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3. An Evidence-Based Antimicrobial Stewardship Smartphone App for Hospital Outpatients: Survey-based Needs Assessment Among Patients

Author

Micallef, Christianne, McLeod, Monsey, Castro-Sánchez, Enrique, Gharbi, Myriam, Charani, Esmita, Moore, Luke SP, Gilchrist, Mark, Husson, Fran, Costelloe, Ceire, and Holmes, Alison H

Subjects
Information technology, T58.5-58.64, Public aspects of medicine, RA1-1270
Abstract

BackgroundCurrent advances in modern technology have enabled the development and utilization of electronic medical software apps for both mobile and desktop computing devices. A range of apps on a large variety of clinical conditions for patients and the public are available, but very few target antimicrobials or infections. ObjectiveWe sought to explore the use of different antimicrobial information resources with a focus on electronic platforms, including apps for portable devices, by outpatients at two large, geographically distinct National Health Service (NHS) teaching hospital trusts in England. We wanted to determine whether there is demand for an evidence-based app for patients, to garner their perceptions around infections/antimicrobial prescribing, and to describe patients’ experiences of their interactions with health care professionals in relation to this topic. MethodsA cross-sectional survey design was used to investigate aspects of antimicrobial prescribing and electronic devices experienced by patients at four hospitals in London and a teaching hospital in the East of England. ResultsA total of 99 surveys were completed and analyzed. A total of 82% (80/98) of respondents had recently been prescribed antimicrobials; 87% (85/98) of respondents were prescribed an antimicrobial by a hospital doctor or through their general practitioner (GP) in primary care. Respondents wanted information on the etiology (42/65, 65%) and prevention and/or management (32/65, 49%) of their infections, with the infections reported being upper and lower respiratory tract, urinary tract, oral, and skin and soft tissue infections. All patients (92/92, 100%) desired specific information on the antimicrobial prescribed. Approximately half (52/95, 55%) stated it was “fine” for doctors to use a mobile phone/tablet computer during the consultation while 13% (12/95) did not support the idea of doctors accessing health care information in this way. Although only 30% (27/89) of respondents reported on the use of health care apps, 95% (81/85) offered information regarding aspects of antimicrobials or infections that could be provided through a tailored app for patients. Analysis of the comments revealed the following main global themes: knowledge, technology, and patient experience. ConclusionsThe majority of respondents in our study wanted to have specific etiological and/or infection management advice. All required antimicrobial-related information. Also, most supported the use of electronic resources of information, including apps, by their doctors. While a minority of people currently use health apps, many feel that apps could be used to provide additional support/information related to infections and appropriate use of antimicrobials. In addition, we found that there is a need for health care professionals to engage with patients and help address common misconceptions around the generation of antimicrobial resistance.

Published
2016
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4. Description and Cross-Sectional Analyses of 25,880 Adults and Children in the UK National Registry of Rare Kidney Diseases Cohort

Author

Abat, Sharirose, Adalat, Shazia, Agbonmwandolor, Joy, Ahmad, Zubaidah, Alejmi, Abdulfattah, Almasarwah, Rashid, Annear, Nicholas, Asgari, Ellie, Ayers, Amanda, Baharani, Jyoti, Balasubramaniam, Gowrie, Kpodo, Felix Jo-Bamba, Bansal, Tarun, Barratt, Alison, Barratt, Jonathan, Bates, Megan, Bayne, Natalie, Bendle, Janet, Benyon, Sarah, Bergmann, Carsten, Bhandari, Sunil, Bingham, Coralie, Boddana, Preetham, Bond, Sally, Braddon, Fiona, Bramham, Kate, Branson, Angela, Brearey, Stephen, Brocklebank, Vicky, Budwal, Sharanjit, Byrne, Conor, Cairns, Hugh, Camilleri, Brian, Campbell, Gary, Capell, Alys, Carmody, Margaret, Carson, Marion, Cathcart, Tracy, Catley, Christine, Cesar, Karine, Chan, Melanie, Chea, Houda, Chess, James, Cheung, Chee Kay, Chick, Katy-Jane, Chitalia, Nihil, Christian, Martin, Chrysochou, Tina, Clark, Katherine, Clayton, Christopher, Clissold, Rhian, Cockerill, Helen, Coelho, Joshua, Colby, Elizabeth, Colclough, Viv, Conway, Eileen, Cook, H. Terence, Cook, Wendy, Cooper, Theresa, Coward, Richard J., Crosbie, Sarah, Cserep, Gabor, Date, Anjali, Davidson, Katherine, Davies, Amanda, Dhaun, Neeraj, Dhaygude, Ajay, Diskin, Lynn, Dixit, Abhijit, Doctolero, Eunice Ann, Dorey, Suzannah, Downard, Lewis, Drayson, Mark, Dreyer, Gavin, Dutt, Tina, Etuk, Kufreabasi, Evans, Dawn, Finch, Jenny, Flinter, Frances, Fotheringham, James, Francis, Lucy, Gale, Daniel P., Gallagher, Hugh, Game, David, Garcia, Eva Lozano, Gavrila, Madita, Gear, Susie, Geddes, Colin, Gilchrist, Mark, Gittus, Matt, Goggolidou, Paraskevi, Goldsmith, Christopher, Gooden, Patricia, Goodlife, Andrea, Goodwin, Priyanka, Grammatikopoulos, Tassos, Gray, Barry, Griffith, Megan, Gumus, Steph, Gupta, Sanjana, Hamilton, Patrick, Harper, Lorraine, Harris, Tess, Haskell, Louise, Hayward, Samantha, Hegde, Shivaram, Hendry, Bruce, Hewins, Sue, Hewitson, Nicola, Hillman, Kate, Hiremath, Mrityunjay, Howson, Alexandra, Htet, Zay, Huish, Sharon, Hull, Richard, Humphries, Alister, Hunt, David P.J., Hunter, Karl, Hunter, Samantha, Ijeomah-Orji, Marilyn, Inston, Nick, Jayne, David, Jenfa, Gbemisola, Jenkins, Alison, Johnson, Sally, Jones, Caroline A., Jones, Colin, Jones, Amanda, Jones, Rachel, Kamesh, Lavanya, Kanigicherla, Durga, Frankl, Fiona Karet, Karim, Mahzuz, Kaur, Amrit, Kavanagh, David, Kearley, Kelly, Kerecuk, Larissa, Khwaja, Arif, King, Garry, King, Grant, Kislowska, Ewa, Klata, Edyta, Kokocinska, Maria, Lambie, Mark, Lawless, Laura, Ledson, Thomas, Lennon, Rachel, Levine, Adam P., Maggie Lai, Ling Wai, Lipkin, Graham, Lovitt, Graham, Lyons, Paul, Mabillard, Holly, Mackintosh, Katherine, Mahdi, Khalid, Maher, Eamonn, Marchbank, Kevin J., Mark, Patrick B., Masoud, Sherry, Masunda, Bridgett, Mavani, Zainab, Mayfair, Jake, McAdoo, Stephen, Mckinnell, Joanna, Melhem, Nabil, Meyrick, Simon, Moochhala, Shabbir, Morgan, Putnam, Morgan, Ann, Muhammad, Fawad, Murray, Shona, Novobritskaya, Kristina, Ong, Albert CM., Oni, Louise, Osmaston, Kate, Padmanabhan, Neal, Parkes, Sharon, Patrick, Jean, Pattison, James, Paul, Riny, Percival, Rachel, Perkins, Stephen J., Persu, Alexandre, Petchey, William G., Pickering, Matthew C., Pinney, Jennifer, Pitcher, David, Plumb, Lucy, Plummer, Zoe, Popoola, Joyce, Post, Frank, Power, Albert, Pratt, Guy, Pusey, Charles, Rabara, Ria, Rabuya, May, Raju, Tina, Javier, Chadd, Roberts, Ian SD., Roufosse, Candice, Rumjon, Adam, Salama, Alan, Saleem, Moin, Sandford, R.N., Sandu, Kanwaljit S., Sarween, Nadia, Sayer, John A., Sebire, Neil, Selvaskandan, Haresh, Shah, Sapna, Sharma, Asheesh, Sharples, Edward J., Sheerin, Neil, Shetty, Harish, Shroff, Rukshana, Simms, Roslyn, Sinha, Manish, Sinha, Smeeta, Smith, Kerry, Smith, Lara, Srivastava, Shalabh, Steenkamp, Retha, Stott, Ian, Stroud, Katerina, Swift, Pauline, Szklarzewicz, Justyna, Tam, Fred, Tan, Kay, Taylor, Robert, Tischkowitz, Marc, Thomas, Kay, Tse, Yincent, Turnbull, Alison, Turner, A. Neil, Tyerman, Kay, Usher, Miranda, Venkat-Raman, Gopalakrishnan, Walker, Alycon, Walsh, Stephen B., Waters, Aoife, Watt, Angela, Webster, Phil, Wechalekar, Ashutosh, Welsh, Gavin Iain, West, Nicol, Wheeler, David, Wiles, Kate, Willcocks, Lisa, Williams, Angharad, Williams, Emma, Williams, Karen, Wilson, Deborah H., Wilson, Patricia D., Winyard, Paul, Wong, Edwin, Wong, Katie, Wood, Grahame, Woodward, Emma, Woodward, Len, Woolf, Adrian, Wright, David, Downward, Lewis, Griffin, Sian, Hall, Matt, Karet Frankl, Fiona, Maher, Eamonn R., Pinney, Jenny, Tam, Frederick W.K., Wilson, Patricia, Sy, Karla Therese L., Huang, Kui, Ye, Jamie, Nitsch, Dorothea, and Bockenhauer, Detlef

