khÁng sinh.pdf

8/10/2019 KHNG SINH.pdf

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T H UOC SD UNG T R ON G H OA T R L I E U

T huoc khang sinh.

T huoc tr benh lao.

T huoc tr benh phong.

T huoc khang nam.

T huoc phong nga vatr nhiem vir us.

T huoc tr nhiem H er pes (H SV) vanhiem V SV.

T huoc tr nhiem H I V /A I D S.

T huoc tr viem gan.

T huoc tr sot r et .

T huoc tr l amib.

T huoc tr giun san.

T huoc tr ung th.


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KHNG SINH

T R N G A I H OC Y D C CA N T H

K hoa D c

Bomon D c ly


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M UC T I E U BA I G I A NG

Sau bai hoc nay, sinh vien cothe:

L iet kec cac nhom thuoc khang sinh chuyeu.

T r nh bay c cac c chetac ong chnh cua thuoc.

H ieu c nguyen nhan, cac dang vac cheekhang thuoc cua vi khuan.

Biet c oc tnh vacac tac dung phucua

cac nhom khang sinh quan tr ong.

T r nh bay c nguyen tac cach sdung

an toan, hp lycac khang sinh thong dung.


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Tai lieu tham khao


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I . I C NG

LCH SPH AT M I N H

Louis Pasteur

(1822-1895)

A lexander Fleming

(1881-1955)

Antony van

Leeuwenhoek(1632-1723)


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I . NH NG H A

K hang sinh lanhng chat xuatxtnhng sinh thenh vi khuan,nam, A ctinomycetes hoac do bantong hp hay tong hp c.

H esotr lieu cua khang sinhr at cao, cok ha nang ngan chanmot vai dien tien tr ong quatr nhsong cua mot sovi khuan, vi sinh

vat, sinh vat a bao ngay lieulng nho, vavi lieu ln hn cungkhong hoac t gay hai en tebaongi sdung.


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I . NH NG H A

K hanang ngan chan quatr nh song cua vi khuan thehien: T nh kiem khuan (Bacteriostatic): K hang sinh chc chetam

thi sphat tr ien cua vi k huan. N eu ngng thuoc, vi k huan cothephat tr ien tr lai, gay nhiem tr ung tai phat.

T nh diet khuan (Bactercidal): K hang sinh ganvao cac vtr tac ong cua notr en tebao

vi khuan vatieu diet chung.

Khi nim v tc dng kim khun v d it khun

gip sdngng khng sinh:- Trong nhim trng nh: Khng sinh kim khun.

- Trong nhim trng nng: Khng sinh dit khun.

Tuy nhin sphn loi ny ch mang tnhtng i.


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Phokhang khuan:

D o khang sinh cotac dung theo c cheac hieu nen

moi khang sinh chcotac ong tr en mot sochung vikhuan nhat nh, goi laphokhang khuan cua

khang sinh.

I . NH NG H AM ot sokhai niem vehoat tnh cua khang sinh


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Phokhang khuan:


V i khuan nhay cam vi khang sinh A vaE , ekhang vikhang sinh C vaD ; comot s ekhang tr ung bnh vikhang sinh B


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V i khuan G r (+) vaG r (-)

Escherichia coli

H ans Christian Joachim Gr am

(1853 1938)

Staphylococcus aureus


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Phokhang khuan:


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Phokhang khuan:

Phokhang khuan hep.

Phokhang khuan rong.



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T hong thng M BC = 2-8 lan M I C.

Cac khang sinh diet khuan coM BC gan vi

M I C vadeat nong obang M BC trong

huyet tng, nh PN C, cephalosporin,

aminoglycosid,

Cac khang sinh kiem khuan coM BC> M IC

vakhoat c nong obang M BC trong

huyet tng, nh tetracyclin ,

chloramphenicol, macrolid,..



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Snhay cam:

V i khuan nhay cam vi mot khang sinh khivi khuan ob diet lieu vang dung

thong thng.Nong okhang sinh/huyet tng > M I C .

Skhang thuoc

(Sekhang khang sinh cua vi khuan):

Nong oan toan cua khang sinh/huyet

tng (mcg/ml)


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T ysodiet khuan: L athc o hieu lc khang sinh invivo; giup xac nh khanang diet khuan cua mot loaikhang sinh tai nong onh tr ong huyet tng vatr ongsuot thi gian cach lieu.

N ong othuoc trong huyet tng (mcg/ml)

Tysodiet khuan =

N ong oc chetoi thieu (mcg/ml)

T ysodiet khuan ln hn hoac bang 2 c xem

lagiatr mong i vadoan cotheloai tr het

vi khuan trong trlieu lam sang.



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Tysodiet khuan

M I C trung bnh cuacephalothin tren S. aureus la0,5 mcg/mlvacua cefazolin la1,0 mcg/ml. N h vay cephalothin cohoat tnhtren S.aur eus gap 2 lan cefazolin.

T ren thc te, Cmax/huyet thanh cua cephalothin sau mot l ieu 2g lakhoang 100mcg/ml . Tysodiet khuan cua thuoc tren S.aureus

sela100/0,5 = 200.

Khi I V lieu 1g cefazolin, Cmax/huyet thanh cua thuoc

khoang 200mcg/ml . Tysodiet khuan cua cefazol inla200/1 = 200. N h vay tysodiet khuan cua 2 thuoc

tng tnhau.

D o nong ocao hn tr ong mau cua cefazolin abutr

vao M I C 90 cua thuoc cao hn M I C 90 cua cephalothin.



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oc tnh chon loc: L aoc tnh lam ton hai en

quatr nh tong hp hoac chuyen hoa cua vi

sinh vat gay benh matebao ong vat cothe

dung nhan c.



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I I . PH AN L OA I K H ANG SI NH (T heo cau tr uc hoa hoc)1. N hom BE TA-LACTAM :

1.1. Phan nhom Penicill in.1.1.1. Benzylpenicillin:PNC G, procain-PNC, B enzathine-PNC

1.1.2. Phenoxypenicillin:PNC V

1.1.3. PN C khang penicillinase (chong tucau):Oxacil li n, Cloxacil li n

Dicloxacilli n, M ethicill in, Nafcill in1.1.4. A minoPNC :Ampicillin, Amoxicillin, bacampicillin,

Methampicillin

1.1.5. CarboxyPNC:Carbenicill in, Ticarcill in

1.1.6. Ur eidoPNC :Azlocillin, Mezlocillin, Piperacillin

1.1.7. C ar bapenem:I mipenem, Ertapenem, meropenem.

1.1.8. M onobactam: Aztreonam.

1.1.9. c chebeta- lactam ase:A cid clavulanic, Sulbactam


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1. N hom BE TA-L ACT AM :

1.2. Phan nhom Cephalosporin:

1.2.1. Thehe1: C ephalothin, Cephalexin, Cephalor idin,

C efatr izin, Cefapir in, Cefadroxil.1.2.2. Thehe2: C efuroxime, Cefuroxime acetyl, C efamandole,

Cefoxitin, Cefotetan, Cefmetazole.

1.2.3. Thehe3: C efotaxime, C efoper azone,

C eftr iaxone, C eftizoxime, M oxalactam,Ceftazidime, Cefixime, Latamoxef.

1.2.4. Thehe4: Cefpirome (Cefron), cefepim (Axepim).

I I . PH A N L OA I K H A NG SI NHT heo cau tr uc hoa hoc


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2. N hom AM I N OGL Y COSI D E (AM I N OSI D E ):

Streptomycin, Gentamicin, T obramycin, Amikacin, Netilmicin,F ramycetin, N eomycin, Sisomicin, Paromomycin, Kanamycin,

Dibekacin, Spectinomycin.

3.Nhom PH EN I COL:

Chloramphenicol, Thiamphenicol

4. N hom L I N COSAM I D E:

Lincomycin, Clindamycin.



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5. N hom M ACRO L I D E :

Erythromycin, Oleandomycin, Spiramycin, Josamycin,Azithr omycin, Roxithromycin, C lar ithr omycin.

6. N hom TE TRACY CL I N E :

T etr acycline, Oxytetr acycline, M ethacycline,

D oxycycline, M inocycline.

7. N hom khang sinh chong nam:

Nystat in, A mphoter icin B, G r iseofulvin,Flucytosine, K etoconazole, M iconazole,

Fluconazole, Clotrimazole...



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8. Cac nhom khac :

8.1. Cac QU I N OL ON E :

1.1. Kinh ien: F lumequin, Acid nal idixic, Acid oxolinic,

Acid pipemidic1.2. Thehe2 (Fluoroquinolone): Norfloxacin,Ofloxacin, E noxacin, Ciprofloxacin,

Rosoxacin, L omefloxacin, Sparfloxacin.

