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BỘ Y TẾ TRƯỜNG ĐẠI HỌC DƯỢC HÀ NỘI TRẦN NGỌC ÁNH KHẢO SÁT TÌNH HÌNH SỬ DỤNG KHÁNG SINH TRÊN BỆNH NHÂN NHIỄM KHUẨN HUYẾT ĐIỀU TRỊ TẠI KHOA TRUYỀN NHIỄM - BỆNH VIỆN 103 KHÓA LUẬN TỐT NGHIỆP DƯỢC SĨ HÀ NỘI - 2015

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B Y T TRNG I HC DC H NI TRN NGC NH KHO ST TNH HNH S DNG KHNG SINH TRN BNH NHN NHIM KHUN HUYT IU TRTI KHOA TRUYN NHIM- BNH VIN 103

KHA LUN TT NGHIP DC S H NI - 2015 B Y T TRNG I HC DC H NI TRN NGC NH KHO ST TNH HNH S DNG KHNG SINH TRN BNH NHN NHIM KHUN HUYT IU TRTI KHOA TRUYN NHIM- BNH VIN 103 KHA LUN TT NGHIP DC S Ngi hng dn: 1.PGS. TS. Trnh Th Xun Ha 2.ThS. Phan Th T Nh Ni thc hin: 1. B mn Y hc c s 2. Bnh vin 103 H NI - 2015 LI CM N Trc ht, vi lng knh trng v bit n su sc, em xin gi li cm n ti: PGS.TS.TrnhThXunHa-ChnhimBmnTruyn nhim Bnh vin Qun y 103 ThcsPhanThTNh-GingvinbmnYhccs, trng i hc Dc H Ni lnhngngithytrctiphngdn,tntnhchbovgip em trong sut qu trnh thc hin v hon thnh tt kha lun. EmxinchnthnhcmnBangimhiunhtrng,ccthyc trong bmn Yhccs to miiukinchoem trong sutqu trnh hc tp ti trng, ging dy cho em nhiu kin thc qu bu. Em cng xin chn thnh cm n Ban gim c bnh vin Qun y 103, KhoaTruynnhimcngcccnb,dcstomiiukingip em hon thnh kha lun. Cuicng,emxingilicm nsusctigianh,bnb,ngi thn lun bn ng vin, chia s,gip em trong sut qu trnh hc tp v thc hin kha lun. H Ni, ngy 12 thng 05 nm 2015 Sinh vin Trn Ngc nh MC LC DANH MC CC K HIU, CH VIT TT DANH MC CC BNG DANH MC CC HNH CHNG 1: TNG QUAN TI LIU ......................................................... 3 1.1. I CNG V BNH NHIM KHUN HUYT ........................... 3 1.1.1. Dch t hc nhim khun huyt ...................................................... 3 1.1.1.1. Tnh hnh nhim khun huyt trn th gii ............................... 3 1.1.1.2. Tnh hnh nhim khun huyt Vit Nam ................................ 3 1.1.2. Cn nguyn vi khun gy nhim khun huyt ................................ 4 1.1.2.1. Vi khun Gram m gy nhim khun huyt .............................. 4 1.1.2.1.1. Escherichia coli ............................................................... 4 1.1.2.1.2. Klebsiella ........................................................................ 5 1.1.2.1.3. Pseudomonas aeruginosa .................................................. 5 1.1.2.1.4. Acinetobactor baumannii .................................................. 6 1.1.2.2. Vi khun Gram dng gy nhim khun huyt ......................... 6 1.1.2.2.1. Staphylococcus aureus (S.aureus) ................................... 6 1.1.2.2.2. Staphyllococci coagulase (-) ............................................ 7 1.1.2.2.3. Streptococci .................................................................... 7 1.1.2.2.4. Streptococcus pneumoniae .............................................. 7 1.1.3. c im lm sng v cn lm sng nhim khun huyt ................ 8 1.1.3.1. c im lm sng ca nhim khun huyt ............................. 8 1.1.3.2. c im cn lm sng ca nhim khun huyt ....................... 9 1.1.3.2.1. Xt nghim huyt hc ..................................................... 9 1.1.3.2.2. Xt nghim sinh ha mu .............................................. 10 1.1.3.2.3. Xt nghim chc nng ng mu .................................. 10 1.1.3.2.4. Phn lp vi khun t mu .............................................. 10 1.2.VNSDNGKHNGSINHTRONGIUTRNHIM KHUN HUYT ...................................................................................... 11 1.2.1. Nguyn tc s dng khng sinh trong iu tr nhim khun huyt 11 1.2.2.Mtsnhmkhngsinhsdngtrnbnhnhnnhimkhun huyt..................................................................................................... 11 1.2.2.1. Nhm beta lactam ................................................................ 11 1.2.2.2. Aminoglycosid (gentamycin, streptomycin, tobramycin) .... 13 1.2.2.3. Quinolon ................................................................................ 13 1.2.2.4. Peptid ..................................................................................... 13 1.2.3. La chn khng sinh iu tr nhim khun huyt ......................... 14 CHNG 2: I TNG V PHNG PHP NGHIN CU ............. 16 2.1. I TNG NGHIN CU ............................................................ 16 2.1.1. i tng nghin cu ................................................................... 16 2.1.2. Tiu chun la chn ..................................................................... 16 2.1.3. Tiu chun loi tr ....................................................................... 16 2.2. PHNG PHP NGHIN CU ....................................................... 16 2.2.1. Thit k nghin cu ...................................................................... 16 2.2.2. Phng tin nghin cu ................................................................ 16 2.2.3. Phng php ly mu ................................................................... 16 2.2.4. Ni dung nghin cu .................................................................... 16 2.2.4.1. c im chung ca i tng nghin cu ............................. 16 2.2.4.2. c im ca vi khun gy nhim khun huyt ...................... 17 2.2.4.3.Khosttnhhnhsdngkhngsinhtrnbnhnhnnhim khun huyt ......................................................................................... 17 2.3. PHNG PHP X L S LIU ................................................... 17 CHNG 3:KT QU NGHIN CU .................................................... 18 3.1. C IM CHUNG CA I TNG NGHIN CU ................ 18 3.1.1. c im chung ca bnh nhn nghin cu .................................. 18 3.1.2. Thi im mc bnh trong nm .................................................... 19 3.2.CIMVIKHUNGYNHIMKHUNHUYTVTNH HNH KHNG KHNG SINH ................................................................ 20 3.2.1. Xt nghim tm vi khun .............................................................. 20 3.2.2. c im vi khun phn lp c ................................................ 20 3.2.3. Tnh hnh khng khng sinh ca vi khun gy bnh ................. 21 3.2.3.1. Tnh hnh khng khng sinh ca E. coli ............................. 22 3.2.3.2. Tnh hnh khng khng sinh ca P. aeruginosa ................... 22 3.2.3.3. Tnh hnh khng khng sinh ca A. baumannii .................. 23 3.2.3.4. Tnh hnh khng khng sinh ca S. aureus ......................... 24 3.3.KHOSTTNHHNHSDNGKHNGSINHTRNBNH NHN NHIM KHUN HUYT ............................................................ 24 3.3.1. Tnh hnh s dng khng sinh trc khi nhp vin ....................... 24 3.3.2. c im khng sinh s dng ....................................................... 25 3.3.2.1. Danh mc khng sinh c s dng trong nghin cu ........... 25 3.3.2.2. S ln thay i phc trong thi gian iu tr: ..................... 27 3.3.3. Phc khng sinh khi u khi cha c xt nghim vi sinh ....... 27 3.3.3.1. Cc phc n c khi u ................................................ 27 3.3.3.2. Cc phc phi hp khi u............................................... 28 3.3.4. Phc khng sinh thay th khi c kt qu xt nghim vi sinh ..... 