Analysis of Mutations in Pneumocystis jirovecii Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China

Purpose: Pneumocystis jirovecii pneumonia (PJP) shows a high fatality rate in non-HIV patients. However, there are limited data on P. jirovecii drug resistance-related gene mutations in these patients. This study aimed to describe the prevalence of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of P. jirovecii in non-HIV patients in China, providing a reference for drug usage.

Methods: We analyzed the polymorphisms of DHPS and DHFR genes from 45 non-HIV patients in China, including P. jirovecii infection (n = 14) and P. jirovecii colonization (n = 31). This analysis also considered clinical characteristics, P. jirovecii burden, treatment response, and prognosis.

Results: Compared to the P. jirovecii colonization, P. jirovecii infection had significantly altered blood indicators (GR%, LY%, HGB, TP, ALB, CRP, P<0.05) with higher P. jirovecii burden (P<0.05) and worse prognosis (P<0.05). Additionally, patients with P. jirovecii infection were more susceptible to infections, such as the Epstein-Barr virus, Cytomegalovirus, Mycoplasma and Klebsiella pneumoniae. Although no known drug-resistance mutations were detected in the DHPS gene in this study, 10 nonsynonymous mutations were identified. Furthermore, 10 nonsynonymous and 2 synonymous mutations were found in the DHFR gene. However, these mutations were not associated with a worse prognosis.

Conclusion: Our results implied that TMP-SMX prophylaxis is still recommended for PJP in high-risk non-HIV patients in China.