8.2. Cac N I TROI M I D AZOL E :M etronidazole, Ornidazole, Secnidazole,

T rinidazole, T ernidazole.



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8. Cac nhom khac :8.3. Cac dan xuat cua SU L F AN I LAM I D E (Sulfamide, sulfonamide):

8.3.1. T hai nhanh: Sulfafurazol, Sulfamethizol

8.3.2. T hai trung bnh: Sulfadiazine, Sulfamethopyrazin,

Sulfamethoxazole (trong co-tr imoxazole)8.3.3. T hai cham: Sulfadimetoxine, Sulfamethoxydiazin,

Sulfamethoxypyridazin.

8.3.4. T hai rat cham: Sulfadoxine (trong F ansidar )

8.3.5. t hap thu khi uong: Sulfaguanidin,Phtalylsulfathiazole, Sulfasalazin.

8.3.6. D ung ngoai: Sulfanilamid, Sulfacetamid.



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8. Cac nhom khac :

8.4. Cac GL YCOPE PT I D E :

Vancomycin, Teioplanin, Bacitracin.

8.5. Cac N I TROF U RAN :N itrofurantoin, N ifuroxazid, N ifuzid.

8.6. POL YM YX I N B vaCOL I ST I N .



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a. N hom c chestong hp vach tebao vi khuan:

C ac Penicillin vaC ephalospor in, C ycloser in, V ancomycin vaBacitracin.

b. N hom tac ong trc tiep len mang tebao cua vi sinh vat:

Polymixin, C olist in, cac Poliene khang nam, Nystat in,Amphoter icin-B, I midazole.

c. N hom anh hng len chc nang cac r ibosom cua

tebao vi khuan:

C hlor amphenicol, cac T etr acyclin, E r ythr omycin,

C lindamycin, cac Aminoglycoside.

I I . PH A N L OA I K H A NG SI NHT heo c chetac ong


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d. Cac tac nhan anh hng en schuyen hoa acid nucleic cua visinh vat:

R ifampicin, cac Quinolone.

e. Cac chat chong chuyen hoa:

T r imethopr im, cac Sulfonamide.

f. Cac chat ong dang cua acid nucleic.

I I . PH A N L OA I K H A NG SI NHT heo c chetac ong


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Can cvao tac dung ieu tr, cothechia khang sinhthanh 3 loai chnh:

Khang sinh khang khuan.

Khang sinh trnam.Khang sinh chong ung th.

I I . PH A N L OA I K H A NG SI NHT heo tac dung ieu tr


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Can cvao s lien quan gia nong ova

toc odiet khuan, chia khang sinh thanh:

Khang sinh phu thuoc nong o: T ac

ong diet khuan tang theo nong otr ongmau. V du: Aminoglycosid,

Fluoroquinolon.

Khang sinh phu thuoc thi gian: T ac

ong diet khuan khong tang theo nong

otrong mau. V dunhom beta- lactam.

I I . PH A N L OA I K H A NG SI NHD a vao dc lc dc ong (PK /PD )


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Tac dung sau khang sinh PAE (Post Antibiotic E ffect):

Cho V K tiep xuc vi KS trong mot thi gian ngan,

sau oloai KS khoi moi trng. Sphat trien trlai

cua V K cham tretrong mot khoang thi gian.

PAE latac dung c chesphat

trien cua V K khi nong ohuyet tng

cua khang sinh thap hn M I C,

tham ch khong con trong moi trng.



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Tac dung sau khang sinh PAE (Post Antibiotic E ffect):

KS coPAE keo dai: Aminoglycosid, Rifampicin,

F luoroquinolon, Glycopeptid, T etracyclin,

Azithromycin, F luconazol. N gay dung 1 lan.

KS coPAE ngan hoac khong coPAE,

ngay dung nhieu lan: Beta lactam,

Clindamycin, M acrolid ( trAzithromycin) .



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Cac thong soPK/PD doan hieu lc tac dung cua KS:

A U C / M I CCmax/M I C vaA U C / M I C

T > M I C(T hi gian [C ] /

mau ln hn M I C

T hong sodoan

AzithromycinClarithromycinTetracyclinFluconazol

AminoglycosidFluoroquinolonM etronidazolRifampicin.

Amphotericin B

Beta lactamM acrolidOxazolidinonClindamycin

K hang sinh

Phuthuoc thi gian.

PA E keo dai.

Phuthuoc nong o.

PA E keo dai

Phuthuoc thi gian.

PAE khong co

hoac ngan

T nh chatkhangkhuan


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K hang sinh cotac dung ngng tr ung hoac diet khuan theo mot

tr ong 4 c chechuyeu sau:

c chestong hp vach tebao vi khuan.

L am thay oi tnh tham cua mang tebao chat.

c chetong hp pr otein cua vi khuan.

c chetong hp acid nucleic.

I I I . C C H E T A C ONG C UA K H ANG SI NH


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I I I . C C H E T AC ONG C UA K H A NG SI NH3.1. C C H E ST ON G H P V A C H T E BA O V I K H UA N.

V ach tebao vi khuan (C ell -walls): Chiem 20% so vi trong lng khocuatebao, bao quanh mang bao tng.


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C au tr uc cua vach tebao vi khuan: M ucopept ide (M ur ein, Pept idoglycan)


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I I I . C C H E T AC ONG C UA K H ANG SI NH

3.1. C C H E ST ONG H P V AC H T E BAO V I K H UAN.

C au tr uc vach tebao vi khuan cua

Staphylococcus aureus


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I I I . C C H E T A C ONG C U A K H A NG SI NH

3.1. C C H E ST ON G H P V A C H T E BA O V I K H UA N.

Sinh tong hp Peptidoglycan gom 3 giai oan vi khoang 30 enzym:

Giai oan 1: Tao tien chat U ridindiphosphat (U D P) acetyl muramylpentapeptid. Cuoi giai oan lasthanh lap dipeptide: D -alan in-D -alanin vaotan cung etao thanh pentapeptid, vi sxuc tac cuaAlaninr acemase vaD -

alanin-D-alanin synthetase. Giai oan nay dien ra ben tr ong bao tng. Giai oan 2: Ket hp UD P acetyl muramyl pentapeptide va

U D P acetyl glucosamin thanh chuoi dai polysaccharide,

di xuc tac cuaTransglucosidase. Cuoi giai oan nay cac

day polysaccharide sedi chuyen ra ben ngoai mang bao tng. Giai oan 3: H oan tat noi ngang cua 2 peptidoglycan kecan.

Phan ng xay r a ben ngoai mang bao tng di sxuc tac

cua cacT ranspeptidase.


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I I I . C C H E T A C ONG C UA K H A NG SI NH


Sinh tong hp Peptidoglycan: 3 giai oan vi khoang 30 enzym GI AI OAN 1: Xay ra ben trong mang bao tng, tao UD P-acetylmuramin-pentapeptid.

M : acetylmuramic acid L-Lys: L- lysin

L-Ala: L -alanin D -Ala: D -alanin

D -Glu: D -glutamic

M M L-Ala

D-Glu

L-Lys

ML-Ala

D-Glu

L-Lys

D-Ala

ML-Ala

D-Glu

L-Lys

D-Ala

D-Ala

L-Ala

D-Glu

L-Lys

D-alanin-D-alanin

synthetaseAlanin

racemase

D-Ala D-Ala


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Sinh tong hp Pept idoglycan Giai oan 2: T ao chuoi dai polysaccharide.

G M

L-Ala

D-Glu

L-Lys

D-Ala

D-Ala

M

L-Ala

D-Glu

L-Lys

D-Ala

D-Ala

G

G

ML-Ala

R

M

L-Ala

D-Glu

L-Lys

D-Ala

D-Ala

G

G

ML-Ala

R

+

-[Gly] 5

Glycyl-tRNATransglucosidase

M : Acetylmuramic acid

G: N -acetyl-glucosamin

[G ly]5: Pentaglycin

D i chuyen r aben ngoai mang

bao tng


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3.1. C C H E ST ON G H P V A C H T E BA O V I K H UA N. Sinh tong hp Peptidoglycan.

Giai oan 3: Xay ra ben ngoai mang bao tng.

M

L-Ala

D-Glu

L-Lys

D-Ala

D-Ala

G

G

M

L-Ala

R

[Gly]5

M

L-Ala

D-Glu

L-Lys

D-Ala

D-Ala

G

G

ML-Ala

R

[Gly]5

G

G

M

L-Ala

R

M

L-Ala

D-Glu

L-Lys

D-Ala

[Gly]5

M

L-Ala

D-Glu

L-Lys

D-Ala

D-Ala

G

G

ML-Ala

R

[Gly]5

Transpeptidase

D-Ala


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Sinh tong hp Pept idoglycan: hnh thanh li peptidoglycan cua vach tebao.


