Bact cell wall synth inhibitor Flashcards
Name 2 classes of bacterial cell wall synthesis inhibitors.
Beta-lactams, Glycopeptide
Beta lactams bind to the active site of which enzyme?
Transpeptidase (penicillin binding protein)
Effect of beta lactams
Bacteriocidal on actively growing cells
Name 4 types of beta lactams
Penicillins, cephalosporins, carbapenems, monobactam
Name the 4 classes of penicillins
- natural penicillins (Pen G and Pen V),
- penicillinase resistant penicillins (cloxacillin, flucloxacillin),
- aminopenicillins (amoxicillin, ampicillin),
- antipseudomonal penicillins (piperacillin)
Which natural penicillin is administered parenterally?
Penicillin G
vs V (phenoxymethylpenicilin) oral - more acid stable
3 types of Penicillin G
Potassium
Procaine
Benzathine
- slow release
Syphilis caused by Treponema pallidum can be treated with which penicillin?
Penicillin G
Natural penicillin indications
- gram +ve except staph
- gram -ve (meningococcus, gonorrhea)
- Treponema pallidum (syphilis)–G
What’s IV aq pencilin G used for?
Inflamed meninges– greater CSF penetration
Are natural penicillins commonly used against Staphylococcus aureus?
No
How does methicillin sensitive Staphylococcus aureus acquire resistance against the natural penicillins?
They produce penicillinases
Which class of penicillin is commonly used against methicillin sensitive Staphylococcus aureus?
Penicillinase resistant penicillin
Penicillinase resistant penicillin – 3 drugs
Cloxacillin
Flucloxacillin
Oxacillin
Indications of Penicillinase resistant penicillin
- Staph
- Ineffective against gram -ve
- if strain susceptible to penicillin G, shld use (as PRP will be less effective in this case)
Why Penicillinase resistant penicillin ineffective against gram -ve
Bulky side group
which limits pencillinase access to catalytic site
limits entry to gram -ve bact
Which bacteria is cloxacillin effective against?
Methicillin Sensitive Staphylococcus Aureus (MSSA)
So since PRP cannot target gram -ve, what is used?
Aminopenicillin (broad spectrum penicillins)
List 2 drugs under this class
Ampicillin
Amoxicillin
Which of the aminopenicillins (amoxicillin or ampicillin) has better oral absorption?
Amoxicillin
Why aminopenicillins can target gram -ve?
Addnal Hydrophilic group– allow penetration
Indications of aminopenicillins
Non beta-lactamase producing strains of gram -ve/+ve bacteria
Aminopenicillins does not cover…
Pseudomonas & klebsiella
nosocomial infections
So you need…
Extended spectrum penicillins (antipseudomonals penicillins)
Drug under this class
Piperacillin
How is piperacillin administered?
IV
Indications of piperacillin
- Pseudomonas, proteus, klebsiella
- Anaerobes
- Non beta-lactamase gram +ve : S pyogenes + Enterococcus
Which 2 types of penicillins are used w beta-lactamase inhibitors?
Broad spectrum- aminopenicillins (ampicillin/amoxicillin)
Extended spectrum- antipseudom p (piperacillin)
MOA of beta-lactamase inhibitors (BLI)
Clavulanic acid – suicide inhibitor covalent bonds w beta-lactamase & restructures it
Sulbactam & tazobactam- irrev bind to active site
Name 3 beta lactams- beta-lactamase inhibitor combination drugs.
- Augmentin (Amoxicillin + clavulanic acid)
- Unasyn (ampicillin + sulbactam)
- Zosyn (piperacillin + tazobactam)
How are all penicillins cleared by?
Renal clearance
Name a microbe that commonly causes nosocomial infections and is resistant to all penicillins.
MRSA (methicillin resistant Staphylococcus aureus)
Mechanism of resistance to penicillin
- PBP2a (altered transpeptidase reduced affinity for penicillins)– MRSA
- beta-lactamase (hydrolysis of b-l rings)
- Increased efflux pumps
- Decreased porins (for penicillin influx)
Name at least 2 penicillins related life-threatening allergic reactions.
- Hypersensitivity (Anaphylaxis, SJS, TEN)
- CDAD (clostridium difficile associated diarrhea)- BSP amox (augm)/amp
- Neurotoxicity (esp in renal imp–> high doses seizures)
- Hepatic toxicity (PRP ox/fluclox/cloxacillin)
- Anosmia
Str of cephalosporin
- modification at position 7 of BL ring associated w alteration in antibacterial activity
- Sub at position 3 of dht ring alters metab & pk
Which generation of cephalosporins does cefazolin and cephalexin belong to?
