# N g h i e n CLFU - Ky t h u a t
Nhan xet Theo k i t qud d bang 4, d u lidu GPDC t d vien d i i e h i l u vd vien bao c h i d u y c t u y l n tinh vdi cdn bdc hai eua thdi gian h o n v d i hp s i R^~1 (0,9908). Vi vdy ddng hpe cua vidn ndn TRI thyc nghipm t u o n g t y n h u vidn d i i e h i l u v d phu hpp vdi m d hinh gidi phdng eua Higuchi hon Id ddng hpe bdc 0.
Ket lu^in
Da nghidn c u u sdng Ipe vd xdy d y n g d u y c cdng thdc bdo c h i vidn ndn trimetazidin 35 m g gidi phdng kdo ddi 12 gid hd e l t thdn n u d c dgt tidu c h u i n v l gidi phdng in vitro theo ydu c l u d l ra, Ddng hpe gidi phdng d u p e c h i t t u vidn tudn theo m d hinh Higuchi hon Id bdc 0 - gidi phdng d u y c c h i t theo eo e h i k h u l c h tdn t u hd c i t thdn n u d c truong n d tgo hdng rdo gel. Ddy cd t h i Id md hinh d l u n g dyng eho nghidn c d u bdo c h i dgng c i t thdn n u d e k i l m sodt gidi phdng cho ede d u p c c h i t tan t i t trong nude.
S u m m a r y
Sustained-release hydrophiiic matrix tablets of Trimetazidine hydrochloride were prepared. Influences of the excipients including HPMC K4M, DCP, Cros, and Avicel on the drug release of the formulated tablets were studied. The compression force hardly affected the drug release. The release profile of trimetazidine hydrochloride from our
proposed formula was similar to that of the reference tablets. The kinetics of drug release from the obtained tablets was complied witli Higuchi model.
Tdi li#u tham khao
1. Costa P. et al. (2001), "An alternative method lo the evaluation of similarity factor in dissduljon testing". Int. J. Pharm., (^00), p. 77-83,2. Dabbagh A, M. et al. (1999), "Release of propranolol hydroclonde from matrix tablets containing sodium carboxymethylcellulose and hydroxy propylm ethyl cellulose". Pharmaceutical Development and Technology, 4(3), p. 313-324,
3. Food and Drug Administration - CDER (2000), Guidance for industry Extended release oral dosage forms; Development, evaluation, and application of i i vitro/in vh/o correlations.
4. Marikanti K, R, et al (2010). "Fomulation and evaluation of controlled release matnx tablets of trimetazidine di hydrochloride", Journal of Chemical and Pharmaceutical Research 2(3), p. 746-753,
5. Parekh D. et al,(2008), "Formulation and evaluation of sustained release tablets of Inmetazidine di hydrochloride using vanous polymersT, Padm. Dr D. V. Patil Institute of Pharmaceutical Sciences and Research, Pune.
6. Vasrhney et al. (2009), "Controlled release pharmaceutical dosage fomis of trimetazidine', International application published under the patent cooperation treaty (POT) WO 20009/034541 A2.
Nghien ctfu viec lira chon va su* dung khang sinh trong dieu tri viem phoi tai Khoa Noi - Benh vien Trung uo^ng Hue
tir 1/2009 den 8/2010
D a t v a n 6e
Trong nhung nam gan day, cung v d i s y d nhidm mdi trudng, bdnh ly phdi - p h i quan ed
Nguyen Ky NhSt', Hoing Thj Kim Huyen^
Benh vien Trung uang Hue
^ Tru&ng Dai hpc DuQC Hd Npi xu hudng gia tang v d cung v d i vipc s d dyng khdng sinh qud rdng rai, bp mgt djch t l vd ldm sang cua cae logi vidm p h i i cdng t r d nen phi>c
TAP CHI DirgfC HQC - 07/2012 (S6 435 NAM 52)
• Ngnien cu>u - Ky thuat
tap: s y thay ddi v l md hinh vi k h u i n gdy bpnh, dae bipt ed s y gia tang cdc chung vi khuan khdng khdng sinh lam cho vide d i l u tn vidm p h l l ngdy nay ggp nhieu khd khan'^l
Khoa Npi - Bpnh vipn Trung u o n g H u l thudc bdnh vidn da khoa hoan chinh Idn n h i t m i l n Trung, t u y l n cuoi eung t i l p nhdn cae trudng hpp dwcfc c h u y i n t u cdc bpnh vien d cdc dja phuong gui d i n . Chfnh vi vgy, vipc ddnh gid s u dung khdng sinh trong d i l u trj se gdp p h i n ndng cao hipu qua, giam gid thdnh va hgn c h i tinh trgng khdng thude cua vl k h u i n gay bpnh.
