Pneumocystis Jirovecii (PJP)


Epidemiology

Risk Factors

Immunodeficiency States

  • Agammaglobulinemia (see Agammaglobulinemia)
    • Clinical Syndromes
      • Autosomal Recessive Agammaglobulinemia: severe hypogammaglobulinemia, antibody deficiency, and increased susceptibility to infection
      • X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia): severe hypogammaglobulinemia, antibody deficiency, and increased susceptibility to infection
  • Common Variable Immunodeficiency (CVID) (see Common Variable Immunodeficiency)
  • Good Syndrome
    • Physiology
      • B-Cell Immunodeficiency Syndrome
    • Diagnosis
      • Hypogammaglobulinemia
      • Thymoma (Usually Spindle Cell Histology) (see Thymoma)

Hematologic Malignancy

  • Acute Lymphocytic Leukemia (ALL) (see Acute Lymphocytic Leukemia)
    • Epidemiology
      • Pneumocystis Jirovecii Predominantly Occurs in Childhood Acute Lymphocytic Leukemia Cases
  • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia)
    • Epidemiology
      • While there are a Few Reported Cases of Pneumocystis Jirovecii with Chronic Lymphocytic Leukemia Alone, the Risk Appears to Be the Greatest in Patients Who Have Received Corticosteroids and/or Fludarabine

Other Immunosuppression

  • Anti-CD20 Therapy (see Anti-CD20 Therapy)
    • Epidemiology
      • Anti-CD20 Therapy is a Clear Risk Factor for Pneumocystis Jirovecii
      • Majority of Reported Cases Had Also Received Cytotoxic Chemotherapy and Significant Doses of Glucocorticoids (Chest, 2013) [MEDLINE]
    • Agents
      • Rituximab (Rituxan) (see Rituximab): monoclonal antibody that binds to the CD20 antigen on B lymphocytes
    • Prognosis
      • Mortality Rate is High in These Cases
  • Anti-Tumor Necrosis Factor-α (Anti-TNFα) Therapy (see Anti-Tumor Necrosis Factor-α Therapy)
    • Epidemiology
      • Pneumocystis Jirovecii Cases Had Received an Average of 2 Drug Infusions
      • Mean Latency Between Drug Infusion and Onset of Symptoms: 21 days
    • Relative Risk: infliximab > etanercept/adalimumab
    • Physiology
      • Little is Known About the Role of TNFα in the Host Defense Against Pneumocystis Jirovecii, But Infliximab Decreases Peripheral and Gut Mucosal CD4 Counts in Patients with Crohn’s Disease (Dig Dis Sci, 2004) [MEDLINE] (Gastroenterology, 1999) [MEDLINE]
    • Prognosis
      • Mortality Rate: 27% (Dig Dis Sci, 2007) [MEDLINE]
  • Bendamustine (Treakisym, Ribomustin, Levact, Treanda, SDX-105, Bendeka) (see Bendamustine)
    • Epidemiology
      • Case Reports of at Least 14 Cases of Bendamustine-Associated Pneumocystis Jirovecii (Health Sci Rep, 2022) [MEDLINE]
        • Rituximab was Also Used in the Majority of These Cases (see Rituximab)
    • Pharmacology
      • Bendamustine is Associated with the Development of Lymphopenia
  • Chlorambucil (see Chlorambucil)
    • Epidemiology
      • Case Reports of Chlorambucil-Associated Pneumocystis Jirovecii (Postgrad Med J, 2004) [MEDLINE]
  • Corticosteroids (see Corticosteroids)
    • Epidemiology
      • Corticosteroid Use is One of the Strongest Risk Factors for Pneumocystis Jirovecii Infection
      • Pneumocystis Jirovecii is Associated with Corticosteroid Equivalent to >16 mg Prednisone/Day for at Least 8 wks (Arch Intern Med, 1995) [MEDLINE]
  • Cyclophosphamide (Cytoxan) (see Cyclophosphamide)
    • Epidemiology
      • Risk of Cyclophosphamide-Associated Pneumocystis Jirovecii Appears to Be Low (J Clin Rheumatol, 2008) [MEDLINE]
  • Cyclosporine A (see Cyclosporine A)
  • Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) (see Human Immunodeficiency Virus)
    • Epidemiology
      • Pneumocystis Jirovecii Occurs Most Frequently with (T-Helper) CD4 Count <250 Cells/mm3
        • Only 5% of Cases Occur in HIV Patients with CD4 Count >400
      • Incidence of Pneumocystis Jirovecii Has Decreased in the Era of Antiretroviral Therapy for HIV
  • Janus Kinase (JAK) Inhibitors (see Janus Kinase Inhibitors)
    • Ruxolitinib (Jakafi) (see Ruxolitinib)
      • Epidemiology
        • Case Report of Ruxolitinib-Associated Pneumocystis Jirovecii (BMJ Case Rep, 2014) [MEDLINE]
    • Tofacitinib (Xeljanz) (see Tofacitinib)
  • Methotrexate (see Methotrexate)
    • Epidemiology
      • Cases of Methotrexate-Associated Pneumocystis Jirovecii Have Been Reported (Some with Low-Dose Methotrexate Therapy for Rheumatoid Arthritis) (J Rheumatol, 1991) [MEDLINE] (Respir Med Case Rep, 2020) [MEDLINE]
      • Cases of Methotrexate-Associated Pneumocystis Jirovecii Have Been Reported in Patients Also Receiving Corticosteroids (Although at Corticosteroid Doses Lower than that Generally Associated with Pneumocystis Jirovecii) (Rev Rhum Engl Ed, 1996) [MEDLINE]


