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11. New Delhi Metallo-[beta]-Lactamase--Producing Enterobacterales Bacteria, Switzerland, 2019-2020

Author

Findlay, Jacqueline, Poirel, Laurent, Kessler, Julie, Kronenberg, Andreas, and Nordmann, Patrice

Subjects
Beta lactamases -- Health aspects, Enterobacteriaceae infections -- Diagnosis -- Care and treatment, Health
Abstract

Carbapenem-resistant Enterobacterales (CRE) bacteria are considered by the World Health Organization to be a critical global health concern; they were placed in the organization's critical-priority group of the priority pathogens [...]

Published
2021
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12. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Author

Koshy, Cherian, Wise, Emma, Cortes, Nick, Lynch, Jessica, Kidd, Stephen, Mori, Matilde, Fairley, Derek J., Curran, Tanya, McKenna, James P., Adams, Helen, Fraser, Christophe, Golubchik, Tanya, Bonsall, David, Moore, Catrin, Caddy, Sarah L., Khokhar, Fahad A., Wantoch, Michelle, Reynolds, Nicola, Warne, Ben, Maksimovic, Joshua, Spellman, Karla, McCluggage, Kathryn, John, Michaela, Beer, Robert, Afifi, Safiah, Morgan, Sian, Marchbank, Angela, Price, Anna, Kitchen, Christine, Gulliver, Huw, Merrick, Ian, Southgate, Joel, Guest, Martyn, Munn, Robert, Workman, Trudy, Connor, Thomas R., Fuller, William, Bresner, Catherine, Snell, Luke B., Charalampous, Themoula, Nebbia, Gaia, Batra, Rahul, Edgeworth, Jonathan, Robson, Samuel C., Beckett, Angela, Loveson, Katie F., Aanensen, David M., Underwood, Anthony P., Yeats, Corin A., Abudahab, Khalil, Taylor, Ben E.W., Menegazzo, Mirko, Clark, Gemma, Smith, Wendy, Khakh, Manjinder, Fleming, Vicki M., Lister, Michelle M., Howson-Wells, Hannah C., Berry, Louise, Boswell, Tim, Joseph, Amelia, Willingham, Iona, Bird, Paul, Helmer, Thomas, Fallon, Karlie, Holmes, Christopher, Tang, Julian, Raviprakash, Veena, Campbell, Sharon, Sheriff, Nicola, Loose, Matthew W., Holmes, Nadine, Moore, Christopher, Carlile, Matthew, Wright, Victoria, Sang, Fei, Debebe, Johnny, Coll, Francesc, Signell, Adrian W., Betancor, Gilberto, Wilson, Harry D., Feltwell, Theresa, Houldcroft, Charlotte J., Eldirdiri, Sahar, Kenyon, Anita, Davis, Thomas, Pybus, Oliver, du Plessis, Louis, Zarebski, Alex, Raghwani, Jayna, Kraemer, Moritz, Francois, Sarah, Attwood, Stephen, Vasylyeva, Tetyana, Torok, M. Estee, Hamilton, William L., Goodfellow, Ian G., Hall, Grant, Jahun, Aminu S., Chaudhry, Yasmin, Hosmillo, Myra, Pinckert, Malte L., Georgana, Iliana, Yakovleva, Anna, Meredith, Luke W., Moses, Samuel, Lowe, Hannah, Ryan, Felicity, Fisher, Chloe L., Awan, Ali R., Boyes, John, Breuer, Judith, Harris, Kathryn Ann, Brown, Julianne Rose, Shah, Divya, Atkinson, Laura, Lee, Jack C.D., Alcolea-Medina, Adela, Moore, Nathan, Cortes, Nicholas, Williams, Rebecca, Chapman, Michael R., Levett, Lisa J., Heaney, Judith, Smith, Darren L., Bashton, Matthew, Young, Gregory R., Allan, John, Loh, Joshua, Randell, Paul A., Cox, Alison, Madona, Pinglawathee, Holmes, Alison, Bolt, Frances, Price, James, Mookerjee, Siddharth, Rowan, Aileen, Taylor, Graham P., Ragonnet-Cronin, Manon, Nascimento, Fabricia F., Jorgensen, David, Siveroni, Igor, Johnson, Rob, Boyd, Olivia, Geidelberg, Lily, Volz, Erik M., Brunker, Kirstyn, Smollett, Katherine L., Loman, Nicholas J., Quick, Joshua, McMurray, Claire, Stockton, Joanne, Nicholls, Sam, Rowe, Will, Poplawski, Radoslaw, Martinez-Nunez, Rocio T., Mason, Jenifer, Robinson, Trevor I., O'Toole, Elaine, Watts, Joanne, Breen, Cassie, Cowell, Angela, Ludden, Catherine, Sluga, Graciela, Machin, Nicholas W., Ahmad, Shazaad S.Y., George, Ryan P., Halstead, Fenella, Sivaprakasam, Venkat, Thomson, Emma C., Shepherd, James G., Asamaphan, Patawee, Niebel, Marc O., Li, Kathy K., Shah, Rajiv N., Jesudason, Natasha G., Parr, Yasmin A., Tong, Lily, Broos, Alice, Mair, Daniel, Nichols, Jenna, Carmichael, Stephen N., Nomikou, Kyriaki, Aranday-Cortes, Elihu, Johnson, Natasha, Starinskij, Igor, da Silva Filipe, Ana, Robertson, David L., Orton, Richard J., Hughes, Joseph, Vattipally, Sreenu, Singer, Joshua B., Hale, Antony D., Macfarlane-Smith, Louissa R., Harper, Katherine L., Taha, Yusri, Payne, Brendan A.I., Burton-Fanning, Shirelle, Waugh, Sheila, Collins, Jennifer, Eltringham, Gary, Templeton, Kate E., McHugh, Martin P., Dewar, Rebecca, Wastenge, Elizabeth, Dervisevic, Samir, Stanley, Rachael, Prakash, Reenesh, Stuart, Claire, Elumogo, Ngozi, Sethi, Dheeraj K., Meader, Emma J., Coupland, Lindsay J., Potter, Will, Graham, Clive, Barton, Edward, Padgett, Debra, Scott, Garren, Swindells, Emma, Greenaway, Jane, Nelson, Andrew, Yew, Wen C., Resende Silva, Paola C., Andersson, Monique, Shaw, Robert, Peto, Timothy, Justice, Anita, Eyre, David, Crooke, Derrick, Hoosdally, Sarah, Sloan, Tim J., Duckworth, Nichola, Walsh, Sarah, Chauhan, Anoop J., Glaysher, Sharon, Bicknell, Kelly, Wyllie, Sarah, Butcher, Ethan, Elliott, Scott, Lloyd, Allyson, Impey, Robert, Levene, Nick, Monaghan, Lynn, Bradley, Declan T., Allara, Elias, Pearson, Clare, Muir, Peter, Vipond, Ian B., Hopes, Richard, Pymont, Hannah M., Hutchings, Stephanie, Curran, Martin