Adult HSCT recipients without using antifungal treatment were recruited from start of stem cell transfusion in Vietnam National Institute of Hematology and Blood Transfusion (from April[r]
(1)2
fan cm
DUOC
HO
SO 499 * NAM THl> 57 * THANG RA KY * ISSN 0866 - 7861
@hiia
mil'si
(j
^Mi/di/ ^tl/iis t^isso (I)lit Glas
11
'
20- 11
'
¥ TCDH
B O Y T £ X U A T B A N
(2)TAP CHI Dime HOC
I S S N 0866 - 7861
11/2017 ( S o 499 NAM 57)
P H A R M A C E U T I C A L J O U R N A L
I S S N 0866 - 7861
11/2017 (N° 499 Vol 57)
MUC L U C
C O N T E N T S
TONG QUAN
• PHUNG THANH H U O N G , PHAM THUY LINH, NGUYEN T H ! MAI H U O N G , NGUYEN THANH HUYEN: Tong quan ve dung thuoc theo ca the
dieu trj ung thir • TRAN TRONG BlEN, VU MAI H U O N G , BUI
TH| THUY LUYEN, NGUYEN VAN HAN: Nhya trao doi ion va cac tiem nang irng dung
Y Dirge hoc NGHlEN CITU - K Y THUAT
• PHAM THj THUY VAN, l_£ TH! H U O N G GIANG, PHAM CAM P H U O N G : Phan tich tinh hinh sir dung va tac dung khong mong muon cua sorafenib dieu tri ung thir bieu mo te bao gan tai Trung tarn Y
hoc hat nhan va Ung bircru, Benh vien Bach Mai 13 • DANG T H ! CHUNG THUY, TR|NH HOANG
D U O N G , HA DIEU LY, NGUYEN O U C TUAN: Phan tich v l t piperacillin moi trirong san xuat cua nha may san xuat khang sinh
piperacillin 17 • NGUYEN T H ! THANH MAI, TRAN BAO TRAM,
T R U O N G T H | CHlEN, NGUYEN T H | HlEN, NGUYEN TH! HA LY, P H U O N G T H E N T H U O N G : Danh gia kha nang sinh hoat chat cordycepin cua mot so giong Cordyceps militaris len men chim 22 • NGUYEN HOANG TUAN, NGUYEN THj T U O I ,
NGUYEN THANH TUNG: Dac diem vi hoc va xac dinh ham lirgng diosgenin cua than r l cay ran trau
thu hai tai Da Nang 25 • T R U O N G P H U O N G , TRAN NGQC HOANG
DUNG: Nghien ciru dieu che benfotiamin 30 • PHAM T H | THUY VAN, D U O N G T H | THANH:
Tac dong cua cac can thiep dirge lam sang tren ke don khang sinh nhom carbapenem tai mot benh vien
da khoa tuyen tinh 35 • NGUYEN TUNG S O N , NGUYEN DUY TAN,
NGUYEN MAI HOA, V O T H | THANH BINH, NGUYEN HOANG ANH: Phan tich tinh hinh sir dung thuoc khang n i m d g phong tren benh nhan ghep te bao g6c tai Vien Huyet hoc - Truyen mau
Trung irong 39 • HUYNH NGOC TRINH, L£ THI HOAl THAO,
HUYNH THj NGOC P H U O N G : Ctng dung phan irng Ellman danh gia hoat tinh khang acetylcholinesterase in vitro cua mot so dan chat
hydrazon va mu6i pyridinium cua hydrazon 42
O V E R V I E W
• PHUNG THANH H U O N G , PHAM THUY LINH, NGUYEN TH! MAI H U O N G , NGUYEN THANH HUYEN: Review on personalized medication or
medicine in cancer treatment • TRAN TRONG BIEN, VU MAI H U O N G , BUI THj
THUY LUYEN, NGUYEN VAN HAN: Ion exchange resins and application potential to medicine and
medical care R E S E A R C H - T E C H N I Q U E S
• PHAM TH| THUY VAN, L£ T H | H U O N G GIANG, PHAM CAM P H U O N G : Study on actual use of the sorafenib for treatment hepatocellular carcinoma at The Nuclear Medicine and Oncology Center - Bach
Mai Hospital 13 • DANG T H | CHUNG THUY, TRjNH HOANG
D U O N G , HA DIEU LY, NGUYEN D U C TUAN: Tracing analysis of piperacillin in the working environments of pharmaceutical factories
manufacturing piperacillin preparations 17 • NGUYEN T H | THANH MAI, TRAN BAO TRAM,
T R U O N G T H | C H E N , NGUYEN T H | HlEN, NGUYEN TH! HA LY, P H U O N G T H E N T H U O N G : Cordycepin productivity of Cordyceps militaris trains
grown by submerged culture 22 • NGUYEN HOANG TUAN, NGUYEN TH! TUOI, NGUYEN
THANH TUNG: Microscopic characterization and diosgenin content of the rhizomes of Dioscorea dissimulans Prain &
Burkill collected at Da Nang province 25 • T R U O N G P H U O N G , TRAN NGOC HOANG
DUNG: Study on synthesis of benfotiamine 30 • PHAM T H | THUY VAN, D U O N G THI THANH:
Effects of clinical pharmacists's interventions on prescription of antibiotics of carbapenem group at a
provincial central hospital 35 • NGUYEN TUNG S O N , NGUYEN DUY T A N ,
NGUYEN MAI HOA, V O T H | THANH BlNH, NGUYEN HOANG ANH: Critic analysis of the use of antifungal prophylaxis for hematopoietic stem cell transplantation recipients in National Institute of