Physiology

Microbiology

Pneumocystis Jirovecii (Formerly Pneumocystis Carinii)

Pneumocystis Jirovecii Colonization

There is a Greater Degree of Lung Inflammation in Pneumocystis Jirovecii Patients Who are Not HIV-Positive (Am Rev Respir Dis, 1989) [MEDLINE]


Diagnosis

Serum (1–3)-β-D-Glucan (see Serum (1-3)-β-D-Glucan)

  • Diagnostically Useful, as the Cyst Wall Contains β-D-Glucan

Induced Sputum

General Comments

  • Widely-Used Diagnostic Method

Sensitivity/Specificity

  • Sensitivity (with Staining) in HIV-Related Cases: approximately 50-90%
    • Sensitivity is Lower in Non-HIV-Related Cases (Due to Decreased Organism Burden)

Staining for Pneumocystis Jirovecii

  • Gomori Methenamine Stain: useful to stain cyst forms
  • Wright–Giemsa Stain: can be used for identification of trophic forms within foamy exudates (sputum, bronchoalveolar lavage)
    • However, Requires a High Organism Burden and Expertise in Interpretation
  • Calcofluor White Stain: fungal cyst-wall stain that can be used for identification of cyst forms
  • Immunofluorescence Staining: can sensitively and specifically identify both pneumocystis trophic forms and cysts

Polymerase Chain Reaction (PCR) for Pneumocystis Jirovecii

  • Improves the Sensitivity for the Detection of Pneumocystis Jirovecii, Particularly in Non-HIV-Related Cases: however, due to high sensitivity, it may be difficult to differentiate organism carriage from infection
  • Sensitivity/Specificity (J Med Microbiol, 2002) [MEDLINE]
    • Induced Sputum: Sensitivity = 100%, Specificity = 90%
    • Bronchoalveolar Lavage: Sensitivity = 84%, Specificity = 93%
    • Negative Predictive Value: near 100%
      • Negative PCR Has Been Suggested to Allow Safe Discontinuation of Treatment (Chest, 2009) [MEDLINE]
  • Real-Time PCR: may allow differentiation of carriage vs infection (using threshold values of organism load)

Bronchoscopy (see Bronchoscopy)