Tren c o s d dd, chCing tdl t h y c hien nghien c u u nay vdi hai mye tidu sau:
1. Khao sat tinh hinh s u dyng khdng smh trong mdu nghien edu.
2. Phan tich tfnh hpp 1^ cua vipc lua chpn va s d dyng khdng sinh qua tinh khdng thudc eua vi khuan vdi khdng sinh vd hipu qud d i l u trj.
D o i tLFOTig v a p h i r c n g p h a p n g h i e n CLPU
Doi t u v n g nghien ci>u Tieu chuan chgn b$nh
Ho so benh dn cua cdc benh nhan d u p c ehan dodn Id vidm phoi vao d i l u tri npi tru tgi khoa Npi - BVTW Hud t d thdng 1/2009 d i n thdng 8/2010 vdi cac tieu c h u i n sau^^':
- Ldm sang: cd it nhit 2 trong sd 4 tridu chung cua vidm phdi va cdc tridu chdng ndy x u i t hidn tru-dc khi vdo vien: sdt, ho, cac tridu chdng khac (dau ngye, khd thd, met mdi, chdn an...). Kham
phoi t h i y ed hpi chdng ddng dgc, ran I m , ran no.
- Cd d i y du cdc xdt nghipm cgn Idm sang thudng quy e i n thilt.
- S l ngdy didu trj t i i t h l l u : 05 ngdy.
Tieu chuin lo^i trip
Vidm phoi mde phdi bpnh vidn. bdnh nhan lao phdi. n h i l m HIV, cdc bdnh vidm phoi khdng do vi k h u i n .
Phuong phdp nghidn cdu Nghidn edu hoi edu.
Cv miu va cich chgn mau
Trong thdi gian t u 1/2009 d i n 8/2010. ehpn d u y c 205 bdnh dn theo dung tidu c h u i n lya ehpn vd logi t r u da neu.
Mgt so tieu chuin de phan tich kit qua - Phdn tich vipc chi dinh khdng sinh khi chua cd k i t qud khdng sinh d l (dieu trj kinh nghiem):
cac khdng sinh d u p c kd phai phu hpp vdi hinh anh vi khuin hay ggp va dd khdng khdng smh eua chiing.
- Phan tfch vipc ehi djnh khdng sinh khi da ed k i t qua khdng sinh d l : khdng sinh dupe ehi djnh phai phCi hpp vdi dp nhgy cdm eua vi khuan phdn ldp.
Phuxrng phap xir ly so lieu
Sd lieu sau khi thu thap d u p c x u ly bdi Microsoft Excel 2003.
K e t q u a n g h i e n CLPU
Mpt so dac diem cua mdu nghien cuu Bac diem ve tuoi va gioi
Bang 1 : B$c tuoi 16->29 30->49 60->69
>70 T6ngs6
Phan do tuoi va gioi cua cac doi tuong nghien cuv Tlnh
Chung 17 57 60 71 205
%
8,3 27,8 29,3 34,6 100,0
Nam Solwcmg
7 33 26 44 110
Tyi$%
3,4 16,1 12,7 21,5 53,66
Nir So lifting
10 24 34 27 95
TflS'/o 4,87 11,7 16,6 12,2 46,34
z'.P
X^=1,914 p>0,05 - Trong so 205 bpnh nhdn cd 110 bpnh nhan
nam, e h i l m 53,66% va 95 bpnh nhan n u c h i l m 46,34%. Tuoi thap nhat ggp phai Id 17, cao n h i t Id 95.