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C chetac ong:

Cac thuoc: Cac PN C vaCephalosporin, Bacitracin, Ristocelin,Cycloserine vaV ancomycin.

Gom cac bc:

Gan ket cac khang sinh len cac receptor cua notren tebao vikhuan, thng lacac protein c goi chung la

Penicillin B inding Protein (PBP).

N gan chan stong hp peptidoglycan nhng

giai oan khac nhau.

H oat hoa cac enzym thuy trong vi sinh vat,

gay phan huy tebao vi khuan.


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V tr tac ong cua cac khang sinh tr en sc chetong hp vach tebao vi k huan

CacPN C, C ephalosporinc chemen T ranspeptidase.

Cycloserine(chat ong dang cua D -alanin) c cheenzym

Alanine racemase.

Vancomycinngan chan stach ra khoi mang

bao tng cua tien chat peptidoglycan.

Bacitracin, Ristoceinc cheTransglucosidase

trong nhng bc tong hp au tien

peptidoglycan.


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I I I . C C H E T A C ONG C UA

K H A NG SI NH3.1. C C H E ST ON G H P

V A C H T E BA O V I K H UA N.

V tr tac ong cua cac

khang sinh tr en s c chetong hp vach te bao vikhuan.


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I I I . C C H E T A C ONG C UA

K H A NG SI NH3.1. C C H E ST ON G H P

V A C H T E BA O V I K H UA N.

V tr tac ong cua cac

khang sinh tr en s c chetong hp vach te bao vikhuan.


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T nh nhay cam cua vi khuan oi vi cac thuoc khang sinh th phuthuoc vao: L p pept idoglycan hnh thanh.


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T nh nhay cam cua vi khuan oi vi cac thuoc khang sinh th phuthuoc vao:

Shien dien cua cac PBP, cac por ins, lp lipid oi phan t.


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Tnh nhay cam cua vi khuan

oi vi cac thuoc khang sinh thphuthuoc vao:

S hien dien cua Beta-lactamase.


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T nh nhay cam cua vi khuan oi vi cac thuoc khang sinh th phuthuoc vao:

Ban chat cua lien ket ngang. H oat ong cua cac hethong enzym thuy.

Cac yeu tonay sequyet nh: H oat tnh khang khuan cua dc pham. Phokhang khuan cua thuoc.

Sekhang cua vi khuan oi vi khang sinh.


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Cac yeu toquyet nh tac dung cua thuoc:


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I I I . C C H E T AC ONG C UA K H A NG SI NH3.2. T H A Y OI T NH T H A M C UA M A NG T E BA O C H A T .

Cac tac nhan

nhom nay gom:

Amphotericin-B,

Colistin,

Nystatin,

Polymyxins.


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I I I . C C H E T AC ONG C UA K H A NG SI NH3.2. T H A Y OI T NH T H A M C UA M A NG T E BA O C H A T .


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I I I . C C H E T AC ONG C UA K H A NG SI NH3.3. C C H E T ONG H P PR OT E I N C UA V I K H UA N.

Cac khang sinh nhom nay gom: cac Aminoglycoside,Tetracycline, M acrolide, Chloramphenicol, Lincomycin.

T ebao vi khuan coRibosome 70S gom 2 subunits la50S va30S.


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Sinh tong hp protein cua tebao vi khuan gom cac giai oan:

T ao phc khi au Amino acyl tR NA.

T ao f-meth-tRN A 70S.

G iai oan keo dai hnh thanh chuoi pept id.


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I I I . C C H E T A C ONG

C UA K H A NG SI NH3.3. C C H E T ONG H P

PROT E I N C UA V I

K H UA N.

Sinh tong hp proteincua tebao vi khuan.


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T ac ong cua khang sinh: C ac Aminoglycosie

c chetac ong cua phchp khi au mR NA-f-meth-tRNA.

K et hp vi r eceptor chuyenbiet tr en tieu n v30S gaybien dang r ibosom, lam oc saima, tao cac pr otein khong hoat

tnh. L am t oan cac polysomesthanh monosome.


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T ac ong cua khang sinh: C ac T etr acyclin

c chesconhaminoacyl-R NA t tai tr ung tamA cua r ibosom 30S, ngan channg vao cua cac tR NA comang goc aminoacyl, dan enkhong a c acid amin mivao chuoi pept id ang thanh

lap.


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3.3. C C H E T ONG H P PR OT E I N C UA V I

K H UA N.

T ac ong cua khang sinh: Chloramphenicol

G an vao r ibosom 50S c che

pept idylt r ansfer ase, nen ngan chan sket hp cua mot acid amin mi vaochuoi pept id noi sinh ang thanh lap.


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3.3. C C H E T ONG H P PR OT E I N C UA V I

K H UA N.

T ac ong cua khang sinh:

C ac M acrolide vaL incosamid

G an vao r ibosom 50S, can thiep phanng chuyen vaminoacyl t tr ung tamA sang tr ung tam P.


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C UA K H A NG SINH

3.3. C C H E T ONG H PPR OT E I N C UA V I K H UA N .

Sinh tong hp proteincua tebao vi khuan vatac ong cua khangsinh.


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C UA K H A NG SINH

3.3. C C H E T ONG H PPR OT E I N C UA V I K H UA N .

Sinh tong hp pr oteincua tebao vi khuanvatac ong cua

khang sinh:

1 & 5: Streptomycin vacac aminoglycosidekhac.

2: Tetracyclin.3: Chloramphenicol.

4: Erythromycin,Clindamycin.


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I I I . C C H E T AC ONG C UA K H A NG SI NH3.4. C C H E T ONG H P A C I D NUC L E I C C UA T E BA O V I K H UA N.

Cac khang sinh nhom nay gom: cac Quinolone, Novobiocin,Rifampin, Pyrimethamine, T rimethoprim, cac Sulfonamide.

Phan tD N A cokhanang:

D NA D NA mi

D N A polymerase

ProteinmRNA

Giai maT nhan oi Sao ma

RNA polymerase


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T ac ong cua khang sinh: C ac Quinolone

Phong toa D NA gyrase, ngan chan smxoan cac day oi D NA .


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Tac ong cua khang sinh: C ac Sulfamid

c checanh tr anh vi PA BA , ngan chanstong hp acid folic.

Tac ong cua khang sinh:Trimethoprim.

Pyrimethamine

c cheenzym dihydr ofolate r eductase,ngan chan stao thanh acid folinic.


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T ac ong cua khang sinh: Rifampin, Actinomycin.

c cheR NA polymer ase,ngan chan stao thanh R NA .


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I I I . C C H E T AC ONG C UA K H A NG SI NHDNA dang vong xoan

DNA dang mvong

DNA

mRNA

Phc hp khi au 30S

K eo dai day peptid

Thanh lap noi peptid

DNA gyrase

Phc hp khi au 70S

RN A polymerase

Peptidyltransferase

DNA polymerase

E R Y T H R O M Y C I N , C L I N D A M Y C I N

C H L O R A M P H E N I C O L

A MIN O G L Y C O S ID

R I F A M P I N

QUINOLON

Ribosom 30S

Ribosom 50S

V T R TAC ON G CU A CAC TH U OC C CH ETO NG H P P ROT EI N V AACI D N U CL E I C


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I I I . C C H E T AC ONG C UA K H A NG SI NH


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I V . S E K H A NG K H A N G SI NH C UA V I K H UA N

4.1. CA C D A NG E K H A NG

ekhang gia: H ethong mien dch cua c thebsuy yeu. V i khuan trang thai ngh. Khang sinh khong en c oviem.


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ekhang that:1. ekhang tnhien: M ot sovi k huan khong boi vi mot vai khang sinh:

E scherichia coli vi erythromycin .T ucau vi colistin.Pseudomonas aeruginosa vi PN G.

V i khuan khong covach tebao nh M ycoplasmasekhong btac dung cua nhom khang sinh

c chetong hp vach tebao.


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ekhang that:2. ekhang thu c:

D o bien covedi tr uyen, vi khuantchokhong cotr nen comang

gen ekhang.2.1. ot bien gen: ot bien mot bc. ot bien nhieu bc: L ien quan

en nong okhang sinh.2.2. N han gen ekhang: cac genekhang cothenam tr en nhiemsac the, plasmid hay tr ansposon.

ot bien gen

Nhan gen ekhang


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ekhang that:

2. ekhang thu c:

2.2. Nhan gen ekhang:

T iep hp (Conjugation). Bien nap hay chuyen the

(Transformation).

T ai nap hay chuyen nap

(Transduction ).


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4.2. C C H E K H A NG T H U OC

T ao r a cac enzym lam bienoi hoac phahuy i cau tr uc cuathuoc. L am thay oi t nh tham qua

mang tebao vi khuan cua thuoc. T hay oi cac cau tr uc chac hieu cua thuoc tr en tebaovi khuan.

