日本化学療法学会雑誌第58巻第2号
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- こうしろう このえ
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1 Key words β Candida
2 Table1. MCFGCPAstudygroup Investigator (representative) YoshitsuguMiyazaki NaoyukiMiyashita RyoichiAmitani KenjiOgawa AtsuyukiKurashima ToshiroKiguchi MichiakiMishima YuichiInoue HiroshiSaito HiroyukiTaniguchi HirofumiMiyawaki KunihikoYoshimura AkihikoKawana YosukeAoki MasaoTateyama YoshiroMochizuki YoshihiroYamamoto TadashiIshida YoshioTaguchi TakeshiOguma HirokiTakahashi OsamuTaguchi JiroOkimoto MichiakiHoriba AkitakaIwagaki JunichiKadota KiyoyasuFukushima YasumasaDohtsu AtsushiNagai AtsuoSato TakefumiSaito KatsuhiroSuzuki YasuhiroYamazaki MasaruOritsu HidekiNishiyama ( ):CurentAfiliation Institution SecondDepartmentofInternalMedicine,NagasakiUniversityHospitalofMedicineandDentistry (DepartmentofBioactiveMolecules,NationalInstituteofInfectiousDiseases) DivisionofRespiratoryDiseases,KawasakiMedicalSchoolHospital DepartmentofPulmonaryMedicine,OsakaRedCrossHospital DepartmentofPulmonaryMedicine,NationalHospitalOrganizationHigashiNagoyaNationalHospital DepartmentofRespiratoryDiseases,NationalHospitalOrganizationTokyoNationalHospital (DepartmentofRespiratoryMedicine,Double-BaredCrossHospital) DepartmentofRespiratoryMedicine,TachikawaMedicalCenter,TachikawaGeneralHospital (DepartmentofRespiratoryMedicine,KiguchiInternalMedicineClinic) DepartmentofRespiratoryMedicine,KyotoUniversityHospital InternalMedicine,IsahayaHealthInsuranceGeneralHospital DepartmentofRespiratoryMedicine,AichiCancerCenter,AichiHospital DepartmentofRespiratoryMedicineandAlergy,ToseiGeneralHospital DepartmentofInternalMedicine,KagawaPrefecturalCentralHospital DepartmentofRespiratoryMedicine,ToranomonHospital DepartmentofRespiratoryMedicine,InternationalMedicalCenterofJapan,ToyamaHospital (SecondDepartmentofInternalMedicine,NationalDefenseMedicalColegeHospital) DepartmentofLaboratoryMedicine,SagaUniversityHospital FirstDepartmentofInternalMedicine,FacultyofMedicineandUniversityHospital,UniversityoftheRyukyus InternalMedicineDepartment,NationalHospitalOrganization,HimejiMedicalCenter DepartmentofRespiratoryMedicine,SaseboCityGeneralHospital (SecondDepartmentofInternalMedicine,NagasakiUniversityHospital) DepartmentofRespiratoryMedicine,KurashikiCentralHospital DepartmentofRespiratoryMedicine,TenriHospital DepartmentofInternalMedicine,SaitamaSocialInsuranceHospital (DepartmentofRespiratoryMedicine,KawasakiMunicipalHospital) ThirdDepartmentofInternalMedicine,SapporoMedicalUniversityHospital ThirdDepartmentofInternalMedicine,MieUniversityHospital DepartmentofRespiratoryMedicine,KawasakiHospital (CenterofRespiratoryDiseases,KawasakiMedicalSchoolKawasakiHospital) DepartmentofChestDisease,OgakiMunicipalHospital (GeneralInternalMedicine,GotoClinic) FirstDepartmentofInternalMedicine,OsakaMedicalColegeHospital (InternalMedicine,KinshukaiGroup,HanwasumiyoshiHospital) DepartmentofInternalMedicineI,OitaUniversityHospital DepartmentofInternalMedicine,NagasakiPrefectureTaramiHospital (DivisionofRespiratoryMedicine,JapaneseRedCrossNagasakiGenbakuIsahayaHospital) DepartmentofMedicine,NagasakiMunicipalHospital (DepartmentofInternalMedicine,HouseikaiHospital) DepartmentofRespiratoryMedicine,TokyoWomen'sMedicalUniversityHospital DepartmentofRespiratoryMedicine,NationalHospitalOrganizationMinami-KyotoHospital DepartmentofRespiratoryMedicine,NationalHospitalOrganizationIbarakihigashiNationalHospital DepartmentofRespiratoryMedicine,NationalHospitalOrganizationKinki-ChuoChestMedicalCenter DepartmentofRespiratoryMedicine,NationalHospitalOrganizationDohokuNationalHospital DepartmentofRespiratoryMedicine,JapaneseRedCrossMedicalCenter DepartmentofRespiratoryDiseases,JapaneseRedCrossWakayamaMedicalCenter Aspergillus Candida Aspergillus I