D., Parmar, Surendra, Lackenby, Angie, Mbisa, Tamyo, Platt, Steven, Miah, Shahjahan, Bibby, David, Manso, Carmen, Hubb, Jonathan, Chand, Meera, Dabrera, Gavin, Ramsay, Mary, Bradshaw, Daniel, Thornton, Alicia, Myers, Richard, Schaefer, Ulf, Groves, Natalie, Gallagher, Eileen, Lee, David, Williams, David, Ellaby, Nicholas, Harrison, Ian, Hartman, Hassan, Manesis, Nikos, Patel, Vineet, Bishop, Chloe, Chalker, Vicki, Osman, Husam, Bosworth, Andrew, Robinson, Esther, Holden, Matthew T.G., Shaaban, Sharif, Birchley, Alec, Adams, Alexander, Davies, Alisha, Gaskin, Amy, Plimmer, Amy, Gatica-Wilcox, Bree, McKerr, Caoimhe, Moore, Catherine, Williams, Chris, Heyburn, David, De Lacy, Elen, Hilvers, Ember, Downing, Fatima, Shankar, Giri, Jones, Hannah, Asad, Hibo, Coombes, Jason, Watkins, Joanne, Evans, Johnathan M., Fina, Laia, Gifford, Laura, Gilbert, Lauren, Graham, Lee, Perry, Malorie, Morgan, Mari, Bull, Matthew, Cronin, Michelle, Pacchiarini, Nicole, Craine, Noel, Jones, Rachel, Howe, Robin, Corden, Sally, Rey, Sara, Kumziene-Summerhayes, Sara, Taylor, Sarah, Cottrell, Simon, Jones, Sophie, Edwards, Sue, O’Grady, Justin, Page, Andrew J., Wain, John, Webber, Mark A., Mather, Alison E., Baker, David J., Rudder, Steven, Yasir, Muhammad, Thomson, Nicholas M., Aydin, Alp, Tedim, Ana P., Kay, Gemma L., Trotter, Alexander J., Gilroy, Rachel A.J., Alikhan, Nabil-Fareed, de Oliveira Martins, Leonardo, Le-Viet, Thanh, Meadows, Lizzie, Kolyva, Anastasia, Diaz, Maria, Bell, Andrew, Gutierrez, Ana Victoria, Charles, Ian G., Adriaenssens, Evelien M., Kingsley, Robert A., Casey, Anna, Simpson, David A., Molnar, Zoltan, Thompson, Thomas, Acheson, Erwan, Masoli, Jane A.H., Knight, Bridget A., Hattersley, Andrew, Ellard, Sian, Auckland, Cressida, Mahungu, Tabitha W., Irish-Tavares, Dianne, Haque, Tanzina, Bourgeois, Yann, Scarlett, Garry P., Partridge, David G., Raza, Mohammad, Evans, Cariad, Johnson, Kate, Liggett, Steven, Baker, Paul, Essex, Sarah, Lyons, Ronan A., Caller, Laura G., Castellano, Sergi, Williams, Rachel J., Kristiansen, Mark, Roy, Sunando, Williams, Charlotte A., Dyal, Patricia L., Tutill, Helena J., Panchbhaya, Yasmin N., Forrest, Leysa M., Niola, Paola, Findlay, Jacqueline, Brooks, Tony T., Gavriil, Artemis, Mestek-Boukhibar, Lamia, Weeks, Sam, Pandey, Sarojini, Berry, Lisa, Jones, Katie, Richter, Alex, Beggs, Andrew, Smith, Colin P., Bucca, Giselda, Hesketh, Andrew R., Harrison, Ewan M., Peacock, Sharon J., Palmer, Sophie, Churcher, Carol M., Bellis, Katherine L., Girgis, Sophia T., Naydenova, Plamena, Blane, Beth, Sridhar, Sushmita, Ruis, Chris, Forrest, Sally, Cormie, Claire, Gill, Harmeet K., Dias, Joana, Higginson, Ellen E., Maes, Mailis, Young, Jamie, Kermack, Leanne M., Hadjirin, Nazreen F., Aggarwal, Dinesh, Griffith, Luke, Swingler, Tracey, Davidson, Rose K., Rambaut, Andrew, Williams, Thomas, Balcazar, Carlos E., Gallagher, Michael D., O'Toole, Áine, Rooke, Stefan, Jackson, Ben, Colquhoun, Rachel, Ashworth, Jordan, Hill, Verity, McCrone, J.T., Scher, Emily, Yu, Xiaoyu, Williamson, Kathleen A., Stanton, Thomas D., Michell, Stephen L., Bewshea, Claire M., Temperton, Ben, Michelsen, Michelle L., Warwick-Dugdale, Joanna, Manley, Robin, Farbos, Audrey, Harrison, James W., Sambles, Christine M., Studholme, David J., Jeffries, Aaron R., Darby, Alistair C., Hiscox, Julian A., Paterson, Steve, Iturriza-Gomara, Miren, Jackson, Kathryn A., Lucaci, Anita O., Vamos, Edith E., Hughes, Margaret, Rainbow, Lucille, Eccles, Richard, Nelson, Charlotte, Whitehead, Mark, Turtle, Lance, Haldenby, Sam T., Gregory, Richard, Gemmell, Matthew, Kwiatkowski, Dominic, de Silva, Thushan I., Smith, Nikki, Angyal, Adrienn, Lindsey, Benjamin B., Groves, Danielle C., Green, Luke R., Wang, Dennis, Freeman, Timothy M., Parker, Matthew D., Keeley, Alexander J., Parsons, Paul J., Tucker, Rachel M., Brown, Rebecca, Wyles, Matthew, Constantinidou, Chrystala, Unnikrishnan, Meera, Ott, Sascha, Cheng, Jeffrey K.J., Bridgewater, Hannah E., Frost, Lucy R., Taylor-Joyce, Grace, Stark, Richard, Baxter, Laura, Alam, Mohammad T., Brown, Paul E., McClure, Patrick C., Chappell, Joseph G., Tsoleridis, Theocharis, Ball, Jonathan, Grammatopoulos, Dimitris, Buck, David, Todd, John A., Green, Angie, Trebes, Amy, MacIntyre-Cockett, George, de Cesare, Mariateresa, Langford, Cordelia, Alderton, Alex, Amato, Roberto, Goncalves, Sonia, Jackson, David K., Johnston, Ian, Sillitoe, John, Palmer, Steve, Lawniczak, Mara, Berriman, Matt, Danesh, John, Livett, Rich, Shirley, Lesley, Farr, Ben, Quail, Mike, Thurston, Scott, Park, Naomi, Betteridge, Emma, Weldon, Danni, Goodwin, Scott, Nelson, Rachel, Beaver, Charlotte, Letchford, Laura, Jackson, David A., Foulser, Luke, McMinn, Liz, Prestwood, Liam, Kay, Sally, Kane, Leanne, Dorman, Matthew J., Martincorena, Inigo, Puethe, Christoph, Keatley, Jon-Paul, Tonkin-Hill, Gerry, Smith, Christen, Jamrozy, Dorota, Beale, Mathew A., Patel, Minal, Ariani, Cristina, Spencer-Chapman, Michael, Drury, Eleanor, Lo, Stephanie, Rajatileka, Shavanthi, Scott, Carol, James, Keith, Buddenborg, Sarah K., Berger, Duncan J., Patel, Gaurang, Garcia-Casado, Maria V., Dibling, Thomas, McGuigan, Samantha, Rogers, Hazel A., Hunter, Adam D., Souster, Emily, Neaverson, Alexandra S., Volz, Erik, McCrone, John T., O’Toole, Áine, Johnson, Robert, Rey, Sara M., Nicholls, Samuel M., Colquhoun, Rachel M., Shepherd, James, Pascall, David J., Shah, Rajiv, Jesudason, Natasha, Li, Kathy, Jarrett, Ruth, Goodfellow, Ian, and Pybus, Oliver G.