- Cdc benh nhan d dp tuoi t u 50 trd Idn
c h i l m mpt ty le ldn (63,9%). Rieng cac bpnh mau nghidn cuv
nhdn > 70 t u l i ehilm 34,63%. tdc hon 1/3 so bpnh nhdn d i l u trj.
K i t qua nghidn ciru ve vi khuan gay bdnh Cac Chung vi khuan phdn l$p duyc trong
T^P CHI DlTQIC HOC - 07/2012 (SO 435 NAM 52)
• N g h i e n CLFU - Ky t h u a t
Bang 2: Cdc chung vi khuin gdp trong miu nghidn cOvTT Lo^i VK Tdn VK Tin Tyld Tyld suit % chung K. pneumoniae 17 25,4
P. aeruginosa 6 8,9
Gram
im H. Influenzae Pseudo cepacia
Enterobacter agglomerans 9 Enterotiacter
cloacae 10 S aueus 11 Gram S pneumoniae 12 ducmg Enlerococcus
faecalis Tdng
8
2 5 2 6711,9
3,0 7,4 3,0 100,0
17,9
100,0 Trong sd 12 ehung vi k h u i n chung tdi ggp vi k h u i n Gram dm chiem tdi 8 2 , 1 % , vi k h u i n Gram d u o n g ehi chidm 17,9%. Cd 3 logi vi k h u i n hay gdp trong m i u la K. pneumoniae (20,9%); Enterobacter cloacae (11,9%) vd H.
influenzae (10,4%).
So toai vi Miuin phdt hien tren mgt ixnh nhan Bang 3: So loai vi khuin phdn lap dirac tren mot t>dnh nhdn
So loai vi khuin
1 loai 2 ton Tong so
S6 BN 27 20 47
KiSu So ket hgp BN
Gr (+) • (Gr (-) 6 Gr(-) + (Gr(-) 14
Tyle%
57,4 ' ' • ' 1 - 6 29,8 ' " "
100,0 Nhung bpnh nhdn cd ca hai chung vi k h u i n ddu Id Gr (-) (14 bdnh nhdn) n h i l u g i p 2,3 lan s l bdnh nhdn nhiem ed vi k h u i n Gr(+) va Gr(-).
Bang 6: Dii phde did bdnh nhdn VK (-) dung
Ddy Id ddc d i l m c i n luu y khi l y a ehpn khdng sinh trong d i l u trj d bdnh vidn t u y l n cuoi.
Cdc phdc d6 khdi diu diiu tn viem ph6l khi chwa c6 kit qui xdt nghidm vi khuin
Bdng 4: Tf' 1$ b$nh nhdn s u dyng mdt khdng sinh vd khdng sinh phdi h<?p
Phic 06 1 khSng sinh Ph6i ho-p 2 khdng smh Ph6i hp'p 3 khdng sinh
T6ng s6
S6 tj^nh nhin 51 141 13 205
TyiiV, 24,9 68,8 6,3 100,0 Sy thay d6l phdc d6 & nhuvjg b^nh nhan ciy vi khuin duvng tlnh
Bdng 5: Ty Id chuyin dii cdc phdc di trong SU" dyng thudc sau khi cd kit qui khdng sinh d6
Ly do chuyin dii Chuydn Do vi khudn khdng phdc Ob Do ph6 khfing 6ii
Od phij htfp
!h!f'in ^^"'^ ''*" '"*" **'
Bdc sy khflng chuydnT6ng
n 11 3 25 4 4 47
T//#W
23,46,4 53,2
8,5 8,5 100,0 - 23,4% s y e h u y i n doi phde d l la do vi k h u i n khdng thuoc.
- 6.4% sy ehuyin phdc do do p h i khdng du rpng.
- 53,2% cdc phdc dd khdi d i u khdng can phdi e h u y i n do phij hpp v d i dp nhgy cdm vi k h u i n phdn ldp. 8,5% khdng e h u y i n do bpnh ddp ung tdt trdn Idm sdng.
