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გზა MDR-TB ახალი თერაპიისკენ. marika erisTavi “samSabaToba”, 04.05.10. amJamad gamoyenebuli reJimebi multikomponentiani da xangrZlivad iniSneba; - PowerPoint PPT Presentation
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marika erisTavi
“samSabaToba”, 04.05.10.
amJamad gamoyenebuli reJimebi multikomponentiani da xangrZlivad iniSneba;
Znelia aseTi grZeli da kompleqsuri reJimis Sesruleba, xSiria mkurnalobaSi Secdomebic, im pacientTa Sorisac ki, romelTac wamlisadmi mgrZnobiare tuberkulozi aqvT;
swored amitom mniSvnelovania Zlieri antibiotikis arseboba, romelic ufro swrafad daamarcxebs infeqcias.
Moxifloxacin PA-824 TMC 207 Quinolone TBK-613 Nitroimidazoles Mycobacterial Gyrase Inhibitors Riminophenazines InhA Inhibitors New Generation Diarylquinoline Bi-functional Molecules Phenotypic Screening Tryptanthrins LeuRS Inhibitors GSK Whole-Cell Screening Malate Synthase Inhibitors Energy Metabolism Inhibitors RNA Polymerase Inhibitors Natural Products Menaquinone Biosynthesis Inhibitors Protease Inhibitors Topoisomerase I Inhibitors
TMC207: uaxlesi antibaqteriuli preparatebis jgufi; diarqinoloni (Dairylquinoline):
axasiaTebs antituberkulozuri moqmedebis axali meqanizmi _ ainhibirebs mikobaqteriul ATP-sinTetazas;
in vitro ainhibirebs wamlebisadmi mgrZnobiare da wamlebisadmi rezistentul M. tuberculosis;
iCens baqteriocidul aqtivobas pacientebSi, romlebsac aqvT wamlisadmi mgrZnobiare filtvis tuberkulozi
kvlevis meTodebi:
Catarda orsafexuriani, randomizebuli, multicentruli, placeboTi kontrolirebadi cda, romelic miznad isaxavda TMC 207-is:
usafrTxoebis; farmakokinetikisa; antimikrobuli aqtivobis Sefasebas;
kvleva Catarda 47 filtvis formis, mgb(+), warsulSi II rigis TB preparatebiT aranamkurnaleb MDR-TBpacientze:
maTgan 23-s mkurnalobdnen: I etapze TMC207/400 mg; 2 kviris
ganmavlobaSi, erTxel dReSi II etapze TMC207/200 mg; 6 kviris
ganmavlobaSi, 3-jer dReSi;
24 pacients umkurnales placeboTi;
sakvlevi populacia ZiriTadad Sedgeboda mamri (74%), Savkaniani (55%), aiv
negatiuri (87%) individebisagan, saSualo asakiT 33 weli (18dan 65
wlamde)
pacientebi gaanawiles kvlevis centrebis;
filtvis kavitaciis mixedviT
≥2 sm bilateralurad, ≥2 sm unilateralurad, <2 sm.
mocemuli dozebi winaswar Catarebuli kvlevis safuZvelze SeirCa
dRiuri 400 mg-iani doza saWiroa maqsimaluri baqteriociduli aqtivobisaTvis;
kviraSi 3jer 200 mg-iani dozireba ki plazmuri koncentraciis SesanarCuneblad;
preparatebis mimarT mgrZnobeloba ganisazRvra molekuluri genotipirebis meTodebiT, xolo kulturis konvertaciis Sefaseba xdeboda Txevad niadagze MGIT sistemiT;
orive SemTxvevaSi TMC207-Tan erTad samkurnalo reJimSi gamoiyeneboda II rigis 5 standartuli TB preparati:
Km, Ofx, Eth, Z, Cs (an terizidoni);
TMC207-Tan kombinaciaSi 8 kviriani kursis Semdeg standartuli mkurnaloba 96 kvira gagrZelda;
kvlevaSi ar moxda Semdegi kategoriis pacientebis CarTva:
eqstrapulmonaluri TB pacientebi; pacientebi visi testic dadebiTi iyo aiv-ze, CD4+
iyo 300-ze naklebi da miRebuli hqondaT antiretrovirusuli da/an antimikozuri medikamentebi ukanaskneli 90 dRis ganmavlobaSi;
pacientebi mniSvnelovani kardialuri ariTmiiT;
aseve gamoiricxnen pacientebi Semdegi maxasiaTeblebiT:
hipermgrZnobeloba wamlebisadmi, alkoholis an narkotikis moxmareba, Tanmxlebi daavadebebi, atipiuri laboratoriuli Sedegebi, fexmZimoba, an ZuZuTi kveba, monawileoba sxva klinikur kvlevebSi.
monacemebi statistikurad SAS Software-is programis daxmarebiT damuSavda
47 CarTuli pacientidan kvlevaSi sabolood monawileoba 41-ma miiRo (20-ma TMC207-is jgufidan da 21-ma placebos jgufidan);
atipiuri, an mwvave gverdiTi movlenebi ar gamovlenila, IV xarisxis diabeturi ketoacidozi ganviTarda 1 SemTxvevaSi TMC207 jgufidan da IV xarisxis pnevmoToraqsi 1 SemTxvevaSi placebos jgufidan;
Sedegebi:
TMC207-is jgufis pacientebSi placebos jgufis pacientebisgan gansxvavebiT gamovlinda mniSvnelovnad gaxSirebuli gulisreva (26% vs. 4%, P = 0.04);
plazmur koncentraciaSi ar iqna SeniSnuli araviTari mniSvnelovani gansxvaveba TMC207-is pacientebis im jgufebs Soris, romelTac ganicades an ar ganicades kulturebis konversia;
standartul Terapiaze TMC207-is damatebam
Seamcira kulturis konversiis dro placebos jgufTan SedarebiT;
gazarda konversirebuli naxvelis kulturis mqone pacientebis ricxvi (48% vs 9%).
TMC207 jgufSi mkveTrad daeca koloniis warmomqmneli erTeulebis ricxvi placebos jgufTan SedarebiT;
TMC207-is klinikuri aqtivoba adasturebs,
rom ATP-sinTetaza kargi samiznea tuberkulozis
samkurnalod
tuberkulozis Tagvis modelSi TMC207 aris aqtiuri izoniazidTan, rifampinTan da pirazinamidTan kombinaciaSi, amasTan TMC207-is damatebam am sami wamlis kombinaciasTan daaCqara bacilebis ganadgureba da gvaCvena rom is sinergistulad urTierTqmedebs pirazinamidTan;
wamlebisadmi sensitiuri tuberkulozian Tagvis modelSi TMC207 aZlierebs meore rigis wamlebis kombinaciis antibaqteriul aqtivobas
gmadlobT
yuradRebisaTvis