29 3.3.4.1.Phckhngsinhthaythkhicktqucykhundng tnh ...................................................................................................... 29 3.3.4.2. Phc khng sinh thay th khi c kt qu cy khun m tnh31 CHNG 4: BN LUN ........................................................................... 33 4.1. C IM CHUNG CA I TNG NGHIN CU ................ 33 4.1.1. c im chung ca bnh nhn nghin cu .................................. 33 4.1.2. Thi im mc bnh trong nm .................................................... 34 4.2.CIMVIKHUNGYBNHVTNHHNHKHNG KHNG SINH .......................................................................................... 34 4.2.1. Xt nghim tm vi khun .............................................................. 34 4.2.2. c im vi khun phn lp c ................................................ 35 4.2.3. Tnh hnh khng khng sinh ca vi khun gy bnh ................. 37 4.2.3.1. Tnh hnh khng khng sinh ca E.coli .............................. 38 4.2.3.2. Tnh hnh khng khng sinh ca P. aeruginosa ................... 38 4.2.3.3. Tnh hnh khng khng sinh ca A.baumannii ................... 39 4.2.3.4. Tnh hnh khng khng sinh ca S.aureus .......................... 40 4.3.KHOSTTNHHNHSDNGKHNGSINHTRNBNH NHN NHIM KHUN HUYT ............................................................ 41 4.3.1. Tnh hnh s dng khng sinh trc khi nhp vin ....................... 41 4.3.2. c im khng sinh s dng ....................................................... 41 4.3.2.1. Danh mc khng sinh c s dng trong nghin cu ........... 41 4.3.2.2. S ln thay i phc trong thi gian iu tr ...................... 42 4.3.3. Phc khng sinh khi u khi cha c xt nghim vi sinh ....... 43 4.3.4.Sthayiphckhngsinhsaukhicktquxtnghimvi sinh ........................................................................................................ 44 KT LUN V XUT ......................................................................... 46 I. KT LUN: .......................................................................................... 46 II. XUT: ........................................................................................... 47 TI LIU THAM KHO PH LC DANH MC CC K HIU, CH VIT TT A. baumannii: Acinetobacter baumannii BN: Bnh nhn C3 : Khng sinh cephalosporin th h 3 C4 : Khng sinh cephalosporin th h 4 CRP : protein phn ng C cs: cng s E. coli: Escherichia coli ESBL: Extended spectrum betalactamase FQ : Flouroquinolon Gram (-): Gram m Gram (+): Gram dng KS: Khng sinh KS: khng sinh MRSA: T cu vng khng methicillin NKH : Nhim khun huyt P. aeruginosa: Pseudomonas aeruginosa PCT: Procalcitonin S. aureus: Staphyllococcus aureus S. epidermidis: Staphyllococcus epidermides Str. pyogenes: Streptococcus pyogenes VK: vi khun DANH MC CC BNG BngTn bngTrang 1.1La chn khng sinh theo thng tin vi khun gy bnh14 3.1c im bnh nhn18 3.2T l cy mu dng tnh20 3.3Kt qu phn lp vi khun21 3.4Tnh hnh s dng khng sinh trc khi nhp vin24 3.5Danh mc cc thuc khng sinh c s dng25 3.6S ln thay i phc khng sinh27 3.7 Cc phc n c khi u trong iu tr nhim khun huyt 28 3.8 Cc phc phi hp khi u trong iu tr nhim khun huyt 29 3.9Phc thay th khi c kt qu cy khun dng tnh29 3.10Phc thay th khi c kt qu cy khun m tnh32 DANH MC CC HNH HnhTn hnhTrang 3.1Phn b bnh nhn theo thi im mc bnh trong nm19 3.2T l cc loi vi khun20 3.3Tnh hnh khng khng sinh ca E. coli22 3.4Tnh hnh khng khng sinh ca P. aeruginosa23 3.5Tnh hnh khng khng sinh ca A. baumannii23 3.6Tnh hnh khng khng sinh ca S. aureus24 1 T VN Nhim khun huyt l mt bnh nhim khun ton thn nng, gy ra do vi khun v c t ca vi khun lu hnh trong mu. Nhim khun huyt c nguyctvongcaodoscnhimkhunvrilonchcnngnhiuc quan. Lm sng ca nhim khun huyt rt a dng, din bin thng nng v khng c chiu hng t khi nu khng c iu tr kp thi [1], [47], [50].Nhiunmqua,nhimkhunhuytvnlnguynnhngytvong hng u ti cc n v hi sc khng phi tim mch. Mi nm, ti M c ti 750.000trnghpnhimkhunhuytnngnhpvin,trong215.000 trng hp t vong - chim 9,3% tng s t vong ti t nc ny. Ti c, nhim khun huyt c xc nhn 60.000 trng hpmt nm v l nguyn nhn th ba ph bin nht gy t vong [45]. Cnnguyngynhimkhunhuytrtadngnhngthngc3 loi: vi khun Gram m, cu khun Gram dng v trc khun Gram dng kkh.Ccvikhunnycthxmnhpvocthquanhiuconng khc nhau nh ng da v nim mc, ng h hp, tiu ha, tit niu [2]. Vic iu tr khng sinh sm v thch hp cho thy hiu qu ln trong kt qu iutr cabnh nhn.Ngi ta c tnhrngtrung bnhvimigichm iutrkhngsinhchiuthgim8%khnngsngcaccbnhnhn [29]. Tuynhin,thctrngsdngkhngsinhkhngkimsotnhhin nay lm tng hin tng khng khng sinh ca vi khun v gy kh khn cho viciutrnhimkhunhuyt.Trnthgii,nhiuchngvikhungy bnhtrnnngycngkhngthuckhngsinh.Cckhngsinhthh mtgnnhkhng c lachntrongnhiutrng hp.Cc khngsinh th h mi t tin, thm ch c mt s khng sinh thuc nhm la chn cui cng cng ang mt dn hiu lc. Do t l khng khng sinh cao, nhiu liu 2 phpkhngsinhckhuyncotrongcctiliuhngdniutr khngcnhiulc[22].Do,vic khosttnhhnhsdngkhng sinh trong iu tr nhim khun huyt l rt cn thit. LmtbnhvinthchnhcaHcvinquny,Bnhvin103l bnhvinakhoahngI,viquymhn1000gingbnhthamgiavo cng tc khm, cha bnhtheo tuyn vkhu vcchobi, ccitng chnh sch, v nhn dn; phc v nhu cu iu tr cho mt s lng ln BN t tuyndichuynthngln(trongckhoaAM5-khoatruynnhim). Nhmtmhiuthctrngsdngkhngsinhtrongiutrnhimkhun huyt,tccinhntngquanviutrbnhnhimkhunhuytti khoa truyn nhim, chng ti tin hnh ti nghin cu Kho st tnh hnh sdngkhngsinhtrnbnhnhnnhimkhunhuytiutrtiKhoa truyn nhim - bnh vin 103 vi hai mc tiu sau: 1.Xcnhccchngvikhungynhimkhunhuytvtnhhnh khng khng sinh ca chng ti khoa truyn nhim - Bnh vin 103. 2.Khosttnhhnhsdngkhngsinhtrongiutrnhimkhun huyt ti khoa truyn nhim - Bnh vin 103. 3 CHNG 1: TNG QUAN TI LIU 1.1. I CNG V BNH NHIM KHUN HUYT 1.1.1. Dch t hc nhim khun huyt 1.1.1.1. Tnh hnh nhim khun huyt trn th gii Nhimkhunhuythinnaylmttrongnhngcnnguynchyu gybnhnngvtvong.ChringHoaKthminmckhong 750.000trnghpmcbnh,trongs215.000trnghptvong, chim9,3%tngstvongtitncny[44].Php,tlscnhim trngl13,7%[72].n,ccnhnghincuthngkctl nhimkhunhuytnngl16,5%.Tltvongsaunhpvinvtvong sau 28 ngy do nhim khun huyt nngtng ng l 65,2% v 64,6% [76]. TiAnh,nghincucaHarrisonvcs,nm2006trn92.673bnhnhn nhp vin cho thy, tnh trng nhim khun huyt nng xut hin trong vng 24 gi u tng t 23,5% (1996) ln n 28,7% (2004) v t vong cng tng t9.000ca(48,3%)nm1996lnn14.000ca(44,7%)nm2004[58]. NghincucaJasonvcsnm2011ti150khoahisctchccca16 nc trong khu vc chu , t l nhim khun huyt dao ng t 5 - 53% ty theoqucgia[63].thtrnIle-Ife-Nigeria,nghincucahaitcgi KomolatevAdegokenm2008chot hytlnhimkhunhuytdao ng t 15 - 20% [64]. 1.1.1.2. Tnh hnh nhim khun huyt Vit Nam TiVitNam,trongbococaNguynVnKnhvcsnm2008, khiphntchthctrngsdngkhngsinhtiVitNamchothy,tl nhim khun huyt ni chung l 8% [22]. Mi y, nghin cu ca V nh Ph v cs nm 2013 cc khoa hi sc tch cc ca 15 bnh vin trong ton quc cho thy t l nhim khun huyt chim 10,4% [26]. 4 Ti Bnh vin Bch Mai, nm2008, on Mai Phng v cng s phnlpcctcnhngynhimkhunhuytchothytldngtnhl 8,1%, trong , vi khun Gram m 71,9%, vi khun Gram dng 23,4%, nm 4,7% [27]. Ti Bnh vin trung ng Hu, t l NKH do E.coli chim 35,1%, K.pneumoniae14,9%,S.suis16,2%[7].Nm2010,tcgiPhmThNgc Tho tng hp tc nhn gynhim khun huyt thng gp nht ti bnh vin Ch Ry l Acinetobacter baumanii v Pseudomonas aeruginosa, chim 40,5% cc trng hp [32]. 