NHNG KHI NIM C

BN V KHNG SINH
BS Phm Th L Hoa

NI DUNG
1. NH NGHA V PHN LOI
2. DC NG HC CA KHNG SINH
3. NGUYN TC S DNG
4. PHNG TIN NH GI HIU QU KHNG

SINH
5. TAI BiN S DNG KHNG SINH
6. NHNG iM LU KHI CHN LA KHNG

SINH

1. NH NGHA V PHN
LOI
KHNG SINH: cht tc dng dit/ngn
cn sinh sn, pht trin ca vi sinh vt.
C ngun gc: Chit xut t cc vi sinh vt
Bn tng hp
Tng hp

1. NH NGHA V PHN LOI

LCH S KHNG SINH
1926: Alexander Fleming pht hin PNC t nm men.
1939, Edward Chain v Howard Florey: nghin cu
trn ngi bnh nhim trng nng.
1945: Fleming, Florey v Chain cng nhn gii Nobel
m ra th k ca KS.
1948: Chlortetracycline c s dng (Tetracycline
ACHROMYCIN, SUMYCIN) iu tr H. influenzae, S.
pneumoniae, M. pneumoniae, Chlamydia, N. gonorrhoeae...

Sau nhiu nhm KS mi c pht trin.

1. NH NGHA V PHN LOI

Nhiu cch phn loi KHNG SINH
Theo cu trc phn t (lipid, peptid, nucleosid)
Theo hot ph:
Hp: ch tc dng trn mt loi vi khun (nhm
khng lao, khng nm, khng siu vi)
Gii hn: ch tc dng trn vi trng gram (+)
(nhm macrolides, nhm synergistine)
Rng: tc dng trn vi trng gram (-) & gram (+)
Theo c ch tc dng: trn thnh TB, c ch STH
protein, c ch DNA.

HOT PH CA CC KHNG SINH THNG

DNG

PHN LOI KHNG SINH

CC NHM KHNG SINH THEO C CH TC
DNG
Tng hp thnh t bo

Tng hp Protein

Tng hp acid nucleic

Sao chp v sa cha
DNA

1. PHN LOI KHNG SINH

CC NHM KHNG SINH THEO C CH TC
DNG
NHM C CH TNG HP THNH T BO: gm

I. NHM LACTAM: c ch tng hp thnh t bo

Penicilline: Khng sinh t nm men
Penicilline G sodium (TM), potassium (TM,TB)
Pnicilline G procaine (TB),

Pnicilline V ( ung)

Isoxazolyl-penicilline: chng t cu: Methicilline,

Oxacilline/Dicloxacilline
Amino-penicilline: LACTAM tng hp, ph rng: Ampicilline,
Amoxicilline, BacAmpicilline
Carbapenem: ph rng: Imipenem, Meropenem
Monobactam: ph rng: Astreonam

1. PHN LOI KHNG SINH

CC NHM KHNG SINH THEO C CH TC
DNG
NHM C CH TNG HP THNH T BO (tip)

II. NHM CEPHALOSPORINE: c ch tng hp thnh t bo

Th h I: chng VT gram (+): Cephalexin, Cefadroxyl,
Cephazolin
Th h II: chng VT gram (+): Cefaclor, Cefamandole,
Cefotetan, Cefuroxime
Th h III: ph rng, chng VT gram (-), qua mng no tt,
thng dng cho nhim trng nng.
Cefotaxime, Ceftriaxone, Ceftazidime (dng chch)
Cefoperazone, Cefixime, Cefpodoxime (dng ung)
Th h IV: tng t th h III, dng trong nhim trng nng,
nhim trng BV. Gm Cefpirom, Cefepime (dng chch)

PHN LOI KHNG SINH

CC NHM KHNG SINH THEO C CH TC
DNG
NHM C CH TNG HP THNH T BO (tip)

III. NHM C CH LACTAMASE: Gm

Acid clavulanic
Sulbactam.
Thng c kt hp nhm Aminopnicilline:
Amoxcicilline+A.Clavulinic (Augmentin)
IV. NHM GLUCOPEPTIDE: gm Vancomycine, Teicoplamin.

