1. Antibacterial Agents - Inhibitors Of Cell Wall Synthesis Flashcards
What’s one Synergistic combination of cell wall synthesis inhibitors
Penicillin + aminoglycosides
What’s one Antagonistic combination of cell wall synthesis inhibitors
Penicillin + tetracycline
Mechanisms of action of antimicrobial agents?
- inhibition of bacterial cell wall synthesis
- inhibition of bacterial protein synthesis
-inhibition of nucleic synthesis
-inhibition of folic acid synthesis
Primary mechanisms of resistance to penicillins and cephalosporins?
- Change in penicillin binding proteins +++
- Production of Beta Lactamase enzymes
- Change in porins
What is the largest group of antimicrobial agents and what does it include?
Bacterial cell wall synthesis inhibitors
It includes:
Penicillins
Cephalosporins
What are Beta Lactam antibiotics?
Penicillins
Cephalosporins
Penicillin action mechanism
Bind to Penicillin Binding Protein PBP which inhibits transpeptifation reaction involved in cross linking (final step in cell wall synthesis)
Why is the Beta-lactam ring so important ?
It irreversibly inhibits transpeptidase
Hiw does bacteria resists to penicillins?
- Producing beta-lactamase (penicillinase)
- Changing the structure of penicillin cell wall targets aka PBPs
- Preventing penicillin entry to the bacteria by changing the porin structure
How many penicillin subgroups are there?
4 subgroups
Penicilin subgroup 1 ?
Narrow spectrum, only works on Gram+ cocci , beta lactamase sensitive
Includes: Penicillin G and V
Spectrum: streprococci, pneumococci, meningococcii, treponema pallidum (syphilis)
Espcecially used got Streptococcus
What is the drug of choice for syphilis ?
Pen G
More specifically Benzathine Pen G - repository form which has the half life of 2 weeks
Penicillin subgroup 2
Aka anti staph pens
Very narrow specturm
Beta lactamase resistant
Includes: Nafcillin, methicillin, oxacillin
What is MRSA?
Cross resistance to all the anti staph drugs
What is the only Pencillin subgroup that is beta lactamase resistant?
Subgroup 2 Aka Anti staph pens
How do you kill MRSA
With a drug that doesn’t bind to PBPs cuz the resistance here is by changing the PBPs
Penicillin sub group 3
Broad spectrum
Betalactamase sensitive
Includes: amoxicillin and ampicillin
Kills: Gram+ cocci and some gram-
What is the drug of choice for Listeria?
Ampicillin
The drug of choice for Otits Media (otite moyenne)?
Amoxicillin
Because it’s broad enough to kill all the causative organisms
Penicillin subgroup 4
Very Broad Spectrum
Aka antipseudomonal but kill a lot more bacteria i e gram+ and gram-
Beta lactamase sensitive
Include ticarcillin and piperacillin
Increased activity against gram- rods
Penicillin coverage hack?
All penicillins have some gram+ coverage, then the broader their spectrum the more Gram- coverage they have
What’s clavulanic acid?
Beta lactamase inhibitor
Beta lactamase inhibitors ?
Aka suicide inhibitors
Clavulanic acid
Sumbactam
Taeobactam
Synergy against pseudomonas, listeria and enteroccus?
Penicillin + aminoglycoside
Penicillin renal dysfunction adjustment ?
Like most antibiotics, they’re eliminated via active tubular secretion
And thus renal dysfunction requires dose reduction
Probenecid (anti-gout drug) effect on penicillins?
It decreases penicillin tubular secretion and thus it prolong their plasma half-life and increase serum concentrations
2 examples of an exception of penicillin elimination in renal tubes?
Nafcillin & oxacillin
Eliminated largely in the bile
2 examples of an exception of penicillin elimination in renal tubes?
Nafcillin & oxacillin
Eliminated largely in the bile
Penicillins side effects?
- hypersensitivity (from mild rash to anaphylaxis) / should assume complete cross allerginicity between individual penicillins / eliminates the entire group of treatment plan
- GI distress i.e nausea vomitting diarrhea (NVD) especially ampicillin
- Jarisch-Herxheimer reaction involved syphylis: it’s a result of the dying organisms i.e cytokines release
Jarisch-Herxheimer reaction involved syphylis?
Starts 1h after starting treatment:
Patient experience fever, muscle pain
Cephalosporin mechanisms of action and resistance
Identical to penicillin as they are also B lactam molecules
How money subgroups cephalosporin habe?
4 subgroups aka generations
1st gen cephalosporins?
- Cefazolin, cephalexin (there are soooo many)
- if a drug has a ph in its name it’s a phirst gen cephalosporin (but some have an f)
- narrow spectrum: gram + cocci (not MRSA) , e. Cholo, klebsiella, pneumoniae and some proteus
- think abt strep and staph
- used as surgical prophylaxis
- they do NOT enter the central nervous system
2nd gen cephalosporins?
- Ex: cefotetan, cefaclot, cefuroxime
- Broad spectrum: increased gram - coverage, including some anaerobes
- do not enter the CNS execpt cefuroxime
-Mnemonic: it’s a FACt (cefaclor) that I dont want a FOXy (cefoxitin), FURy (cefuroxime) man!