Efficacy Of Caspofungin Combined With Trimethoprim/Sulfamethoxazole As First-line Therapy To Treat Non-HIV Patients With Severe Pneumocystis Pneumonia

ObjectiveCombined 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.MethodsA retrospective cohort study was conducted at the Second Affiliated Hospital,Zhejiang University School of Medicine between March 2016 and February 2017.PCP patients treated with caspofungin combined with TMP/SMZ was included.PCP diagnosed base on pulmonary symptoms,pulmonary imaging expressions and positive PCR and/or GMS results for respiratory secretions sample,simultaneously.And patients that were<18 years old,HIV positive or pregnant were excluded from the current study.Patient clinical characteristics and outcomes were compared between two groups receiving first-line and second-line therapy respectively.In addition,we screened the literature using the key words "Pneumocystis pneumonia","Pneumocystis jirovecii pneumonia","Pneumocystis carinii pneumonia" and "caspofungin" in the PubMed database,and similar cases from previous studies were assessed.ResultsA 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.ConclusionsTherefore,the current study indicate that combined caspofungin and TMP/SMZ as first-line therapy increased the positive response rate of non-HIV positive patients with severe PCP,and it may be a promising and effective strategy,particularly for those requiring invasive mechanical ventilation.However,due to a small sample size,the current study need some larger prospective or retrospective randomized trials to support.