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2. Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study

Author

Wozniak, Hannah, Tabah, Alexis, Barbier, François, Ruckly, Stéphane, Loiodice, Ambre, Akova, Murat, Leone, Marc, Conway Morris, Andrew, Bassetti, Matteo, Arvaniti, Kostoula, Ferrer, Ricard, de Bus, Liesbet, Paiva, Jose Artur, Bracht, Hendrik, Mikstacki, Adam, Alsisi, Adel, Valeanu, Liana, Prazak, Josef, Timsit, Jean-François, and Buetti, Niccolò

Published
2024
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6. The rapid detection of respiratory pathogens in critically ill children

Author

Clark, John A., Conway Morris, Andrew, Curran, Martin D., White, Deborah, Daubney, Esther, Kean, Iain R. L., Navapurkar, Vilas, Bartholdson Scott, Josefin, Maes, Mailis, Bousfield, Rachel, Török, M. Estée, Inwald, David, Zhang, Zhenguang, Agrawal, Shruti, Kanaris, Constantinos, Khokhar, Fahad, Gouliouris, Theodore, Baker, Stephen, and Pathan, Nazima

Published
2023
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7. Differentiating infection, colonisation, and sterile inflammation in critical illness: the emerging role of host-response profiling

Author

Jeffrey, Mark, Denny, Kerina J., Lipman, Jeffrey, and Conway Morris, Andrew

Subjects
Microbiota (Symbiotic organisms) -- Health aspects, Inflammation -- Diagnosis, Immune response -- Health aspects, Infection -- Diagnosis, Medical colleges -- Health aspects, Health care industry
Abstract

Infection results when a pathogen produces host tissue damage and elicits an immune response. Critically ill patients experience immune activation secondary to both sterile and infectious insults, with overlapping clinical phenotypes and underlying immunological mechanisms. Patients also undergo a shift in microbiota with the emergence of pathogen-dominant microbiomes. Whilst the combination of inflammation and microbial shift has long challenged intensivists in the identification of true infection, the advent of highly sensitive molecular diagnostics has further confounded the diagnostic dilemma as the number of microbial detections increases. Given the key role of the host immune response in the development and definition of infection, profiling the host response offers the potential to help unravel the conundrum of distinguishing colonisation and sterile inflammation from true infection. This narrative review provides an overview of current approaches to distinguishing colonisation from infection using routinely available techniques and proposes matrices to support decision-making in this setting. In searching for new tools to better discriminate these states, the review turns to the understanding of the underlying pathobiology of the host response to infection. It then reviews the techniques available to assess this response in a clinically applicable context. It will cover techniques including profiling of transcriptome, protein expression, and immune functional assays, detailing the current state of knowledge in diagnostics along with the challenges and opportunities. The ultimate infection diagnostic tool will likely combine an assessment of both host immune response and sensitive pathogen detection to improve patient management and facilitate antimicrobial stewardship., Author(s): Mark Jeffrey [sup.1] [sup.2], Kerina J. Denny [sup.3] [sup.4], Jeffrey Lipman [sup.5] [sup.6] [sup.7], Andrew Conway Morris [sup.1] [sup.2] [sup.8] Author Affiliations: (1) grid.24029.3d, 0000 0004 0383 8386, John [...]

Published
2023
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8. Effect of adequacy of empirical antibiotic therapy for hospital-acquired bloodstream infections on intensive care unit patient prognosis: a causal inference approach using data from the Eurobact2 study

