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Mechanisms of Resistance Against Different Antimicrobial Classes

(Forbes et al., 1998; Berger-Bachi, 2002)

 

ANTIMICROBIAL CLASS

MECHANISM OF RESISTANCE

SPECIFIC MEANS TO ACHIEVE RESISTANCE

EXAMPLES

Beta-lactams

Examples: penicillin, ampicillin, mezlocillin, peperacillin, cefazolin, cefotaxime, ceftazidime, aztreonam, imipenem

Enzymatic destruction

Destruction of beta-lactam rings by beta-lactamase enzymes.  With the beta-lactam ring destroyed, the antibiotic will no longer have the ability to bind to PBP (Penicillin-binding protein), and interfere with cell wall synthesis.

Resistance of staphylococi to penicillin;  

Resistance of Enterobacteriaceae to penicllins, cephalosporins, and aztreonam

Altered target

Changes in penicillin binding proteins. Mutational changes in original PBPs or acquisition of different PBPs will lead to inability of the antibiotic to bind to the PBP and inhibit cell wall synthesis

Resistance of staphylococci to methicillin and oxacillin

Decreased uptake

Porin channel formation is decreased. Since this is where beta-lactams cross the outer membrane to reach the PBP of Gram-negative bacteria, a change in the number or character of these channels can reduce  betalactam uptake..

Resistance of Enterobacter aerogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa to imipenem

Glycopeptides

Example: vancomycin

Altered target

Alteration in the molecular structure of cell wall precursor components decreases binding of vancomycin so that cell wall synthesis is able to continue.

Resistance of enterococci to vancomycin

Aminoglyosides

Examples: gentamicin, tobramycin, amikacin, netilmicin, streptomycin, kanamycin

Enzymatic modification

Modifying enzymes alter various sites on the aminoglycoside molecule so that the ability of this drug to bind the ribosome and halt protein synthesis is greatly diminished or lost entirely.

Resistance of many Gram-positive and Gram negative bacteria to aminoglycosides

Decreased uptake

Change in number or character of porin channels (through which aminoglycosides cross the outer membrane to reach the ribosomes of gram-negative bacteria) so that aminoglycoside uptake is diminished.

Resistance of a variety of Gram-negative bacteria to aminoglycosides

Altered target

Modification of ribosomal proteins or of 16s rRNA. This reduces the ability of aminoglycoside to successfully bind and inhibit protein synthesis

Resistance of Mycobacterium spp to streptomycin

Quinolones

Examples: ciprofloxacin, levofloxacin, norfloxacin, lomefloxacin

Decreased uptake

Alterations in the outer membrane diminishes uptake of drug and/or activation of an “efflux” pump that removes quinolones before intracellular concentration is sufficient for inhibiting DNA metabolism.

Resistance of Gram negative and staphylococci (efflux mechanism only) to various quinolones

Altered target

Changes in DNA gyrase subunits decrease the ability of quinolones to bind this enzyme and interfere with DNA processes

Gram negative and Gram positive resistance to various quinolones

 

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