Phat tr ien quatr nh chuyenhoa qua mot ngakhac. Phat tr ien enzym van conchc nang chuyen hoa nhng tnhay cam hn vi thuoc.


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4.2. C C H E K H A NG T H U OC


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4.3. S E K H A NG C H E O (C R OSS-R E SI ST A NC E )

nh ngha:V i sinh vat ekhang vi mot khang sinh nao ocothesee

khang vi cac khang sinh khac cocung c chetac ong.

C ach han che: D uy tr nong okhang sinh cao tr ong mo. C hphoi hp cac khang sinh khong coekhang cheo. T r anh dung khang sinh ac hieu neu vi khuan

van con nhay cam vi khang sinh thong thng. T r anh gieo r ac mam benh vaboi nhiem.


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4.4. Y NG H A L A M SANG C UA S E K H A NG T H U OC

ekhang colien quan mat thiet en sdung thuoc.

ekhang do plasmid: detao khanang chon loc tat cacac

gen ekhang nam tr en plasmid.

V i khuan ekhang khotr lieu khi gay thanh dch, benh. G ay nhiem khuan benh vien:

Staphyloccus aureus khang M ethicillin va

Gentamicin.

T r c khuan ng r uot khang gentam icin. P. aer uginosa khang gentamicin.


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4.5. BI E N PH A P H A N C H E SG I A T A NG T NH K H A NG T H UOC

C hdung khang sinh ieu tr khi nhiem khuan.

L a chon khang sinh hp ly.

C hon khang sinh khuyech tan tot nhat vao onhiem khuan.

Phoi hp khang sinh hp ly, nhat lakhi ieu tr keo dai. G iam sat tnh hnh ekhang.

C hutr ong cac bien phap khkhuan vavokhuan.


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V . TA C D UNG PH UV A OC T NHT H NG G A P M OT SOK H A NG SI NH

C ac tac dung khong mong muon thng gap: Phan ng quaman.

oc tnh tr c tiep.

Boi nhiem do cac vi sinh vat ekhang.


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V . TA C D UNG PH U V A OC T NHT H NG G A P M OT SOK H A NG SI NH

N H OM BE T A-L ACT AM D ng:

C hoang phan ve(PN C )

Ngoai da: nga, may ay

(Ampicillin) Benh vehuyet thanh: sot, lach to,

giam bach cau, viem khp.

L oan khuan r uot

Benh nao cap: co c, hon me(tr uyenPN C lng ln, Oxacill in lieu cao)

T ai bien vemau: ban o, xuat huyet.

G ay viem than: M ethicill in, cephalospor in.


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NH OM AM I N OGLY COSI D E R oi loan thnh giac, tr en tien nh

vaoc tai. oc tnh gia tang ngisuy than, ngi gia, dung lieu cao va

lau dai. Ton thng tr en tai khonghoi phuc.

oc tnh tren than: H oi phuc,nhng chc nang than giam lamgiam bai tiet thuoc, gay tch tr thuoc, tao oc tnh khong hoi phuctr en tai.


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N H OM T E TRACY CL I N E T ch tr tr ong lach, t uy xng, ngarang,

men r ang, qua nhau thai vavao sa me.

L ang ong tr en moahoa voi (xng, r ang),

lam thay oi mau r ang. G ay r oi loan tieu hoa, gay boi nhiem vi

khuan, nam, dan en gay viem r uot giamac.

oc tnh tr en gan, nhat laphunmang thai.

R oi loan chc nang than. L am da nhay cam vi anh sang

G ay huyet khoi khi tiem tr uyen tnh mach,gay au tai chotiem bap.


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N H OM TE TRACY CL I N E


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V . T A C D UNG PH UV A OC T NH T H NG G A P M OT SOK H A NG SINH

N H OM L I N COSAM I D E G ay viem r uot ket giamac.

T ieu chay.

Buon non.

Ban oda.

N H OM PH EN I COL

T ai bien vemau: Suy tuy gay thieu

mau, thieu mau bat san. H oi chng xam: tr es sinh.

Chlostridium difficile


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V . T A C D UNG PH UV A OC T NHT H NG G A P M OT SOK H A NG SI NH

N H OM QU I N OL ON E G ay r oi loan tieu hoa vathan kinh (ao giac,

lulan, co giat).

K hong sdung cho tr eem, phu nmang

thai hoac cho con bu. K hong dung cho benh nhan di 18 tuoi.


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NH OM SU LF ON AM I D E

M an cam: T on thng tr en da vaniem mac(H oi chng Stevens-Johnson), sot, k ho thdang hen.

T hieu mau tan huyet cap, giam vamat bachcau.

G an: gay vang da.

R oi loan than kinh, tieu hoa vatiet nieu.


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NH OM SU LF ON AM I D E M an cam: T on thng tr en da vaniem mac (H oi chng

Stevens-Johnson).


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V I . NH NG OI T NG C A N T H A N T R ONG K H I SD UNG T H UOC

N gi giacao tuoi.

N gi coc a suy giam mien dch, c thesuy nhc.

N gi ang mac cac benh man tnh tai cac phutang

quan trong. Phunmang thai vacho con bu.

Treem.


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M ot sobenh khong c dung khang sinh:

Luput ban o: cac PN C, tetracycline, I N H .

Thieu G 6PD : chloramphenicol, cac sulfamide, cac

quinolone. Suy than vasuy tim: cac khang sinh

cha nhieu natr i.


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V I . NH NG OI T NG C A N T H A N T R ONG K H I SD UNGT H UOC

D ung khang sinh khi cothai:

Cac Aminoglycoside

Amphotericin B

Clindamycin

Ethambutol

INH

Rifampin

VancomycinTrimethoprim

Ketoconazole

Miconazole

Chloramphenicol

Dapson

Griseofulvin

Cac Quinolone

Cac sul famide

Cac tetracycl ine

Co-trimoxazoleCac Nitro-imi dazole

Nitrofurantoin

Mefloquine

D ung than tr ongC am dung


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Cac khang sinh qua c tuyen vungi evao sa:

Gentamicin

Primaquin

Erythromycin

M ot sosul famide

INH

Pyrimethamin

Benzyl-PNC

Ampicillin

Cac cephalosporin

Cac tetracycl ine

Metronidazole

Chloramphenicol

Streptomycin


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M ot sokhang sinh dung than trong ngi gia: CarboxyPN C, fosfomycin: degay giam Kali huyet.

PN C lieu cao: gay cn ong kinh lan toa, giat c.

N hom aminoglycoside .

Chloramphenicol, r ifampicin: han chesdung.

M etronidazole: giam lieu.

Cac thuoc chong lao.

.


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D ung r at than trong ngi suy than:Ciprofloxacin

Co-trimoxazole

Ethambutol

GentamicinINH

Kanamycin

Lincomycin

Methicillin

Netilmicin

Penicil l in G, V

Piperacillin

Pyrazinamide

Streptomycin

Sulfamide

TobramycinThiamphenicol

Vancomycin

Norfloxacin

Ofloxacin

Amikacin

Ampicillin

Amoxicillin

CarbenicillinCefamandole

Cefurox im (tiem)

Cefotaxime

Ceftriaxone

Cephalexin

Cefazolin

Clindamycin


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N gi suy gan:

Khong dung: Sulfamide, tetracycline, l incomycin ,clindamycin, nhom quinolone lieu cao.

N eu covang da, khong dung: chloramphenicol, acidnalidixic, sulfamide.

Than trong: erythromycin, mot sothuoc

chong lao.


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V I I . NG UY E N T AC SD UNG K H A NG SI N H

Sdung khang sinh ba bai dan en:

L an rong snhay cam vi thuoc tr ong cong ong.

L am vi khuan khang thuoc phat tr ien manh.

Khoa lap i nhng dau hieu nhiem trung nang.

Gay hieu ng phubat li. L am gia tang tnh trang khang thuoc trong quan the.

K hang sinh tr thanh tac nhan chon loc tieu diet

cac vi khuan nhay cam, tao dong vi khuan

ekhang vi chnh no.


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Nhng nguyn nhn tht bi trong vic dng khng sinh:Chn khng sinh khngng phtc dng.

Khng sinh khng t c ti ngng tc dng ti

nhim khun do:

Liulng khng hp l.

Dcng hc ca thuc khng thch hp.

Tngtc thuc lm gim tc dng

ca khng sinh.Do vi khun khng thuc.


