Kháng Sinh PDF

THUOC S DUNG TRONG HOA TR LIEU
Thuoc khang sinh.

Thuoc tr benh lao.
Thuoc tr benh phong.
Thuoc khang nam.
Thuoc phong nga va tr nhiem virus.
Thuoc tr nhiem Herpes (HSV) va nhiem VSV.
Thuoc tr nhiem HIV/AIDS.
Thuoc tr viem gan.
Thuoc tr sot ret.
Thuoc tr l amib.
Thuoc tr giun san.
Thuoc tr ung th.
1
KHNG SINH
TRNG AI HOC Y DC CAN TH

Khoa Dc
Bo mon Dc ly
2
MUC TIEU BAI GIANG

Sau bai hoc nay, sinh vien co the:
Liet ke c cac nhom thuoc khang sinh chu yeu.
Trnh bay c cac c che tac ong chnh cua thuoc.
Hieu c nguyen nhan, cac dang va c che e
khang thuoc cua vi khuan.
Biet c oc tnh va cac tac dung phu cua
cac nhom khang sinh quan trong.

Trnh bay c nguyen tac cach s dung
an toan, hp ly cac khang sinh thong dung.
Tai lieu tham khao
I. I CNG
LCH S PHAT MINH
Antony van
Louis Pasteur
Alexander Fleming
Leeuwenhoek
(1822-1895)
(1881-1955)
(1632-1723)
I. NH NGHA
Khang sinh la nhng chat xuat
x t nhng sinh the nh vi khuan,
nam, Actinomycetes hoac do ban
tong hp hay tong hp c.
He so tr lieu cua khang sinh
rat cao, co kha nang ngan chan
mot vai dien tien trong qua trnh
song cua mot so vi khuan, vi sinh
vat, sinh vat a bao ngay lieu
lng nho, va vi lieu ln hn cung
khong hoac t gay hai en te bao
ngi s dung.
6
I. NH NGHA
Kha nang ngan chan qua trnh song cua vi khuan the hien:
Tnh kiem khuan (Bacteriostatic): Khang sinh ch c che tam
thi s phat trien cua vi khuan. Neu ngng thuoc, vi khuan co
the phat trien tr lai, gay nhiem trung tai phat.
Tnh diet khuan (Bactercidal): Khang sinh gan
vao cac v tr tac ong cua no tren te bao

vi khuan va tieu diet chung.
Khi nim v tc dng kim khun v dit khun
gip s dng ng khng sinh:
- Trong nhim trng nh: Khng sinh kim khun.
- Trong nhim trng nng: Khng sinh dit khun.
Tuy nhin s phn loi ny ch mang tnh tng i.
7
I. NH NGHA
Mot so khai niem ve hoat tnh cua khang sinh
Pho khang khuan:
Do khang sinh co tac dung theo c che ac hieu nen

moi khang sinh ch co tac ong tren mot so chung vi
khuan nhat nh, goi la pho khang khuan cua
khang sinh.
I. NH NGHA
Pho khang khuan:
Vi khuan nhay cam vi khang sinh A va E, e khang vi

khang sinh C va D; co mot s e khang trung bnh vi
khang sinh B
9
I. NH NGHA
Vi khuan Gr(+) va Gr(-)
Hans Christian Joachim Gram

(1853 1938)
Staphylococcus aureus
Escherichia coli
10
I. NH NGHA
Pho khang khuan:
11
I. NH NGHA
Pho khang khuan:
Pho khang khuan hep.
Pho khang khuan rong.
12
I. NH NGHA
Nong o kiem khuan toi thieu hay MIC (Minimal Inhibitory
Concentration): nong o toi thieu cua khang sinh can co e ngan
chan s tang trng cua vi khuan trong 18-24 gi.
Nong o diet khuan toi thieu hay MBC (Minimal Bactericidal
Concentration): nong o can co cua khang sinh kh trung moi
trng hoac lam suy giam i 99,9% so lng vi khuan.
MBC
Ty le =
MIC
Neu ty le nay >4: la kiem khuan.
Neu ty le nay 1: la diet khuan.
13
I. NH NGHA
Thong thng MBC = 2-8 lan MIC.
Cac khang sinh diet khuan co MBC gan vi
MIC va de at nong o bang MBC trong
huyet tng, nh PNC, cephalosporin,
aminoglycosid,
Cac khang sinh kiem khuan co MBC> MIC
va kho at c nong o bang MBC trong
huyet
tng,
nh
tetracyclin,
chloramphenicol, macrolid,..
14
I. NH NGHA
S nhay cam:
Vi khuan nhay cam vi mot khang sinh khi
vi khuan o b diet lieu va ng dung
thong thng.
Nong o khang sinh/huyet tng > MIC.
S khang thuoc
(S e khang khang sinh cua vi khuan):
Nong o an toan cua khang sinh/huyet
tng (mcg/ml) << MIC.
15
I. NH NGHA
Ty so diet khuan: La thc o hieu lc khang sinh in
vivo; giup xac nh kha nang diet khuan cua mot loai
khang sinh tai nong o nh trong huyet tng va trong
suot thi gian cach lieu.
Nong o thuoc trong huyet tng (mcg/ml)
Ty so diet khuan =
Nong o c che toi thieu (mcg/ml)
Ty so diet khuan ln hn hoac bang 2 c xem

la gia tr mong i va d oan co the loai tr het
vi khuan trong tr lieu lam sang.
16
I. NH NGHA
Ty so diet khuan
MIC trung bnh cua cephalothin tren S. aureus la 0,5 mcg/ml va
cua cefazolin la 1,0 mcg/ml. Nh vay cephalothin co hoat tnh
tren S.aureus gap 2 lan cefazolin.
Tren thc te, Cmax/huyet thanh cua cephalothin sau mot lieu 2g la
khoang 100mcg/ml. Ty so diet khuan cua thuoc tren S.aureus
se la 100/0,5 = 200.
Khi IV lieu 1g cefazolin, Cmax/huyet thanh cua thuoc
khoang 200mcg/ml. Ty so diet khuan cua cefazolin
la 200/1 = 200. Nh vay ty so diet khuan cua 2 thuoc
tng t nhau.
Do nong o cao hn trong mau cua cefazolin a bu tr
vao MIC90 cua thuoc cao hn MIC90 cua cephalothin.
17
I. NH NGHA
oc tnh chon loc: La oc tnh lam ton hai en
qua trnh tong hp hoac chuyen hoa cua vi

sinh vat gay benh ma te bao ong vat co the
dung nhan c.
18
II. PHAN LOAI KHANG SINH (Theo cau truc hoa hoc)
1. Nhom BETA-LACTAM:
1.1. Phan nhom Penicillin.
1.1.1. Benzylpenicillin: PNC G, procain-PNC, Benzathine-PNC
1.1.2. Phenoxypenicillin: PNC V
1.1.3. PNC khang penicillinase (chong tu cau): Oxacillin, Cloxacillin
Dicloxacillin, Methicillin, Nafcillin
1.1.4. AminoPNC: Ampicillin, Amoxicillin, bacampicillin,
Methampicillin
1.1.5. CarboxyPNC: Carbenicillin, Ticarcillin
1.1.6. UreidoPNC :Azlocillin, Mezlocillin, Piperacillin
1.1.7. Carbapenem: Imipenem, Ertapenem, meropenem.
1.1.8. Monobactam: Aztreonam.
1.1.9. c che beta-lactamase: Acid clavulanic, Sulbactam
19
II. PHAN LOAI KHANG SINH

Theo cau truc hoa hoc
1. Nhom BETA-LACTAM:
1.2. Phan nhom Cephalosporin:
1.2.1. The he 1: Cephalothin, Cephalexin, Cephaloridin,
Cefatrizin, Cefapirin, Cefadroxil.
1.2.2. The he 2: Cefuroxime, Cefuroxime acetyl, Cefamandole,
Cefoxitin, Cefotetan, Cefmetazole.
1.2.3. The he 3: Cefotaxime, Cefoperazone,
Ceftriaxone, Ceftizoxime, Moxalactam,
Ceftazidime, Cefixime, Latamoxef.
1.2.4. The he 4: Cefpirome (Cefron), cefepim (Axepim).
20

2. Nhom AMINOGLYCOSIDE (AMINOSIDE):
Streptomycin, Gentamicin, Tobramycin, Amikacin, Netilmicin,
Framycetin, Neomycin, Sisomicin, Paromomycin, Kanamycin,
Dibekacin, Spectinomycin.
3. Nhom PHENICOL:
Chloramphenicol, Thiamphenicol
4. Nhom LINCOSAMIDE:
Lincomycin, Clindamycin.
21