Hematology and Blood Transfusion 39 • HUYNH NGOC TRINH, LE T H | HOAl THAO,
HUYNH T H | NGOC P H U O N G : The use of Ellman reaction in estimation of in vitro anti-acetylcholinesterase activity of some hydrazone
(3)• Muc luc
• LE B l N H CHI, TRAN NGQC HANG, NGUYEN TH| ANH H U & N G , PHAM T H | NGOC MAI: Xac dinh amlopidin va perindopril b l n g dien di mao
quan 47 • NGUYEN TH! NGOC YEN, D U O N G DiNH CHUNG,
BUI HONG QUAN, TRAN CAT DONG, NGUYEN VAN THANH: Toi iru hoa moi trirang len men
Saccharomyces boulardii sir dung ma tran Plackett-Burman va phirong phap dap i m g be mat - thiet ke
cau true co tarn 49 • NGUYEN QUOC V U O N G , NGUYEN THUY
D U O N G : Danh gia hoat tinh theo hirong ire che mien dich in vitro va in vivo cua auronol glucosid
alphitonin-4-0-3-D glucopyranosid 51 • TRINH TUY AN, HUYNH NGOC THUY: Sang loc in
vitro, in vivo tac dung acid uric mau cua mot so
dirge lieu thu hai tai cac tinh phfa Nam Viet Nam 53 • L£ TH! LOAN, HA VAN OANH, D O THj HA, C H U
TH| THANH HUYEN, LE Vl£T DUNG: Nghien c i m dac diem thgc vat cay bac thau (Argyreia acuta
Lour.), ho Khoai lang (Convolvulaceae) 58 • NGUYEN HUY KHIEM, TA MANH C U O N G , PHAM
TH| THUY VAN: Phan tich tinh hinh sir dung khang
sinh tren benh nhan tho may 62 • DANG KIM T H U , NGUYEN THj KIM T H U , BUI
THANH TUNG: Tac dung ire che enzym xanthin oxidase va acid uric mau cua dich chiet la tia to
(Perilla frutescens L.) 65
• NGUYEN TH! TRANG OAl, HUYNH NGOC THUY: Nghien ciru hoat tinh khang viem tir than cay bim bjp (Clinacanthus nutans (Burm f.) Lindau,
Acanthaceae) 68 • NGUYEN MINH LUYEN, HOANG T H ! Dl£U
H U O N G , HA VAN OANH, LE V l £ T DUNG, D A O TH| THANH HlEN: Nghien ciru dac diem thirc vat va
so bo phan hoa hoc cay nhirong le kirn cang
(Myxopyrum smilacifolium (Wall.) Blume, hp Nhai
(Oleaceae)) 70 • PHAM THANH MANH, NGUYEN VAN Ll£U, D O
VAN BlNH, NGUYEN VAN T H U , HOANG Vl£T DUNG: Phan lap hai hop c h i t oligomer resveratrol tir re cay lac (Arachis hypogaea L., hp Oau
-Fabaceae) 73 • NGUYEN PHUC DAM, THAI TH! TUYET NHUNG,
PHAM T H U A NGHIER NGUYEN TH| NGOC VAN, NGUYEN TH! THU TRAM: S O bo khao sat hoat tinh khang vi sinh vat va phan hoa hoc cua day vac
(Cayratia trifolia (L.) Domin, ho Nho - Vitaceae) 76 • VU D U C LOI, NGUYEN THI KIM THU: Ba hop chat
flavonoid phan lap tir la cay dau t l m (Morus alba L.)
thu hai tai tinh Thai Nguyen 79 • TRAN N H U NGUYEN, TRAN THI P H U O N G UYEN,
T R U O N G CONG TR|, D O T H | HONG T U O I : Xay dirng mo hinh ung tho gan tren chuot n h l t b l n g te bao HepG2 va khao sat tac dong khang ung t h o
cua che pham liposom paclitaxel 82
• LE DlNH CHI, TRAN NGOC HANG, NGUYEN THj A N H HUO'NG, PHAM THj NGQC MAI: Determination of amlopidine and perindopril by
capillary electrophoresis 47 • NGUYEN TH! NGOC YEN, D U O N G BINH CHUNG,
BUI HONG QUAN, TRAN CAT DONG, NGUYEN VAN THANH: Optimization of fermentation medium for the probiotic bacterium Saccharomyces boulardii
using plackett-burman design and response surface
methodology applied central composite design 49 • NGUYEN QUOC V U O N G , NGUYEN T H O Y
D U O N G : Immunosuppressive property in vitro
and in vivo of auronol glucoside alphitonin-4-O-p-D
glucopyranoside 51 • TRjNH TUY AN, HUYNH NGOC THUY: Screening
some medicinal plants grown in the South Vietnam
for the reduction of the blood uric acid level 53 • LE TH! LOAN, H A VAN OANH, D O TH! H A , C H U
TH! THANH HUYEN, LE Vl£T DUNG: Study on the botanic characterization of the plant "bac thau"
(Argyreia acuta Lour., Convolvulaceae) 58
• NGUYEN HUY KHlEM, TA MANH C U O N G , PHAM TH! THUY VAN: The actual antibiotics used for the
patient in mechanical ventilation-breathing 62 • DANG KIM T H U , NGUYEN THI KIM T H U , BUI
THANH TUNG: Inhibitory activity on and the xanthine oxidase enzyme and hypouricemic effect of the leaf
extracts from Perilla frutescens L 65 • NGUYEN TH! TRANG OAl, HUYNH NGOC THl)Y:
Study on the inflammatory activity of the stem extracts of the plant Clinacanthus nutans (Burm f.)
