ABs : inhibitors of cell wall synthesis Flashcards
A AB that inhibit cell wall synthesis is only bactericidal when? do these ABs affect humans cells, why?
What microbe is intrinsically resistant to cell wall synthesis inhibitors?
Bactericidal ONLY when bacteria are growing
Do not effect humans cells bc human cells have no cell wall
Resistant= Mycoplasma (no cell wall) and L forms of bacteria (no cell walls)
Penicillin will not work against Mycoplasma and L forms of bacteria why?
Bc mycoplasma and L form bacteria do NOT have cell walls
What AB inhibits the first step of cell wall synthesis: L ala to D ala and linkage of two Dala.
This AB is used for what?
cycloserine
2nd line tx for TB
The 5 step of cell wall synthesis: sugar peptide added to peptidoglycan strands via peptidoglycan synthase is prevented by what AB
Bacitracin binds to the isoprenyl phosphate thus preventing it from carrying a sugar peptide to the cell membrane
How does Vancomycin prevent cell wall synthesis?
Vancomycin prevents cell wall synthesis by preventing transfer of sugar pentapeptide from carrier molecule to growing peptidoglycan chain : inhibition of peptidoglycan synthase and inhibition of cross linking of peptidolglycans
How do B lactams (ie penicillin) inhibit cell wall synthesis
B lactam act by binding to various penicillin binding proteins (PBPs) and inhibiting transpeptidation reaction
what is the specificity of B lactam due to?
How doe resistance to B lactams form?
B lactams specificity due to structural similarity w D-Ala dipeptide
resistance of B lactams comes from production of B lactamases which break the B lactam ring
What are the 4 ABs that are considered B lactams?
penicillins, cephalosporins, monobactams, carbapenems
What is the MoA of Penicillins?
Are penicillins cidal or static?
Penicillins mimic the D-ala-D- ala structure of pentapeptide on peptidoglycan and ties up transpeptidases
Penicillins are bactericidal!
what are naturally occurring penicillins effective against?
What are the 2 naturally occurring penicillins?
narrow or broad spectrum?
Penicilli G and V - narrow spectrum
they are effective against streps, many anaerobes, enterococcus, a few gram negative
what are Penicillin G and V not effective against?
Gram negative bacteria like E coli and Klebsiella
What are narrow spectrum penicillins that are active again staph and strepococci?
Anti- Staphlococcal (B lactamase resistant) penicillins
what are examples of B lactamase resistant penicillins?
Nafcillin, Oxacillin, Cloxacillin,
All end in cilin!
Resistance to penicillin has been acquired thru Methicillin resistant S aureus and methicillin resistant S epidermis what are these two phenotypes known as
MRSA and MRSE
All beta lactam drugs exhibit what type of resistance?
MRSA
What are amino penicillins? broad or narrow? B lactamase resistant or not? effective against?
Amino penicillins= ampicillin, and Amoxicillin
Broad spectrum,
effective against streps, enterococci and some gram neg
NOT B lactamase resistant!
What are Ampicillin and Amoxicillins considered?
what are they not effective against?
Amino penicillins!
NOT effective Pseudomonas aeruginosa
What are the 3 anti- pseudomonal penicillins?
broad or narrow spectrum?
effective against what
anti pseudomonal penicillins= carbenicillin, piperacillin, ticarcillin
EXTENDED spectrum
effective against pseudomonas aeruginosa, streps, enterobacteriaceae and many gram negs
clinical uses of penicillins
streps, pneumoniae, haemophilus infections (meningitis, epiglotitis)
STDs - syphilis
UTIs
Describe the 4 drug resistance scenarios facing penicillins and the bacteria associated with each
- B lactamase (gram + and gram -)
2 altered PBPs: MRSA and S pneumoniae - Altered Porins - gram -
- INC efflux
MRSA resistance bacteria are associated with what resistance factor?
Altered PBPs
when does one take penicillins and why
take penicillin before eating bc food dec oral absorption
penicillin
distribution: CNS Or not?
Excretion:
Toxicity:
Penicillins do NOT easily cross BBB but inflammation of meninges INC CSF entry. excreted really
Mild toxicities but direct toxic effects on kidney and some hypersensitivity rxns
What is the special note about classification of Penicillins?
Penicillins are TIME DEPENDENT ABs- so concentrations must be maintained for bacterial killing
Cephalosporins
cidal or static?
MoA
Cephalosporins are CIDAL
MoA: inhibitor of bacterial cell wall synthesis, but generally B lactamase resistant!
As one goes along the generations of 1 to 4th gen cephalosporins what is the general trend of their spectrum of action
as you inc generation the cephalosporin becomes more active against Gram neg but less effective against gram pos (especially against staph)
so 1st generation best against gram + but least against gram -
4th gen best against gram neg but worst against gram pos
each generation gets better spectrum of activity
1st generation cephalosporins include what AB?
effective against what? given how?
cefazolin = 1st gen cephalospin give IV or IM effective against gram +
3rd generation cephalosporins include what? most effective against what?
3rd gen cephalosporins= Ceftazidime, ceftriaxon
most effective against gram negative
what is the only 3rd gen cephalosporin effective against Pseudomonas?