1. PHN LOI KHNG SINH

CC NHM KHNG SINH THEO C CH TC
DNG
NHM C CH SINH TNG HP PROTEIN CA RIBOSOME:

V. NHM AMINOGLYCOSIDE: c ch tng hp

protein ribosome, td ch yu VT gram (-), mt s
gram (+), khng tc dng trn k kh v VT ni t bo.
Dng chch, Gentamycine, Streptomycine, Amikacine,
Netilmycine, Tobramycine.
VI. NHM TETRACYCLINE: c ch tng hp protein
ribosome. dng ung. Gm Tetracycline, Doxycycline,
Minocycline,

1. PHN LOI KHNG SINH

CC NHM KHNG SINH THEO C CH TC
DNG
NHM C CH SINH TNG HP PROTEIN CA RIBOSOME (tip)
VII. NHM MACROLIDE : Gm
Macrolide th h c (Erythromycine, Rovamycine,
Josamycine)
Macrolide th h mi c dc ng tt hn
(Roxithromycine, Azithromycine, Clarithromycine)
v cc LINCOSAMiDE: Lincocin, Clindamycin
VIII. NHM CHLORAMPHNICOL: dng ung hay chch

1. PHN LOI KHNG SINH

CC NHM KHNG SINH THEO C CH TC
DNG
NHM NH HNG TRN TNG HP DNA v ACID NUCLEIC
IX. NHM SULFAMIDES: (Sufamethoxazole,
Sulfadoxine) thng c kt hp vi nhm
Diaminopyrimidin nh Trimethoprim
X. NHM DI-AMINOPYRIMIDINE: Trimethoprim,
Pyrimethamine

1. PHN LOI KHNG SINH

CC NHM KHNG SINH THEO C CH TC
DNG
NHM NH HNG TRN TNG HP DNA v ACID NUCLEIC (tip)

XI. NHM QUINOLONE: c ch men ADN gyrase ca qu trnh tng

hp acid nucleic. Gm:
Cc quinolone c khng cha fluor (Acid nalidixic, A.pipemidic)
Cc quinolone mi hay cc Fluoroquinolone nh (Ofloxacine,
Pefloxacine, Ciprofloxacine, Gatifloxacine, Levofloxacine)
NHM TC NG LN MNG T BO CHT
XII. NHM NITROIMIDAZOLE: tc dng trn mng t bo VT gm
Metronidazole, Secnidazole (iu tr amp v nhim trng k kh)

1. PHN LOI KHNG SINH

CC NHM KHNG SINH THEO C CH TC
DNG
CC NHM KHNG SINH KHC
XIII. NHM MYCOBACTER: chng VT lao (INH,
Ethambutol, Rifampicine)
XIV. NHM KHNG NM: Amphotericine B (chch),
Nystatin, Itraconazole, Fluconazole, Ketoconazole (ung)
XV. NHM KHNG VIRUS: c ch s pht trin ca siu vi
Acyclovir, Valacyclovir
Lamivudine, Tenofovir, Adefovir
Zidovudine, nevirapine, Efavirenz
Oseltamivir, Zanamivir

2. DC NG HC
S HP THU: qua ng tiu ha ty thuc vo c tnh
ha hc ca KS v pH t trng.
VN CHUYN TRONG HUYT TNG: dng t do
hay gn kt vi protein trong huyt tng.
S KHUCH TN VO M: ty thuc:
Kh nng gn kt vi protein trong huyt tng (gn
kt nhiu lu li trong mu lu hn)
Bn cht m hc v ti mu: c quan su, t mch
mu: thuc kh vo hn.

2. DC NG HC
S CHUYN HA: Sau khi n m hay qua gan, thuc
chuyn ha thnh cht bin dng khc:
Cht bin dng cn c hot tnh khng khun
hay

khng ty bn cht KS.

Cht bin dng c li lu trong c th v nh
hng tt hay xu i vi c th ty loi KS.

HiU NG P.A.E: Post Antibiotic Effect: hiu ng hu

khng sinh: l hiu ng vn cn tc dng c ch c
VT d nng KS khng cn cao hay khi ngng KS.