  • Techniques
    • Bronchoalveolar Lavage (BAL): widely-used diagnostic method
      • Typically Higher BAL Neutrophil Counts and Lower Organism Counts are Found in Non-HIV-Related Cases
      • Sensitivity (with Staining) in HIV-Related Cases: >90%
      • Similar to Induced Sputum, Sensitivity is Lower (Approximately 38-53%) in Non-HIV-Related Cases (Due to Decreased Organism Burden)
    • Transbronchial Biopsy (TBB): may add to the diagnostic yield of induced sputum and bronchoalveolar lavage

Transthoracic Fine Needle Aspiration (TTNA) (see Transthoracic Fine Needle Aspiration)

  • May Be Required in Some Cases

Video-Assisted Thoracoscopic Surgery (VATS) with Lung Biopsy (see Video-Assisted Thoracoscopic Surgery)

  • May Be Required in Some Cases


Clinical Manifestations

General Comments

  • Pneumocystis Jirovecii Cases Associated with Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus)
  • Pneumocystis Jirovecii Cases Not Associated with HIV
    • Clinical Presentation is Generally Less Typical Than HIV-Associated Cases (Am Rev Respir Dis, 1989) [MEDLINE]
    • Clinical Course is More Fulminant Than HIV-Associated Cases (Am Rev Respir Dis, 1989) [MEDLINE]
    • Mortality Rate is Higher than in HIV-Associated Cases (Am Rev Respir Dis, 1989) [MEDLINE]
    • Disease is Often Associated with the Tapering of an Immunosuppressive Agent (Such as Prednisone or Cyclophosphamide)

Normal Chest X-Ray (CXR) Presentation

  • Epidemiology
    • Occurs in Approximately 10% of Cases
    • However, in Such Cases, Chest CT is Abnormal

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

  • Epidemiology
    • Respiratory Failure (with ARDS) May Occur (Chest, 2005) [MEDLINE]

Alveolar Pneumonia

  • Diagnosis
    • Serum Lactate Dehydrogenase (LDH) (see Serum Lactate Dehydrogenase)
      • Serum LDH Elevation is Highly Sensitive, But Not Very Specific (as Serum LDH Can Also Be Elevated in Other Pulmonary Processes, Such as Bacterial Pneumonia or Tuberculosis)
    • Chest X-Ray (CXR) (see Chest X-Ray)
      • Alveolar Infiltrates
    • Chest Computed Tomography (Chest CT) (see Chest Computed Tomography)
      • Mosaic Pattern or Ground-Glass Infiltrates: most common pattern is that with central densities
      • Lymphadenopathy: uncommon
      • Pneumatoceles/Pneumocysts: may occur (see Cystic-Cavitary Lung Lesions)
  • Clinical
    • Pneumonia-Like Presentation

Cryptogenic Organizing Pneumonia (COP) (see Cryptogenic Organizing Pneumonia)

  • Clinical
    • May Present with Pneumonia-Like Presentation

Interstitial Pneumonia (see Interstitial Lung Disease)

  • Diagnosis
    • Serum Lactate Dehydrogenase (LDH) (see Serum Lactate Dehydrogenase)
      • Serum LDH Elevation is Highly Sensitive, But Not Very Specific (as Serum LDH Can Also Be Elevated in Other Pulmonary Processes, Such as Bacterial Pneumonia or Tuberculosis)
    • Chest X-Ray (CXR) (see Chest X-Ray)
      • Interstitial Infiltrates
    • Chest Computed Tomography (Chest CT) (see Chest Computed Tomography)
      • Mosaic Pattern or Ground-Glass Infiltrates
      • Lymphadenopathy is Uncommon
  • Clinical
  • Example: 40 y/o white female on prednisone 40 mg PO qday, tapered to 30 mg qday 1 wk prior to admission (not on Pneumocystis Jirovecii prophylaxis)
    • Patient Presented with Dry Cough 2 Days Prior to Admission, at Which Time CXR was Read as Normal
    • On the Day of Admission, CXR was Remarkable for Faint Interstitial Infiltrates
    • On the Day After Admission, CXR was Remarkable for Alveolar and Interstital Infiltrates
    • Pneumocystis Jirovecii was Subsequently Diagnosed by Bronchoscopy with Bronchoalveolar Lavage