5. Nhom MACROLIDE:
Erythromycin, Oleandomycin, Spiramycin, Josamycin,
Azithromycin, Roxithromycin, Clarithromycin.
6. Nhom TETRACYCLINE:
Tetracycline, Oxytetracycline, Methacycline,
Doxycycline, Minocycline.
7. Nhom khang sinh chong nam:
Nystatin, Amphotericin B, Griseofulvin,
Flucytosine, Ketoconazole, Miconazole,
Fluconazole, Clotrimazole...
22

8. Cac nhom khac :
8.1. Cac QUINOLONE:
1.1. Kinh ien: Flumequin, Acid nalidixic, Acid oxolinic,
Acid pipemidic
1.2. The he 2 (Fluoroquinolone): Norfloxacin,
Ofloxacin, Enoxacin, Ciprofloxacin,
Rosoxacin, Lomefloxacin, Sparfloxacin.
8.2. Cac NITROIMIDAZOLE:
Metronidazole, Ornidazole, Secnidazole,
Trinidazole, Ternidazole.
23

8. Cac nhom khac :
8.3. Cac dan xuat cua SULFANILAMIDE (Sulfamide, sulfonamide):
8.3.1. Thai nhanh: Sulfafurazol, Sulfamethizol
8.3.2. Thai trung bnh: Sulfadiazine, Sulfamethopyrazin,
Sulfamethoxazole (trong co-trimoxazole)
8.3.3. Thai cham: Sulfadimetoxine, Sulfamethoxydiazin,
Sulfamethoxypyridazin.
8.3.4. Thai rat cham: Sulfadoxine (trong Fansidar)
8.3.5. t hap thu khi uong: Sulfaguanidin,
Phtalylsulfathiazole, Sulfasalazin.
8.3.6. Dung ngoai: Sulfanilamid, Sulfacetamid.
24

8. Cac nhom khac :
8.4. Cac GLYCOPEPTIDE:
Vancomycin, Teioplanin, Bacitracin.
8.5. Cac NITROFURAN:
Nitrofurantoin, Nifuroxazid, Nifuzid.
8.6. POLYMYXIN B va COLISTIN.
25

Theo c che tac ong
a. Nhom c che s tong hp vach te bao vi khuan:
Cac Penicillin va Cephalosporin, Cycloserin, Vancomycin va
Bacitracin.
b. Nhom tac ong trc tiep len mang te bao cua vi sinh vat:
Polymixin, Colistin, cac Poliene khang nam, Nystatin,
Amphotericin-B, Imidazole.
c. Nhom anh hng len chc nang cac ribosom cua
te bao vi khuan:
Chloramphenicol, cac Tetracyclin, Erythromycin,
Clindamycin, cac Aminoglycoside.
26

Theo c che tac ong
d. Cac tac nhan anh hng en s chuyen hoa acid nucleic cua vi
sinh vat:
Rifampicin, cac Quinolone.
e. Cac chat chong chuyen hoa:
Trimethoprim, cac Sulfonamide.
f. Cac chat ong dang cua acid nucleic.
27

Theo tac dung ieu tr
Can c vao tac dung ieu tr, co the chia khang sinh
thanh 3 loai chnh:
Khang sinh khang khuan.
Khang sinh tr nam.
Khang sinh chong ung th.
28

Da vao dc lc dc ong (PK/PD)
Can c vao s lien quan gia nong o va

toc o diet khuan, chia khang sinh thanh:
Khang sinh phu thuoc nong o: Tac
ong diet khuan tang theo nong o trong
mau.
du:
Aminoglycosid,
Fluoroquinolon.
Khang sinh phu thuoc thi gian: Tac
ong diet khuan khong tang theo nong
o trong mau. V du nhom beta-lactam.
29

Tac dung sau khang sinh PAE (Post Antibiotic Effect):

Cho VK tiep xuc vi KS trong mot thi gian ngan,
sau o loai KS khoi moi trng. S phat trien tr lai
cua VK cham tre trong mot khoang thi gian.
PAE la tac dung c che s phat

trien cua VK khi nong o huyet tng
cua khang sinh thap hn MIC,
tham ch khong con trong moi trng.
30

Tac dung sau khang sinh PAE (Post Antibiotic Effect):

KS co PAE keo dai: Aminoglycosid, Rifampicin,
Fluoroquinolon, Glycopeptid, Tetracyclin,
Azithromycin, Fluconazol. Ngay dung 1 lan.
KS co PAE ngan hoac khong co PAE,

ngay dung nhieu lan: Beta lactam,
Clindamycin, Macrolid ( tr Azithromycin).
31

Cac thong so PK/PD d oan hieu lc tac dung cua KS:
Tnh chat
khang
khuan
Phu thuoc thi gian. Phu thuoc nong o.

PAE khong co
PAE keo dai
hoac ngan
Khang sinh Beta lactam

Macrolid
Oxazolidinon
Clindamycin
Thong so
d oan
T>MIC
(Thi gian [C]/
mau ln hn MIC
Aminoglycosid
Fluoroquinolon
Metronidazol
Rifampicin.
Amphotericin B
Cmax/MIC va
AUC/MIC
Phu thuoc thi gian.

PAE keo dai.
Azithromycin
Clarithromycin
Tetracyclin
Fluconazol
AUC/MIC
32
III. C CHE TAC ONG CUA KHANG SINH

Khang sinh co tac dung ngng trung hoac diet khuan theo mot
trong 4 c che chu yeu sau:
c che s tong hp vach te bao vi khuan.
Lam thay oi tnh tham cua mang te bao chat.
c che tong hp protein cua vi khuan.
c che tong hp acid nucleic.
33

3.1. C CHE S TONG HP VACH TE BAO VI KHUAN.
Vach te bao vi khuan (Cell-walls): Chiem 20% so vi trong lng kho cua
te bao, bao quanh mang bao tng.
34

Cau truc cua vach te bao vi khuan: Mucopeptide (Murein, Peptidoglycan)
35

Cau truc vach te bao vi khuan cua

36

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

Giai oan 1: Tao tien chat Uridindiphosphat (UDP) acetyl muramyl
pentapeptid. Cuoi giai oan la s thanh lap dipeptide: D-alanin-D-alanin vao
tan cung e tao thanh pentapeptid, vi s xuc tac cua Alaninracemase va Dalanin-D-alanin synthetase. Giai oan nay dien ra ben trong bao tng.
Giai oan 2: Ket hp UDP acetyl muramyl pentapeptide va
UDP acetyl glucosamin thanh chuoi dai polysaccharide,
di xuc tac cua Transglucosidase. Cuoi giai oan nay cac
day polysaccharide se di chuyen ra ben ngoai mang bao tng.
Giai oan 3: Hoan tat noi ngang cua 2 peptidoglycan ke can.

Phan ng xay ra ben ngoai mang bao tng di s xuc tac
cua cac Transpeptidase.
37

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

GIAI OAN 1: Xay ra ben trong mang bao tng, tao UDP-acetylmuramin-pentapeptid.
D-alaninD-alanin
synthetase
Alanin
racemase
M
M
L-Ala
L-Ala
D-Glu
D-Glu
L-Lys
M
L-Ala
D-Ala
D-Glu
L-Lys
L-Lys
D-Ala
L-Ala
D-Ala
D-Glu
L-Lys
D-Ala
D-Ala
M: acetylmuramic acid
L-Lys: L-lysin
L-Ala: L-alanin
D-Ala: D-alanin
D-Glu: D-glutamic
38

Sinh tong hp Peptidoglycan
Giai oan 2: Tao chuoi dai polysaccharide.
Glycyl-tRNA
Transglucosidase
G
D-Glu
M
L-Ala
L-Ala
Di chuyen ra
ben ngoai mang
bao tng
L-Ala
L-Lys
D-Ala
M
L-Ala
L-Ala
D-Ala
D-Glu
D-Glu
L-Lys
L-Lys -[Gly]
D-Ala
D-Ala
D-Ala
D-Ala
M: Acetylmuramic acid
G: N-acetyl-glucosamin
[Gly]5: Pentaglycin
39

Sinh tong hp Peptidoglycan.
Giai oan 3: Xay ra ben ngoai mang bao tng.
M
L-Ala
L-Ala
M
L-Ala
L-Ala
Transpeptidase
M
L-Ala
D-Ala
M
L-Ala
D-Glu
L-Lys
D-Glu
L-Ala
M
L-Ala
[Gly]5
G
L-Lys
D-Ala
[Gly]5
D-Ala
D-Ala
L-Lys [Gly]5
D-Glu
L-Lys
D-Glu
[Gly]5
D-Ala
D-Ala
D-Ala
D-Ala
40

Sinh tong hp Peptidoglycan: hnh thanh li peptidoglycan cua vach te bao.
41

C che tac ong:

Cac thuoc: Cac PNC va Cephalosporin, Bacitracin, Ristocelin,
Cycloserine va Vancomycin.
Gom cac bc:
Gan ket cac khang sinh len cac receptor cua no tren te bao vi
khuan, thng la cac protein c goi chung la
Penicillin Binding Protein (PBP).

