1 / 22

გზა MDR-TB ახალი თერაპიისკენ

გზა MDR-TB ახალი თერაპიისკენ. marika erisTavi “samSabaToba”, 04.05.10. amJamad gamoyenebuli reJimebi multikomponentiani da xangrZlivad iniSneba;

meriel
Download Presentation

გზა MDR-TB ახალი თერაპიისკენ

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. გზა MDR-TB ახალი თერაპიისკენ marika erisTavi “samSabaToba”, 04.05.10.

  2. 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.

  3. 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

  4. 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

  5. The new englandjournal of medicinejune 4, 2009 vol. 360 no. 23 kvlevis meTodebi: Catarda orsafexuriani, randomizebuli, multicentruli, placeboTi kontrolirebadi cda, romelic miznad isaxavda TMC 207-is: • usafrTxoebis; • farmakokinetikisa; • antimikrobuli aqtivobis Sefasebas;

  6. kvleva Catarda 47filtvis 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;

  7. sakvlevi populacia ZiriTadad Sedgeboda mamri (74%), Savkaniani (55%), aiv negatiuri (87%) individebisagan, saSualo asakiT 33 weli (18dan 65 wlamde)

  8. pacientebi gaanawiles kvlevis centrebis; • filtvis kavitaciis mixedviT • ≥2 sm bilateralurad, • ≥2 sm unilateralurad, • <2 sm.

  9. 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;

  10. preparatebis mimarT mgrZnobeloba ganisazRvra molekuluri genotipirebis meTodebiT, xolo kulturis konvertaciis Sefaseba xdebodaTxevad 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;

  11. 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;

  12. 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

  13. 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;

  14. Sedegebi: • TMC207-is jgufis pacientebSi placebos jgufis pacientebisgan gansxvavebiT gamovlinda mniSvnelovnad gaxSirebuli gulisreva (26% vs. 4%, P = 0.04);

  15. plazmur koncentraciaSi ar iqna SeniSnuli araviTari mniSvnelovani gansxvaveba TMC207-is pacientebis im jgufebs Soris, romelTac ganicades an ar ganicades kulturebis konversia;

  16. 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 ricxviplacebos jgufTan SedarebiT;

  17. დასკვნა TMC207-is klinikuri aqtivoba adasturebs, rom ATP-sinTetaza kargi samiznea tuberkulozis samkurnalod

  18. 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

  19. gmadlobT yuradRebisaTvis

More Related