Infectious Diseases II
The antibiotic pipeline has slowed down considerably, with consistent decreases in FDA approvals of
antimicrobial agents during the past 3 decades. The combination of prevailing resistance, including the
emergence of pan-resistant pathogens, with the lack of new antimicrobial agents presents a potential
global health problem.
An understanding of resistance mechanisms would assist the ICU clinician in effectively treating
current resistant pathogens while incorporating antimicrobial stewardship principles to prevent further
resistance. See Table 9 for common mechanisms of resistance.
Pathogen
CLABSI %
Resistance
CAUTI %
Resistance
SSI %
Resistance
Gram-negative Bacteria
Multidrug-resistanta
P aeruginosa
14.2
8.7
3.9
Gram-positive Bacteria
S. aureus
Oxacillin resistant
44.9
39.8
39.2
E. faecalis
Vancomycin resistant
3.8
2.8
2.4
aMultidrug resistant is defined as being either intermediate or resistant to at least 1 drug in 3 of the following 5 classes: third- and fourth-generation cephalosporins,
fluroquinolones, aminoglycosides, carbapenems, and piperacillin and/or piperacillin-tazobactam (definition according to the CDC National Healthcare Safety
Network).
CAUTI = catheter-associated urinary tract infection; CLABSI = centralβline associated bloodstream infection; SSI = surgical site infection.
Antibacterial Agent
Mechanism of Resistance
Ξ²-Lactams
Ξ²-Lactamases (AmpC, ESBL, KPC)
Reduced permeability
Altered penicillin binding proteins
Increased efflux
Fluoroquinolones
Altered DNA gyrase and topoisomerase
Increased efflux
Decreased protein targets
Macrolides
Increased efflux
Methylating enzymes
Aminoglycosides
Aminoglycoside-modifying enzymes
Increased efflux
Modification of target proteins
Glycopeptides
Altered target
Decreased permeability
Tetracyclines
Increased efflux
Protection of target proteins
Trimethoprim
Increased efflux
Altered dihydrofolate reductase
Rifamycin
Altered RNA polymerase