Bacterial resistance: origins, epidemiology, and impact.

The basic mechanisms of antibacterial resistance are well known, but critical new aspects continue to be discovered. Recently discovered factors with major implications for the emergence, dissemination, and maintenance of resistance include multidrug efflux, hypermutability, integrons, and plasmid addiction. Some resistances are widespread and others local, with prevalence rates often worst in newly prosperous countries and in those specialist units where antibacterial use is heaviest. Multidrug-resistant epidemic strains are critical to the total accumulation of resistance (e.g., among Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae), but it remains unclear why some bacterial lineages achieve epidemic spread whereas others that are equally resistant do not. The correlation between in vitro resistance and treatment failure is imperfect, but resistance undoubtedly increases mortality, morbidity, and costs in many settings. Recent concern has led to a plethora of governmental and agency reports advocating less antibacterial use, better antibacterial use, better infection control, and the development of new antibacterials. The evidence that better prescribing can reduce resistance rates is mixed, and although changes to hospital regimens may reduce one resistance problem, other opportunistic bacteria may fill the vacant niche. Overall, the best that can reasonably be anticipated is an improved balance between the accumulation of resistance and new antibacterial development.