A Clinical Study Of Pneumocystis Pneumonia And The Efficacy Of Caspofungin In HIV-negative Moderate-to-severe Patients

[Objectives]The aims of this study was to:(1)Investigate the efficacy of combination therapy of caspofungin and TMP/SMZ in moderate to severe pneumocystis jirovecii pneumonia(PJP)in patients without HIV infection,the relationship between therapeutic effect and plasma ?-1-3-D-Glucan(BDG)levels.(2)Find out the independent risk factors of prognosis in HIV negative patients with PJP.(3)Compare the clinical manifestations of HIV negative and HIV positive patients with PJP.(4)Analyze the relationship between lymphocyte subsets and prognosis in HIV negative patients with PJP.[Methods]The retrospective study conducted 684 patients with PJP clinical diagnosis in Peking Union Medical College Hospital from January 2012 to June 2018.The patients with positive real-time fluorescence quantitative PCR test and/or Gomori' s methena mine silver nitrate stain were confirmed PJP diagnosed.Patients with moderate or severe PJP were defined as PaO2?70 mmHg and/or D(A-a)O2?35 mmHg through the blood gas analysis.The peripheral blood lymphocyte levels of patients were measured by flow cytometry.[Results]1.In the first part,a total of 126 HIV negative moderate to severe PJP patients were enrolled.91 patients were treated with TMP/SMZ monotherapy,the other 35 patients were treated with combination therapy of caspofungin and TMP/SMZ.In the multivariate analysis,low lymphocyte counts(P=0.030),high serum LDH level(P=0.025)and shock(P<0.001)were significant risk factors for death.In all patients,there was no significant difference in the survival rate between the two treatments(P=0.842);In the group of BDG?800 pg/ml,the survival rate of patients receiving combined treatment was significant increased(P=0.039);Whereas,in the group of BDG<800 pg/ml,there was no statistically significant difference in the survival rate between two treatments(P=0.082).2.In the second part,a total of 105 PJP patients were enrolled,including 17 HIV positive and 88 HIV negative patients.Compared with HIV positive patients,HIV negative patients have the following characteristics:Laboratory tests showed that PaO2 was lower(P=0.054),D(A-a)O2 was higher(P<0.001),and LDH was higher(P=0.024);Pulmonary imagings showed that there were more consolidation of the lungs(P=0.029),while less cystic changes(P=0.001);In terms of prognosis,there were more demand of ICU(P=0.025)and mechanical ventilation(P=0.004),and 3-month mortality was higher(44%vs 12%,p=0.012).3.In the second part,HIV negative patients were divided into four groups according to the levels of CD4+T and CD8+T lymphocytes:19 patients in group 1(CD4+T<100 cells/?L,CD8+T<100 cells/?L),19 patients in group 2(CD4+T<100 cells/?L,CD8+T?100 cells??L),9 patients in group 3(CD4+T?100 cells/?L,CD8+T<100 cells/?L),and 41 patients in group 4(CD4+T?100 cells/?L,CD8+T?100 cells/?L).Patients in group 1 had the highest mortality rate(68%,the other three groups were 58%,33%and 29%,respectively,P=0.018)and LDH level(P=0.045).[Conclusions]1.High initial BDG may be a predictor of satisfactory caspofungin and TMP/SMZ response to PJP.2.A better choice of caspofungin and TMP/SMZ combination therapy in HIV negative patients with moderate or severe PJP when BDG?800 pg/ml.3.The initial low lymphocyte counts,high LDH level and shock were independent risk factors for the death of PJP patients.4.Compared with HIV positive PJP patients,HIV negative PJP patients have more acute onset,more severe symptoms and worse prognosis.5.There were more solid variant and less cystic variant in the lungs in HIV negative PJP patients compared with HIV positive PJP patients.6.Significant decrease in CD4+T and CD8+T cell counts at the same time indicates a poor prognosis in HIV negative patients with PJP.