Lung Nodules (see Lung Nodule or Mass)

Pleural Effusion (see Pleural Effusion-Exudate)

  • Epidemiology
    • Pneumocystis Jirovecii Rarely Causes Pleural Effusion
  • Diagnosis
    • Usually Exudative

Pneumothorax (see Pneumothorax)

  • Epidemiology
    • Predisposed by Presence of Pneumocysts

Upper Lobe Cavitary Disease (see Cystic-Cavitary Lung Lesions)

  • Epidemiology
    • May Be Seen in Patients Who Have Been Receiving Inhaled Pentamidine Prophylaxis
  • Diagnosis
    • Bronchoscopy with Bronchoalveolar Lavage (BAL) (see Bronchoscopy)
      • Typically Higher BAL Neutrophil Counts and Lower Organism Counts are Seen in Non-AIDS Cases
  • Clinical
    • Mimics Tuberculosis


Prophylaxis (Med Mal Infect, 2014) [MEDLINE]

Indications

Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus)

Transplant

Immunosuppressive Administration

Primary Immunodeficiency States

Other

Prophylaxis Regimens


Treatment

Treatment of Pneumocystis Jirovecii in the Setting of Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) (see Human Immunodeficiency Virus)

General Comments

  • Indications for Hospitalization
    • Anticipated Significant Disease Worsening During Initial Therapy
      • Since Some Patients with Pneumocystis Jirovecii May Initially Worsen After the First 2-3 Days of Therapy
    • Moderate-Severe Disease Requiring Corticosteroid Therapy
    • Initial Treatment with Pentamidine Therapy (Due to the Potential Side Effects of Hypotension and/or Hypoglycemia)
    • Poor Outpatient Compliance with Medication or Laboratory Monitoring

Mild Disease (A-a Oxygen Gradient <35 mm Hg and/or pO2 ≥70 mm Hg)

  • Oral Therapy (in Patient with Adequate Oral Drug Absorption) x 21 Days
    • Sulfamethoxazole-Trimethoprim (Bactrim) (see Sulfamethoxazole-Trimethoprim)
      • First-Line Regimen
      • Dose: 15-20 mg/kg/day of the trimethoprim component PO or IV given in 3-4 divided doses
      • In Cases with Prior Sulfa Allergy, Some Patients Can Be Desensitized to Sulfamethoxazole-Trimethoprim
      • Cases of Sulfamethoxazole-Trimethoprim Resistance Have Been Reported
    • Dapsone + Trimethoprim (see Dapsone and Trimethoprim)
      • Second-Line Regimen
      • For Dapsone-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Setting of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Dapsone Dose: 100 mg PO qday
      • Trimethoprim Dose: 5 mg/kg PO TID
    • Clindamycin + Primaquine (see Clindamycin and Primaquine)
      • Third-Line Regimen
      • For Primaquine-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Setting of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Clindamycin Dose: 900 mg IV q8hrs or 600 mg IV q6hrs or 600 mg PO TID
      • Primaquine Dose: 30 mg (Base) PO qday
    • Atovaquone (Mepron, Malarone) (see Atovaquone)
      • Fourth-Line Regimen (Indicated in the Setting of Sulfa Allergy and Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Dose: 750 mg PO BID (Taken with Food)
    • Echinocandins (see Echinocandins)
      • Cyst Wall of Pneumocystis Jirovecii Contains β-D-Glucan
      • While Studies Have Suggested that Echinocandins May Be Used in the Setting of Sulfamethoxazole-Trimethoprim Intolerance or Failure, Their Role Requires Further Study
  • Corticosteroids are Not Required

Moderate Disease (A-a Oxygen Gradient ≥35 and <45 mm Hg and/or pO2 ≥60 and <70 mm Hg)