Published
2024
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5. Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Author

Abat, Sharirose, Adalat, Shazia, Agbonmwandolor, Joy, Ahmad, Zubaidah, Alejmi, Abdulfattah, Almasarwah, Rashid, Annear, Nicholas, Asgari, Ellie, Ayers, Amanda, Baharani, Jyoti, Balasubramaniam, Gowrie, Kpodo, Felix, Bansal, Tarun, Barratt, Alison, Barratt, Jonathan, Bates, Megan, Bayne, Natalie, Bendle, Janet, Benyon, Sarah, Bergmann, Carsten, Bhandari, Sunil, Bingham, Coralie, Boddana, Preetham, Bond, Sally, Braddon, Fiona, Bramham, Kate, Branson, Angela, Brearey, Stephen, Brocklebank, Vicky, Budwal, Sharanjit, Byrne, Conor, Cairns, Hugh, Camilleri, Brian, Campbell, Gary, Capell, Alys, Carmody, Margaret, Carson, Marion, Cathcart, Tracy, Catley, Christine, Cesar, Karine, Chan, Melanie, Chea, Houda, Chess, James, Cheung, Chee Kay, Chick, Katy-Jane, Chitalia, Nihil, Christian, Martin, Chrysochou, Tina, Clark, Katherine, Clayton, Christopher, Clissold, Rhian, Cockerill, Helen, Coelho, Joshua, Colby, Elizabeth, Colclough, Viv, Conway, Eileen, Cook, H Terence, Cook, Wendy, Cooper, Theresa, Coward, Richard J, Crosbie, Sarah, Cserep, Gabor, Date, Anjali, Davidson, Katherine, Davies, Amanda, Dhaun, Neeraj, Dhaygude, Ajay, Diskin, Lynn, Dixit, Abhijit, Doctolero, Eunice, Dorey, Suzannah, Downard, Lewis, Drayson, Mark, Dreyer, Gavin, Dutt, Tina, Etuk, Kufreabasi, Evans, Dawn, Finch, Jenny, Flinter, Frances, Fotheringham, James, Francis, Lucy, Gale, Daniel P, Gallagher, Hugh, Game, David, Garcia, Eva, Gavrila, Madita, Gear, Susie, Geddes, Colin, Gilchrist, Mark, Gittus, Matt, Goggolidou, Paraskevi, Goldsmith, Christopher, Gooden, Patricia, Goodlife, Andrea, Goodwin, Priyanka, Grammatikopoulos, Tassos, Gray, Barry, Griffith, Megan, Gumus, Steph, Gupta, Sanjana, Hamilton, Patrick, Harper, Lorraine, Harris, Tess, Haskell, Louise, Hayward, Samantha, Hegde, Shivaram, Hendry, Bruce, Hewins, Sue, Hewitson, Nicola, Hillman, Kate, Hiremath, Mrityunjay, Howson, Alexandra, Htet, Zay, Huish, Sharon, Hull, Richard, Humphries, Alister, Hunt, David P J, Hunter, Karl, Hunter, Samantha, Ijeomah-Orji, Marilyn, Inston, Nick, Jayne, David, Jenfa, Gbemisola, Jenkins, Alison, Johnson, Sally, Jones, Caroline A, Jones, Colin, Jones, Amanda, Jones, Rachel, Kamesh, Lavanya, Kanigicherla, Durga, Karet Frankl, Fiona, Karim, Mahzuz, Kaur, Amrit, Kavanagh, David, Kearley, Kelly, Kerecuk, Larissa, Khwaja, Arif, King, Garry, King, Grant, Kislowska, Ewa, Klata, Edyta, Kokocinska, Maria, Lambie, Mark, Lawless, Laura, Ledson, Thomas, Lennon, Rachel, Levine, Adam P, Lai, Ling Wai Maggie, Lipkin, Graham, Lovitt, Graham, Lyons, Paul, Mabillard, Holly, Mackintosh, Katherine, Mahdi, Khalid, Maher, Eamonn, Marchbank, Kevin J, Mark, Patrick B, Masoud, Sherry, Masunda, Bridgett, Mavani, Zainab, Mayfair, Jake, McAdoo, Stephen, Mckinnell, Joanna, Melhem, Nabil, Meyrick, Simon, Moochhala, Shabbir, Morgan, Putnam, Morgan, Ann, Muhammad, Fawad, Murray, Shona, Novobritskaya, Kristina, Ong, Albert CM, Oni, Louise, Osmaston, Kate, Padmanabhan, Neal, Parkes, Sharon, Patrick, Jean, Pattison, James, Paul, Riny, Percival, Rachel, Perkins, Stephen J, Persu, Alexandre, Petchey, William G, Pickering, Matthew C, Pinney, Jennifer, Pitcher, David, Plumb, Lucy, Plummer, Zoe, Popoola, Joyce, Post, Frank, Power, Albert, Pratt, Guy, Pusey, Charles, Rabara, Ria, Rabuya, May, Raju, Tina, Javier, Chadd, Roberts, Ian S D, Roufosse, Candice, Rumjon, Adam, Salama, Alan, Saleem, Moin, Sandford, Richard, Sandu, Kanwaljit S, Sarween, Nadia, Sayer, John A, Sebire, Neil, Selvaskandan, Haresh, Sharma, Asheesh, Sharples, Edward J, Sheerin, Neil, Shetty, Harish, Shroff, Rukshana, Simms, Roslyn, Sinha, Manish, Sinha, Smeeta, Smith, Kerry, Smith, Lara, Srivastava, Shalabh, Steenkamp, Retha, Stott, Ian, Stroud, Katerina, Swift, Pauline, Szklarzewicz, Justyna, Tam, Fred, Tan, Kay, Taylor, Robert, Tischkowitz, Marc, Thomas, Kay, Tse, Yincent, Turnbull, Alison, Turner, A Neil, Tyerman, Kay, Usher, Miranda, Venkat-Raman, Gopalakrishnan, Walker, Alycon, Walsh, Stephen B, Waters, Aoife, Watt, Angela, Webster, Phil, Wechalekar, Ashutosh, Welsh, Gavin I, West, Nicol, Wheeler, David, Wiles, Kate, Willcocks, Lisa, Williams, Angharad, Williams, Emma, Williams, Karen, Wilson, Deborah H, Wilson, Patricia D, Winyard, Paul, Wong, Edwin, Wong, Katie, Wood, Grahame, Woodward, Emma, Woodward, Len, Woolf, Adrian, Wright, David, Downward, Lewis, Chrysochou, Constantina, Griffin, Sian, Hall, Matt, Maher, Eamonn R, Pinney, Jenny, Tam, Frederick W K, Turner, Andrew Neil, Wilson, Patricia, Taylor, Christopher Mark, Nitsch, Dorothea, and Bockenhauer, Detlef

Published
2024
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6. Use of cidofovir in a patient with severe mpox and uncontrolled HIV infection

Author

Stafford, Adam, Rimmer, Stephanie, Gilchrist, Mark, Sun, Kristi, Davies, Ella P, Waddington, Claire S, Chiu, Christopher, Armstrong-James, Darius, Swaine, Thomas, Davies, Frances, Gómez, Carlos H M, Kumar, Vagish, ElHaddad, Ahmad, Awad, Zaid, Smart, Christopher, Mora-Peris, Borja, Muir, David, Randell, Paul, Peters, Joanna, Chand, Meera, Warrell, Clare E, Rampling, Tommy, Cooke, Graham, Dhanji, Sara, Campbell, Vivienne, Davies, Carys, Osman, Sana, and Abbara, Aula

Published
2023
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7. Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study

