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Transcript of Antimicrobials Pharm
8/13/2019 Antimicrobials Pharm
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"Drug of Last Choice"(brain abscesses,
typhoid fever, rocky mountain)
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Cholarmphenico
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1st generation
cephalosporins
clinical uses (name
the drugs)
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Sugical prophylaxis
Soft tissue infections
Cefazolin (p)Cephalexin (o)
Cefadroxil (o)
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2nd generation
cephalosporins
clinical uses (name
the drugs)
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intra-abdominal infections
Cefoxitin (p)
Cefotetan (p)Cefuroxime (o)
Cefprozil (o)
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All lactams have
sulfur in their
structure, what is th
purpose of this?
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increase lipid
solubility andhypersensitivit
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Aminoglycosid
toxicity
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nephrotoxicity ototoxicity
not for pregnantneuromuscular blocka
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Aminoglycosides
Chloramphenicol
Macrolides
Tetracyclines
StreptograminsLinezolid
Clindamycin
Tigecycline
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Inhibit bacteria
protein synthesi(translation)
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Aminoglycoside
are bacteriostatic?
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False...Bacteriocidal...uniq
to this group
Cause misreading of mRN
template
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Aminoglycosides demonstrate
concentration dependent killing?
Does it demonstrate post-antibiotic eff
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True - high levels of antibiot
facilitate entry through cel
wall and membrane
Yes
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Ampicillin
Amoxicillin
TicarcillinPiperacillin
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Extended Range Penicilli
Think (more gram - use
amoxicillin = oral mode
ampicilin = parenteral/or
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As one moves down the
generations of
cephalosporins what is th
general trend in terms o
spectrum of activity?
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Tend to be mor
effective againsGram - bacteria
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Augmentin
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amoxicillin +
clavulonic acid
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Bacteroides infectio
would be suitable t
be treated with Aztreonam
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False....NO
Anaerobes
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Bacteroides, clostridium
and actinomyces are alrelevant organisms to b
treated with
aminoglycosides
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False...dont treatanaerobes
Killing mechanism is Odependent uptake
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Besides Clavulonic
acid what are othe
Beta-Lactamaseinhibitors?
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Sulbactam
Tazobactam
Amoxicillin-Clavulanic Acid - Augment
Ticarcillin/Clavulanic Acid - Timentin Ampicillin/Sulbactam - Unasyn P
Piperacillin/Tazobactam - Zosy P
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Blurred vision
GI disturbancesProlonged QT interval
Exacerbation of
Myasthenia gravis
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Telithromycin
Toxicity symptoms
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Cefatrixone
treats what the best?
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3rd generation -> H Influenzae
and Gram -, Lym
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Cefazolin (p)
Cephalexin (o)Cefadroxil (o)
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First generation
Cephalosporin
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Cefepime (p)
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4th generation
cephalosporin
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Cefepime is
used to tx what
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4th generationcepha-->
pseudomonas
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Cefotaxime (p)
Ceftriaxone (p)
Ceftazidime (p)Cefdinir (o)
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3rd generation
cephalosporin
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Cefotetan tx
what the best?
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2nd generation
--> Bacteriode
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Cefoxitin (p)
Cefotetan (p)
Cefuroxime (o)Cefprozil (o)
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Secondgeneration
cephalsporins
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Ceftazidime
used to tx what
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3rd generation
--> pseudom
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Cephalosporin
Toxicity
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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
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CephalosporinDO NOT tx
what?
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LAME
listeriaatypicals
MRSA enterococci
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Cephalosporinexcreted into
biliary tract
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Ceforperazone(3rd generation
Ceftriaxone (3rd
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Chloramphenicolmechanism of
action
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binds 50s subunit
inhibits peptidyl
transferase bacteriostatic
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Chloramphenicolmechanism or
resistance
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plasmid mediated producti
of antibiotic inactivatingenzyme (acetyl transferase
Reduced permeability of bacterial organism to drug
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Clavulonic Aci
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beta-lactamase inhibit
often used with
penicillins to enhanceaction
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Clindamycin isprimary
absorbed?
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Clindomycinused against
what spectrum
G d
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Gram + and
Anaerobes
NOTENTEROCOCCI
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Clinical uses o
aminoglycoside
less potent when used alone often
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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
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Clinical Uses o
penicillin
t h iti
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strep pharyngitis
rheumatic fever
prophylaxissyphilis
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Clinical uses o
Tetracyclines
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prostatitisgingavitis
SIADH
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Concentrates inphagocytic cells
and other tissue
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Azithromycin
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Concentrates inrespiratory
secretions
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Macrolides
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Daptomycin isused in all age
groups?