  • Oral Therapy (in Patient with Adequate Oral Drug Absorption) x 21 Days
    • Sulfamethoxazole-Trimethoprim (Bactrim) (see Sulfamethoxazole-Trimethoprim)
      • First-Line Regimen
      • Dose: 15-20 mg/kg/day of the trimethoprim component PO or IV given in 3-4 divided doses
      • In Cases with Prior Sulfa Allergy, Some Patients Can Be Desensitized to Sulfamethoxazole-Trimethoprim
      • Cases of Sulfamethoxazole-Trimethoprim Resistance Have Been Reported
    • Dapsone + Trimethoprim (see Dapsone and Trimethoprim)
      • Second-Line Regimen
      • For Dapsone-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Settin of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Dapsone Dose: 100 mg PO qday
      • Trimethoprim Dose: 5 mg/kg PO TID
    • Clindamycin + Primaquine (see Clindamycin and Primaquine)
      • Third-Line Regimen
      • For Primaquine-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Settin of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Clindamycin Dose: 900 mg IV q8hrs or 600 mg IV q6hrs or 600 mg PO TID
      • Primaquine Dose: 30 mg (Base) PO qday
    • Echinocandins (see Echinocandins)
      • Cyst Wall of Pneumocystis Jirovecii Contains β-D-Glucan
      • While Studies Have Suggested that Echinocandins May Be Used in the Setting of Sulfamethoxazole-Trimethoprim Intolerance or Failure, Their Role Requires Further Study
  • Corticosteroids (see Corticosteroids)
    • Prednisone: 40 mg PO BID x 5 Days, then 40 mg PO qday x 5 Days, then 20 mg PO qday x 11 Days (see Prednisone)
      • For Patients Unable to Take Oral Prednisone, Methylprednisolone IV Can Be Used Instead at 75% of the Prednisone Dose (see Methylprednisolone)
      • In HIV Patients with Pneumocystis Jirovecii Infection, Adjunctive Corticosteroids Decrease the Mortality Rate and Risk of Respiratory Failure (Cochrane Database Syst Rev, 2015) [MEDLINE]

Severe Disease (A-a Oxygen Gradient ≥45 mm Hg, pO2 <60 mm Hg, and/or Potential for Hypoxemic-Hypercapnic Respiratory Failure)

  • Intravenous Therapy (Until Clinically Stable with pO2 ≥60 mmHg and Respiratory Rate <25 Breaths/min, Then, May Switch to Oral Therapy) x 21 Days
    • Sulfamethoxazole-Trimethoprim (Bactrim) (see Sulfamethoxazole-Trimethoprim)
      • First-Line Regimen
      • Dose: 15-20 mg/kg/day of the trimethoprim component PO or IV given in 3-4 divided doses
      • In Cases with Prior Sulfa Allergy, Some Patients Can Be Desensitized to Sulfamethoxazole-Trimethoprim
      • Cases of Sulfamethoxazole-Trimethoprim Resistance Have Been Reported
    • Clindamycin + Primaquine (see Clindamycin and Primaquine)
      • Second-Line Regimen
      • For Primaquine-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Settin of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Clindamycin Dose: 900 mg IV q8hrs or 600 mg IV q6hrs or 600 mg PO TID
      • Primaquine Dose: 30 mg (Base) PO qday
    • Pentamidine (see Pentamidine)
      • Third-Line Regimen
      • Dose: 4 mg/kg IV qday
      • Adverse Effects (Common and May Be Severe): hypotension, hypoglycemia, nephrotoxicity, and pancreatitis
      • Contraindications: pregnancy
    • Echinocandins (see Echinocandins)
      • Cyst Wall of Pneumocystis Jirovecii Contains β-D-Glucan
      • While Studies Have Suggested that Echinocandins May Be Used in the Setting of Sulfamethoxazole-Trimethoprim Intolerance or Failure, Their Role Requires Further Study
  • Corticosteroids (see Corticosteroids)
    • Prednisone: 40 mg PO BID x 5 Days, then 40 mg PO qday x 5 Days, then 20 mg PO qday x 11 Days (see Prednisone)
      • For Patients Unable to Take Oral Prednisone, Methylprednisolone IV Can Be Used Instead at 75% of the Prednisone Dose (see Methylprednisolone)
      • In HIV Patients with Pneumocystis Jirovecii Infection, Adjunctive Corticosteroids Decrease the Mortality Rate and Risk of Respiratory Failure (Cochrane Database Syst Rev, 2015) [MEDLINE]

