Pneumocystis Prophylaxis

Pneumocystis jirovecii pneumonia (PJP) primary prophylaxis in adults

Inclusion/Exclusion

Inclusion: Adults who may require PJP prophylaxis and are not covered by another guideline

Exclusion: Pediatric patients, patients undergoing solid organ transplant, patients with hematologic malignancies, and patients with HIV are beyond the scope of this guidance. They should be managed according to their respective internal protocols (HBC/CAR-T, SOT) or society/national guidance (HIV)

Selection of agent: 

Trimethoprim/Sulfamethoxazole (TMP/SMX) is the most effective regimen for PJP prophylaxis and the most well studied. Every effort should be made to use this agent when possible, including interrogation of reported allergies, and even consideration of induction of tolerance (desensitization) for truly allergic, high-risk patients.[i] Distant histories of benign cutaneous reactions may be able to undergo a one-step drug challenge with TMP/SMX.

Indications:

Risk for PJP is mediated by defects in cell mediated immunity, although other factors (underlying lung disease, other comorbidities) also play a role. Risks should be considered on a patient-by-patient basis. In general, benefits of prophylaxis are felt to outweigh the risks when a patient’s risk of PJP is ~6%.[ii] The list below includes some of the common indications but is not meant to be comprehensive. Society guidelines are a valuable resource, when available. If it is unclear whether a patient is indicated for prophylaxis, discuss with infectious diseases consult service (if inpatient) or e-consult infectious diseases (outpatient). Refer to society guidance when available (Rheumatology: EULAR[iii], HIV)

Prophylaxis generally indicated (not a comprehensive list): 

• Primary immunodeficiencies affecting cell mediated immunity
• Patients receiving a glucocorticoid dose ≥20mg prednisone equivalent daily for one month or longer with another cause of immunocompromise. 
  • Many clinicians will also provide prophylaxis to patients receiving high dose steroids alone, though this indication is less well studied, and risk likely varies based on other underlying risk factors (lymphopenia, rheumatic disease).[iv]^,[v]
• Lymphodepleting monoclonal antibodies (CD-52, anti-CCR4, anti-SLAMF, polatuzumab)
• Bruton tyrosine kinase inhibitors and phosphatidyl 3-kinase inhibitors
• Patients receiving cyclophosphamide, particularly when associated with other immunosuppression (data is limited)

Indications where prophylaxis may be considered in specific patients, but data is limited. Consider individual patient factors (underlying condition, other immunosuppression, underlying lung disease, duration of therapy)

• JAK inhibitors
• Anti CD-20 monoclonal antibodies; in particular, in patients with ANCA vasculitis, this is recommended by ACR[vi]
• Checkpoint inhibitors
• Other high dose immunosuppression
• mTOR kinase inhibitors
• Patients without HIV with CD4 counts <200 cell/mm3, including Sarcoidosis with lymphopenia

Duration of prophylaxis: 

Duration of prophylaxis should be individualized and generally is continued until the underlying risk factor is no longer present. High dose steroids and other medications can cause prolonged immunosuppression after discontinuation of the agent, and care should be taken in these cases. Refer to individual prescribing information, disease-state, or service-specific guidelines when available