1.1.2. Cn nguyn vi khun gy nhim khun huyt Tcnhngynhimkhunhuytrtadng,cthldovikhun Gramdng,Grammvnm.Cmtskhcnhauvtnsutmcbnh cngnhloivikhungynhimkhunhuytgiaccbnhvin,vng, quc gia. 1.1.2.1. Vi khun Gram m gy nhim khun huyt 1.1.2.1.1. Escherichia coli Escherichiacoli(E.coli)lthnhvinthucvihbnhthngca ngtiu ho, chim t l cao nht trong s cc vi khun hiu kh (khong 80%). Tuynhin,E.colicnglvi khungybnhquantrng,nghng u trong cc cn nguyn gy nhim khun huyt [39]. TheonghincucacctcgitiMt1999n2008thnhim khun huyt nng do vi khun Gram m chim 51,5%, trong ph bin nht l E.coli chim 39,9% [43]. Tc gi L Th Thanh Hng v cs cng xc nhtcnhnE.coligynhimkhunhuytbnhvinNhing1chim 17,8%[17].TheotcgiCaoMinhNga,tlnybnhvinThngNht TP.HCM l 24,11% [25]. 5 1.1.2.1.2. Klebsiella Klebsiellalmttrongnhngchiquantrngcahvi khunng rut,ctronghvikhunbnhthngrutngitrngthnh,vis lngnh(di102vikhun/1gamphn).Klebsiellachyugybnhc hi,cngnghoctrongbnhvin-lmttrongcccnnguyngy nhim trng bnh vin thng gp. HuhtcccquanucthbnhimtrngdoKlebsiella.Nc khnnggynhimkhunhuyt,vimmngno,vimtaigia,vim xoang,nhimkhun ng tit niu, p xe gan[10]. Theo nghin cu ca Ghotaslou v cs nm 2007 Klebsiella pneumoniae l vikhungrammthnggpnhtgynhimkhunhuytssinhTabriz, Iran,cnglvikhungytvongcaohnccvikhunkhc[54].TiVit Nam, cc tc gi cng chng minhKlebsiella l nguyn nhn ng u trong cc vi khun Gram m gy nhim khun huyt s sinh [31], [12].1.1.2.1.3. Pseudomonas aeruginosa Pseudomonasaeruginosa(P.aeruginosa)lmtloitrckhunhaiu trn, khng sinh nha bo, di ng c nh mt lng nm mt cc ca t bo. Tnh cht c trng caP.aeruginosa l sinh sc t mu xanh v cht c mi.P.aeruginosa l tc nhn gy nhim trng c hi quan trng trn cc i tngbnhnhncvnvmindchdobngnng,ux,bnhnhnmc bnh suy gim min dch hoc iu tr ung th. y l vi khun gy nhim trng bnh vin nguy him v iu ng lo ngi nht l tnh khng khng sinh cao i vi hu ht cc khng sinh thng thng. P.aeruginosa cng c th gy nhim khunhuyt do nhim trng t cc v tr khc nhau trn c th, nhng hu ht nhimkhunhuytclinquanncanthipnimchvtruynmutnh mch trung tm [15]. 6 1.1.2.1.4. Acinetobactor baumanniiAcinetobactor baumannii (A. baumannii)l cc vi khun c tm thy ph bin trong t, nc v mi trng. Chng d dng c phn lp t da, hng v nhiu dch tit ca ngi kho mnh v cng l tc nhn gy nhim trng ngi.A. baumanniingvai trquantrngtrongnhiunhim trngc hi vnhimtrngbnhvin.Ccyutnguycthunlichonhimkhun huytvngunlyphbinlvikhuntbnhnhnbvimphi,sang chn, phu thut, t catheter, ng truyn tnh mch, lc mu v bng. S suygimmindchhocthiunnghhplcvovinlmtngnguyc nhimkhunhuytln3ln.Nmvinlungy,chonungquang thngvsdngkhngsinhcephalosporinsthhbatrcul nhngyutnguyccavicvikhunctrvnhimtrngdoA. baumannii, dovylmtngnguycnhim khun huytdoAcinetobacter. Tlnhim khun huyt do A. baumanniixp th hai sau vim phi v tin lng ph thuc nhiu vo bnh nn ca bnh nhn [37]. 1.1.2.2. Vi khun Gram dng gy nhim khun huyt 1.1.2.2.1. Staphylococcus aureus (S.aureus) S.aureus l nhng cu khun, ng thnh hnh chm nho, khng c lng, khngsinhnhabo,thngkhngcv.S.aureusthngksinhmi hng v c th c da. Vi khun ny gy bnh cho ngi b suy gim sc khnghocchngcnhiuyutclc.S.aureuslvikhungybnh thng gp nht v c kh nng gy nhiu loi bnh khc nhau: nhim khun ngoi da, nhim khun huyt, vim phi, nhim c thc n, vim rut cp. Trong cc vi khun Gram dng, S.aureus l vi khun gy nhim khun huyt nhiu nht, do chng c th gy nn nhiu loi nhimkhun, c bit 7 lccnhimkhunngoida,tyvikhunxmnhpvomugynn nhim khun huyt [9].1.1.2.2.2. Staphyllococci coagulase (-) Staphyllococci coagulase (-) l t cu khng c enzym coagulase - mt thnh phnca hvi khunbnh thng cada vnimmc,idin quan trng nht ca nhm ny l S.epidermidis. Cc vi khun ny l nguyn nhn nhim trng thng gp sau chn thng chnh hnh v cng l nguyn nhn canhimtrngbnhvin.Chngckhnngsinhralpmngnhy,v di lp mng ny vi khun pht trin thnh cc khun lc nh bm vo cc ngthngbngchtdo.Lpnhynycngbovvikhunkhngbtn cng bi cc t bo min dch v khng b tc ng bi khng sinh [18]. 1.1.2.2.3. StreptococciStreptococci l nhng vi khun gram dng, khng c enzym catalase, k kh ty tin, hnh cu v hnh trng. LincunhmA(S.pyogenes):lnhnglincutanhuytbta,i dinchomttrongnhngtcnhngybnhngiphbinnht.Nhiu yu t c lc ca n (protein M, acid lipoteichoic) gy ra hng lot cc nhimkhunnghimtrngtvimhng,vimnghhp,vimdav vim m mm, vim mng no, nhim khun mu do v vim khp. LincunhmB:lnguynnhnchyugynhimtrngssinh nng vi cc th nhim khun huyt v vim mng no [19]. 1.1.2.2.4. Streptococcus pneumoniaeStreptococcuspneumoniae(phcu)lthnhvinphbincahvi khunchvnghuhngnhngcnglmtcnnguynchyucavim phivvimmngnotremvngiln.Ngoiraphculnguyn nhn ca 40-50% s trng hp vim tai gia cp. Trong qu trnh xm nhp 8 cctchc,phcucthvomugynhimkhunhuytviccbin chng nghim trng nh nhim khun lan trn, sc nhim khun.Ti Vit Nam,tltvongca vimphidophcuchim6-19% nhng t l t vong s cao hn gp 2 n 5 ln khi b nhim khun huyt do ph cu [20]. 1.1.3. c im lm sng v cn lm sng nhim khun huyt 1.1.3.1. c im lm sng ca nhim khun huyt Nhim khun huyt l tp hp nhng biu hin lm sng ca mt tnh trng nhim khun, nhim c ton thn mc t nh n nng v c nguy c t vong nhanh do bnh cnh sc v suya tng, gyra bi s xm nhp lintccavikhunvccctcachngvomu,xutphttmt nhim khun khi im. Vi khun d c c lc gy bnh thp hay cao u c thc kh nng gy nhim khun huyt khi sc khng ca c thca bnhnhnsuygim,thigiannmvinkodi,chungnhiuththut xm ln [50], [57]. Lm sng ca nhim khun huyt thng c nhng biu hin sau y:Ri lon thn nhit: thng gp l st khi pht t ngt. C s tng quan gia nhit v nng ca bnh. Triu chng st c th khng r rng hoc khng st trn cc tr s sinh hoc bnh nhn gi. C khong 13% bnh nhn khngcbiuhinst mlichnhit(< 36,5C), trong 40% trng hp h thn nhit l do tnh trng nhim khunnnghayvngkhun huyt v nhng trng hp ny thng c t l t vong cao hn nhm h thn nhit do nguyn nhn khc [2], [46].Rilontimmch:mchthngnhanh,tingtimm,huytpng mch thng h, i khi c th nghe thy ting thi tm thu trong trng hp thiumu,suytimhocngmunimchlanta,nhngbnhnhnc biu hin nhim khun huyt nng, sc nhim khun khc [2], [46]. 9 Tngthngkh:lmtbiuhinsmcanhimkhunhuyt.Triu chngnycthctrckhistvlnhrun.Nhpthnhanhtrn20ln/ pht,hocPaCO2 10% bch cu non mu ngoi bin. Gim bch cu l mt yu t tin lng nng.Hngcu,Hemoglobinbnhthnghocgimtrongnhimkhun huyt nng. 10 Tiucu:bnhthnghocgim30%gitrbnhthngkhicnhimkhunhuytnngvsc nhim khun. 1.1.3.2.2. Xt nghim sinh ha mu Nng CRP tng. Creatininthngtngcao(>2,0mg/dlhoc176,8mol/l)khinhim khunhuyt cbiuhinsuythn,hocbnhnhncnhimkhun huyt nng v c sc nhim khun. Glucose mu bnh thng hoc tng. Lactatehuytthanhbnhthnghoctngcaohn2lngitrbnh thng. Nng Procalcitonin (PCT) tng.Ri lon chc nng gan: bilirubin v SGOT, SGPT c th bnh thng hoctngtrongtrnghpctnthnggan,vimgancphaysuy chc nng gan trong nhim khun huyt nng, sc nhim khun.1.1.3.2.3. Xt nghim chc nng ng mu Gim t l Prothrombin 1.5. 1.1.3.2.4. Phn lp vi khun t mu Phnlpvikhuntmudngtnh:ltiuchunvngtrongchn on nhim khun huyt. Phnlpvikhuntmumtnhcngkhngloitrcnhim khun huyt, c bit nhng bnh nhn dng khng sinh [1], [50]. 