Antimicrobials Pharm

8/13/2019 Antimicrobials Pharm

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"Drug of Last Choice"(brain abscesses,

typhoid fever, rocky mountain)



Cholarmphenico



1st generation

cephalosporins

clinical uses (name

the drugs)



Sugical prophylaxis

Soft tissue infections

Cefazolin (p)Cephalexin (o)

Cefadroxil (o)



2nd generation

cephalosporins

clinical uses (name

the drugs)



intra-abdominal infections

Cefoxitin (p)

Cefotetan (p)Cefuroxime (o)

Cefprozil (o)



All lactams have

sulfur in their

structure, what is th

purpose of this?



increase lipid

solubility andhypersensitivit



Aminoglycosid

toxicity



nephrotoxicity ototoxicity

not for pregnantneuromuscular blocka



Aminoglycosides

Chloramphenicol

Macrolides

Tetracyclines

StreptograminsLinezolid

Clindamycin

Tigecycline



Inhibit bacteria

protein synthesi(translation)



Aminoglycoside

are bacteriostatic?



False...Bacteriocidal...uniq

to this group

Cause misreading of mRN

template



Aminoglycosides demonstrate

concentration dependent killing?

Does it demonstrate post-antibiotic eff



True - high levels of antibiot

facilitate entry through cel

wall and membrane

Yes



Ampicillin

Amoxicillin

TicarcillinPiperacillin



Extended Range Penicilli

Think (more gram - use

amoxicillin = oral mode

ampicilin = parenteral/or



As one moves down the

generations of

cephalosporins what is th

general trend in terms o

spectrum of activity?



Tend to be mor

effective againsGram - bacteria



Augmentin



amoxicillin +

clavulonic acid



Bacteroides infectio

would be suitable t

be treated with Aztreonam



False....NO

Anaerobes



Bacteroides, clostridium

and actinomyces are alrelevant organisms to b

treated with

aminoglycosides



False...dont treatanaerobes

Killing mechanism is Odependent uptake



Besides Clavulonic

acid what are othe

Beta-Lactamaseinhibitors?



Sulbactam

Tazobactam

Amoxicillin-Clavulanic Acid - Augment

Ticarcillin/Clavulanic Acid - Timentin Ampicillin/Sulbactam - Unasyn P

Piperacillin/Tazobactam - Zosy P



Blurred vision

GI disturbancesProlonged QT interval

Exacerbation of

Myasthenia gravis



Telithromycin

Toxicity symptoms



Cefatrixone

treats what the best?



3rd generation -> H Influenzae

and Gram -, Lym



Cefazolin (p)

Cephalexin (o)Cefadroxil (o)



First generation

Cephalosporin



Cefepime (p)



4th generation

cephalosporin



Cefepime is

used to tx what



4th generationcepha-->

pseudomonas



Cefotaxime (p)

Ceftriaxone (p)

Ceftazidime (p)Cefdinir (o)



3rd generation

cephalosporin



Cefotetan tx

what the best?



2nd generation

--> Bacteriode



Cefoxitin (p)

Cefotetan (p)

Cefuroxime (o)Cefprozil (o)



Secondgeneration

cephalsporins



Ceftazidime

used to tx what



3rd generation

--> pseudom



Cephalosporin

Toxicity



Allergic/Hypersensitivity

Cross allergy/sensitivity bw penicillins and cephalospo

uncommon

Disulfiram-like reaction (cefoperazone) (ingestion with

alcohol produced headache, nausea, vomiting, abdomi

pain)

Bleeding diathesis

Phlebitis

Biliary obstruction



CephalosporinDO NOT tx

what?



LAME

listeriaatypicals

MRSA enterococci



Cephalosporinexcreted into

biliary tract



Ceforperazone(3rd generation

Ceftriaxone (3rd



Chloramphenicolmechanism of

action



binds 50s subunit

inhibits peptidyl

transferase bacteriostatic



Chloramphenicolmechanism or

resistance



plasmid mediated producti

of antibiotic inactivatingenzyme (acetyl transferase

Reduced permeability of bacterial organism to drug



Clavulonic Aci



beta-lactamase inhibit

often used with

penicillins to enhanceaction



Clindamycin isprimary

absorbed?





Clindomycinused against

what spectrum

G d



Gram + and

Anaerobes

NOTENTEROCOCCI



Clinical uses o

aminoglycoside

less potent when used alone often



less potent when used alone...often

combination

synergistic with cell wall active dru

gram - nosocomial

empirically for neonatal infections1st and 2nd line against

mycobacterial infections



Clinical Uses o

penicillin

t h iti



strep pharyngitis

rheumatic fever

prophylaxissyphilis



Clinical uses o

Tetracyclines



prostatitisgingavitis

SIADH



Concentrates inphagocytic cells

and other tissue



Azithromycin



Concentrates inrespiratory

secretions



Macrolides



Daptomycin isused in all age

groups?