Author

Dunning, Jake, Fink, Douglas L, Milligan, Iain D, Luintel, Akish, Rodger, Alison J, Bhagani, Sanjay R, Lamb, Lucy E, Moores, Rachel C, Lee, Simon F K, Brown, Colin S, Hopkins, Susan, Mepham, Stephen, Warren, Simon, Molloy, Aoife, Cropley, Ian, Kew, Alex, Karunaharan, Natasha, Scobie, Antonia, Hart, Jennifer, Irish, Dianne, Haque, Tanzina, Jalal, Hamid, Smith, Robin, Mack, Damien, Barber, Tristan, Burns, Fiona, Miller, Robert, Hamlyn, Eleanor, Simoes, Pedro, Athan, Breda, Abrahamsen, Jennifer, Joyce, Jessica, Taylor, Caroline, Reddecliffe, Sally, Miller, Chloe, Reeve, Brooke, Kingston, Hugh, Crocker-Buque, Tim, Massie, Nicolas, Dhariwal, Ankush, Jayakumar, Angelina, Hammond, Robert, Bramley, Alexandra, Kanitkar, Tanmay, Maynard-Smith, Laura, Gil, Eliza, O'Connor, Cavan, Cocker, Derek, Spicer, Wendy, Lanzman, Marisa, Thacker, Meera, Anorson, Zoe O, Patel, Dharmesh, Williams, Alan, Houlihan, Catherine F, Wakerley, Dominic, Gordon, Claire N, Callaby, Helen, Bailey, Daniel J, Furneaux, Jenna, Bown, Abbie M, Truelove, Elizabeth J, Killip, Marian J, Jackson, David, Beetar-King, Tracy L B, Arnold, Ulrike M V, Strachan, Rhea M, Matthew, Jones, Matthew, Hannah J, Osborne, Jane C, Rampling, Tommy, Vipond, Richard, Gibney, Barry, Owen, Jodie, Bond, Helena, Beynon, Will, Hunter, Michael, McCorry, Louise, Emerson, Carol, Quah, Say, Todd, Suzanne, McCarty, Emma, Walker, Eoin, Feeney, Susan, Curran, Tanya, Li, Kathy, Mullan, JD, Jackson, Kate, Nelson, Peter, Lewis, Kevin, McNicol, Mark, Pratt, Marcus, Smith, Anna, Vos, Erin, Alsalemee, Fahad, O Leary, Daniel, Canny, John, McGinnity, Katherine, Culbert, Carly, McDowell, Conor, McQuillan, Cathy, Jeong, Eunjin, Glass, Lynsey, Dyche, Jessica, McClean, Paula, Stewart, Rebecca, Ursolino, Harold, Perry, Melissa, McCormick, Hannah, Lim, Eleanor Y, Gkrania-Klotsas, Effrossyni, Bracchi, Margherita, Heskin, Joseph, Brown, Nicklas, Juniper, Thomas, Mora-Peris, Borja, Dalla-Pria, Alessia, Mackie, Nicola, Garvey, Lucy, Winston, Alan, Cooke, Graham, Nelson, Mark, Kilbride, Emer, Elbishi, Ala, Kerrigan, William, Silva, Joshua, Gohil, Jesal, Payagala, Sasha, Walters, Yasmin, Smith, Joanna, Goodfellow, Jonathan, Lyons, Kitty, Tung, Hsiu, Patel, Kinjal, Henderson, Merle, Butler, Michael, Peres, Edu, Silva Carvalho, Taiana, Joly, Antoine, Dickinson, Molly, Moore, Luke S P, Mughal, Nabeela, Hughes, Stephen, Chitlangia, Shrada, Viramgana, Priyanka, Byrne, Ruth, Randell, Paul, Strangis, Luigi, Poveda, Nicola, Bovey, Deborah, Richardson, Poppy, Heaslip, Vivian, Higgs, Christopher, Boffito, Marta, Girometti, Nicolo, Whitlock, Gary, Tittle, Victoria, Jones, Rachel, Rayment, Michael, Scott, Christopher, Asboe, David, Pond, Marcus, Muir, David, Rathish, Balram, O'Hara, Geraldine, Abeywickrema, Movin, Bailey, Sarah-Lou, Boyd, Sara E, Da Silva Fontoura, Dayana, Daunt, Anna, Mason, Claire Y, Murphy, Jamie, Naidu, Vasanth V, Patel, Aatish, Pley, Caitlin, Redmore, Ethan, Sharrocks, Katherine, Snell, Luke B, Sundramoorthi, Rohan, Tam, Jerry C H, Brown, Aisling, Douthwaite, Sam, Goodman, Anna, Nebbia, Gaia, Newsholme, William, Price, Nicholas, Shaw, Emily, Salam, Alex, van Nispen tot Pannerden, Claire, Winslow, Helen, Bilinska, Julia, Keegan, Sarah, Coleman, Harry, Doctor, Jessica, Moini, Nasreen, Chilton, Daniella, Haidari, Golaleh, Simons, Rebecca, Kulasegaram, Rajababu, Larbalestier, Nick, Nori, Achyuta, Potter, Jack R, Tuudah, Cecilia, Wade, Paul, Travers, Alexandra, Dunford, Sarah, Greenwood, Joshua, Oledimmah, Georgina, Gyampo, Lesley, SA Pinto, Pedro, Muse, AbdulKadir, Parker, Zoe, Alexander, Charlotte, Khan, Alexander, Ajayi, Medinat, Baltazar, Abigail, Sharella, Davis, Hersi, Nasra, Nguyen, Thuy, Timbo, Rugiatu, Jalloh, Ismail, Bryan, Susan, Clarke, Patricia, Kerr, Marcia, Amedu, Fidelis, BohoBonaba, Maria, Haque, Sarah, Howson, Michelle, Tambilawan, Norbai, Yupanqui Estay, Soledad, Bangura, Hawanatu, Gideon, Tseday, Jerome-oboh, Damilola, Tetteh, Linda, Nwagu, Chioma, Agbaglah, Viwoalo, Narag, Nona, Zaveri, Mahima, Ni Luanaigh, Maedhbh, Keane, Peggy, Peters, Joanna