Ngan chan s tong hp peptidoglycan nhng
giai oan khac nhau.

Hoat hoa cac enzym t huy trong vi sinh vat,
gay phan huy te bao vi khuan.

42

V tr tac ong cua cac khang sinh tren s c che tong hp vach te
bao vi khuan
Cac PNC, Cephalosporin c che men Transpeptidase.
Cycloserine (chat ong dang cua D-alanin) c che enzym
Alanine racemase.
Vancomycin ngan chan s tach ra khoi mang
bao tng cua tien chat peptidoglycan.

Bacitracin, Ristocein c che Transglucosidase
trong nhng bc tong hp au tien

peptidoglycan.
43
III. C CHE TAC ONG CUA

KHANG SINH
3.1. C CHE S TONG HP
VACH TE BAO VI KHUAN.
V tr tac ong cua cac

khang sinh tren s c che
tong hp vach te bao vi
khuan.
44
III. C CHE TAC ONG CUA

KHANG SINH
3.1. C CHE S TONG HP
VACH TE BAO VI KHUAN.
V tr tac ong cua cac

khang sinh tren s c che
tong hp vach te bao vi
khuan.
45

Tnh nhay cam cua vi khuan oi vi cac thuoc khang sinh th phu thuoc vao:
Lp peptidoglycan hnh thanh.
46

Tnh nhay cam cua vi khuan oi vi cac thuoc khang sinh th phu thuoc vao:
S hien dien cua cac PBP, cac porins, lp lipid oi phan t.
47

Tnh nhay cam cua vi khuan
oi vi cac thuoc khang sinh th
phu thuoc vao:
S hien dien cua Betalactamase.
48

Tnh nhay cam cua vi khuan oi vi cac thuoc khang sinh th phu
thuoc vao:
Ban chat cua lien ket ngang.
Hoat ong cua cac he thong enzym t huy.
Cac yeu to nay se quyet nh:
Hoat tnh khang khuan cua dc pham.
Pho khang khuan cua thuoc.
S e khang cua vi khuan oi vi khang sinh.
49

Cac yeu to quyet nh tac dung cua thuoc:
50

3.2. THAY OI TNH THAM CUA MANG TE BAO CHAT.
Cac tac nhan
nhom nay gom:

Amphotericin-B,
Colistin,
Nystatin,
Polymyxins.
51

3.2. THAY OI TNH THAM CUA MANG TE BAO CHAT.
52

3.3. C CHE TONG HP PROTEIN CUA VI KHUAN.
Cac khang sinh nhom nay gom: cac Aminoglycoside,

Tetracycline, Macrolide, Chloramphenicol, Lincomycin.
Te bao vi khuan co Ribosome 70S gom 2 subunits la 50S va 30S.
53

Sinh tong hp protein cua te bao vi khuan gom cac giai oan:
Tao phc khi au Amino acyl tRNA.
Tao f-meth-tRNA 70S.
Giai oan keo dai hnh thanh chuoi peptid.
54
III. C CHE TAC ONG

CUA KHANG SINH
3.3. C CHE TONG HP
PROTEIN CUA VI
KHUAN.
Sinh tong hp protein

cua te bao vi khuan.
55
56

Tac ong cua khang sinh: Cac Aminoglycosie

c che tac ong cua phc
hp khi au mRNA-f-methtRNA.
Ket hp vi receptor chuyen
biet tren tieu n v 30S gay
bien dang ribosom, lam oc sai
ma, tao cac protein khong hoat
tnh.
Lam t oan cac polysomes
thanh monosome.
57

Tac ong cua khang sinh: Cac Tetracyclin

c che s co nh
aminoacyl-RNAt tai trung tam
A cua ribosom 30S, ngan chan
ng vao cua cac tRNA co
mang goc aminoacyl, dan en
khong a c acid amin mi
vao chuoi peptid ang thanh
lap.
58

3.3. C CHE TONG HP PROTEIN CUA VI
KHUAN.
Tac ong cua khang sinh: Chloramphenicol

Gan vao ribosom 50S c che
peptidyltransferase, nen ngan chan s
ket hp cua mot acid amin mi vao
chuoi peptid noi sinh ang thanh lap.
59

3.3. C CHE TONG HP PROTEIN CUA VI
KHUAN.
Tac ong cua khang sinh:
Cac Macrolide va Lincosamid

Gan vao ribosom 50S, can thiep phan
ng chuyen v aminoacyl t trung tam
A sang trung tam P.
60
III. C CHE TAC ONG

CUA KHANG SINH
3.3. C CHE TONG HP
PROTEIN CUA VI KHUAN.

cua te bao vi khuan va
tac ong cua khang
sinh.
61
III. C CHE TAC ONG

CUA KHANG SINH
3.3. C CHE TONG HP
PROTEIN CUA VI KHUAN.

cua te bao vi khuan
va tac ong cua
khang sinh:
1 & 5: Streptomycin va
cac aminoglycoside
khac.
2: Tetracyclin.
3: Chloramphenicol.
4: Erythromycin,
Clindamycin.
62

3.4. C CHE TONG HP ACID NUCLEIC CUA TE BAO VI KHUAN.
Cac khang sinh nhom nay gom: cac Quinolone, Novobiocin,

Rifampin, Pyrimethamine, Trimethoprim, cac Sulfonamide.
Phan t DNA co kha nang:
T nhan oi
DNA
Sao ma
DNA mi
DNA polymerase
Giai ma
mRNA
Protein
RNA polymerase
63

Tac ong cua khang sinh: Cac Quinolone

Phong toa DNA gyrase, ngan chan s
m xoan cac day oi DNA.
64

Tac ong cua khang sinh: Cac Sulfamid

c che canh tranh vi PABA, ngan chan
s tong hp acid folic.
Tac ong cua khang sinh:

Trimethoprim.
Pyrimethamine
c che enzym dihydrofolate reductase,
ngan chan s tao thanh acid folinic.
65

Tac ong cua khang sinh: Rifampin, Actinomycin.
c che RNA polymerase,

ngan chan s tao thanh RNA.
66

DNA dang vong xoan
DNA gyrase
QUINOLON
DNA dang m vong

RNA polymerase
RIFAMPIN
DNA polymerase
mRNA
Ribosom 30S
DNA
Phc hp khi au 30S

Ribosom 50S
AMINOGLYCOSID
Phc hp khi au 70S
Peptidyltransferase
CHLORAMPHENICOL
Thanh lap noi peptid

ERYTHROMYCIN, CLINDAMYCIN
Keo dai day peptid
V TR TAC ONG CUA CAC THUOC C CHE

TONG HP PROTEIN VA ACID NUCLEIC
67
68
IV. S E KHANG KHANG SINH CUA VI KHUAN

4.1. CAC DANG E KHANG
e khang gia:
He thong mien dch cua c the b suy yeu.
Vi khuan trang thai ngh.
Khang sinh khong en c o viem.
69

e khang that:
1. e khang t nhien:
Mot so vi khuan khong b oi vi mot vai khang sinh:
Escherichia coli vi erythromycin.
Tu cau vi colistin.
Pseudomonas aeruginosa vi PNG.
Vi khuan khong co vach te bao nh Mycoplasma
se khong b tac dung cua nhom khang sinh
c che tong hp vach te bao.
70

ot bien gen
e khang that:
2. e khang thu c:
Do bien co ve di truyen, vi khuan
t cho khong co tr nen co mang
gen e khang.
2.1. ot bien gen:
ot bien mot bc.
ot bien nhieu bc: Lien quan
en nong o khang sinh.
2.2. Nhan gen e khang: cac gen
e khang co the nam tren nhiem
sac the, plasmid hay transposon.
Nhan gen e khang
71

e khang that:
2. e khang thu c:
2.2. Nhan gen e khang:
Tiep hp (Conjugation).
Bien nap hay chuyen the
(Transformation).
Tai nap hay chuyen nap
(Transduction).
72

4.2. C CHE KHANG THUOC
Tao ra cac enzym lam bien

oi hoac pha huy i cau truc cua
thuoc.
Lam thay oi tnh tham qua
mang te bao vi khuan cua thuoc.
Thay oi cac cau truc ch
ac hieu cua thuoc tren te bao
vi khuan.
Phat trien qua trnh chuyen
hoa qua mot nga khac.
Phat trien enzym van con
chc nang chuyen hoa nhng t
nhay cam hn vi thuoc.
73

4.2. C CHE KHANG THUOC
74

4.3. S E KHANG CHEO (CROSS-RESISTANCE)
nh ngha:
Vi sinh vat e khang vi mot khang sinh nao o co the se e
khang vi cac khang sinh khac co cung c che tac ong.
Cach han che:
Duy tr nong o khang sinh cao trong mo.
Ch phoi hp cac khang sinh khong co e khang cheo.
Tranh dung khang sinh ac hieu neu vi khuan
van con nhay cam vi khang sinh thong thng.
Tranh gieo rac mam benh va boi nhiem.
75

4.4. Y NGHA LAM SANG CUA S E KHANG THUOC
e khang co lien quan mat thiet en s dung thuoc.

e khang do plasmid: de tao kha nang chon loc tat ca cac
gen e khang nam tren plasmid.

