Microbial resistance to newer generation beta-lactam antibiotics: clinical and laboratory implications

Certain nonfastidious, gram-negative bacilli possess the ability to rapidly develop resistance to many of the newer "enzyme stable" beta-lactam antibiotics. This finding poses many clinical problems including emergence of resistance during therapy with the drugs. Therapeutic alternatives for patients are severely limited when this problem occurs because multiple drug resistance may arise simultaneously. To date, two mechanisms have been found to be responsible for this resistance. The first, which produces multiple beta-lactam resistance, is the induction of chromosomal beta-lactamases that mediate resistance to nonsubstrate drugs by the creation of a nonhydrolytic barrier that blocks access to target proteins within the cell. The second mechanism, which produces beta-lactam/aminoglycoside resistance, involves a change in outer membrane permeability. Outbreaks of nosocomial infections with these multiple drug-resistant organisms and spread of the strains throughout the hospital are already being seen. Control of these problems can only be achieved through the judicious and restricted use of these new antibiotics.