Lindau, (Acanthaceae) 68 • NGUYEN MINH LUYEN, HOANG TH! Dl£U
H U O N G , H A V A N OANH, LE V l E T D U N G , D A O T H j THANH HlEN: Detailed botanic characterization and preliminary phytochemical study on the "nhirong le kirn cang" (Myxopyrum smilacifolium (Wall.) Blume,
(Oleaceae)) 70 • PHAM THANH MANH, NGUYEN V A N Ll£U, D O
VAN BlNH, NGUYEN VAN T H U , HOANG V l £ T DUNG: Isolation of oligomer resveratrol compounds from the roots of the groundnut (Arachis hypogaea
L., Fabaceae) 73 • NGUYEN PHUC DAM, THAI TH! TUYET NHUNG,
PHAM T H U A NGHIEP, NGUYEN TH! NGOC VAN, NGUYEN T H ! THU TRAM: Preliminary study on antimicrobial activity and natural compounds of
Cayratia trifolia (L.) Domin, Vitaceae 76
• VU D U C LOI, NGUYEN TH| KIM THU: Isolation of three flavonoids from the Morus alba L growing in
Thai Nguyen province 79 • TRAN N H U NGUYEN, TRAN TH| P H U O N G UYEN,
T R U O N G CONG TRj, D O T H | HONG T U O I : The model of HepG2 cell line-induced hepatic tumour in mice for evaluation of anti-cancer power of
the paclitaxel liposome preparation 82
(4)• Nghien
CLFU
- Ky thuat
cua d i r g e sT a hai khoa la khac nhau. 0 Khoa Ngoai tieu hoa, viec thieu thai gian trao doi tare tiep giira bac sy va d i r g e sT lam sang ( t h i r d n g trao doi qua dien thoai hoac qua giay n h l n ) gay kho khan tao d u n g moi quan he thau hieu v a chia se giira hai ben D a y co le nguyen nhan chinh khien cho nhCrng tac dgng d e xuat cua d i r g e sT lam sang chira d i r g e c h i p thuan nhieu d Khoa Ngoai tieu hoa
Tai Khoa HSNK, d i r g e sT lam sang hoat dgng tai khoa, cac bac sy rat vui v e va thang than trao doi v d i d i r g e sT lam sang nhieu v a n de dieu tri D o vay, n h o m nghien ciru nhan dinh c a n thiep d i r g e lam sang tao d i r g e nhCrng thay doi va hieu q u a nhat dinh t h g c te dieu trj m a c du nhieu chl tieu n h a s o l i r g n g D R P trung binh, ty le benh nhan dung c a r b a p e n e m s a u co can thiep giam c h i r a c o y nghTa thong ke, co the thai gian nghien c d u c h a a dai, c d m i u nhd
Cac c a n thiep v e Iga chpn thuoc d i r g e chap nhan v d i ty le 5 - % , nhien hieu q u a c u a can thiep tren viec giam D R P v e Iga chpn thuoc lai chira the hien ro rang, d a c biet d Khoa Ngoai tieu hoa Ly d o co the la s d l i r g n g benh nhan sir dung khang sinh c a r b a p e n e m tang m a n h giai doan va, d o thieu nhan Igc, hoat dpng x e m xet sir dung thuoc c u a d i r g e sT khdng d i r g e tidn hanh tren tat ca cac benh nhan, thieu thai gian t i r a n g tac v d i bac sy Trong cac can thiep, can thiep ve lieu d u n g , each dung nhan d i r g e s g ung hp tich c g c tir phi'a b a c sT v d i ty le c a o nhat (75 v a 0 % d H S N K va 66,7 va 0 % d Ngoai tieu hda), co le d o day la nhCrng can thiep co can c d x a c djnh ro rang va kha nang t h g c hien cao Hieu q u a c u a cac bien phap can thiep v e lieu d u n g , each dung d i r g e the hien kha ro rang, giam D R P ve each dung c d y nghTa thong ke
Ket luan
V d i nghien c d u b a n d a u tren mot qui m o nho, can thiep c u a d i r g e sT lam sang da giup giam thieu cac v l n de lien quan d e n thuoc, so l i r g n g va chi phi s i r dung khang sinh c a r b a p e n e m tai hai khoa he ngoai c u a m o t benh vien da khoa tuyen tinh C a c d i r g e sT co the then khai cac m o hinh hoat dpng tren cac ITnh v g c khac d e toi i r u hda sir dung thuoc cho benh nhan
Tai lieu tham khao
1 Lima A L , Oliveira P R., et al., (2011) "Carbapenem stewardship: positive impact on hospital ecology", Braz J Infect Dis., 15(1), pp 1-5
2 Livermore D M., Sefton A M et al (2003), "Properties and potential of ertapenem", J Antimicrob Chemother., 52(3), pp 331-344
3 Lucca J M., Ramesh M et al (2012), "Impact of clinical pharmacist interventions on the cost of drug therapy in intensive care units of a tertiary care teaching hospital", J Pharmacol Pharmacother, 3(3), pp 242-247
4 Molino Cde G., Carnevale R C et al (2014), "Impact of pharmacist interventions on drug-related problems and laboratory markers in outpatients with human immunodeficiency virus infection", Ther Clin Risk Manag., 10, pp 631-639
5 Naivalulevu L (1990), "Training for rational drug use", ARI News, 18,
6 Shah P M (2008), "Parenteral carbapenems", Clin Microbiol Infect, 14 Suppl 1, pp 175-180
7 Van Mil Foppe (2005), "Drug related problems: A cornerstone for pharmaceutical care", J Malta Pharm Pract, 10 5-8
(Ngay nhan bai: 19/09/2017 - Ngay phan bien: 27/09/2017 - Ngay duyet dang: 20/10/2017)
r r
Phan tich tinh hinh su* dung thuoc khang nam dy phong