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AN T OA N, H P L Y

M uc ch:

ieu tr hieu qua T ranh tao chung vi khuan ekhang thuoc

T ranh nhng tac dung cohai cua khang sinh

H agiathanh trlieu


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AN T OA N, H P L Y

Nguyen tac:

Chdung khang sinh khi bnhiem khuan Phai chon ung khang sinh

Biet chon dang thuoc thch hp

Phai sdung ung lieu lng

D ung khang sinh ung thi gian qui nh Sdung khang sinh dphong hp ly

Chphoi hp khang sinh khi that can thiet


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Chdung khang sinh khi bnhiem khuan

C ac khang sinh chcotac dung vi mot soloai vikhuan nhat nh.

T r c khi sdung, can lam cac bc sau:

T ham kham lam sang.

C ac xet nghiem lam sang thng qui.

T m vi khuan gay benh: khang sinh o.

C hnh theo photac dung. Neu nhiem khuanaxac nh, dung khang sinh phohep.


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L a chon khang sinhD a vao c s:

Onhiem khuan vavt r nhiem khuan.

V i khuan gay benh.

T nh tr ang benh nhan: Benh nang hay nhe.

T uoi.

T hi kymang thai-cho con bu.

C hc nang gan, than.

T ien s: dng, ekhang, di tr uyen.

K hang sinh: D cng hc ca thuc.


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V I I . NG UY E N T AC SD UNG K H A NG SI N H Cac vi khuan gay benh.

V du:

-V iem phequan-V iem phoi-V iem mang nao (ngi ln vatr eem )-V iem hong hau xoang

Streptococcuspneumoniae(Pneumococcus)

-Nhiem tr ung huyet-V iem mang nao (t r es sinh)-Nhiem tr ung do say thai

-V iem mang tr ong tcung

Streptococcus tan mau

-Nhiem tr ung da vamomem, viem xng tuy,nhiem tr ung huyet.-V iem khp cap do vi khuan-V iem mang tr ong tim cap

C au khuan G r am(+)Staphylococcus aur eusK hong tiet penicill inaseT iet penicillinase

BenhV i khuan hieu kh


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V I I . NG UY E N T AC SD UNG K H A NG SI N H Cac vi khuan gay benh

V du:

-Benh bach hauCorynebacteriumdiphtheriae

-Benh l au

C au khuan G r am(-)

N eisseria gonorr hoeae(Gonococcus)

-V iem mang nao (ngi ln vatreem)

-Nhiem khuan huyet

N eisseria meningiditis(M eningococcus)

-Ton thng than kinh (viem mang nao)-Nhiem trung huyetListeria monocytogens

-Benh than

T r c khuan G r am(+)Bacillus anthracis

BenhV i khuan hieu kh


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La chon khang sinh

CiprofloxacinCeftriaxon

Cefotaxim

Minocyclin

Penicillin-G

Rifampicin

V iem mang naoC au khuanGr( - )Neisseriameningitis

Clindamycin

Erythromycin

Trimethoprim+Sulfamethoxazol

Ciprofloxacin

+ Rif ampicin

Cephalosporin 1

Vancomycin

Oxacillin

Nafcilin

Abces

Nhiem khuanhuyet

V iem noi tammac

V iem phoi V iem

xng-tuy

C au khuanGr(+ )Tucau vang

ThbaThhaiThnhat

T huoc c chonBenhV i khuan


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La chon khang sinh

Aztreonam

Nitrofurantoin

Doxycycline

PNC+ c chemen PNCase

Aminoglycoside

TM P- SM Z

Ciprofloxacin

Ampicillin+

Aminoglycoside

Nhiem khuantiet nieu

Nhiem khuankhac

T r c khuanGr( - )

Escheria coli

Cephalosporin 1

Rifampicin

ClindamycinErythromycinV iem hongV iem phoiV iem thanhphequan

T r c khuanGr(+ )Corynebacterium

ThbaThhaiThnhat

T huoc c chonBenhV i khuan


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L a chon dang khang sinh thch hp Sdung ung lieu lng

Sdung ung thi gian qui nh

T ao c nong oieu tr hieu qua

T r anh c sekhang thuoc cua vi khuan gay benh


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L a chon dang khang sinh thch hp- C n cvao v tr nhim khun vamc nhim khun chn dng thuc.

- H n ch sdng khang sinh ti ch.

C h dung khi nhim khunmt. i vi nhim khun ngoai da nen

dung thuoc sat khun: con etylic,

con iod, polyvidone iod, thuoc o,

thuoc tm, clor hexidin, cetr imide.


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Phai sdung ung l ieu lng.- D ung ngay khang sinh lieu ieu tr can thiet.

- D ung ulieu eat nong ouvaon nh.

- K hong bat au tlieu nhor oi tang dan lieu.

- ieu tr lien tuc, khong ngat quang hoac ngng otngot.

- K hong giam lieu ttetr anh ekhang thuoc.


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D ung khang sinh ung thi gian qui nh.

-T hi gian sdung thuoc phuthuoc vao nhieu yeu to:

-T nh tr ang nang nhecua benh nhan.

-T ac nhan gay benh.

-Ni nhiem tr ung.-T nh tr ang hemien dch cua benh nhan.

- Nguyen tac chung: sdung khang sinh enhet vi khuan tr ong c the+ 2-3 ngay ngi

bnh thng; hoac + 5-7 ngay ngi suygiam mien dch.

- Sau 2 ngay dung khang sinh, sot khong giamth can thay hoac phoi hp khang sinh.


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Sdung khang sinh dphong hp ly

Nham:

Ngan chan snhiem tr ung.

Sdung lai khi codau hieu nhiem tr ung tai phat.

T hng chnh phong nga tr ong cac tr ng hp:

T iep xuc vi cac tac nhan gay benh

Benh nhan conguy c nhiem tr ung cao

T r ong phau thuat

T heo nguyen tac: T hi iem cho thuoc vang cho thuoc ung

L a chon khang sinh ung, theo loi phau thuat.

odai cua t ieu tr .


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Phoi hp khang sinh khi that can thietNham:

ieu tr nhiem khuan do nhieu loai vi khuan.

T r ong benh nang cha r onguyen nhan.

T ao sc manh hp ong khang khuan. Ngan nga vi k huan phat tr ien dong

khang thuoc.

G iam oc tnh do dung lieu cao hay dai ngay.


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Phoi hp khang sinh khi that can thietBat li:

T ao tam lyan tam cho ngi thay thuoc,khong con tch cc tm kiem tac nhan gay

benh.T ang tac dung phucua khang sinh.

T ang chi ph ieu tr .

Nen han chephoi hp v acokhang sinh phor ong.

T ot nhat latm r a tac nhan gay benh echsdung mot khang sinh manh nhatvahieu quanhat.


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Phoi hp khang sinh khi that can thietK hi phoi hp khang sinh phai:

at c hieu quahp ong. V du:

PN C + A minoglycoside

T r imethopr im + Sulfamethoxazole A ci clavulanic+ A moxicillin (Augmentin).

K hong phoi hp cac khang sinh gay hieu quaoi khang nhau. V du: T etr acycline vaPN C .

T r anh phoi hp cac khang sinh coekhangcheo, gay tac dung oc tr en cung mot cquan.


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Phoi hp khang sinh khi thatcan thiet

K hi phoi hp khang sinh phaiat c hieu quahp ong.

V du:PN C + A minoglycoside


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Phoi hp khang sinh khi that can thietK hi phoi hp khang sinh phai at c hieu quahp ong.V du:

T r imethopr im + Sulfamethoxazole


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Phoi hp khang sinh khi that can thiet

K hi phoi hp khang sinh phai at c hieu quahp ong. V du:

Sulbactam + A mpicillin (U nasyl).


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K hi phoi hp khang sinh phai:

K hong phoi hp cac khang sinh gay hieu quaoikhang nhau. V du:

T etr acycline vaPNC .

E r ythr omycin,lincomycin, Chlor amphenicol.

G entamicin bmat hoat tnh bi PNCkhi tr on chung tr ong tiem tr uyen tnh mach.

T r anh phoi hp cac khang sinh coekhangcheo, hoac gay tac dung oc tr en cungmot c quan.


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Nguyen tac phoi hp khang sinh:

Nam 1952, Jawetz neu nguyen tac phoi hp khang sinh, theookhang sinh c chia lam 2 nhom ln theo tac dung:

Nhom I : K hang sinh cotac dung khang khuan, gom:

Beta-lactam. Polypeptid.

Aminosid. V ancomycin.

Nhom I I : K hang sinh cotac dung km khuan, gom:

T etracyclin. M acrolid.Chloramphenicol. Lincomycin.

Sulfamid.


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V I I . NG UY E N T AC SD UNG K H A NG SI N H Phoi hp khang sinh khi that can thiet

Nguyen tac phoi hp khang sinh:

Phoi hp cac khang sinh tr ong nhom I vi nhau secotacdung cong hoac boi tang.

Phoi hp cac khang sinh tr ong nhom I I chcotac dung cong.