11 1.2.VNSDNGKHNGSINHTRONGIUTRNHIM KHUN HUYT 1.2.1. Nguyn tc s dng khng sinh trong iu tr nhim khun huytiutrsm.Dngkhngsinhngaysaukhilybnhphmcy khun. liu,liucaohayphihpkhngsinhvithigiancnthitcho iu tr. Lm khng sinh v la chn khng sinh theo mc nhy cm. Khichacktqucykhuncniutrphngondavo nhim khun tin pht v c a bnh nhn. Ngngsdngkhngsinhsaukhibnhnhnhtst,tnhtrngton thn tt ln, gii quyt c nhim khun tin pht [2], [11]. 1.2.2.Mtsnhmkhngsinhsdngtrnbnhnhnnhimkhun huyt [4], [5] 1.2.2.1. Nhm beta lactam Penicillin t nhin (penicillin G, penicillin V): c tc dng ph hp, chyutrnccvikhungram(+)nh:Staphylococcus, Streptococcus,Pneumococcus;trckhunvtrnmtsvikhun gram (-) nh: lu cu, mng no cu. Penicillinkhngpenicillinase(methicillin, oxacilin, nafcilin):c tc dngtttrnccvi khuntitpenicilinase,tcdngkmpenicillinG trn vi khun khng tit penicilinase v cng khng c tc dng vi hu ht cc vi khun gram (-). Ccpenicillinphrng(ampicillin,amoxicillin):ctcdngtrn ccvikhungram(+)gingpenicillintnhin,nhngcthmtc 12 dngtrnmtsgram(-)nh:E.coli,Enterococci,Salmonelat, Shigella, Proteus Carboxypenicillin(ticarcillin,temocillin):cphtcdngging aminopenicillinnhngrnghn,thucctcdngtrnc Enterobacter,Bacteroides,Proteus,Pseudomonaskhng aminopenicillin.Nhmthucnychyudngiutrnhimkhun nng do P.aeruginosa gy ra. Ureidopenicillin(mezocillin,piperacillin):cphkhngkhunging carboxypenicillincngthmKlebsiellavmtsvikhungram(-) khc. Cephalosporin:lkhngsinhphrng,cchiathnh4thhda theophtcdng.CephalosporinthhI(cefazolin,cefradin, cefadroxil)cphtcdngtrnvikhungram(+)nhtcu,lin cu,phcu(trMRSA),nhngtcdngttrnvikhungram(-). CephalosporinthhII(cefuroxim,cefoxitin)ctcdngtrnvi khun gram (+) yu hn nhng trn vi khun gram (-) th mnh hn th hI.CephalosporinthhIII(cefotaxime,cefoperazon,ceftriaxon) tc dng tt trn vi khun gram (-) (nh cc trc khun ng rut, vi khunkkhvP.aeruginosa),bnvngvibeta-lactamasenhng kmtcdngivivikhungram(+).CephalosporinthhIV (cefepime, cefpirome) c ph tc dng rng tng t nhng mnh hn thhIII,thuctcdngtttrnEnterobacteriaceae,Pseudomonas, Streptococcus, lu cu, no m cu. Carbapenem(imipenem,meropenem):lnhmkhngsinhditkhun c ph khng khun rng nht hin nay. C tc dng trn nhiu loi vi khun gram (+) v gram (-), vi khun a kh v k kh, cc vi khun tit ra beta-lactamase k c chng khng methicillin. 13 1.2.2.2. Aminoglycosid (gentamycin, streptomycin, tobramycin) Lnhmkhngsinhphrng,ctcdngmnhtrnvikhunGram (-), cn trn vi khun Gram (+) th tc dng km penicillin. L nhm thuccchnchonhimkhunbnhvindoEnterococcusvP. aeruginosa. Thucthngcdngkthpvinhmbeta-lactammrng phtcdng.Tuynhinnhcimcanhmnylcvithnvthn kinh thnh gic, do cn phi ch ti liu dng hp l v thi gian iu tr khng qu di (khng qu 7 ngy). 1.2.2.3. Quinolon Quinolon th h I (acid nalidixic, oxolinic): c ph tc dng hp, ch tc dng trn vi khun a kh gram (-) nh: E. coli, proteus, Klebsiella, Enterobacter, tr P.aeruginosa.Quinolon th h II (fluoroquinolon): c hot tnh trn vi khun gram (-) mnhhnthh I,c bitlP.aeruginosa.Ngoi ra,chngcntc dnglncmtsvikhungram(+),chyulStaphylococcus, Streptococcus,vvikhunnibo,ttcdngtrnvikhunkkh. Thuc c tc dng dit khun ton thn (tc dng mc tun hon v m). 1.2.2.4. Peptid Glycopeptid (vancomycin, teicoplanin): ph tc dng hp, ch tc dng trn vi khun hiu kh v k kh gram (+), c bit l Streptococcus v Staphylococcus (k c chng khng methicilin); khng c tc dng trn vi khun gram (-). Polypeptid (polymyxin B, polymyxin E): c ph tc dng hp trn cc vikhungram(-)nh:E.coli,Klebsiella,Salmonella,Shigellavc bit l P.aeruginosa, khng tc dng trn vi khun gram (+). 14 1.2.3. La chn khng sinh iu tr nhim khun huyt Bng 1.1. La chn khng sinh theo thng tin vi khun gy bnh [3] Vi khunKhng sinh la chnKhng sinh thay th VikhunGrammng rut h Enterobacteriaceae (khng sinh ESBL) - Ciprofloxacin - Ceftriaxon -Cckhngsinh Cephalosporinthh 3 v 4 khc -Cckhngsinh nhm flouroquinolon VikhunGrammng rut h Enterobacteriaceae (sinh ESBL) - Ertapenem- Imipenem-cilastatin - Meropenem - Doripenem Pseudomonas aeruginosa- Ceftazidim - Cefepim - Piperacillin - Tazobactam - Ciprofloxacin - Imipenem-cilastatin - Meropenem Burkholderia pseudomallei - Cefazidim- Imipenem-cilastatin - Meropenem Streptococcus pneumoniae- Ceftriaxon - Cefotaxim - Levofloxacin - Vancomycin Staphylococcusaureus (nhy Methicilin) - Oxacilin- Vancomycin 15 Vi khunKhng sinh la chnKhng sinh thay th Staphylococcusaureus (khng Methicilin) - Vancomycin- Daptomycin Streptococcus suis- Ampicillin- Ceftriaxone Clostridium perfringens- Penicilin - Metronidazole - Clindamycin Bacteroides fragilisMetronidazole 16 CHNG 2: I TNG V PHNG PHP NGHIN CU 2.1. I TNG NGHIN CU 2.1.1. i tng nghin cu Bnh n ca bnh nhn c chn on nhim khun huyt iu tr ti khoa Truyn nhim - Bnh vin 103 t thng 1/2010 n thng 10/2014 (tnh theo thi im ra vin). 2.1.2. Tiu chun la chn cchnonkhinhpvinvchnonxcnhkhiravinl nhim khun huyt. 2.1.3. Tiu chun loi tr Bnh n ca bnh nhn t vong. 2.2. PHNG PHP NGHIN CU 2.2.1. Thit k nghin cu Phng php m t hi cu ct ngang. 2.2.2. Phng tin nghin cu Thuthpthngtintbnhnvinvomubnhnnghincu (ph lc 1) 2.2.3. Phng php ly mu Ly ton b bnh n ca khoa Truyn nhim - Bnh vin 103 t thng 1/2010nthng 10/2014(tnhtheothi imravin)thamntiu chun la chn v tiu chun loi tr. Tng s bnh n la chn c: 150 bnh n. 2.2.4. Ni dung nghin cu 2.2.4.1. c im chung ca i tng nghin cu c im v tui, gii tnh. Thi im mc bnh trong nm. ng vo ca vi khun gy bnh. 17 2.2.4.2. c im ca vi khun gy nhim khun huyt Xtnghimtmvikhun:gmccxtnghimcymu,dchcth (m, dch no ty, dch khp..). Phnbvikhun:thngkccchngvikhunphnlpctrn bnh nhn nhim khun huyt. Kho st tnh hnh khng khng sinh ca vi khun phn lp c da trn kt qu khng sinh . 2.2.4.3.Khosttnhhnhsdngkhngsinhtrnbnhnhnnhim khun huyt Kho st tnh hnh s dng khng sinh trc khi vo vin. Khostdanhmccckhngsinhc sdngtrong iutrnhim khun huyt. Kho st vic la chn phc khng sinh trong iu tr. 2.3. PHNG PHP X L S LIU Sliucxltheoccthuttonthngkyhc,sdngphn mm SPSS 22.0, bao gm: Gitrtrungbnh,lchchun:viccbinnhlngphnphi chun. Gi tr trung v - cc gi tr gii hn (cao nht - thp nht): vi cc bin nh lng phn phi khng chun. 18 CHNG 3:KT QU NGHIN CU Nghin cu trn 150 bnh nhn iu tr ti khoa Truyn nhim (AM5) - Bnhvin103tthng1/2010nthng10/2014,ktqunghincuthu c nh sau: 3.1. C IM CHUNG CA I TNG NGHIN CU 3.1.1. c im chung ca bnh nhn nghin cu c im chung ca bnh nhn nghin cu c trnh by bng 3.1 Bng 3.1. c im bnh nhn Thng sS bnh nhnT l (%) Tui trung bnh (n = 150)58,3 18,1 Nhm tui (n = 150) < 2074,7 20 - 402114,0 41 - 604328,6 > 607952,7 Gii tnh (n = 150) Nam8456,0 N6644,0 ngvocavikhun gy bnh (n = 150) Khng r 2919,3 Hhp4127,3 Tiu ha3523,3 Tit niu3120,8 Da v m mm53,3 C xng khp53,3 Sau phu thut42,7 19 Nhn xt: Tui trung bnh ca bnh nhn trong mu nghin cu l 58,3 18,1.Nhmtuichimtlcaonhtltrn60tui(52,7%),saun nhm tui 41 - 60 (28,6%). Nhm tui chim t l thp nht l di 20 tui (4,7%). V gii tnh, t l bnh nhn nam (56,0%) cao hn t l bnh nhn n (44,0%). ng vo ph bin ca vi khun l h hp (27,3%), tiu ha (23,3%) vtitniu(20,8%).C19,3%cctrnghpkhngxcnhc ng vo ca vi khun. 3.1.2. Thi im mc bnh trong nm Thi im mc bnh trong nm c trnh by hnh 3.1. Hnh 3.1. Phn b bnh nhn theo thi im mc bnh trong nm Nhn xt: Tlbnhnhnnhpvinvothng7(15,3%),thng8(13,3%)v thng 9 (11,3%) l nhiu nht trong nm. 20 3.2. C IM VI KHUN GY NHIM KHUN HUYT V TNH HNH KHNG KHNG SINH 3.2.1. Xt nghim tm vi khun Kt qu xt nghim vi sinh ca 150 bnh nhn vi 150 mu bnh phm t mu c th hin chi tit ti bng 3.2. Bng 3.2. T l cy mu dng tnh Thng sS muT l (%) m tnh4932,7 Dng tnh10167,3 Tng150100 Nhn xt: 100% bnh nhn c lm xt nghim cy mu xc nh vi khun. T l bnh phm c kt qu cy mu m tnh kh cao (32,7%). 