Immune Reconstitution Inflammatory Syndrome (IRIS) (see Immune Reconstitution Inflammatory Syndrome)

  • Background
    • Immune Reconstitution Inflammatory Syndrome is a Common Complication of Antiretroviral Therapy for Human Immunodeficiency Virus in the Setting of Various AIDS-Defining Illnesses
      • Immune Reconstitution Inflammatory Syndrome Represents a Paradoxical Worsening of a Treated Opportunistic Infection or Unmasking of Previously Subclinical, Untreated Infection
    • Initiating Antiretroviral Therapy Within 2 wks After Starting Treatment for Pneumocystis Jirovecii (with Clinical Stability) Provides the Best Benefit (PLoS One, 2009) [MEDLINE]
  • Clinical Data
    • Systematic Review and Meta-Analysis of Immune Reconstitution Inflammatory Syndrome (Lancet Infect Dis, 2010) [MEDLINE]
      • Incidence of IRIS is Variable Across Different AIDS-Defining Illnesses
        • Illnesses Associated with the Highest Incidence of IRIS: CMV retinitis, cryptococcal meningitis, tuberculosis
        • Illnesses Associated with the Lowest Incidence of IRIS: Kaposi sarcoma, herpes zoster
      • Incidence of IRIS is Inversely Correlated with the CD4 Count at Baseline
        • Higher Incidence of IRIS is Observed in Patients with CD4 <50 cells/μL: particularly in patients with tuberculosis, CMV-associated immune recovery uveitis, and cryptococcal meningitis
        • Higher Incidence of IRIS at Lower CD4 Counts is Not Surprising, Since CMV Retinitis is Typically an Infection Which Occurs at CD4 <50 cells/μL, Cryptococcal Meningitis Typically Occurs at Low CD4 Counts (While Tuberculosis and Kaposi Sarcoma Tend to Occur at Higher CD4 Counts)
      • Mortality Rate Associated with IRIS: 4%
        • Mortality Rate from IRIS is Much Higher with Cryptococcal Meningitis

Treatment Failure

  • Treatment Failure is Defined as Failure to Demonstrate Clinical Improvement After 4-8 Days of Therapy

Treatment of Pneumocystis Jirovecii in Other Settings

Mild Disease (A-a Oxygen Gradient <35 mm Hg and/or pO2 ≥70 mm Hg)

  • Oral Therapy (in Patient with Adequate Oral Drug Absorption) x 21 Days
    • Sulfamethoxazole-Trimethoprim (Bactrim) (see Sulfamethoxazole-Trimethoprim)
      • First-Line Regimen
      • Dose: 15-20 mg/kg/day of the trimethoprim component PO or IV given in 3-4 divided doses
      • In Cases with Prior Sulfa Allergy, Some Patients Can Be Desensitized to Sulfamethoxazole-Trimethoprim
      • Cases of Sulfamethoxazole-Trimethoprim Resistance Have Been Reported
    • Atovaquone (Mepron, Malarone) (see Atovaquone)
      • Second-Line Regimen
      • Dose: 750 mg PO BID (Taken with Food)
    • Clindamycin + Primaquine (see Clindamycin and Primaquine)
      • Third-Line Regimen
      • For Primaquine-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Setting of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Clindamycin Dose: 900 mg IV q8hrs or 600 mg IV q6hrs or 600 mg PO TID
      • Primaquine Dose: 30 mg (Base) PO qday
    • Dapsone + Trimethoprim (see Dapsone and Trimethoprim)
      • Third-Line Regimen
      • For Dapsone-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Setting of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Dapsone Dose: 100 mg PO qday
      • Trimethoprim Dose: 5 mg/kg PO TID
    • Echinocandins (see Echinocandins)
      • Cyst Wall of Pneumocystis Jirovecii Contains β-D-Glucan
      • While Studies Have Suggested that Echinocandins May Be Used in the Setting of Sulfamethoxazole-Trimethoprim Intolerance or Failure, Their Role Requires Further Study
  • Corticosteroids are Not Required