Published
2021
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14. Molecular analysis of metallo-beta-lactamase-producing Pseudomonas aeruginosa in Switzerland 2022-2023

Author

Findlay, Jacqueline; https://orcid.org/0000-0002-7335-9001, Raro, Otavio Hallal Ferreira, Poirel, Laurent, Nordmann, Patrice, NARA Network, Findlay, Jacqueline; https://orcid.org/0000-0002-7335-9001, Raro, Otavio Hallal Ferreira, Poirel, Laurent, Nordmann, Patrice, and NARA Network

Abstract

OBJECTIVES The occurrence of metallo-beta-lactamase-producing Pseudomonas aeruginosa (MBL-PA) isolates is increasing globally, including in Switzerland. The aim of this study was to characterise, phenotypically and genotypically, the MBL-PA isolates submitted to the Swiss National Reference Center for Emerging Antibiotic Resistance (NARA) reference laboratory over a 12-month period from July 2022 to July 2023. METHODS Thirty-nine non-duplicate MBL-PA Isolates were submitted to NARA over the study period from across Switzerland. Susceptibility was determined by broth microdilution according to EUCAST methodology. Whole-genome sequencing was performed on 34 isolates. Sequence types (STs) and resistance genes were ascertained using the Centre for Genomic Epidemiology platform. MBL genes, bla$_{NDM-1}$, bla$_{IMP-1}$, and bla$_{VIM-2}$, were cloned into vector pUCP24 and transformed into P. aeruginosa PA14. RESULTS The most prevalent MBL types identified in this study were VIM (21/39; 53.8%) followed by NDM (11/39; 28.2%), IMP (6/39; 15.4%), and a single isolate produced both VIM and NDM enzymes. WGS identified 13 different STs types among the 39 isolates. They all exhibited resistance to cephalosporins, carbapenems, and the beta-lactam-beta-lactamase inhibitor combinations, ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam, and 8 isolates were cefiderocol (FDC) resistant. Recombinant P. aeruginosa strains producing bla$_{NDM-1}$, bla$_{IMP-1}$, and bla$_{VIM-2}$ exhibited FDC MICs of 16, 8, and 1 mg/L, respectively. CONCLUSIONS This study showed that the MBL-PA in Switzerland could be attributed to the wide dissemination of high-risk clones that accounted for most isolates in this study. Although FDC resistance was only found in 8 isolates, MBL carriage was shown to be a major contributor to this phenotype.

Published
2024

21. Plasmid-mediated fosfomycin resistance in Escherichia coliisolates of worldwide origin

Author

Findlay, Jacqueline, Sierra, Roberto, Raro, Otavio Hallal Ferreira, Aires-de-Sousa, Marta, Andrey, Diego O., and Nordmann, Patrice

Abstract

•Phenotypic and genotypic characterisation of fosA-positive Escherichia coli.•Complete fosAplasmid sequences were determined for 12 isolates.•fosAgenes were often found encoded on MDR plasmids, highlighting the potential for co-selection.

Published
2023
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23. Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission

Author

Martin, Jessica, Phan, Hang T. T, Findlay, Jacqueline, Stoesser, Nicole, Pankhurst, Louise, Navickaite, Indre, De Maio, Nicola, Eyre, David W, Toogood, Giles, Orsi, Nicolas M, Kirby, Andrew, Young, Nicola, Turton, Jane F, Hill, Robert L. R, Hopkins, Katie L, Woodford, Neil, Peto, Tim E. A, Walker, A. Sarah, Crook, Derrick W, and Wilcox, Mark H

Published
2017
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25. Multifactorial resistance mechanisms associated with resistance to ceftazidime-avibactam in clinical Pseudomonas aeruginosa isolates from Switzerland.

Author

Flury, Baharak Babouee, Bösch, Anja, Gisler, Valentin, Egli, Adrian, Seiffert, Salome N., Nolte, Oliver, and Findlay, Jacqueline

Subjects
PSEUDOMONAS aeruginosa, WHOLE genome sequencing, MULTIDRUG resistance, DRUG resistance in microorganisms, AGAR plates
Abstract

Background: Increasing reports of multidrug resistance (MDR) in clinical Pseudomonas aeruginosa have led to a necessity for new antimicrobials. Ceftazidime-avibactam (CZA) is indicated for use against MDR P. aeruginosa across a broad range of infection types and particularly those that are carbapenem resistant. This study sought to determine the molecular mechanisms of CZA and imipenem (IPM)-resistance in clinical P. aeruginosa isolates obtained from Swiss hospitals. Methods: Clinical P. aeruginosa isolates were obtained from inpatients in three hospitals in Switzerland. Susceptibility was determined by either antibiotic disc testing or broth microdilution according to EUCAST methodology. AmpC activity was determined using cloxacillin and efflux activity was determined using phenylalanine-arginine β-naphthylamide, in agar plates. Whole Genome Sequencing was performed on 18 clinical isolates. Sequence types (STs) and resistance genes were ascertained using the Centre for Genomic Epidemiology platform. Genes of interest were extracted from sequenced isolates and compared to reference strain P. aeruginosa PAO1. Results: Sixteen different STs were identified amongst the 18 isolates in this study indicating a high degree of genomic diversity. No carbapenemases were detected but one isolate did harbor the ESBL blaPER-1. Eight isolates were CZAresistant with MICs ranging from 16-64 mg/L, and the remaining ten isolates had either low/wildtype MICs (n=6; 1-2 mg/L) or elevated, but still susceptible, MICs (n=4; 4-8 mg/L). Ten isolates were IPM-resistant, seven of which had mutations resulting in truncations of OprD, and the remaining nine IPM-susceptible isolates had intact oprD genes. Within CZA-R isolates, and those with reduced susceptibility, mutations resulting in ampC derepression, OprD loss, mexAB overexpression and ESBL (blaPER-1) carriage were observed in various combinations and one harbored a truncation of the PBP4 dacB gene. Within the six isolates with wildtype-resistance levels, five had no mutations that would affect any antimicrobial resistance (AMR) genes of interest when compared to PAO1. Conclusion: This preliminary study highlights that CZA-resistance in P. aeruginosa is multifactorial and could be caused by the interplay between different resistance mechanisms including ESBL carriage, increased efflux, loss of permeability and derepression of its intrinsic ampC. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Limited phylogenetic overlap between fluoroquinolone-resistant Escherichia coli isolated on dairy farms and those causing bacteriuria in humans living in the same geographical region

Author

Mounsey, Oliver, primary, Schubert, Hannah, additional, Findlay, Jacqueline, additional, Morley, Katy, additional, Puddy, Emma F, additional, Gould, Virginia C, additional, North, Paul, additional, Bowker, Karen E, additional, Williams, O Martin, additional, Williams, Philip B, additional, Barrett, David C, additional, Cogan, Tristan A, additional, Turner, Katy M, additional, MacGowan, Alasdair P, additional, Reyher, Kristen K, additional, and Avison, Matthew B, additional

Published
2021
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31. Reduced antibacterial drug resistance and blaCTX-M β-lactamase gene carriage in cattle-associated Escherichia coli at low temperatures, at sites dominated by older animals and on pastureland:implications for surveillance

