β Key words Candida albicans albicans Candida C. albicans Candida glabrata Candida krusei albicans Candida C. glabrata
C. albicans albicans Candida β in vitro in vivo C. glabrata C. krusei I β γ µ Candida
Table. Institutionstakingpartinthisstudy FirstDepartmentofSurgery,SapporoMedicalUniversityHospital DepartmentofSurgery,KeiyukaiSapporoHospital DepartmentofCriticalCareMedicine,IwateMedicalUniversityHospital DepartmentofGastroenterologicalandGeneralSurgery,YamagataUniversitySchoolofMedicine TohokuUniversityHospitalEmergencyCenter DepartmentofSurgery,TohokuKoseinenkinHospital DepartmentofChestSurgery,TohokuKoseinenkinHospital DepartmentofSurgery,AshikagaRedCrossHospital DepartmentofSurgery,NagaokaChuoGeneralHospital EmergencyandCriticalCareMedicine,SchoolofMedicine,KeioUniversity ThirdDepartmentofSurgery,TohoUniversityOhashiMedicalCenter DepartmentofSurgery,JikeiUniversitySchoolofMedicine DepartmentofSurgery,TeikyoUniversityHospital TraumaandCriticalCareCenter,TeikyoUniversitySchoolofMedicine ThirdDepartmentofSurgery,NihonUniversityItabashiHospital DepartmentofEmergency,NihonUniversityItabashiHospital EmergencyMedicalCenter,NipponMedicalSchoolTamaNagayamaHospital DepartmentofEmergency,TokyoMedicalUniversityHachiojiMedicalCenter DepartmentofSurgery,KitazatoUniversityHospital EmergencyCenter,KitazatoUniversityHospital GastroenterologicalCenter,YokohamaCityUniversityMedicalCenter AdvancedCriticalCareandEmergencyCenter,YokohamaCityUniversityMedicalCenter DepartmentofEmergencyandCriticalCareMedicine,SaiseikaiKanagawakenHospital DepartmentofSurgery,YokohamaMinamiKyosaiHospital DepartmentofEmergencyandCriticalCareMedicine,ChibaUniversityHospital DepartmentofSurgery,DokkyoMedicalUniversity,KoshigayaHospital DepartmentofTraumaandCriticalCareCenter,DokkyoMedicalUniversity,KoshigayaHospital DepartmentofEmergencyandIntensiveCareMedicine,TeikyoUniversitySchoolofMedicine,IchiharaHospital EmergencyandCriticalCareMedicine,KimitsuChuouHospital EmergencyandCriticalCareMedicine,NaritaRedCrossHospital DepartmentofEmergencyandCriticalCareMedicine,KamedaMedicalCenter IntensiveCareUnit,ChibaHokusohHospital,NipponMedicalSchool AnesthesiologyandMedicalCrisisManagement,NagoyaCityUniversityGraduateSchoolofMedicalSciences DepartmentofEmergencyandCriticalCareMedicine,FujitaHealthUniversitySchoolofMedicine DepartmentofEmergencyMedicine,SocialInsuranceChukyoHospital DepartmentofTransplantationandImmunology,GraduateSchoolofMedicineKyotoUniversity DepartmentofDigestiveSurgery,KyotoPrefecturalUniversityofMedicine DepartmentofSurgery,ShigaUniversityofMedicalScience DepartmentofThoracicSurgery,ShigaUniversityofMedicalScience DepartmentofEmergencyandCriticalCareMedicine,SchoolofMedicine,KanazawaUniversity DepartmentofSurgery,FukuiPrefectureSaiseikaiHospital SecondDepartmentofSurgery,ToyamaMedicalandPharmaceuticalUniversity DepartmentofTraumatologyandAcuteCriticalMedicine,OsakaUniversityGraduateSchoolofMedicine