Vi khuan e khang kho tr lieu khi gay thanh dch, benh.
Gay nhiem khuan benh vien:
Staphyloccus aureus khang Methicillin va
Gentamicin.
Trc khuan ng ruot khang gentamicin.
P. aeruginosa khang gentamicin.
76

4.5. BIEN PHAP HAN CHE S GIA TANG TNH KHANG THUOC
Ch dung khang sinh ieu tr khi nhiem khuan.

La chon khang sinh hp ly.
Chon khang sinh khuyech tan tot nhat vao o nhiem khuan.
Phoi hp khang sinh hp ly, nhat la khi ieu tr keo dai.
Giam sat tnh hnh e khang.
Chu trong cac bien phap kh khuan va vo khuan.
77
V. TAC DUNG PHU VA OC TNH

THNG GAP MOT SO KHANG SINH
Cac tac dung khong mong muon thng gap:

Phan ng qua man.
oc tnh trc tiep.
Boi nhiem do cac vi sinh vat e khang.
78

NHOM BETA-LACTAM
D ng:
Choang phan ve (PNC)
Ngoai da: nga, may ay
(Ampicillin)
Benh ve huyet thanh: sot, lach to,
giam bach cau, viem khp.

Loan khuan ruot
Benh nao cap: co c, hon me (truyen
PNC lng ln, Oxacillin lieu cao)

Tai bien ve mau: ban o, xuat huyet.
Gay viem than: Methicillin, cephalosporin.
79

NHOM AMINOGLYCOSIDE
Roi loan thnh giac, tren tien nh
va oc tai. oc tnh gia tang ngi
suy than, ngi gia, dung lieu cao va
lau dai. Ton thng tren tai khong
hoi phuc.
oc tnh tren than: Hoi phuc,
nhng chc nang than giam lam
giam bai tiet thuoc, gay tch tr
thuoc, tao oc tnh khong hoi phuc
tren tai.
80

NHOM TETRACYCLINE
Tch tr trong lach, tuy xng, nga rang,
men rang, qua nhau thai va vao sa me.
Lang ong tren mo a hoa voi (xng, rang),
lam thay oi mau rang.
Gay roi loan tieu hoa, gay boi nhiem vi
khuan, nam, dan en gay viem ruot gia mac.
oc tnh tren gan, nhat la phu n mang thai.
Roi loan chc nang than.
Lam da nhay cam vi anh sang
Gay huyet khoi khi tiem truyen tnh mach,
gay au tai cho tiem bap.
81

NHOM TETRACYCLINE
82
V. TAC DUNG PHU VA OC TNH THNG GAP MOT SO KHANG SINH
NHOM LINCOSAMIDE
Gay viem ruot ket gia mac.
Tieu chay.
Buon non.
Chlostridium difficile
Ban o da.
NHOM PHENICOL
Tai bien ve mau: Suy tuy gay thieu
mau, thieu mau bat san.
Hoi chng xam: tre s sinh.
83

NHOM QUINOLONE
Gay roi loan tieu hoa va than kinh (ao giac,
lu lan, co giat).
Khong s dung cho tre em, phu n mang
thai hoac cho con bu.
Khong dung cho benh nhan di 18 tuoi.
84

NHOM SULFONAMIDE
Man cam: Ton thng tren da va niem mac
(Hoi chng Stevens-Johnson), sot, kho th
dang hen.
Thieu mau tan huyet cap, giam va mat bach
cau.
Gan: gay vang da.
Roi loan than kinh, tieu hoa va tiet nieu.
85

NHOM SULFONAMIDE
Man cam: Ton thng tren da va niem mac (Hoi chng
Stevens-Johnson).
86
VI. NHNG OI TNG CAN THAN TRONG KHI S DUNG THUOC
Ngi gia cao tuoi.

Ngi co c a suy giam mien dch, c the suy nhc.
Ngi ang mac cac benh man tnh tai cac phu tang
quan trong.
Phu n mang thai va cho con bu.
Tre em.
87
Mot so benh khong c dung khang sinh:

Luput ban o: cac PNC, tetracycline, INH.
Thieu G6PD: chloramphenicol, cac sulfamide, cac
quinolone.
Suy than va suy tim: cac khang sinh
cha nhieu natri.
88
VI. NHNG OI TNG CAN THAN TRONG KHI S DUNG

THUOC
Dung khang sinh khi co thai:
Cam dung
Chloramphenicol
Dapson
Griseofulvin
Cac Quinolone
Cac sulfamide
Cac tetracycline
Co-trimoxazole
Cac Nitro-imidazole
Nitrofurantoin
Mefloquine
Dung than trong

Cac Aminoglycoside
Amphotericin B
Clindamycin
Ethambutol
INH
Rifampin
Vancomycin
Trimethoprim
Ketoconazole
Miconazole
89

THUOC
Cac khang sinh qua c tuyen vu ngi e vao sa:

Benzyl-PNC
Ampicillin
Cac cephalosporin
Cac tetracycline
Metronidazole
Chloramphenicol
Streptomycin
Gentamicin
Primaquin
Erythromycin
Mot so sulfamide
INH
Pyrimethamin
90
Mot so khang sinh dung than trong ngi gia:

CarboxyPNC, fosfomycin: de gay giam Kali huyet.
PNC lieu cao: gay cn ong kinh lan toa, giat c.
Nhom aminoglycoside .
Chloramphenicol, rifampicin: han che s dung.
Metronidazole: giam lieu.
Cac thuoc chong lao.
.
91

THUOC
Dung rat than trong ngi suy than:
Amikacin
Ampicillin
Amoxicillin
Carbenicillin
Cefamandole
Cefuroxim (tiem)
Cefotaxime
Ceftriaxone
Cephalexin
Cefazolin
Clindamycin
Ciprofloxacin
Co-trimoxazole
Ethambutol
Gentamicin
INH
Kanamycin
Lincomycin
Methicillin
Netilmicin
Penicillin G, V
Piperacillin
Pyrazinamide
Streptomycin
Sulfamide
Tobramycin
Thiamphenicol
Vancomycin
Norfloxacin
Ofloxacin
92
Ngi suy gan:

Khong dung: Sulfamide, tetracycline, lincomycin,
clindamycin, nhom quinolone lieu cao.
Neu co vang da, khong dung: chloramphenicol, acid
nalidixic, sulfamide.
Than trong: erythromycin, mot so thuoc
chong lao.
93
VII. NGUYEN TAC S DUNG KHANG SINH

S dung khang sinh ba bai dan en:
Lan rong s nhay cam vi thuoc trong cong ong.
Lam vi khuan khang thuoc phat trien manh.
Khoa lap i nhng dau hieu nhiem trung nang.
Gay hieu ng phu bat li.
Lam gia tang tnh trang khang thuoc trong quan the.
Khang sinh tr thanh tac nhan chon loc tieu diet

cac vi khuan nhay cam, tao dong vi khuan
e khang vi chnh no.
94

Nhng nguyn nhn tht bi trong vic dng khng sinh:
Chn khng sinh khng ng ph tc dng.
Khng sinh khng t c ti ngng tc dng ti
nhim khun do:
Liu lng khng hp l.
Dc ng hc ca thuc khng thch hp.
Tng tc thuc lm gim tc dng
ca khng sinh.
Do vi khun khng thuc.
95

AN TOAN, HP LY
Muc ch:
ieu tr hieu qua
Tranh tao chung vi khuan e khang thuoc
Tranh nhng tac dung co hai cua khang sinh
Ha gia thanh tr lieu
96

AN TOAN, HP LY
Nguyen tac:
Ch dung khang sinh khi b nhiem khuan
Phai chon ung khang sinh
Biet chon dang thuoc thch hp
Phai s dung ung lieu lng
Dung khang sinh ung thi gian qui nh
S dung khang sinh d phong hp ly
Ch phoi hp khang sinh khi that can thiet
97