Author

Schubert, Hannah, Morley, Katy, Puddy, Emma F, Arbon, Robert, Findlay, Jacqueline, Mounsey, Oliver, Gould, Virginia C, Vass, Lucy, Evans, Madeleine, Rees, Gwen M, Barrett, David C, Turner, Katy M, Cogan, Tristan A, Avison, Matthew B, and Reyher, Kristen K

Subjects
antibiotic resistance, food-borne pathogens, mathematical modeling, surveillance studies
Abstract

Little is known about the drivers of critically important antibacterial resistance in species with zoonotic potential present on farms (e.g. CTX-M β-lactamase-positive Escherichia coli). We collected samples - monthly, between January 2017 and December 2018 - on 53 dairy farms in South West England along with data for 610 variables concerning antibacterial usage, management practices and meteorological factors. We detected E. coli resistant to amoxicillin, ciprofloxacin, streptomycin and tetracycline, respectively, in 2754/4145 (66%), 263/4145 (6%), 1475/4145 (36%) and 2874/4145 (69%) of all samples from faecally contaminated on-farm and near-farm sites. E. coli positive for blaCTX-M were detected in 224/4145 (5.4%) of samples. Multilevel, multivariable logistic regression showed antibacterial dry cow therapeutic choice (including use of cefquinome or framycetin) to be associated with higher odds of blaCTX-M positivity. Low average monthly ambient temperature was associated with lower odds of blaCTX-ME. coli positivity in samples and with lower odds of finding E. coli resistant to each of the four test antibacterials. This was additional to the effect of temperature on total E. coli density. Furthermore, samples collected close to calves had higher odds of having E. coli resistant to each antibacterial as well as positive for blaCTX-M Samples collected on pastureland had lower odds of having E. coli resistant to amoxicillin or tetracycline as well as lower odds of being positive for blaCTX-MImportance Antibacterial resistance poses a significant threat to human and animal health and global food security. Surveillance for resistance on farms is important for many reasons, including to track the impacts of interventions aimed at reducing the prevalence of resistance. In this longitudinal survey of dairy farm antibacterial resistance, we showed that local temperature - as it changes over the course of a year - was associated with the prevalence of antibacterial-resistant E. coli We also showed that prevalence of resistant E. coli was lower on pastureland and higher in environments inhabited by young animals. These findings have profound implications for routine surveillance and for surveys carried out for research. They provide important evidence that sampling at a single time-point and/or single location on a farm is unlikely to be adequate to accurately determine the status of the farm regarding the presence of samples containing resistant E. coli.

Published
2021
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32. In vitro-obtained meropenem-vaborbactam resistance mechanisms among clinical Klebsiella pneumoniaecarbapenemase-producing K. pneumoniaeisolates

Author

Findlay, Jacqueline, Poirel, Laurent, and Nordmann, Patrice

Abstract

•MEM-VAB resistant mutants were difficult to select for most strains.•MEM-VAB resistant mutants required multiple rounds of selection.•MEM-VAB resistant mutants resulted from a combination of permeability changes.•MEM-VAB resistant mutants increased blaKPCcopy number.•Cross-resistance was observed between MEM-VAB and other BLBI combinations.•Cross-resistance was observed to CAZ-AVI, IPM-REL, and to a lesser extent ATM-AVI.

Published
2023
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33. New Delhi Metallo-��-Lactamase-Producing Enterobacterales Bacteria, Switzerland, 2019-2020

Author

Findlay, Jacqueline, Poirel, Laurent, Kessler, Julie, Kronenberg, Andreas, and Nordmann, Patrice

Subjects
570 Life sciences, biology, 610 Medicine & health
Abstract

Carbapenemase-producing Enterobacterales (CPE) bacteria are a critical global health concern; New Delhi metallo-��-lactamase (NDM) enzymes account for >25% of all CPE found in Switzerland. We characterized NDM-positive CPE submitted to the Swiss National Reference Center for Emerging Antibiotic Resistance during a 2-year period (January 2019-December 2020) phenotypically and by using whole-genome sequencing. Most isolates were either Klebsiella pneumoniae (59/141) or Escherichia coli (52/141), and >50% were obtained from screening swabs. Among the 108 sequenced isolates, NDM-1 was the most prevalent variant, occurring in 56 isolates, mostly K. pneumoniae (34/56); the next most prevalent was NDM-5, which occurred in 49 isolates, mostly E. coli (40/49). Fourteen isolates coproduced a second carbapenemase, predominantly an OXA-48-like enzyme, and almost one third of isolates produced a 16S rRNA methylase conferring panresistance to aminoglycosides. We identified successful plasmids and global lineages as major factors contributing to the increasing prevalence of NDMs in Switzerland.

Published
2021
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34. Evidence that faecal carriage of resistantEscherichia coliby 16-week-old dogs in the United Kingdom is associated with raw feeding and thatE. colifrom these dogs are shared with humans and cause opportunistic infections

Author

Mounsey, Oliver, primary, Wareham, Kezia, additional, Hammond, Ashley, additional, Findlay, Jacqueline, additional, Gould, Virginia C., additional, Morley, Katy, additional, Cogan, Tristan A., additional, Turner, Katy M.E., additional, Avison, Matthew B., additional, and Reyher, Kristen K., additional

Published
2021
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35. Reduced Antibacterial Drug Resistance and bla CTX-M β-Lactamase Gene Carriage in Cattle-Associated Escherichia coli at Low Temperatures, at Sites Dominated by Older Animals, and on Pastureland: Implications for Surveillance

Author

Schubert, Hannah, primary, Morley, Katy, additional, Puddy, Emma F., additional, Arbon, Robert, additional, Findlay, Jacqueline, additional, Mounsey, Oliver, additional, Gould, Virginia C., additional, Vass, Lucy, additional, Evans, Madeleine, additional, Rees, Gwen M., additional, Barrett, David C., additional, Turner, Katy M., additional, Cogan, Tristan A., additional, Avison, Matthew B., additional, and Reyher, Kristen K., additional

Published
2021
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36. Characterisation of a novel AmpC beta-lactamase, DHA-33, resistant to inhibition by cloxacillin.

Author

Findlay, Jacqueline, Poirel, Laurent, Cherkaoui, Abdessalam, Schrenzel, Jacques, and Nordmann, Patrice

Subjects
*ESCHERICHIA coli, *INFECTION control, *LACTAMS, *AGAR plates, *ENZYME inhibitors, *PRODUCTION methods, *AGAR
Abstract

Plasmid-encoded DHA-type AmpCs have been extensively reported in Enterobacterales. The expression of the genes encoding these plasmid-mediated enzymes are inducible and these enzymes are capable of conferring resistance to a wide spectrum of beta-lactams including penicillins and broad-spectrum cephalosporins. The identification of infections caused by AmpC-producing bacteria is a necessity, both for infection control/epidemiology purposes and to inform treatment choices. A common testing method for AmpC production in the clinical laboratory setting is to supplement Mueller-Hinton agar plates used for antibiotic disk diffusion with cloxacillin, a potent inhibitor of AmpC enzymes. Here we describe a novel DHA variant, produced by a clinical Escherichia coli isolate, which is resistant to cloxacillin inhibition. [ABSTRACT FROM AUTHOR]