3.2.2. c im vi khun phn lp c Kt qu phn lp vi khun c th hin chi tit ti hnh 3.2, bng 3.3. Hnh 3.2. T l cc loi vi khun 21 Bng 3.3. Kt qu phn lp vi khun Chng vi khunS lng (n = 101)T l (%) Gram (-)7776,3 Acinetobacter baumannii2221,8 Escherichia coli2726,7 Pseudomonas aeruginosa2322,8 Klebsiella pneumoniae55,0 Gram (+)2423,7 Statphyllococcus aureus1211,9 Staphyllococcus epidermidis21,9 Streptococcus suis II76,9 Burkholderia cepacia group33,0 Tng101100,0 Nhn xt: C 8 chng vi khun gy bnh phn lp c khi cy mu. Vi khun gy bnh ch yu l vi khun Gram (-) chim 76,3%, trong 3chnggpnhiunhtlnltllE.coli(26,7%),P.aeruginosa (22,8%), A. baumannii (21,8%). T l vi khun Gram (+) gy bnh chim 23,7%, trong nhiu nht l S. aureus (11,9%). 3.2.3. Tnh hnh khng khng sinh ca vi khun gy bnh Tlkhngkhng sinh camichngvikhunctnh bng t sgiaschngkhngvitngschngcthkhngsinhcho tng loi khng sinh. Theohnh3.2,tcnhngynhimkhunhuythaygpc4loiE. coli, P. aeruginosa, A. baumannii v S. aureus, nn chng ti ch tp trung 22 kho st tnh hnh khng khng sinh ca 4 chng ny. Cc loi cn li do s lng qu t nn chng ti khng kho st, do cng khng c c bn lun tha ng. 3.2.3.1. Tnh hnh khng khng sinh ca E. coli Tnh hnh khng ca E. coli c th hin ti hnh 3.3. Hnh 3.3. Tnh hnh khng khng sinh ca E. coli Nhn xt: E.colikhngmnhviceftriaxon(59,3%),ceftazidim(44,4%),vn cnnhyvicckhngsinhnhmcarbapenem,cbitlnhycm hon ton vi ertapenem. 3.2.3.2. Tnh hnh khng khng sinh ca P. aeruginosa TnhhnhkhngcaP.aeruginosacthhintihnh3.4. Nhn xt: P.aeruginosa khngvigentamicin,fosfomycin,cefotaximv ceftazidim,vncnnhycmvimtskhngsinhnhimipenem, meropenem v colistin. 23 Hnh 3.4. Tnh hnh khng khng sinh ca P. aeruginosa 3.2.3.3. Tnh hnh khng khng sinh ca A. baumannii Tnh hnh khng ca A. baumannii c th hin ti hnh 3.5. Hnh 3.5. Tnh hnh khng khng sinh ca A. baumannii Nhn xt: A.baumanniikhngmnhvihuhtcckhngsinh,cbitlvi ceftazidim(77,3%),cefriaxon(68,2%),ciprofloxacin(63,6%).Vikhuncn nhy cm vi 1 s khng sinh nh: imipenem, meropenem v nhy 100% vi colistin. 24 3.2.3.4. Tnh hnh khng khng sinh ca S. aureus Tnh hnh khng ca S. aureus c th hin ti hnh 3.6. Hnh 3.6. Tnh hnh khng khng sinh ca S. aureus Nhn xt: S.aureus khngmnhvigentamicin(83,3%),erythromycin (75,0%), amikacin (66,7%). S. aureus cn nhy cm vi nhiu khng sinh nh vancomycin (100%), fosfomycin (91,7%), rifampicin (83,3%). 3.3.KHOSTTNHHNHSDNGKHNGSINHTRNBNH NHN NHIM KHUN HUYT3.3.1. Tnh hnh s dng khng sinh trc khi nhp vin Bng 3.4. Tnh hnh s dng khng sinh trc khi nhp vin S bnh nhnT l (%) dng khng sinh4630,7 Cha dng khng sinh7952,6 Khng r2516,7 Tng150100 25 Nhn xt: T l bnh nhn dng khng sinh kh cao, chim 30,7%. T l bnh nhn cha dng khng sinh l 52,6%. 3.3.2. c im khng sinh s dng 3.3.2.1. Danh mc khng sinh c s dng trong nghin cu Bng 3.5. Danh mc cc thuc khng sinh c s dng Nhm KSTn quc tTn bit dc Beta-lactam Amoxicillin+ Clavunalic (Penicillin) Augmentin Cefuroxim (C2)Cefuroxime ActavisCefotaxim (C3)Cefotaxime Claforan Cefotaxone Ceftriaxon (C3)Ceftriaxone TV-Ceftri Cefoperazon (C3)Cefoperazone Beesencef Ceftazidim (C3)Ceftazidime Cefepime (C4) Fujiject Spectrax Cefistar Suprapime Necpime Cemoxi Empixil Harcepime Vipimax Micropime 26 Cefpirome (C4)Cefire Laxazero Pentirome Imipenem (Carbapenem)Tienam Meropenem (Carbapenem)Meronem Meropenem Monan MJ Quinolon LevofloxacinTavanic Siratam Levobac Getzlox Amlox PL Flocix Levofloxacin MoxifloxacinAvelox Cinmox Plenmoxi CiprofloxacinCiprobay Aminoglycosid AmikacinSelemycin Amikacin Glycopeptid VancomycinOscamicin Vancomycin Vagonxin FosfomycinFosfomycinFosmicin 5-nitro imidazoleMetronidazoleMetronidazole Cotrimoxazole Trimethoprim+ Sulfamethoxazole Sulfaprim 27 Nhn xt: Cckhngsinhcsdngtrongmunghincuphnlntheo hngdnsdngkhngsinhcaBYthoccngnhmvicc khng sinh c khuyn co. 3.3.2.2. S ln thay i phc trong thi gian iu tr: Bng 3.6. S ln thay i phc khng sinh S ln thay i phc S bnh nhn (n = 150)T l (%) 010771,4 13221,3 264,0 353,3 Nhn xt: Bnhnhnchyuchthayiphc1lnsaukhicktqucy khun (21,3%), vic phi thay i phc n ln 3 rt t (3,3%). T l bnh nhn khng phi thay i phc kh cao (71,4%). 3.3.3. Phc khng sinh khi u khi cha c xt nghim vi sinh Trongnghincu,ttc150bnhnhnucsdngphc khng sinh khi u ngay sau khi nhp vin. Trong : Phc n c: 33/150 bnh nhn, chim t l 22,0%. Phc phi hp: 117/150 bnh nhn, chim t l 78,0%.3.3.3.1. Cc phc n c khi u Cc phc nckhiutrong iutrnhimkhunhuytc trnh by bng 3.7. 28 Bng 3.7. Cc phc n c khi u trong iu tr nhim khun huyt Phc Tn hot chtS bnh nhn (n) T l(%) Beta-lactam Amoxicillin + Acid Clavulanic26,0 Cefotaxim1339,4 Cefepime39,1 Meropenem39,1 Tng2163,6 Quinolon Ciprofloxacin412,1 Levofloxacin39,1 Tng721,2 FosfomycinFosfomycin515,2 Tng33100,0 Nhn xt: Nhmbeta-lactamcsdngnhiunht(63,6%),cbitl cefotaxim thuc nhm cephalosporin th h III (39,4%). S dng nhiu th hai l nhm quinolon chim 21,2%. 3.3.3.2. Cc phc phi hp khi u Cc phc phi hp khi u trong iu tr nhim khun huyt c trnh by bng 3.8. Nhn xt: C 111 phc phi hp 2 khng sinh (chim 94,9%), 6 phc phi hp3khngsinh(chim5,1%)vkhngcphcnophihp nhiu hn 3 khng sinh. Sphihpcabeta-lactam+quinolonchimtlnhiunht (70,9%), tip theo l fosfomycin + quinolon (11,1%). 29 Bng 3.8. Cc phc phi hp khi u trong iu tr nhim khun huyt Phc S bnh nhn (n) T l(%) Aminoglycosid + Beta-lactam54,3 Aminoglycosid + Quinolon32,6 Beta-lactam + 5 -nitroimidazole21,7 Beta-lactam + Fosfomycin21,7 Beta-lactam + Quinolon8370,9 Beta-lactam + Quinolon + 5-nitroimidazole65,1 Fosfomycin + Quinolon1311,1 Quinolon + 5-nitro imidazole32,6 Tng117100,0 3.3.4. Phc khng sinh thay th khi c kt qu xt nghim vi sinh 3.3.4.1. Phc khng sinh thay th khi c kt qu cy khun dng tnh Phc khng sinh thay th khi c kt qu cy khun dng tnh c trnh by bng 3.9. Bng 3.9. Phc thay th khi c kt qu cy khun dng tnh Phc ban u Phc thay th ln 1 Phc thay th ln 2 Phc thay th ln 3 S bnh nhn Beta-lactamBeta-lactam + Quinolon + 5 - nitroimidazole 1 Beta-lactamBeta-lactam + Quinolon 12 30 Beta-lactamBeta-lactam + Fosfomycin2 Beta-lactamBeta-lactam + Quinolon Aminoglycosid + Beta-lactamAminoglycosid + Beta-lactam + Quinolon 1 FosfomycinFosfomycin + Quinolon Fosfomycin + Quinolon + 5-nitroimidazole1 FosfomycinBeta-lactam + Fosfomycin + Quinolon Fosfomycin + Quinolon Fosfomycin +Glycopeptid + Quinolon 1 QuinolonBeta-lactam + Quinolon 2 QuinolonFosfomycin + Quinolon 2 Beta-lactam + Quinolon Aminoglycosid + Quinolon 3 Beta-lactam + 5 -nitroimidazole Beta-lactam + Quinolon Aminoglycosid + Quinolon Beta-lactam + Cotrimoxazole + Glycopeptid + Quinolon 1 Beta-lactam + Fosfomycin Beta-lactam + Fosfomycin + Quinolon 1 31 Beta-lactam + Quinolon Glycopeptid + Quinolon Beta-lactam + Glycopeptid + Quinolon1 Beta-lactam + Quinolon Fosfomycin + Quinolon Beta-lactam + Fosfomycin + Quinolon2 Fosfomycin + Quinolon Aminoglycosid + Glycopeptid + Quinolon 1 Quinolon + 5-nitroimidazole Aminoglycosid + Beta-lactam + Quinolon 1 Tng32 Nhn xt: T l thay i phc trn bnh nhn cy khun dng tnh l 32/101 (chim 31,7%).Skthpcanhmbeta-lactam+quinolonlthngcsdng nht (12/32 = 37,5%). 