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False..notapproved for
children
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Daptomycinmechanism of actio
and clinical uses
new lipopeptide antibiotic...IV only
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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
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Difference in
excretion bw
tetracycline anddoxycycline
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tetra = urine
doxy = feces
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Do penicillin crosseinto CNS, prostate
and eye
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Minimally
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DOC for borellia
bergdorfi?
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Ceftriaxone -->
3rd generation
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DOC for
legionella
think atypical
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think atypical
Think Macrolide
KAPLAN FACT
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DOC for nosocomilife threatening
diseases
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Imipenem/Meropene
DOC fo o al
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DOC for oral
treatment of
animal bites
Augmentin
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Augmentin
(ampicillin +
clavulonic)
DOC for Rocky
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DOC for Rocky
Mountain
Spotted Fever
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tetracycline
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DOC fortularemia, TB an
Bubonic blague
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DOC of Atypica
Mycobacteria
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Clarithromycin
(macrolide)
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DOC of Atypica
Organisms
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macrolides/ketolid
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DOC of C Diff
Metronidazole
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Metronidazole
May have to use it afterampicillin side effect
2nd DOC = oral vancomycKAPLAN FACT
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DOC of Salmonella(typhoid) and
bordatella pertussi
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Azythromycin
(macrolide)
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DOC to treat
syphillis
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Drugs that are
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Drugs that are
contraindicated
in children
Daptomycin
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Daptomycin
Tetracycline
(tigecycline)
Enterococcus
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infection would be
suitable to be treate with Aztreonam
False only use
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False...only use
this drug with
gram - rods
Extended Range
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Extended Range
Ampicillin/AmoxicilliPenicillins Tx what
bugs? what clinical use
B.H. HEELS
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B.H. HEELS
Borrelia, H pylori, H influenzae,Entorocci, E coli, Listeria, Strep pneum
Otitis media, sinusitis, pneumonia, Ulyme
Give an exampl
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Give an exampl
of an
oxazolidione
Linezolid = first in
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class
Blocks 50s initiatioBacteriostatic
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Gray-Baby
Syndrome
Chloramphenicol can be
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Chloramphenicol can be
conjugated because of
immaturity/decreased lev
of glucuronsyl transferas
Groups/Names of drug
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Groups/Names of drug
that inhibit bacterialprotein synthesis
(translocation)
Aminoglycosides
Chloramphenicol
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p
MacrolidesTetracyclines
Streptogramins
LinezolidClindamycin
Tigecycline
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Idiosyncratic/dosrelated aplastic
anemia
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chloramphenico
toxicity
If i use combo a
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If i use combo a
tetracycline with a betlactam how would you
describe the relationshi
Antagonistic
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Antagonistic
Static and Cidal
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If it ends in "-
thromycin"
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Think
Macrolides
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Imipenem
excretion
Administered with Cilastatin which
inhibits renal inactivation
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b
(dehydropeptidase effect) to prevekidney metabolism from occurring
too quickly
Dont mix...co-administer
Possible seizure side effect
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Imipenem toxicit
can cause
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seizures and/o
renal failure
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Inhibit cell wallsynthesis
(6 categories/drugs
Penicillins
Cephalosporins
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Cephalosporins
Aztreonam
Meropenem/Imipenem
VancomycinDaptomycin
Inhibits
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b
cytochrome
P450
Chloramphenicol
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Macrolides
(exception =azithromycin)
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Jarish
Herxheimer
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Systemic side effects results frompenicillin during treatment of syphill
Also seen with Tetracyclines
Linezolid has
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oral
bioavailability?
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yes 100%
Linezolid
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mechanism of
resistance
decreased affinity of
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antimicrobial agent to bacterial target site
(target alteration)
Linezolid would be
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Linezolid would be
preferred over whic
cell wall inhibitor?
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Loves the bone and
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stays active
Used to txosteomyelitis
Clindamycin
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y
Kaplan fact
Macrolides
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mechanism of
action
bind to 50s subunit
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prevents ribosomaltranslocation down mRN
Bacteriostatic
Mechanism of
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action of
Aminoglycoside
Binds to 30s subunit of
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3
bacterial ribosome
Bacteriocidal Inhibitor of
protein synthesis
Mechanism of
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action of
synercid
binds to 50 s
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preventstranslocation
Bacteriocidal
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production of inactivating
enzyme (methyltransferases)
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Target alteration that alters 5 binding
increased effluxdecrease permeability
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Most potent
lactam
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Imipenem/meropene
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Name 3
tetracyclines
doxycycline
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minocycline (tigecyclinetetracycline
Kaplan fact: demeclocyli
Only one in its class
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(protein translationinhibitor)
Rarely used today in the U because of feared toxicit
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Chloramphenico
Oxacillin
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NafacillinDicloxacillin
MethicillinCloxacillin
Penicillinase-
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Resistant
Penicillin
Penicillin G and V
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used to tx all strain
of
Syphilis
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GAS (strp
pyogenes)
Pharmacology of
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Aminoglycosides?Oral?