Published
2024
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37. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Author

Volz, Erik, primary, Hill, Verity, additional, McCrone, John T., additional, Price, Anna, additional, Jorgensen, David, additional, O’Toole, Áine, additional, Southgate, Joel, additional, Johnson, Robert, additional, Jackson, Ben, additional, Nascimento, Fabricia F., additional, Rey, Sara M., additional, Nicholls, Samuel M., additional, Colquhoun, Rachel M., additional, da Silva Filipe, Ana, additional, Shepherd, James, additional, Pascall, David J., additional, Shah, Rajiv, additional, Jesudason, Natasha, additional, Li, Kathy, additional, Jarrett, Ruth, additional, Pacchiarini, Nicole, additional, Bull, Matthew, additional, Geidelberg, Lily, additional, Siveroni, Igor, additional, Goodfellow, Ian, additional, Loman, Nicholas J., additional, Pybus, Oliver G., additional, Robertson, David L., additional, Thomson, Emma C., additional, Rambaut, Andrew, additional, Connor, Thomas R., additional, Koshy, Cherian, additional, Wise, Emma, additional, Cortes, Nick, additional, Lynch, Jessica, additional, Kidd, Stephen, additional, Mori, Matilde, additional, Fairley, Derek J., additional, Curran, Tanya, additional, McKenna, James P., additional, Adams, Helen, additional, Fraser, Christophe, additional, Golubchik, Tanya, additional, Bonsall, David, additional, Moore, Catrin, additional, Caddy, Sarah L., additional, Khokhar, Fahad A., additional, Wantoch, Michelle, additional, Reynolds, Nicola, additional, Warne, Ben, additional, Maksimovic, Joshua, additional, Spellman, Karla, additional, McCluggage, Kathryn, additional, John, Michaela, additional, Beer, Robert, additional, Afifi, Safiah, additional, Morgan, Sian, additional, Marchbank, Angela, additional, Kitchen, Christine, additional, Gulliver, Huw, additional, Merrick, Ian, additional, Guest, Martyn, additional, Munn, Robert, additional, Workman, Trudy, additional, Fuller, William, additional, Bresner, Catherine, additional, Snell, Luke B., additional, Charalampous, Themoula, additional, Nebbia, Gaia, additional, Batra, Rahul, additional, Edgeworth, Jonathan, additional, Robson, Samuel C., additional, Beckett, Angela, additional, Loveson, Katie F., additional, Aanensen, David M., additional, Underwood, Anthony P., additional, Yeats, Corin A., additional, Abudahab, Khalil, additional, Taylor, Ben E.W., additional, Menegazzo, Mirko, additional, Clark, Gemma, additional, Smith, Wendy, additional, Khakh, Manjinder, additional, Fleming, Vicki M., additional, Lister, Michelle M., additional, Howson-Wells, Hannah C., additional, Berry, Louise, additional, Boswell, Tim, additional, Joseph, Amelia, additional, Willingham, Iona, additional, Bird, Paul, additional, Helmer, Thomas, additional, Fallon, Karlie, additional, Holmes, Christopher, additional, Tang, Julian, additional, Raviprakash, Veena, additional, Campbell, Sharon, additional, Sheriff, Nicola, additional, Loose, Matthew W., additional, Holmes, Nadine, additional, Moore, Christopher, additional, Carlile, Matthew, additional, Wright, Victoria, additional, Sang, Fei, additional, Debebe, Johnny, additional, Coll, Francesc, additional, Signell, Adrian W., additional, Betancor, Gilberto, additional, Wilson, Harry D., additional, Feltwell, Theresa, additional, Houldcroft, Charlotte J., additional, Eldirdiri, Sahar, additional, Kenyon, Anita, additional, Davis, Thomas, additional, Pybus, Oliver, additional, du Plessis, Louis, additional, Zarebski, Alex, additional, Raghwani, Jayna, additional, Kraemer, Moritz, additional, Francois, Sarah, additional, Attwood, Stephen, additional, Vasylyeva, Tetyana, additional, Torok, M. Estee, additional, Hamilton, William L., additional, Goodfellow, Ian G., additional, Hall, Grant, additional, Jahun, Aminu S., additional, Chaudhry, Yasmin, additional, Hosmillo, Myra, additional, Pinckert, Malte L., additional, Georgana, Iliana, additional, Yakovleva, Anna, additional, Meredith, Luke W., additional, Moses, Samuel, additional, Lowe, Hannah, additional, Ryan, Felicity, additional, Fisher, Chloe L., additional, Awan, Ali R., additional, Boyes, John, additional, Breuer, Judith, additional, Harris, Kathryn Ann, additional, Brown, Julianne Rose, additional, Shah, Divya, additional, Atkinson, Laura, additional, Lee, Jack C.D., additional, Alcolea-Medina, Adela, additional, Moore, Nathan, additional, Cortes, Nicholas, additional, Williams, Rebecca, additional, Chapman, Michael R., additional, Levett, Lisa J., additional, Heaney, Judith, additional, Smith, Darren L., additional, Bashton, Matthew, additional, Young, Gregory R., additional, Allan, John, additional, Loh, Joshua, additional, Randell, Paul A., additional, Cox, Alison, additional, Madona, Pinglawathee, additional, Holmes, Alison, additional, Bolt, Frances, additional, Price, James, additional, Mookerjee, Siddharth, additional, Rowan, Aileen, additional, Taylor, Graham P., additional, Ragonnet-Cronin, Manon, additional, Johnson, Rob, additional, Boyd, Olivia, additional, Volz, Erik M., additional, Brunker, Kirstyn, additional, Smollett, Katherine L., additional, Quick, Joshua, additional, McMurray, Claire, additional, Stockton, Joanne, additional, Nicholls, Sam, additional, Rowe, Will, additional, Poplawski, Radoslaw, additional, Martinez-Nunez, Rocio T., additional, Mason, Jenifer, additional, Robinson, Trevor I., additional, O'Toole, Elaine, additional, Watts, Joanne, additional, Breen, Cassie, additional, Cowell, Angela, additional, Ludden, Catherine, additional, Sluga, Graciela, additional, Machin, Nicholas W., additional, Ahmad, Shazaad S.Y., additional, George, Ryan P., additional, Halstead, Fenella, additional, Sivaprakasam, Venkat, additional, Shepherd, James G., additional, Asamaphan, Patawee, additional, Niebel, Marc O., additional, Li, Kathy K., additional, Shah, Rajiv N., additional, Jesudason, Natasha G., additional, Parr, Yasmin A., additional, Tong, Lily, additional, Broos, Alice, additional, Mair, Daniel, additional, Nichols, Jenna, additional, Carmichael, Stephen N., additional, Nomikou, Kyriaki, additional, Aranday-Cortes, Elihu, additional, Johnson, Natasha, additional, Starinskij, Igor, additional, Orton, Richard J., additional, Hughes, Joseph, additional, Vattipally, Sreenu, additional, Singer, Joshua B., additional, Hale, Antony D., additional, Macfarlane-Smith, Louissa R., additional, Harper, Katherine L., additional, Taha, Yusri, additional, Payne, Brendan A.I., additional, Burton-Fanning, Shirelle, additional, Waugh, Sheila, additional, Collins, Jennifer, additional, Eltringham, Gary, additional, Templeton, Kate E., additional, McHugh, Martin P., additional, Dewar, Rebecca, additional, Wastenge, Elizabeth, additional, Dervisevic, Samir, additional, Stanley, Rachael, additional, Prakash, Reenesh, additional, Stuart, Claire, additional, Elumogo, Ngozi, additional, Sethi, Dheeraj K., additional, Meader, Emma J., additional, Coupland, Lindsay J., additional, Potter, Will, additional, Graham, Clive, additional, Barton, Edward, additional, Padgett, Debra, additional, Scott, Garren, additional, Swindells, Emma, additional, Greenaway, Jane, additional, Nelson, Andrew, additional, Yew, Wen C., additional, Resende Silva, Paola C., additional, Andersson, Monique, additional, Shaw, Robert, additional, Peto, Timothy, additional, Justice, Anita, additional, Eyre, David, additional, Crooke, Derrick, additional, Hoosdally, Sarah, additional, Sloan, Tim J., additional, Duckworth, Nichola, additional, Walsh, Sarah, additional, Chauhan, Anoop J., additional, Glaysher, Sharon, additional, Bicknell, Kelly, additional, Wyllie, Sarah, additional, Butcher, Ethan, additional, Elliott, Scott, additional, Lloyd, Allyson, additional, Impey, Robert, additional, Levene, Nick, additional, Monaghan, Lynn, additional, Bradley, Declan T., additional, Allara, Elias, additional, Pearson, Clare, additional, Muir, Peter, additional, Vipond, Ian B., additional, Hopes, Richard, additional, Pymont, Hannah M., additional, Hutchings, Stephanie, additional, Curran, Martin