What is PJP (Pneumocystis jirovecii Pneumonia)?
PJP is a potentially life-threatening opportunistic fungal pneumonia caused by Pneumocystis jirovecii that occurs in immunocompromised patients and can rapidly progress to severe respiratory failure and death if not recognized and treated promptly. 1, 2
Pathophysiology and Risk
P. jirovecii is a unicellular fungal organism that colonizes the respiratory tract of healthy individuals (20-50% of adults carry it asymptomatically), but causes severe pneumonia when cell-mediated immunity is impaired 3, 4
The infection progresses from minor illness to severe inflammatory pneumonia with respiratory failure, particularly in patients with compromised T-cell function 3
High-Risk Populations Requiring Prophylaxis
HIV/AIDS patients with CD4+ counts <200 cells/μL or <20% of total T-lymphocytes are at highest risk 1
Hematologic malignancy patients including:
- Acute lymphoblastic leukemia (ALL) patients throughout anti-leukemic therapy 3
- Allogeneic stem cell transplant recipients for at least 6 months post-transplant and while receiving immunosuppressive therapy 3, 1
- Patients receiving bispecific antibodies (teclistamab, elranatamab) due to 3.6-4.9% incidence in trials 3, 1
Solid organ transplant recipients for at least 6-12 months post-transplantation 1
Patients on prolonged corticosteroids receiving ≥20 mg prednisone daily (or equivalent) for ≥4 weeks 3, 1
Patients receiving specific immunosuppressive agents including:
- Alemtuzumab (minimum 2 months, until CD4 >200 cells/μL) 3
- Purine analogs and T-cell depleting agents (until CD4 >200 cells/μL) 3
- Triple immunosuppression regimens 1
Clinical Presentation
Non-HIV patients experience rapid progression with severe respiratory failure and poor prognosis compared to HIV patients 5
Key clinical features include:
- Intense hypoxemia and impaired lung diffusing capacity 6
- Subacute hypoxic respiratory failure 7
- Diffuse bilateral ground glass opacities with consolidations on imaging 7
- Elevated lactate dehydrogenase (LDH) 1, 2
Diagnostic Approach
Do not delay treatment while awaiting bronchoscopy if PJP is suspected based on clinical presentation, CT findings, and elevated LDH 1, 2
Obtain respiratory samples immediately before starting treatment:
- Bronchoalveolar lavage (BAL) with PCR for P. jirovecii DNA is the gold standard 2, 7
- BAL remains positive for several days despite appropriate therapy 1
- Immunofluorescence with monoclonal antibodies followed by fluorescent microscopy 6
- Serum (1-3)-β-D-glucan has high negative predictive value for ruling out PJP 6
First-Line Treatment
High-dose trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line treatment at 15-20 mg/kg/day of the trimethoprim component, divided every 6-8 hours for 14-21 days 1, 2
Adjunctive corticosteroids reduce mortality in severe PJP (PaO₂ <70 mmHg or A-a gradient >35 mmHg):
- Prednisone 40 mg twice daily for 5 days, then 40 mg once daily for 5 days, then 20 mg once daily for 11 days 1
- This benefit is well-established in HIV patients; less clear in non-HIV immunocompromised patients 1
Alternative Treatment Regimens
Clindamycin (600-900 mg IV every 6-8 hours) plus primaquine (15-30 mg base PO daily) is the preferred alternative when TMP-SMX cannot be used, and is superior to pentamidine for both efficacy and safety 1, 2
Critical: Check G6PD levels before using primaquine or dapsone to prevent life-threatening hemolytic anemia 1, 2
Atovaquone 750 mg PO twice daily with food is an alternative for mild-to-moderate disease only 2
Prophylaxis Regimens
TMP-SMX is the gold standard prophylaxis providing 91% reduction in PJP occurrence and 83% reduction in PJP-related mortality 1
Alternative prophylaxis options for TMP-SMX intolerant patients:
- Atovaquone 1500 mg daily (must be taken with food for adequate absorption) 3, 8
- Dapsone 100 mg daily (requires G6PD testing) 3, 8
- Aerosolized pentamidine 300 mg monthly 3, 8
Common Pitfalls to Avoid
Cognitive bias across providers may delay diagnosis in patients without overt risk factors, leading to fatal outcomes 7
Do not abruptly discontinue baseline steroids in chronic steroid users during PJP treatment, as this can precipitate adrenal crisis; adjunctive corticosteroids for PJP should be given in addition to baseline steroid requirements 1
Consider drug interactions: TMP-SMX with methotrexate increases risk of severe cytopenia 1
Failure to take atovaquone with food results in subtherapeutic levels and prophylaxis failure 8
Reassess if no response after 7 days with repeat imaging and consider bronchoscopy 1
Secondary Prophylaxis
All patients successfully treated for PJP require secondary prophylaxis to prevent recurrence 1, 2
Continue prophylaxis: