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Llinezolidi- realoba da perspeqtivebi leila goginaSvili; 22.12.09.

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Presentation on theme: "Llinezolidi- realoba da perspeqtivebi leila goginaSvili; 22.12.09."— Presentation transcript:

1 Llinezolidi- realoba da perspeqtivebi leila goginaSvili;

2 linezolidi saerTaSoriso saxelwodeba _ linezolidi ( Linezolid) laTinuri saxelwodeba _ Linezolide savaWro saxelwodeba _ zivoqsi (Zyvox) qimiuri dasaxeleba (struqturuli formula): N-[[S ]-3-[3-ftor-4-(4-morfolinil) fenil]-2-oqso-5- oqsazolidilini] metal] acetamidi bruto formula C16H20FN3O4

3 farmakodinamika moqmedebis meqanizmi linezolidi ((PNU ) warmoadgens sinTezur antimikrobul saSualebas da ganekuTvneba antimikrobuli aqtivobis mqone axal klass _ oqsazolidinonebs, romlebic aqtiuria aerobuli, (gramdadebiTi da gramuaryofiTi), aseve anaerobuli baqteriebisa da sxva mikroorganizmebis mimarT. rogorc proteinis sinTezis inhibitori aCerebs baqteriis zrdas, vinaidan arRvevs, Slis baqteriis mier proteinis producirebas (gamomuSavebas) linezolidi

4 mgrZnobeloba: cxrilSi moyvanilia is mikroorganizmebi, romlebzec linezolidis gavlena dadasturebulia eqsperimentulad. gramdadebiTi aerobebi: Corynebacterium jeikeium Enterococcus faecalis ( maT Soris glikopeptiduri Stamebi) Enterococcus faecium ( maT Soris glikopeptiduri Stamebi) Enterococcus casseliflavus Enterococcus gallinarum mgrZnobiare mikroorganizmebi Listeria monocytogenes Staphylococcus aureus ( maT Soris meTicilin-rezistentuli Stamebi) Staphylococcus aureus (maT Soris glikopeptidebisadmi saSualod mgrZnobiare Stamebi) Staphylococcus epidermidis ( maT Soris meTicilin-rezistentuli Stamebi Staphylococcus haemolyticus M. Tuberculosis MDR Stami Streptococcus intermedius Streptococcus pneumoniae( maT Soris penicilin-rezistentuli Stamebi)

5 Streptococcus pyrogenes streptokoki Viridans jgufis streptokoki C jgufis streptokoki GГ gramuaryofiTi aerobebi : Pasteurella canis Pasteurella multocida gramdadebiTi anaerobebi: Clostridium perfringens gramuaryofiTi anaerobebi: Bacteroides fragilis Chlamydia pnevmonie saSualod mgrZnobiare mikroorganizmebi Legionella spp. Moraxella catarrhalis Mycoplasma spp. rezistentuli mikroorganizmebi Haemophilus influenzae Neisseria spp. Enterobacteriaceae Pseudomonas spp.

6 linezolidi linezolidis moqmedebis meqanizmi gansxvavdeba sxva klasis antimikrobuli preparatebis (mag. aminoglikozidebi, beta_ laqtamebis, folis mJavas antagonistebis, glikopeptidebis, linkozamidebis, qinolonebis, rifamicinebis, streptograminebis, tetraciklinebis, qloramfenikolis moqmedebis meqanizmisagan. Sesabamisad, linezolidis rezistentuli Tanxvedra am preparatebis mimarT ar arsebobs. igi aqtiuria am preparatebis mimarT, rogorc mgrZnobiare, aseve rezistentuli mikroorganizmebisadmi.

7 linezolidi Sewova (absorbcia): peroralurad miRebisas linezolidi swrafad da intensiurad Seiwoveba kuW-nawlavis traqtidan. misi maqsimaluri koncentracia miRebidan miiRweva 2 saaTSi da absoluturi bioSeRwevadoba daax. 100%-ia. aseve analogiuria linezolidis miRebisas sxva formiT (infuzia da suspenzia). kvebis reJimi Sewovaze araviTar gavlenas ar axdens. gadanawileba qsovilebSi xorcieldeba kargi perfuziis xarjze. misi moculoba saSualod Seadgens daax l. rac daaxloebiT organizmSi wylis saerTo raodenobis tolia. sisxlis cilebTan kavSiri daax. 31%-ia da ar aris dakavSirebuli maT koncentraciaze. linezolidi kargad aRwevs kansa da rbil qsovilebSi, sasunTq sistemaSi, gulSi, nawlavebSi, RviZlSi, TirkmlebSi, centralur nervul sistemaSi da Seadgens sisxlis Sratismier koncentracias 60-70%-iT; zomierad _ sinovialur siTxeSi, ZvlebSi, naRvlis buStSi. linezolidis koncentracia zurgis tvinis siTxeSi Seadgens 14-23%-s. igi akumulirdeba gulis sarqvlebis vegetaciaSi da saSualo koncentracia Seadgens 2.2mkg/gr 5 dRis ganmavlobaSi 40mg/kg dozis miRebisas.

8 linezolidi Cveneba linezolidi gamoiyeneba iseTi mikroorganizmebiT gamowveuli infeqciebis dros, romlebic mocemulia z/a cxrilSi, anu, rodesac cnobilia daavadebis gamomwvevi linezolidze mgrZnobiare mikroorganizmebi: anaerobuli da aerobuli gramdadebiTi, maT Soris baqteriemiiT gamowveuli infeqciebis drosac. _ arahospitaluri pnevmonia _ hospitaluri pnevmonia _ kanisa da rbili qsovilebis infeqciebi _ enterokokuri infeqciebi, maT Soris gamowveuli vankomicinis Stamebisadmi rezistentuli mikroorganizmebis mier _ Sard-sasqeso gzebis (urogenitaluri) garTulebuli infeqciebi _ baqteriemia an/da sefsisi _ intraabdominaluri infeqciebi (maT Soris peritoniti) _ rodesac infeqciis Tanxmlebia gramuaryofiTi mikroorganizmebiT gamowveuli infeqciebi. mocemul SemTxvevaSi rekomendirebulia kombinirebuli Terapia.

9 L linezolidi miRebis wesebi da dozireba Cveneba (maT Soris baqteriemiiT, rogorc Tanxmlebi infeqcia) erTjeradi doza da miRebis wesebi mkurnalobis rekomendirebuli xangrZlivoba arahospitaluri pnevmonia 600 mg i/v an SigniT dRe hospitaluri pnevmonia600mg i/v an SigniT kanisa da rbili qsovilebis infeqciebi mg an 600mg i/v miuxedavad daavadebis simZimisa enterokokuri infeqcia 600 mg i/v an SigniT dRe mkurnalobis xangrZlivoba damokidebulia gamomwvev faqtorze, infeqciis lokalizaciaze, mimdinareobis simZimeze da klinikur efeqtze. bavSvebi >5 welze rekomendirebuli dozaa 10mg/kg sxeulis masaze 24 saaTSi 2-jer SigniT misaRebad. bavSvebSi da mozrdilebSi maqsimaluri doza ar unda aRematebodes 600 mg-s 2-jer 24 saaTSi.

10 gverdiTi movlenebi: preparatis gamoyenebisas dafiqsirda Semdegi saxis arasasurveli movlenebi, romlebic ar aRemateboda 1%-s: linezolidisa sxva antibiotikebis miRebiT gamowveuli arasasurveli efeqtebis Sedarebis tabula A arasasurveli efeqtebi linezolidipreparatebi 1200 mg/24sT (n=1498) Sedareba (n=1464) arasasurveli efeqtebis sixSire 20,414,3 arasasurveli efeqtebis Sedegad medikamentis Sewyvetis sixSire 2,11,7 diarea 4,02,7 gulisreva 3,31,8 Tavis tkivili (cefalgia) 1,91,0 gemos Secvla (disgevzia) 0,90,2 sokovani infeqciebi 0,1<0,1 RviZlis fermentebis cvlilebebi 1,30,5 Rebineba (vomitusi) 1,20,4 enis gauferuleba 0,20 Tavbru (vertigo) 0,40,3

11 linezolidi arasasurveli reaqciebi sustad an zomierad iyo manifestirebuli da epizodurad, romelic ar iyo dakavSirebuli medikamentis dozasTan da aseve ar iyo medikamentis Sewyvetis aucilebloba. Zalzed iSviaTad dafiqsirda periferiuli neiropaTia da mxedvelobis nervis neiropaTiebi, rac savaraudod dakavSirebuli iyo mkurnalobis vadis gaxangrZlivebasTan (28 dRe). garda amisa, eqsperimentSi pacientebi paralelurad iRebdnen iseT preparatebs, romlebsac gaaCniaT neiropaTiebis SesaZlo ganviTarebis efeqti (amitriptilini, paroqsetini, izoniazidi da sxv). anda pacientebs anamnezSi hqondaT neiropaTiebis maprovocirebeli daavadebebi (Saqriani diabeti, arteriuli hipertonia, Tirkmlis qronikuli ukmarisoba, osteosarkoma, Tavis tvinis abscesi da sxv).

12 linezolidi sabolood unda aRiniSnos, rom klinikur praqtikaSi Cndeba axali, Zalzed mniSvnelovani, saWiro da perspeqtiuli antibaqteriuli preparati, romelsac SeuZlia arsebiTi roli Seasrulos im problemebis gadaWraSi, romelic iqmneba gramdadebiTi rezistentuli baqteriebiT gamowveul infeqciebSi. linezolidis yvelaze mniSvnelovani Tvisebebi mdgomareobs SemdegSi: _ gramdadebiTi baqteriebisadmi aSkarad gamoxatuli efeqturoba, maT Soris multirezistentuli Stamebisadmi; _ enterokokebis iseTi Stamebisadmi aqtiurobis SenarCuneba, romlebic mdgradia vankomicinisadmi; _ moxerxebuli mkurnaloba, SesaZlebelia safexurebrivi Terapiis Catareba (i/v da SigniT), kargi individualuri amtanoba (vankomicinTan SedarebiT), stacionaridan adreuli gaweris realoba Semdgomi ambulatoriuli mkurnalobiT; _ vankomicinTan SedarebiT qsovilebSi kargi SeRwevisa da perfiziis unariT, maT Soris centralur nervul sistemaSi da gulis sarqvlebSi; _ mZime pacientebSi SesaZlo kargi efeqti, maT Soris imunokomprometirebul pacientebSi.

13 Llinezolidis klinikuri efeqturoba filtvis tuberkulozis multirezistentuli formis mkurnalobis reJimSi Kkvlevis mizani iyo preparatis klinikuri efeqturoba meore rigis sxva antituberkulozur preparatebTan erTad.Y meTodi: SeirCa or jgufad gayofili 91 pacienti.O 46 pacienti L linezolidi klariTromicini Kkapreomicini Ppirazinamidi Eetambutoli protionamidi I-jgufiII -jgufi 45 pacienti streptomicini pirazinamidi Eetambutoli etionamidi mkurnalobis xangrZlivoba 18 Tve (linezolidi 6 Tve

14 Sedegebi: 1. mkurnalobis dasruleba 2. naxvelis konversia 3. rentgenologiuri dinamika 4 kavernis daxurva.

15 daskvna Llinezolidis kombinacia sxva meore rigis antituberkulozur medikamentebTan erTad aris efeqturi, usafrTxo da SesaZlebelia gamoyenebuli iqnes MDR-TB- is mkurnalobis reJimSi. avtori: Sudhir. K, Agarwal

16 jgufipreparatebi I jgufi _ I rigis tubsawinaaRmdego abebi izoniazidi (H); rifampicini (R); etambutoli (E); pirazinamidi (Z); rifabutini (Rfb) II jgufi _ saineqcio preparatebikanamicini (Km); amikacini (Am); kapreomicini (Cm); streptomicini (S) III jgufi _ fTorqinolonebimoqsifloqsacini (Mfx); levofloqsacini (Lfx); ofloqsacini (Ofx); IV jgufi _ II rigis baqteriostatikuri moqmedebis abebi eTionamidi (Eto); proTionamidi (Pto); cikloserini (Cs); terizidoni (Trd); para- amino salicilis mJava (PAS). V jgufi _ dauzustebeli efeqturobis mqone preparatebi ( MDR-TB pacientebis rutinuli mkurnalobisaTvis janmo-s mier rekomendirebuli ar aris) klofazimini (Cfz); linezolidi (Lzd); amoqsacilin/klavulinati (Amx/Clv); Tioacetazoni (Thz); imipenem/cilastatini (Ipm/Cln); didi dozis izoniazidi (high-dose H); klaritromicini (Clr)

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18 gmadlobT yuradRebisaTvis


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