Ceftazidime = Pseudomonas = 3rd gen!
4th generation cephalosporins include what?
Cefepime, Ceftolozane
Cephalosporin absorption distribution metabolism toxicity
absorption= oral and parenteral distribution: 3rd and 4th gens cross BBB metabolism: none excreted like penicillins really toxicity: better tolerated than penicillins, low tox
What B lactam has a broad spectrum and is used against gram - and gram + bacteria? what drug is under this class
Carbapenems = Imipenem
describe the interaction between carbapenems and B lactamase
Carbapenems are resistant to B lactamase
what is the interaction between Imipenem and gram negative bacteria
imipenem binds well to PBP 1 and PBP2 of gram - bacteria especially effective against pseudomonas and Acinetobacter
what are carbapenems (imipenem) reserved for
carbapenems are used ONLY for serious nosocomial infections - very restricted!
Carbapenems route of admin
what is administered with carbapenems to increase their half life and block hydrolysis in renal tubules
Carbapenems are IV Only! admin with Cilastatin to INC half life
What is a narrow spectrum AB that is used for serious nosocomal gram negative infections?
Monobactams
What is Monobactams effective against?
Monobactams are effective against Gram negatives including pseudomonas aeruginosa
What are Monobactams not effective against?
GRAM POSITIVE!
MONOBACTAMS GRAM NEG ONLY!
What are the 3 B lactamase inhibitors that inactivate B lactamase?
Clavulanic acid, sulbactam, tazobactam
What does Clavulanic acid, Sulbactam, and Tazobactam do?
Clavulanic acid, Sulbactam, and Tazobactam are inhibitors of B lactamase, binding irreversibly to serine active site
What are Clavulanic acid, Sulbactam, and Tazobactam used for clinically?
used in combo with B lactam ABs to extend spectrum.
Amoxacillin + Clavulanate for Oral and IV use
What is a large tricyclic glycopeptide from Streptomycin orientalis?
what 2 drugs fall under this?
Vancomycin
Teicoplanin
Telavancin
MoA of Vancomycin (teicoplanin and telavancin)
Vancomycin binds to carboxyl terminus of D ala D ala inhibiting peptidoglycan synthase thus inhibiting transpeptidation crosslinking
Is Vancomycin static or cidal?
Vancomycin is CIDAL! but resistance is making it more static
Resistance to Vancomycin is rampant, why?
Vancomycin binds to D ala D ala and bacteria are changing this sequence to D ala D Lac or to D ala D see leading to VRE and VRSA
What is the spectrum of Vancomycin and what is it used against?
Vancomycin is NARROW! used against GRAM + staphyococci, strep, E faceless,
what is Vancomycin not effective against!
GRAM Negative!
what is Vancomycin used often to treat?
Methicillin resistant staphylococci (MRSA)
clinical use of Vancomycin
MRSA, enterococci, meningitis
severe C difficile infection from overuse of penicillin is best treated how
SEVERE colitis = Vancomycin
for moderate C difficile infection (moderate pseudomonas colitis) (moderate Colitis) what is used for TX?
Metronidazole or Fidaxomicin
Vancomycin route of admin, metabolism, excretion
Vancomycin given orally or by IV, no metabolism, excreted renally
what is the Toxicity associated with Vancomycin?
other toxicities?
RED man syndrome:
also hearing loss
what is the MoA of bacitracin
Bacitracin binds to isoprenyl phosphate lipid carriers inhibiting dephosphorylation and utilization
Bacitracin spectrum and effectiveness
Bacitracin used against Gram + cocci, some gram neg
what specific infections are bacitracin used for
superficial and ophthalmic infections
what is used to treat penicillin resistant S pneumoniae
3rd and 4th generation quinolones
what is used to treat MRSA
Vancomycin
what are 2 cell membrane disrupting AB
daptomycin and polymyxins
what are polymyxins effective against?
POLYMIXIN= GRAM - !!
what is a type E polymyxin that accumulates in outer portion of cell membrane
Colistin
are Polymyxins cidal or static
Polymyxins are CIDAL!
MoA of Polymyxins
Polymyxins act as cationic detergent disrupting cell membrane of gram NEG.
what are Polymyxins NOT effective against?
Polymyxins are not effective against GRAM + bacteria!
what is used to treat pan resistant, gram neg infections including pseudomonas and acinetobacter?
Polymyxin = Colistin
Polymyxins used to treat what
Polymyxin useful against pseudomonas infections in ears, eyes by topical
Polymyxin is what kind of toxicity drug
Polymyxin is DOSE RELATED!
resistance of Polymyxin
Polymyxin resistance is rare! altered LPS anionic lipid content
Daptomycin is a cidal or static drug, acting on what
Daptomycin is CIDAL acting on disrupting cell membrane thus disrupting DNA, RNA and protein synthesis
what is Daptomycin useful against
GRAM POSITIVE ONLY! = DAPTOMYCIN
What is special about the usefulness of Daptomycin?
Daptomycin useful against VRE, and MRSA
where is daptomycin not useful?
DAPTOMYCIN NOT useful for Lung infections
what is Daptomycin considered
Daptomycin= Concentration dependent drug!
