When should we switch from Atovaquone to Septra (trimethoprim/sulfamethoxazole) for Pneumocystis jirovecii pneumonia (PJP) prophylaxis following a stem cell transplant?

When to Switch from Atovaquone to Septra for PJP Prophylaxis After Stem Cell Transplant

Start trimethoprim-sulfamethoxazole (Septra/TMP-SMX) at engraftment and continue for at least 6 months post-transplant and throughout the duration of immunosuppressive therapy, as TMP-SMX is the preferred first-line agent for PJP prophylaxis in allogeneic stem cell transplant recipients. 1

Primary Recommendation

• TMP-SMX should be initiated as the preferred prophylactic agent from the time of engraftment (Category 1 recommendation), not switched to from atovaquone 1
• Atovaquone is designated as an alternative agent only for patients who are TMP-SMX intolerant, not as a first-line option 1

Duration of Prophylaxis

Allogeneic HCT recipients require:

• Minimum of 6 months of prophylaxis post-transplant 1
• Continuation throughout the entire period of immunosuppressive therapy (IST) 1
• Extension beyond 6 months if still receiving IST or if CD4 count remains <200 cells/mcL 1

Clinical Context for Switching TO Septra

If a patient is currently on atovaquone, consider switching to TMP-SMX when:

• Tolerance improves: If atovaquone was started due to temporary TMP-SMX intolerance (e.g., cytopenias, hyperkalemia) that has now resolved 2
• Breakthrough risk concerns: Atovaquone has documented higher breakthrough PCP rates (9.6% in one study) compared to zero cases under TMP-SMX 2
• Additional infection coverage needed: TMP-SMX provides broader antimicrobial activity against Nocardia, Toxoplasma, Listeria, and common bacterial infections—benefits not provided by atovaquone 1

Important Caveats

Common pitfall: Many transplant centers inappropriately use atovaquone as first-line therapy due to concerns about TMP-SMX toxicity, but studies show only 45% of patients can tolerate TMP-SMX throughout the entire at-risk period 2

Before switching from atovaquone to TMP-SMX, verify:

• Resolution of prior adverse effects (leukopenia, hyperkalemia, rash) 2, 3
• Adequate renal function for TMP-SMX dosing 3
• No current acute GVHD requiring dose adjustments 1

TMP-SMX Desensitization Option

• If TMP-SMX intolerance occurred previously, consider desensitization protocols rather than continuing atovaquone indefinitely 1
• This approach allows patients to receive the superior prophylactic agent with broader antimicrobial coverage 1

Monitoring After Switch

Once switched to TMP-SMX, monitor:

• Complete blood counts for cytopenias (particularly leukopenia) 2, 3
• Serum potassium levels for hyperkalemia 3
• Serum creatinine for renal function 3
• Clinical tolerance during the first 2-4 weeks post-switch 3

Alternative Scenario: Staying on Atovaquone

Continue atovaquone instead of switching if:

• Documented severe TMP-SMX allergy or anaphylaxis occurred 1
• Persistent cytopenias preclude TMP-SMX use 2
• Severe renal dysfunction limits TMP-SMX dosing 3
• Patient experienced life-threatening TMP-SMX toxicity 1

Note: Patients maintained on atovaquone have higher rates of urinary tract infections (33% vs 7%) compared to those on TMP-SMX, representing another reason to favor switching when tolerable 3