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Temozolomide with cranial radiation increases risk for opportunistic infections, notably Pneumocystis jirovecii pneumonia (PJP). Clinical standards recommend PJP prophylaxis—first line is trimethoprim–sulfamethoxazole (TMP-SMX) given on daily or thrice-weekly schedules; alternatives (atovaquone, dapsone, or inhaled pentamidine) are used for sulfa allergy or intolerance with appropriate G6PD screening when relevant. Herpes prophylaxis (acyclovir) may be added based on steroid use or institutional policy but does not replace PJP prevention. Routine fluoroquinolone prophylaxis (Option D) is not standard and raises resistance/C. difficile concerns. The APRN should counsel on adherence, monitor for cytopenias (TMP-SMX can exacerbate myelosuppression), manage rash or GI intolerance, and coordinate vaccinations (inactivated influenza; avoid live vaccines during immunosuppression). Baseline and periodic CBCs guide therapy, and ongoing steroid exposure further elevates PJP risk. Clear documentation of start/stop criteria—often continuing until lymphopenia resolves or radiation/temozolomide phase ends—prevents gaps in protection.