Low-Dose Trimethoprim-Sulfamethoxazole Prophylaxis for Pneumocystis jirovecii Pneumonia in a Critically Ill Patient with HIV/TB Coinfection: Pharmacokinetics and Clinical Outcomes

Xiaoqing Ma, Ruoying Zhang, Ren Zheng, Junjie Cheng, Chongyang Wu, Xinjun Cai, Jinmeng Li Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, 310000, People’s Republic of ChinaCorrespondence: Jinmeng Li, Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Email [email protected]: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection disease in immunocompromised patients, particularly those with advanced HIV and tuberculosis (TB) co-infection. Trimethoprim-sulfamethoxazole (TMP-SMZ) is recommended for PJP prophylaxis, but its pharmacokinetics (PK) and clinical efficacy in critically ill patients receiving multi-drug therapies (anti-TB, antiretroviral, and antifungals) remain poorly characterized.Case Presentation: This study reported the PK profile, multi-drug management strategies and clinical outcomes of low-dose TMP-SMZ (a combined dose of 480 mg once daily, 50% of the standard prophylactic dose) for PJP prophylaxis in a critically ill patient with disseminated TB, advanced HIV (CD4+ count: 21 cells/μL), and concurrent infections. The patient received TMP-SMZ alongside anti-TB therapy (isoniazid, rifabutin, levofloxacin, linezolid), voriconazole, and antiretroviral therapy. Therapeutic drug monitoring (TDM) showed peak concentrations of sulfamethoxazole (SMZ) and trimethoprim (TMP) were 18.58 μg/mL and 0.48 μg/mL, with trough concentrations of 1.75 μg/mL and 0.03 μg/mL, respectively. No drug–drug interactions were observed with concurrent voriconazole. The patient achieved stable recovery and without PJP or TMP-SMZ-related adverse events occurred during treatment and 6-month follow-up.Conclusion: This case reported the feasibility of low-dose TMP-SMZ for PJP prevention in high-risk, critically ill patients with HIV/TB coinfection, and described its PK characteristics. It provides a reference for optimizing prophylaxis in resource-limited settings or patients intolerant to standard regimens.Keywords: TMP-SMZ, low-dose, pharmacokinetics, case report