First generation
What’s the second generation cephalosporin?
Cefuroxime
Which generation of cephalosporins are primarily administered orally?
First & second generation EXCEPT cefazolin can IV
How are the 3rd, 4th and 5th generation cephalosporins administered?
Parenterally
1st to 4th generation are ineffective against?
- Listeria monocytogenes,
- Atypicals (Mycoplasma, Chlamydia, Legionella spp.),
- MRSA, and
- Enterococcus species
What are the drugs under 3rd, 4th and 5th generation cephalosporins?
3rd- ceftriaxone, ceftazidime
4th- cefepime
5th- ceftobiprole, ceftaroline
Which cephalosporins could be used for pseudomonas?
Third generation – Ceftazidime
Fourth generation - Cefepime
& 5th gen
Which generation of cephalosporins has coverage against MRSA?
Fifth generation (ceftobiprole, ceftaroline)
Indications for cephalosporin
First gen- Gram +ve: staph & strep
**(except pencillinase producing strep + MRSA)
Second gen- 1st&2nd g Cannot be used for enterococcus/pseudomonas
Third gen- Enteroc, Pseud, N. gonorrhea & gram +ve
** (except Bacteroides spp.
How are most cephalosporins cleared?
Renal clearance
How is ceftriaxone cleared?
Hepatic clearance (40% bile)
What should ceftriaxone not be mixed with?
Ca2+ containing soln (eg. Hartmann’s / Ringer’s)
Name 3 advantages the third generation and fourth generation cephalosporins have over the first and second generations.
- Higher activity against Gram-negative bacteria
- Greater resistance against the beta-lactamase producing strains
- Greater CSF penetration
What are the adverse reactions to cephalosphorins?
- hypersensitivity
- GIT - diarrhea (esp oral ceph) + CDAD
- Thrombophlebitis
What are the adverse reactions to carbapenems?
- GIT-related (N/V, diarrhea)
- Neurotoxicity (at high blood [ ])
- Rashes
- Cross hypersensitivity w pencillin
What are carbapenems prescribed for?
Commonly used against extended spectrum beta-lactamase (ESBL) producing bacteria
Gram -ve & anaerobes spp.
Name 3 carbapenems.
- Imipenem,
- meropenem,
- ertapenem
Carbapenems are resistant to?
MRSA
Imipenem is combined with __________, which works by __________.
Cilastatin
inhibiting dehydropeptidase 1 (DHP1) found in the brush border of the proximal renal tubule. (DHP1 is necessary for the hydrolysis of imipenem. It is not a beta lactamase inhibitor.)
Which carbapenem has good CSF penetration?
Meropenem
Which of the following carbapenems is not effective against Pseudomonas aeruginosa (&enterococcus)?
Ertapenem
How are carbapenems administered?
Parenterally (as poor absorption)
If pt is allergic (anaphylaxis) to penicillin, what drugs can you not give her?//
Which drug classes of beta lactams have cross reactivity with penicillins?
Cephalosporins, carbapenems (cross hypersensitivity)
Which drug class does aztreonam belong to?
Monobactam
Aztreonam is effective against Gram-
negative bacteria (no activity against Gram positive and anaerobic microbes)
Does aztreonam have cross-sensitivity to penicillin?
No
How is aztreonam administered?
Parenterally IM/IV
Which drug class does vancomycin belong to?
Glycopeptide- bact cell wall inhibitor
Vancomycin is useful against Gram ___________
positives
How is vancomycin commonly administered?
Intravenously
When is oral vancomycin preferred?
Clostridium difficile-associated diarrhea (CDAD)
or the more severe antibiotic-associated pseudo-membranous colitis (AAPMC).
What is the first line of antibiotics for CDAD?
Vancomycin
Vancomycin interferes with cell wall synthesis by inhibiting ___________
transglycosylation
b/n Ala-Ala of NAM & NAG
Name 3 antibiotics that work by inhibiting bacterial cell wall synthesis, and are effective against MRSA?
- ceftobiprole (Fifth generation cephalosporins)
- ceftaroline (Fifth generation cephalosporins)
- Vancomycin
How is vancomycin cleared?
Renal clearance
Name 3 adverse effects related to vancomycin
- Nephrotoxicity,
- Ototoxicity,
- Red man syndrome (rash above nipple line due to histamine release w rapid infusion)
- rare thrombph
How to resolve red man syndrome?
- Antihistamine
2. Prolong infusion vancomycin to 1-2 hrs
Vancomycin resistance due to?
substituting terminal D-alanine for D-lactate/serine reducing vancomycin binding affinity –> VREnterococcus
Vancomycin ineffective against?
all Gram -ve & mycobacteria