False..notapproved for

children



Daptomycinmechanism of actio

and clinical uses

new lipopeptide antibiotic...IV only



p p p y

Cidal --> disrupts multiple aspects of bacteriplasma membrane function --> inhibits cell w

Resistance mechanism not yet defined

Skin and soft tissue infections, sepsis,

endocarditis (resistant gram + infections)

Difference in



Difference in

excretion bw

tetracycline anddoxycycline



tetra = urine

doxy = feces



Do penicillin crosseinto CNS, prostate

and eye



Minimally



DOC for borellia

bergdorfi?



Ceftriaxone -->

3rd generation



DOC for

legionella

think atypical



think atypical

Think Macrolide

KAPLAN FACT



DOC for nosocomilife threatening

diseases



Imipenem/Meropene

DOC fo o al



DOC for oral

treatment of

animal bites

Augmentin



Augmentin

(ampicillin +

clavulonic)

DOC for Rocky



DOC for Rocky

Mountain

Spotted Fever



tetracycline



DOC fortularemia, TB an

Bubonic blague





DOC of Atypica

Mycobacteria



Clarithromycin

(macrolide)



DOC of Atypica

Organisms



macrolides/ketolid



DOC of C Diff

Metronidazole



Metronidazole

May have to use it afterampicillin side effect

2nd DOC = oral vancomycKAPLAN FACT



DOC of Salmonella(typhoid) and

bordatella pertussi



Azythromycin

(macrolide)



DOC to treat

syphillis



Drugs that are



Drugs that are

contraindicated

in children

Daptomycin



Daptomycin

Tetracycline

(tigecycline)

Enterococcus



infection would be

suitable to be treate with Aztreonam

False only use



False...only use

this drug with

gram - rods

Extended Range



Extended Range

Ampicillin/AmoxicilliPenicillins Tx what

bugs? what clinical use

B.H. HEELS



B.H. HEELS

Borrelia, H pylori, H influenzae,Entorocci, E coli, Listeria, Strep pneum

Otitis media, sinusitis, pneumonia, Ulyme

Give an exampl



Give an exampl

of an

oxazolidione

Linezolid = first in



class

Blocks 50s initiatioBacteriostatic



Gray-Baby

Syndrome

Chloramphenicol can be



Chloramphenicol can be

conjugated because of

immaturity/decreased lev

of glucuronsyl transferas

Groups/Names of drug



Groups/Names of drug

that inhibit bacterialprotein synthesis

(translocation)

Aminoglycosides

Chloramphenicol



p

MacrolidesTetracyclines

Streptogramins

LinezolidClindamycin

Tigecycline



Idiosyncratic/dosrelated aplastic

anemia



chloramphenico

toxicity

If i use combo a



If i use combo a

tetracycline with a betlactam how would you

describe the relationshi

Antagonistic



Antagonistic

Static and Cidal



If it ends in "-

thromycin"



Think

Macrolides



Imipenem

excretion

Administered with Cilastatin which

inhibits renal inactivation



b

(dehydropeptidase effect) to prevekidney metabolism from occurring

too quickly

Dont mix...co-administer

Possible seizure side effect



Imipenem toxicit

can cause



seizures and/o

renal failure



Inhibit cell wallsynthesis

(6 categories/drugs

Penicillins

Cephalosporins



Cephalosporins

Aztreonam

Meropenem/Imipenem

VancomycinDaptomycin

Inhibits



b

cytochrome

P450

Chloramphenicol



Macrolides

(exception =azithromycin)



Jarish

Herxheimer



Systemic side effects results frompenicillin during treatment of syphill

Also seen with Tetracyclines

Linezolid has



oral

bioavailability?



yes 100%

Linezolid



mechanism of

resistance

decreased affinity of



antimicrobial agent to bacterial target site

(target alteration)

Linezolid would be



Linezolid would be

preferred over whic

cell wall inhibitor?



