canh giac duoc nghiên cứu khoa học

Trong nghien cPu cua chung tdi chi ghi nhan dupe 3,2% trUdng hop sP d u n g linezolid vdi ly do phu hop vdi cac khuyen cao sPdung linezolid ma mot so qudc gia ap d u n g [15] bao g[r]

Khdo sdt sir dung khdng sinh linezolid tai Benh vien Bach Mai nam 2015

• • • •

DoanThi PhPOng1, LeVan Anh2,Tran Nhan Thang2,

VP Oinh H6a\ Nguyen Hoang Anh1 ' Trifdng Dai hoc Dupe Ha Npi

2Khoa Dupe - Benh vien Bach Mai SUMMARY

This study aimed to explore prescribing behavior in the use of linezolid, a new antibiotic for Gram positive infections, in Bach Mai hospital in first three quaters of 2015 A retrospective study was conducted on 311 medical records of Inpatients prescribed with linezolid admited in Bach Mai hospital from January to September of 2015 Of 311 selected medical records, 74 (23.8%) were prescribed linezolid with approved indications in which the most common was community arquired pneumoniae with 37 (11.9%>) cases A minor number of 10 (3.2%) cases were found to have rational reason for linezolid use Up to 237 (76.2%) patients were prescribed linezolid with off-label indications and the majority of those were for treatment or prevention of neutropenic fever which account for 44.7%> Fourty seven pathogens were isolated including one Enterococcus spp strain with decreased susceptiblility and one methicilin resistant Staphylococcus aureus strain with resistance to linezolid Oral route was indicated in 95.2% of the cases Linezolid was commonly prescribed for off-label indications or approved indications without rational reason for its use Interventions to limit the irrational use of linezolid are required

Ttfkhoa: chi dinh dupe phi duyet, linezolid, ly lua chgn, viem phoi mac phai cpng dong

Dqt van de

N h i e m khuan b e n h vien la m o t t r o n g n h d n g nguyen nhan hang dau lam tang t y le mac benh va tCr vong toan cau [14] M o t so nghien cub gan day chi rang, cac vi khuan Gram(+) cang co vai t r o quan t r p n g t r o n g nhPng tac nhan gay n h i e m khuan benh vien [10], [11] Hien nay, vancomycin dang la thuoc dope Ida chqn dau tay cho cac b e n h n h i e m khuan cac cau khuan Gram(+) dac biet la vi khuan khang t h u o c Tuy nhien, viec sCr d u n g rpng rai vancomycin t r o n g dieu tri n h i e m khuan b e n h vien vi khuan Gram(+) dang lam gia tang ty le Enterococcus cung n h d t u cau khang methicilin (MRSA) de khang vPi khang sinh [6]

TP nam 2000, m o t n h o m khang sinh mPi co tac dung tren cac chung Gram(+) da khang thuoc dope FDA phe duyet sP d u n g tren lam sang la oxazolidinon vPi dai dien dau tien la linezolid [8] Khang sinh co kha nang Pc che t o n g h o p protein cua vi khuan, co hoat tinh t o t tren cac vi khuan Gram (+) bao g o m ca cac chung khang thuoc

[7] Mac du da dPpc sP d u n g P nhieu nppc tren the gipi hdn m o t thap ky qua nhPng linezolid mPi chi dPpc dPa vao s P d u n g tai Benh vien Bach Mai tP nam 2015 va t h o n g tin ve viec sP d u n g khang sinh rat han che Do do, chung toi tien hanh nghien cPu vPi muc tieu khao sat dac diem chi dinh linezolid cung n h u m o t so dac d i e m xet nghiem vi sinh va dac diem s P d u n g linezolid t r o n g mau nghien cPu tP thang den thang nam 2015 nham cung cap nhPng t h o n g tin ban dau ve thpc trang ke don va sP d u n g linezolid tai Benh vien Bach Mai

Doi tuong va phuong phap nghien cuu Dot tUctng nghien citu

Nghien cPu tien hanh hoi cPtren cac ho so benh an cua benh nhan npi tru tai Benh vien Bach Mai dPpc ke don linezolid tP 01/01/2015 - 30/9/21015 Tieu chuan Ipa chpn la tat ca cac benh an co ke don linezolid t r o n g khoang thPi gian tP thang den thang nam 2015 va loai trPcac benh an khong t i m dPpc qua trinh t h u thap d p lieu