Author

Tabah, Alexis, Lipman, Jeffrey, Pollock, Hamish, Ben Margetts, Udy, Andrew, Young, Meredith, Bhadange, Neeraj, Tyler, Steven, Ledtischke, Anne, Finnis, Mackenzie, Dwivedi, Jyotsna, Saxena, Manoj, Biradar, Vishwanath, Soar, Natalie, Sarode, Vineet, Brewster, David, Regli, Adrian, Weeda, Elizabeth, Ahmed, Samiul, Fourie, Cheryl, Laupland, Kevin, Ramanan, Mahesh, Walsham, James, Meyer, Jason, Litton, Edward, Maria Palermo, Anna, Yap, Timothy, Eroglu, Ege, George Attokaran, Antony, Jaramillo, C'havala, Nafees, Khalid Mk, Nafees, Khalid Mahmood Khan, Aqilah Haji Abd Rashid, Nurhikmahtul, Adi Muhamad Ibnu Walid, Haji, Mon, Tomas, Dhakshina Moorthi, P., Sudhirchandra, Shah, Sridharan, Dhadappa Damodar, Haibo, Qiu, Xie, Jianfeng, Jianfeng, Xie, Wei-Hua, Lu, Zhen, Wang, Qian, Chuanyun, Luo, Jili, Chen, Xiaomei, Wang, Hao, Zhao, Peng, Zhao, Juan, Wusi, Qiu, Mingmin, Chen, Xu, Lei, Yin, Chengfen, Wang, Ruilan, Wang, Jinfeng, Yin, Yongjie, Zhang, Min, Ye, Jilu, Hu, Chungfang, Zhou, Suming, Huang, Min, Yan, Jing, Wang, Yan, Qin, Bingyu, Ye, Ling, Weifeng, Xie, Peije, Li, Geng, Nan, Ling, Lowell, Hayashi, Yoshiro, Karumai, Toshiyuki, Yamasaki, Masaki, Hashimoto, Satoru, Hosokawa, Koji, Makino, Jun, Matsuyoshi, Takeo, Kuriyama, Akira, Shigemitsu, Hidenobu, Mishima, Yuka, Nagashima, Michio, Yoshida, Hideki, Fujitani, Shigeki, Omori, Koichiro, Rinka, Hiroshi, Saito, Hiroki, Atobe, Kaori, Kato, Hideaki, Takaki, Shunsuke, Sulaiman, Helmi, Shahnaz Hasan, M., Fadhil Hadi Jamaluddin, Muhamad, Pheng, Lee See, Visvalingam, Sheshendrasurian, Thing Liew, Mun, Ling Danny Wong, Siong, Khang Fong, Kean, Bt Abdul Rahman, Hamizah, Md Noor, Zuraini, Lee, Kok Tong, Hamid Azman, Abd., Zulfakar Mazlan, Mohd, Ali, Saedah, Hernandez, Aaron Mark, Abello, Anton, Jeon, Kyeongman, Lee, Sang-Min, Park, Sunghoon, Park, Seung Yong, Yoon Lim, Sung, Kwa, Andrea Lay Hoon, Yuan Goh, Qing, Ng, Shin Yi, An Lie, Sui, Junyang Goh, Ken, Yunkai Li, Andrew, Ong, Caroline Yu Ming, Yan Lim, Jia, Lishan Quah, Jessica, Ng, Kangqi, Xiang Long Ng, Louis, Yeh, Tony Yu-Chang, Chang Yeh, Yu, Chou, Nai-Kuan, Cia, Cong-Tat, Hu, Ting-Yu, Kuo, Li-Kuo, Ku, Shih-Chi, Wongsurakiat, Phunsup, Apichatbutr, Yutthana, Chiewroongroj, Supattra, Alsisi, Adel, Nadeem, Rashid, El Houfi, Ashraf, Elhadidy, Amr, Barsoum, Mina, Osman, Nermin, Mostafa, Tarek, Elbahnasawy, Mohamed, Saber, Ahmed, Aldhalia, Amer, Elmandouh, Omar, Elsayed, Ahmed, Elbadawy, Merihan A., Awad, Ahmed K., Hemead, Hanan M., Zand, Farid, Ouhadian, Maryam, Hamid Borsi, Seyed, Mehraban, Zahra, Kashipazha, Davood, Ahmadi, Fatemeh, Savaie, Mohsen, Soltani, Farhad, Rashidi, Mahboobeh, Baghbanian, Reza, Javaherforoosh, Fatemeh, Amiri, Fereshteh, Kiani, Arash, Amin Zargar, Mohammad, Mahmoodpoor, Ata, Aalinezhad, Fatemeh, Dabiri, Gholamreza, Sabetian, Golnar, Sarshad, Hakimeh, Masjedi, Mansoor, Tajvidi, Ramin, Nasirodin (S.M.N.) Tabatabaei, Dr Seyed Mohammad, Ahmed, Abdullah