KS M

KS THN

KS
DNG
T
DO

KS
DNG
KT
HP

MU

KS VNG SANG
THNG

2. DC NG HC
S THI TR:
Qua ng tit niu: C tc dng tt vi nhim trng tiu
nhng c th c cho thn hay b tch ly thuc nu suy
thn
Qua ng gan mt: C tc dng tt vi nhim trng gan
mt, c th c cho gan hay b tch ly thuc nu suy gan
Qua ng h hp

2. DC NG HC
THI GIAN BN HY (Half Life)
l thi gian nng khng sinh trong huyt
tng gim cn 50% nng ban u
TG bn hy di khong cch dng xa, s ln dng t
hn
TG bn hy tng:
khi suy thn i vi KS thi qua thn (Aminoglycoside)
khi suy gan i vi KS thi qua ng gan mt
(Roxithromycine)
Cc c tnh dc ng c nh hng rt nhiu n vn
s dng, chn la KS

3. NGUYN TC S DNG KHNG

SINH

1. Xc nh ch nh s dng khng sinh:

Khng phi tt c cc trng hp st u do nhim trng

Cn ch nh KS cht ch trnh cc tai bin ph
C th m rng ch nh KS c a c bit (ngi gi, tr em
nh..)
2. Ch dng khng sinh sau khi ly bnh phm nui cy
(Cy mu, cy nc tiu, dch no ty, pht m da, pht m
tai)
3. Chn khng sinh ty theo tc nhn gy bnh d on:
da vo: Bnh cnh lm sng. Kinh nghim ca thy thuc
(trc khi c kt qu soi cy vi trng)
4. Chn khng sinh c hiu qu nht, t c, t gy tai bin.

3. NGUYN TC S DNG KHNG

SINH

5. Theo c a bnh nhn:

Gim min dch: t nhin hay mc phi.

Gim chuyn ha KS ( trng thnh, chc nng gan, thn)
Tr s sinh: gan thn cha trng thnh, tch ly KS)
Ph n c thai, cho con b: KS khuch tn qua nhau gy c cho bo
thai (Sulfamide, Aminoside, Rifampicine qui thai nu s dng 3 thng
u thai k; Sulfamide vng da nhn; Ttracycline tn thng mm
rng, xng)

3. NGUYN TC S DNG KHNG

SINH

5. Theo c a bnh nhn:

Tr s sinh thiu thng: Thi gian bn hy di tch t thuc

tng kh nng c tnh (TD: hi chng xm do chloramphenicol tr
nh nhi; gim pht trin rng, xng do Ttracycline)
Ngi nhiu tui: Km hp thu qua ng tiu ha, o thi chm
qua thn, khuch tn vo m chm, gim gn kt vi albumine, Phn
ng d ng nhiu.

3. NGUYN TC S DNG KHNG

SINH
6. PHI HP KHNG SINH: Mt s tnh hung cn phi
hp:
Nhim trng nng, e da tnh mng
C a suy gim min dch
Do nhiu loi vi khun gy bnh cng lc
Cn ngn nga to cc dng vi khun khng thuc
Ch phi hp khi c tc dng hip ng.

3. NGUYN TC S DNG KHNG

SINH
7. NG A KHNG SINH VO C TH:
ng ung: nu bn khng i, hp thu c
ng chch: nu nhim trng nng e da tnh mng
ng qua da, kh dung
8. CH BiN PHP H TR iU TR KHNG
SINH:
Khng c t (SAD, SAT)
Ngoi khoa: Dn lu m, ct lc.
Dinh dng

4. CC PHNG TIN NH GI HIU

QU KHNG SINH
nh gi v lm sng (in-vivo)
Ht st, ht du hiu nhim trng, ht cc triu chng bnh
Dng KS thi gian (ty vo loi bnh khc nhau)
nh gi v cn lm sng:
Theo di cy bnh phm sau khi dng khng sinh
MIC (Minimal Inhibitor Concentration)
MBC (Minimal bacteriostatic concentration)
E test
.

4. PHNG TIN NH GI HIU QU KHNG

SINH

Cc test NH GI NHY ca vi trng vi KS:

MIC (Minimal Inhibitory Concentration): Xc nh nng
c ch ti thiu ca vi trng vi mt loi khng sinh: L nng
KS ti thiu c th c ch 50-90% dn s vi trng trong
mi trng cy.
MBC: Minimal Bactericide Concentration Nng dit
khun ti thiu: l nng khng sinh thp nht ch li
0,01% vi khun sng sau 18-24h
Phng php a khng sinh :
a khng sinh (Disk diffusion test): o ng knh v
khun
E test: tnh c nng mc nhy hoc khng ca vi
trng i vi tng loi khng sinh.

