Siahposht Khachki, Amir

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,(?o'2&;l' , /',,lt"uft\i. I I arrrUL)/$)) it,{/t)fI,S* ,rhl .;*,.ri( o ,rS,}j; o '('i"'l.l.f;,i .+G6r1-3 c:,},J .l,itt s-l'..).Jt< &3- *UA!!:,llJi.J Js-rf,sq.;s .Jsjl3JSl*l ,i*+LiJt-,tS 6la3-1l.r .r+;13 ,. ' crt;it f)):..,-s!j-yl oUcrS qJ.* p t+ :,:5-r -,.r s dW A v gt-,*iJi-Iin Vitro .t1l-€ -2r 1313. 3 ._,pl ,,.- o.r-,KJ-Ju,rS"Li c..i.{ oF ,. .1,-,-l : L. ,.r;6J-',Ji,ra.Lll,-.ri ;yl .l:.,. i(l ;l ^'.atr .ll':.,.1J+ +"^ iS.l :r3l 'r' ^ .ll':'"l\Y11-1V : .,l-r,a.'i Jt-,,,.iJlIKerman University of Medical SciencesFaculty of MedicineIn Partial Fulfillment of the Requirements for the Degree of MScTitle:Iru vitro Antifungal of Caspofungin, Itraconazole, Voriconazole andAmphotericin B alone and incommbination against azale'susceptible and -resistant Asp ergillus fumig atusBy:Amir SiahposhtSupervisor:1- Dr. Seyed Amin Ayatollahi MosaviAdvisor:Dr. Hamid BadaliYear:January 2018.*.rG or5+.rf.rl*r st ,Js: o"r5 r.,-.ra; )*-t; ora.c e* .i- alro + Jtji { p9li, 41yfuf ,y*-i;.,l.5[oaJe;-l :{.ri..c*lolr.a.r,qai,-JiE e lSy 9 e)f !,,oo c-L...rL.lr 9 Lfi,'$ li Lncj9"t;19 c*l ,t; ,jlf e ;-&*.ir?-i ,sl,+:,f ,rnL .;aL5 6U 6F-"i> ,eL 4,o*-1L*>,' ,: I .rl,,t* I Jili.5lo91lr .ir* ,:::)L-";11t"*;L,,r,|5-i t 4;,51y.n+3 rlir,.i- alrr +,rS; rLlr,4,1; o9),G.c-l olr.o )91i 4,;,-9 cr-Lp or.alrl, +i-L..';*;,altt ;l;l.iro .rrs )i *i )tt" sll.r Jt;i * esL ,**-;l;'i c;r;t -! JI1UF__, e e,_y.);V*,tt t+ Jl,,Lt'lp_l .4j;Gl-"15 ! v *--iy-i,JilEJ:..r L v.-,*"-f*i ;-+;--.:;!cr ;6a- r.rfult cil.o+9'- o"iK.yf ,y*-i*i d,L*> 9 f 9b 3[^*f '=rlr ,,;,;,G,+--;--r*:*t5.ri'-::.rl-:;;l ,"r;Lfug ,-**-jr-i Js;i + d"L-> al9;l Y. I Jili u. p9U. al9;ll' t4'igs g )1rt+ Jljufi.,, s s *.'iie?-g \ JilLflr;,-l ,6,-;13y-lJ l+ v *--ia".i ,JilN,J ...,tL. v ,-v+.iy^i .sl.r. -Gyl ,r-Lg- 9 #.J1.^4-i9,", 6"9;t3'',,29 ,-**.ir"i d"!.-,"- 9 Pgli' 6L^'if +* r+ ,s-y!:---)).Fe c*; CLSI .].5;sx 9 G+-lrtf-.<r('.r,L|.,.r checkerbo":*0.125 - 4 ,4; a: .r-Lt- .: grGr-lJ MECs t JilLf11,s le;Nf\r.-l ,+ e*.if.il,tiCs e., :E-t-,x--i,bi ,5\r'. ;r31r--l 3-'-tr ;*::-..o ..:y 0.008 - 0.5 pghl ,0.031 - 8 pg/ml , >16 prg/rnl-0.063 ,pr- -r",--iitr" 4t (FICI range: 0.18 - 0.5) 61;ls*tJ q c, ,y*.;e*i,FICI range:0.21- 0.5) ) JiiUr(-,: - *(FICI 4,-;lsr-,tt ! JrV.S1)s, GICI range= 0.75 -2.5) 6r;lirr"ts L )e;Ueil;l a:*+K.ty il ,S c,-tf * range: 0.- j -J.1.,,.r, ,t9;i .5toc-r1-0." .;;* ,s+b ;l ,SrS* Sly,#i rLrrl.i;lU-Ft+.f,,1! r,o.st^.Sil,;-t-r B ir--r 9;*l y-Jt* J ,Ur" 1...il d-Jll- e-L:j ,.|5 -rr .ri!.r .-j!2 yt. ,1,,1*t,r) p"\r )+-i-*; 6t;-:+.outt ..:1.:61-i; \ Ji { feli" ,-r*jx-l.5LoaJeil .i.y p cxj,E*+K ! e i,..--fds JilVfi)g sLJr t+ B O---i9-i ;*;*:.-V Lyr, oYlr- y 6t*t.5lr- in vivo 9 in r l::.Jrr.r Jii ar,r,.