Khudhur, Singer, Pierre, Kagan, Ilya, Rigler, Merav, Belman, Daniel, Levin, Phillip, Harara, Belal, Diab, Adei, Abillama, Fayez, Abilama, Fayez, Ibrahim, Rebecca, Fares, Aya, Elhadi, Muhammed, Buimsaedah, Ahmad, Gamra, Marwa, Aqeelah, Ahmed, Ali Mohammed Ali, Almajdoub, Gaber Sadik Homaidan, Ahmed, Almiqlash, Bushray, Bilkhayr, Hala, Bouhuwaish, Ahmad, Sa Taher, Ahmed, Abdulwahed, Eman, Abousnina, Fathi A., Khaled Hdada, Aisha, Jobran, Rania, Ben Hasan, Hayat, Shaban Ben Hasan, Rabab, Khalid Abidi, Serghini, Issam, Seddiki, Rachid, Boukatta, Brahim, Kanjaa, Nabil, Mouhssine, Doumiri, Ahmed Wajdi, Maazouzi, Dendane, Tarek, Ali Zeggwagh, Amine, Housni, Brahim, Younes, Oujidi, Hachimi, Abdelhamid, Ghannam, A., Belkhadir, Z., Abu Jayyab, Mustafa, Aithssain, Ali, Lance, Marcus, Nissar, Shaikh, Sallam, Hend, Elrabi, Omar, Almekhlafi, Ghaleb A., Awad, Maher, Aljabbary, Ahmed, Karam Chaaban, Mohammad, Abu-Sayf, Natalia, Al-Jadaan, Mohammad, Bakr, Lubna, Mounir Bouaziz, Bouaziz, Mounir, Turki, Olfa, Sellami, Walid, Vidal, Gabriela, Centeno, Pablo, Morvillo, Natalia, Oscar Acevedo, José, Mabel Lopez, Patricia, Fernández, Rubén, Segura, Matías, Aparicio, Marta, Alonzo, Irene, Nuccetelli, Yanina, Montefiore, Pablo, Arias, Mario, Felipe Reyes, Luis, Ñamendys-Silva, Silvio A., Romero-Gonzalez, Juan P., Hermosillo, Mariana, Alejandro Castillo, Roberto, Nicolás Pantoja Leal, Jesús, Garcia Aguilar, Candy, Ocotlan Gonzalez Herrera, Mara, Vladimir Espinoza Villafuerte, Missael, Lomeli-Teran, Manuel, Dominguez-Cherit, Jose G., Davalos-Alvarez, Adrian, Sánchez-Hurtado, Luis, Tejeda-Huezo, Brigitte, Perez-Nieto, Orlando R., Deloya Tomas, Ernesto, De Bus, Liesbet, De Waele, Jan, Francois, Guy, Hollevoet, Isabelle, Denys, Wouter, Bourgeois, Marc, Vanderhaeghen, Sofie F.M., Mesland, Jean-Baptiste, Henin, Pierre, Haentjens, Lionel, Biston, Patrick, Noel, Cindérella, Layos, Nathalie, Misset, Benoît, De Schryver, Nicolas, Serck, Nicolas, Wittebole, Xavier, De Waele, Elisabeth, Opdenacker, Godelive, Kovacevic, Pedja, Zlojutro, Biljana, Ina, Filipovic-Grcic, Custovic, Aida, Filipovic-Grcic, Ina, Radonic, Radovan, Vujaklija Brajkovic, Ana, Persec, Jasminka, Sakan, Sanja, Nikolic, Mario, Lasic, Hrvoje, Leone, Marc, Timsit, Jean-François, Ruppe, Etienne, Ruckly, Stephane, Montravers, Philippe, Arbelot, Charlotte, Patrier, Juliette, Zappela, N., Montravers, P., Dulac, Thierry, Castanera, Jérémy, Auchabie, Johann, Le Meur, Anthony, Marchalot, A., Beuzelin, M., Massri, Alexandre, Guesdon, Charlotte, Escudier, Etienne, Mateu, Philippe, Rosman, Jérémy, Leroy, Olivier, Alfandari, Serge, Nica, Alexandru, Souweine, Bertrand, Coupez, Elisabeth, Duburcq, Thibault, Kipnis, Eric, Bortolotti, Perrine, Le Souhaitier, Mathieu, Mira, Jean-Paul, Garcon, Pierre, Duprey, Matthieu, Thyrault, Martial, Paulet, Rémi, Philippart, François, Tran, Marc, Bruel, Cédric, Weiss, Emmanuel, Janny, Sylvie, Foucrier, Arnaud, Perrigault, Pierre-François, Djanikian, Flora, Barbier, François, Gainnier, Marc, Bourenne, Jérémy, Louis, Guillaume, Smonig, Roland, Argaud, Laurent, Baudry, Thomas, Mekonted