r r
tren benh nhan ghep te bao goc
tai Vien Huyet hoc - Truyen mau Trung irotig
Nguyen Tung Son
1, Nguyen Duy Tan
2, Nguyen Mai Hoa
1V6
Th| Thanh Binh
3, Nguyen Hoang Anh
1*
'Trung tarn DI & ADR Quoc gia, Truong Dai hoc Duac Ha Noi
2Khoa Duqc, Vien Huyet hoc - Truyen mau Trung uang 3Khoa Ghep te bao gdc, Vien Huyet hoc - Truyen mau Trung ucmg
'E-mail: anh90tk@yahoo.com
S u m m a r y
Characteristics of the pattern of use of antifungal prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients were studied for detailed description Adult HSCT recipients without using antifungal treatment were recruited from start of stem cell transfusion in Vietnam National Institute of Hematology and Blood Transfusion (from April to December 2016) to the end of antifungal prophylaxis or start of antifungal treatment Appropriateness was defined based on National Comprehensive Cancer Network (NCCN) guidelines Clinically significant dmg-drug interactions related to antifungals were defined based on Hansten and Horn's Drug interaction and management 2013 The study involved 38 patients (mean age: 35.7 ± 12.0; 57.9% male), all were admitted, included 21 autologous and 17 allogenic HSCT recipients Azoles prophylaxis was given to
(5)• Nghien
CLFU
- Ky thuat
100% of patients with median 17.5 days (13 - 47.5), fluconazole as an antifungal agent of the most use to 94.7% of patients and in 74.5% of episodes Indication was appropriate in 44.7% - 0% in autologous and 100% in allogeneic group In patients with appropriate indication, choice of antifungal agents was 100% appropriate 100% of patients used inappropriate dosage, mostly lower than the recommeded dosage with azoles 12.7% had appropriate prophylactic time Potential drug-drug interactions were identified in 92.1% of patients Most frequent interactions involved azoles-diazepam (80.4% of episodes) and azoles-immunosuppressive drugs (49% of episodes) In conclusion, a considerably high proportion of non-adherence of antifungal prophylaxis guidelines was revealed, that seemingly called for an adequate programme for antifungal stewardship to strengthen rational use of antifungal in such specific circumstances
Keywords: Antifungal prophylaxis, drug use evaluation, hematopoietic stem cell transplantation
Trong bp tieu chf, tieu chf chi djnh thuoc khang n a m d i r g e tinh theo so benh nhan, tieu chf Iga chpn thuoc, lieu dung, d i r d n g dung cua cac thuoc d i r g e tinh theo so d g t dieu tri (tire la khoang thai gian tinh tir luc b i t d a u den luc ket thuc s i r dung mot thuoc khang n a m v d i m u c dfch d g phdng) Ngoai ra, tieu chf Iga chpn thuoc khang
O a t v a n d e
G h e p te b a o g o c tao m a u (Hematopoietic stem cell transplantation - H S C T ) la mot ky thuat p h d c tap, c d the gay nhieu bien c h i r n g nghiem trpng c h o benh nhan, d o co nhiem n a m m S i r d u n g thuoc khang n a m d g
phdng tren doi t i r g n g benh nhan ghep te bao g o c d e m lai nhieu Igi fch, nhien, viec s i r dung khdng h g p ly cac thuoc lam tang chi phi dieu trj c h o benh nhan, tang xuat hien cac c h u n g vi n a m khang thuoc cung nhir tang nguy c a xuat hien tac dung khdng m o n g m u o n d o thuoc khang n a m hoac d o h a u q u a c u a t i r a n g tac c d lien quan d e n thuoc khang n a m M Khoa G h e p te b a o
goc, Vien Huyet hoc - Truyen m a u Trung i r a n g la c a s d dau nganh ITnh v g c g h e p te bao goc tai Viet N a m D a y cung la n a i co ty le nhiem n a m cao, chiem , % so benh p h a m n a m toan Vien, dong t h a i , Khoa Vi sinh cua Vien cung d a ghi nhan hien t i r g n g g i a m nhay c a m cua Candida tropicalis v d i fluconazol P l Tren c a s d d o ,
chung tdi tien hanh d e tai v d i m u c tieu phan tich phac d o d g phdng b l n g thuoc khang n a m tren benh nhan ghep te b a o goc, tir d o , d e xuat d i r g e c a c bien phap gdp phan nang cao hieu qua s i r dung thuoc khang n a m cua Vien
D o i t i r g n g v a p h i r o n g p h a p
Doi t i r g n g nghien c i r u : Toan bp benh nhan d i r g e
tien hanh H S C T tai Khoa G h e p te bao goc, Vien Huyet hoc - Truyen m a u Trung i r a n g tir 01/4/2016 d e n 31/12/2016; loai t n r benh nhan cd tuoi < 18 tuoi v a benh nhan d a n g s i r d u n g phac d o dieu tri khang n a m tai thai diem ghep
Phiromg phap nghien cu>u: Nghien c i r u m o ta,
