Ch 20: Antimirobial Drugs

7/26/2019 Ch 20: Antimirobial Drugs

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"igure 20%#2 The structure of the antibacterial antibiotic erythromycin( a representative macrolide%


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2013 Pearson Education, Inc.

igure 20%#2 The structure of the antibacterial antibiotic erythromycin( a representative macrolide%

>rythromycin

:acrocycliclactone ring

h b f h


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Chec 1our nderstanding+hy does erythro#ycin, a #acrolide antibiotic,ha(e a spectru# of acti(ity li#ited largely togra#-positi(e bacteria e(en though its #ode ofaction is si#ilar to that of the broad-spectru#tetracyclines 20-;

f the three drugs often found in o(er-the-

counter antiseptic crea#sFpoly#y!in


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ulfonamides +sulfa drugs,Inhibit folic acid synthesis


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Action of >n@yme


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ulfametho!a@ole( asulfonamide that is astructural analog of*A3A( competitivelyinhibits the synthesisof dihydrofolic acidfrom *A3A%

Trimethoprim( astructural analog ofa portion of dihydrofolicacid( competitivelyinhibits the synthesisof tetrahydrofolic acid%

*A3A

ulfametho!a@ole

Dihydrofolic acid

Trimethoprim

Tetrahydrofolic acid

*A3A

ulfametho!a@ole

Dihydrofolic acid

Trimethoprim

*recursors of proteins(D4A( /4A

D4A/4A


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Chec 1our nderstanding+hat group of antibiotics interferes &ith the

$ -replicating en/y#e $ gyrase 20-11


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Commonly sed Antimicrobial Drugs

20-13 E!plain the #odes of action of currently usedantifungal drugs.

20-1 E!plain the #odes of action of currently usedanti(iral drugs.

20-1 E!plain the #odes of action of currently usedantiproto/oan and antihel#inthic drugs.

Learning Objectives

Antifungal Drugs?


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Antifungal Drugs? rgosterol ynthesis

*olyenes #photericin test +for epsilometer,( a gradient diffusion method that determines antibioticsensitivity and estimates minimal inhibitory concentration +:


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:


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2013 Pearson Education, Inc.Decreasing concentration of drug

Do!ycycline+9ro5th in all 5ells( resistant,

ulfametho!a@ole+Trailing end pointF usually read 5here thereis an estimated -0G reduction in gro5th,

treptomycin+4o gro5th in any 5ellF sensitive at allconcentrations,

>thambutol

+9ro5th in fourth 5ellsFe ually sensitive toethambutol and anamycin,

anamycin


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Chec 1our nderstanding

In the dis'-diffusion 94irby-


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/esistance to Antimicrobial Drugs

20-16 escribe the #echanis#s of drug resistance.

Learning Objective

"igure 20%2# The development of an antibiotic'resistant mutant during antibiotic therapy%

A ibi i i f b i l


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Days

3 a c

t e r i a

+ n u m

b e r

I m l ,

A n t i b i o t i c r e s i s t a n c e

+ m g

I m l ,

3acteriacount


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(ariety of #utations can lead to antibioticresistance

esistance genes are often on plas#ids ortransposons that can be transferred bet&een

bacteria

Antibiotic /esistance


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isuse of antibiotics selects for resistance #utantsisuse includes%

Gsing outdated or &ea'ened antibioticsGsing antibiotics for the co##on cold and other

inappropriate conditionsGsing antibiotics in ani#al feed"ailing to co#plete the prescribed regi#enGsing so#eone else s lefto(er prescription

$I *I $ ntibiotic esistance% "or#s of esistance

$I *I $ ntibiotic esistance% rigins of esistance

"igure 20%20 3acterial /esistance to Antibiotics%
http://antibiotic_origins.html/http://antibiotic_forms.html/


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#% 3loc ing entry

2% fflu! of antibiotic

Antibiotic

Antibiotic

Antibiotic

n@ymatic action

Clinical "ocus Antibiotics in Animal "eed Lin ed to Human Disease( "igure A%


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/esistanceplasmid

E .

c o l i

S .

e n t e r i c a

S . e

n t e r i c a

a f t e r c o n

j u g a t

i o n

Cephalosporin'resistance in E.coli transferred by conjugation

to Salmonella enterica in theintestinal tracts of tur eys%

Clinical "ocus Antibiotics in Animal "eed Lin ed to Human Disease( "igure 3%


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"E forhumans

"E forpoultry

"E for poultrydiscontinued

#$- #$-- #$$0 #$$2 #$$. #$$ #$$- 2000 2002 200. 200 200-

1ear

* e r c e n

t " E ' r e s

i s t a n t C a m p y l o

b a c t e r

0

&

#0

#&

20

2&

60"louro uinolone'resistant Campylobacter jejuni in the nited tates( #$- )200-%


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+hat is the #ost co##on #echanis# that abacteriu# uses to resist the effects of penicillin20-16

>ffects of Combinations of Drugs


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g

20-18 Co#pare and contrast synergis# andantagonis#.

Learning Objective

>ffects of Combinations of Drugs


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g

ynergism occurs &hen the effect of t&o drugstogether is greater than the effect of either aloneAntagonism occurs &hen the effect of t&odrugs together is less than the effect of either

alone

"igure 20%26 An e!ample of synergism bet5een t5o different antibiotics%


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Dis 5ith antibioticamo!icillin'clavulanicacid

Dis 5ith antibiotica@treonam

Area of synergisticinhibition( clear

Area of gro5th(cloudy

Antibiotic afety


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y

*herapeutic inde!% ris' (ersus benefit


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*etracycline so#eti#es interferes &ith the acti(ityof penicillin. )o& 20-18

"uture of Chemotherapeutic Agents


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p g

20-1; Identify three areas of research on ne&che#otherapeutic agents.

Learning Objective

"uture of Chemotherapeutic Agents


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Antimicrobial peptides


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Cytoplasm

D4A

/4Atranscript

m/4A

An abnormal gene(cancer gene( or virusgene is transcribed in ahost cell%

si/4A bindsm/4A%

/< C brea sdo5n the /4Acomple!%

4o proteine!pression occurs%

si/4A


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+hat are defensins 20-1;

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Ch 20: Antimirobial Drugs