Yun Wu,1 Huixin Shi,1 Wei Li,1 Yijun An,1 Yuhan Shao,1 Xia Rao,1 Nicholas R Waterfield,2 Wei Wang,3 Guowei Yang1 

1Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Warwick Medical School, Warwick University, Coventry, UK; 3Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China

Correspondence: Yun Wu; Guowei Yang, Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, Xi Cheng District, Beijing, 100050, People’s Republic of China, Tel +86-10-63139853 ; +86-10-63139130, Email wuyun@ccmu.edu.com; yangguowei@hotmail.com

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.

Keywords: Pneumocystis jirovecii pneumonia, mutation, drug resistance, prognosis, non-HIV