D., additional, Parmar, Surendra, additional, Lackenby, Angie, additional, Mbisa, Tamyo, additional, Platt, Steven, additional, Miah, Shahjahan, additional, Bibby, David, additional, Manso, Carmen, additional, Hubb, Jonathan, additional, Chand, Meera, additional, Dabrera, Gavin, additional, Ramsay, Mary, additional, Bradshaw, Daniel, additional, Thornton, Alicia, additional, Myers, Richard, additional, Schaefer, Ulf, additional, Groves, Natalie, additional, Gallagher, Eileen, additional, Lee, David, additional, Williams, David, additional, Ellaby, Nicholas, additional, Harrison, Ian, additional, Hartman, Hassan, additional, Manesis, Nikos, additional, Patel, Vineet, additional, Bishop, Chloe, additional, Chalker, Vicki, additional, Osman, Husam, additional, Bosworth, Andrew, additional, Robinson, Esther, additional, Holden, Matthew T.G., additional, Shaaban, Sharif, additional, Birchley, Alec, additional, Adams, Alexander, additional, Davies, Alisha, additional, Gaskin, Amy, additional, Plimmer, Amy, additional, Gatica-Wilcox, Bree, additional, McKerr, Caoimhe, additional, Moore, Catherine, additional, Williams, Chris, additional, Heyburn, David, additional, De Lacy, Elen, additional, Hilvers, Ember, additional, Downing, Fatima, additional, Shankar, Giri, additional, Jones, Hannah, additional, Asad, Hibo, additional, Coombes, Jason, additional, Watkins, Joanne, additional, Evans, Johnathan M., additional, Fina, Laia, additional, Gifford, Laura, additional, Gilbert, Lauren, additional, Graham, Lee, additional, Perry, Malorie, additional, Morgan, Mari, additional, Cronin, Michelle, additional, Craine, Noel, additional, Jones, Rachel, additional, Howe, Robin, additional, Corden, Sally, additional, Rey, Sara, additional, Kumziene-Summerhayes, Sara, additional, Taylor, Sarah, additional, Cottrell, Simon, additional, Jones, Sophie, additional, Edwards, Sue, additional, O’Grady, Justin, additional, Page, Andrew J., additional, Wain, John, additional, Webber, Mark A., additional, Mather, Alison E., additional, Baker, David J., additional, Rudder, Steven, additional, Yasir, Muhammad, additional, Thomson, Nicholas M., additional, Aydin, Alp, additional, Tedim, Ana P., additional, Kay, Gemma L., additional, Trotter, Alexander J., additional, Gilroy, Rachel A.J., additional, Alikhan, Nabil-Fareed, additional, de Oliveira Martins, Leonardo, additional, Le-Viet, Thanh, additional, Meadows, Lizzie, additional, Kolyva, Anastasia, additional, Diaz, Maria, additional, Bell, Andrew, additional, Gutierrez, Ana Victoria, additional, Charles, Ian G., additional, Adriaenssens, Evelien M., additional, Kingsley, Robert A., additional, Casey, Anna, additional, Simpson, David A., additional, Molnar, Zoltan, additional, Thompson, Thomas, additional, Acheson, Erwan, additional, Masoli, Jane A.H., additional, Knight, Bridget A., additional, Hattersley, Andrew, additional, Ellard, Sian, additional, Auckland, Cressida, additional, Mahungu, Tabitha W., additional, Irish-Tavares, Dianne, additional, Haque, Tanzina, additional, Bourgeois, Yann, additional, Scarlett, Garry P., additional, Partridge, David G., additional, Raza, Mohammad, additional, Evans, Cariad, additional, Johnson, Kate, additional, Liggett, Steven, additional, Baker, Paul, additional, Essex, Sarah, additional, Lyons, Ronan A., additional, Caller, Laura G., additional, Castellano, Sergi, additional, Williams, Rachel J., additional, Kristiansen, Mark, additional, Roy, Sunando, additional, Williams, Charlotte A., additional, Dyal, Patricia L., additional, Tutill, Helena J., additional, Panchbhaya, Yasmin N., additional, Forrest, Leysa M., additional, Niola, Paola, additional, Findlay, Jacqueline, additional, Brooks, Tony T., additional, Gavriil, Artemis, additional, Mestek-Boukhibar, Lamia, additional, Weeks, Sam, additional, Pandey, Sarojini, additional, Berry, Lisa, additional, Jones, Katie, additional, Richter, Alex, additional, Beggs, Andrew, additional, Smith, Colin P., additional, Bucca, Giselda, additional, Hesketh, Andrew R., additional, Harrison, Ewan M., additional, Peacock, Sharon J., additional, Palmer, Sophie, additional, Churcher, Carol M., additional, Bellis, Katherine L., additional, Girgis, Sophia T., additional, Naydenova, Plamena, additional, Blane, Beth, additional, Sridhar, Sushmita, additional, Ruis, Chris, additional, Forrest, Sally, additional, Cormie, Claire, additional, Gill, Harmeet K., additional, Dias, Joana, additional, Higginson, Ellen E., additional, Maes, Mailis, additional, Young, Jamie, additional, Kermack, Leanne M., additional, Hadjirin, Nazreen F., additional, Aggarwal, Dinesh, additional, Griffith, Luke, additional, Swingler, Tracey, additional, Davidson, Rose K., additional, Williams, Thomas, additional, Balcazar, Carlos E., additional, Gallagher, Michael D., additional, O'Toole, Áine, additional, Rooke, Stefan, additional, Colquhoun, Rachel, additional, Ashworth, Jordan, additional, McCrone, J.T., additional, Scher, Emily, additional, Yu, Xiaoyu, additional, Williamson, Kathleen A., additional, Stanton, Thomas D., additional, Michell, Stephen L., additional, Bewshea, Claire M., additional, Temperton, Ben, additional, Michelsen, Michelle L., additional, Warwick-Dugdale, Joanna, additional, Manley, Robin, additional, Farbos, Audrey, additional, Harrison, James W., additional, Sambles, Christine M., additional, Studholme, David J., additional, Jeffries, Aaron R., additional, Darby, Alistair C., additional, Hiscox, Julian A., additional, Paterson, Steve, additional, Iturriza-Gomara, Miren, additional, Jackson, Kathryn A., additional, Lucaci, Anita O., additional, Vamos, Edith E., additional, Hughes, Margaret, additional, Rainbow, Lucille, additional, Eccles, Richard, additional, Nelson, Charlotte, additional, Whitehead, Mark, additional, Turtle, Lance, additional, Haldenby, Sam T., additional, Gregory, Richard, additional, Gemmell, Matthew, additional, Kwiatkowski, Dominic, additional, de Silva, Thushan I., additional, Smith, Nikki, additional, Angyal, Adrienn, additional, Lindsey, Benjamin B., additional, Groves, Danielle C., additional, Green, Luke R., additional, Wang, Dennis, additional, Freeman, Timothy M., additional, Parker, Matthew D., additional, Keeley, Alexander J., additional, Parsons, Paul J., additional, Tucker, Rachel M., additional, Brown, Rebecca, additional, Wyles, Matthew, additional, Constantinidou, Chrystala, additional, Unnikrishnan, Meera, additional, Ott, Sascha, additional, Cheng, Jeffrey K.J., additional, Bridgewater, Hannah E., additional, Frost, Lucy R., additional, Taylor-Joyce, Grace, additional, Stark, Richard, additional, Baxter, Laura, additional, Alam, Mohammad T., additional, Brown, Paul E., additional, McClure, Patrick C., additional, Chappell, Joseph G., additional, Tsoleridis, Theocharis, additional, Ball, Jonathan, additional, Grammatopoulos, Dimitris, additional, Buck, David, additional, Todd, John A., additional, Green, Angie, additional, Trebes, Amy, additional, MacIntyre-Cockett, George, additional, de Cesare, Mariateresa, additional, Langford, Cordelia, additional, Alderton, Alex, additional, Amato, Roberto, additional, Goncalves, Sonia, additional, Jackson, David K., additional, Johnston, Ian, additional, Sillitoe, John, additional, Palmer, Steve, additional, Lawniczak, Mara, additional, Berriman, Matt, additional, Danesh, John, additional, Livett, Rich, additional, Shirley, Lesley, additional, Farr, Ben, additional, Quail, Mike, additional, Thurston, Scott, additional, Park, Naomi, additional, Betteridge, Emma, additional, Weldon, Danni, additional, Goodwin, Scott, additional, Nelson, Rachel, additional, Beaver, Charlotte, additional, Letchford, Laura, additional, Jackson, David A., additional, Foulser, Luke, additional, McMinn, Liz, additional, Prestwood, Liam, additional, Kay, Sally, additional, Kane, Leanne, additional, Dorman, Matthew J., additional, Martincorena, Inigo, additional, Puethe, Christoph, additional, Keatley, Jon-Paul, additional, Tonkin-Hill, Gerry, additional, Smith, Christen, additional, Jamrozy, Dorota, additional, Beale, Mathew A., additional, Patel, Minal, additional, Ariani, Cristina, additional, Spencer-Chapman, Michael, additional, Drury, Eleanor, additional, Lo, Stephanie, additional, Rajatileka, Shavanthi, additional, Scott, Carol, additional, James, Keith, additional, Buddenborg, Sarah K., additional, Berger, Duncan J., additional, Patel, Gaurang, additional, Garcia-Casado, Maria V., additional, Dibling, Thomas, additional, McGuigan, Samantha, additional, Rogers, Hazel A., additional, Hunter, Adam D., additional, Souster, Emily, additional, and Neaverson, Alexandra S., additional