khdng can thiep, theo ddi doc tien c i r u Moi benh nhan d i r g e theo ddi v a ghi lai thong tin bat dau tir ghep tdi thai diem benh nhan ngirng s i r dung thuoc khang nam, benh nhan chuyen sang phac d d dieu tri khang nam, benh nhan tir vong hoac chuyen hoi sire tfch c g c Bp tieu c h i danh gia d i r g e n h d m nghien c i r u x a y d g n g d g a tren h i r d n g d a n c u a M a n g lirdi Ung thir Q u o c gia Hoa K y (National Comprehensive Cancer Network -N C C -N ) phien ban 2.2015 w v a 2.2016 ®. Rieng cac tieu chf v e lieu dung cua voriconazol v a fluconazol d g phdng khang n a m d i r g e tham khao tir t d thong tin s a n p h a m d i r g e phe duyet tai A n h [ ) d o khdng d i r g e d e c a p
trong H i r d n g dan cua N C C N T i r a n g tac lien quan d i n thuoc khang n a m d i r g e xac djnh d g a tren cudn Hansten and Horn's Drug Interaction Analysis and Management 2013 va Iga chpn cac t i r a n g tac tir m i r e d p t r d len m
n a m chf xet tren benh nhan c d chi dinh phu h g p v a tieu chf v e thai gian d g phdng khang n a m c h i tfnh tren so benh nhan khdng tir v o n g , chuyen hoi sire tfch c g c hoac n h i l m n l m qua trinh dieu trj
X i r ly s o lieu: S o lieu d i r a c x i r ly bang Microsoft
Excel 2016 v a S P S S 22.0
Ket qua
D a c diem c u a b e n h n h a n H S C T m i u nghien c i m
D a c diem c u a benh nhan H S C T m i u nghien c i r u d i r g e m o ta d bang , hinh v a hinh
Bang Dac diem nhan khiu hoc cua benh nhan nghien cuv
Chi tieu nghien ciru Ghep to than Ghep dong loai Toan bp miu
So benh nhan theo doi (%) 21/38(55,3%) 17/38(44,7%) 38/38(100%)
Tudi
(nam - trung binh ± SD) 36,6 + 13,5 34,7 + 10,3 35,7 ±12,0 Tuoi nhd nhat - Ion nhat - 18-52 18-65 So benh nhan nam (%) 11/21(52,4%) 11/17(64,7%) 22/38(57,9%)
Trong m a u nghien ciru, s o benh nhan g h e p t g than nhieu h a n so benh nhan g h e p d o n g loai D p tuoi c u a benh nhan m i u nghien c i r u phan b o rpng (18 -65), n h d m benh nhan ghep t g than c d d p tuoi c a o h a n (19 - 65) n h d m benh nhan ghep dong loai (18 - ) Benh nhan n a m cd ty le cao h a n m l u nghien c i r u D a so c a c benh nhan khdng ghi nhan tien s i r v a benh mac kern (81,6%) T a t c a benh nhan g a p bien c o s a u ghep deu n a m n h d m g h e p dong loai
DS tftnt nhilm | nam 2.6%
Dang nhiem khuan niem mac miena
2.6% Suy giam chiic nang than
5.3%
Hinh 1. Tien sir cua benh nhan nghien cuv
(6)• Nghien cCm - Ky thuat
100% of patients with median 17.5 days (13 - 47.5), fluconazole as an antifungal agent of the most use to 94.7% of patients and in 74.5% of episodes Indication was appropriate in 44.7%-0% in autologous and 100% in allogeneic group In patients with appropriate indication, choice of antifungal agents was 100% appropriate 100% of patients used inappropriate dosage, mostly lower than the recommeded dosage with azoles 12.7% had appropriate prophylactic time Potential drug-drug interactions were identified in 92.1% of patients Most frequent interactions involved azoles-diazepam (80.4% of episodes) and azoles-immunosuppressive drugs (49% of episodes) In conclusion, a considerably high proportion of non-adherence of antifungal prophylaxis guidelines was revealed, that seemingly called for an adequate programme for antifungal stewardship to strengthen rational use of antifungal in such specific circumstances
Keywords: Antifungal prophylaxis, drug use evaluation, hematopoietic stem cell transplantation
Trong bo tieu chf, tieu chf chf dinh thuoc khang n a m d i r g e tfnh theo so benh nhan, tieu chf Iga chpn thuoc, lieu dung, d i r d n g diing cua cac thuoc d i r g e tfnh theo so
O a t v a n d e
Ghep te b a o goc tao m a u (Hematopoietic stem cell transplantation - H S C T ) la mot ky thuat phire tap, cd the gay nhieu bien chirng n g h i l m c h o benh nhan, dd c d n h i l m n l m m Sir dung thudc khang n a m d g
phdng tren doi t i r g n g benh nhan ghep te b a o g o c d e m lai nhieu Igi fch, n h i l n , viec s i r dung khdng h g p ly cac thuoc lam tang chi phi dieu trj c h o benh nhan, tang xuat hien cac chung vi n a m khang thuoc cung nhir tang nguy ccr xuat hien tac dung khdng m o n g m u o n d o thuoc khang n a m hoac hau q u a c u a t i r a n g tac c d lien quan d i n thuoc khang n a ml ] Khoa G h e p te b a o
goc, Vien Huyet hoc - Truyen m a u Trung i r a n g la c a s d dau nganh ITnh v g c g h e p te bao goc tai Viet N a m D a y cung la n a i c d ty I I n h i l m n a m cao, chiem , % so benh p h a m n a m toan Vien, dong thai, Khoa Vi sinh cua Vien cung d a ghi nhan hien t i r g n g giam nhay cam cua Candida tropicalis v d i fluconazol P l Tren c a s d d d ,
