Antibiotic resistance is a powerful model for studying evolutionary biology and population genetics. For the purpose of these evolutionary studies, fitness data have been approximated through susceptibility testing methods designed for clinical use in providing appropriate antibiotic therapies. An alternative approach for measuring fitness of microbes has experienced growing popularity: growth rates are a highly sensitive approach for measuring the fitness effects of antibiotics and resistance genes, but they differ from susceptibility testing in that a single concentration of antibiotic is used for the assay. Here we show that despite this key difference, the results of growth rates correlate well with clinical determination of resistance by minimum inhibitory concentration (MIC), while providing the sensitivity required for direct input as fitness values into mathematical models. This means that growth rates at a single sublethal inhibitory concentration can help us understand the fitness effects that result in clinical antibiotic resistance. By measuring the growth rates of sequenced clinical isolates obtained from Dignity Health Mercy Medical Center, we detected the fitness effects of individual resistance genes on bacteria exposed to different antibiotics. In our study, the CTX-M-15 gene conferred the highest fitness in assays with cephalosporins. These results show the strong fitness benefit conferred by CTX-M-15.
The evolution and dissemination of antibiotic resistance genes throughout the world are clearly affected by the selection and migration of resistant bacteria. However, the relative contributions of selection and migration at a local scale have not been fully explored. We sought to identify which of these factors has the strongest effect through comparisons of antibiotic resistance gene abundance between a distinct location and its surroundings over an extended period of six years. In this work, we used two repositories of extended spectrum β-lactamase (ESBL)-producing isolates collected since 2013 from patients at Dignity Health Mercy Medical Center (DHMMC) in Merced, California, USA, and a nationwide database compiled from clinical isolate genomes reported by the National Center for Biotechnology Information (NCBI) since 2013. We analyzed the stability of average resistance gene frequencies over the years since collection of these clinical isolates began for each repository. We then compared the frequencies of resistance genes in the DHMMC collection with the averages of the nationwide frequencies. We found DHMMC gene frequencies are stable over time and differ significantly from nationwide frequencies throughout the period of time we examined. Our results suggest that local selective pressures are a more important influence on the population structure of resistance genes in bacterial populations than migration. This, in turn, indicates the potential for antibiotic resistance to be controlled at a regional level, making it easier to limit the spread through local stewardship.
In response to the COVID-19 pandemic, many higher educational institutions moved their courses on-line in hopes of slowing disease spread. The advent of multiple highly-effective vaccines offers the promise of a return to “normal” in-person operations, but it is not clear if—or for how long—campuses should employ non-pharmaceutical interventions such as requiring masks or capping the size of in-person courses. In this study, we develop and fine-tune a model of COVID-19 spread to UC Merced’s student and faculty population. We perform a global sensitivity analysis to consider how both pharmaceutical and non-pharmaceutical interventions impact disease spread. Our work reveals that vaccines alone may not be sufficient to eradicate disease dynamics and that significant contact with an infectious surrounding community will maintain infections on-campus. Our work provides a foundation for higher-education planning allowing campuses to balance the benefits of in-person instruction with the ability to quarantine/isolate infectious individuals.
In response to the COVID-19 pandemic, many higher educational institutions moved their courses on-line in hopes of slowing disease spread. The advent of multiple highly-effective vaccines offers the promise of a return to "normal" in-person operations, but it is not clear if -- or for how long -- campuses should employ non-pharmaceutical interventions such as requiring masks or capping the size of in-person courses. In this study, we develop and fine-tune a model of COVID-19 spread to UC Merced's student and faculty population. We perform a global sensitivity analysis to consider how both pharmaceutical and non-pharmaceutical interventions impact disease spread. Our work reveals that vaccines alone may not be sufficient to eradicate disease dynamics and that significant contact with an infected surrounding community will maintain cases on-campus. Our work provides a foundation for higher-education planning allowing campuses to balance the benefits of in-person instruction with the ability to quarantine/isolate infected individuals.
Ceftolozane/tazobactam (c/t) is a potent β-lactam antibiotic which combines the fifth generation cephalosporin ceftolozane and tazobactam, a β-lactamase inhibitor. The c/t combination therapy was approved in 2014 for the treatment of multidrug resistant (MDR) Enterobacteriaceae, especially intra-abdominal and urinary tract infections. The aim of this study is to assess c/t activity and to examine the association of c/t resistance with four common β-lactamase resistance genes found in clinical Enterobacteriaceae isolates collected from mainly urinary tract infections in an agricultural region in California (USA) between 2013-2020. We tested 993 Extended Spectrum β-lactamases (ESBL) producing Enterobacteriaceae isolates (885 E. coli, 94 K. pneumoniae, 14 other) for c/t susceptibility by Kirby-Bauer disk diffusion and screened using PCR for four common resistance genes with β-lactamase activity(blaTEM, blaOXA, blaSHV, and blaCTX-M) for 855 of the isolates. We also investigated co-resistance of c/t and nine other β-lactam antibiotics. We found that most isolates were susceptible to c/t (58.3%), while 38.5% showed intermediate resistance, and 3.2% were resistant. We also found that K. pneumoniae isolates were more resistant to c/t than E. coli isolates, and that c/t may be a good alternative to carbapenems, in that that some carbapenem resistant isolates were susceptible to c/t. Genotypic analysis showed blaSHV and blaCTX-M are independently associated with elevated c/t resistance. Although c/t demonstrated strong activity against Enterobacteriaceae, the high percentage of isolates with intermediate susceptibility emphasizes the need for close monitoring and continued surveillance for c/t resistance among ESBLs
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.