excretion?activity is _____ depende
Not absorbed orally, the
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are polarRenal excretion
pH dependent - acidosimay decrease activity
Precludes widespread us
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drug interactions, phlebi40%, jaundice 30%,
arthralgia and myalgia 20
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Synercid
Toxicity
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Probenecid
Blocks
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Penicillin
Excretion
Protein Inhibitors
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Contraindicated in
pregnancy
Aminoglycosides
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TetracyclineMacrolides (excep
azithromycin)
These protein synthesis
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inhibitors work on the 30
subunit
Aminoglycosides
bl k
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block initiationTetraclycines block
site
These Protein Synthesi
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inhibitors work on the 50
subunit
Linezolide - blocks initiation
Streptogramins block A site
hl h i l bl id
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Chloramphenicol blocs peptid bond
Macrolides/Clindamycin bloctranslocation
d
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Psuedotumor
Cebri
Tetracycline toxicity
( i li )
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(tigecycline)impairs CSF reabsorption
-> increase cranial pressu
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Macrolide toxicity
KAPLAN FACT lid
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KAPLAN FACT --> macrolideincrease GI distress by
stimulating motlin receptors -increased peristalsis
Red Man
d h
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syndrome...otherside effects in sam
drug?
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Side effect of this
d b
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drug can be contac
dermatitis
Neomycin - aminoglycosi
Found in triple Ab ointme
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(neosporin) used topicall
KAPLAN FACT
Side effects includ
i l
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transient muscle
weakness, myalgia
D i
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Daptomycin
Side effects of
P i ilil
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Penicililn
Toxicity
Allergic hypersensitivity, rash, urticaria
GI distress, diarrhea
Seizures
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SeizuresHametologic -penias, anemia (coombs
nephritis (especially Methicillin)
drug fever
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Chl h i
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Chloramphenico
Someone has a macrolid
resistnat strain of
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resistnat strain of pneumococci...what drug
I give
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Someone Has a Staph
infection hat o ld b
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infection, what would bthe progression of dru
to use to try to cure?
Penicillin/Methicill
> V >
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--> Vanco -->Linezolide -->
Daptomycin
Someone is allergic to
Penicillin, and has a
P d l
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Pseudomonal
infection...what drug
should i give them?
AZTREONAM
resistant to beta lactamases
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resistant to beta lactamasesTx gram - rods
NO CROSS ALLERGENICITY WIPENICILLS/CEPHALOSPORIN
S t f
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Specturm of
Linezolid
All aerobic gram +
i i ll
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organisms especiall
resistant strains
Streptogramins
(Synercid) typicall
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(Synercid) typicall
used to treat?
VRSA/VRE
according to
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according to
Kaplan
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e amples of
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examples of
aminoglycoside
Tetracycline
mechanism of
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mechanism of
action
Bacteriostatic
Binds reversible to 30
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Binds reversible to 30subunit of ribosome
Inhibits A-site
Tetracycline
mechanism of
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mechanism of
resisitance
facilitated efflux o
drug
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drug
decreased entry
Tetracycline
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Tetracycline
toxicity
GI - nausea, abd pain, diarrheaFetal and childhood effects on bon
and teeth
Liver necrosis with doxy
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Liver necrosis with doxy
Nephrotoxic
Photosensitivity/toxicity --> get rain sun
Tetracyclines
cannot be taken
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cannot be taken
with food...why
chelators
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chelators
(ca/mg)
Tetracyclines
usually used to
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usually used to
tx?
Atypicals (mycoplasma,chlamydia, chancroid,
rickettsia, borrelia, entamoeb
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rickettsia, borrelia, entamoeb
**macrolides are preferred DOfor atypicals
This cell wall
inhibitor is known t
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inhibitor is known thave a "post-
antibiotic effect"
Daptomycin
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Daptomycin
This cell wall
inhibitor is not
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inhibitor is not
lactam
Vancomycin
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Vancomycin
This cephalosporin is know
to cause biliary obstructio
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to cause biliary obstructio
when rapidly infused
Ceftriaxone (3r
generation) >
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generation) -->
excreted in bile
This macrolide is considered
be safer for use during
pregnancy because it is more
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pregnancy because it is more
water soluble then the rest of
class and does not inhibit p45
Azithromycin
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Azithromycin
This penicillin
causes interstital
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causes interstital
nephritis
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This penicillin is
mostly excreted int
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mostly excreted int
the biliary tract
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This protein synthesis inhibitmay be associated with
incidence of d b liti ?