3 Aspergillus γ β β
4 χ II
5 Table2. Patientprofilesinmonotherapyversuscombinationtherapy Diagnosis Gender Age (years) Bodyweight(kg) Underlying disease * Durationof treatment (days) Meandaily micafungindose (mg) Variable/category CNPA Aspergiloma Male Female 24to64 65to79 8to9 Mean±SD Mean±SD Absent Present Mainunderlyingdisease Tuberculosissequela Non-tuberculousmycobacteriosis COPD Pneumonia(pathogenunknown) 4to14 15to28 29to84 Mean±SD <_ 15 <_ 3 Mean±SD Numberof patients n= 91(%) 57(62.6) 34(37.4) 62(68.1) 29(31.9) 31(34.1) 49(53.8) 11(12.1) 67.8± ±9.5 2(2.2) 89(97.8) 27(3.3) 15(16.9) 12(13.5) 12(13.5) 15(16.5) 16(17.6) 6(65.9) 42.5± (63.7) 33(36.3) 181.±58.2 Micafungin monotherapy n= 48(%) 29(6.4) 19(39.6) 3(62.5) 18(37.5) 12(25.) 29(6.4) 7(14.6) 69.7± ±1.4 1(2.1) 47(97.9) 14(29.8) 1(21.3) 6(12.8) 5(1.6) 11(22.9) 14(29.2) 23(47.9) 32.6±2.7 35(72.9) 13(27.1) 169.9±55.1 Antifungal combination therapy n= 43(%) 28(65.1) 15(34.9) 32(74.4) 11(25.6) 19(44.2) 2(46.5) 4(9.3) 65.6± ±8.6 1(2.3) 42(97.7) 13(31.) 5(11.9) 6(14.3) 7(16.7) 4(9.3) 2(4.7) 37(86.) 53.6± (53.5) 2(46.5) 193.3±59.6 Typeof Itraconazole 39(42.9) 39(9.7) concomitant antifungaldrug Amphotericin-B 11(12.1) 11(25.6) Imaging-based severity Severityscore Mild Moderate Severe 1to3 4to6 32(35.2) 34(37.4) 25(27.5) 66(72.5) 25(27.5) 21(43.8) 16(33.3) 11(22.9) 36(75.) 12(25.) * :Somepatientshadmorethan1underlyingdisease. :Bothitraconazoleandamphotericin-Bwereadministeredto7patients. :Totalscorecalculatedfrom imaging,age,bun,andpao2points;eachpointisdefinedasfolows: Imaging:1pointformildcases,2pointsformoderatecases,and3pointsforseverecases. Age:1pointformalesaged7yearsorolderandfemalesaged75yearsorolder. BUN:1pointforpatientswithBUNof21mg/dLormore,ordehydration. PaO2:1pointforPaO2of6mmHgorless. :Doserangeofitraconazolewas5 4mg/day.(Mean±SD:213.2±82.6mg/day) :Chi-squaretestformonotherapyvs.combinationtherapy. 11(25.6) 18(41.9) 14(32.6) 3(69.8) 13(3.2) Statistical test p=.5
6 Table3. Overaleficacyrateandimprovementinclinicalsymptoms/findings,imagingfindings,mycologicaleficacy,orserologicalfungal findings Al CNPA Aspergiloma Micafungin monotherapy Antifungal combination therapy Variable/category Overalclinicaleficacy Clinicalsymptoms/findings Imagingfindings Mycologicaleficacy Serologicalfungalfindings Overalclinicaleficacy Clinicalsymptoms/findings Imagingfindings Mycologicaleficacy Serologicalfungalfindings Number of patients Marked improvement 2 6 * 3 1 Responders Improvement Non-responders No change Aggravation * :Fungaleradicationornegativeconversion. :Improvementinclinicalsymptoms/findings,imagingfindings,mycologicaleficacy,orserologicalfungalfindings Overaleficacy 63.8% (51/8) 62.% (31/5) 66.7% (2/3) 57.1% (24/42) 63.4% 36.6% 54.5% 4.% 71.1% (27/38) 65.8% 39.5% 55.6% 36.4% Table4. Overaleficacybymicafunginduration Variable/category Durationof treatment (days) <_ 14 15to28 >_ 29 Alpatients (n= 8)(%) 3/9(33.3) 11/15(73.3) 37/56(66.1) Numbersinparenthesesrepresentresponse. Micafungin monotherapy (n= 42)(%) 3/7(42.9) 11/14(78.6) 1/21(47.6) Antifungalcombinationtherapy (n= 38)(%) /2(.) /1(.) 27/35(77.1) Table5. Overaleficacybyconcomitantantifungaltherapytiming Responders Non-responders Overaleficacy(%) Timingof concomitant antifungal Beforemicafunginuse (n= 2) Concurentlywithmicafunginuse (n= 4) Aftermicafunginuse (n= 14) Al (n= 38)