Ch dung khang sinh khi b nhiem khuan
Cac khang sinh ch co tac dung vi mot so loai vi

khuan nhat nh.
Trc khi s dung, can lam cac bc sau:
Tham kham lam sang.
Cac xet nghiem lam sang thng qui.
Tm vi khuan gay benh: khang sinh o.
Ch nh theo pho tac dung. Neu nhiem khuan

a xac nh, dung khang sinh pho hep.
98

La chon khang sinh
Da vao c s:
O nhiem khuan va v tr nhiem khuan.
Vi khuan gay benh.
Tnh trang benh nhan:
Benh nang hay nhe.
Tuoi.
Thi ky mang thai-cho con bu.
Chc nang gan, than.
Tien s: d ng, e khang, di truyen.
Khang sinh: Dc ng hc ca thuc.
99

Cac vi khuan gay benh.
V du:
Vi khuan hieu kh
Cau khuan Gram(+)
Khong tiet penicillinase
Tiet penicillinase
Benh
-Nhiem trung da va mo mem, viem xng tuy,
nhiem trung huyet.
-Viem khp cap do vi khuan
-Viem mang trong tim cap
Streptococcus tan mau
-Nhiem trung huyet

-Viem mang nao (tre s sinh)
-Nhiem trung do say thai
-Viem mang trong t cung
Streptococcus
pneumoniae
(Pneumococcus)
-Viem phe quan

-Viem phoi
-Viem mang nao (ngi ln va tre em)
-Viem hong hau xoang
100

Cac vi khuan gay benh
V du:
Vi khuan hieu kh
Trc khuan Gram(+)
Bacillus anthracis
Benh
-Benh than
Listeria monocytogens
-Ton thng than kinh (viem mang nao)

-Nhiem trung huyet
Corynebacterium
diphtheriae
-Benh bach hau
Cau khuan Gram(-)

Neisseria gonorrhoeae
(Gonococcus)
-Benh lau
Neisseria meningiditis
(Meningococcus)
-Viem mang nao (ngi ln va tre em)

-Nhiem khuan huyet
101

La chon khang sinh
Vi khuan
Benh
Thuoc c chon
Th nhat
Cau khuan
Gr(+)
Tu cau vang
Abces
Oxacillin
Nhiem khuan
Nafcilin
huyet
Viem noi tam
mac
Viem phoi Viem
xng-tuy
Cau khuan
Gr(-)
Neisseria
meningitis
Viem mang nao
Th hai
Th ba
Cephalosporin 1
Vancomycin
Clindamycin
Erythromycin
Trimethoprim+
Sulfamethoxazol
Ciprofloxacin
+ Rifampicin
Penicillin-G Ceftriaxon
Rifampicin Cefotaxim
Minocyclin
Ciprofloxacin
102

La chon khang sinh
Vi khuan
Benh
Viem hong
Trc khuan
Viem phoi
Gr(+)
Corynebacterium Viem thanh
phe quan
Trc khuan
Gr(-)
Escheria coli
Nhiem khuan
tiet nieu
Nhiem khuan
khac
Thuoc c chon
Th nhat
Th hai
Erythromycin
Clindamycin
Th ba
Cephalosporin 1
Rifampicin
TMP- SMZ
PNC+ c che
Aztreonam
men PNCase
Ciprofloxacin
Nitrofurantoin
Aminoglycoside Doxycycline
Ampicillin+
Aminoglycoside
103

La chon dang khang sinh thch hp
S dung ung lieu lng
S dung ung thi gian qui nh
Tao c nong o ieu tr hieu qua

Tranh c s e khang thuoc cua vi khuan gay benh
104

La chon dang khang sinh thch hp
- Cn c vao v tr nhim khun va mc nhim khun

chn dng thuc.
- Hn ch s dng khang sinh ti ch.
Ch dung khi nhim khun mt.
i vi nhim khun ngoai da nen
dung thuoc sat khun: con etylic,

con iod, polyvidone iod, thuoc o,
thuoc tm, clorhexidin, cetrimide.
105

Phai s dung ung lieu lng.
- Dung ngay khang sinh lieu ieu tr can thiet.

- Dung u lieu e at nong o u va on nh.
- Khong bat au t lieu nho roi tang dan lieu.
- ieu tr lien tuc, khong ngat quang hoac ngng ot
ngot.
- Khong giam lieu t t e tranh e khang thuoc.
106

Dung khang sinh ung thi gian qui nh.
-Thi gian s dung thuoc phu thuoc vao nhieu yeu to:
-Tnh trang nang nhe cua benh nhan.
-Tac nhan gay benh.
-Ni nhiem trung.
-Tnh trang he mien dch cua benh nhan.
- Nguyen tac chung: s dung khang sinh en
het vi khuan trong c the + 2-3 ngay ngi
bnh thng; hoac + 5-7 ngay ngi suy
giam mien dch.
- Sau 2 ngay dung khang sinh, sot khong giam
th can thay hoac phoi hp khang sinh.
107

S dung khang sinh d phong hp ly
Nham:
Ngan chan s nhiem trung.
S dung lai khi co dau hieu nhiem trung tai phat.
Thng ch nh phong nga trong cac trng hp:

Tiep xuc vi cac tac nhan gay benh
Benh nhan co nguy c nhiem trung cao
Trong phau thuat
Theo nguyen tac:

Thi iem cho thuoc va ng cho thuoc ung
La chon khang sinh ung, theo loi phau thuat.
o dai cua t ieu tr.
108

Phoi hp khang sinh khi that can thiet
Nham:
ieu tr nhiem khuan do nhieu loai vi khuan.
Trong benh nang cha ro nguyen nhan.
Tao sc manh hp ong khang khuan.
Ngan nga vi khuan phat trien dong
khang thuoc.
Giam oc tnh do dung lieu cao hay dai ngay.
109

Bat li:
Tao tam ly an tam cho ngi thay thuoc,
khong con tch cc tm kiem tac nhan gay
benh.
Tang tac dung phu cua khang sinh.
Tang chi ph ieu tr.
Nen han che phoi hp v a co khang sinh pho rong.

Tot nhat la tm ra tac nhan gay benh e ch
s dung mot khang sinh manh nhat
va hieu qua nhat.
110

Khi phoi hp khang sinh phai:

at c hieu qua hp ong. V du:
PNC + Aminoglycoside
Trimethoprim + Sulfamethoxazole
Aci clavulanic+ Amoxicillin (Augmentin).
Khong phoi hp cac khang sinh gay hieu qua

oi khang nhau. V du: Tetracycline va PNC.
Tranh phoi hp cac khang sinh co e khang
cheo, gay tac dung oc tren cung mot c
quan.
111

Phoi hp khang sinh khi that
can thiet
Khi phoi hp khang sinh phai

at c hieu qua hp ong.
V du:
PNC + Aminoglycoside
112

Khi phoi hp khang sinh phai at c hieu qua hp ong.

V du:
Trimethoprim + Sulfamethoxazole
113

Khi phoi hp khang sinh phai at c hieu qua hp ong. V du:

Sulbactam + Ampicillin (Unasyl).
114

Khi phoi hp khang sinh phai:

Khong phoi hp cac khang sinh gay hieu qua oi
khang nhau. V du:
Tetracycline va PNC.
Erythromycin,lincomycin, Chloramphenicol.
Gentamicin b mat hoat tnh bi PNC
khi tron chung trong tiem truyen tnh mach.
Tranh phoi hp cac khang sinh co e khang
cheo, hoac gay tac dung oc tren cung
mot c quan.
115

Nguyen tac phoi hp khang sinh:

Nam 1952, Jawetz neu nguyen tac phoi hp khang sinh, theo
o khang sinh c chia lam 2 nhom ln theo tac dung:
Nhom I: Khang sinh co tac dung khang khuan, gom:
Beta-lactam.
Polypeptid.
Aminosid.
Vancomycin.
Nhom II: Khang sinh co tac dung km khuan, gom:
Tetracyclin.
Macrolid.
Chloramphenicol.
Lincomycin.
Sulfamid.
116

Nguyen tac phoi hp khang sinh:
Phoi hp cac khang sinh trong nhom I vi nhau se co tac

dung cong hoac boi tang.
Phoi hp cac khang sinh trong nhom II ch co tac dung cong.
Phoi hp khang sinh trong nhom I + nhom II se co tac dung
oi khang. V du:
- Leper va Dowling (1951), tren viem mang nao
do phe cau khuan: ieu tr ch PNC, t vong la 21%;
khi phoi hp PNC la chlotetracyclin, t vong la 71%.
- Mathies et al. (1967), ieu tr viem mang nao do
trc khuan thay: neu dung ampicillin mot mnh,
t vong la 4,3%; khi phoi hp ampicillin vi
chloramphenicol va streptomycin th t vong la 10,5%.
117
VIII. CC KHNG SINH CHNH