Moderate Disease (A-a Oxygen Gradient ≥35 and <45 mm Hg and/or pO2 ≥60 and <70 mm Hg)

  • Oral Therapy (in Patient with Adequate Oral Drug Absorption) x 21 Days
    • Sulfamethoxazole-Trimethoprim (Bactrim) (see Sulfamethoxazole-Trimethoprim)
      • First-Line Regimen
      • Dose: 15-20 mg/kg/day of the trimethoprim component PO or IV given in 3-4 divided doses
      • In Cases with Prior Sulfa Allergy, Some Patients Can Be Desensitized to Sulfamethoxazole-Trimethoprim
      • Cases of Sulfamethoxazole-Trimethoprim Resistance Have Been Reported
    • Clindamycin + Primaquine (see Clindamycin and Primaquine)
      • Second-Line Regimen
      • For Primaquine-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Setting of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Clindamycin Dose: 900 mg IV q8hrs or 600 mg IV q6hrs or 600 mg PO TID
      • Primaquine Dose: 30 mg (Base) PO qday
    • Dapsone + Trimethoprim (see Dapsone and Trimethoprim)
      • Third-Line Regimen
      • For Dapsone-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Setting of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Dapsone Dose: 100 mg PO qday
      • Trimethoprim Dose: 5 mg/kg PO TID
    • Echinocandins (see Echinocandins)
      • Cyst Wall of Pneumocystis Jirovecii Contains β-D-Glucan
      • While Studies Have Suggested that Echinocandins May Be Used in the Setting of Sulfamethoxazole-Trimethoprim Intolerance or Failure, Their Role Requires Further Study
  • Corticosteroids (see Corticosteroids)
    • Studies Indicate that There is a Greater Degree of Inflammation in Non-HIV Patients with Pneumocystis Jirovecii, Suggesting that Corticosteroid Treatment May Be Required (as it is in HIV Patients with Pneumocystis Jirovecii) (Am Rev Respir Dis, 1989) [MEDLINE]
      • Early Small Studies Indicated that High-Dose Adjunctive Corticosteroids May Accelerate Recovery in Severe Adult Non-HIV Pneumocystis Jirovecii (Chest, 1998) [MEDLINE]
      • Other Small Retrospective Studies Indicated that Corticosteroids Do Not Improve the Survival of Non-HIV-Infected Patients with Severe Pneumocystis Jirovecii, as Had Been Described for HIV-Infected Patients with Severe Pneumocystis Jirovecii Patients (Clin Infect Dis, 1999) [MEDLINE]
      • However, Larger Retrospective Studies Suggest that Addition of Early Corticosteroids to Anti-Pneumocystis Therapy in Non-HIV Patients is Not Associated with Improved Respiratory Outcomes (Chest, 2018) [MEDLINE]

Severe Disease (A-a Oxygen Gradient ≥45 mm Hg, pO2 <60 mm Hg, and/or Potential for Hypoxemic-Hypercapnic Respiratory Failure)

