Lecture 7 Antimicrobials Flashcards
What are the key biological processes of bacteria?
- Cell wall
- Cell membrane
- DNA replication
- Transcription
- Protein synthesis
What are some sources of antimicrobials?
- Natural (Penicillin)
- Semi-synthetic
- synthetic
What are some things to consider on drug choice?
- absorption
- Tissue distribution
- Metabolism/excretion
- Time-dependent killing
- concentration-dependent killing
Bactericidal vs bacteriostatic .
Death versus inhibit growth- use cidal when immunocompromised or using prosthetics.
MIC, MBC
minimum inhibitory concentration, minimum bactericidal concentration
When would you want to to give combination therapy?
• Empiric therapy • Prevent resistance • Enhanced efficacy - Synergy - Additive
What are some susceptibility tests?
- Broth Dilution
- Diffusion tests (Kirby-bauer disc diffusion, ETEST)
Which antibiotics attack cell walls?
- β-lactams (penicillins and cephalosporins)
- Glycopeptides (vancomycin)
What are abx for cell membrane?
- Polymyxins
What abx is used for DNA synthesis?
- [Fluro]quinolones (e.g. ciprofloxacin)
- Sulfonamides and trimethoprim (e.g. Bactrim)
- Metronidazole
What abx attacks transcription?
- Rifampin
Which abx attacks protein synthesis?
- Aminoglycosides (e.g. gentamycin)
- Macrolides (e.g. azithromycin, “Z-pack”)
- Tetracyclines
- Lincosamides (e.g. clindamycin)
Which abx are 30s inhibitors?
- aminoglycosides
- tetracyclines
- glycineglycine
What are some 50s inhibitors
- erythromycin
- clindamycin
- chloraphenocol
- oxazolidonone
- streptogramine
Why care about resistant mechs?
helps in:
- susceptibility testing
- predict resistance without testing
- predict MIC
- Risk of infection control
What are some mechs of resistant?
- efflux
- restricting enzymes
- target modification
- Restrict access to target
How is resistance expressed?
- intrinsic (chromosomal)
- De Novo mutations
- acquired
What are the biggest concern for infection control
- constitutive
- inducible
What are some intrinsic resistance?
- Impermeability
- biofilms
What is Target site mutation
A mutation of the actual site can occur, inhibiting a abx,
e.g. mutations in topoisomerase confer fluoroquinolone resistance
What is target site protection?
Blocks target site from abx
e.g. methylation of 16S rRNA alters binding of erythromycin to ribosome
How does inactivation by hydrolysis help pathogens resist?
e.g. β-lactamase inactivation of β- lactams by hydrolysis of drug
What is inactivation by steric hinderance?
- Modify abx
e. g. aminoglycoside- modifying enzymes
What is the problem with efflux pump resistance?
- Can be broad or narrow spectrum
- Up regulation of pumps can lead to multi-drug resistance (tetracylcines, macrolides etc)
How can you end up with multi drug resistance?
- encode multiple genes
- Encode gene that can target multiple abx
- selective pressure
What are some hints in drug names?
- cef… = cephalosporin
- …cillin = penicillin
- …cillin/… = beta-lactam/beta-lactamase inhibitor
- …floxacin = fluroquinolone
- …cycline = tetraclycine
- …mycin does not indicate drug class
What are some Beta-Lactams?
(most are broad) • Penicillins • Cephalosporins • Monobactams • Carbapenems (most effective)
How do Beta-lactams work?
Bind to penicillin binding protein, disrupts peptidoglycan and prevents crosslinks form occurring. Inhibits cell growth
What are some adverse affects of Beta-lactams?
- Allergies mild to anaphylaxis
- Diarrhea
- Stevens-Johnson syndrome
- Interstitial nephritis
- Neutropenia and thrombocytopenia
- Clostridium difficile infection/overgrowth • Seizures
What is a relatively broad spectrum penicillin?
Ampicillin, Penicillin G/V
What is a narrow spectrum penicillin?
Nafcillin
What is a broad spectrum penicillin combo that is good for resistant strains?
Piperacillin/tazobactam (Zosyn)
What are the subclasses for cephalosporins?
Gen 1-5 (5 is best) . Going down to 5, goes from good with g+ to good with G+ and -. 5th is best for resistance.
What do cephalosporins do not work on what organism?
Cephalosporins don’t treat Enterococcus!
What are three general mechs to resist Beta-lactams?
- decreased penetration (barrier)
- inactivation of abx by enzyme
- Alteration of target site
What type of resistance is resistant to all beta-lactamses?
AmpC Beta- lactamases, Enterobacters biggest problem.