DepartmentofEmergencyandCriticalCareMedicine,KansaiMedicalUniversityHospital DepartmentofGastrointestinalSurgery,OsakaCityGeneralHospital DepartmentofSurgery,OsakaGeneralMedicalCenter CriticalCareandTraumaCenter,OsakaGeneralMedicalCenter NakakawachiMedicalCenterofAcuteMedicine IntensiveCareUnit,HyogoMedicalColegeHospital MedicalCenterforEmergencyandCriticalCare,NaraPrefecturalNaraHospital ThirdDepartmentofSurgery,JapaneseRedCrossSocietyWakayamaMedicalCenter KagawaUniversityHospitalEmergencyMedicalCenter DepartmentofSurgery,MatsuyamaShiminHospital DepartmentofGastroenterologicalSurgery,HiroshimaUniversityHospital DepartmentofEmergency,HiroshimaUniversityHospital DepartmentofAnesthesiologyandIntensiveCareMedicine,HiroshimaCityHospital DepartmentofEmergencyandCriticalCareMedicine,KurumeUniversityHospital DepartmentofEmergency,IizukaHospital DepartmentofSurgery,IizukaHospital DepartmentofNeurosurgery,IizukaHospital DepartmentofCardiovascularSurgery,IizukaHospital DepartmentofSurgery,SagaPrefecturalHospitalKoseikan DepartmentofAnesthesiology,KagoshimaMedicalAssociationHospital
Clinical Symptoms/Findings (Fungi Bacteria) Clinical Symptoms/Findings (Fungi alone) Marked improvement Marked improvement Improvement /Aggravation Bacterial tests Identification of causative bacteria Identified Not identified Not conducted Administration of antibacterial agent during MCFG Treatment Administered Not administered Results of bacterial cultures Eradicated Decreased Increased Improvement /Aggravation (a)akottalgorithm Step
From Step Clinical Symptoms/Findings (Fungi alone) Marked improvement Improvement Aggravation Results of fungal cultures Results of fungal cultures Eradicated Decreased Increased Eradicated Decreased Increased Imaging findings (X-ray, CT, etc.) Imaging findings (X-ray, CT, etc.) Imaging findings (X-ray, CT, etc.) Disappeared Improved Aggravated Disappeared Improved Aggravated Disappeared Improved Aggravated Disappeared Improved Aggravated Serological test values Serological test values Serological test values Normalized Decreased Increased Normalized Decreased Increased Normalized Decreased Increased Overall Clinical Effects of Antifungals Effective Ineffective (b)akottalgorithm Step Fig.. AKOTTalgorithm StepandStepforobjectivelyevaluatingantifungalagenteficacyinpatientswithbothfungalandbacterialinfections. Inordertoevaluatetheeficacyofantifungalagentsinpatientshavingbothbacterialandfungalinfections,atwo-stepalgorithm wascreated. IntheStep(a),theresultsofclinicaleficacyforbothbacterialandfungalinfectionarere-evaluatedbyconsideringthecausativebacteriaandtheirsensitivitytoantibacterialagentsgivenduringtheantifungaltherapy,andclinicaleficacyforfungalinfectionaloneisassessed. IntheStep(b),theresultsoftheclinicaleficacyforfungalinfectionalonefrom Step-arere-evaluatedbyconsideringtheresultsoffungalcultures,imagingfindings, andserologicaltestvalues,andoveralclinicaleficacyofantifungalagentsisobtained.