7 Severityscore Variable/category Table6. Overaleficacybyseverityscore Meandailydose ofmicafungin (mg/day) Alpatients (n= 8)(%) Micafungin monotherapy (n= 42)(%) Antifungal combinationtherapy (n= 38)(%) 1to3 <_ 15 3/43(69.8) 17/26(65.4) 13/17(76.5) (mildilness) > 15 13/19(68.4) 5/7(71.4) 8/12(66.7) 4to6 <_ 15 2/7(28.6) 1/5(2.) 1/2(5.) (severeilness) > 15 6/11(54.5) 1/4(25.) 5/7(71.4) Numbersinparenthesesrepresentresponse. Micafungin monotherapy n= 61 Antifungal combination therapy n= 48 Table7. Adversedrugreactionprofile(safetyanalysisset) Typeofadversedrugreaction * Abnormalhepaticfunction (AST,ALT,γ -GTP,orBilincreased) Renalimpairment Lymphocytecountdecreased Others 1) Total Incidenceofadversedrugreactions Abnormalhepaticfunction (ALPincreased,etc.) Rash Nausea Others 2) Total Incidenceofadversedrugreactions Numberof patients (11) 22 (35) 36.1% 5 (5) 3 (3) 2 7 (12) 14 (22) 29.2% Serious () (1) () () (1) () () () Severityofilness Moderate (8) (1) () (4) (13) () () (1) (3) Mild Numbersinparenthesesrepresentthenumberofreportedadversedrugreactions. * :Thistablelistsadversedrugreactionsin2ormorecases. :Includingsomepatientswithtwoormoreadversedrugreactions. Breakdownof1):Thefolowingeventwasobserved:thrombocytopenia,vertigo,angiopathy,rash,injection siteextravasation,oedemaperipheral,bloodpotassium increased,eosinophilcountincreased,proteintotaldecreased,plateletcountincreased,andeosinophilpercentage increased. Breakdownof2):Thefolowingeventwasobserved:pseudomembranouscolitis,hemolyticanemia,vomiting,injectionsiteerythema,injectionsitepain,injectionsitewarmth,pyrexia,bloodchloridedecreased,bloodsodium decreased,lymphocytecountdecreased,whitebloodcel countdecreased,andplateletcountincreased. (12) () (7) (21) (5) (3) (1) (8) (17) γ
8 Variable/category Numberofpatients(n= 19) Age (years) Table8. Profileofadversedrugreactionsbyageandmeandailymicafungindose(safetyanalysisset) 24to64 65to79 8to9 Number of patients Micafunginmonotherapy Numberof patients withany adversedrug reaction Incidence (%) Statistical test * Number of patients Antifungalcombinationtherapy Number ofpatients withany adversedrug reaction Incidence (%) Meandailydoseof <_ micafungin(mg/day) > *:Cochran-Armitagetest :Chi-squaretest :Nosignificantdiference Statistical test * III in vitro iv vivo Candida Aspergillus
9 in vitro in vivo γ
10 Aspergillus Candida albicans Aspergillus fumigatus in vitro Candida albicans Aspergillus fumigatus
11 Candida Aspergillus Candida Aspergillus Candida Aspergillus β Candida albicans
12
日本化学療法学会雑誌第56巻第3号
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
日本化学療法学会雑誌第54巻第S-1号
β β Key words β Candida krusei Candida glabrata β I β Drugadministration Baselinecharacteristics Clinicalsymptom Mycologicaltests Plasmadrugconcn Adverseevents Laboratorytests ) -leadecg Clinicalphotograph
日本化学療法学会雑誌第65巻第4号
Mycoplasma pneumoniae M. pneumoniae M. pneumoniae M. pneumoniae M. pneumoniae M. pneumoniae Key words Mycoplasma pneumoniae Mycoplasma pneumoniae M. pneumoniae I M. pneumoniae M. pneumoniae M. pneumoniae
日本化学療法学会雑誌第57巻第6号
Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis S. pneumoniae S. pneumoniae β β H. influenzae S. pneumoniae H. influenzae M. catarrhalis Key words Otalgia Fever Item Crying,Iritation,
日本化学療法学会雑誌第54巻第1号
Chlamydophila pneumoniae Chlamydophila psittaci Mycoplasma pneumoniae Legionella pneumophila C. pneumoniae C. psittaci C. pneumoniae C. psittaci M. pneumoniae M. pneumoniae C. psittaci L. pneumophila C.