Phoi hp khang sinh tr ong nhom I + nhom I I secotac dungoi khang. V du:

-Leper vaD owl ing (1951), tren viem mang naodo phecau khuan: ieu tr chPN C, tvong la21%;khi phoi hp PN C lachlotetracyclin, tvong la71%.

- M athies et al. (1967), ieu trviem mang nao dotrc khuan thay: neu dung ampicillin mot mnh,tvong la4,3%; khi phoi hp ampicillin vichloramphenicol vastreptomycin th tvong la10,5%.

VIII CC KHNG SINH CHNH


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VIII. CC KHNG SINH CHNH1. Nhm Beta-lactam

VIII. CC KHNG SINH CHNH


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VIII. CC KHNG SINH CHNH1. Nhm Beta-lactam

V ecau tr uc eu covong beta-lactam.D a theo cau tr uc hoahoc, c chia lam:

Cac penam: gom cac penicillin.

Cac cephem: gom cac cephalosporin.

Cac penem: gom imipenem, ertapenem.

Cac monobactam: khang sinh tong hp nh aztreonam.



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VIII. CC KHNG SINH CHNH1. Nhm Beta-lactam-Cc penicillin.

C hot tnh viStaphylococcusaureus vS. epidermidis tit-lactamase khng khng methicillin.

Khng c hot tnh viListeriamonocytogenes vEnterococcus spp.

KmTt

Thayi

PNC phrt hp

(PNC khng PNCase)

-Methicillin-Oxacillin,Dicloxacillin.

-Nafcillin

Tt trnstreptococci, enterococci,Listeria, N.meningitidis.

Rt tt vi vi khun k kh (trB.fragilis). t tc dng trntrc khunGr(-) v vi khun tit-lactamase.

Km

PNC phhp (tnhin)

BenzylPNC (PNC G)

Ph khng khunHp thuqua rut

Loi Penicillin



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Penicillin G- c Fleming tm r a au tien nam 1928, tnamPenicillium

notatum hayP . chrysogenum.

-1 m l m oi tr ng nuoi cay cho 300UI ; 1UI = 0,6 g Na benzylPNC .

-D ung dch nc chben pH =6-6,5, mat tac dung nhanh pH 7,5.

-Phokhang khuan:

+ Cau khuan Gr(+): Strep., phecau vatucau

khong tiet PN Case.+ Cau khuan Gr(-): lau cau, mang nao cau.

+ T rc khuan Gr(+) ai kh vayem kh.

+ X oan khuan: Treponema pallidum (giang mai).




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Penicillin G-D c ong hoc:

+ H ap thu: bdch vphahuy nen khong uong c. C max at c

15-30 phut khi I M , nhng giam nhanh (can tiem 4 gi/ lan).

+ Phan phoi: 40-60% gan vi pr otein huyet tng. K hovao xng vanao, nhng khi mang nao viem, [c] /dch nao tuy bang

1/10 huyet tng. T 1/2=30-60 phut ngi bnh thng.

+ 60-70% thai tr qua than dang khong con hoat tnh.

90% cua lng thai tr labai xuat qua ong than. Pr obenecid

c chequatr nh nay, lam cham thai tr PN C .- oc tnh: t oc, nhng tylegay dng khacao (1-10% ),

C othegay tvong do choang phan ve.

-C odng cheo vi moi bet a-lactam vacephalospor in.




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Penicillin V , uong (Or acillin, Ospen)K hong bdch vphahuy, hap thu tatr ang, nhng phai dung lieu gap

oi PN G mi at c nong ohuyet thanh tng ng. D ung cach 6h/

lan.

PN C khang Penicillinase hay PN C ban tong hp:Phokhang khuan vathi gian tac dung tng tPNG ,

nhng cng otac dung yeu hn.

+ M ethicillin: I M hoac I V 2-8g/24h, chia lam 4 lan,

khong uong c.

+ Oxacillin (Br istopen), C loxacillin (Or benin):

ben vi dch v, dung uong.

C hnh: Nhiem khuan do tucau san xuat PNC ase.

C othegay viem than ke, c chetuy xng lieu cao.




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Tthn PNC trnListeriamonocytogenes vEnterococci nhycm.

Mrng ph trn vi khun Gr(-):E.coli, Proteus mirabilis, Salmonella,

Shigella, Haemophilus influenzae,

Helicobacter pylori.

Thng phi hp vi clavulanat hoc

sulbactam.B thy gii bi-lactamase

Dngng ung.

Tt

Rt tt

PNC phrng

(AminoPNC)

-Ampicillin

-Amoxicillin

-Bacampicillin

Ph khng khunHp thuqua rutLoi Penicillin




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Penicillin cophor ongL aPN C ban tong hp, aminoPN C .K hong bdch vphahuy, uong c nhng hap thu khong hoan toan

(khoang 40% /v ampicil lin; A moxicillin cotylehap thu qua ng

uong cao, khoang 90% ).

M etam picil lin , Bacampicil lin, khi uong bthuy phan giai phong

ampicillin.

C hnh chnh:viem mang nao mu, thng han, nhiem

khuan ng mat, t iet nieu.




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Penicillin khang tr c khuan muxanh (Pseudomonasaeruginosa):L aPNC ban tong hp, coac iem:

+ T ac dung tr en cau khuan G r (+) kem hn A mpicillin.

+ ac biet tac dung tr en tr c khuan muxanh vamot sochung san xuat

cephalospor inase (Enterobacter, Proteus).

C hnh chnh:nhiem khuan G r (-) nang akhang vi am picil lin

hay C ephalospor in, nhiem khuan khung chau, tr ong obung.

G om co:

+ Nhom car boxyPNC (S c thay thebang C ):C ar benicillin, I V , t1/2= 2 gi.

+ Nhom Ur eidoPN C : T ham nhap vao motot hn.

C hcodang I M hoac tr uyen tnh mach. t 1/2=1-2 gi.




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VIII. CC KHNG SINH CHNH1. Nhm Beta-lactam-cc cephalosporin

-Nhim trng nhng tiu, nhimtrng da hoc m

mm dostaphylococci hocstreptococci.

-Cefazolin l thucla chn phng nga

trong phu thut, thayth chotrng hp dng vi PNC khinhim staphylococcihoc streptococci

Ph hp, nhy cm vi-lactamase.

Gr(+): hu ht cu khun

gram(+), tr enterococci vMRSA.

Gr(-):E.coli, K. pneumoniae,P.mirabilis, M. catarrhalis.

Cu khun k kh:Peptococcus,

Peptostreptococcus.

Thh 1

Dng ung:

-Cephadroxil

Dng ung v tim

-Cephradin

Dng tim

-Cephalothin

-Cephapirin-Cefazolin

Ch nhPh khng khunLoiCephalosporin



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-Nhim H.influenzaenh vim tai gia,vim xoang, vim

phi thu nhn cngng.

-Cefoxitin,cefmetazol, cefotetanthay th Cefazolin

phng nga trongphu thut.

- Khng tr nhimEnterobacter vkhng.

-Gr(+): nh th h 1, nhngkmhn.

-Gr(-): Mrnghn th h 1,

Enterobacter spp, Proteusindol(+), Klebsiella spp.

--fragilis nhy cm vicefoxitin, cefmetazol,cefotetan.

-Khng tc dng viEnterococci v Pseudomonas.

Thh2

Dng ung:

-Cefaclor

-Cefuroim axetil

Dng ung v tim

-Cefuroxim

Dng tim

-Cefoxitin-Cefamandol

-Cefmetazol

-Cefotetan


VIII. CC KHNG SINH CHNH1. Nhm Beta-lactam-cc cephalosporin



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-Tr nhim trng nng khngcepha. khc, AG, PNC.

-Thuc la chn nhimKlebsiella, Enterobacter

-Tr lu.

-Vim mng no domeningococci, pneumococci,

H. influenzae, Pseudomonas.

-Vim phi thu nhn cngng doH.influenzae,S.aureus.

-Nhim trng da, h hp,ng tiu, xng khp,mu, mt, vim mng trongtim, bng vng chu, sn

ph khoa

-Ph mrnghn th h 2 trnvi khun Gr(-). Khng hu ht-lactamase.

-Gr(+): Kmhn th h 1.

-Gr(-): mrngn hu htEnterobacteriaceae, c hot tnhtt viHaemophillus vNeisseria tit-lactamase,Pseudomonas.

-Vi khun k kh:-fragilis

-Khng c hot tnh tin cy vienterococci, C.difficile, L.

monocytogenes

Thh3-4

Dng ung:

-Cefixim

-Ceftibuten

-CepodoximDng tim

-Ceftriaxon

-Cefotaxim

-Ceftazidim

-CefoperazonMoxalactam

Cefepim (th h 4)

Ch nhPh khng khunLoi Cephalosporin

V C C NG S N C N1. Nhm Beta-lactam-cc cephalosporin



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-Tr nhim trng bnhvin do vi khun Gr(-),

Enterobacteriaceae,

Pseudomonas.