3.3.4.2. Phc khng sinh thay th khi c kt qu cy khun m tnh Phckhngsinhthaythkhicktqucykhunmtnhc trnh by bng 3.10. Nhn xt: Trong s bnh nhn c kt qu cy khun m tnh, c 11/49 trng hp thay i phc chim 22,4%. Skthpcanhmbeta-lactam+quinolonlthngcsdng nht (4/11 = 36,4%). 32 Bng 3.10.Phc thay th khi c kt qu cy khun m tnh Phc khi u Phc thay th ln 1 Phc thay th ln 2 Phc thay th ln 3 S bnh nhn Beta-lactamBeta-lactam + Quinolon 4 Beta-lactamBeta-lactam + Fosfomycin 1 Beta-lactamBeta-lactam + Quinolon Aminoglycosid + Beta-lactam Beta-lactam + Fosfomycin 1 FosfomycinBeta-lactam + Fosfomycin + Quinolon Fosfomycin + Quinolon + 5-nitroimidazole1 QuinolonBeta-lactam + Quinolon Beta-lactam + Fosfomycin Aminoglycosid + Beta-lactam + Quinolon 1 QuinolonFosfomycin + Quinolon 1 Beta-lactam + Quinolon Aminoglycosid + Quinolon Aminoglycosid + Beta-lactam + Quinolon1 Beta-lactam + Fosfomycin Beta-lactam + Fosfomycin + Quinolon 1 Tng11 33 CHNG 4: BN LUN Cn c vo kt qu nghin cu trn 150 bnh nhn c chn on v iutrNKH tikhoaTruynnhim(AM5)-Bnhvin103, chngtibn lun mt s vn nh sau: 4.1. C IM CHUNG CA I TNG NGHIN CU 4.1.1. c im chung ca bnh nhn nghin cu Trong nghin cu ca chng ti, tui trung bnh ca bnh nhn nghin cu l 58,3 18,1, (tui thp nht l 17 v cao nht l 89), trong gp nhiu nht nhm tui trn 60 (52,7%)(bng3.1). Kt qu ny cng ph hp vi nghincucaTrnVnStibnhvinakhoaKinGiangnm2012 (nhmtuitrn60chimtl56,48%)[30],TrnXunChngtibnh vin TW Hu (nhm tui trn 60 chim tl 47,3%) [7]. Theo chng ti,s d nhm tui trn 60 chim t l nhiu nht v tui cng cao, cng nhiu bnh l kt hp, sc khng yu, d b nhim khun v khi mc bnh th d b nhim khun nng hn. V gii tnh khng c s khc bit r rng gia nam v n. T l bnh nhnnamtrongnghincul56%,bnhnhnn44%.Ktqunyca chng ti cng tng ng vi cc nghin cu ca Trn Xun Chng (2012) (nam 55,4%, n 44,6%) (2013) [7] v Nguyn Th Hng Thy (2002) [35].Trongbnhnhimkhunhuyt,vikhuncthxmnhptcc nhimkhunnnghocsutrncth.Vicxcnhngvocavi khun gy bnh rt quan trng trong vic la chn khng sinh ban u iu tr nhim khun huytkhichacktqukhngsinh . Tuynhin,khng philcnocngcthxcnhcngvocavikhun.Trong nghincucachngti,c19,3%cctrnghpkhngxcnhc ngvoca vikhun, tng ng viktqunghin cucaTrnXun Chng cng cs (18,9%) [7], Trn Th Lin (23,8%) [24]. ng vo ch yu 34 trongnghincunylnghhp(27,3%),ngtiuha(23,3%)v ng tit niu (20,8%) (bng 3.1). Cc con ng c th d dng pht hin c qua iu tra bnh s v thm khm lm sng. Bn thn bnh nhn cng cthphthinc,tuynhinbnhnhnthngchquankhngiutr sm hoc t iu tr ti nh khng ng cch, dn n bnh din bin nng v vi khun xm nhp vo mu gy nhim khun huyt. Kt qu ny tng ng viktqunghincucaPhmLuNhtHong(2011)[16],PhmTh Ngc Tho [33] v nghin cu a quc gia ca Vincent cng cs (2009) [78]. 4.1.2. Thi im mc bnh trong nm Theoktqunghincucachngtithbnhnhnmcbnhrirc quanhnmnhngthiimmcbnhnhiuhntptrungvothng7 (15,3%), thng 8 (13,3%) v thng 9 (11,3%) (hnh 3.1). C th y l khong thigiangiaoma,thititbini-thiimthunlichosphttrin caccvikhungybnh,ngthidlmgimsckhngcacon nginnvikhundgybnh.TheoktqunghincucaNguynTh Hng Thy nm 2002 th thi im mc bnh nhiu nht trong nm vo thng 3, 4, 5 [35]. Kt qu ca chng ti hi c s khc bit vi kt qu nyv s bng pht ca vi khun ph thuc vo iu kin a l v kh hu ca tng a phng. 4.2.CIMVIKHUNGYBNHVTNHHNHKHNG KHNG SINH 4.2.1. Xt nghim tm vi khun Xt nghim xc nh vi khun gy bnh c vai tr rt quan trng trong vicchnonnguynnhngynhimkhunhuyt,khivicsdng khngsinhstrnnhplvhiuquhn,ngthihnchctnh trngkhngkhngsinhcavikhun.Chonnay,cymuphthinvi khun vn c coi l tiu chun vng chn on nhim khun huyt v t 35 l pht hin vi khuntrongmu rt cao (90%). Trong nghin cu ca chng ti, 100% bnh nhn u c lm xt nghim phn lp vi khun trong mu. Ngoi ra, bnh nhn c th c cy dch ti nhim khun tin pht (m, dch m, dch khp..). Hu ht cc bnh nhn c lm xt nghim nhiu ln kim tra dinbinbnhvhiuquiutrcaphckhngsinh. Kt qu nghin cu cho thy, 67,3% mu bnh phm dng tnh vi mt s chng vikhun,32,7%mubnhphmchoktqumtnh(bng3.2).Tlcy khun m tnh trong nghin cu ny kh cao, theo chng ti l do khi iu tra bnh s thy c ti 30,7% s bnh nhn s dng khng sinh trc khi n vin, iu lm nh hng rt nhiu n kt qu cy khun. 4.2.2. c im vi khun phn lp c T 101 mu bnh phm phn lp c 8 chng vi khun. Kt qu phn lp vi khun trong mu nghin cu cho thy vi khun Gram (-) (76,3%) chim tlcaohnvikhunGram(+)(23,7%)(bng3.3).Ktqunycngph hp vi mt s nghin cu c cng b [79], [76], [27].Theoktqucanghincuny,bachngvikhunctnsxut hincaonhttrongnhmvikhungram(-)lchngE.coli(26,7%),P.aeuruginosa (22,8%) vA.baumanii(21,8%), trongnhm vikhungram (+) l S. aureus (11,9%) (bng 3.3). Nh vy, vi s tri dy ca cc vi khun GrammnhE.coli,A. baumannii, P. aeruginosa,chngthc s tr thnh nhng ngun vi khun gy nhim khun huyt quan trng, l mt thch thc choccnhlmsngviutr,dokhnnggytvongcaovkhng vi nhiu loi thuc khng sinh thng c s dng trong iu tr. Chng ti khng tmc stng ngviktqucanhngnghincukhcmc d cc chng vi khun k trn vn c bit n l cc tc nhn ph bin nht gy nhim khun huyt, tuy nhin, tn sut mc ca tng chng vi khun khc 36 nhautythucvotngthik,latuicngnhmtsyutlinquan n sc khng ca c th bnh nhn.NhimkhunhuytdotrckhunGram(-)lmtthchthctrong iutrlmsngdotlvikhunsinhmenESBLngycnggiatng,c bit i vi E. coli.Nghin cu ca Chamberland 10 bnh vin ti Canada chothynhimkhunhuytGram(-)chyulE.coli(52,5%)[49].Ti bnh vin Trung ng Hu, tc nhn chnh gy nhim khun huyt l E. coli (35,1%)[7].Nghin cutibnhvin103t2005-2010cngchoktqu mm bnh gp nhiu nht l E.coli (38,4%) [38]. Ngaytkhicphthin,P.aeruginosanhncrtnhius quan tm ca cc nh y hc. Nghin cu ca Hsieh ti i Loan trong 07 nm (2000-2006),tlnhimkhunhuytdoP.aeruginosal36%,nghng utrongsnhngcnnguynvikhungram(-)gynhimkhunhuyt [62]. c tnh vo nm 2010, ti M c khong 40.000 ngi t vong c lin quannnhimkhunhuytdoP.aeruginosa[44].PhmThNgcTho (2010), khi nghin cu 234 trng hp nhim khun huyt ti bnh vin ch Ry P. aeruginosa chim t l 17,9% [32].Vi khun Gram m gy nhim khun huyt c ni n nhiu trn th gii hin nay l A. baumannii,, do kh nng gy bnh, tnh khng khng sinh, chi ph iu tr, thi gian nm vin v t vong cao hn so vi cc trng hp nhim khun huyt do cc tc nhn khc. Nghin cu ca Grupper v cs, nm 2007tiIsraeltrong3nmc219trnghpnhimkhunhuytdoA. baumannii, t l t vong ca nhim khun huyt do A. baumannii l 36,5% v c s dng th thut xm ln chim ti 50% trong khi do cc vi khun khc l 26% [56].Nghin cu ca Deris v cs nm2009 Malaysia cho thy, t l hinmcnhimkhunhuytdoA.baumanniil6,11%vchimmttl cao khoa hi sc tch cc hn l khoa khc (53,4% so vi 46,6%), thi gian 37 xut hin nhim khun huyt do A. baumannii trung bnh l 16,6 ngy, trong khidovikhunkhcl13,52ngy[51].MtnghincucaonMai Phngvcsnm2012tibnhBchMaichothy,tnhhnhnhimA. baumanniichungttcccngunbnhphmtngt24,9%(2002)ln 42%(2009),trongtlbnhnhnccymudngtnhvcchn onlnhimkhunhuytl11,8%[28].NghincucaPhmHng Vn vcsnm2010 t16bnhvinVit Namchothy,tlcymudng tnhviA.baumannii18/188(9,5%)[40].Nghincucacctcgithc hin ti bnh vin Nhi ng 1 cng cho thy, t l bnh nhn c chn on l nhim khun huyt c cy mu dng tnh vi A. baumannii chim 21,1% (2005)giatngln32,2%(2009)[34].MtnghincumiycaV nh Ph v cs nm 2013 thc hin trn 16 khoa hi sc tch cc 16 bnh vin trong ton quc cho thy, nhim khun huytmcphi trongbnhvin ch chim 10,4%, nhng trong do A. baumannii l 31% [26]. TrongnhmvikhunGram(+),nhimkhunhuytdoS.aureusvn lunlvnnhcnhitrongchnonviutrnhimkhunhuytt trcnnay.Quanghin cu, chng ti nhn thyS.aureus l cn nguyn gy bnh hng u trong cc vi khun Gram dng (11,9%). Kt qu ny ph hp vi nghin cu ca Vincent J.L., Samuel S.O., Negussie A. cng cc cng s vi t l ln lt l: 20%, 35,85% v 23,2% [78], [74], [68]. Tsering DC nghincuticcbnhvinSikkim(n)vnhnthytcnhnGram (+) gy bnh ph bin nht l S.aureus (97%) [77]. Cc nghin cu ti Vit Nam ca Hoa NT von Mai Phng cng cho kt qu tng t [60], [27]. 