BAI NGHIEN Ctfll

Phitcfng phdp nghien CLTU

Nghien cPu mo ta hoi cPu tren cac benh an co ke don linezolid khoang thPi gian khao sat Cac t h o n g tin co ban ve benh nhan va dac diem sP dung thuoc dupe t h u thap tP benh an g o m : chi djnh, ly Ipa chpn linezolid; ket qua xet nghiem vi sinh va khang sinh cua cac vi khuan Gram(+); dPPng dung va thPi gian s P d u n g linezolid

Khao sat chi djnh cua linezolid bao g o m cac chi dinh da dPpc phe duyet hoac chPa dPpc phe duyet can cP vao t h o n g tin tren tP hPPng dan sP d u n g thuoc dupe Bp Yte phe duyet cua che pham sPdung tai benh vien [2], [3] Ben canh do, nghien cPu cung khao sat ly Ipa chpn linezolid moi chi djnh VPi cac trPdng hop khong ghi ro chi djnh benh an, chi djnh se dope xac djnh theo tieu chuan chan doan cac hPPng dan dieu trj lien quan Cu the la: Cac trPPng hop co dau hieu nhiem trung dPPng ho hap (sot, ho co dPm, kho t h d , hoi chPng nhiem t r u n g (moi kho, IdPi ban, hoi thP hoi) hoi chPng dong dac P phoi) va CRP > 0,5 xuat hien vong 48 giP dau tP nhap vien dPpc xac djnh la viem phoi cpng d o n g (3 trPPng hop) [1] TrPPng hop co ghi chuyen tP benh vien tuyen dPPi len hoac co it nhat hai trieu chPng bao g o m sot tren 38°C, bach cau trung tinh tang hoac giam dPPi G/L, djch tiet P phoi co mu va cac dau hieu tren xuat hien sau 48 giP nhap vien dope xac djnh la viem phoi benh vien (6 trPPng hop) [4]; Cac trPPng hop co bach cau trung tinh tuyet doi dPPi 0,5 G/L va co sot tren 38,5°C dPpc xac djnh la sot giam bach cau trung tinh (46 trPPng hop), cac trPPng hop khong co dau hieu sot cao tren 38,5°C va/hoac bach cau t r u n g tinh tuyet doi dPPi 0,5 G/L nhPng co chan doan u lympho, da u xuong, leukemia cap hoac man) hoac sP d u n g linezolid t r o n g thPi gian 48-72 giP sau hoa trj lieu ung t h u dupe xac djnh la d p phong sot giam bach cau trung tinh (68 trPPng hop) [12]; Cac truPng hop khong co chan doan nhiem khuan va dau hieu lam sang, can lam sang dupe xac djnh la "khong ro" Thong tin ve dUPng d u n g va thPi gian sP d u n g linezolid cung dupe t h u thap Cac vi khuan phan lap dupe mau nghien cPu va dp nhay cam cua cac vi khuan Gram(+) vPi m o t so khang sinh dac hieu g o m methicilin, vancomycin/teicoplanin va linezolid cung dupe ghi nhan Thong tin hoi cPu tP benh an dPpc t h u thap vao phieu t h u thap t h o n g tin DP lieu sau dupe t o n g ket va xP ly t h o n g ke mo ta bang phan mem Microsoft Excel 2010

Ket qua nghien cuu

Trong thPi gian khao sat, phan m e m quan ly xac djnh dupe 375 benh nhan co sP dung linezolid Sau loai bo 64 benh an khong the tiep can tP 375 benh an tren lai 311 benh an dupe dua vao nghien cPu Dac diem benh nhan va phac dieu trj chPa linezolid dupe trinh bay bang

Bang Dgc diem phac dieu tri chita linezolid (N=311)

Dac diem Ket qua, n (%)

Vi tri phac 66 co linezolid

Phac ban dau 195 (62,7) Phac thay the 116(37,3) Loai phac 66 co linezolid

Phac don doc 241 (77,5) Phac phoi hop n 129 (41,5)

(*): Cac khang sinh phoi hpp g o m : cephalosporin (20,3%), carbapenem (15,1%), quinolon (10,0%) va aminoglycosid (chi co amikacin) (9,6%)

Cac dac diem ve chi djnh linezolid ghi nhan tP cac benh an dPpc trinh bay bang

Bang Dgc diem chi dinh linezolid mau nghien cdu (n=31l)

