β-lactam resistance

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
• Class A: original active-site serine ß-lactamases
• Class B: original metallo-ß-lactamases
• Class C: AmpC ß-lactamases
• Class D: OXA ß-lactamases

Specific ß-lactamases

NDM-1

• Broad-spectrum metallo-beta-lactamase and carbapenemase
• Can be treated empirically with ceftazidime-avibactam and aztreonam +/- colistin

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