Published
2021
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39. Molecular Epidemiology of Escherichia coli Producing CTX-M and pAmpC β-Lactamases from Dairy Farms Identifies a Dominant Plasmid Encoding CTX-M-32 but No Evidence for Transmission to Humans in the Same Geographical Region

Author

Findlay, Jacqueline, primary, Mounsey, Oliver, additional, Lee, Winnie W. Y., additional, Newbold, Nerissa, additional, Morley, Katy, additional, Schubert, Hannah, additional, Gould, Virginia C., additional, Cogan, Tristan A., additional, Reyher, Kristen K., additional, and Avison, Matthew B., additional

Published
2020
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42. In vitro activity of sulbactam-durlobactam against carbapenem-resistant Acinetobacter baumanniiand mechanisms of resistance

Author

Findlay, Jacqueline, Poirel, Laurent, Bouvier, Maxime, and Nordmann, Patrice

Abstract

•SUL-DUR exhibited excellent in-vitroantibacterial activity against MDR A. baumannii•Mutations in penicillin binding protein 3 were associated with resistance to SUL-DUR•Efflux and permeability played no role in SUL-DUR resistance in these isolates

Published
2022
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43. Molecular epidemiology of cefotaxime-resistant Escherichia coli from dairy farms in South West England identifies a dominant plasmid encoding CTX-M-32

Author

Findlay, Jacqueline, Schubert, Hannah, Morley, Katy, Mounsey, Oliver, Gould, Virginia C., Puddy, Emma F., Newbold, Nerissa, Reyher, Kristen K., Cogan, Tristen A., and Avison, Matthew B.

Subjects
biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses
Abstract

Objectives The objective of this study was to identify the mechanisms of cefotaxime resistance (CTX-R) in 1226 Escherichia coli from 4581 environmental samples collected on 53 dairy farms over a 2-year period in South West England and to characterise a bla CTX-M-32 -producing plasmid, pMOO-32, found to be widely distributed. Methods CTX-R isolates were identified using MIC breakpoint agar plates. β-lactamase genes of interest (GOIs) were detected by PCR. WGS was performed and analysed using the Center for Genomic Epidemiology platform. A plasmid-specific multiplex PCR was designed to indicate the presence of plasmid pMOO-32. Results Amongst 1226 CTX-R isolates, PCR identified bla CTX-M group 1 (549 isolates), bla CTX-M group 9 (100 isolates), bla CMY (12 isolates), bla DHA (1 isolate) and no GOI (566 isolates). WGS analysis of 184 representative isolates identified bla CTX-M (131 isolates; encoding CTX-M-1, -14, -15, -32 and the novel variant, CTX-M-214), bla CMY-2 (6 isolates), bla DHA-1 (one isolate) and presumed AmpC-hyperproduction in 46 isolates that were PCR negative for GOIs. A highly conserved plasmid was identified in 73 isolates, representing 27 E. coli STs. This ∼220 kb IncHI2 plasmid carrying bla CTX-M-32 was designated pMOO-32, was found to be stable in cattle and human transconjugant E. coli even in the absence of selective pressure, and was found by multiplex PCR to be present on 26/53 study farms. Conclusions β-lactamases capable of conferring resistance to third generation cephalosporins were evident on 47/53 farms within this study. This was largely because of the widespread dissemination of an IncHI2 plasmid carrying bla CTX-M-32 .

