Antibacterials I Flashcards
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
aminoglycoside mechanism
binds to several 30S/50S interfce to stop initiation and causes premature release of ribosome from mRNA and mRNA mistreading
How do bacteria resist aminoglycosides?
enzymatic modification of the aminoglycosides
more effective against gram-neg. than gram-pos.
• poor activity against anaerobes
• primarily for gram-neg. ‘aerobic’ bacilli, incl. Enterobacteriaceae and Pseudomonas
aeruginosa
Aminoglycosides
aminoglycosides are better for gram negative or positive
for anaerobes or aerobes
gram negative
aerobes
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
Gentamicin, tobramycin and amikacin are examples of
aminoglycosides
which aminoglycoside is most resistant to bacterial inactivation
amikacin
What four bacteria do aminoglycosides work great for
P.aeruginoa, Klebsiella, Enterobacter, Serratia
P.aeruginoa, Klebsiella, Enterobacter, Serratia are all suspeptible to what class of drugs
aminoglycosides used with B-lactams
How are aminoglycoside metabolized?
glomerular filtration
Adverse rxn of aminoglycosides
nephrotoxic and ototoxic and is related to dose and duration of therapy. less common is neuromuscular blockade
How are aminoglycosides administered?
IV or IM with poor penetration to CSF
*serious infection~~ combined with other antibiotics
MEch of Tetracyclines
transported into cell via carrier… binds to 30S ribosomal to stop attachment of aminoacly-tRNA to acceptor site
bacteriostatic
transported into cell via carrier… binds to 30S ribosomal to stop attachment of aminoacly-tRNA to acceptor site
bacteriostatic
tetracyclines
Modern tetracyclines such as _____ and ______ have longer 1/2 lives and are more lipophilic
minocycline and doxycycline
How does bacteria devo resistance to tetracyclines
increased transport of drug out of cells… resistant to one tetracylcine, likely resistant to all of them
Tetracyclines are no longer used bc
increased resistance
Preferred agents for rickettsia and chylamydia
Tetracyclines
Preferred agent for Mycoplasma and ureplasma and Borrelia (or lymes)
tetracyclines
alternative drug for syphilis and gonorrhea
tetracyclines
What can tetracyclines be used for
Rickettsia Chylamydia Mycoplasma and Ureaplasma Borrelia alt for gonorrhea and syphilis
You shouldn’t used antacids with tetracycline because
the Ca++ in them will bind to tetracyclines and inhibit absorption
Adverse rxns to tetracyclines
GI disturbance, pseudomembranous enterocolitis, Candida superinfection, photosensitive, teeth discoloration, DONT USE IF PREGNANT
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
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)
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
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
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
- Prophylactic
- Empiric
- Pathogen-directed
- Susceptibility-guided
