AST and bacterial mechanisms of resistance Flashcards
Discuss the difference in cell structure of gram positives vs gram negatives
Gram positive - PBPs in plasma membrane
Gram negative - ABs need to reach periplasmic space
What are the broad mechanisms of action of antibiotics?
- Disruption of cell wall synthesis
- Effects on cell membrane integrity
- Inhibition of protein synthesis
- Interference with nucleic acid metabolism
- Inhibition of enzymes that synthesise folic acid
Which antibiotics work on the cell wall?
Beta lactase
Bacitracin
Which antibiotics work on cell membrane?
Ampho B
Nystatin
Colistin
Clotrimazole
Ketoconazole
Which antibiotics work on nucleic acids?
Quinolones
Rifampin
Flucytosine
Which antibiotics work on antimetabolites?
Sulfonamides
Trimethoprim
Ethambutol
Isoniazid
Which antibiotics work on protein synthesis?
Tetracyclines
Aminoglycosides
Erythromycin
Chloramphenicol
What is the value of mechanism of resistance data?
- Local epidemiology
- Antibiotic therapy selection
- Outbreak detection
- Unusual AST detection and troubleshooting
- Design of new drugs
What are the kinds of mechanisms of resistance?
- Antibiotic modification
- Target modification
- Target access restriction
- Efflux pumps
Give examples of chromosomal beta lactamases
SHV (klebs pneumonia- ampicillin)
AmpC (e. cloacae)
Give examples of plasmid mediated beta lactamases
Penicillinases
Cephalosporinase
Carbapenemase
Which gene is common in ESBLs?
CTX - M
Name weak ampC inducers
Piptaz
Cefepim
Give examples of oxacillinases
OXA-48 (enterobacterales)
OXA-23 (a.baumanii)
Which antibiotic is useful in OXA-23s?
Sulbactam-durlobactam
Which carbapenemase groups is durlobactam effective against?
A, C, D
Name the MBLs
NDM
VIM
IMP
Which antibiotic is used in MBLs?
Aztreonam (not stable against ESBLs)
Which carbapenemase class are MBLs?
B
Which class is varbobactam/relebactam effective against?
Class A
Which class does KPC belong to?
Class A
What is the most important of the 4 amino glycoside resistance mechanisms and why?
Aminoglycoside modifying enzymes (AMEs)
Frequency and level of resistance
In which organisms are altered PBPs more common?
Gram positive
Which gene in staph aureus codes for PBP2A to confer cloxacilin resistance?
mecA
What is the resistance mechanism in VREs?
Altered cell wall precursors
What is the usual mechanism of aciba resistance to colistin?
Chromosomal
Altered lipopolysaccharide with reduced cell membrane negative charge
What is the usual mechanism of enterobacterale resistance to colistin?
Plasmid
mcr genes which code enzymes to cause modified lipid A in LPS
In which organism is porin loss an important mechanism?
Pseudomonas aeruginosa
What is the MOA of cefiderocol?
Enters bacterial cells using active iron transporters
What is the usual resistance mechanism to tigecycline?
- Efflux pump
- Ribosome modification
Which enzyme is modified in s.aureus to confer quinolone resistance?
Topoisomerase IV
Which enzyme is modified in p. aeruginosa to confer quinolone resistance?
DNA gyrase