- 8,5% phdc d l bdc sy khdng thay doi thuoc ngay sau khi cd k i t qua KSB mac du khdng phii hpp vdi dd nhgy cam vi k h u i n phan ldp.
Sy thay dii phdc do & nhOng benh nhan xdt nghidm vi khuin am tlnh va khdng xet nghifn^*^
Bdnh nhdn khdi diu dung khdng sinh dan doc khdng sinh dan d0c
HiP&ng chuyin PD
Don dpc chuyen sang phoi hop •
Tong so
Phic do kh&l diu Cefuroxim (n=1) Ceftnaxon (n=1) Amoxicilin/kali clavulanat(n'
Clarithromycin (n=1) C3G1 (n=19) C3G2(n=17)
44
Phic di thay the
=5) Amoxicilin/kali clavulanat + amikacin Ceftazidim + amikacin C3G1 hodc C3G2 + aminosid
C3G2 + macrolid C3G2 + aminosid hogc FQL
N 1 1 2 1 3 1 3 12
TAP CHi Difgrc H Q C - 07/2012 ( s 6 435 NAM 52)
• Nghien CCFU - Ky thuat
Trong dd:
- C 3 G 1 : cefotaxim, ceftriaxon - C3G2: ceftazidim, cefoperazon - 32/44 benh nhdn d u p c d i l u trj thdnh cdng vdi phac do la khdng sinh p-laetam p h i rpng don dpc. s d bpnh nhan phdi ehuyin phdc d l e h i l m 27,3%
- Cac phde do chuyen doi theo hudng tdc dung mgnh hon trdn vi khuan Gr(-); 10/12 bdnh nhan ehuyin sang dung khang sinh phdi hpp: hoge vdi aminosid hope vdi FQL. Chi cd 1 taidng hpp md rdng phd tdc dyng vdi vi khuin npi bdo,
Bdnh nhdn VK (-) kh&i diu dung phdc dd phdi hti^f/^^
Bang 7: Doi phdc dd a bdnh nhdn VK (-) dung khdng smh phdi hop Phic do kha diu
p-lactam + vtc chd
^-lactamase Cefuroxim
C3G1 Phdc ad 1
Aminosid (n=5) FQL (n=4) Macrolid (n=1}
FQL(n=1) Aminosid (n=63)
FQL (n=22) Metronodazol (n=11) phdi hop 3 khdng smh
Tdng sd
N 9 1 1 96 7 114
Phic di thay thi Khdng chuydn phdc dd Ceftazidim + amikacin
C3G1 + amikacin C3G2 + amikacin + Q2G + metromdazol
C3G2 + Q2G C3G1 + amikacin Khong chuydn phdc dd
N
1 1 9 10 5 26 - 88/114 bdnh nhdn (77,2%) d u p e d i l u tri
thdnh cdng vdi phde do khdng sinh phdi hpp.
Cd 26/114 bdnh nhan phai c h u y i n phac do d i l u tn, c h i l m ty lp 22,8%, Qua khdo sdt, nhung bpnh nhan nay thudng Id bdnh nang, hoge gia ydu va cd nhieu benh mde kem nhu nghidn r u p u , x o gan, tjpnh phoi mgn tinh, hoac cd dung thudc giam m i l n dich.
- Cdc phac do chuyen doi d u p c lua ehpn theo hudng tac dung trdn tn^c khuan mu xanh va vi khuan Gr(-) manh hon, khdng sinh cd dp nhgy cam cao vdi vi khuan:
+ Vdi C3G: cefotaxim, ceftriaxon - >
cefoperazon, ceftazidim.
+ Vdi aminosid; gentamiein, tobramycin - >
amikacin.
- Cdc phac do phoi hpp 3 khdng sinh ch!
c h i l m 6,3% va h i u nhu deu k i t hpp vdi khdng sinh dipt vi k h u i n ky khi. Cac bdnh nhdn nay khdng phai c h u y i n phde do.
K e t l u a n
- Ty Id bdnh nhan xdt nghipm vi k h u i n d u o n g tinh la 22,9%.