chung tdi tien hanh de tai v d i m u c tieu phan tfch phac d g phdng b l n g thuoc khang n a m tren b i n h nhan g h l p te b a o goc, tir dd, d e xuat d i r g e c a c bien phap gdp phan nang cao hieu qua s i r dung thudc khang n a m cua V i | n
Doi tirgng va phircrng phap
Doi tirgng nghien cu>u: Toan bo b | n h nhan d i r g e t i l n hanh H S C T tai Khoa G h e p te bao goc, V i | n Huyet hoc - T r u y l n m a u Trung i r a n g tir 01/4/2016 d e n 31/12/2016; loai trir b | n h nhan cd tuoi < 18 tuoi va b | n h nhan dang s i r dung phac d i l u trj khang n a m tai thai diem ghep
P h a a n g phap nghien c i n i : N g h i l n ciru m l ta, khdng can thiep, theo ddi dgc tien ciru Moi b | n h nhan d i r g e theo ddi va ghi lai thong tin bat dau tir ghep tdi thai d i l m b | n h nhan ngirng s i r dung thuoc khang nam, b | n h nhan chuyen sang phac d o d i l u trj khang nam, b | n h nhan tir vong hoac chuyen hoi sire tfch cgc Bp t i l u chf danh gia d i r g e nhdm n g h i l n ciru x a y d g n g d g a t r l n h i r d n g dan c u a Mang lirdi Ung thir Quoc gia Hoa Ky (National Comprehensive Cancer Network -N C C -N ) phien ban 2.2015 M va 2.2016 w Rieng cac tieu chf ve lieu dung cua voriconazol va fluconazol d g phdng khang n a m d i r g e tham khao tir t d thong tin s a n pham d i r g e phe d u y | t tai A n h [ ) d o khdng d i r g e d l c a p
trong H i r d n g dan c u a N C C N T i r a n g tac lien quan d i n thuoc khang n l m d i r g e xac djnh d g a tren cuon Hansten and Horn's Drug Interaction Analysis and Management 2013 va Iga chpn cac t i r a n g tac tir m d e dp t r d l l n m
d g t d i l u trj (tire la khoang thai gian tfnh tir luc bat d a u den luc k i t thuc s i r dung mot thuoc khang n a m v d i m u c dfch d g phdng) Ngoai ra, tieu chf Iga chpn thuoc khang n a m chf x l t t r l n b | n h nhan c d chi djnh phu h g p va t i l u chf v l thai gian d g phdng khang n a m c h i tfnh t r l n so b | n h nhan khdng tir vong, c h u y l n hoi sire tfch c g c hoac n h i l m n l m qua trinh dieu trj
X i r ly s o lieu: S o lieu d i r a c x i r ly bang Microsoft Excel 2016 va S P S S 22.0
K e t q u a
D a c diem c u a benh n h a n H S C T m a u nghien cu>u
D a c diem cua b | n h nhan H S C T m i u n g h i l n ciru d i r g e m o ta d bang 1, hinh va hinh
Bang 1. Dac diim nhan khau hoc cua benh nhan nghien cuv Chi tieu nghien cuv Ghep to than Ghep dong loai Toan bp mau
So benh nhan theo ddi (%) 21/38 (55,3%) 17/38 (44,7%) 38/38 (100%)
Tuoi
(nam - trung binh ± SD) 36,6 ±13,5 34,7 ±10,3 35,7 ±12,0 Tuoinhd nhat-Ion nhat - 18-52 18-65
So benh nhan nam (%) 11/21(52,4%) 11/17(64,7%) 22/38(57,9%)
Trong m a u n g h i l n ciru, s o b | n h nhan g h e p t g than nhieu h a n so b | n h nhan ghep dong loai D p tuoi c u a b | n h nhan m a u nghien ciru phan bo rpng (18 -65), nhdm b | n h nhan ghep t g than c d d p tuoi c a o h a n (19 - 65) n h d m b | n h nhan ghep dong loai (18 - 52) B | n h nhan n a m cd ty l | cao h a n m a u n g h i l n ciru D a so c a c b | n h nhan khdng ghi nhan tien s i r v a b | n h m l c k e m (81,6%) T a t ca b | n h nhan g a p bien co s a u g h e p deu n a m nhdm ghep dong loai
Da time nhiem Dang nhiem khuan niem mac miens
2.6% Suy giam chiic nangthan
5.3% Viem gan B
7.9%
Hinh 1. 77en sCrcua benh nhan nghien ciiv
(7)• Nghien cfru - Ky thuat
40
30 .1
3
20x
10
33
21 0 0
12
1
1 0 % s o benh nhan g h e p d e u d i r g e d g phdng bang thuoc khang n a m azol Thudc d g g c s i r dung nhieu n h l t la fluconazol (36 benh nhan, chiem , % ) Posaconazol v a voriconazol chi d i r g e s i r dung d benh nhan g h e p dong loai
Ket q u a phan tich p h a c d o k h a n g n a m d g p h o n g v a lieu d u n g t h g c te tren benh n h a n s o v d i lieu k h u y e n c a o
Bang 3. Ket qua phan tich phac dd khang nam dir phdng
Ghep tv than Ghep dong loai Toan bo mau
B Nhiem nam • Chuyen ICU H Tu vong O Hoan dieu tri
Hinh 2. Bien co sau ghep cua benh nhan nghien cuv
Dac diem lien q u a n d e n c h i dinh t h u o c k h a n g n l m d g p h o n g
Bang 2. Dac diim lien quan den chi dinh thuoc khang nam dg phdng Chi tieu nghien ciru Ghep to than Ghep dong loai Toan bp mau S6 benh nhan dir phdng
nam(%) 21/21 (100,0%) 17/17(100,0%) 38/38 (100,0%) Thdi gian diing
(ngay-trung vivalQR) 16(13-17) 62(31 -73) 17,5 (13-47,5) Sd luvng va ty le sir dung thuoc (%)
Fluconazol 20/21 (95,2%) 16/17(94,1%) 36/38 (94,7%) Itraconazol 2/21 (9,5%) 2/17(11,8%) 4/38(10,5%) Voriconazol 0/21 (0,0%) 4/17(23,5%) 4/38(10,5%) Posaconazol 0/21 (0,0%) 4/17(23,5%) 4/38(10,5%)
Tieu chi Ghep to than
Ghep dong loai
Toan bp
mau Chi dinh phu hop 0/21 (0,0%) 17/17(100,0%) 17/38(44,7%)