1. Nhm Beta-lactam
118

1. Nhm Beta-lactam
Ve cau truc eu co vong beta-lactam.
Da theo cau truc hoa hoc, 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.
119

1. Nhm Beta-lactam-Cc penicillin.
Loi Penicillin
PNC ph hp (t
nhin)
BenzylPNC (PNC G)
PNC ph rt hp
(PNC khng PNCase)
-Methicillin
-Oxacillin,
Dicloxacillin.
-Nafcillin
Hp thu
qua rut
Km
Km
Tt
Ph khng khun
Tt trn streptococci, enterococci,
Listeria, N.meningitidis.
Rt tt vi vi khun k kh (tr
B.fragilis). t tc dng trn trc khun
Gr(-) v vi khun tit -lactamase.
C hot tnh vi Staphylococcus
aureus v S. epidermidis tit lactamase khng khng methicillin.
Khng c hot tnh vi Listeria
monocytogenes v Enterococcus spp.
Thay i
120

Penicillin G
-c Fleming tm ra au tien nam 1928, t nam Penicillium

notatum hay P. chrysogenum.
-1 ml moi trng nuoi cay cho 300UI; 1UI= 0,6 g Na benzylPNC.
-Dung dch nc ch ben pH=6-6,5, mat tac dung nhanh pH<5
va >7,5.
-Pho khang khuan:
+ Cau khuan Gr(+): Strep., phe cau va tu cau
khong tiet PNCase.
+ Cau khuan Gr(-): lau cau, mang nao cau.
+ Trc khuan Gr(+) ai kh va yem kh.
+ Xoan khuan: Treponema pallidum (giang mai).
121

Penicillin G
-Dc ong hoc:
+ Hap thu: b dch v pha huy nen khong uong c. Cmax at c
15-30 phut khi IM, nhng giam nhanh (can tiem 4 gi/ lan).
+ Phan phoi: 40-60% gan vi protein huyet tng. Kho vao xng va
nao, nhng khi mang nao viem, [c]/dch nao tuy bang
1/10 huyet tng. T1/2=30-60 phut ngi bnh thng.
+ 60-70% thai tr qua than dang khong con hoat tnh.
90% cua lng thai tr la bai xuat qua ong than. Probenecid
c che qua trnh nay, lam cham thai tr PNC.
-oc tnh: t oc, nhng ty le gay d ng kha cao (1-10%),
Co the gay t vong do choang phan ve.
-Co d ng cheo vi moi beta-lactam va cephalosporin.
122

Penicillin
V, uong (Oracillin, Ospen)
Khong b dch v pha huy, hap thu ta trang, nhng phai dung lieu gap
oi PNG mi at c nong o huyet thanh tng ng. Dung cach 6h/
lan.
PNC khang
Penicillinase hay PNC ban tong hp:
Pho khang khuan va thi gian tac dung tng t PNG,

nhng cng o tac dung yeu hn.
+ Methicillin: IM hoac IV 2-8g/24h, chia lam 4 lan,
khong uong c.
+ Oxacillin (Bristopen), Cloxacillin (Orbenin):
ben vi dch v, dung uong.
Ch nh: Nhiem khuan do tu cau san xuat PNCase.
Co the gay viem than ke, c che tuy xng lieu cao.
123

Loi Penicillin
PNC ph rng
(AminoPNC)
-Ampicillin
-Amoxicillin
-Bacampicillin
Hp thu
qua rut
Tt
Rt tt
Ph khng khun
Tt hn PNC trn Listeria
monocytogenes v Enterococci nhy
cm.
M rng 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
Dng ng ung.
124

Penicillin co pho rong
La PNC ban tong hp, aminoPNC.
Khong b dch v pha huy, uong c nhng hap thu khong hoan toan
(khoang 40% /v ampicillin; Amoxicillin co ty le hap thu qua ng
uong cao, khoang 90%).
Metampicillin, Bacampicillin, khi uong b thuy phan giai phong
ampicillin.
Ch nh chnh:viem mang nao mu, thng han, nhiem
khuan ng mat, tiet nieu.
125

Penicillin khang trc khuan mu xanh (Pseudomonas
aeruginosa):
La PNC ban tong hp, co ac iem:
+ Tac dung tren cau khuan Gr(+) kem hn Ampicillin.
+ ac biet tac dung tren trc khuan mu xanh va mot so chung san xuat
cephalosporinase (Enterobacter, Proteus).
Ch nh chnh:nhiem khuan Gr(-) nang a khang vi ampicillin
hay Cephalosporin, nhiem khuan khung chau, trong o bung.
Gom co:
+ Nhom carboxyPNC (S c thay the bang C):
Carbenicillin, IV, t1/2= 2 gi.
+ Nhom UreidoPNC: Tham nhap vao mo tot hn.
Ch co dang IM hoac truyen tnh mach. t1/2=1-2 gi.
126

1. Nhm Beta-lactam-cc cephalosporin
Loi
Cephalosporin
Ph khng khun
Ch nh
Th h 1
Dng ung:
-Cephadroxil
Dng ung v tim
-Cephradin
Dng tim
-Cephalothin
-Cephapirin
-Cefazolin
Ph hp, nhy cm vi lactamase.

Gr(+): hu ht cu khun
gram(+), tr enterococci v
MRSA.
Gr(-): E.coli, K. pneumoniae,
P.mirabilis, M. catarrhalis.
Cu khun k kh:
Peptococcus,
Peptostreptococcus.
-Nhim trng nh
ng tiu, nhim
trng da hoc m
mm do
staphylococci hoc
streptococci.
-Cefazolin l thuc
la chn phng nga
trong phu thut, thay
th cho trng hp d
ng vi PNC khi
nhim staphylococci
hoc streptococci
127

Loi
Cephalosporin
Ph khng khun
Ch nh
Th h 2
Dng ung:
-Cefaclor
-Cefuroim axetil
Dng ung v tim
-Cefuroxim
Dng tim
-Cefoxitin
-Cefamandol
-Cefmetazol
-Cefotetan
-Gr(+): nh th h 1, nhng
km hn.
-Gr(-): M rng hn th h 1,
Enterobacter spp, Proteus
indol(+), Klebsiella spp.
--fragilis nhy cm vi
cefoxitin, cefmetazol,
cefotetan.
-Khng tc dng vi
Enterococci v Pseudomonas.
-Nhim H.influenzae
nh vim tai gia,
vim xoang, vim
phi thu nhn cng
ng.
-Cefoxitin,
cefmetazol, cefotetan
thay th Cefazolin
phng nga trong
phu thut.
- Khng tr nhim
Enterobacter v
khng.
128

Loi Cephalosporin
Th h 3-4
Dng ung:
-Cefixim
-Ceftibuten
-Cepodoxim
Dng tim
-Ceftriaxon
-Cefotaxim
-Ceftazidim
-Cefoperazon
Moxalactam
Cefepim (th h 4)
Ph khng khun
Ch nh
-Ph m rng hn th h 2 trn

vi khun Gr(-). Khng hu ht lactamase.
-Gr(+): Km hn th h 1.
-Gr(-): m rng n hu ht
Enterobacteriaceae, c hot tnh
tt vi Haemophillus v
Neisseria tit -lactamase,
Pseudomonas.
-Vi khun k kh: -fragilis
-Khng c hot tnh tin cy vi
enterococci, C.difficile, L.
monocytogenes
-Tr nhim trng nng khng

cepha. khc, AG, PNC.
-Thuc la chn nhim
Klebsiella, Enterobacter
-Tr lu.
-Vim mng no do
meningococci, pneumococci,
H. influenzae, Pseudomonas.
-Vim phi thu nhn cng
ng do H.influenzae,
S.aureus.
-Nhim trng da, h hp,
ng tiu, xng khp,
mu, mt, vim mng trong
tim, bng vng chu, sn
ph khoa
129

Loi
Cephalosporin
Th h 4
Cefepim
Ph khng khun
Ch nh
-Tng t ceftazidim, chng

c Enterobacteriaceae v
Pseudomonas, c hot tnh
cao hn streptococci,
Enterobacter, MSSA.
-Thm tt qua no.
-Tr nhim trng bnh

vin do vi khun Gr(-),
Enterobacteriaceae,
Pseudomonas.
130

1. Nhm Beta-lactam
Ph khng khun
CARBAPENEM
Imipenem
Meropenem
Ertapenem
Pseudomonas
Gram
(+)
++
++
+
++
+
Gram (-) Acinetobacte

hiu kh
r
+
++
++
++
+
Mt hot tnh bi
dihydropeptidase
( ng thn)
+
-
Imipenem:
khng cao vi hu ht Beta-lactamase.
Mt hot tnh bi dihydropeptidase ng thn, thng
c phi hp vi cilastatin (cht c ch dihydropeptidase)
ko di t1/2 v ngn cn thnh lp cht chuyn ho
gy c cho thn.
131