日本化学療法学会雑誌第56巻第1号
β β β β β Streptococcus pneumoniaehaemophilus influenzaemoraxella catarrhalismycoplasma pneumoniaechlamydia pneumoniae β Key wordsβ mys nilc laci ngis Table. Assessmentschedule Parameters Patientcharacteristics
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Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis S. pneumoniae H. influenzae M. catarrhalis S. pneumoniae H. influenzae M. catarrhalis S. pneumoniae H. influenzae M. catarrhalis S.
O1-1 O1-2 O1-3 O1-4 O1-5 O1-6
O1-1 O1-2 O1-3 O1-4 O1-5 O1-6 O1-7 O1-8 O1-9 O1-10 O1-11 O1-12 O1-13 O1-14 O1-15 O1-16 O1-17 O1-18 O1-19 O1-20 O1-21 O1-22 O1-23 O1-24 O1-25 O1-26 O1-27 O1-28 O1-29 O1-30 O1-31 O1-32 O1-33 O1-34 O1-35
日本化学療法学会雑誌第55巻第S-1号
µ µ Key words Streptococcus pneu- moniae S. pneumoniae µ µ I γ H H C HN F F O N O CO H H C SO H H O Fig.. ChemicalstructureofGRNX. γ γ II Haemophilus influenzae Pseudomonas aeruginosa Streptococcus intermedius
日本化学療法学会雑誌第57巻第S-2号
Key words β I Table. Observationandtestschedule Testschedule Observation/Tests Beforetreatment Endoftreatment 5 9days aftercompletion oftreatment 4 6weeks aftercompletion oftreatment Informedconsent Patientbackground
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第１部 一般的コメント
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日本化学療法学会雑誌第54巻第S-1号
β β β Key words β β I HP- -CD CHR RHC R R R R CHR R R R R RHC R R R CHR R R R RHC CHR R H CH CH Fig.. Structuralformulaofhydroxypropyl-β -cyclodextrin(hp-β -CD). CH n H β β β β Table-. Dosageandadministration(Singleadministrationstudy)
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日本化学療法学会雑誌第60巻第4号
Streptococcus pneumoniae Haemophilus influenzae S. pneumoniae H. influenzae Key words β Streptococcus pneumoniae Haemophilus influenzae S. pneumoniae H. influenzae μ μ S. pneumoniae H. influenzae S. pneumoniae
日本化学療法学会雑誌第57巻第5号
in vitro Key words Streptococcus pneumoniae β Haemophilus influenzae Escherichia coli I Table. Antibacteriallevofloxacinactivityagainstclinicalisolates Organism Year Susceptibility(%)(Numberofstrains)
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1.8.2 Page MIC () MIC 50 / MIC 90 µg/ml Candida albicans (54) / Candida glabrata (25) 0.25 / 0.5 Candida guilliermondii a) (2)
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ACCESS ACCESS i ii ACCESS iii iv ACCESS v vi ACCESS CONTENTS ACCESS CONTENTS ACCESS 1 ACCESS 1 2 ACCESS 3 1 4 ACCESS 5 1 6 ACCESS 7 1 8 9 ACCESS 10 1 ACCESS 11 1 12 ACCESS 13 1 14 ACCESS 15 1 v 16 ACCESS
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1 2 3 4 5 6 7 8 9 10 I II III 11 IV 12 V 13 VI VII 14 VIII. 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 _ 33 _ 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 VII 51 52 53 54 55 56 57 58 59
Fig. 1 Chemical structure of TE-031 Code number: TE-031 Chemical name: (-) (3R, 4S, 5S, 6R, 7R, 9R, 11R, 12R, 13S, 14R)-4-[(2, 6-dideoxy-3-C-methyl-3-
Fig. 1 Chemical structure of TE-031 Code number: TE-031 Chemical name: (-) (3R, 4S, 5S, 6R, 7R, 9R, 11R, 12R, 13S, 14R)-4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl-a-L-ribo-hexopyranosyl) oxy]-14-ethyl-12,