II C. albicans C. glabrata Candida tropicalis Candida parapsilosis C. krusei Aspergillus fumigatus Aspergillus niger
Patients enrolled and collected (n 8) Safety analysis (n 78) Efficacy analysis (n ) Removed from safety analysis (n ) Did not obtain information regarding the presence or absence of adverse effects (n ) Removed from efficacy analysis (n 66) Did not meet inclusion criteria (n 54) Received MCFG for less than 5 days (n 8) Provided too little information to determine effectiveness (n ) Fig.. Patientanalysisbreakdown. Table. Baselinedemographicsandpatientprofilesineficacyanalysis Baselineprofiles Sex Male Female Age(years) Mean±SD Range Underlyingdisease Surgeryofdigestiveorgans GItractperforation Cerebrovasculardisease(stroke) Burns Diabetesmelitus Trauma Pneumonia Post-livertransplantation Severeacutepancreatitis Others Field Surgery Emergency/Intensive-caremedicine Classificationofmycosis Proven Probable/Possible No.(%)ofpatients (n=) 69( 6. 6) 43( 38. 4) 6.6±7.8 3 9 8( 6. ) (. 7) (9. 8) (9. 8) 8(7. ) 8(7. ) 6(5. 4) 4(3. 6) 4(3. 6) 3( 6. 8) 7( 4. ) 85( 75. 9) 59( 5. 7) 53( 47. 3) C. albicans C. glabrata γ
AKOTT Algorithm Step Step Marked improvement (N 4) Improvement (N 44) (N 38) Aggravation (N 6) Marked improvement (N 3) (N 4) (N ) (N 43) Improvement (N 44) (N ) (N ) (N ) Aggravation (N ) (N ) (N ) (N ) Effective (N 7) (N 6) Ineffective (N 8) (N 4) (N ) Fig.3. ResultsofAKOTTalgorithm evaluation. Table3. Classificationofprovenfungalinfections Provenfungalinfection No.ofpatients(total= 59) Candidiasis 58 Candidemia 9 Pulmonarycandidiasis 7 Urinarycandidiasis Candidaperitonitis 7 Candidaabscess 3 Candidacholangitis Aspergilosis Invasivepulmonaryaspergilosis Fungiisolated No.ofstrains(total= 78) C.albicans 36 C.glabrata C.tropicalis 5 C.parapsilosis C.krusei Candidaspp,nonspecific 9 A.fumigatus A.niger Yeast-likefungus γ III
Table4. Overalclinicaleficacy Field Surgery Emergencyand intensive-caremedicine Total Efective 9 53 7 Inefective Eficacy(%) 5 3 9/4 (79.) 3 9 53/76 (69.7) 8 7/ (7.) Table5. Eficacybydiagnosisoffungalinfections FungalInfection Proven Candidiasis Candidemia Pulmonarycandidiasis Urinarycandidiasis Candidaperitonitis Candidaabscess Candidacholangitis Aspergilosis Invasivepulmonaryaspergilosis Probable/Possible Total Eficacy(%) 44/57 (77. ) 44/56 (78. 6) 7/9 (77. 8) /6 (84. 6) 8/ (7. 7) 4/6 (66. 7) /3 (66. 7) / ( ) / (. ) / (. ) 8/43 (65. ) 7/ (7. ) Table8. Commondrug-relatedadversereactionsduringmicafungintherapy Adversereaction Abnormalhepaticfunction Elevatedγ-GTP ElevatedAl-p Elevatedbilirubin ElevatedALT Increasedplateletcount Mild 3 4 4 No.ofepisodes Moderate Serious 3 Total 6 6 5 4 4 4 Of78patientsevaluableforsafetyassessment,37sufered69 drug-relatedadversereactions. Table6. Eradicationoffungibymicafungintreatment Fungi C.albicans C.glabrata C.tropicalis C.parapsilosis C.krusei Candidaspp,nonspecific A.niger Yeast-likefungus Total Strainseradicated(%) 3/3 6/8 3/4 / / 7/9 / / 5/67 (74. ) (88. 9) (75. ) (. ) ( ) (77. 8) (. ) ( ) (77. 6) Table7. Eficacybymaximum dailymicafungindose Dose(mg) Efective Inefective Eficacy(%) 5 75 5 3 Total 5 5 3 5 3 7 7 7 6 4 8 6 4 / 5/3 ( 78. ) 5/7 3/3 ( 76. 7) 5/ ( 7. 4) 3/4 /5 7/( 7. )
C. albicans C. glabrata C. albicans C. glabrata C. krusei albicans C. albicans albicans C. albicans C. glabrata C. krusei C. albicans C. glabrata γ
β Candida Candida albicans Candida glabrata Candida albicans Aspergillus fumigatus β Candida albicans
Candida Aspergillus β
β