Browsing by Subject "antibiotic"
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Item Microbial Population Structure Impacts Antibiotic Resistance(2015-03) Ratnayeke, Nalin; Gordon, VernitaAntibiotic resistance is an urgent and growing concern, and developing novel therapeutic approaches to overcome antibiotic-resistant infections has assumed immense significance. Recently, it has been shown that heterogeneity in a microbial environment can accelerate the development of antibiotic resistance. However, the effect of the spatial distribution of the microbial population itself remains to be investigated. Using the human pathogen Pseudomonas aeruginosa, we show that increasing cell density can drastically impact the survival and growth of antibiotic-resistant mutants in the presence of aminoglycoside antibiotics in a density-dependent manner. Increasing density confers both positive and negative effects to mutant survival, which we term “protection” and “inhibition”, respectively. Using a combination of microbiological assays and biophysical modeling, we find that inhibition is mediated by a low-molecular weight, native by-product of bacterial metabolism that acts in conjunction with aminoglycosides through an effected increase in pH. A wide range of bacterial species are capable of producing inhibition, which is related to their growth by amino acid catabolism. We additionally develop a stochastic model of inhibition in homogeneous environments, which indicates that local density fluctuations on the scale of individual bacteria can significantly alter bacterial survival when colonizing a new environment. This work raises the possibility that the manipulation of population structure and the nutrient environment of microbes in conjunction with the use existing antibiotics could provide novel therapeutic approaches to combat antibiotic resistance.Item Outpatient Antibiotic Prescribing in the United States: 2000 to 2010(2014-06) Lee, Grace C.; Reveles, Kelly R.; Attridge, Russell T.; Lawson, Kenneth A.; Mansi, Ishak A.; Lewis, James S.; Frei, Christopher R.; Lee, Grace C.; Reveles, Kelly R.; Lawson, Kenneth A.; Lewis, James S.; Frei, Christopher R.The use of antibiotics is the single most important driver in antibiotic resistance. Nevertheless, antibiotic overuse remains common. Decline in antibiotic prescribing in the United States coincided with the launch of national educational campaigns in the 1990s and other interventions, including the introduction of routine infant immunizations with the pneumococcal conjugate vaccine (PCV-7); however, it is unknown if these trends have been sustained through recent measurements. Methods: We performed an analysis of nationally representative data from the Medical Expenditure Panel Surveys from 2000 to 2010. Trends in population-based prescribing were examined for overall antibiotics, broad-spectrum antibiotics, antibiotics for acute respiratory tract infections (ARTIs) and antibiotics prescribed during ARTI visits. Rates were reported for three age groups: children and adolescents (<18 years), adults (18 to 64 years), and older adults (>= 65 years). Results: An estimated 1.4 billion antibiotics were dispensed over the study period. Overall antibiotic prescribing decreased 18% (risk ratio (RR) 0.82, 95% confidence interval (95% CI) 0.72 to 0.94) among children and adolescents, remained unchanged for adults, and increased 30% (1.30, 1.14 to 1.49) among older adults. Rates of broad-spectrum antibiotic prescriptions doubled from 2000 to 2010 (2.11, 1.81 to 2.47). Proportions of broad-spectrum antibiotic prescribing increased across all age groups: 79% (1.79, 1.52 to 2.11) for children and adolescents, 143% (2.43, 2.07 to 2.86) for adults and 68% (1.68, 1.45 to 1.94) for older adults. ARTI antibiotic prescribing decreased 57% (0.43, 0.35 to 0.52) among children and adolescents and 38% (0.62, 0.48 to 0.80) among adults; however, it remained unchanged among older adults. While the number of ARTI visits declined by 19%, patients with ARTI visits were more likely to receive an antibiotic (73% versus 64%; P < 0.001) in 2010 than in 2000. Conclusions: Antibiotic use has decreased among children and adolescents, but has increased for older adults. Broad-spectrum antibiotic prescribing continues to be on the rise. Public policy initiatives to promote the judicious use of antibiotics should continue and programs targeting older adults should be developed.