1. Nhm Beta-lactam
Imipenem:
Ph khng 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 kh nh Bacteroides, k c
B. fragilis, Clostridium.
Vi khun khng: Enterococcus faecium, MRSA,
Clostridium difficile.
Ch nh: Cc nhim trng nng khng vi cc
thuc khc cc vi khun nhy cm.
132

1. Nhm Beta-lactam
AZTREONAM:
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 gy c 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 c
tin 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 (-).
133

2. Cc cht c 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 v tng cng hot tnh khng khun
ca khng sinh ny.
134

3. Nhm Aminoglycoside
135

Cn gi l aminosid
C 4 c tnh chung cho c nhm:
Hu nh khng hp thu qua ng tiu ho v c PM cao.
Cng mt c ch tc dng.
Ph khng khun rng, ch yu chng vi khun
hiu kh Gr(-).
c tnh chn lc vi dy thn kinh VIII v
vi thn (tng creatinin huyt, protein-niu c hi phc).
136

Hot tnh khng khun:
Tc ng trn hu ht trc khun gram(-) hiu
kh (k c Pseudomonas).
Tc ng gii hn trn vi khun gram(+): S.
aureus v S. epidermidis, khng vi hu ht
enterococci. t tc dng i vi streptococci.
t tc ng trn vi khun k kh.
137

Thuc
Ch nh
Gentamicin, Amikacin, Nhim vi khun Gr(-) hiu kh nng k c

Tobramycin, Netilmicin E.coli v Enterobacter, Klebsiella,
(IM/IV)
Proteus, Pseudomonas v Serratia sp.
Streptomycin (IM/IV)
Lao phi, dch hch, nhim Brucella,

vim mng trong tim.
Neomycin (PO, ti ch).

Kanamycin (IM/IV)
-Nhim trng da, rut.

-Tr lao.
Spectinomycin (IM)
Lu.
138

4. Nhm Phenicol
Hot tnh khng khun:
Ph khng khun rng, c ch hu ht vi khun
k kh, hiu kh gram(-) v gram (+).
Tc ng km khun l ch yu nhng l cht
dit khun vi H. influenzae, S. pneumoniae,
Neisseria meningitidis v mt s Bacteroides.
139

4. Nhm Phenicol
Dc ng hc: t nng ti a trong mu 2h
sau khi ung, t1/2 t 1,5-3h, khong 60% gn vo
protein huyt tng.
Hai c tnh l suy ty v hi chng xm
(thng gp tr s sinh).
L cht c ch enzym chuyn ho thuc gan
nn ko di t1/2 v lm tng nng trong huyt
tng ca phenytoin, tolbutamid, warfarin,..
140

5. Nhm Tetracycline
141

5. Nhm Tetracycline
L khng sinh km khun ph rng. Hot tnh ca cc cht c
xp theo th t sau:
Minoxyclin>Doxycyclin>tetracycline, oxytetracyclin
Tc dng:
Cu khun Gr(+) v Gr(-), nhng km hn 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.
142

5. Nhm Tetracycline
Dc ong hoc:
- Hap thu qua ng tieu hoa 60-70%. De tao phc vi sat, calci,
magne va casein trong thc an, lam giam hap thu. Nong o toi a
trong mau at c sau 2h.
- Gan vao protein huyet tng 30% (oxytetracyclin) en 50%
(tetracyclin) hoac tren 90% (doxycyclin). Tham vao
c dch nao tuy, nhau thai, sa. Do tham vao c
trong te bao nen co tac dung tot trong ieu tr cac
benh do Brucella. Gan manh vao he li noi mo
cua gan, lach, xng, rang.
- Thai tr qua gan (chu ky gan-ruot) va than.
143

5. Nhm Tetracycline
Ten thuoc
Hap thu theo
CL than
t1/2
Phan loai
PO (%)
(mL/phut)
(gi)
tac dung
Clotetracyclin
30
35
6-8
Ngan
Oxytetracyclin
60-70
90
Tetracyclin
65
Demeclocyclin
35
12
Methacyclin
31
Doxycyclin
90-100
16
16-18
Minocyclin
10
Trung bnh
Dai
144

5. Nhm Tetracycline
Ch nh
Tr nhim Mycoplasma pneumoniae (vim phi ngi ln), Rickettsia, Vibrio

v Chlamydia (vim trong c t cung, ng tiu, trc trng, mo tinh hon,
bnh mt ht).
Thay th penicillin tr nhim Actinomyces, bnh than, giang mai, nhim trng
h hp do H.influenzae.
Tr nhim Brucella, tularemia, dch hch (phi hp vi AG).
Tr vim ph qun, mn trng c
Tr nhim protozoa (Entamoeba histolytica hoc Plasmodium falciparum), tr

vim d dy ti pht do H.pylopri (phi hp).
Doxycyclin nga tiu chy du khch, tr st rt v amib, vim phi thu nhn
cng ng. Thuc c o thi qua phn nn l loi tetracycline an ton
iu tr nhim trng ngoi thn cho ngi suy thn. Khng dng cho iu tr
nhim trng ng tiu.
145

6. Nhm Macrolide
Ph khng khun ging PNC: tc ng trn vi khun gram(+), t tc
ng trn vi khun gram (-). Hon ton khng tc dng trn trc
khun ng rut v Pseudomonas.
Ch nh
Tr nhim Corynebacteria (bch hu, nhim trng huyt), mycoplasma
pneumoniae (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 do
S.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 nhn
bnh van tim.
Ph n mang thai nhim trng niu-sinh dc: erythromycin l thuc lc chn,
azithromycin l thuc thay th.
Phong n gnh do C. tetani.
Tr bnh phong: Clarithromycin + minocyclin.
146

7. Nhm Lincosamide
Clindamycin c hot tnh mnh hn v sinh kh dng ng ung cao hn
Lincomycin. Hot tnh khng khun trn hu ht vi khun gram (+) (tr
enterococci), vi khun k kh gram (+) v (-) (tr Clos. Difficile). Khng c tc
ng trn vi khun gram (-) hiu kh hoc ty . Hp thu gn hon ton bng
ng ung, t chu nh hng ca thc n. Thi tr ch yu qua ng mt.
Ch nh
Hiu qu cho nhim cu khun gram (+). Ch yu tr nhim trng vng bng
v ng niu sinh dc n do B.fragilis.
Thay th PNC trong abces phi.
Tr nhim Pneumocytis carrinii v toxoplasma gondii no.
Phng nga vim mng trong tim cho ngi bnh van tim d ng vi
penicillin.
Do thm tt vo xng, nn dng tr vim ty xng.
Dng ti ch tr mn trng c.
147

8. Cc QUINOLON
Khang sinh tong hp, la cac acid yeu, gom co:
+ Loai kinh ien (hay the he 1): acid nalidixic (1963).
+ Loai mi: gan them fluor vao v tr 6, goi la 6-fluoroquinolon
Cac quinolon the he 1 ch c che ADN-gyrase nen ch co tac
dung diet khuan Gr(-) ng tiet nieu va tieu hoa. Khong co
tac dung tren P. aeruginosa.
Cac fluoroquinolon co tac dung tren 2 enzym ch la ADNgyrase va topoisomerase IV cua vi khuan nen pho khang
khuan rong hn, hoat tnh khang khuan manh hn 10-30 lan.
148

8. Cc QUINOLON
+ Cac fluoroquinolon the he au, con goi quinolon the he 2:
- Gom: pefloxacin, norfloxacin, ofloxacin, ciprofloxacin.
- Khac nhau ve tac ong tren gyrase va topoisomerase IV:
Tren vi khuan Gr(-): Hieu lc khang gyrase manh hn.
Tren vi khuan Gr(+): co hieu lc khang topoisomerase IV
manh hn.
+ Cac fluoroquinolon the he mi, con goi la quinolon the he 3:
- Gom: levofloxacin, trovafloxacin, gatifloxacin.
- Co tac ong can bang tren ca 2 enzym, nen pho khang khuan
m rong tren ca Gr(+), nhat la cac nhiem khuan ng ho hap;
va vi khuan cung kho khang thuoc hn v phai ot bien 2 lan
tren 2 enzym ch.
149