Lira chon phu hop 0/0
(Khong danh gia) 29/29(100,0%) 29/29(100,0%)
Lidu, dudng dung
phu hop 0/22 (0,0%) 0/29 (0,0%) 0/51 (0,0%) Thoi gian dung
phii hop 0/21 (0,0%) 4/12 (33,3%) 4/33(12,1%) Tieu chi ve Iga chgn thuoc khang n a m dat ty le p h u h g p cao nhat, cac tieu c h i lai deu co ty le phu h g p rat thap Nhin chung, ty le phu h g p d n h d m benh nhan g h e p t g than thap h a n n h d m benh nhan g h e p dong loai D a e biet, v e lieu dung va d i r d n g d u n g , tat ca benh nhan deu d i r g e sir dung thuoc khang n a m phu h g p ve d i r d n g dung nhirng lieu dung t h g c te c u a c a c thuoc d e u thap h a n lieu d i r g e khuyen cao C u the, lieu dung c u a benh nhan d i r g e trinh bay bang
Bang 4. Lidu dung thirc te tren benh nhan so v&i lidu khuyen cao Lieu thirc te Ghep to than
(So dot didu tri)
Ghep dong loai
(So dot dieu tri) Lieu khuyen cao Fluconazol
Cla > 50ml/phut 300 mg/ngay 19 16 400 mg/ngay
Cla > 50ml/phut
150 mg/ngay 0 1 400 mg/ngay
CICr < 50 ml/phut
khdng toe mau
300 mg/ngay 0 1
200 mg/ngay CICr < 50 ml/phut
khdng toe mau 150 mg/ngay 1 0 200 mg/ngay
Itraconazol 200 mg/ngay 2 2 400 mg/ngay
Voriconazol
Bdnh nhan > 40 kg 200 mg*2 Idn/ngay 0 4
Ngay dau: 400 mg x 2 Idn/ngay Duy tri: 200 mg * 2 lan/ngay Posaconazol 200 mg*2 Idn/ngay 0 5 200 mg x 3 lan/ngay
Dac diem tircrng t a c t h u o c c o y nghTa lam s a n g lien q u a n den t h u o c k h a n g n a m
Bang 5. Dac diem tuung tac thudc cd y nghTa lam sang lien quan den thudc khang ndm
Chi tieu nghien ciru Ghep to than Ghep dong loai Toan bp mau
S6dptdieutricdtuungtac(%) 20/22(90,9%) 27/29(93,1%) 47/51 (92,2%)
Trung binh 01 dot didu tri 1,15 1,85 1,55
Cac cap tirong tac
Azol1 - diazepam 20 (90,9%) 21 (72,4%) 41 (80,4%) Azol1 - thuoc dc che mien dich2 0(0%) 25 (86,2%) 25 (49%) Azol3 - omeprazol 2(9,1%) 3(10,3%) (9,8%) Voriconazol - omeprazol (0%) (3,4%) (2%) Itraconazol - methylprednisolon (4,5%) (0%) (2%)
Ghi chii: 'Fluconazol, itraconazol, voriconazol, posaconazol
2Ciclosporin, tacrolimus ritraconazol, posaconazol
T i r a n g tac lien quan den thuoc khang n a m d i r g e ghi nhan m a u nghien ciru v d i ty le rat cao, v d i , % benh nhan gap it nhat t i r a n g tac T i r a n g tac bien nhdt la giCfa cac azol v d i d i a z e p a m , gap d , % so d g t d i i u tri cua benh nhan T i r a n g tac giCra cac azol v d i cac thuoc ire che mien djch (ciclosporin v a tacrolimus) cung d i r g e phat hien d g t dieu trj, chiem , %
Ban luan
Ket q u a c u a nghien ciru c h o thay, d g phong bang thuoc khang n a m d i r g e c h i dinh tren toan bp benh nhan tham gia nghien ciru Tuy nhien, chi co 17/38 chi djnh (chiem 4 , % ) la phu h g p Didu xuat phat tir viec benh nhan g h e p t g than khong c d bieu hien viem niem m a c v a n d i r g e c h i djnh thuoc khang n a m khdng c a n thiet T i n h trang tren cung d i r g e ghi nhan (Xem tiep trang 46)
(8)• Nghien ci>u - Ky thuat
6 Rhee I K etal (2001), "Screening for acetylcholinesterase inhibitors from Amaryllidaceae using silica gel thin-layer chromatography in combination with bioactivity staining", J of Chromatography A, 915(1-2), 217-223
7 Schneider L S (2000), "A critical review of cholinesterase inhibitors as a treatment modality in Alzheimer's disease", Dialogues Clin Neurosci., 2(2), 111-128
(Ngay nhan bai: 21/07/2017 - Ngay phan bien: 24/09/2017 - Ngay duyet dang: 20/10/2017)
Phan tich tinh hinh
(THp theo trang41)
trong nghien c d u cua Vazin va C S theo doi s 6 benh nhan s i r dung fluconazol, co 19,4% d i r g e chi djnh khong phu h g p tren benh nhan g h e p t g than khong co viem niem m a c [ ! Tinh trang co the xuat phat tir
khd khan viec quydt djnh chi djnh thuoc cho benh nhan g h e p t g than chira co cdng cu n a o c h o phep d g d o l n trinh trang viem niem m a c va giam bach c l u trung tinh
Toan b d benh nhan m i u nghien c d u d i r g e d g phong bang c a c thuoc khang n a m n h d m azol Trong do, fluconazol la thuoc d i r g e s i r dung p h d bien nhat Tuy nhien, fluconazol cung d d n g d a u c a c thuoc d i r g e chi djnh khong phu h g p , v d i ly d a d i r g e d e cap d phan c h i djnh chira h g p ly d tren H a n n a a , khong co benh nhan n a o d i r g e s i r dung fluconazol v d i lieu phu h g p Hien t i r g n g t i r a n g t g d a d i r g e ghi nhan nghien c d u c u a Nivoix va C S M Dieu c d the lien