Published
2019
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44. Evidence for reduced CTX-M carriage in cattle-associated Escherichia coli at low temperatures and on publicly accessible farmland: implications for surveillance and potential for farm-to-human transmission

Author

Schubert, Hannah, Findlay, Jacqueline, Morley, Katy, Puddy, Emma F., Arbon, Robert, Gould, Virginia C., Mounsey, Oliver, Evans, Madeleine, Rees, Gwen M., Barrett, David C., Turner, Katy M., Cogan, Tristan A., Avison, Matthew B., and Reyher, Kristen K.

Subjects
biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses
Abstract

Little is known about the drivers of critically important antibacterial resistance in species with zoonotic potential present on farms (e.g. CTX-M β-lactamase-positive Escherichia coli ). There is also debate about the influence of farms on the circulation of resistance in local human populations. This was a two-year surveillance study on 53 dairy farms. E. coli positive for bla CTX-M were detected in 224/4145 (5.4%) of all samples from faecally-contaminated sites. E. coli positive for bla CTX-M were more prevalent (98/631; 15.5%) in calf samples and less prevalent (12/630; 1.9%) in samples collected from pastureland, including publicly accessible sites. Multilevel, multivariable logistic regression showed antibiotic dry cow therapeutic choice to be associated with risk of bla CTX-M positivity, including use of cefquinome or framycetin; 74% of bla CTX-M -positive E. coli were framycetin-resistant. Low temperature was associated with low risk of bla CTX-M positivity. This was additional to the effect of temperature on total E. coli density, a finding with profound implications for surveillance. There was no evidence that study farms had a significant impact on circulating bla CTX-M plasmids in the local human population: across 296 fully sequenced E. coli isolates, two cattle isolates shared bla CTX-M plasmids with eight urinary isolates collected in parallel.

Published
2019
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45. Resistance to aztreonam, in combination with a bicyclic boronate β-lactamase inhibitor in Escherichia coli identified following mixed culture selection

Author

Cheung, Ching Hei Phoebe, Findlay, Jacqueline, Heesom, Kate J., and Avison, Matthew B.

Subjects
polycyclic compounds, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses
Abstract

Background Bicyclic boronates are a new and potentially important class of β-lactamase inhibitor, with the ability to inhibit β-lactamases from all molecular classes, including mobile metallo-β-lactamases. Objective Our objective was to identify mutants resistant to the actions of the bicyclic boronate inhibitor 2 , when being used in combination with aztreonam. Methods Overnight cultures were plated on to agar containing increasing concentrations of aztreonam with a fixed 10 mg/L concentration of the inhibitor. Resistant derivatives and parent strains were analysed by whole genome sequencing and LC-MS/MS proteomics to identify mechanism of resistance. Results When using a mixed overnight culture containing one Escherichia coli (TEM-1, CTX-M-15, CMY-4 producer) and one Klebsiella pneumoniae (SHV-12, CTX-M-15, NDM-1 producer) mobilisation of an IncX3 plasmid carrying bla SHV-12 from the K. pneumoniae into the E. coli generated an aztreonam/boronate resistant derivative. Conclusions High-level production of three bicyclic boronate susceptible enzymes (CMY-4, CTX-M-15, SHV-12) capable of hydrolysing aztreonam plus TEM-1, which binds the inhibitor, overcomes the fixed inhibitor dose used. This was only identified when using a mixed culture for selection. It would seem prudent that to allow for coalescence of the myriad β-lactamase genes commonly found in bacterial populations colonising humans, this mixed culture approach should be the norm when testing the potential for generating β-lactamase inhibitor resistance in pre-clinical analysis.

Published
2019
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46. In-Vitro Activity of Dimercaptosuccinic Acid in Combination with Carbapenems Against Carbapenem-Resistant Pseudomonas aeruginosa.

Author

Bouvier, Maxime, Freire, Samanta, Findlay, Jacqueline, and Nordmann, Patrice

Abstract

Carbapenenemase producers, particularly the metallo-β-lactamase (MBL) types in Pseudomonas aeruginosa, have emerged as an urgent threat in health care settings. MBLs require zinc at their catalytic site and can be inhibited by dimercaptosuccinic acid (DMSA), a metal chelator known for the treatment of lead and mercury intoxication. Isogenic strains of wild-type and OprD-deleted P. aeruginosa PA14, were constructed, producing the MBLs VIM-2, NDM-1, SPM-1, IMP-1, and AIM-1, or the non-MBL carbapenemases, GES-5 and KPC-2. In addition, 59 previously characterized clinical isolates of P. aeruginosa producing different ß-lactamases (including carbapenemases), and with known outer-membrane porin OprD status, were utilized. Minimal inhibitory concentrations values of imipenem and meropenem, and DMSA combinations were determined, and time-kill assays were performed with PA14 expressing VIM-2. Results indicated a significant additive effect of DMSA (most effective at 3 mM) and carbapenems in recombinant and clinical strains of P. aeruginosa expressing MBLs, in particular against VIM producers, which are the most prevalent carbapenemases in P. aeruginosa. This effect was best evidenced with meropenem and in strains without OprD modification. DMSA shows promising efficacy, particularly in combination therapy with meropenem, for treating infections caused by MBL-producing P. aeruginosa. [ABSTRACT FROM AUTHOR]

Published
2025
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47. A Multispecies Cluster of GES-5 Carbapenemase–Producing Enterobacterales Linked by a Geographically Disseminated Plasmid

Author

Ellington, Matthew J, primary, Davies, Frances, additional, Jauneikaite, Elita, additional, Hopkins, Katie L, additional, Turton, Jane F, additional, Adams, George, additional, Pavlu, Jiri, additional, Innes, Andrew J, additional, Eades, Christopher, additional, Brannigan, Eimear T, additional, Findlay, Jacqueline, additional, White, Leila, additional, Bolt, Frances, additional, Kadhani, Tokozani, additional, Chow, Yimmy, additional, Patel, Bharat, additional, Mookerjee, Siddharth, additional, Otter, Jonathan A, additional, Sriskandan, Shiranee, additional, Woodford, Neil, additional, and Holmes, Alison, additional

Published
2019
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48. Molecular epidemiology of Escherichia coli producing CTX-M and plasmid AmpC-type β-lactamases from dairy farms identifies a dominant plasmid encoding CTX-M-32 but no evidence for transmission to humans in the same geographical region

Author

Findlay, Jacqueline, primary, Mounsey, Oliver, additional, Lee, Winnie W.Y., additional, Newbold, Nerissa, additional, Morley, Katy, additional, Schubert, Hannah, additional, Gould, Virginia C., additional, Cogan, Tristan A., additional, Reyher, Kristen K., additional, and Avison, Matthew B., additional

Published
2019
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50. Reduced antibacterial drug resistance and blaCTX-M β-lactamase gene carriage in cattle-associated Escherichia coli at low temperatures, at sites dominated by older animals and on pastureland: implications for surveillance

Author

Schubert, Hannah, primary, Morley, Katy, additional, Puddy, Emma F., additional, Arbon, Robert, additional, Findlay, Jacqueline, additional, Mounsey, Oliver, additional, Gould, Virginia C., additional, Vass, Lucy, additional, Evans, Madeleine, additional, Rees, Gwen M., additional, Barrett, David C., additional, Turner, Katy M., additional, Cogan, Tristan A., additional, Avison, Matthew B., additional, and Reyher, Kristen K., additional

Published
2019
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