{"610417":{"#nid":"610417","#data":{"type":"news","title":"Cycling Antibiotics to Treat Infections","body":[{"value":"\u003Cp\u003EAs microorganisms evolve to resist antibiotics, the world risks running out of drugs to treat bacterial infections. One way to slow this trend is to find new modes of using existing drugs, even those now ineffective because of microbial resistance.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EOne strategy is based on the phenomenon of collateral sensitivity: When some microbes develop resistance to one antibiotic, they become hypersensitive to another. For example, when an \u003Cem\u003EEscherichia coli\u003C\/em\u003E strain became indifferent to chloramphenicol, it also became highly vulnerable to polymyxin B. For this strain, chloramphenicol and polymyxin B form a collaterally sensitive pair.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESometimes the drug pair exhibits mutual collateral sensitivity (MCS) for a pathogen: The pathogen\u0026rsquo;s evolution of resistance to drug A increases its sensitivity to drug B and vice versa.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EResearchers have identified several MCS pairs for pathogens like \u003Cem\u003EE. coli\u003C\/em\u003E and \u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E. Some have proposed exploiting the phenomenon to treat infections by cycling through the drugs, A-B-A-B.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;This sounds very clever,\u0026rdquo; says Georgia Tech biomathematician \u003Ca href=\u0022https:\/\/math.gatech.edu\/people\/howie-weiss\u0022\u003EHoward \u0026ldquo;Howie\u0026rdquo; Weiss\u003C\/a\u003E. \u0026ldquo;Bbut what could prevent this scheme from working is the rapid emergence and ascent of a population of cells that are resistant to both antibiotics.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe prospect is exciting, but no experiments have yet been performed to test efficacy.\u003C\/p\u003E\r\n\r\n\u003Cblockquote\u003E\r\n\u003Cp\u003E\u003Cem\u003E\u0026nbsp;\u0026ldquo;This was a real team effort between a microbiologist and a biomathematician.\u0026rdquo;\u003C\/em\u003E\u003C\/p\u003E\r\n\u003C\/blockquote\u003E\r\n\r\n\u003Cp\u003EWith Stockholm University microbiologist \u003Ca href=\u0022https:\/\/www.su.se\/mbw\/research\/research-groups\/infection-and-immunobiology\/group-udekwu\u0022\u003EKlas Udekwu\u003C\/a\u003E, Weiss has tested the plausibility of such schemes, using a mathematical model that considers factors affecting efficacy. Applying treatment protocols consisting of pairs MCS antibiotics, they examined how fast multiply-resistant mutants would emerge. They reported results in \u003Cem\u003E\u003Ca href=\u0022https:\/\/www.dovepress.com\/pharmacodynamic-considerations-of-collateral-sensitivity-in-design-of--peer-reviewed-article-DDDT\u0022\u003EDrug Design, Development and Therapy\u003C\/a\u003E\u003C\/em\u003E\u003Cem\u003E.\u003C\/em\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThey found some treatments that did not produce multiply-resistant mutants for several weeks, for several months, and even indefinitely. That means some combinations of an MCS pair prevented further development of the bacteria\u0026rsquo;s resistance to either drug.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u0026ldquo;This was a real team effort between a microbiologist and a biomathematician,\u0026rdquo; Weiss says. \u0026ldquo;My job was to construct the model using a system of differential equations and very carefully simulate their solution using a computer.\u0026rdquo;\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe first experiment used low\u0026nbsp;to\u0026nbsp;moderate concentrations of antibiotics and daily cycling: drug A on day 1, drug B on day 2, drug A on day 3. At these drug levels, treatment failed. Resistant mutants rapidly developed and dominated.