Pneumocystis jirovecii (PJ) is one of the most important fungal pathogens that causes pneumonia in immunocompromised patients [1]. The clinical characteristics and prognosis differ between human immunodeficiency virus (HIV) and non-HIV-infected patients [2]. Previous studies have shown that the hospital mortality for PJ pneumonia (PCP) in HIV-infected patients ranges 4–17.3% [3,4], and the reported mortality of PCP in immunocompromised non-HIV patients ranges 48–67% [5]. Trimethoprim and sulfamethoxazole (TMP-SMX) is the first-line treatment and prophylaxis regimen, which inhibits dihydropteroate synthase (DHPS), an essential enzyme in the folate synthesis pathway of PJ [1]. Anidulafungin, as an alternative regimen for PCP, has similar outcomes [6]. Widespread use of sulfa drugs has decreased the incidence of PCP, but mutations in the DHPS gene of PJ have recently increased because of prior exposure to sulfa drugs or transmission [7], [8], [9].

Two point mutations causing amino acid substitutions in the DHPS protein, Thr55Ala and Pro57Ser, have been found to possibly be associated with resistance against standard therapy with sulfa drugs [9]. However, the clinical implications of DHPS mutations on clinical outcomes remain uncertain, especially in the non-HIV-infected group. A multicentre prospective study in 2001, which enrolled 136 patients with HIV-1 infection and PCP, showed that patients with mutations in the DHPS (mDHPS) PCP did not have poorer outcomes than those with wild-type DHPS (wDHPS) PCP [10]. A large epidemiological study in 2010 found that the outcomes of PCP were primarily related to the underlying comorbidities and severity of PCP, and the presence of mutations was not the leading cause [11]. However, a recent study in Chile, which enrolled 46 HIV-infected and 10 non-HIV-infected patients, without TMP-SMX for prophylaxis, reported that mDHPS PCP patients had a significantly longer duration of mechanical ventilation [12]. Therefore, this study was conducted to investigate the association between mutations in the DHPS gene and clinical outcomes among non-HIV-infected patients with PCP.