Antibacterials I Flashcards by Meghan May

transported into the cell by an energy-requiring aerobic process (does not occuranaerobically)
• bind to several ribosomal sites, usually at 30S/50S interface; stops initiation, causes
premature release of ribosome from mRNA, and mRNA misreading
• post-antibiotic effect
• concentration-dependent killing

Aminoglycosides

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aminoglycoside mechanism

binds to several 30S/50S interfce to stop initiation and causes premature release of ribosome from mRNA and mRNA mistreading

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How do bacteria resist aminoglycosides?

enzymatic modification of the aminoglycosides

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more effective against gram-neg. than gram-pos.
• poor activity against anaerobes
• primarily for gram-neg. ‘aerobic’ bacilli, incl. Enterobacteriaceae and Pseudomonas
aeruginosa

Aminoglycosides

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aminoglycosides are better for gram negative or positive

for anaerobes or aerobes

gram negative

aerobes

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due to toxicity, use restricted to serious infections in which other agents are unsuitable
• often used in conjunction with other agents (e.g. β-lactams)—- streptomycin

aminoglycosides

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Gentamicin, tobramycin and amikacin are examples of

aminoglycosides

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which aminoglycoside is most resistant to bacterial inactivation

amikacin

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What four bacteria do aminoglycosides work great for

P.aeruginoa, Klebsiella, Enterobacter, Serratia

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P.aeruginoa, Klebsiella, Enterobacter, Serratia are all suspeptible to what class of drugs

aminoglycosides used with B-lactams

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How are aminoglycoside metabolized?

glomerular filtration

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Adverse rxn of aminoglycosides

nephrotoxic and ototoxic and is related to dose and duration of therapy. less common is neuromuscular blockade

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How are aminoglycosides administered?

IV or IM with poor penetration to CSF

*serious infection~~ combined with other antibiotics

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MEch of Tetracyclines

transported into cell via carrier… binds to 30S ribosomal to stop attachment of aminoacly-tRNA to acceptor site
bacteriostatic

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transported into cell via carrier… binds to 30S ribosomal to stop attachment of aminoacly-tRNA to acceptor site
bacteriostatic

tetracyclines

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Modern tetracyclines such as _____ and ______ have longer 1/2 lives and are more lipophilic

minocycline and doxycycline

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How does bacteria devo resistance to tetracyclines

increased transport of drug out of cells… resistant to one tetracylcine, likely resistant to all of them

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Tetracyclines are no longer used bc

increased resistance

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Preferred agents for rickettsia and chylamydia

Tetracyclines

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Preferred agent for Mycoplasma and ureplasma and Borrelia (or lymes)

tetracyclines

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alternative drug for syphilis and gonorrhea

tetracyclines

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What can tetracyclines be used for

Rickettsia
Chylamydia
Mycoplasma and Ureaplasma
Borrelia
alt for gonorrhea and syphilis

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You shouldn’t used antacids with tetracycline because

the Ca++ in them will bind to tetracyclines and inhibit absorption

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Adverse rxns to tetracyclines

GI disturbance, pseudomembranous enterocolitis, Candida superinfection, photosensitive, teeth discoloration, DONT USE IF PREGNANT

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Tigecycline mech

binds to 30S and blocks aminoacyle-tRNA as well as other unique sites in ribosomes

This tetracycline doesn't have cross resistance with other antiBacts including tetracyclines

Tigecycline

Uses of Tigecycline by SITE

skin/skin strucutre infections complicated intrabdominal infections Community acquired pneumonia (CAP)

