Current challenges in antibiotic resistance.

The striking, widespread increase in bacterial resistance to antibiotics is an issue of great concern. Worldwide emergence of antibiotic resistances in our common gram-positive coccal pathogens is probably the most serious problem we have in the realm of bacterial infections. The most important of these organisms are penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus, and methicillin- (and now vancomycin-) resistant Staphylococcus aureus. Although known by the above names, all of these organisms are multidrug-resistant. Beta-lactam and vancomycin resistances in gram-positive cocci are caused by altered cell wallñbinding sites with decreased affinity for the drug. Another serious problem is that of resistance in certain gram-negative bacilli due to extended-spectrum beta-lactamase production. These antibiotic resistances in common pathogens have made antimicrobial therapy of many infections extremely difficult or virtually impossible in some instances. The extensive, and often inappropriate, use of antibiotics in the U.S. and worldwide is the major factor in the emergence and spread of antimicrobial resistance. Microbial mechanisms, epidemiology, clinical importance, treatment, and prevention of these antibiotic resistance problems are discussed.