4.2.3. Tnh hnh khng khng sinh ca vi khun gy bnh Vnvthctrngkhngkhngsinhmangtnhtoncuvc bit ni tri cc nc ang pht trin, trong c Vit Nam vi gnh nng 38 caccbnhnhimkhunvnhngchiphbtbucchovicthaythcc khngsinhcbngcckhngsinhmi,ttin.Khosttnhkhng khng sinh ca vi khun gip thy thuc la chn khng sinh mt cch hp l hn,nngcaohiuquiutrvlmgimchiphchobnhnhn.Trong nghin cu ca chng ti, E. coli, P.aeruginosa, A. baumanii vS. aureus l bn chngvi khun gp nhiunht v cng c t l khng tng i cao vi mt s khng sinh ph rng thng dng.4.2.3.1. Tnh hnh khng khng sinh ca E.coli MckhngkhngsinhcaE.colicbongtrongnhiu nmtrcy nhiunctrnthgii.yl vikhungybnhthng gp nht nhng hin nay ang c t l khng cao vi mt s khng sinh thng thng.Theohnh3.2,E.colikhngmnhvi2khngsinhthhIII: ceftriaxon(59,3%),ceftazidim(44,4%),tngngviktqunghincu tibnh vin ChRynm2010[32]. Nghincutrn 15bnhvinVit Nam, cc tc gi thng k c E.coli khng khng sinh cephalosporin th h III vo khong 30 - 70% [69]. VikhunE.colicnnhycmvikhngsinhnhmcarbapenem: meropenem, imipenem v c bit l cn nhy cm hon ton viertapenem. KtqunyphhpvinghincucaMaiThLanHng,PhmTh NgcTho,NguynVnKnh[32],[21],[69].Hinnayertapenemang c khuyn co hng u trong cc hng dn iu tr bnh nhim khun do E. coli [3]. 4.2.3.2. Tnh hnh khng khng sinh ca P. aeruginosa Pseudomonasaeruginosalmttrongnhngnguynnhnhngu gynhimkhunbnhvin.Cngvitlgybnhngycngcaoltnh hnh a khng khng sinh ngy cng nghim trng ca vi khun ny. 39 So snh vi mt s nghin cu trn th gii, chng ti nhn thy c s tngngvtlkhngmtskhngsinh.TheoGolshani(2012),tl khnggentamicin,ciprofloxacinlnltl60%,58%,cachngtil 65,2%v 43,4%[55]. NghincucaPitt T.L. vcng s(2003) cngcho thy50%schngvikhunkhngvigentamicin,30%khngvi ciprofloxacin [70]. Ti Vit Nam, theo Bi Khc Hu t l khng gentamicin, ciprofloxacin, amikacin ln lt l 54%, 30,9% v 29,1% [14]. Ti bnh vin PasterTp.HCM,tlkhngciprofloxacin,amikacin,colistinl44,4%, 39,3%, 10,7% [6], kh tng ng vi kt qu ca chng ti. Cho n nay, carbapenem v colistin l nhng v kh hu hiu nht iutrnhimtrngdoP.aeruginosagynnvmaymnltrongnghin cu, P. aeruginosa vn cn nhy cm cao vi 2 khng sinh ny. 4.2.3.3. Tnh hnh khng khng sinh ca A.baumannii SkhngkhngsinhcaA.baumanniigiatngtheothigianv hin nay n tr thnh mt ni lo lng cho cc nh iu tr khi m vi khun ny tr thnh tc nhn ca nhiu v dch xy ra khng ch khoa hi sc tch cc, mcthnhiukhoalmsngkhc,trnnhiuloiitngbnhnhn trong cc bnh vin nhiu quc gia trn th gii [48], [67].NghincucaSisrackvcsnm2012,trn93.215bnhphmmu cho thy, c 6,8% dng tnh vi A. baumannii. v vi khun ny khng vi tt cccloikhngsinh,daongt45-70%,ringvinhmkhngsinh carbarpenem, mc khng dao ng t 0 - 52,8% [75]. khu vc Chu , tnh trng nhim khun huyt do A. baumannii cng c bo co ti mt s nc nh n , Thi Lan, Trung Quc, Hn Quc, Singapore daong t 10 -30% v tnh trng khng vi tt c khng sinh gia tng t 50% ln ti trn 70%, nht l nhm carbapenem c s gia tng ng bo ng [66], [52]. 40 VitNam,tnhhnhkhngkhngsinhcaA.baumanniicngthay i ty theo bnh vin, khoa iu tr v i tng bnh nhn. Nghin cu ca onMaiPhngvcsnm2012 thchintikhoahisctchccbnh vinBchMaitlmcl18,6%,trongmckhngKSlkhcao: khng 100% vi ceftazidim, ciprofloxacin, aminoglycosid [28]. NC ca Trn Xun Chng v cs, nm 2011, Bnh vin Trung ng Hu, cy mu dng tnh A. baumannii chim 19% v khng vi imipenem l 45% [8].Trong nghin cu ca chng ti,A. baumannii khng mnh vi hu ht cckhngsinh,cbitlviceftazidim(77,3%),cefriaxon(68,2%), ciprofloxacin(63,6%).Vikhuncnnhycmvi1skhngsinhnh: imipenem (63,6%), meropenem (59,1%) v nhy 100% vi colistin (hnh 3.5). KtqunykhtngngvinghincucaNguynThNamLin (2011) [23] v Nguyn Th Thanh H [13] v Vn nh Trng [36]. 4.2.3.4. Tnh hnh khng khng sinh ca S.aureus VikhunS.aureuskhngmnhvigentamicin(83,3%)v erythromycin(75%),vncnnhycmvinhiuloikhngsinhnh oxacillin,rifampicin,fosfomycinvvancomycin.Vancomycinlkhngsinh thaythkhitcuvngkhngmethicillinhocbnhnhndngvicc beta-lactamkhc.Trongnghincucachngti,S.aureusvncnnhy 100%vivancomycin,tngngviktqunghincucaPhmHng Vn(2005),MaiThLanHng(2011)[41],[21].Tuynhin,theotiliu [59], [73], xut hin chng hetero S. aureus khng vi vancomycin, ngha l vancomycin ang gim dn hiu qu iu tr trong lm sng. Do cn c sgimstchtchvsdngmtcchthntrngkhilachn vancomycin. 41 4.3.KHOSTTNHHNHSDNGKHNGSINHTRNBNH NHN NHIM KHUN HUYT 4.3.1. Tnh hnh s dng khng sinh trc khi nhp vin Nh chng ta bit,bnh vin 103 l bnh vin ln, tip nhn nhiu trnghpbnhnng,bnhnhnchuyntccbnhvintuyndi, ciutrbngkhngsinhhocbnhnhntmuathucungtinh. Do,tlbnhnhnsdngkhngsinhtrckhivovinkhcao (30,7%) cng l iu d hiu. Tuynhin, iu nynh hngkhng nh ti ktqucykhunbimttrongnhngnguyntckhixtnghimtmvi khun l phi lm xt nghim trc khi dng khng sinh. Thc trng ny gy kh khn cho vic xc nh cn nguyn gy bnh v lm tng nguy c khng thuc ca vi khun. 4.3.2. c im khng sinh s dng 4.3.2.1. Danh mc khng sinh c s dng trong nghin cu ThngkcckhngsinhcsdngtikhoaTruynnhimbnh vin103,chngtinhnthyhuhtcckhngsinhuphhptheo khuyncocaBYt.Ccnhmkhngsinhcsdngl:beta-lactam,quinolon,aminoglycosidvmtsnhmkhc(glycopeptid, fosfomycin,5-nitroimidazole,cotrimoxazol).Trongcsdngnhiu nht l cc beta-lactaml cc khng sinh ph rng, tc dng c trn c vi khun Gram m v Gram dng. Trong cc beta-lactam, nhm cephalosporin th h III, IV c s dng nhiu hn c. c im ca hai phn nhm ny l tc dng tt hn trn cc vi khun Gramm v bnvng vi betalactamase. S la chn khng sinh nh vy l ph hp vi bnh vin 103 bi cn nguyn ch yu gy nhim khun huyt trong nghin cu l cc vi khun Gram m.Quinolon l nhmkhng sinh c s dng nhiu th hai bnh vin mchyulfloroquinolon(FQ).FQcphkhngkhunrng,tcng 42 mnh trn vi khunGram (-) a kh,bao gm c P. aeruginosa do kh nng xmnhpvotbovikhuncao.Tibnhvin103,sdngc ciprofloxacin,levofloxacinvmoxifloxacin.Ciprofloxacintcdngttvi cc vikhunkhnglikhng sinh nhmkhc(cephalosporin,aminglycosid, penicillin,.)vccoilmttrongcckhngsinhmnhnhttrong nhmFQ.Soviciprofloxacin,levofloxacincuimchcnathuc mt ln trong ngy, m rng ph tc dng trn vi khun Gram (+), k c cc cu khun khng thuc. Amikacinlkhngsinhcphrngnhttrongnhmaminoglycosid, c tc dng rt mnh trn vi khun Gram (-), cn trn vi khun Gram (+) th tc dng hn ch. Tuy nhin khng sinh nhm ny gy c trn thn v thnh gic nn khng s dng n c m ch yu phi hp vi KS nhm khc.Vancomycin l khngsinh dit khun bng cch c ch qu trnh sinh tnghpvtbovikhun,ckhuyncodngditvikhun Gram(+)S.aureusgynhimkhunhuyt,kcccchngkhng methicillin [3]. Cckhngsinhcsdngchyutheongtim,truyntnh mch v hu ht cc bnh nhn tnh trng nng, cn a khng sinh t nng c tc dng iu tr mt cch nhanh nht, trnh cc bin chng nguy him cho bnhnhn.4.3.2.2. S ln thay i phc trong thi gian iu tr Khiccphcbanukhngchiuquthvicthayiphc iu tr l iu tt yu. S thay i ny ph thuc vo vi khun phn lp c vkhngsinh.Trongnghincucachngti,cttc43trnghp phi thay i phc khng sinh. Trong ch yu l thay i phc 1 ln (21,3%). T l bnh nhn phi thay i phc n ln 3 rt thp (3,3%). 