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pseudomembranous colitis?
which cell wall inhibitor isrelated?
Clindamycin
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Clindamycin
Ampiciliin
This specific tetracyclin
is metabolized in lived h ti
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is metabolized in liveand can cause hepatic
necrosis
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Thrombocytopenia,
neutropenia
Reversible Bone marrow
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suppression
weak MAO inhibitor
Linezolid toxicity
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Linezolid toxicity
Ticarcillin and
Piperacillin tx
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Piperacillin tx
what?
Gram negative microbesEspecially Pseudomonas,
Bacteroides and E. Coli, ProtePiper > Ticar
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Piper > Ticar
Tx mixed-intra abdominalabscesses
Tigecycline is used
for what spectrumdi ? d h
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for what spectrum diseases? and wha
clinical uses
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Tigecycline
mechanism of
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mechanism of
action
new glycylcycline derivative of minocycline for IV use only
High affinity binding to 30s unit o
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ribosome to block A site
No known resistance yet
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Aminoglycosidedecrease ACh, similar to
Botulism
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Gentamycin specifically
Treats gram -b i f ti
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Treats gram bone infection
quinilones
(dont confuse withclindamycin)
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( clindamycin)
KAPLAN FACT
Used for bell'sl
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Used for bell spalsy
tetracycline
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tetracycline
Vancomycin
mechanism of
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mechanism of
action
binds to D-ala-D-alamuramyl pentapeptide --
blocks transglycosylation
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> block elongation of
peptidoglycal cell wall
Vancomycin
used to tx wha
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used to tx wha
organisms
MRSA, MRSE, Pnemococc
(Gram +)C Diff (but not DOC....that i
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C Diff (but not DOC....that i
metronidazole)
What are mechanisms o
microbial resistance to
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penicillin?
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What are the carbapenem
What is a monobactam
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What is a monobactam
example?
Meropenem (p)Imipenem (p)
Ertapenem (p)
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ex of mono = aztreonam (
What does first
generationcephalosporins trea
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gcephalosporins trea
best?
Gram +
(strep/staph), somGram -
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( p/ p ),Gram -
Cefazolin (p)
What is a unique
characteristic of aztreonam, imipenem
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aztreonam, imipenem
and meropenem
All are resistant tobeta-lactamases
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beta-lactamases
What is penicillin'
chief mechanism o
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action?
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What is reccommende
dosage of Aminoglycosides to
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Aminoglycosides to
avoid toxicity?
1 or 2 large daildoses each day
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1 or 2 large daildoses each day
What isSynercid?
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What isSynercid?
streptogramin combinaton(quinupristin/dalfopristin)
metabolized and excreted by t
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liver
Only IV
What is the
mechanism of reaction for
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reaction for
aminoglycosides
Plasmid mediated formation oinactivating enzymes --> grou
transferasesporin protein mutation
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decreased affinity of 30s
subunit target
What is the
mechanism of resistance of
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resistance of
Vancomycin
D-ala-D-lactatemutation
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mutation
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it is not a lactam
used to tx Gram +IV only
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IV only
NO CNS
What organisms d
Aminoglycosides
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work on?
Gram - aerobes
Pseudo-Keeps
Pseudomonas
Klebsiella
E coliEnterobacter
Proteus
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Proteus
Serratia
some gram +
Where is tigecyclinemetabolized/excrete
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/
Liver/biliary
tract
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tract
Which carbapenem
is known to
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penetrate the CN
Meropenem
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p
Which carbapenem
is not effective
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against anaerobes?
Ertapenem
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p
Whichcephalosporins hav
been proven to reac
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p
good CNS levels?
3rd generationCefotaxime (p)
Ceftriaxone (p)Ceftazidime (p)
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Ceftazidime (p)
Cefdinir (o)
Which generationcephalosporins use
to tx meningitis?
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g
name the drugs?
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Which generation ocephalosporins ha
the best effect
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against anaerobes?
2ndCefoxitin (p)
Cefotetan (p)Cefuroxime (o)
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Cefuroxime (o)
Cefprozil (o)
Which penicillin is knowto cause GI distress and
lead to C DIFFsuperinfection
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superinfection
(pseudomembrane colliti
Ampicillin
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p