- Vi khuan Gram dm Id logi vi k h u i n gdy bdnh viem phoi c h i l m uu t h i trong mau nghidn c u u tgi Khoa Ndi - Bdnh vidn Trung u o n g Hue (82,1%)
- Cdc vi khuan hay ggp d Khoa Ndi Id:
Klebsiella pneumoniae (25,4%), Enterobater
TAP CHI DirgiC HQC - 07/2012 (S6 435 N A M 52)
cloacae (11,9%), H. influenzae (10,2%), Pseudomonas aeruginosa (8,9%).
Ty Id benh nhdn khdi dau dung phde do don ddc Id 24,9%; phde dd phoi hpp la 75,1%. Phdc dd phdi hpp 2 khdng sinh id chu y l u (68,8%).
- Cac phac dd (^en hinh id: p-iaetam + aminosid hoge |3-lactam +fluoroquinolon.
- Cd 47/205 bdnh nhdn cd k i t qud xet nghidm vi khuin duong tinh, e h i l m t]y' Id rdt thap: cd t h i do benh nhan da s d dyng khdng sinh trude khi vao vidn nen k i t qua thudng am tinh va mdt sd ft do bdc sT khdng chi dinh.
Cae khang sinh thudng dung nhu cefuroxim, ceftriaxon, amoxicilin/clavulanic, gentamiein bj cdc vi k h u i n hay gap d khoa Ndi de khdng cao, can chi (^nh thgn trpng khi dieu tn theo kinh nghipm,
Cdc khdng sinh ceftazidim, cefepim, imipenem, amikacin, netilmicin, bi cdc vi k h u i n hay gap d Khoa Ndi d l khdng t h i p , cd t h i xem xet ehi djnh eho nhung tn/dng hpp bdnh cd tidn lupng ndng,
- P h i n Idn ede khdng sinh d u y c s d dung d i l u trj viem phoi tgi Khoa Npi phii hpp vdi hinh anh vi khuan hay ggp vd mdc dp khdng khdng smh eua ehung.
- o l dgt hidu qud d i l u trj cao. an toan, hop ly, nen l l y benh p h i m gdi Khoa Vi sinh trudc khi dCing khdng sinh cho bpnh nhan; Khi xet nghipm tim vi khuin vd Idm khdng smh do, nen ghi khdng
25
' Nghien c i j u - Ky thuat
smh dupe chpn theo kinh nghipm d l phdng xdt nghidm thu dd nhgy cua khdng sinh dd.
Summary
Antibiotics use of the Internal Departement of Hue Central Hospital from January 2009 to August 2010 was investigated with 205 inpatients involved. Gram negative bacteria were the most common pathogens (82.1%), the typical ones were Klet)sielia pneumoniae (25.4%), Entem^ter cloacae (11.9%,), H. influenzae (10.2%), Pseudavonas aemginosa (8.9%i). Caution should be paid to the mnpencal use of cefuroxim. ceftriaxon.
amoxicilin/clavulanic, gentamiein and those antibiotics of high bacterial resistance. As bacterial resistance to ceftazidim, cefepim.
imipenem, amikacin and netilmicin were found relatively low. they could be used for patients with severe prognosis. Most antibiotics used were appropriate to bacterial pathogens as well
as their resistance and well observing the hospital drug lists and essential drug lists by the Ministry of Health.
Key words: antibiotics, bacterial resistance,
use of drug.
Tdi li$u tham khdo
1. Bd Y t l (2005), Hw&ng din diiu tq , tdp 1, NXB Yhpc,
2 BCii Xudn Tdm (2001). "Quan ni$m mdi vi chin dodn vd dilu In nhilm khuin dudng hd h^p dudi", Hdl thdo nhiSm khuin duttng hd hip vd m^tsd quan diim mdi, trang 1-11
3. Bartlett J. G., Scott F. D., Lionel A. M. and Fine M, J (2000), "Practice guidelines for the management of community-acquired pneumonia in adults', Infectious diseases socidy of America.
4. Beyan et al. (2001). "Acute community- acquired pneumonia". Current diagnosis and treatment. JSG Medicine association Jan.
Nghien ciru sy thay doi pH, ap lyc tham thau va SVC ben hong cau cua khoi hong cau bao
• ^