sanford Guide (accessed IOS version 8/3/2017)
  3. Weller (2001) BMJ 322:1350-4 [PubMed]

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