What is the treatment for PCP (Pneumocystis pneumonia or Phencyclidine use)?

Treatment of Pneumocystis Pneumonia (PCP)

First-Line Treatment

Trimethoprim-sulfamethoxazole (TMP-SMX) is the definitive first-line treatment for PCP at a dose of 15-20 mg/kg/day of the trimethoprim component, divided into doses every 6-8 hours for 21 days. 1, 2, 3

• For severe disease (PaO₂ <70 mmHg or A-a gradient >35 mmHg): Administer TMP-SMX intravenously at the same dosing with mandatory adjunctive corticosteroids 1, 2
• For mild-to-moderate disease: TMP-SMX can be given orally at 750 mg (5 mL of atovaquone suspension equivalent dosing) twice daily for 21 days 4
• TMP-SMX provides dual coverage against both PCP and encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae) 3

Adjunctive Corticosteroid Therapy

Add corticosteroids when PaO₂ is <70 mmHg on room air or alveolar-arterial gradient is >35 mmHg. 1, 2

The recommended regimen is:

• Prednisone 40 mg orally twice daily for 5 days 1
• Then prednisone 40 mg once daily for 5 days 1
• Then prednisone 20 mg once daily for 11 days (total 21 days) 1

Critical caveat: In non-HIV immunocompromised patients with critical respiratory insufficiency, adjunctive corticosteroids are not generally recommended and should only be considered on an individual basis 5, 2

First-Line Alternative Regimens (When TMP-SMX Cannot Be Used)

Clindamycin plus primaquine is the preferred alternative for TMP-SMX intolerance or treatment failure. 1, 2, 3

• Dosing: Clindamycin 600-900 mg IV every 6-8 hours (or 300-450 mg orally every 6 hours) plus primaquine 15-30 mg base orally daily 1, 2
• Mandatory pre-treatment: Check G6PD levels before initiating primaquine due to risk of hemolytic anemia in G6PD-deficient patients 1, 2
• Clindamycin plus primaquine is superior to pentamidine for both efficacy and safety 2

Second-Line Alternative Regimens

Pentamidine isethionate 4 mg/kg/day IV once daily over 60-90 minutes for 21 days is reserved for patients who cannot tolerate other options 2, 3, 4

• After 7-10 days of clinical improvement with IV pentamidine, consider switching to oral atovaquone to complete the 21-day course 2
• Do not combine pentamidine with TMP-SMX due to increased toxicity without added benefit 2
• Monitor for pentamidine-specific toxicities: renal toxicity, severe hypotension, prolonged QT interval, cardiac arrhythmias, and hypoglycemia 2

Atovaquone 1,500 mg (10 mL) orally twice daily with food for 21 days is an option for mild-to-moderate PCP 4

• Critical administration requirement: Must be taken with food to avoid lower plasma concentrations that limit therapeutic response 4
• Limited to mild-to-moderate disease only (A-a gradient ≤45 mmHg) 4

Treatment Monitoring and Response Assessment

Do not order repeat imaging earlier than 7 days after treatment initiation. 2

• Evaluate patients daily for clinical improvement 2
• If no clinical improvement within 5-8 days, consider switching to an alternative agent 2
• Treatment failure criteria include persistent fever, progressive or new infiltrates, and rising inflammatory markers after 7 days 2

Critical pitfall to avoid: Do not delay treatment while awaiting bronchoscopy if PCP is suspected based on clinical presentation, CT findings suggestive of PCP, and elevated lactate dehydrogenase 5, 2

Secondary Prophylaxis (Mandatory After Successful Treatment)

All patients successfully treated for PCP require secondary prophylaxis to prevent recurrence. 5, 1, 2

Preferred regimen: TMP-SMX 800/160 mg (one double-strength tablet) three times weekly or daily 1, 2, 3

Alternative options for sulfa-allergic patients:

• Atovaquone 1,500 mg orally daily 2, 3, 4
• Dapsone 100 mg orally daily (requires G6PD testing) 2, 3
• Aerosolized pentamidine 300 mg monthly 5, 1, 2

Duration of secondary prophylaxis:

• HIV patients: Continue until CD4 count >200 cells/μL for at least 3 months 2
• Solid organ transplant recipients: Continue for at least 6-12 months post-transplant 2
• Other immunocompromised patients: Continue indefinitely while immunosuppression persists 2

Special Populations and Considerations

Patients on chronic corticosteroids (≥20 mg prednisone daily for ≥4 weeks):

• Require PCP prophylaxis with TMP-SMX, which provides 91% reduction in PCP occurrence 2
• During active PCP treatment, do not abruptly discontinue baseline steroids (risk of adrenal crisis) 2
• Adjunctive corticosteroids for severe PCP should be given in addition to baseline steroid requirement 2

Patients receiving bispecific antibodies (teclistamab, elranatamab):

• Require PCP prophylaxis due to 3.6-4.9% incidence in clinical trials 2
• Temporarily discontinue bispecific antibody therapy during active PCP treatment until symptom resolution 2

Patients with severe hepatic impairment:

• Closely monitor following atovaquone administration due to risk of cholestatic hepatitis and fatal liver failure 4