R, Rimmer, Stephanie, Abbara, Aula, Dosekun, Olamide, Bolland, Mhairi, Stafford, Adam, Saleh, Dina, Sheridan, Rhianna, Davies, Ella, Sun, Kristi, Gilchrist, Mark, Kukadia, Priti, Embrahimsa, Muhammed, Chiu, Christopher, Taylor, Lauren, Short, Charlotte, Alagratnam, Jasmini, Jayaweera, Iresh, Gundugola, Kavitha, Payne, Lara V S, Mody, Nisha, Quinn, Killian, Nic Fhogartaigh, Caoimhe, Kaur, Nivenjit, Bholah, Salmaan, Kantha, Kajann, Youngs, Jonathan, Lampejo, Temi, Pitto, Nicholas, Lawrence, David S, Middleditch, Holly, Dominguez-Dominguez, Lourdes, Ratnappuli, Ayoma, Al-Hashimi, Sara, Oliveira, Amelia, Ottaway, Zoe, Mulka, Larissa, Hodgson, Bethany, Lewthwaite, Penny, Neary, Anne M, Downey, Michael R, Lucy, Danielle C, McCallum, Craig I, Beadsworth, Michael, Ratcliffe, Libuse, Fletcher, Tom E, Davies, Gerry, Wong, Nicholas, Aston, Stephen, Wingfield, Thomas E, Blanchard, Thomas, Hine, Paul, Lester, Rebecca, Woolley, Stephen D, Gould, Susie, Smith, Christopher, Abouyannis, Michael, Atomode, Abolaji, Cruise, James, Samual, Merna, Scott, Nicola, Srirathan, Vino, Lewis, Joseph, Richards, Lauren, Cummings, Mary-Ann, Gillan, Emily, Peers, Rebecca, Tickle, Amy, Keating, Grace, Chinyanda, Tendi, Sanchez, Mav, Harrison, Daniel, Hoyle, Metcalfe, Ben, Taylor, Jennifer, Johnson, Nicky, Kelle, Neil, McDowell, Kirsty, Richardson, Ian, Saguidan, Monette, Farmer, Nicky, Gillespie, Angella, Willoughby, Shay, Parker, Samantha, Avulan, Shamseena, Arif, Shazia, Marshall, Suzanne, Carlisle, David, Rezaei, Mohsen, Booth, Angela, Watts, Joanne, Tremarco, Lauren, Jeyanayagam, Priyanga, Ubochi, Odinaka, Vagianos, Daniel, Richardson, Mark, Jarvis, Anthony, Gow, Kyra, Walmsley, Jade, O'keefe, Adam, Smielewska, Anna, Hopkins, Mark, Balane, Fatima, Bradley, Sarah, Corrah, Tumena, Daquiz, Venus, Dugan, Christopher, Elliot, Joshua, Foley, Fiona, Friday, Dawn, Gamit, May, Garner, David, Gokani, Karishma, John, Laurence, Joseph, Deepa, Khan, Nuzhath, Mamuyac, Cherifer, McGregor, Alastair, McSorley, John, Parris, Victoria, Rubinstein, Luciana, Rycroft, Julian, Salinas, Kelcy, Salinas, Jason, Sebatian, Jency, Smith, Melanie, Tejero Garcia, Marina, Ume, Uchenna, Vicentine, Margarete, Wallis, Gabriel, Sturdy, Ann, Whittington, Ashley, Jacobs, Nathan, Johnson, Leann, Bonington, Alec, Uriel, Alison, Ustianowski, Andrew, Dancso, Balazs, Hogan, Celia, van Halsema, Clare, Vilar, F Javier, Devine, Karen, Ajdukiewicz, Katherine, Rajendran, Rajesh, Ghosh, Samit, Riste, Michael, Machin, Nicholas, Babu, Chitra, Ahmad, Shazaad, Obeng, Dorcas, Dave, Farnaz, Conolley, Gavin, Thompson, Joseph, Tickell-Painter, Maya, Chakravorty, Prasun, Pringle, Rachel, Zafar, Mohammad R, Lawrence, Sarah, Sanchez-Gonzalez, Amada, Fernandez, Cristina, Goodwin, Lynsey, Carey, David, Howarth-Maddison, Molly, Moody, Samuel, Upton, Rebecca, Apthorp, Christina, Murray, Charlotte, Salthouse, Kirstie, Nadeem, Sabah, Ridley, Grant, White, Francesca, Brown, Andrew, Lawless, Michael, Mohamed, Mohamed, Mulligan, Robert, Belfield, Amy, Brolly, Jacob, Calderon, Maria, Cheveau, James, Cullinan, Milo, Garrad, Sophie, Griffiths, Will, Ireland, Aidan, Ireland, Peter, Milne, Charlotte, Nwajiugo, Paul, Quartey, John, Ghavami-Kia, Bijan, Duncan, Chris, Evans, Adam, Hunter, Ewan, Price, Ashley, Schmid, Matthias, Schwab, Uli, Taha, Yusri, Payne, Brendan, Elliott, Ivo A M, Crowe, Stewart, Woodrow, Charles J, Karageorgopoulos, Drosos E, Davis, Peter J, Lord, Emily, Bannister, Oliver J, Dagens, Andrew B, Harrison, Thomas, Cole, Joby, Tunbridge, Anne, Choudry, Saher, Telfer, Adam, Jhibril, Ihsan, Atta, Syed N, Stone, Ben, Evans, Cariad, Ankcorn, Mike, Akili, Suha, Yavuz, Mehmet, Goodall, Vicky, Farrow, Sam, Mountford, Georgina, Cusack, Tomas-Paul, Beard, Kate, Sutton, Julian, Clark, Tristan, Mason, Annette, Vickers, Mike, Macallan, Derek, Bicanic, Tihana, Houston, Angela, Pope, Cassie, Tan, NgeeKeong, Ward, Christopher, Jones, Imogen, Banerjee, Rishi, Cohen, Jonathan, Emonts-le Clercq, Marieke, Porter, David, Riordan, Andrew, Sinha, Ruchi, Whittaker, Elizabeth, Beynon, William, Heskin, Jospeh, Milligan, Iain, Payne, Lara, AI Payne, Brendan, Elliott, Ivo AM, and Beard, Katie

