The threat to human health posed by antibiotic resistance is of growing concern. Many commensal and pathogenic organisms have developed resistance to well established and newer antibiotics. The major selection pressure driving changes in the frequency of antibiotic resistance is the volume of drug use. However, establishing a quantitative relationship between the frequency of resistance and volume of drug use has proved difficult. Using population genetic methods and epidemiological observations, we report an analysis of the inf luence of the selective pressure imposed by the volume of drug use on temporal changes in resistance. Analytical expressions are derived to delineate key relationships between resistance and drug consumption. The analyses indicate that the time scale for emergence of resistance under a constant selective pressure is typically much shorter than the decay time after cessation or decline in the volume of drug use and that significant reductions in resistance require equally significant reductions in drug consumption. These results highlight the need for early intervention once resistance is detected.The increasing frequency with which antimicrobial-resistant microorganisms are recovered from patients in hospital and community settings has been commented on widely in recent years (1-3). Many species and strains of bacteria that are pathogenic to humans have developed resistance to both well established and newer antibiotics. Multiply resistant organisms give special cause for concern because they are responsible for increasing numbers of infections in intensive care units, hospitals in general, and communities (4). A recent example is the emergence of heteroresistant vancomycin resistant Staphylococcus aureus in hospital settings in Japan and the USA after 30 years of use as the drug of choice for the treatment of methicillin-resistant S. aureus and other Gram-positive infections (5). More alarming still is a recent report of the extensive spread of vancomycin-resistant (heteroresistant), methicillinresistant S. aureus strains in Japanese hospitals (6).A number of pathogen-specific epidemiological models of drug resistance have been proposed for both communityacquired (7-10) and hospital-acquired infections (11,12,14). The major selective pressure driving changes in the frequency of resistance is, in each case, the volume of drug use. Establishing a precise quantitative relationship between the frequency of resistance to a defined antibiotic and the volume of drug use has proved difficult because of the paucity of longitudinal studies that record resistance and drug use patterns (15-23). It is important to do so, however, given the urgent need to develop national and international antibiotic prescribing policies based on precise scientific understanding of key factors, which minimize the rate of evolution and spread of resistant organisms.In both clinical and community settings, patterns of emergence tend to be similar; typically, a long period of very low-level resistance precedes a...

In patients with recurrent nasal polyposis receiving topical corticosteroids who required surgery, mepolizumab treatment led to a greater reduction in the need for surgery and a greater improvement in symptoms than placebo.

Vancomycin-resistant enterococci (VRE) recently have emerged as a nosocomial pathogen especially in intensive-care units (ICUs) worldwide. Transmission via the hands of health-care workers is an important determinant of spread and persistence in a VRE-endemic ICU. We describe the transmission of nosocomial pathogens by using a microepidemiological framework based on the transmission dynamics of vector-borne diseases. By using the concept of a basic reproductive number, R 0 , defined as the average number of secondary cases generated by one primary case, we show quantitatively how infection control measures such as hand washing, cohorting, and antibiotic restriction affect nosocomial cross-transmission. By using detailed molecular epidemiological surveillance and compliance monitoring, we found that the estimated basic reproductive number for VRE during a study at the Cook County Hospital, Chicago, was approximately 3-4 without infection control and 0.7 when infection control measures were included. The impact of infection control was to reduce the prevalence from a predicted 79% to an observed 36%. Hand washing and staff cohorting are the most powerful control measures although their efficacy depends on the magnitude of R 0 . Under the circumstances tested, endemicity of VRE was stabilized despite infection control measures, by the constant introduction of colonized patients. Multiple stochastic simulations of the model revealed excellent agreement with observed pattern. In conjunction with detailed microbiological surveillance, a mathematical framework provides a precise template to describe the colonization dynamics of VRE in ICUs and impact of infection control measures. Our analyses suggest that compliance for hand washing significantly in excess of reported levels, or the cohorting of nursing staff, are needed to prevent nosocomial transmission of VRE in endemic settings.