Study On Efficacy And Safety Of Different Antifungal Treatment Regimens For Cryptococcal Meningitis In Non-HIV Infected People

Objective: To investigate the clinical efficacy and safety of different antifungal regimens for the treatment of cryptococcal meningitis in non-HIV infected individuals,and to provide a reference for the selection of rational antifungal treatment regimens and reduction of adverse events for non-HIV infected cryptococcal meningitis.Methods:A retrospective study about the clinical data of 88 patients with Non-HIV infected cryptococcal meningitis who were admitted to the First Affiliated Hospital of Guangxi Medical University.There were divided into four groups according to different treatment regimens,including amphotericin B plus fluconazole and 5-fluorocytosine group(AMB plus FCZ and 5-FC group)37 cases,amphotericin B and fluconazole group(AMB and FCZ group)9 cases,amphotericin B and 5-fluorocytosine group(AMB and 5-FC group)14 cases,fluconazole and 5-fluorocytosine group(FCZ and 5-FC group)28 cases.Compared with each group efficacy was evaluated in terms of pathogen negative rate,biochemical improvement of cerebrospinal fluid(CSF),decreased latex agglutination test titer,clinical symptoms and signs improvement.The safety were evaluated by comparing the incidence of hepatorenal impairment,hypokalemia,and thrombocytopenia in each group.All the data were by the SPSS17.0 for processing analysis.Result:1.General information:The male to female ratio was 2.52 to 1.The peak incidence was in the middle-aged and young stage.43 cases(48.86%)were with the basic disease,6 cases(6.82%)had pigeon contact history,and 8 cases(10.22%)were given hormones and immunosuppressive agents.The clinical manifestations of the disease are non-specific and all patients have headache symptoms.Biochemical changes in cerebrospinal fluid were characterized by elevated protein levels and decreased sugar and chloride levels.Baseline data except for CSF chloride were not statistically difference(p>0.05).2.Efficacy assessment:(1)Cumulative negative conversion rate of CSF cryptococcosis: The eight-week cumulative negative rate of AMB plus FCZ and 5-FC group,AMB and FCZ group,AMB and 5-FC group,FCZ and 5-FC group were respectively 94.59%,88.89%,85.71%,71.46%;AMB plus FCZ and 5-FC group cumulative negative rate is higher than FCZ and 5-FC group,there are statistically difference(p<0.05);There were not statistically difference between AMB plus FCZ and 5-FC group,AMB and 5-FC group,AMB and FCZ group(p>0.05);There were not statistically difference between AMB and 5-FC group,AMB and FCZ group,FCZ and 5-FC group(p>0.05).The two-week cumulative negative rate of FCZ and 5-FC group,AMB and 5-FC group are respectively 25%,28.57%,compared with AMB plus FCZ and 5-FC group(59.45%)Significantly low,there are statistically difference(p<0.05).(2)Accumulated negative rate of CSF cryptococcosis smear: The four-week cumulative negative rate of AMB plus FCZ and 5-FC group,AMB and FCZ group,AMB and 5-FC group,FCZ and 5-FC group were respectively 35.13%、44.44%、35.71%、21.42%,there were not statistically difference(p> 0.05).(3)After the antifungal treatment,the CSF protein decreased,and the CSF sugar and chlorine increased.All groups had different degrees of improvement.After treatment for 4 weeks,the median decrease in CSF protein in the AMB plus FCZ and 5-FC group,AMB and FCZ group,AMB and 5-FC group,FCZ and 5-FC group were respectively 136 mg/l,126.1 mg/l,242.75mg/l,21.9mg/l;The average CSF glucose rises were respectively 0.93±0.97 mmol/l,0.75±1.03 mmol/l,1.66±0.89 mmol/l,0.55±0.55 mmol/l;The average values of chloride rise were respectively 7.08±7.88 mmol/l,6.80±4.64 mmol/l,8.29±10.49 mmol/l,5.30 ± 8.23 