-Tng t ceftazidim, chngcEnterobacteriaceae vPseudomonas, c hot tnh

caohnstreptococci,Enterobacter, MSSA.

-Thm tt qua no.

Thh4

Cefepim


1. Nhm Beta-lactam-cc cephalosporin



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1. Nhm Beta-lactam

+

--

+ +

+ ++

+

+ +

+ +

+

+ +

+ ++

Imipenem

MeropenemErtapenem

Acinetobacter

Gram (-)hiu kh

Gram(+)

Pseudomonas

Mt hot tnh bidihydropeptidase

( ng thn)

Ph khng khunCARBAPENEM

Imipenem:

khng cao vi hu ht Beta-lactamase.

Mt hot tnh bi dihydropeptidase ng thn, thngc phi hp vi cilastatin (chtc ch dihydropeptidase)

ko di t1/2 vngn cn thnh lp cht chuyn ho

gyc cho thn.



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1. Nhm Beta-lactam

Imipenem: Phkhng khun rng nht hin nay:

Trc khun Gr (-):Enterobacteriaceae, hu ht loi

Pseudomonas khng PNC,Acinetobacter.

Hu ht cu khun Gr (+)

Nhiu vi khun k khnh Bacteroides, k c

B. fragilis, Clostridium.

Vi khun khng:Enterococcus faecium, MRSA,Clostridium difficile.

Ch nh: Cc nhim trng nng khng vi cc

thuc khccc vi khun nhy cm.



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1. Nhm Beta-lactamAZTREONAM:

L hp cht beta-lactam mt vng (monobactam), khng beta-lactamase

ca hu ht vi khun Gr (-).

Hot tnh khng khun khng ging cc beta-lactam khc m gn vi cc

AG hn, nhng khng gyc trn thn v tai:C hot tnh rt tt vi trc khun Gr (-).

Khng c hot tnh vi vi khun Gr (+) v vi khun k kh.

Khng d ng cho vi PNC v cephalosporin, nn

thay th cho beta-lactam tr nhim khun Gr(-) khi ctin s d ng vi nhm ny.

Tc dng ph: bun nn, i ma, tiu chy, ban da.

Ch nh: Cc nhim trng do vi khun hiu kh Gr (-).



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2. Cc chtc ch -lactamase

Amoxicilin + Acid clavulanic = Augmentin

Ticarcillin + Acid clavulanic = Claventin

Ampicilin + Sulbactam = Unasyn

Piperacilin + Tazobactam = Tazocilin

L nhng cht c tc dng khng khun yu,

nhng gn kt khng hi phc vi beta-lactamase.

Khi phi hp vi khng sinh nhm beta-lactam s

lm vng bn vtng cng hot tnh khng khun

ca khng sinh ny.



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3. Nhm Aminoglycoside



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Cn gi l aminosid

C 4 c tnh chung cho c nhm:

Hunhkhng hp thu qua ng tiu ho v c PMcao.

Cng mtcchtc dng.Phkhng khun rng, chyu chng vi khun

hiu kh Gr(-).

c tnh chn lc vi dy thn kinh VIII v

vi thn (tngcreatinin huyt, protein-niu c hi phc).



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Hot tnh khng khun:

Tc ng trn hu ht trc khun gram(-) hiu

kh (k cPseudomonas).

Tc ng gii hn trn vi khun gram(+): S.

aureus v S. epidermidis, khng vi hu ht

enterococci. t tc dngi vistreptococci.

t tcng trn vi khun k kh.



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VIII. CC KHNG SINH CHNH3. Nhm Aminoglycoside

Lao phi, dch hch, nhim Brucella,vim mng trong tim.

Streptomycin (IM/IV)

Nhim vi khun Gr(-) hiukh nng k cE.coli vEnterobacter, Klebsiella,Proteus, Pseudomonas vSerratia sp.

Gentamicin, Amikacin,Tobramycin, Netilmicin(IM/IV)

-Nhim trng da, rut.

-Tr lao.

Neomycin (PO, ti ch).

Kanamycin (IM/IV)

Lu.Spectinomycin (IM)

Ch nhThuc


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V C C NG S N C N4. Nhm Phenicol

Dcng hc: t nng tia trong mu 2h

sau khi ung, t1/2 t1,5-3h, khong 60% gn vo

protein huyttng.

Hai c tnh l suy ty v hi chng xm(thng gp trssinh).

L cht c ch enzym chuyn ho thuc gan

nn ko di t1/2 v lmtng nng trong huyttng ca phenytoin, tolbutamid, warfarin,..



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5. Nhm Tetracycline



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L khng sinh km khun ph rng. Hot tnh ca cc chtcxp theo thtsau:

Minoxyclin>Doxycyclin>tetracycline, oxytetracyclin

Tc dng:

Cu khun Gr(+) v Gr(-), nhng kmhn PNC.

Trc khun Gr(+) i kh v ym kh.

Trc khun Gr(-), nhng Proteus v

trc khun m xanh t nhy cm.

Xon khun, Rickettsia, amip, Trichomonas.

5. Nhm Tetracycline



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5. Nhm Tetracycline

D c ong hoc:- Hap thu qua ng tieu hoa60-70%. Detao phc vi sat, cal ci ,

magne vacasein trong thc an, lam giam hap thu. Nong otoi a

trong mau at c sau 2h.

- Gan vao protein huyet tng 30% (oxytetracycl in) en 50%

(tetracycl in) hoac tren 90% (doxycycl in). Tham vao

c dch nao tuy, nhau thai , sa. Do tham vao c

trong tebao nen cotac dung tot trong ieu trcac

benh do Brucel la. Gan manh vao heli noi mocua gan, lach, xng, rang.

- Thai trqua gan (chu kygan-ruot) vathan.

VIII. CC KHNG SINH CHNH5 Nh T li


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5. Nhm Tetracycline

D ai16-18

-

16

10

90-100

-

Doxycyclin

M inocyclin

Trungbnh12

-

35

31

-

-

Demeclocyclin

M ethacyclin

Ngan6-8

-

-

35

90

65

30

60-70

-

Clotetracyclin

Oxytetracyclin

Tetracyclin

Phan loai

tac dung

t1/2

(gi)

C L than

(mL /phut)

H ap thu theo

PO (% )

T en thuoc

VIII. CC KHNG SINH CHNH5 Nh T li


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5. Nhm TetracyclineCh nh

Tr nhimMycoplasma pneumoniae (vim phingi ln), Rickettsia, Vibriov Chlamydia (vim trong c t cung, ng tiu, trc trng, mo tinh hon,

bnh mt ht).

Thay thpenicillin tr nhimActinomyces, bnh than, giang mai, nhim trng

h hp doH.influenzae

. Tr nhim Brucella, tularemia, dch hch (phi hp vi AG).

Tr vim ph qun, mn trng c

Tr nhim protozoa (Entamoeba histolytica hocPlasmodium falciparum), trvim d dy ti pht doH.pylopri (phi hp).

Doxycyclin nga tiu chy du khch, tr st rt v amib, vim phi thu nhncngng. Thucco thi qua phn nn l loi tetracycline an toniu tr nhim trng ngoi thn chongi suy thn. Khng dng choiu trnhim trngng tiu.

VIII. CC KHNG SINH CHNH6 Nh M lid


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6. Nhm MacrolidePh khng khun ging PNC: tcng trn vi khun gram(+), t tcng trn vi khun gram (-). Hon ton khng tc dng trn trckhunng rut vPseudomonas.

Ch nh

Tr nhim Corynebacteria (bch hu, nhim trng huyt), mycoplasmapneumoniae (vim phi), Chlamydia tracomatis (nhim trng mt, h hp, sinh

dc),Bordetella pertussis (ho g). L thuc thay th tr nhim trng h hp do Strep. Pneumoniae, vim hng doS.pyogenes, h cam v lu do bnh nhn d ng vi penicillin.

D phng vim ni tm mc trong phu thut rng ming cho bnh nhnbnh van tim.

Ph n mang thai nhim trng niu-sinh dc: erythromycin l thuc lc chn,azithromycin l thuc thay th.

Phongn gnh do C. tetani.

Trbnh phong: Clarithromycin + minocyclin.

VIII. CC KHNG SINH CHNH7 Nh Li id


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7. Nhm LincosamideClindamycin c hot tnh mnh hn v sinh kh dng ng ung cao hn

Lincomycin. Hot tnh khng khun trn hu ht vi khun gram (+) (trenterococci), vi khun k kh gram (+) v (-) (trClos. Difficile). Khng c tcng trn vi khun gram (-) hiu kh hoc ty . Hp thu gn hon ton bngng ung, t chunhhng ca thcn. Thi tr ch yu qua ng mt.