Dac diem n (%)

Chi djnh dtlpc phe duyet 74 (23,8)

Viem phoi cpng dong 37 (11,9)

Viem phoi benh vien 16 (5,1)

Nhiem khuan da va mo mem 13 (4,2)

Viem phoi cpng dong + nhiem khuan da va mo mem (1,0) Viem phoi benh vien + nhiem khuan da va mo mem (1,6) Chi dinh chtia dtipephe duyet 237 (76,2)

Sot giam bach cau trung tinh 71 (22,8) Du phong sot giam bach cau trung tinh 68 (21,9)

Nhiem khuan huyet (1,6)

Viem mang nao (1,3)

Viem phe quan (0,6)

Nhiem khuan rang mieng (0,6)

Nhiem khuan tieu hoa("1 (1,3)

Nhiem khuan tiet nieu (0,3)

Nhiem khuan Gram(-) (1,0)

Khong ro benh ly nhiem khuan 77 (24,8)

Cac ly Ipa chon linezolid ghi nhan difdc 10 (3,2)

Dj Png vancomycin (0,6)

Khong dap Png vcfi vancomycin/teicoplanin (1,9) Nhiem khuan Enterococcus spp khang vancomycin (0,6)

(*) g o m ap xe gan, tieu chay, nhiem t r u n g djch mang bung va nghi ap xe gan, tieu chay

Linezolid dupe dung n h u phac ban dau 195 benh nhan t u o n g Png 62,7%, ty le benh an co sP d u n g linezolid t r o n g phac thay the t h a p hon khoang 37,3% Ty le benh nhan dupe nhan phac linezolid don doc la 77,5% va khoang 41,5% benh nhan s P d u n g linezolid cung khang sinh khac

Co 74 (23,8%) benh an dPpc ke ddn theo chi dinh phe duyet va hau het khong ghi nhan dPpc ly Ida chon linezolid Co 10 trUdng hop (3,2%) dPa dPpc ly Ipa chpn linezolid bao gom trUdng hop (0,6%) di Png vancomycin, (1,9%) trifdng hop khong dap Png dieu tri vdi khang sinh glycopeptid va trUdng hop (0,6%) nhiem khuan gay bdi Enterococcus spp khang vancomycin Trong 237 trUdng hop (76,2%) sP dung linezolid v6i chi djnh chUa dupe phe duyet, bien nhat la chi djnh dieu trj va d p phong sot giam bach cau trung tinh vdi 139 trUdng hop (44,7%) Ben canh do, co 77 trUdng hop (24,8%) benh nhan sP dung linezolid ma khong xac djnh ro benh ly nhiem khuan

Thong tin ghi nhan dPpc tP cac xet nghiem vi sinh cac benh an nghien cPu dPpc t h u thap va trinh bay eg the bang

Bang Dgc diem vi sinh mau nghien cdu

Dac diem n (%)

Benh an co xet nghiem nuoi cay vi khuan (n=311) 125 (40,2) Benh an ghi nhan phan lap dupe vi khuan (n=311) 32 (10,3) So chung vi khuan dupe phan lap ( n = )n 47 (13,5)

Gram(+) 10 (2,9)

Staphylococcus aureus (1,7)

Tu cau khong sinh coagulase(QoNS) (0,3)

Enterococcus spp (0,6)

Streptococcus pneumoniae (0,3)

Gram (-) 37 (10,7)

Acinobacter baumannii 11 (3,2)

Pseudomonas aeruginosa (1,2)

Escherichia coli (2,0)

Klebsiella pneumoniae (1,7)

Gram (-) khac (2,6)

(*): Tinh tren so iPpt xet nghiem nuoi cay vi khuan dPpc chi djnh

Co 125 benh an dPpc lam xet nghiem nuoi cay vi khuan chiem 40,2% co 32 (10,3%) benh an ghi nhan ket qua dPong tinh Vdi 347 IPpt xet nghiem vi sinh, cd 47 chung vi khuan dPpc phan lap cd 37 (10,7%) trUdng hop la vi khuan Gram(-) va chi cd 10 (2,9%) trddng hop la vi khuan Gram(+) Cac chung vi khuan Gram(+) phan lap dPpc g o m Staphylococcus aureus, CoNS, Enterococcus spp

va Streptococcus pneumoniae. Cd chung

Enterococcus spp dope phan lap va ca hai deu de khang vdi vancomycin, mot chung nhay cam vdi teicoplanin (MIC = 0,5 mcg/ml), t r o n g chung