What pathogens are Tigecycline effective for

``` E.coli, Klebsiella, enterobacter but NOT psuedonomas Staph (both MSSA and MRSA) Bacteriodes Clostridium perfringes CAP: S. pneumoniae, Haemophilus ```

Drug to tx E.coli, Klebsiella, enterobacter but NOT psuedonomas

Tigecycline

Drug that can tx bacteriodes and Clostridium perfringes

Tigecycline

Tetracycline that can take care of both MSSA and MRSA

Tigecycline

Adverse affects of Tigecycilne

nausea and vomit and cant use with antacids

interferes with binding of aminoacyl-tRNA to 50S subunit and inhibits peptide bond formation (blocks peptidyl transferase)

Chloramphenicol

Mech of Cloramphenicol

fucks with binding of amino-tRNA to 50s and inhibits peptide bond formaiton

administration of tigecycline

iv only

alternative for Pen G sensitive syphilis and uncomplicated gonhorea

Doxycycline and minocycline

Tricycline least sensitive for Ca++ antiacids

Doxycycline

most lipophilic tetracycline thats used prophylactictly for N. Meningitis

Minocycline

1/2 life of minocycline

11-26 hours

1/2 for doxycycline

24 hours

Uses of Chloramphenicol

broad spectrum but VERY serious side effects

Major used of Chloramphenicol

alternative tx of meningitis in B lactam allergic pts brain abscesses severe slamonella infections

Drug of choice for rickettsia in children

doxycycline

Used to tx chronic granulomatois, bacterial ophthalmic issues

Chloramphenicol

Chloramphenicol is toxic because

Bone marrow depression (most common effect and limits its use to life-threatening infections); can progress to a fatal aplastic anemia

Chloramphenicol

What causes Grey baby syndrome

high level of unmetabolized Chloramphenicol

Adverse affects of chloramphenicol

Grey baby/aplastic anemia/ optic neuritis/ enterocolitis | ~~ binds to mitochondrial 70S

3 key macrolides

Azithromycin, Clarithromycin, Erythromycin

Mech of macrolides

bind to 50S and block protein synthesis by blocking translocation

Macrolides are bacteriostatic or bacteriacidal

bacteriostatic

Bacteria devo resistance to chloramphenicol via:

CAT: acetylated by bacteria

When is the activity of macrolides reduced

when pH is below 7

Resistance to macrolides

they methylate the 23S of teh 50S and inhibit binding or drug efflux

Macrolide for gram-pos. | → e.g. Streptococcus, only some Staphylococcus (MSSA)

Erythromycin

Uses of Erythromycin

gram +streptococcus and some staph

Macrolide for Chlamydia, mycoplasma, Legionella and Bordetela

Erythromycin

What bacteria does Erythormycin tx

Chlamydia, mycoplasma, Legionella and Bordetela

Toxicity of Erythromycin

inhibits CYP3A4, increase risk of arrhthymias and cardiac arrest and nausea

What macrolide inhibits CYP3A4

Erythromycin

alternative to erythromycin for treatment of: pharyngitis, respiratory infections

Clarithromycin

Clarithromycin tx the same bacteria as Erythromycin as well as

H. influenza, Moraxella, penicillin-resistant Strep.pneumoniae, Helicobacter pylori

Tx H. influenza, Moraxella, penicillin-resistant Strep.pneumoniae, Helicobacter pylori

Clarithromycin

Macrolide to tx atypical mycobacterial infections

Clarithromycin

Adverse rxn of Clarithromycin

less GI issues then Erythro but INCREASED cardiovascular risk (longer QT interval)

Clarithromycin

Macrolide for respiratory infections such as S.penumonai, H.influenza, mycoplasm

Azithromycin

Used to be 1st line for chlamydia and N. gonorrheoae

Azithromycin | for gonorrhea, use ceftriaxone + azithromycin

Is Azithromycin used for Helicobacter?

NOPE

Adverse rxn of azithromycin

less GI then erythromycin, fewer drug interations and slight QT prolonged

which macrolide has long 1/2 of 3 days and is more acid stable

azithromycin

Mech of Clindamycin

binds to 50S ribosomal subunit, | blocks translocation along ribosomes

Uses of Clindamycin

most gram-pos. cocci and many anaerobes incl. Bacteroides fragilis

Clindamycin

What do we NOT use Clindamycin for?

hospital aquired MRSA

What limits our use of Clindamycin

serious colitis

Adverse rnxs of Clindamycin

Antibiotic associated enterocolitis GI and diarrhea hepatotoxic

Mech of Linezolid

interferes with protein synthesis: binds to 50S ribosomal subunit, interfering with formation of 70S initiation complex

Uses of Linezolid

VRE MRSA and MSSA Group A and B strep S. pneumonia (even if its multidrug resistant)

``` What can treat all of these VRE MRSA and MSSA Group A and B strep S. pneumonia (even if its multidrug resistant) ```

Linezolid

Linezolid is _______ for staph and enterooccus

Bacteriostatic

This drug is a non-selective inhibitor of MAO

Linezolid

Sides of Linezolid

non-selective inhibitor of MAO (many possible drug interactions, avoid foods with tyramine), bone marrow suppresion, superinfection, enterocolitis

inhibit folate synthesis in bacteria by competitive inhibition of dihydropteroate synthase

Sulfonamides

______ is necessary co-factor for key rxns in all cells and bacteria make their own

folate

humans are different from bacteria in regards to folate bc

we get it from diet, they make it, thus its a good target for therapies

Sulfonamides work by:

inhibiting folate synthesis in bacteria... done via competitive inhibition of dihydropteroate synthase

Main uses of sulfonamides

UTI

most common: sulfamethoxazole given with trimethoprim is used for

``` urinary tract infections bacillary dysentery (Shigella) typhoid fever (Salmonella typhi) ```

Used to tx UTIs Bacillary dynsteary or Shigella typhoid fever

Sulfamethoxazole + trimethoprim

Used to tx burn pts

silver sulfadiazine

Two sulfonamide drugs

sulfamethoxazole | silver sulfadiazine

Adverse rxns of sulfonamides

CYP2C9 inhibitors | renal damage dt cystalluria, rashes or hypersensitive

sulfonamides

inhibits folate synthesis in bacteria by competitively inhibiting dihydrofolate reductase

Trimethoprim

Trimpethoprim mechanism

inhibits folate synthesis by competitively inhibiting dihyrofolate reductase

How is trimethoprim more specific for bacteria then humans

while humans have dihydrofolate reductase, it is 100,000-fold less sensitive to trimethoprim than is the bacterial enzyme

Adverse rxn to trimethoprim

nausea, vomiting, diarrhea, rashes • eosinophilia, neutropenia, bone marrow suppression inhibits CYP2C9, causing increased levels of warfarin, etc.

most often in conjunction with sulfamethoxazole to have bactericidal affects

Trimethoprim

urinary infections (Enterobacteriaceae and coagulase-negative Staphylococcus) • upper respiratory tract and ear infections (H. influenzae, Moraxella, S. pneumoniae) • also for Pneumocystis jiroveci (carinii), Salmonella, Shigella,

Trimethoprim

Drug choice based on

susceptibility of the pathogen site of infection, drug penetration emergence of resistance superinfection with another organism

Four categories of antibacterials use

1. Prophylactic 2. Empiric 3. Pathogen-directed 4. Susceptibility-guided