8. Cc QUINOLON
Quinolone th h 1 c ph tc dng hp, ch tc dng trn vi khun gram (-),
ch yu dng iu tr nhim khun tit niu. Cc Fluoroquinolone c hot tnh
trn: E.coli, Salmonella, Shigella, Enterobacter, Neisseria, P.aeruginosa,
Enterococci, pneumococci, staphylococci khng meticillin.
Ch nh
Tr nhim trng ng tiu, vim tuyn tin lit
Tr nhim trng tiu ha nh tiu chy nhim trng: hu ht cc vi khun
gy bnh ng rut u nhy cm nh E.coli, Salmonella, Shigella
Tr nhim trng m mm, xng khp, da, vim xoang cp, nhim trng
bng (phi hp vi metronidazole), nhim trng h hp di k c vi khun
a khng thuc nh pseudomonas, Enterobacter, vim ni tm mc, nhim
trng bnh vin.
Tr cc bnh ly truyn theo ng tnh dc: bnh lu (ofloxacin hoc
ciprofloxacin), h cam (ciprofloxacin), vim niu o v c t cung.
150

9. Cc thuc khng nm
4 nhm bnh nm chnh
Bnh nm b mt.
Bnh nm ngoi da
Bnh nm di da
Bnh nm ni tng:
Nhim nm c hi.
Nhim nm khng c hi.
151
Ringworm
152
9. CAC KHANG SINH KHANG NAM
153

9. Cc thuc khng nm
I. Thuc khng nm ni tng

Amphotericin B.
Flucytosin.
Cc azol:
Imidazol: Clotrimazol, miconazol,
ketoconazol.
Triazol: Fluconazol, itraconazol,
Voriconazol.
Echinocandn.
154

9. Cc thuc khng nm
II. Thuc tr nm 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.
155

9. Cc thuc khng nm
9.1 GRISEOFULVIN :
C tnh km nm. Tc ng trn nhiu dng vi nm ngoi da.
Khng c tc ng trn vi khun hoc cc nm gy bnh ni tng.
9.2. NYSTATIN :
Thuc nhm khng nm loi polyen. Hu nh khng hp thu
qua da, nim mc, rut. Khng dng cho ng hp thu ton thn
(tim chch) v gy c.
9.3. KETOCONAZOL :
Thuc nhm khng nm imidazol. Thuc hp thu tt qua qua
dng ung, tt nht pH acid (ngi thiu acid dch v hoc ang
dng thuc antacid, thuc khng th th H1 s lm gim hp thu
ketoconazol).
156
9.1. GRISEOFULVIN:
a. Tac dung phu:
Nhc au, chong mat.
Gay roi loan nhe da day, ruot.
b. Ch nh:
Cac benh nam ngoai da.
Nam mong tay, mong chan.
Benh nc an chan.
Nam toc.
c. Chong ch nh:
Phu n co thai.
Suy gan nang.
D ng vi thuoc.
157
9.1. GRISEOFULVIN:
d. Cach dung:
Uong ngay sau ba an va uong
nhieu nc. Dang vien 250, 500mg:
Ngi ln: 0,5-1g, chia 2-4 lan.
Tre em: 10-20mg/kg/ngay.
Boi ngoai da: thuoc m 5%.
Nen phoi hp thuoc uong vi thuoc
boi ngoai da e tang hieu qua ieu
tr.
e. Bao quan: Chai lo nut kn, theo doi
han dung.
158
9.2. NYSTATIN (Mycostatin):

a. Tac dung phu: Gay roi loan nhe ng tieu
hoa (buon non).
b. Ch nh:
Nhiem nam do Candida ng tieu hoa,
niem mac mieng, ngoai da, am ao,.
Phoi hp vi khang sinh pho rong
(Tetracyclin) e e phong nhiem nam
Candida.
c. Dang thuoc:
Thuoc vien 250.000 UI-500.000 UI.
Thuoc m 100.000 UI.
Vien at am ao 100.000 UI.
159
9.2. NYSTATIN (Mycostatin):

d. Cach dung:
Uong:
Ngi
ln:
250.000-500.000
UI/lan x 3-4 lan/ngay x 4-5 ngay.
Tre em: 75.000-750.000 UI/ngay,
tuy theo tuoi, chia 4 lan.
Boi ngoai da: dang thuoc m
100.000 UI.
at am ao: dang vien 100.000UI, 12 vien/ngay. Moi t 20 ngay.
c. Bao quan: Chong am, tranh anh sang.
160
9.3. KETOCONAZOLE (Nizoral)

a. Ch nh:
Nhiem nam do Candida va cac
nam khac.
t hay khong hieu qua ngi b
suy giam mien dch, benh viem
mang nao.
b. Cach dung:
Uong 200-600mg/ngay, chia lam 23 lan.
Dang kem 2%boi tai cho.
Dau goi.
161

10. VANCOMYCIN
- La glycopeptid, co nguon goc t Streptococcus orientalis, co tnh
diet khuan. Phan t lng=1500, tan trong nc.
- Tac dung chu yeu tren Gr(+), phan ln la tu cau gay benh, ke ca
tu cau tiet beta-lactamase va khang methicillin. Co tac ong
hiep ong vi gentamicin va streptomycin tren Enterococcus.
- Dc ong hoc: t hap thu qua ng tieu hoa nen thng c
dung ieu tr viem ruot ket gia mac do tetracyclin hay
clindamycin. Gan vi protein huyet tng khoang 55%. Tren
90% thai qua loc cau than. t1/2 khoang 6 gi.
- Tac dung khong mong muon (10%): viem tnh mach tai cho tiem
truyen, ret run, sot.
162

10. VANCOMYCIN
- La thuoc hang th 2 cho hau het cac nhiem trung.
- Dang uong: Tr viem ruot gia mac do Clostridium difficile khi
khong ap ng, khong dung nap hoac a e khang vi
metronidazol. Lieu 0,125-0,25mg moi 6 gi.
- Dang tiem:
- Tr nhiem staphylocci nang hoac nhiem Gr(+) a e khang
hoac khong dung nap vi cac thuoc khac.
- Nhiem MRSA nh abces nao, viem mang nao, viem mang
bung, nhiem trung huyet,.
- Cac nhiem trung nang o enterococci khang ampicillin.
- Phong nga trong phau thuat.
163

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THUOC S DUNG TRONG HOA TR LIEU

Thuoc khang sinh.

TRNG AI HOC Y DC CAN TH

MUC TIEU BAI GIANG

cac nhom khang sinh quan trong.

an toan, hp ly cac khang sinh thong dung.

Tai lieu tham khao

vao cac v tr tac ong cua no tren te bao

Do khang sinh co tac dung theo c che ac hieu nen

Pho khang khuan:

Vi khuan nhay cam vi khang sinh A va E, e khang vi

Hans Christian Joachim Gram

Ty so diet khuan ln hn hoac bang 2 c xem

qua trnh tong hp hoac chuyen hoa cua vi

II. PHAN LOAI KHANG SINH

II. PHAN LOAI KHANG SINH

II. PHAN LOAI KHANG SINH

II. PHAN LOAI KHANG SINH

II. PHAN LOAI KHANG SINH

II. PHAN LOAI KHANG SINH

II. PHAN LOAI KHANG SINH

II. PHAN LOAI KHANG SINH

II. PHAN LOAI KHANG SINH

II. PHAN LOAI KHANG SINH

Can c vao s lien quan gia nong o va

II. PHAN LOAI KHANG SINH

Tac dung sau khang sinh PAE (Post Antibiotic Effect):

PAE la tac dung c che s phat

II. PHAN LOAI KHANG SINH

Tac dung sau khang sinh PAE (Post Antibiotic Effect):

KS co PAE ngan hoac khong co PAE,

II. PHAN LOAI KHANG SINH

Phu thuoc thi gian. Phu thuoc nong o.

Khang sinh Beta lactam

Phu thuoc thi gian.

III. C CHE TAC ONG CUA KHANG SINH

III. C CHE TAC ONG CUA KHANG SINH

III. C CHE TAC ONG CUA KHANG SINH

Cau truc cua vach te bao vi khuan: Mucopeptide (Murein, Peptidoglycan)

III. C CHE TAC ONG CUA KHANG SINH

Cau truc vach te bao vi khuan cua

III. C CHE TAC ONG CUA KHANG SINH

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

Giai oan 3: Hoan tat noi ngang cua 2 peptidoglycan ke can.

III. C CHE TAC ONG CUA KHANG SINH

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

III. C CHE TAC ONG CUA KHANG SINH

III. C CHE TAC ONG CUA KHANG SINH

III. C CHE TAC ONG CUA KHANG SINH

III. C CHE TAC ONG CUA KHANG SINH

C che tac ong:

Penicillin Binding Protein (PBP).

giai oan khac nhau.

gay phan huy te bao vi khuan.

III. C CHE TAC ONG CUA KHANG SINH

bao tng cua tien chat peptidoglycan.

trong nhng bc tong hp au tien

III. C CHE TAC ONG CUA

V tr tac ong cua cac

III. C CHE TAC ONG CUA

V tr tac ong cua cac

III. C CHE TAC ONG CUA KHANG SINH

Lp peptidoglycan hnh thanh.