E gallinarum lai chi nhay cam trung gian vdi linezolid Cd mot chung tu cau khong sinh coagulase phan lap dPpcva nhay cam vdi cac glycopeptid cung n h u linezolid Cd chung S.aureus dupe phan lap va dp nhay cam cua chung m o t so khang sinh ddpc the hien hinh

Linezolid Teicoplanin Vancomycin c Clindamycin ug Moxifloxacin | C3G se Meropenen

Methiallin Penicillin

H Nhay cam GD Nhay cam trung gian • De khang Linezolid

Teicoplanin Vancomycin c Clindamycin ug Moxifloxacin | C3G se Meropenen

Methiallin Penicillin

H Nhay cam GD Nhay cam trung gian • De khang Linezolid

Teicoplanin Vancomycin c Clindamycin ug Moxifloxacin | C3G se Meropenen

Methiallin Penicillin

H Nhay cam GD Nhay cam trung gian • De khang Linezolid

Teicoplanin Vancomycin c Clindamycin ug Moxifloxacin | C3G se Meropenen

Methiallin Penicillin

H Nhay cam GD Nhay cam trung gian • De khang Linezolid

Teicoplanin Vancomycin c Clindamycin ug Moxifloxacin | C3G se Meropenen

Methiallin Penicillin

H Nhay cam GD Nhay cam trung gian • De khang Linezolid

Teicoplanin Vancomycin c Clindamycin ug Moxifloxacin | C3G se Meropenen

Methiallin Penicillin

H Nhay cam GD Nhay cam trung gian • De khang Linezolid

Teicoplanin Vancomycin c Clindamycin ug Moxifloxacin | C3G se Meropenen

Methiallin Penicillin

H Nhay cam GD Nhay cam trung gian • De khang

( 2

So chung vi khuar i

H Nhay cam GD Nhay cam trung gian • De khang

Hinh Dp nhgy cam cua cac chung S aureus phan lap dugc (n=6)

Tat ca chung S.aureus deu de khang vdi penicilin, so chung nhay cam vdi methicilin (MSSA) va chung de khang methicilin (MRSA) Chi cd chung MRSA dude lam khang sinh vdi cac glycopeptid va ca chung deu nhay cam vdi cac khang sinh Cd chung

S.aureus dude lam khang sinh vdi linezolid cho ket qua chung MSSA de khang vdi khang sinh

Linezolid dupe d u n g vdi lieu la 600 m g Ian Cac dac diem ve d u d n g d u n g va thdi gian sd d u n g linezolid cua cac benh an nghien cud dupe trinh bay bang

Bang Cac dgc diem set dung linezolid (n = 311)

Dac diem Sd benh nhan, (%) Duong dung

Llong 296 (95,2)

Truyen tinh mach 15 (4,8)

Truyen tinh mach va uong (0)

Thdi gian dung linezolid ( - 1 )n

(*) So lieu bieu dien dudi dang trung vj (khoang tu" phan vj)

Phan Idn benh nhan dupe sd d u n g linezolid d u d n g uong (95,2%), chi 4,8% benh nhan d u n g linezolid dudng truyen tinh mach.Thdi gian s d d u n g linezolid cd trung vj la va va khoang t d phan vj la t d den 11 Khong cd trUdng hpp nao dung linezolid qua 28

