The vast majority of infections that people acquire in hospitals, for example, are caused by bacterial agents, such as Staphylococcus aureus, that are resistant to penicillin. In many hospitals in the United States, nearly half of these penicillin-resistant staphylococci are also resistant to second-generation, penicillinase-resistant drugs, such as methicillin. Compounding matters, the antibiotic vancomycin, currently one of the few available treatments for methicillin-resistant staphyloccocal infections, is now showing increasing signs of losing ground as vancomycin resistance becomes ever more common among the most frequent infectious agents in hospitals (i.e., staphylococci, streptococci, pneumococci, enterococcus, and Clostridium difficile). Indeed, since this workshop, two different strains of S. aureus with full-fledged vancomycin resistance mediated by the vanA gene were isolated in the United States. Moreover, bacteria are now beginning to appear that are resistant to linezolid, introduced in 2000 for the treatment of vancomycin-resistant infections.

Drug-resistant microbes also are becoming more common in the community. At least five major bacterial pathogens,2 including Streptococcus pneumoniae, which remains a major worldwide cause of pneumonia, meningitis, sepsis, and otitis media, and Mycobacterium tuberculosis, which causes tuberculosis, have developed resistance to a number of drugs. This problem is further compounded by the ability of microbes to share important resistance genes within and across bacterial species via a variety of genetic transfer mechanisms.

Infections caused by resistant microbes that fail to respond to treatment result in prolonged illness and greater risk of death. When infections become resistant to first-line antimicrobials, treatment must be switched to second-line or even third-line drugs, which are sometimes more toxic than the drugs they replace. Treatment failures also lead to longer periods of infection, and this factor increases the numbers of infected people moving from hospitals into the community. Moreover, even healthy patients colonized with drug-resistant, hospital-acquired bacterial flora may be discharged from hospitals. Both phenomena enhance the likelihood that resistant pathogens will spread into the community.

In addition to its direct threat to human health, microbial resistance exacts an economic cost that can trigger adverse health consequences. Treating individuals with alternative drugs is nearly always much more expensive than conventional treatment. In some settings, the drugs needed to treat multi-drug-resistant forms of tuberculosis, for example, are more than 100-fold more expensive than the standard drug regimen used to treat nonresistant forms of the bacteria. In many resource-poor countries, the


Staphylococci, enterococci, pneumococci, tuberculosis, and salmonella.

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