Published
2023
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9. Current practices and challenges of outpatient parenteral antimicrobial therapy: a narrative review.

Author

Wolie, Zenaw T, Roberts, Jason A, Gilchrist, Mark, McCarthy, Kate, and Sime, Fekade B

Subjects
MEDICAL personnel, INPATIENT care, NARRATIVE therapy, PATIENT readmissions, PATIENT preferences
Abstract

Extended hospitalization for infection management increases inpatient care costs and the risk of healthcare-associated adverse events, including infections. The growing global demand for healthcare, the diminishing availability of hospital beds and an increasing patient preference for care within their own home have been the primary drivers of the expansion of hospital-in-the-home programmes. Such programmes include the use of IV antimicrobials in outpatient settings, known as outpatient parenteral antimicrobial therapy (OPAT). However, OPAT practices vary globally. This review article aims to describe the current OPAT practices and challenges worldwide. OPAT practice begins with patient evaluation and selection using eligibility criteria, which requires collaboration between the interdisciplinary OPAT team, patients and caregivers. Depending on care requirements, eligible patients may be enrolled to various models of care, receiving medication by healthcare professionals at outpatient infusion centres, hospital clinics, home visits or through self-administration. OPAT can be used for the management of many infections where an effective oral treatment option is lacking. Various classes of parenteral antimicrobials, including β-lactams, aminoglycosides, glycopeptides, fluoroquinolones and antifungals such as echinocandins, are used globally in OPAT practice. Despite its benefits, OPAT has numerous challenges, including complications from medication administration devices, antimicrobial side effects, monitoring requirements, antimicrobial instability, patient non-adherence, patient OPAT rejection, and challenges related to OPAT team structure and administration, all of which impact its outcome. A negative outcome could include unplanned hospital readmission. Future research should focus on mitigating these challenges to enable optimization of the OPAT service and thereby maximize the documented benefits for the healthcare system, patients and healthcare providers. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Integrated Analysis of Patient Networks and Plasmid Genomes to Investigate a Regional, Multispecies Outbreak of Carbapenemase-Producing Enterobacterales Carrying Both blaIMP and mcr-9 Genes.