Loves the bone and



stays active

Used to txosteomyelitis

Clindamycin



y

Kaplan fact

Macrolides



mechanism of

action

bind to 50s subunit



prevents ribosomaltranslocation down mRN

Bacteriostatic

Mechanism of



action of

Aminoglycoside

Binds to 30s subunit of



3

bacterial ribosome

Bacteriocidal Inhibitor of

protein synthesis

Mechanism of



action of

synercid

binds to 50 s



preventstranslocation

Bacteriocidal



production of inactivating

enzyme (methyltransferases)



Target alteration that alters 5 binding

increased effluxdecrease permeability



Most potent

lactam



Imipenem/meropene



Name 3

tetracyclines

doxycycline



minocycline (tigecyclinetetracycline

Kaplan fact: demeclocyli

Only one in its class



(protein translationinhibitor)

Rarely used today in the U because of feared toxicit



Chloramphenico

Oxacillin



NafacillinDicloxacillin

MethicillinCloxacillin

Penicillinase-



Resistant

Penicillin

Penicillin G and V



used to tx all strain

of

Syphilis



GAS (strp

pyogenes)

Pharmacology of



Aminoglycosides?Oral?

excretion?activity is _____ depende

Not absorbed orally, the



are polarRenal excretion

pH dependent - acidosimay decrease activity

Precludes widespread us



drug interactions, phlebi40%, jaundice 30%,

arthralgia and myalgia 20



Synercid

Toxicity



Probenecid

Blocks



Penicillin

Excretion

Protein Inhibitors



Contraindicated in

pregnancy

Aminoglycosides



TetracyclineMacrolides (excep

azithromycin)

These protein synthesis



inhibitors work on the 30

subunit

Aminoglycosides

bl k



block initiationTetraclycines block

site

These Protein Synthesi



inhibitors work on the 50

subunit

Linezolide - blocks initiation

Streptogramins block A site

hl h i l bl id



Chloramphenicol blocs peptid bond

Macrolides/Clindamycin bloctranslocation

d



Psuedotumor

Cebri

Tetracycline toxicity

( i li )



(tigecycline)impairs CSF reabsorption

-> increase cranial pressu



Macrolide toxicity

KAPLAN FACT lid



KAPLAN FACT --> macrolideincrease GI distress by

stimulating motlin receptors -increased peristalsis

Red Man

d h



syndrome...otherside effects in sam

drug?



Side effect of this

d b



drug can be contac

dermatitis

Neomycin - aminoglycosi

Found in triple Ab ointme



(neosporin) used topicall

KAPLAN FACT

Side effects includ

i l



transient muscle

weakness, myalgia

D i



Daptomycin

Side effects of

P i ilil



Penicililn

Toxicity

Allergic hypersensitivity, rash, urticaria

GI distress, diarrhea

Seizures



SeizuresHametologic -penias, anemia (coombs

nephritis (especially Methicillin)

drug fever



Chl h i



Chloramphenico

Someone has a macrolid

resistnat strain of



resistnat strain of pneumococci...what drug

I give



Someone Has a Staph

infection hat o ld b



infection, what would bthe progression of dru

to use to try to cure?

Penicillin/Methicill

> V >



--> Vanco -->Linezolide -->

Daptomycin

Someone is allergic to

Penicillin, and has a

P d l



Pseudomonal

infection...what drug

should i give them?

AZTREONAM

resistant to beta lactamases



resistant to beta lactamasesTx gram - rods

NO CROSS ALLERGENICITY WIPENICILLS/CEPHALOSPORIN

S t f



Specturm of

Linezolid

All aerobic gram +

i i ll



organisms especiall

resistant strains

Streptogramins

(Synercid) typicall



(Synercid) typicall

used to treat?

VRSA/VRE

according to



according to

Kaplan



e amples of



examples of

aminoglycoside

Tetracycline

mechanism of



mechanism of

action

Bacteriostatic

Binds reversible to 30



Binds reversible to 30subunit of ribosome

Inhibits A-site

Tetracycline

mechanism of



mechanism of

resisitance

facilitated efflux o

drug



drug

decreased entry

Tetracycline



Tetracycline

toxicity

GI - nausea, abd pain, diarrheaFetal and childhood effects on bon

and teeth

Liver necrosis with doxy



Liver necrosis with doxy

Nephrotoxic

Photosensitivity/toxicity --> get rain sun

Tetracyclines

cannot be taken



cannot be taken

with food...why

chelators



chelators

(ca/mg)

Tetracyclines

usually used to



usually used to

tx?