Ch nh

Hiu qu cho nhim cu khun gram (+). Ch yu tr nhim trng vng bngvng niu sinh dc n doB.fragilis.

Thay th PNC trong abces phi.

Tr nhimPneumocytis carrinii vtoxoplasma gondii no.

Phng nga vim mng trong tim cho ngi bnh van tim d ng vipenicillin.

Do thm tt voxng, nn dng tr vim tyxng.

Dng ti ch tr mn trng c.

VIII. CC KHNG SINH CHNH8 C QUINOLON


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K hang sinh tong hp, lacac acid yeu, gom co:+ L oai k inh ien (hay thehe1): acid nalidixic (1963).

+ L oai mi: gan them fluor vao vtr 6, goi la6-f luor oquinolon

C ac quinolon thehe1 chc cheA D N-gyr ase nen chcotac

dung diet khuan G r (-) ng tiet nieu vatieu hoa. K hong cotac dung tr enP. aeruginosa.

C ac fluoroquinolon cotac dung tr en 2 enzym ch laA D N-

gyr ase vatopoisomer ase I V cua vi khuan nen phokhang

khuan r ong hn, hoat tnh khang khuan manh hn 10-30 lan.

8. Cc QUINOLON



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+ C ac fluor oquinolon theheau, con goi quinolon thehe2:- G om:pefloxacin, norf loxacin, ofloxacin, ciprofloxacin.

- K hac nhau vetac ong tr en gyrase vatopoisomer ase I V :

T r en vi khuan G r (-): H ieu lc khang gyrase manh hn.

T r en vi k huan G r (+ ): cohieu lc khang topoisomer ase I Vmanh hn.

+ C ac fluor oquinolon thehemi, con goi laquinolon thehe3:

- G om: levofloxacin, trovafloxacin, gatifloxacin.

- C otac ong can bang tr en ca2 enzym, nen phokhang khuanmr ong tr en caG r (+), nhat lacac nhiem khuan ng hohap;

vavi khuan cung khokhang thuoc hn v phai ot bien 2 lan

tr en 2 enzym ch.

8. Cc QUINOLON



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8. Cc QUINOLON

Quinolone th h 1 c ph tc dng hp, ch tc dng trn vi khun gram (-),ch yu dngiu tr nhim khun tit niu. Cc Fluoroquinolone c hot tnhtrn: E.coli, Salmonella, Shigella, Enterobacter, Neisseria, P.aeruginosa,Enterococci, pneumococci, staphylococci khng meticillin.

Ch nh

Tr nhim trngng tiu, vim tuyn tin lit

Tr nhim trng tiu hanh tiu chy nhim trng: hu ht cc vi khungy bnhng rutu nhy cmnh E.coli, Salmonella, Shigella

Tr nhim trng m mm, xng khp, da, vim xoang cp, nhim trngbng (phi hp vi metronidazole), nhim trng h hpdi k c vi khuna khng thuc nh pseudomonas, Enterobacter, vim ni tm mc, nhimtrng bnh vin.

Tr cc bnh ly truyn theo ng tnh dc: bnh lu (ofloxacin hocciprofloxacin), h cam (ciprofloxacin), vim niuo v c t cung.

VIII. CC KHNG SINH CHNH9 Cc thuc khng nm


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4 nhm bnh nm chnh

Bnh nm bmt.

Bnh nm ngoi da Bnh nmdi da

Bnh nm ni tng:

Nhim nmchi. Nhim nm khngchi.

9. Cc thuc khng nm


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Ringworm

9. C A C K H A NG SI NH K H A NG NA M


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I. Thuc khng nm ni tng

Amphotericin B.

Flucytosin.

Cc azol:

Imidazol: Clotrimazol, miconazol,

ketoconazol.

Triazol: Fluconazol, itraconazol,Voriconazol.

Echinocandn.

9. Cc thuc khng nm

VIII. CC KHNG SINH CHNH9 C


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II. Thuc trnm da-nim mc

Griseofulvin.

Terbinafin

III. Thuc khng nm ti ch

Loi azol:

Imidazol: Miconazol, clotrimazol, Econazol,

Oxiconazol, ketoconazol, sulconazol.

Loi polyen: Nystatin.

Amphotericin B.

Natamycin.

9. Cc thuc khng nm

VIII. CC KHNG SINH CHNH9 Cc thuc khng nm


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9. Cc thuc khng nm

9.1 GRISEOFULVIN:

C tnh km nm. Tcng trn nhiu dng vi nm ngoi da.Khng c tcng trn vi khun hoc c c nmgybnh ni tng.

9.2. NYSTATIN :

Thuc nhm khng nm loi polyen. Hunh khng hp thuqua da, nim mc, rut. Khng dng chong hp thu ton thn(tim chch) v gyc.

9.3. KETOCONAZOL :

Thuc nhm khng nm imidazol. Thuc hp thu tt qua quadng ung, tt nhtpH acid (ngi thiu acid dch v hocangdng thuc antacid, thuc khng th th H1 s lm gim hp thuketoconazol).



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9.1. GR I SEOFUL V I N:

a. T ac dung phu: Nhc au, chong mat. G ay r oi loan nhedaday, r uot.

b. Chnh:

C ac benh nam ngoai da. Nam mong tay, mong chan. Benh nc an chan. Nam toc.

c. Chong chnh:

Phuncothai. Suy gan nang. D ng vi thuoc.



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9.1. G RI SE OFUL V I N:

d. Cach dung: Uong ngay sau ba an vauong

nhieu nc. D ang vien 250, 500mg:Ngi ln: 0,5-1g, chia 2-4 lan.

T r eem: 10-20mg/kg/ngay. Boi ngoai da: thuoc m5% . Nen phoi hp thuoc uong vi thuoc

boi ngoai da etang hieu quaieutr .

e. Bao quan: C hai lo nut kn, theo doihan dung.



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9.2. NY ST A T I N (M ycostatin):

a. T ac dung phu: G ay r oi loan nhe ng tieuhoa(buon non).b. Chnh: Nhiem nam do C andida ng tieu hoa,

niem mac mieng, ngoai da, am ao,. Phoi hp vi k hang sinh pho r ong

(T etr acyclin) e e phong nhiem namCandida.

c. D ang thuoc: T huoc vien 250.000 U I -500.000 UI . T huoc m100.000 UI . V ien at am ao 100.000 U I .



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9.2. NY ST A T I N (M ycostatin):d. Cach dung:Uong:N gi ln: 250.000- 500.000

U I /lan x 3-4 lan/ngay x 4-5 ngay.

Treem: 75.000-750.000 U I /ngay,tuytheo tuoi, chia 4 lan.

Boi ngoai da: dang thuoc m100.000 UI.

at am ao: dang vien 100.000U I , 1-2 vien/ngay. M oi t 20 ngay.c. Bao quan: C hong am, tr anh anh sang.



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9.3. K E T OCONA Z OLE (Nizor al)

a. Chnh: Nhiem nam do Candida va cac

nam khac. t hay k hong hieu quangi b

suy giam mien dch, benh viemmang nao.

b. Cach dung: Uong 200-600mg/ngay, chia lam 2-

3 lan. D ang kem 2% boi tai cho. D au goi.

VIII. CC KHNG SINH CHNH10. VANCOMYCIN


162/163

- L aglycopept id, conguon goc tStreptococcus orientalis, cotnhdiet khuan. Phan tlng=1500, tan t r ong nc.

- T ac dung chuyeu tr en G r (+), phan ln latucau gay benh, keca

tu cau tiet beta-lactamase vakhang methicillin. C otac ong

hiep ong vi gentamicin vastr eptomycin tr en E nter ococcus.- D c ong hoc: t hap thu qua ng tieu hoanen thng c

dung ieu tr viem ruot ket gia mac do tet racyclin hay

clindamycin. G an vi protein huyet tng khoang 55% . T r en

90% thai qua loc cau than. t1/2 khoang 6 gi.

- T ac dung khong mong muon (10% ): viem tnh mach tai chotiem

tr uyen, r et r un, sot.

10. VANCOMYCIN

VIII. CC KHNG SINH CHNH10. VANCOMYCIN


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- L athuoc hang th2 cho hau het cac nhiem tr ung.- D ang uong: T r viem r uot giamac do C lostr idium difficile khi

khong ap ng, k hong dung nap hoac a e khang vi

metr onidazol. L ieu 0,125-0,25m g moi 6 gi.

- D ang tiem:-T r nhiem staphylocci nang hoac nhiem Gr(+) aekhang

hoac khong dung nap vi cac thuoc khac.

-N hiem M RSA nh abces nao, viem mang nao, viem mang

bung, nhiem trung huyet,.

10. VANCOMYCIN

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