Author

Wan, Yu, Myall, Ashleigh C, Boonyasiri, Adhiratha, Bolt, Frances, Ledda, Alice, Mookerjee, Siddharth, Weiße, Andrea Y, Getino, Maria, Turton, Jane F, Abbas, Hala, Prakapaite, Ruta, Sabnis, Akshay, Abdolrasouli, Alireza, Malpartida-Cardenas, Kenny, Miglietta, Luca, Donaldson, Hugo, Gilchrist, Mark, Hopkins, Katie L, Ellington, Matthew J, and Otter, Jonathan A

Subjects
HORIZONTAL gene transfer, ELECTRONIC health records, GENOMICS, DNA sequencing, ESCHERICHIA coli, KLEBSIELLA pneumoniae
Abstract

Background Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of imipenemase (IMP)–encoding CPE among diverse Enterobacterales species between 2016 and 2019 across a London regional network. Methods We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE–positive patients. Genomes of IMP-encoding CPE isolates were overlaid with patient contacts to imply potential transmission events. Results Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, and Escherichia coli); 86% (72 of 84) harbored an IncHI2 plasmid carrying bla IMP and colistin resistance gene mcr-9 (68 of 72). Phylogenetic analysis of IncHI2 plasmids identified 3 lineages showing significant association with patient contacts and movements between 4 hospital sites and across medical specialties, which was missed in initial investigations. Conclusions Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of bla IMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multimodal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks. Summary This was an investigation, using integrated pathway networks and genomics methods, of the emergence of imipenemase-encoding carbapenemase-producing Enterobacterales among diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network, which was missed on routine investigations. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries: results of an internet-based global point prevalence survey

Author

Koraqi, Andi, Hoxha, Iris, Tafaj, Silva, Lacej, Denada, Hojman, Martin, Quiros, Rodolfo Ernesto, Ghazaryan, Lilit, Cairns, Kelly A, Cheng, Allen, Horne, Kylie C, Doukas, Fiona F, Gottlieb, Thomas, Alsalman, Jameela, Magerman, Koen, Marielle, Gounongbe YT, Ljubovic, Amela Dedeic, Coelho, André Afonso Machado, Gales, Ana Cristina, Keuleyan, Emma, Sabuda, Deana, Boswell, Jennifer Lee, Conly, John M, Rojas, Alvaro, Carvajal, Camila, Labarca, Jaime, Solano, Antonio, Valverde, Carlos Ramírez, Villalobos-Vindas, Juan M, Pristas, Irina, Plecko, Vanda, Paphitou, Niki, Shaqiri, Erjona, Rummukainen, Maija-Liisa, Pagava, Karaman, Korinteli, Irma, Brandt, Tobias, Messler, Sabine, Enimil, Anthony, Iosifidis, Elias, Roilides, Emmanuel, Sow, Mamadou Saliou, Sengupta, Sharmila, George, Joby V, Poojary, Aruna, Patil, Priyanka, Soltani, Jafar, Jafarpour, Zahra, Ameen, Hadi, Fitzgerald, David, Maor, Yasmin, Chowers, Michal, Temkin, Elizabeth, Esposito, Susanna, Arnoldo, Luca, Brusaferro, Silvio, Gu, Yoshiaki, El-Hajji, Feras Darwish, Kim, Nam Joong, Kambaralieva, Baktygul, Pavare, Jana, Zarakauska, Lelde, Usonis, Vytautas, Burokiene, Sigita, Ivaskeviciene, Inga, Mijovic, Gordana, Duborija-Kovacevic, Natasa, Bondesio, Kristen, Iregbu, Kenneth, Oduyebo, Oyinlola, Raka, Denis, Raka, Lul, Rachina, Svetlana, Enani, Mushira Abdulaziz, Al Shehri, Mohamed, Carevic, Biljana, Dragovac, Gorana, Obradovic, Dusanka, Stojadinovic, Aleksandra, Radulovic, Lili, Wu, Jia EN, Wei Teng Chung, Gladys, Chen, Hui Hiong, Tambyah, Paul Anantharajah, Lye, David, Tan, Sock Hoon, Ng, Tat Ming, Tay, Hui Lin, Ling, Moi Lin, Chlebicki, Maciej Piotr, Kwa, Andrea L, Lee, Winnie, Beović, Bojana, Dramowski, Angela, Finlayson, Heather, Taljaard, Jantjie, Ojeda-Burgos, Guillermo, Retamar, Pilar, Lucas, Johan, Pot, Wolter, Verduin, Cees, Kluytmans, Jan, Scott, Michael, Aldeyab, Mamoon A, McCullagh, Bernadette, Gormley, Cairine, Sharpe, David, Gilchrist, Mark, Whitney, Laura, Laundy, Matthew, Lockwood, Debbie, Drysdale, Simon B, Boudreaux, Jennifer, Septimus, Edward J, Greer, Nickie, Gawrys, Gerard, Rios, Edgar, May, Suzanne, Versporten, Ann, Zarb, Peter, Caniaux, Isabelle, Gros, Marie-Françoise, Drapier, Nico, Miller, Mark, Jarlier, Vincent, Nathwani, Dilip, and Goossens, Herman

Published
2018
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25. Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study.

Author

Baltas, Ioannis, Gilchrist, Mark, Koutoumanou, Eirini, Gibani, Malick M., Meiring, James E., Otu, Akaninyene, Hettle, David, Thompson, Ameeka, Price, James R., Crepet, Anna, Atomode, Abolaji, Crocker-Buque, Timothy, Spinos, Dimitrios, Guyver, Hudson, Tausan, Matija, Somasunderam, Donald, Thoburn, Maxwell, Chan, Cathleen, Umpleby, Helen, and Sharp, Bethany

Published
2023
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26. International consensus recommendations for the use of prolonged‐infusion beta‐lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists: An executive summary

Author

Hong, Lisa T., Downes, Kevin J., FakhriRavari, Alireza, Abdul‐Mutakabbir, Jacinda C., Kuti, Joseph L., Jorgensen, Sarah, Young, David C., Alshaer, Mohammad H., Bassetti, Matteo, Bonomo, Robert A., Gilchrist, Mark, Jang, Soo Min, Lodise, Thomas, Roberts, Jason A., Tängdén, Thomas, Zuppa, Athena, and Scheetz, Marc H.