mmol/l.The decrease of CSF protein in AMB plus FCZ and 5-FC group,AMB and FCZ group,AMB and 5-FC group,were more than FCZ and 5-FC group,there are statistically difference(p<0.05).There were not statistically difference between AMB plus FCZ and 5-FC group,AMB and FCZ group,AMB and 5-FC group(p>0.05).The increase of CSF sugar in AMB and 5-FC group was better than AMB plus FCZ and 5-FC group,AMB and FCZ group,FCZ and 5-FC group,there were statistically difference(p<0.05);There were not statistically difference between AMB plus FCZ and 5-FC group,AMB and FCZ group,FCZ and 5-FC group(p>0.05).There were no statistically difference in the increase of CSF chloride between groups(p>0.05).(4)After 4 weeks of treatment,the average titer of CSF latex agglutination test in AMB plus FCZ and 5-FC group,AMB and FCZ group were respectively 1:26.04,1:45.25,there were not statistically difference(p>0.05).(5)The cumulative DDD of CSF cryptococci cultures in AMB plus FCZ and 5-FC group,AMB and FCZ group,AMB and 5-FC group,FCZ and 5-FC group were respectively 53.63±25.16、41.67±22.08、52.45±24.35、58.93±30.85,there were not statistically difference(p>0.05).(6)After the antifungal treatment,the clinical symptoms of patients in all groups were improved to varying degrees.After 4 weeks of treatment,the headache rates in AMB plus FCZ and 5-FC group,AMB and FCZ group,AMB and 5-FC group,FCZ and 5-FC group were respectively 43.24%,44.44%,42.86%,46.42%;The fever rates were respectively 8.11%,11.11%,14.29%,17.86%;The nausea and vomiting rates were respectively 5.14%,11.11%,7.14%,14.28%;The rate of consciousness change were respectively 2.70%,0.00%,0.00%,3.57%;The stimulation rates were respectively 10.81%,22.22%,7.14%,25.00%.There were not statistically difference in the improvement of clinical symptoms and signs between the groups(p>0.05).3.Security assessment:The incidence of adverse events in the AMB plus FCZ and 5-FC group,AMB and FCZ group,AMB and 5-FC group,FCZ and 5-FC group were respectively 39.86%,41.67%,42.85%,19.96%.The safety of FCZ and 5-FC group was significantly higher than that of the other three groups,there were statistically difference(p<0.05).The safety of AMB plus FCZ and 5-FC group,AMB and 5-FC group,AMB and FCZ group were not statistically difference(p>0.05).4.When CSF cryptococcal latex agglutination test titer 1:256,positive rate of cryptococcal CSF smear is 100%;when CSF cryptococcal latex agglutination test is <1:256,The positive rate of CSF cryptococcal smear decreased with the decrease of latex agglutination test titer.Conclusion:(1)The four regimens are effective for treating cryptococcal meningitis in non-HIV-infected individuals and have various degrees of adverse events.(2)The AMB plus FCZ and 5-FC regimen more than AMB and 5-FC regimen,FCZ and 5-FC regimen kill cryptococcal more quickly for treating cryptococcal meningitis in non-HIV-infected individuals.(3)The AMB plus FCZ and 5-FC regimen is effective for treating cryptococcal meningitis in non-HIV-infected individuals and can be used clinically.(4)AMB and 5-FC regimen is used to treat cryptococcal meningitis in non-HIV-infected individuals.The biochemical improvement of CSF is significantly greater than other schemes.(5)The FCZ and 5-FC regimen is the safest option for treating cryptococcal meningitis in non-HIV-infected individuals.The safety of the three AMB-containing regimens are comparable and the adverse events are significant.(6)CSF Cryptococcus Culture of non-HIV infected cryptococcal meningitis are faster than smears and latex agglutination tests.(7)In non-HIV infected cryptococcal meningitis,CSF Cryptococcus latex agglutination test titer 1:256,the positive rate of cerebrospinal fluid cryptococcosis smear was 100%.