Pneumocystis pneumonia (PCP)

Etiology

• infection with Pneumocystis carinii (Pneumocystis jirovecii) in immunosuppressed patients
  • HIV1 infection
  • organ transplantation (1-6 months after transplantation)
  • immunosuppression in association with immunosuppressant drugs
    • long-term treatment with glucocorticoids

Epidemiology

• 20% of patients with HIV develop PCP
• incidence increases with degree of immunosuppression
• most common AIDS-defining condition
• most common opportunistic infection in patients with AIDS
• most common cause of death in patients with AIDS

Pathology

• within the lung Pneumocystis attaches to alveolar type I pneumocytes
• slow propagation
• increased alveolar capillary permeability
• alterations in surfactants
• injury to alveolar type I pneumocytes

Clinical manifestations

• presentation is generally insidious
• progressive dyspnea
• fever, chills, night sweats
• non-productive (dry) cough
• tachypnea
• tachycardia
• weight loss
• lung auscultation unremarkable or may be crackles
• pneumothorax (see Complications:)
• generally more severe with organ transplantation than HIV1 infection
• other signs of HIV1 infection
  • Kaposi sarcoma (pigmented skin lesions, red-purple to dark brown-black)
  • oropharyngeal candidiasis (white, non-adherent, mucosal plaques)

Laboratory

• CD4 count < 200 cells/uL
• histopathological staining
  • specimens
    • sputum (induced by 3% saline)
    • bronchial brushings from bronchoalveolar lavage (BAL)
    • endotracheal aspirates
  • reagents which stain the walls of cysts
    • methenamine silver
    • toluidine blue
    • cresyl echt violet
  • Wright-Giemsa, which stains the nuclei of all developmental stages
  • immunologic methods
    • monoclonal antibodies
    • immunoperoxidase
    • immunofluorescence
  • claofluor (non-specific fluorochrome stain)
  • Papanicolaou stain
• reverse transciptase polymerase chain reaction (RT-PCR) for Pneumocystis jirovecii DNA
• serology not available
• no culture methods available
• complete blood count (CBC): leukocyte count is variable
• arterial blood gas (ABG):
  • hypoxia
  • wide A-a gradient
    • < 35 mm Hg & PaO2 > 70 mm Hg = mild
    • 35-45 mm Hg & PaO2 > 70 mm Hg = moderate
    • > 45 mm Hg & PaO2 < 70 mm Hg = severe
  • respiratory alkalosis
• increased serum lactate dehydrogenase (LDH)
  • reflects pulmonary inflammation
• see ARUP consult

Diagnostic procedures

• bronchoalveolar lavage for bronchial brushings if induced sputum does not yield diagnosis
  • endobronchial lesions are rare
• pulmonary function tests (PFT)

Radiology

• may be normal early in the course of the disease
• bilateral diffuse interstitial infiltrates, beginning in perihilar area
• nodular opacities & cavitary lesions may be seen
• increased incidence of upper lobe infiltrates & pneumothorax in patient receiving aerosolized pentamidine
• pleural effusions & lymphadenopathy are uncommmon & suggest another pathogen

Complications

• pneumothorax (most common cause of pneumothorax in patient with AIDS)
• prognosis more favorable with HIV1 infection than organ transplantation & is worst with long-term glucocorticoids

Differential diagnosis

• pneumonia due to
  • bacteria or mycobacteria
  • fungus
  • virus
• Kaposi's sarcoma
  • endobronchial violaceous macules or papules in the proximal airways
  • confluent hyperemic patches in the distal airways

Management

• antimicrobial therapy: (21 days of therapy)
  • trimethoprim/sulfamethoxazole (Bactrim, Septra)
    • Bactrim DS 2 tabs PO TID for 21 days
    • 5 mg/kg IV every 6 hours (based on trimethoprim)
    • step down to low-dose TMP-SMX (TMP 4-6 mg/kg/day) after 5 days of treatment lowers risk of adverse effects
  • alternatives in mild disease
    • atovaquone 750 mg (5 mL) PO BID with meals
    • dapsone 100 mg PO QD plus trimethoprim 15 mg/kg divided TID
    • clindamycin 600-900 mg IV every 8 hours plus primaquine 15-30 mg PO QD
  • alternatives in moderate to severe disease
    • pentamidine 4 mg/kg IV/IM QD
    • trimetrexate 45 mg/m2 over 60 minutes QD plus tetrahydrofolate (Leucovorin) 20 mg/m2 IV/PO QID
  • toxicity or intolerance often develops during the course of therapy & alternative agents may be necessary
• adjunctive glucocorticoids
  • indications: A-a gradient > 35 mm Hg or PaO2 < 70 mm Hg
  • prednisone (within 72 hours)
    • 40 mg PO BID for 5 days; then
    • 40 mg PO QD for 5 days; then
    • 20 mg QD for duration of anti-PCP therapy
  • benefits
    • minimize inflammatory response provoked by dying organisms
    • diminish deterioration of oxygenation
    • diminish likelihood of death, NNT = 9-22
  • risks
    • increased risk of other infections, NNH = 5
      • increased frequency of oral candidiasis & mucocutaneous Herpes simplex
      • exacerbation of undiagnosed fungal infection or mycobacterial infection
• prophylactic therapy:
  • indications
    • recovery from PCP infection
    • HIV patients with CD4 counts < 200/mm3
    • HIV patients with < 14% CD4/total lymphocytes
    • HIV patients with unexplained fevers lasting < 2 weeks
    • HIV patients with oral candidiasis
    • any AIDS-defining infection or Kaposi's sarcoma
  • antimicrobial prophylaxis
    • TMP/SMZ (Bactrim DS or Septra DS: 1 tab PO QD) (3 times/week may suffice)
    • dapsone 50-100 mg PO QD or 200 mg weekly
      • dapsone plus pyrimethamine 75 mg QD
    • aerosolized pentamidine 300 mg monthly
      • not as effective as Bactrim or dapsone
    • Fansidar (525 mg sulfadoxine & 25 mg pyrimethamine)
    • clindamycin (Cleocin) 450-600 mg BID-TID + primaquine 15 mg QD
    • atovaquone (Mepron) 750 mg QD-BID with or without pyrimethamine
    • sulfasalazine may lower risk in patients with rheumatoid arthritis
  • supplement with tetrahydrofolate (folinic acid) to prevent bone marrow suppression
  • discontinue prophylaxis for PCP when CD4 count > 200/mm3 for 3 months

More general terms

• pneumocystosis

Additional terms

• outpatient management of HIV related pneumonia
• pneumocystis chorioretinitis
• Pneumocystis jirovecii; Pneumocystis carinii (PCP)