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 = central–line associated bloodstream infection; SSI = surgical site infection.

Antibacterial Agent

Mechanism of Resistance

β-Lactams

β-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