Subjects
BETA lactam antibiotics, MEDICAL microbiology, LACTAMS, CRITICAL care medicine, COMMUNICABLE diseases, CYSTIC fibrosis, DRUG monitoring
Abstract

Intravenous β‐lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β‐lactams are well established to display time‐dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous β‐lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of β‐lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI β‐lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β‐lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP). [ABSTRACT FROM AUTHOR]

Published
2023
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29. The Common PKD1 p.(Ile3167Phe) Variant Is Hypomorphic and Associated with Very Early Onset, Biallelic Polycystic Kidney Disease.

Author

Durkie, Miranda, Watson, Christopher M., Winship, Peter, Hogg, Anne-Cecile, Nyanhete, Rodney, Cooley, Sharon, Valluru, Manoj K., Shaw-Smith, Charles, Bingham, Coralie, Gilchrist, Mark, Kenny, Janna, Consortium, Genomics England Research, and Ong, Albert C. M.

Abstract

Biallelic PKD1 variants, including hypomorphic variants, can cause very early onset polycystic kidney disease (VEO-PKD). A family with unexplained recurrent VEO-PKD and neonatal demise in one dizygotic twin was referred for clinical testing. Further individuals with the putative hypomorphic PKD1 variant, p.(Ile3167Phe), were identified from the UK 100,000 genomes project (100 K), UK Biobank (UKBB), and a review of the literature. We identified a likely pathogenic PKD1 missense paternal variant and the putative hypomorphic PKD1 variant from the unaffected mother in the deceased twin but only the paternal PKD1 variant in the surviving dizygotic twin. Analysis of 100 K cases identified a second family with two siblings with similar biallelic inheritance who presented at birth with VEO-PKD and reached kidney failure in their teens unlike other affected relatives. Finally, a survey of 618 UKBB cases confirmed that adult patients monoallelic for PKD1 p.(Ile3167Phe) had normal kidney function. Our data reveals that p.(Ile3167Phe) is the second most common PKD1 hypomorphic variant identified and is neutral in heterozygosity but is associated with VEO-PKD when inherited in trans with a pathogenic PKD1 variant. Care should be taken to ensure that it is not automatically filtered from sequence data for VEO cases. [ABSTRACT FROM AUTHOR]

Published
2023
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31. Recurrent 17q12 microduplications contribute to renal disease but not diabetes.

Author

Cannon, Stuart, Clissold, Rhian, Sukcharoen, Kittiya, Tuke, Marcus, Hawkes, Gareth, Beaumont, Robin N., Wood, Andrew R., Gilchrist, Mark, Hattersley, Andrew T., Oram, Richard A., Patel, Kashyap, Wright, Caroline, and Weedon, Michael N.

Abstract

Background 17q12 microdeletion and microduplication syndromes present as overlapping, multisystem disorders. We assessed the disease phenotypes of individuals with 17q12 CNV in a population-based cohort. Methods We investigated 17q12 CNV using microarray data from 450 993 individuals in the UK Biobank and calculated disease status associations for diabetes, liver and renal function, neurological and psychiatric traits. Results We identified 11 17q12 microdeletions and 106 microduplications. Microdeletions were strongly associated with diabetes (p=2×10−7) but microduplications were not. Estimated glomerular filtration rate (eGFR mL/min/1.73 m² ) was consistently lower in individuals with microdeletions (p=3×10−12) and microduplications (p=6×10−25). Similarly, eGFR <60, including end-stage renal disease, was associated with microdeletions (p=2×10−9, p<0.003) and microduplications (p=1×10−9, p=0.009), respectively, highlighting sometimes substantially reduced renal function in each. Microduplications were associated with decreased fluid intelligence (p=3×10−4). SNP association analysis in the 17q12 region implicated changes to HNF1B as causing decreased eGFR (NC_000017.11:g.37741642T>G, rs12601991, p=4×10−21) and diabetes (NC_000017.11:g.37741165C>T, rs7501939, p=6×10−17). A second locus within the region was also associated with fluid intelligence (NC_000017.11:g.36593168T>C, rs1005552, p=6×10−9) and decreased eGFR (NC_000017.11:g.36558947T>C, rs12150665, p=4×10–15). Conclusion We demonstrate 17q12 microdeletions but not microduplications are associated with diabetes in a population-based cohort, likely caused by HNF1B haploinsufficiency. We show that both 17q12 microdeletions and microduplications are associated with renal disease, and multiple genes within the region likely contribute to renal and neurocognitive phenotypes. [ABSTRACT FROM AUTHOR]

Published
2023
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34. A founder UMOD variant is a common cause of hereditary nephropathy in the British population.

Author

Valluru, Manoj K., Chung, Noelle K. X., Gilchrist, Mark, Butland, Laura, Cook, Jackie, Takou, Anna, Dixit, Abhijit, Weedon, Michael N., and Ong, Albert C. M.

Abstract

Background Monogenic disorders are estimated to account for 10%-12% of patients with kidney failure. We report the unexpected finding of an unusual uromodulin (UMOD) variant in multiple pedigrees within the British population and demonstrate a shared haplotype indicative of an ancestral variant. Methods Probands from 12 apparently unrelated pedigrees with a family history of kidney failure within a geographically contiguous UK region were shown to be heterozygous for a pathogenic variant of UMOD c.278_289delTCTGCCCCGAAG insCCGCCTCCT. Results A total of 88 clinically affected individuals were identified, all born in the UK and of white British ethnicity. 20 other individuals with the variant were identified in the UK 100,000 Genomes (100K) Project and 9 from UK Biobank (UKBB). A common extended haplotype was present in 5 of the UKBB individuals who underwent genome sequencing which was only present in <1 in 5000 of UKBB controls. Significantly, rare variants (<1 in 250 general population) identified within 1 Mb of the UMOD variant by genome sequencing were detected in all of the 100K individuals, indicative of an extended shared haplotype. Conclusion Our data confirm a likely founder UMOD variant with a wide geographical distribution within the UK. It should be suspected in cases of unexplained familial nephropathy presenting in patients of white British ancestry. [ABSTRACT FROM AUTHOR]

Published
2023
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35. Prevalence of Fabry disease-causing variants in the UK Biobank.

Author

Gilchrist, Mark, Casanova, Francesco, Tyrrell, Jess S., Cannon, Stuart, Wood, Andrew R., Fife, Nicole, Young, Katherine, Oram, Richard A., and Weedon, Michael N.