quan d e n viec d Vien c h i co c h e pham fluconazol 150 m g vien nang v a 0 m g truyen tTnh m a c h , viec s i r dung thuoc dung d i r d n g udng d i r g e s i r dung bien va thuan tien h a n c h o benh nhan S i r dung fluconazol v d i lieu thap h a n binh t h i r d n g co the tiem I n nhieu nguy c a D a c biet la Vien dang ghi nhan tinh trang gia tang de khang v d i fluconazol cua Candida tropicalis, ty le khang thuoc n a m 2015 d a len t d i 4 %
Trong nhdm benh nhan ghep t g than, tat ca benh nhan d e u s i r dung thuoc khang n a m bach c l u d a t r d ve mire binh t h i r d n g Thong t h i r d n g , benh nhan chi d i r g e n g d n g thudc khang n l m tinh trang on djnh va x u l t vien VI vay, viec keo dai thuoc khang n a m gay lang phi chi phi dieu trj cho benh nhan N g i r g c lai, nhdm benh nhan ghep dong loai, d a so benh nhan ngirng s i r dung thudc t n r d c t h d sau ghep Dieu la thai gian nam vien cua d a so benh nhan ghep dong loai v i r g t qua tran bao hiem, nen nhCrng benh nhan co tinh trang on djnh t h i r d n g d i r g e x u l t vien t r a d e 75 sau ghep Khi dieu tri ngoai tru, c a c benh nhan cung khdng s i r dung thuoc khang n l m gia kha cao T a a n g t i e bien nhat ghi nhan m i u nghien c d u la t a a n g t i c g i a a c l c azol va diazepam c d nguy c a Urn t i n g nong d p huyet t a a n g cua diazepam, d i n den tang c l c bien c d bat Igi cua thudc n h a an t h i n q u i m d c , g i l m k h i nang phdi h g p c l c c d ddng, p h l n xa ( t h l t d i e u )[ ] V d i benh nhan HSCT, diazepam c h i
d a g c s i r dung v d i m u c dich a n t h i n , vi vay, bac sT nen can nhac viec phdi h g p thudc n l y v d i c l c azol de h a n chd t i c dung bat Igi cho benh nhan T a a n g t i c c l n c h u y n h l t , dong thai I I t a a n g t i c d a g c c l n h b i o H a d n g d i n dieu trj cua N C C N I I t a a n g t i c giira c l c azol k h l n g n a m v i c l c thuoc d c che mien djch (ciclosporin,
tacrolimus), c d the d i n d e n suy than t r a d n g h g p khdng d a g c kiem s o l t c h i t che M Hien nay, Vien d a c d
n h d n g bien p h l p g i l m s i t tich c g c de g i l m thieu t a a n g t i c bat Igi n l y , bao g o m g i l m s i t creatinin q u a b d xet nghiem t h a d n g quy v i djnh l a g n g ndng d d thuoc m i u v d i tan s u i t lan/tuan de kiem s o l t hieu q u i v i ddc tinh cua c l c thuoc d c che mien djch
Ket luan
Ket qua cua nghien c d u cho t h l y t h g c trang s d dung thudc k h l n g n a m d g p h d n g tren benh nhan H S C T tai Vien Huyet hgc - Truyen m i u Trung a a n g Nghien c d u da chi ty le khdng phu h g p cao s d dung thuoc k h l n g n l m d g phdng d doi t a g n g benh nhan n l y v e c l c tieu c h i chi djnh, lieu dung v i thai gian dung Dieu c h o thay c l n thief then khai c h a a n g trinh q u l n ly thuoc k h l n g n l m tai Vien n h a m nang c a o c h i t l a g n g s d dung thudc
Tai lieu tham khao
1 DiPiro J T, Talbert R L et al (2017), Pharmacotherapy: A Pathophysiologic Approach, 10t h Edition, McGraw-Hill
Education, New York, pp 6274-6315
2 Andes D., Azie N et al (2016), "Drug-drug interaction associated with mold-active triazoles among hospitalized patients", Antimicrob Agents Chemother., 60(6), pp 3398-3406
3 Khoa Vi sinh (2015), Bao cao ve tinh hinh nhiem khuan tai Vien Huyet hoc - Truyen mau Trung uvng nam 2015, Vien Huyet hoc - Truyen mau Trung aong
4 National Comprehensive Cancer Network (2015), Prevention and treatment of cancer-related infections (Version 2.2015) , <https://www.nccn.org/professionals/physician_gls/ pdf/infections.pdf> [Accessed: 03/01/2016]
5 National Comprehensive Cancer Network (2016), Prevention and treatment of cancer-related infections (Version 2.2016) , <https://www.nccn.org/professionals/physician_gls/ pdf/infections.pdf> [Accessed 15/12/2016]
6. Summary of Product Characteristics for Diflucan 200 mg Hard Capsule (fluconazole): VFEND 200 mg film-coated tablet (voriconazole) (2016), <http://www.medicines.org.uk/ emc>, [Accessed: 09/3/2016]
7 Hansten P D., Horn J R (2013), Hansten and horn's drug interactions analysis and management, Lippincott Williams & Wilkins, St Louis
8 Vazin A., Davarpanah M A et al (2015), "Antifungal agent utilization evaluation in hospitalized neutropenic cancer patients at a large teaching hospital", Drug Healthc Patient Sat, 7, pp 97-102
9 Nivoix Y , Launoy A et al (2012), "Adherence to recommendations for the use of antifungal agents in a tertiary care hospital", J Antimicrob Chemother, 67(10), pp 2506-2513
(Ngay nhan bai: 19/09/2017- Ngay phan bien: 28/09/2017- Ngay duyet dang: 20/10/2017)
<https://www.nccn.org/professionals/physician_gls/ pdf/infections.pdf> <http://www.medicines.org.uk/ emc>