Atypicals (mycoplasma,chlamydia, chancroid,

rickettsia, borrelia, entamoeb



rickettsia, borrelia, entamoeb

**macrolides are preferred DOfor atypicals

This cell wall

inhibitor is known t



inhibitor is known thave a "post-

antibiotic effect"

Daptomycin



Daptomycin

This cell wall

inhibitor is not



inhibitor is not

lactam

Vancomycin



Vancomycin

This cephalosporin is know

to cause biliary obstructio



to cause biliary obstructio

when rapidly infused

Ceftriaxone (3r

generation) >



generation) -->

excreted in bile

This macrolide is considered

be safer for use during

pregnancy because it is more



pregnancy because it is more

water soluble then the rest of

class and does not inhibit p45

Azithromycin



Azithromycin

This penicillin

causes interstital



causes interstital

nephritis



This penicillin is

mostly excreted int



mostly excreted int

the biliary tract



This protein synthesis inhibitmay be associated with

incidence of d b liti ?



pseudomembranous colitis?

which cell wall inhibitor isrelated?

Clindamycin



Clindamycin

Ampiciliin

This specific tetracyclin

is metabolized in lived h ti



is metabolized in liveand can cause hepatic

necrosis



Thrombocytopenia,

neutropenia

Reversible Bone marrow



suppression

weak MAO inhibitor

Linezolid toxicity



Linezolid toxicity

Ticarcillin and

Piperacillin tx



Piperacillin tx

what?

Gram negative microbesEspecially Pseudomonas,

Bacteroides and E. Coli, ProtePiper > Ticar



Piper > Ticar

Tx mixed-intra abdominalabscesses

Tigecycline is used

for what spectrumdi ? d h



for what spectrum diseases? and wha

clinical uses



Tigecycline

mechanism of



mechanism of

action

new glycylcycline derivative of minocycline for IV use only

High affinity binding to 30s unit o



ribosome to block A site

No known resistance yet



Aminoglycosidedecrease ACh, similar to

Botulism



Gentamycin specifically

Treats gram -b i f ti



Treats gram bone infection

quinilones

(dont confuse withclindamycin)



( clindamycin)

KAPLAN FACT

Used for bell'sl



Used for bell spalsy

tetracycline



tetracycline

Vancomycin

mechanism of



mechanism of

action

binds to D-ala-D-alamuramyl pentapeptide --

blocks transglycosylation



> block elongation of

peptidoglycal cell wall

Vancomycin

used to tx wha



used to tx wha

organisms

MRSA, MRSE, Pnemococc

(Gram +)C Diff (but not DOC....that i



C Diff (but not DOC....that i

metronidazole)

What are mechanisms o

microbial resistance to



penicillin?



What are the carbapenem

What is a monobactam



What is a monobactam

example?

Meropenem (p)Imipenem (p)

Ertapenem (p)



ex of mono = aztreonam (

What does first

generationcephalosporins trea



gcephalosporins trea

best?

Gram +

(strep/staph), somGram -



( p/ p ),Gram -

Cefazolin (p)

What is a unique

characteristic of aztreonam, imipenem



aztreonam, imipenem

and meropenem

All are resistant tobeta-lactamases



beta-lactamases

What is penicillin'

chief mechanism o



action?



What is reccommende

dosage of Aminoglycosides to



Aminoglycosides to

avoid toxicity?

1 or 2 large daildoses each day



1 or 2 large daildoses each day

What isSynercid?



What isSynercid?

streptogramin combinaton(quinupristin/dalfopristin)

metabolized and excreted by t



liver

Only IV

What is the

mechanism of reaction for



reaction for

aminoglycosides

Plasmid mediated formation oinactivating enzymes --> grou

transferasesporin protein mutation



decreased affinity of 30s

subunit target

What is the

mechanism of resistance of



resistance of

Vancomycin

D-ala-D-lactatemutation



mutation



it is not a lactam

used to tx Gram +IV only



IV only

NO CNS

What organisms d

Aminoglycosides



work on?

Gram - aerobes

Pseudo-Keeps

Pseudomonas

Klebsiella

E coliEnterobacter

Proteus



Proteus

Serratia

some gram +

Where is tigecyclinemetabolized/excrete



/

Liver/biliary

tract



tract

Which carbapenem

is known to



penetrate the CN

Meropenem



p

Which carbapenem

is not effective



against anaerobes?

Ertapenem



p

Whichcephalosporins hav

been proven to reac



p

good CNS levels?

3rd generationCefotaxime (p)

Ceftriaxone (p)Ceftazidime (p)



Ceftazidime (p)

Cefdinir (o)

Which generationcephalosporins use

to tx meningitis?



g

name the drugs?



Which generation ocephalosporins ha

the best effect



against anaerobes?

2ndCefoxitin (p)

Cefotetan (p)Cefuroxime (o)



Cefuroxime (o)

Cefprozil (o)

Which penicillin is knowto cause GI distress and

lead to C DIFFsuperinfection



superinfection

(pseudomembrane colliti

Ampicillin



p

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