β β Key words β Candida krusei Candida glabrata
β I β
Drugadministration Baselinecharacteristics Clinicalsymptom Mycologicaltests Plasmadrugconcn Adverseevents Laboratorytests ) -leadecg Clinicalphotograph Pre- Treatment Table. Scheduleofthepresentclinicaltrial Day- Day Day9- Day (endof Treatment) or withdrawal day AfterDay Rrquired, incaseofcontinuedadministrationafterday ) Hematology:WBC,RBC,hemoglobin,hematocrit,plateletcount,anddiferentialWBC(neutrophils,basophils,lymphocytes, monocytes,etc.) Bloodchemistry:AST(GOT),ALT(GPT),LDH,ALP,γ -GTP,totalprotein,totalbilirubin,totalcholesterol,triglyceride,BUN, creatinine,uricacid,andelectrolytes(na,kandcl) Urinalysis:Urinaryprotein(qualitative),urinarysugar(qualitative),andoccultblood(qualitative) Candida
number: : : Full Analysis Set/ Safety Analysis Set: : : Exclusion from Full Analysis Set /Safety Analysis Set: : : Per Protocol Set: 9 : : Exclusion from Per Protocol Set: 9 : : 9 days administration: (include - day administration) : : 9 Continuation & administration after days: : 9 : Exclusion from data of continued administration: : : Fig.. Numberofcasessubjecttoanalysisorexclusion. II Candida Candida albicans C. krusei C. glabrata
Table. BaselinecharacteristicsofpatientswithOPC Item group group Gender male female -9-9 -9 Age -9 9-9 -9 9 Mean±S.D.(Min,Max).±.9(,).±.(,9) In/Outhospital in out 9-9 -9-9 Bodyweight(kg) -9-9 -9 9-99 Mean±S.D.(Min,Max).±.(.,.).9±.(.,9.) oralcavity Siteoflesion pharynx oropharynx Severityof mild oropharyngeal moderate candidiasissymptoms severe Medicalhistory without with Complication without with Previousand/or without concomitanttreatment with 9 Microscopic positive examination negative veryfew afew Fungalrecovery + byculturestudy + + C.albicans 9 C.parapsilosis C.glabrata Candidaspp. C.albicans, C.tropicalis C.albicans, C.krusei C.albicans, C.glabrata 9 C.albicans, Candidaspp. Causativefungus C.tropicalis, C.glabrata C.albicans, C.tropicalis, C.glabrata C.albicans, C.krusei, C.glabrata C.albicans, C.glabrata, Candidaspp. C.tropicalis, C.glabrata, Candidaspp. < μ g/ml -FC Antifungal μ g/ml sceptibility < μ g/ml FLCZ to μ g/ml (MIC) < μ g/ml ITCZ μ g/ml 9 UnidentifiedCandidaspecies ANOVA:analysisofvariance test p=. ANOVA p=.9 p=. ANOVA p=. p=.9 Wilcoxontest p=. p=. p=. p=. p=. Wilcoxontest p=. p=. p=. p=. p=.
% n Cured.% Markedly improved.%.% 9% confidence interval:.-.% Improved.% 9.% Unchanged 9.% Aggravated n 9.%.%.%.9% 9.% 9% confidence interval:.-.%.% Fig.. GlobalimprovementinclinicalsymptomsonDayafteradministration (Primaryevaluation). % n Cured.%.% 9% confidence interval:.-.% Markedly improved.% Unchanged Improved.%.% 9.9% Aggravated n 9.%.%.%.%.%.% 9% confidence interval:.-.9% 9.% Fig.. Finalglobalimprovementinclinicalsymptomsattheendoftherapy.
.... Pain Difficulty in swallowing White patches Redness Scores Mean. Scores Mean... Pre n days days 9 Pre n days days Fig.. Severityscoresforclinicalsymptoms. scores Pre n n days Mean S.D. days 9 Fig.. severityscoresforclinicalsymptoms. C. albicans µ µ
Table. Globalimprovementinclinicalsymptomsinrelationtomycologicaleficacy(onDayafteradministration) group Globalimprovementinclinicalsymptoms Cured Markedly improved Improved Unchanged Aggravated Eradicated Mycological eficacy Reduced Unchanged Aggravated group Globalimprovementinclinicalsymptoms Cured Markedly improved Improved Unchanged Aggravated Eradicated Mycological eficacy Reduced Unchanged Aggravated ng/ml, estimated : individually measured, n 9 estimated : individually measured, n, Itraconazole plasma,, Time after last drug administration h Fig.. Time-courseofplasmadrugconcentrationonDayafteradministration. µ
Table. GlobalimprovementinclinicalsymptomsstratifiedbyseverityonDayafteradministration Severityof clinical symptoms Mild Moderate Severe Group Cured Markedly improved Severityofclinicalsymptoms Mild:Smalnumberofslightwhitepatchesorredness Moderate:Punctatewhitepatchesorredness Severe:Fusedwhitepatchesorredness Globalimprovementinclinicalsymptoms Moderate improved 9 Unchanged Aggravated Curedrate (%)...9. 9.. rateof(cured+ markedlyimproved) Table. GlobalimprovementinclinicalsymptomsstratifiedbytypeofinfectiononDayafteradministration Globalimprovementinclinicalsymptoms Typeof Group infection Markedly Moderate Curedrate Cured Unchanged Aggravated improved improved (%). Systemic ) 9.. Local ) 9. Unknown Localizedinfection ) localmanifestationofsystemiccandidainfection ) localizedcandidainfection.. rateof(cured+ markedlyimproved) Table. GlobalimprovementinclinicalsymptomsstratifiedbycausativefungusonDayafteradministration Globalimprovementinclinicalsymptoms Causative Group fungus Markedly Curedrate Cured Improved Unchanged Aggravated improved (%) C.albicans C.glabrata C.parapsilosis 9 Unidentified Candidaspecies 9 9..9 (-) (-) (-) (-) Twoormore 9 9. diferentcandida species 9. rateof(cured+ markedlyimproved)
Table. GlobalimprovementofclinicalsymptomsstratifiedbythecategoryofFLCZsusceptibilityonDayafteradministration Globalimprovementinclinicalsymptoms FLCZ Group susceptibility Markedly Curedrate Cured Improved Unchanged Aggravated improved (%) Susceptible. (MIC,< μ g/ml). Resistant (MIC, μ g/ml) (-) (-) rateof(cured+ markedlyimproved) Table. Safetyevaluations Adverseevents Group Adverseevents Noadverseevents 9% confidenceinterval (.%) (.%).-. (.%) (.%).-. Sideefects Group Mild Severityofsideefect Moderate Severe Noside efect 9% confidence interval 9 (.%) (.%).-. (.%) (.%) 9.-.9 III C. albicans C. glabrata β
Candida µ β β
in vitro in vitro
β β β