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESimulation results improved with higher drug concentrations. \u0026ldquo;We found that one-day cycling of certain antibiotics kept the double-resistant mutants in check for over two weeks, which would be sufficient to cure many infections,\u0026rdquo; Weiss says.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe simulations also showed that three-day cycling of antibiotics that only inhibit bacterial growth \u0026ndash; not kill \u0026ndash; would never result in double-resistant mutants.\u0026nbsp;\u0026ldquo;This was striking,\u0026rdquo; Udekwu says, \u0026ldquo;but in line with ecological theory.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EUdekwu is now conducting in-vitro cycling experiments. The next step would likely be experiments in mice. \u0026ldquo;It is far too early for clinicians to think about this strategy,\u0026rdquo; he says, \u0026ldquo;other than to keep an ear out for it,\u0026nbsp;perhaps in a \u003Ca href=\u0022#_Hlk521687459\u0022\u003ECochrane\u003C\/a\u003E report someday.\u0026nbsp;\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Simulations suggest a way to avoid microbial resistance"}],"field_summary":[{"value":"\u003Cdiv\u003E\r\n\u003Cp\u003EUsing a mathematical model, Georgia Tech biomathematician Howard \u0026ldquo;Howie\u0026rdquo; Weiss and Stockholm University microbiologist Klas Udekwu open a potential path to slowing microbial resistance to current antibiotics.\u003C\/p\u003E\r\n\r\n\u003Cdiv\u003E\r\n\u003Cp\u003EUsing a mathematical model, Georgia Tech biomathematician Howard \u0026ldquo;Howie\u0026rdquo; Weiss and Stockholm University microbiologist Klas Udekwu open a potential path to slowing microbial resistance to current antibiotics.\u003C\/p\u003E\r\n\u003C\/div\u003E\r\n\u003C\/div\u003E\r\n","format":"limited_html"}],"field_summary_sentence":[{"value":"Simulations suggest a way to avoid microbial resistance."}],"uid":"30678","created_gmt":"2018-08-27 19:18:04","changed_gmt":"2019-02-12 20:40:12","author":"A. Maureen Rouhi","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2018-08-27T00:00:00-04:00","iso_date":"2018-08-27T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"610415":{"id":"610415","type":"image","title":"Howie Weiss","body":null,"created":"1535396633","gmt_created":"2018-08-27 19:03:53","changed":"1535396633","gmt_changed":"2018-08-27 19:03:53","alt":"","file":{"fid":"232441","name":"Howie Weiss.math_.400xX_scale.jpg","image_path":"\/sites\/default\/files\/images\/Howie%20Weiss.math_.400xX_scale.jpg","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/Howie%20Weiss.math_.400xX_scale.jpg","mime":"image\/jpeg","size":23860,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/Howie%20Weiss.math_.400xX_scale.jpg?itok=R3kN1aFq"}},"610416":{"id":"610416","type":"image","title":"Klas Udekwu","body":null,"created":"1535396671","gmt_created":"2018-08-27 19:04:31","changed":"1535396671","gmt_changed":"2018-08-27 19:04:31","alt":"","file":{"fid":"232442","name":"2018 Klas Udekwu.png","image_path":"\/sites\/default\/files\/images\/2018%20Klas%20Udekwu.png","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/2018%20Klas%20Udekwu.png","mime":"image\/png","size":142332,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/2018%20Klas%20Udekwu.png?itok=nt4VMCrz"}}},"media_ids":["610415","610416"],"related_links":[{"url":"https:\/\/cos.gatech.edu\/news\/researchers-determine-routes-respiratory-infectious-disease-transmission-aircraft","title":"Researchers Determine Routes of Respiratory Infectious Disease Transmission on Aircraft"}],"groups":[{"id":"1278","name":"College of Sciences"},{"id":"1279","name":"School of Mathematics"}],"categories":[{"id":"138","name":"Biotechnology, Health, Bioengineering, Genetics"}],"keywords":[{"id":"178865","name":"drug resistance"},{"id":"11571","name":"Antibiotics"},{"id":"173647","name":"_for_math_site_"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EA. Maureen Rouhi, Ph.D.\u003Cbr \/\u003E\r\nDirector of Communications\u003Cbr \/\u003E\r\nCollege of Sciences\u003C\/p\u003E\r\n","format":"limited_html"}],"email":["maureen.rouhi@cos.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}