Xc nh nng c
ch ti thiu (MIC)

PHNG PHP A KHNG SINH PP KIRBY BAUER

(O NG KNH KHNG KHUN)

NG DNG CC CH S V DC LC V DC NG HC
NNG KHNG SINH
C max

Cmax:MIC: t l nng
KS nh so vi MIC
T>MIC: thi gian nng
KS cao hn MIC

MIC

THI GIAN (Gi)

Th d c th v Cmax/MIC

MIC ca:
Cefalosporin-1: 1mcg/ml
Cefalosporin-3: 3mcg/ml
Nng /mu (Cmax) vi liu dng thng
thng:
CEF-1: 100mcg/ml: Cmax/MIC= 100/1
CEF-3: 600mcg/ml: Cmax/MIC=600/3=200/1

Khng tng thch gia in-vitro (+) v invivo (-)

tc dng ca PNC v TMP-SMX vi
Bartonella.
TMP-SMX vi Klebsiella pneumonia
PNC vi Hemophilus influenzae.

Cc nhm khng sinh, dc lc v dc ng hc

C s ti u ha liu s dng ca khng sinh

PK/PD Parameters

Toxicity

Absorption
Distribution
Metabolizatio
Elimination
n
AUC : Area Under the Curve

max

Cmax : Maximum Conc. Observed

Tmax : needed time to rise the
Cmax

Therapeuti
c Interval

T1/2 : half-life, needed time to

observe 50% plasma level
decreasing
Vd : Distribution Volume
Cl : Clearance

Minimum Activity
Concentration

T
max

T 1/2


5. CC TAI BIN S DNG KHNG
SINH
Tai bin do c tnh ca thuc:
Khng dng np thuc ti ch:
TB gy au, vim c.
TM gy vim tnh mach, huyt khi
Ung thuc gy kch thch d dy
Tn thng thn kinh:
SM gy ic, ri lon tn nh
INH gy vim dy thn kinh


5. CC TAI BIN S DNG KHNG
SINH
Tai bin do c tnh ca thuc:
Suy ty (chloramphenicol), gim bch cu
(Cephalosporin)
Tn thng gan: Tetracyclin gy thoi ho m ph
n c thai, INH, PZA gy vim gan
Tn thng thn: Aminoside gy suy thn.


5. CC TAI BIN S DNG KHNG
SINH

Phn ng d ng: Thuc vo c th phi hp vi protein

ca huyt tng khng nguyn phn ng d ng.
Khc nhau ty liu dng, cch dng
St (nhm lactam)
Pht ban da, ni m ay, nga, ni hch, au khp
Hi chng Stevens Johnson: vim da tp trung nhiu
quanh cc l t nhin
Xut huyt di da, xut huyt ni tng, ph Quinke.
Sc phn v
Lon khun ng rut: KS tiu dit cc vi khun
thng tr pht trin cc vi khun gy bnh

6. NHNG LU KHI LA CHN KHNG

SINH
1. Chn KS c hiu qu cao v nhanh (MIC thp)
Tc dng ng vo vi trng (ph khng khun ph hp)
Nng khuch tn vo m cao (tip cn c vi trng)
Khng khng thuc (KS).

C P.A.E.

Pht soi trc tip vi trng trc khi KS

2. An ton: t tai bin ph hoc tai bin thong qua, nh
Cht lng pha ch thuc: an ton (bin php k thut cao, c
kim tra cht lng)
3. Chn on chnh xc v tr v mc lan trn nhim trng.
Nhim trng da : KS ti ch (qua da, ung, ..)
Dn lu nhim. (Rch p xe, KS kh qua vch x)

6. NHNG LU KHI LA CHN KHNG

SINH

4. Tnh trng min dch ca bnh nhn.

Gim min dch: p ng km do khng c h tr ca MD.

Nhiu nguy c bi nhim
5. Tnh trng bnh c sn v th cht ca bnh nhn.
Tui, Thai k (KS qua nhau, qua sa m.
Toan chuyn ha do tiu ng.
acid ca d dy (hp thu KS)
Suy thn (gim thi tr, tch ly)
6. Chi ph: gi c hp l

7. Thun li s dng: Vin d ung, s ln ung d tun th

Thuc chch: khng au, t ln trong ngy
Thi gian dng ph hp vi sinh hot, thi gian ngn