β-lactam resistance
From IDWiki
Mechanisms
- ß-lactamase production: enzymatic breakdown of beta lactam antibiotic
- Penicillin binding protein mutations (e.g. MRSA)
- Efflux pump mutations
- Porin channel mutations that reduce antibiotic influx
β-lactamases
Ambler Classification of ß-lactamases
- Based on amino acid sequences rather than function
- Classes A, C, and D are serine ß-lactamases, while class B are metallo-β-lactamases
| Ambler | Binding Site | Examples | Inhibitors |
|---|---|---|---|
| A | serine | TEM, SHV, KPC, CTX-M, GES | avibactam, vaborbactam, relebactam |
| B | metallo | VIM, NDM, IMP | |
| C | serine | AmpC, P99 | avibactam, vaborbactam, relebactam |
| D | serine | OXA (oxacillinase) enzymes | avibactam (OXA-48) |
Specific ß-lactamases
NDM-1
- Broad-spectrum metallo-beta-lactamase and carbapenemase
Efflux Pumps
- Major cause of resistance in Pseudomonas aeruginosa and similar species
- e.g. MexAB-OprM, which confers broad antimicrobial resistance including cephalosporins and some carbapanems
Porin Loss
- Most common cause of carbapenem resistance in Pseudomonas aeruginosa