-l,o / . vrlrtAbstractIntroduction: Azole-resistant Aspergillus fumigatus isolates have emerged as a major sourceof life threatening aspergillosis in hospitalized patients and these infections have beenassociated with significant morbidity and mortality even when properly diagnosed andtreated. The decreased use of azole drugs in patients and in the environment is clearlyimportant to decrease the emergence of azole-resistant A- fumigatus. In addition, combinationtherapy as a crucial approach to overcome challenges in treatment of patients with azole-resistant Aspergillus infection can be considered. The aim of this study was to determine thein vitro susceptibility testing alone and in combination of amphotericin B with voriconazole,amphotericin B with caspofungin, itraconazole with caspofungin and voriconazole withcaspofungin against azole-resistant and azole-susceptible A. fumigatus clinical andenvironmental isolates.Material and methods: A total of 30 azole-resistant and 20 azole-susceptible A. fumigatusstrains, were tested. The in vitro susceptibility testing of amphotericin B, Itraconazole,voriconazole and caspofungin were tested. In vitro combination between of amphotericin Bwith voriconazole, amphotericin B with caspofungin, itraconazole with caspofungin andvoriconazole with caspofungin against azole-resistant and azole-susceptible A. fumigatusclinical and environmental isolates were tested by using a checkerboard method based on themicrodilution broth reference technique (M38-A2) of the Clinical and Laboratory StandardsInstitute (CLSD.Results: The range of amphotericin B, itraconazole, voriconazole MICs and caspofunginMECs when tested alone were 0.125 - 4 trt"g/ml,0.063 - >16 1,t91m1,0.031 - 8 pglml and 0.008- 0.5 pglml, respectively. The interaction between amphotericin B with voriconazole (FICIrange: 0.21 - 0.5), amphotericin B with caspofungin (FICI range:0.18 - 0.5) were synergisticand combination of itraconazole with caspofungin (FICI range: 0.75 - 2.5) and voriconazolewith caspofungin (FICI range: A.75 - 2) were indifferent.Discussion: Alternative antifungal strategies including combination therapy to avoid furtheremergence of azole-resistance, at the first suspicion of invasive aspergillosis in critical illpatients. In conclusio n, in vitro interaction of amphotericin-B with vorico nazole, amphotericinB with caspofungin were synergistic against azole-resistant and azole susceptible A. fumigatusisolates. An increased likelihood that the resistant A. fumigatus will be susceptible to at leastone of the components makes them a suitable option as an empiric combination regimen.I;iMore in vitro and in vivo studies are necessary to address questions regarding amphotericin Bwith voriconazole and caspofungin combination therapy.Keywords: In vitro combination, synergistic, azole-resistant and azole-susceptible A-fumigatus,rJ&l a-r.ro.U Olr-1," ;l gGo $ 1yOUf *r-; Pt' ,L -otejlc oJ,a.C --.soK-:;l., 6-io.r(;;1, ,#; (#L,*! 6SLS ,;;: r--irl .,-ll;)tt 63v-:;l> gJ, oli r.Eol L56T J-*; ''"U ot-t, ept!: +dx---ir*T gJ$$f{9,J$lidillu1l,,12rGq+*,tf sgl-l9;lco7lL!J-b crl.1-tl \*)1.";str-'o c--i jL-f ;;":-'. 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In vitro antifungal of caspofungin, itraconazole, voriconazole & amphotericin B alone & incommbination against azole- susceptible & -resistant aspergillus fumigatus

http://eprints.kmu.ac.ir/27146/1/6498_20180520_0001.pdf

In vitro antifungal of caspofungin, itraconazole, voriconazole & amphotericin B alone & incommbination against azole- susceptible & -resistant aspergillus fumigatus

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