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, 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