C295 - Atovaquone Therapeutic Drug Monitoring and Real-Time Sequencing in Breakthrough Pneumocystis Jirovecii Pneumonia: A Case Study of Personalized Medicine

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Author Block: S. Panaccione¹, X. Zhou¹, T. Hong¹, S. Papadimatos², A. Tziotis², D. Farmakiotis², ¹The Warren Alpert Medical School of Brown University, Providence, RI, ²Beth Israel Deaconess Medical Center, Boston, MA
*Purpose: Pneumocystis jirovecii pneumonia (PJP) is increasingly diagnosed in transplant patients. Although atovaquone is an acceptable option of PJP prophylaxis and treatment of mild disease, the role of therapeutic drug (level) monitoring (TDM) remains incompletely defined and it is therefore not routinely used.
*Methods: We describe the case of a 63-year-old man with history of T-cell prolymphocytic lymphoma and haploidentical hematopoietic cell transplantation complicated by graft-versus-host disease, who developed breakthrough PJP while receiving atovaquone prophylaxis. The patient was receiving ruxolitinib with tapered prednisone and prophylaxis with letermovir, acyclovir, posaconazole, and atovaquone (1.5 g daily), taken without food. He developed cough, dyspnea, and fever; bronchoalveolar lavage (BAL) direct fluorescent staining and PCR confirmed PJ infection. Oral trimethoprim-sulfamethoxazole was initiated but discontinued due to vomiting, kidney injury and hyperkalemia.
*Results: Atovaquone serum level while on daily prophylaxis was subtherapeutic (6 mg/L). BAL PJ DNA sequencing did not reveal mutations associated with atovaquone resistance (Fig. 1). He was transitioned to treatment-dose atovaquone (750 mg twice daily) with fatty meals, resulting in a therapeutic level (28 mg/L) and resolution of symptoms and radiographic abnormalities (Fig. 2).
*Conclusions: PJP is challenging to manage, largely due to treatment toxicities. This case highlights the importance of individualized, “precision medicine” approaches, such as atovaquone TDM and pathogen gene sequencing from BAL in select cases.