Ban luan

Ket qua nghien cPu cua cho thay cac t r u d n g hop ke don linezolid vdi chi djnh chUa duqc phe duyet chiem tdi 76,2% Day la m o t ty le kha cao neu so vdi ket qua khao sat d cac co sd dieu trj tren the gidi n h u bao cao nghien cPu cua Aubin va cpng sp(13,1 - 26,8%) [5] hay Cebrian va cpng sp (28,6%) [13] Ket qua gpi y rang viec ke don linezolid hien tai cd the van chUa thpc sp dupe can nhac ki cang Cd den 62,7% benh nhan dupe ke don linezolid t r o n g phac khang sinh ban dau va cd den 77,5% trUdng hop sP d u n g linezolid don doc Dieu gpi y rang bac si chUa coi linezolid la m o t khang sinh d p trP ma la khang sinh dau tay nhieu trUdng hop chi djnh dieu trj chUa thpc sp rd rang Can phai lUu y linezolid la m o t khang sinh rat mdi dupe dUa vao dieu trj va viec s P d u n g khdng than t r p n g se la tien de cho viec phat sinh de khang Cu the, nghien cPu cua chung tdi da ghi nhan m o t t r o n g ba chung S. aureus cd lam khang sinh vdi linezolid da de khang vdi khang sinh De t i m hieu rd hon ve cac trPdng hop ke don khdng theo chi djnh dPpc phe duyet, trUdc tien c h u n g tdi da co gang xac d j n h t i n h trang nhiem khuan cua benh nhan dope ghi nhan benh an de tP cd the giai thich cho quyet djnh ke don khang sinh cua bac si Chi djnh dieu trj va d p phdng sot giam bach cau t r u n g t i n h chiem ty le Idn vdi khoang 44,7% trPdng hop t r o n g nghien cPu Theo hudng dan dieu trj va d p phdng sot giam bach cau t r u n g tinh cua Hoi Truyen nhiem Hoa Ky (IDSA) nam 2010, linezolid khdng cd vai t r d n h u phac kinh nghiem cho chi djnh ma chi nen sP d u n g cac trPdng hop dac biet bao g o m cac trUdng hop nghi nhiem t r u n g catether, nhiem trung da m o m e m , viem phoi, benh nhan cd huyet d d n g khdng on djnh hoac cac trUdng hop da xac djnh can nguyen vi khuan hoac s P d u n g theo kinh nghiem d benh nhan ghep te bao goc cd nhiem Enterococcus spp khang vancomycin [9] Theo ket qua cua chung tdi, chi cd m o t trUdng hop sot giam bach cau trung tinh cd nhiem khuan huyet d d n g t h a i MRSA la dupe khang djnh nhay cam vdi cac glycopeptid va linezolid Cac trUdng hop lai deu khdng xac djnh dupe can nguyen vi khuan va chi s P d u n g linezolid nhP phac kinh nghiem Do sp han che ve t h o n g tin hoi cPu nen chung tdi chua the t i m hieu dupe ly Ida chpn linezolid d nhPng benh nhan Tham chi dang lUu y la t r o n g 76,2% trUdng hop ke d o n linezolid ngoai chi djnh phe duyet thi cd den 24,8%

so benh nhan s P d u n g linezolid ma khdng xac djnh dupe m o t ly nao cd t h e lien quan den benh ly nhiem khuan

Trong cac chi djnh dupe phe duyet cua linezolid, viem phdi cdng d d n g la chi djnh p h d bien nhat tren cac benh nhan cua nghien cPu vdi 37 trUdng hop chiem 11,9% Trong 37 trUdng hop chi djnh cho viem phdi cdng d d n g , cd m o t trUdng hop dj Png nang vdi vancomycin vdi bieu hien sdc phan ve va mot trUdng hop xac djnh dupe can nguyen vi khuan la Streptococcus pneumoniae nhay cam vdi penicilin Tuy nhien, tat ca cac benh nhan lai dupe chi djnh dieu trj viem phdi vdi linezolid lai khdng cd t h o n g tin vi sinh gpi y vi khuan gay benh Do do, cd the thay rang hau het cac trUdng hop chi djnh dieu trj viem phdi cdng d d n g la cac chi djnh t h e o kinh n g h i e m Vdi quan d i e m sP d u n g khang sinh than t r p n g t h i linezolid chi nen s P d u n g t r o n g cac trPdng hop cd ly phu hop Trong nghien cPu cua chung tdi chi ghi nhan dupe 3,2% trUdng hop sP d u n g linezolid vdi ly phu hop vdi cac khuyen cao sPdung linezolid ma mot so qudc gia ap d u n g [15] bao g d m ngudi benh dj Png vancomycin, khdng dap Png vdi vancomycin/ teicoplanin va nhiem khuan do Enterococcus spp khang vancomycin Dieu gpi y co sd dieu trj nen cd cac giai phap nham quan ly t o t hon viec sP d u n g n h d m khang sinh mdi nham han che cac trPdng hop chi djnh khdng phu hop Day la yeu cau cap thiet de giam thieu kha nang phat sinh cac chung vi khuan de khang mac phai t r o n g qua trinh dieu trj