  • Intravenous Therapy (Until Clinically Stable with pO2 ≥60 mmHg and Respiratory Rate <25 Breaths/min, Then, May Switch to Oral Therapy) x 21 Days
    • Sulfamethoxazole-Trimethoprim (Bactrim) (see Sulfamethoxazole-Trimethoprim)
      • First-Line Regimen
      • Dose: 15-20 mg/kg/day of the trimethoprim component PO or IV given in 3-4 divided doses
      • In Cases with Prior Sulfa Allergy, Some Patients Can Be Desensitized to Sulfamethoxazole-Trimethoprim
      • Cases of Sulfamethoxazole-Trimethoprim Resistance Have Been Reported
    • Clindamycin + Primaquine (see Clindamycin and Primaquine)
      • Second-Line Regimen
      • For Primaquine-Containing Regimen, Patient Should Be Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, Due to Risk of Hemolytic Anemia in the Setting of Glucose-6-Phosphate Dehydrogenase Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency)
      • Clindamycin Dose: 900 mg IV q8hrs or 600 mg IV q6hrs or 600 mg PO TID
      • Primaquine Dose: 30 mg (Base) PO qday
    • Pentamidine (see Pentamidine)
      • Third-Line Regimen
      • Dose: 4 mg/kg IV qday
      • Adverse Effects (Common and May Be Severe): hypotension, hypoglycemia, nephrotoxicity, and pancreatitis
      • Contraindications: pregnancy
    • Echinocandins (see Echinocandins)
      • Cyst Wall of Pneumocystis Jirovecii Contains β-D-Glucan
      • While Studies Have Suggested that Echinocandins May Be Used in the Setting of Sulfamethoxazole-Trimethoprim Intolerance or Failure, Their Role Requires Further Study
  • Corticosteroids (see Corticosteroids)
    • Studies Indicate that There is a Greater Degree of Inflammation in Non-HIV Patients with Pneumocystis Jirovecii, Suggesting that Corticosteroid Treatment May Be Required (as it is in HIV Patients with Pneumocystis Jirovecii) (Am Rev Respir Dis, 1989) [MEDLINE]
      • Early Small Studies Indicated that High-Dose Adjunctive Corticosteroids May Accelerate Recovery in Severe Adult Non-HIV Pneumocystis Jirovecii (Chest, 1998) [MEDLINE]
      • Other Small Retrospective Studies Indicated that Corticosteroids Do Not Improve the Survival of Non-HIV-Infected Patients with Severe Pneumocystis Jirovecii, as Had Been Described for HIV-Infected Patients with Severe Pneumocystis Jirovecii Patients (Clin Infect Dis, 1999) [MEDLINE]
      • However, Larger Retrospective Studies Suggest that Addition of Early Corticosteroids to Anti-Pneumocystis Therapy in Non-HIV Patients is Not Associated with Improved Respiratory Outcomes (Chest, 2018) [MEDLINE]


Prognosis

Clinical Data

  • Comparative Small Taiwanese Study of Pneumocystis Jirovecii in Patients with/without Human Immunodeficiency Virus Infection (J Microbiol Immunol Infect, 2008) [MEDLINE]: n = 49
    • Most Common Immunocompromising Conditions in Study: HIV, malignancies
      • Mean CD4 Count: 110 cells/μL (higher in malignancy than in HIV, but difference was not statistically significant)
    • Mortality Rate of Pneumocystis Jiroveciii HIV-Positive Patients: 6.7%
    • Mortality Rate of Pneumocystis Jirovecii in HIV-Negative Patients: 50%
  • Retrospective Study of Pneumocystis Jirovecii Pneumonia in Lung Transplant Patients (Respir Med, 2020) [MEDLINE]: n = 47
    • Annual Incidence Rate: 2.7 Cases/1000 Lung Transplant Patients Per Year
    • Median Time from Lung Transplant was 2.4 ± 3.0 years
    • 65% of Patients were Not on Prophylaxis at the Time of PJP Diagnosis While All Patients were Receiving Steroids at the Time of PJP Diagnosis
    • PCP was Associated with a High Mortality in Lung Transplant Patients
      • 28-Day Mortality Rate: 15%
      • 90-Day Mortality: 23%
      • Factors Associated with Increased Mortality in PJP in Lung Translant Patients
        • Decreased FEV1
      • Everolimus treatment
      • Pseudomonas aeruginosa coinfection
      • Fungal coinfection (especially Aspergillus sp.)
      • Mechanical Ventilation
      • Vasopressors
      • Factors Not Associated with Increased Mortality in PJP in Lung Translant Patients
        • PCP Primary Prophylaxis
        • Steroid Modification During PJP
        • Number of Immunosuppressive Molecules
    • Data Suggest the Need for Lifetime PJP Prophylaxis in Lung Transplant Patients
    • Benefit of Adjuvant Steroids Remains Unclear


References

General

Etiology

Physiology

Diagnosis

Treatment

Prognosis