Figure 452

Differences between gram-positive and gram-negative bacteria that affect antibiotic access. A. The cell wall structure of a gram-positive organism. The exposed porous peptidoglycan (murein) layer allows easy antibiotic access. B. The cell wall structure of a gram-negative organism. The outer membrane contains lipopolysaccharides (LPS) and porins with narrow, restrictive channels that function as barriers to antibiotic permeability. (Modified with permission from Nikaido H. Prevention of drug access to bacterial targets: Permeability barriers and active efflux. Science 1994;264:382-388.)

bacteria, protein channels (porins) allow p-lactam antibiotics to traverse the outer membrane and interact with PBPs in the periplasmic space. In resistant bacteria like P. aeruginosa, porin mutants impede the p-lactam transfer across the outer membrane.

Finally, some gram-negative organisms demonstrate a fourth mechanism of resistance. For example, strains of P. aeruginosa produce xenobiotic efflux pumps to eject antibiotics. Drug efflux mechanisms are associated with multiple drug resistance, including resistance to p-lactam antibiotics.

Widespread use of p-lactam antibiotics exerts selective pressure on bacteria and permits the proliferation of resistant organisms. A comparison of current antibi-ograms with those from previous decades shows an alarming increase in bacterial resistance to p-lactam antibiotics.

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