Mechanisms of antimicrobial resistance in Gram-negative bacilli

Annals of Intensive Care

Table 4 Main mechanisms of acquired antimicrobial resistance in Pseudomonas aeruginosa

Mechanism	Genetic event	Antimicrobials
High-level expressed AmpC cephalosporinase	Chromosomal mutation	Penicillins (with or without beta-lactamase inhibitors), cephalosporins, aztreonam
Other beta-lactamases
Penicillinases^a	MGE acquisition	Penicillins
Extended-spectrum beta-lactamases^b		Penicillins, cephalosporins, aztreonam
Metallo-beta-lactamases^c (carbapenemases)		Penicillins, cephalosporins, carbapenems
Loss of OprD (impermeability)	Chromosomal mutation	Imipenem
Active efflux pumps
MexAB-OprM	Chromosomal mutation	Ticarcillin, cephalosporins, aztreonam, meropenem, fluoroquinolones
MexXY-OprM		Cefepime (±penicillins), aminoglycosides, fluoroquinolones
MexEF-OprN		Meropenem, fluoroquinolones
MexCD-OprJ		Cefepime, aztreonam (+/− penicillins), fluoroquinolones
Aminoglycoside-modifying enzymes^d	MGE acquisition	Aminoglycosides
16S rRNA methylases	MGE acquisition	Aminoglycosides
Topoisomerases modifications	Chromosomal mutation	Fluoroquinolones
Lipid A (LPS) modifications	Chromosomal mutation	Polymyxins

MGE mobile genetic element (plasmid or transposon).
Most common enzyme types: ^aPSE and OXA; ^bPER, SHV, GES and OXA; ^cVIM and IMP (SIM, GIM and SPM types are less common); ^dAAC(3)-I, AAC(3)-II, AAC(6′)-I, AAC(6′)-II and ANT(2′)-I.