Mac du linezolid dope chi djnh t r o n g cac trUdng hop nhiem khuan vi khuan Gram(+) nhUng ty le cac chung vi khuan Gram(+) phan lap dupe t r o n g mau nghien cPu t u o n g ddi thap va chi chiem khoang 2,9% trUdng hop Cac chung Gram(+) phan lap dupe bao g d m S.aureus, Enterococcus spp CoNS va S pneumoniae. Ty le dupe chi djnh phan lap vi khuan va djnh danh dupe vi khuan n h u vay la kha thap Dieu dang lUu y la da xuat hienl chung E gallinarum giam nhay cam va c h u n g MSSA de khang vdi linezolid Vdi ket qua vi sinh n h u vay, nguy ca linezolid k h d n g phu h a p vdi tac nhan gay benh la kha cao Khi xem xet t h e m yeu t o chi phi cung n h u ddc tinh thi viec can nhac han nPa t r o n g ke d o n linezolid la dieu can phai tinh den Trong quan ly sP d u n g linezolid, quyet djnh 772/QD-BYT cua nam 2016 ve "Hudng dan thpc hien quan ly sP d u n g khang sinh t r o n g benh vien" quy djnh linezolid dPdng t i e m la m o t t r o n g cac khang sinh can phai

duqc phe duyet trudc sP dung tai benh vien [1 ] Tuy nhien, ket qua khao sat cho thay co tdi 95,2% chi dinh linezolid s P d u n g che pham dPdng uong Can Ipu y la linezolid dPdng uong cd sinh kha dung gan 100%, hoat tinh khang khuan tifdng t u che pham dPdng tiem va che dp lieu sP d u n g d o n gian Tinh chat thuan tien sP d u n g la m o t Ou diem cua linezolid dPdng uong nhUng cung cd the la yeu to thuc day viec lam d u n g khang sinh thpc te dieu trj Do do, viec xem xet dua linezolid dPdng udng vao danh muc can kiem soat sP d u n g nhP khang sinh linezolid d u d n g tiem la kha nang nen dupe can nhac Dieu cd the giup han che viec sP d u n g linezolid qua rang rai tren lam sang n h u ket

qua ghi nhan dupe tP nghien cPu va t P d d tranh kha nang phat sinh cac chung vi khuan de khang cung n h u giam chi p h i dieu trj va doc tinh cd the phat sinh

Ket lugn

Nghien cPu da cho thay mot ti le Idn (76,2%) cac trUdng hop sPdung linezolid khdng phu hop vdi chi djnh dPpc phe duyet hoac khdng cd ly Ida chpn mot each phu hop Tinh trang linezolid dudng udng dPpc ke don mot each phd bien (95,2%) va viec da ghi nhan mot so chung vi khuan de khang hoac giam nhay cam vdi linezolid ddi hoi can phai cd giai phap nham quan ly chat che hon viec sPdung khang sinh

TAI LIEU THAM KHAO

1 Bp Y te', Hudng dan thpc hien quan ly sP d u n g khang sinh benh vien Ban hanh kern theo QD 772/QD-BYT 04/3/2013 2016

2 Forlen (linezolid 600 mg) "Td t h o n g tin san pham", Davi Pharm CO, Viet Nam Linod (lineolid mg/ml) "Td t h o n g tin san pham", Ahlcon parenterals (I) LTD, An Dp

4 American Thoracic Society (2005), "Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia", Am J RespirCrit Care Med, 171, pp 388-416 Aubin G G., Boutoille D., Corvee S., Caillon J., Caillaud A., Moal F., Navas D (2015), "Large discrepancies in

linezolid use between French teaching hospitals: A c o m m e n t on "Antimicrobial stewardship and linezolid"", IntJClin Pharm, 37(3), pp 436-8

6 Balli E P., Venetis C A., Miyakis S (2014), "Systematic review and meta-analysis of linezolid versus daptomycin for treatment of vancomycin-resistant enterococcal bacteremia", Antimicrob Agents Chemother, 58(2), pp 734-739

7 Brickner S J., Barbachyn M R., Hutchinson D K., Manninen P R (2008), "Linezolid (ZYVOX), the first member of a completely new class of antibacterial agents for treatment of serious gram-positive infections", J Med Chem, 51(7), pp 1981-1990

8 Chastre J., Blasi F., et al (2014), "European perspective and update on the management of nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid", Clin Microbiol Infect, 20 Suppl 4, pp 19-36

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