Efficacy of caspofungin combined with trimethoprim/sulfamethoxazole as first‑line therapy to treat non‑HIV patients with severe pneumocystis pneumonia

Abstract

Abstract. Combined treatment with caspofungin and trimethoprim/sulfamethoxazole (TMP/SMZ) as salvage therapy in non-HIV positive patients with severe pneumocystis pneumonia (PCP) yields poor outcomes. It remains unknown whether the use of this combination strategy as a first-line therapy would improve patient outcomes. The present study aimed to assess the efficacy of caspofungin combined with TMP/SMZ as a first-line therapy in non-HIV positive patients with severe PCP. A retrospective cohort study was conducted between March 2016 and February 2017. Patient clinical characteristics and outcomes were compared between two groups receiving first-line and second-line therapy respectively. In addition, similar cases from previous studies were assessed. A total of 14 patients were included in the present study (mean age, 58.79±14.41 years); including 9 patients receiving caspofungin and TMP/SMZ as a first-line therapy and 5 that received it as a second-line therapy. The overall positive response rate was 71.43% (10/14), with 88.89 (8/9) and 40.00% (2/5) in the first-line and second-line therapy groups, respectively (P=0.095). The positive response rates of patients requiring invasive mechanical ventilation differed significantly between the first-line (5/6, 83.33%) and the second-line (0/3, 0%) therapy groups (P=0.048). All-cause hospital mortality was 42.86% (6/14), with mortality rates of 33.33 (3/9) and 60.00% (3/5) in the first-line and second-line therapy groups, respectively (P=0.580). Combined with previously reported cases (n=27), the positive response rate was significantly greater in the first-line therapy group (11/12, 91.67%) than in the second-line therapy group (8/15, 53.33%, P= 0.043). No significant differences were in all-cause mortality rates between the two groups (25.00 vs. 46.67%, P=0.424) were identified, despite the fact that all-course mortality in the first-line therapy group was ~50% that of the second-line therapy group. Therefore, the results of the present study indicate that combined caspofungin and TMP/SMZ as first-line therapy may be a promising and effective strategy to treat non-HIV positive patients with severe PCP, particularly for those requiring invasive mechanical ventilation.

The Long-Acting Echinocandin, Rezafungin, Prevents Pneumocystis Pneumonia and Eliminates Pneumocystis from the Lungs in Prophylaxis and Murine Treatment Models

“…With the increasing complexity of azole-based prophylaxis (e.g., drug-drug interactions), echinocandins have garnered attention for their potential in antifungal prophylaxis [ 38 , 39 ]. However, despite limited alternatives to standard TMP-SMX, micafungin, anidulafungin and CAS have not been recommended for prophylaxis against PCP based on in vivo efficacy [ 26 , 40 , 41 , 42 ]. The PK profile of rezafungin not only sets it apart from other echinocandins in traditional PK analysis; higher penetration of rezafungin at the infected tissue site, as observed compared with micafungin, may explain observed differences in efficacy compared with other echinocandins [ 23 ].…”

Caspofungin combined with TMP/SMZ as a first‐line therapy for moderate‐to‐severe PCP in patients with human immunodeficiency virus infection

“…Several case reports showed that after clinical failure or allergy of first‐line TMP/SMZ, most patients had their prognosis improved with second‐line therapy, which was combined with caspofungin and TMP/SMZ or other agents [15–17]. Moreover, studies focused on HIV‐negative patients with severe PCP showed that caspofungin combined with TMP/SMZ was a promising and effective first‐line therapy [18,19]. Zhang et al .…”

A retrospective study of patients with systemic lupus erythematosus combined with Pneumocystis jiroveci pneumonia treated with caspofungin and trimethoprim/sulfamethoxazole

“…Dr. Zhang Gensheng from Zhejiang University School of Medicine used caspofungin and coSMZ as a first-line treatment regimen for non-HIV PCP patients, and the results were similarly effective. [13] However, the primary disease of the patients in the above studies were not SLE, this study focused on the effect of combined use of caspofungin and coSMZ in patients of SLE with PCP, and hopefully, they could serve as a supplementary report to the treatment regimen. The results of this study are similar to those of the above studies, for both of them had proven that the combination of 2 drugs is effective in the treatment of PCP.…”

“…The combination of caspofungin in the treatment of PCP has been reported both in China and abroad, the prognosis of which was better than that of coSMZ alone. [11–13] From January 2013 to December 2017, 9 patients of SLE with PCP were admitted and treated with caspofungin combined with coSMZ in Rheumatology and Immunology Department, Tangshan Gongren Hospital. The data were analyzed and reported here.…”