107 trnghpcnli,chim71,4%khngphithayiphc,yltl 43 kh cao, chng t cc phc iu tr theo kinh nghim bnh vin 103 kh hiu qu. 4.3.3. Phc khng sinh khi u khi cha c xt nghim vi sinh Chngtnhkimsotnhimkhunhuytnngvscnhimkhun (2012) khuyn co nn s dng khng sinh theo ng tnh mch ngay trong giutinsaukhicchnonnhimkhunhuyt[50].Mtsbng chng chng minh t l t vong tng cao hn nhng bnh nhn s dng khng sinh mun sau biu hin shock [65], [71]. Ti bnh vin 103, theo kho st ca chng ti, hu ht cc bnh nhn u c ch nh khng sinh ngay sau khi thm khm lm sng v chn on nhim khun huyt. iu ny em li hiu qu rt ln trong qu trnh iu tr cho bnh nhn. Khichacktqucykhun,ccbcsdavotriuchnglm sngcabnhnhnvkinhnghimiutrlachnccphckhng sinhnchayphihp.Quakhost,chngtinhnthyc33bnh nhn(22%)csdngphcnckhiucn117bnhnhn (78%) sdngphcphihp. Tl phc phihp caohn hnphc n c, iu ny l hon ton ph hp, v theo y vn v nhiu nghin cu trongvngoincthnhimkhunhuytchyuldoccvikhun gram (-), do vic kt hp hai loi khng sinh c hiu qu hn nhiu so vi vic s dng khng sinh n c. Baphckhngsinhnckhiutrongnghinculbeta-lactam,quinolon vfosfomycin.y ulcc khngsinh phrng,ctc dng chng li c vi khun Gram (-) v Gram (+), c ch nh do cha xc nhcchnhxc vikhun.Trong,beta-lactamcsdngrngri (chim63,6%). Khng sinh nhm ny cng l la chn utay trong hng dncabnhvinNottingham[61].Trongnhmbeta-lactam,khngsinh cefotaximlkhngsinhutincacephalosporinthhIII,tuytcdng 44 trn P. aeruginosa km hn cc khng sinh khc cng nhm nhng vn c cc bc s la chn theo thi quen khi iu tr nhim khun. Vkhngsinhphihpkhiu,cccliuphpphihp2khng sinh v 3 khng sinh. Trong phi hp ch yu l beta-lactam v quinolon, c bit l khng sinh C3 + FQ. S phi hp ny cho kt qu tt trn vi khun Gram (-) a khng thuc hoc hip ng tc dng trn P. aeruginosa [53]. Al-Hasan MN nghin cu trn 2 nhm bnh nhn s dng khng sinh n c vphihp,ktqulnhmsdngphcphihpbeta-lactamv flouroquinolonctltvongthphnsovinhmiutrbngbeta-lactam n c [42]. Chng tikhngtmthyhngdniutrnokhuynco sdng fosfomycin. Tuy nhin bnh vin 103, liu php phi hp gia fosfomycin vquinoloncchnhnhiuth hai.C ldofosfomycinl khngsinh ph rng, tc dng c bit mnh trn cc chngP.aeruginosa, S. aureus v E.colikhnglinhiuloithuc,phihpquinolongipmrngph khng khun v tng cng hiu qu iu tr.4.3.4. S thay i phc khng sinh sau khi c kt qu xt nghim vi sinh Khicktquphnlpvikhunvkhngsinh,ccbcss davoiuchnhkhngsinhsdngvvicthayiphcl khngthtrnhkhi.Phcthaythcththmkhngsinh,tngliu khng sinh hoc thay bng khng sinh khc. bnhnhnckt qu cykhundngtnh,32,7%bnh nhnphi thay i phc do nh hng v vi khun ban u khng ng hoc khng sinh s dng khng ph hp vi kt qu khng sinh . C 3 bnh nhn phi thay i phc 3 ln, phi hp nhiu nht 4 khng sinh. Hu ht cc phc n c trc cy khun u chuyn sang phc phi hp tng tc dng 45 dit khun.Phc thay th nhiu nht vn l phi hp gia beta-lactam v quinolon. Theo tnh hnh khng khng sinh ca 4 vi khun gy bnh ch yu nhtrnhbytrn,ccvikhuncnkhnhycmvicckhngsinh C3,C4,cbitlnhycmcaovinhmcarbapenem.Nhvy,sla chn khng sinh thay th l ph hp vi kt qu khng sinh . bnhnhncktqucykhunmtnh,c11/49bnhnhnc thayiphc,chyuchthayiphc1ln,c2trnghpphi thay i 2 phc v 2 trng hp phi thay i ti 3 phc . C th do tnh trng bnh nhn s dng khng sinh trc lm gim s nhy cm ca vi khun,gimhiuquiutrnnphithaythbngkhngsinhkhc.Do khng xc nh c chnh xc vi khun gy bnh, nn khng c khng sinh phhpnocchnhmchyusdngccphcphihpgia beta-lactam vi quinolon hoc aminoglycosid. 46 KT LUN V XUT I. KT LUN: Sau khi tin hnh kho st trn 150 bnh nhn c chn on v iu trNKHkhoaTruynnhim-bnhvin103tthng1/2010nthng 10/2014, chng ti rt ra mt s kt lun nh sau: 1. c im chung ca i tng nghin cu: Tui trung bnh ca bnh nhn l 58,3 18,1. Nhm tui mc bnh nhiu nht l trn 60 tui (52,7%). Khng c s chnh lch r rng gia t l bnh nhn nam v n (nam56,0%, n 44,0%) ng vo ch yu ca vi khun l h hp, tiu ha v tit niu. 19,3% khng xc nh c ng vo. Thi gian mc bnh quanh nm, tp trung vo thng 7 (15,3%) v thng 8 (13,3%), thng 9 (11,3%) 2. c im vi khun gy NKH: T l cy khun dng tnh l 67,3%, t l cy khun m tnh l 32,7%. Bn chng vi khun gy bnh nhiu nht l: + Escheriachia coli (26,7%) + Pseudomonas aeruginosa (22,8%) + Acinetobacter baumannii (21,8%) + Staphylloccus aureus (11,9%) Tnh hnh khng khng sinh: +E.colikhngviceftriaxonvceftazidim,cnnhycmvi cc carbapenem. + P.aeruginosa khngvi gentamicin, fosfomycin v cefotaxim, cn nhy cm vi carbapenem v colistin. 47 +A.baumanniikhngcaovihuhtkhngsinh,nhycmhon ton vi colistin. + S. aureus khng cao vi gentamicin, erythromycin, amikacin, nhy cm vi fosfomycin v vancomycin. 3. Tnh hnh s dng khng sinh: Tlbnhnhnsdngkhngsinhtrckhivovinkhcao (30,7%). Ccnhmkhngsinhcsdngtrongiutrl:beta-lactam, quinolon,aminoglycosidvmtsnhmkhc(glycopeptid, fosfomycin,5-nitroimidazole,cotrimoxazole).Trongbeta-lactam csdngnhiunhtrinquinolon.Trongccbeta-lactam,s dngcccephalosporinthhIII,IVlchyu.Ciprofloxacinl khng sinh quinolon c s dng nhiu nht. Trc khi c kt qu xt nghim vi sinh, cc khng sinh c th c s dngnchocphihp2,3khngsinh.Trongphcphi hp 2 khng sinh l ch yu.Sau khi c kt qu xt nghim vi sinh, bnh nhnc thayi nhiu nht 3 phc . II. XUT: Nhimkhunhuytlcnbnhnghimtrngvitltvongcao. Vic phn lp vi khun v lm KS c ngha quan trng trong la chn s dng khng sinh. Tuy nhin, thc trng s dng khng sinh ba bi nh hin nay lm tng nguy c khng thuc ca vi khun v gim hiu qu iu tr. Do , chng ti kin ngh: Tip tc tin hnh cc nghin cu v cn nguyn vi khun gy bnh v mckhngkhngsinhcavikhunticckhoa,phngvis lng mu ln hn. 48 Tin hnh thm cc nghin cu nh gi tnh ph hp v hiu qu ca cc phc khng sinh s dng trong iu tr NKH. 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Chn on: II- Bnh s: 1. nhim khun tin pht: Tiu haH hp Tit niu Sinh dcNgoi daSau PT Khng r 2. S dng khng sinh trc khi vo vin: CKhngIII- Triu chng lm sng- Bin chng: Bin chng: Suy thn RL ng mu Tn thng gan ARDS IV- Cn lm sng: 1. Phn lp vi khun: 1.1 Cy mu: 1.2 Cy dch t cc NK: 2. Khng sinh : Khng sinhKQKhng sinhKQKhng sinhKQ Amoxicillin+ A. clavulanic MeropenemPiperacillin+ Tazobactam CefotaximeCiprofloxacinFosfomycin CeftazidimeLevofloxacinAmikacin CeftriaxoneErtapenemColistin CefepimeOxacillinRifampicin ImipenemGentamicinCefuroxime 3. Cc xt nghim khc: 3.1 Xt nghim sinh ha mu: Ch tiun vTr s bnh thngKt qu Glucose mmol/L3.9 - 6.4 Ure mmol/L2.5 - 7.5 Creatininmol/L50-110 Cholesterolmmol/L3.9 - 5.2 Triglyceridmmol/L0.46 - 2.3 Bilirubin TPmol/L0 - 17.1 Bilirubin TTmol/L0 - 5 GOTUI0 - 40 GPTUI0 - 40 in gii 3.2. XN cng thc mu: Ch tiun vTr s bnh thngKt qu WBCG/L4 - 10 NE%%50 - 70 LY%%20 - 44 MO%%1 - 5 EO%%0.9 - 4 BA%%0.3 - 1.5 RBCTest/L4.38 - 5. 77 HGBg/L120 - 160 HCTL/L0.39 - 0.5 MCHpg28 - 32.2 MCHCg/L320 - 360 3.3. Xt nghim nc tiu: Ch tiun vTr s bnh thngKt qu BIL (Bilirubin)Negative BLD (hng cu)Negative GLU (Glucose)Negative KET (ketose)Negative LEU (bch cu)Negative NIT (Nitrit)Negative pH5.0 - 8.0 PRO (protein)Negative SG (T trng)1.015 - 1.025 UBG (Urobilinogen)