Abstract

Background Fabry disease is an X-linked lysosomal storage disorder resulting from deficiency of the alpha-galactosidase A enzyme leading to accumulation of globotriaosylceramide in multiple organ sites with prominent cardiovascular and renal involvement. Global prevalence estimates of Fabry disease based on clinical ascertainment range from 1 in 40 000 to 1 in 170 000. We aimed to determine the prevalence of Fabry disease-causing variants in UK Biobank. Methods We sought GLA gene variants in exome sequencing data from 200 643 individuals from UK Biobank. We used ACMG/AMP guidelines (American College of Medical Genetics/Association for Molecular Pathology) to classify pathogenicity and compared baseline biomarker data, hospital ICD-10 (International Classification of Diseases version-10) codes, general practitioner records and self-reported health data with those without pathogenic variants. Results We identified 81 GLA coding variants. We identified eight likely pathogenic variants on the basis of being rare (<1/10 000 individuals) and either previously reported to cause Fabry disease, or being protein-truncating variants. Thirty-six individuals carried one of these variants. In the UK Biobank, the prevalence of likely pathogenic Fabry disease-causing variants is 1/5732 for late-onset disease-causing variants and 1/200 643 for variants causing classic Fabry disease. Conclusion Fabry disease-causing GLA variants are more prevalent in an unselected population sample than the reported prevalence of Fabry disease. These are overwhelmingly variants associated with later onset. It is possible the prevalence of later-onset Fabry disease exceeds current estimates. [ABSTRACT FROM AUTHOR]

Published
2023
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41. Application of therapeutic drug monitoring to the treatment of bacterial central nervous system infection: a scoping review.

Author

Arkell, Paul, Wilson, Richard, Watkins, Killian, Antcliffe, David B, Gilchrist, Mark, Wilson, Mark, Rawson, Timothy M, and Holmes, Alison

Subjects
ANTIBIOTICS, RESEARCH funding, BETA lactam antibiotics, CENTRAL nervous system infections, DRUG monitoring, VANCOMYCIN, SYSTEMATIC reviews
Abstract

Background: Bacterial central nervous system (CNS) infection is challenging to treat and carries high risk of recurrence, morbidity, and mortality. Low CNS penetration of antibiotics may contribute to poor clinical outcomes from bacterial CNS infections. The current application of therapeutic drug monitoring (TDM) to management of bacterial CNS infection was reviewed.Methods: Studies were included if they described adults treated for a suspected/confirmed bacterial CNS infection and had antibiotic drug concentration(s) determined that affected individual treatment.Results: One-hundred-and-thirty-six citations were retrieved. Seventeen manuscripts were included describing management of 68 patients. TDM for vancomycin (58/68) and the beta-lactams (29/68) was most common. Timing of clinical sampling varied widely between studies and across different antibiotics. Methods for setting individual PK-PD targets, determining parameters and making treatment changes varied widely and were sometimes unclear.Discussion: Despite increasing observational data showing low CNS penetration of various antibiotics, there are few clinical studies describing practical implementation of TDM in management of CNS infection. Lack of consensus around clinically relevant CSF PK-PD targets and protocols for dose-adjustment may contribute. Standardised investigation of TDM as a tool to improve treatment is required, especially as innovative drug concentration-sensing and PK-PD modelling technologies are emerging. Data generated at different centres offering TDM should be open access and aggregated to enrich understanding and optimize application. [ABSTRACT FROM AUTHOR]

Published
2022
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46. How is income generated by outpatient parenteral antibiotic treatment (OPAT) in the UK? Analysis of payment tariffs for cellulitis

Author

Jones, G. R., Cumming, D. V. E., Honeywell, G., Ball, R., Sanderson, F., Seaton, R. A., Healy, B., Hedderwick, S., Gilchrist, M., Dryden, Matthew, Gilchrist, Mark, Seaton, Andrew, Chapman, Ann, Laundy, Matthew, Patel, Sanjay, Jones, Graeme, Cumming, Debbie, Sanderson, Frances, Jefferies, Lorrayne, Hanlon, Sue O., Owen, Kate, Snape, Sue, and Hills, Tim

Published
2015
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47. Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis.

Author

Wilson, Richard C, Arkell, Paul, Riezk, Alaa, Gilchrist, Mark, Wheeler, Graham, Hope, William, Holmes, Alison H, and Rawson, Timothy M

Subjects
GONORRHEA, BETA lactam antibiotics, META-analysis, PROBENECID (Drug), SYSTEMATIC reviews, RESEARCH funding, AMOXICILLIN, ANTIBIOTICS
Abstract

Objectives: To explore the literature comparing the pharmacokinetic and clinical outcomes from adding probenecid to oral β-lactams.Methods: Medline and EMBASE were searched from inception to December 2021 for all English language studies comparing the addition of probenecid (intervention) with an oral β-lactam [flucloxacillin, penicillin V, amoxicillin (± clavulanate), cefalexin, cefuroxime axetil] alone (comparator). ROBINS-I and ROB-2 tools were used. Data on antibiotic therapy, infection diagnosis, primary and secondary outcomes relating to pharmacokinetics and clinical outcomes, plus adverse events were extracted and reported descriptively. For a subset of studies comparing treatment failure between probenecid and control groups, meta-analysis was performed.Results: Overall, 18/295 (6%) screened abstracts were included. Populations, methodology and outcome data were heterogeneous. Common populations included healthy volunteers (9/18; 50%) and those with gonococcal infection (6/18; 33%). Most studies were crossover trials (11/18; 61%) or parallel-arm randomized trials (4/18; 22%). Where pharmacokinetic analyses were performed, addition of probenecid to oral β-lactams increased total AUC (7/7; 100%), Cmax (5/8; 63%) and serum t½ (6/8; 75%). Probenecid improved PTA (2/2; 100%). Meta-analysis of 3105 (2258 intervention, 847 control) patients treated for gonococcal disease demonstrated a relative risk of treatment failure in the random-effects model of 0.33 (95% CI 0.20-0.55; I2 = 7%), favouring probenecid.Conclusions: Probenecid-boosted β-lactam therapy is associated with improved outcomes in gonococcal disease. Pharmacokinetic data suggest that probenecid-boosted oral β-lactam therapy may have a broader application, but appropriately powered mechanistic and efficacy studies are required. [ABSTRACT FROM AUTHOR]

Published
2022
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