Dessap, Armand, Razazi, Keyvan, Kalfon, Pierre, Badre, Gaëtan, Larcher, Romaric, Lefrant, Jean-Yves, Roger, Claire, Sarton, Benjamine, Silva, Stein, Demeret, Sophie, Le Guennec, Loïc, Siami, Shidasp, Aparicio, Christelle, Voiriot, Guillaume, Fartoukh, Muriel, Dahyot-Fizelier, Claire, Imzi, Nadia, Klouche, Kada, Bracht, Hendrik, Hoheisen, Sandra, Bloos, Frank, Thomas-Rueddel, Daniel, Petros, Sirak, Pasieka, Bastian, Dubler, Simon, Schmidt, Karsten, Gottschalk, Antje, Wempe, Carola, Lepper, Philippe, Metz, Carlos, Viderman, Dmitriy, Umbetzhanov, Yerlan, Mugazov, Miras, Bazhykayeva, Yelena, Kaligozhin, Zhannur, Babashev, Baurzhan, Merenkov, Yevgeniy, Temirov, Talgat, Arvaniti, Kostoula, Smyrniotis, Dimitrios, Psallida, Vasiliki, Fildisis, Georgios, Soulountsi, Vasiliki, Kaimakamis, Evangelos, Iasonidou, Cristina, Papoti, Sofia, Renta, Foteini, Vasileiou, Maria, Romanou, Vasiliki, Koutsoukou, Vasiliki, Kristina Matei, Mariana, Moldovan, Leora, Karaiskos, Ilias, Paskalis, Harry, Marmanidou, Kyriaki, Papanikolaou, M., Kampolis, C., Oikonomou, Marina, Kogkopoulos, Evangelos, Nikolaou, Charikleia, Sakkalis, Anastasios, Chatzis, Marinos, Georgopoulou, Maria, Efthymiou, Anna, Chantziara, Vasiliki, Sakagianni, Aikaterini, Athanasa (Athanassa), Zoi (Zoe), Papageorgiou, Eirini, Ali, Fadi, Dimopoulos, Georges, Panagiota Almiroudi, Mariota, Malliotakis, Polychronis, Marouli, Diamantina, Theodorou, Vasiliki, Retselas, Ioannis, Kouroulas, Vasilios, Papathanakos, Georgios, Bassetti, Matteo, Giacobbe, Daniele, Montrucchio, Giorgia, Sales, Gabriele, De Pascale, Gennaro, Maria Montini, Luca, Carelli, Simone, Vargas, Joel, Di Gravio, Valentina, Roberto Giacobbe, Daniele, Gratarola, Angelo, Porcile, Elisa, Mirabella, Michele, Daroui, Ivan, Lodi, Giovanni, Zuccaro, Francesco, Grazia Schlevenin, Maria, Pelosi, Paolo, Battaglini, Denise, Cortegiani, Andrea, Ippolito, Mariachiara, Bellina, Davide, Di Guardo, Andrea, Pelagalli, Lorella, Covotta, Marco, Rocco, Monica, Fiorelli, Silvia, Cotoia, Antonella, Chiara Rizzo, Anna, Adam Mikstacki, Mikstacki, Adam, Tamowicz, Barbara, Kaptur Komorowska, Irmina, Szczesniak, Anna, Bojko, Jozef, Kotkowska, Anna, Walczak-Wieteska, Paulina, Wasowska, Dominika, Nowakowski, Tomasz, Broda, Hanna, Mariusz Peichota, Assoc, Pietraszek-Grzywaczewska, Iwona, Martin-Loeches, Ignacio, Bisanti, Alessandra, Paiva, José Artur, Póvoa, Pedro, Cartoze, Nuno, Pereira, Tiago, Guimarães, Nádia, Alves, Madalena, Josefina Pinheiro Marques, Ana, Rios Pinto, Ana, Krystopchuk, Andriy, Teresa, Ana, Manuel Pereira de Figueiredo, António, Botelho, Isabel, Duarte, Tiago, Costa, Vasco, Pedro Cunha, Rui, Molinos, Elena, Tito da Costa, Ledo, Sara, Queiró, Joana, Pascoalinho, Dulce, Nunes, Cristina, Pedro Moura, José, Pereira, Énio, Carvalho Mendes, António, Valeanu, Liana, Bubenek-Turconi, Serban, Marina Grintescu, Ioana, Cobilinschi, Cristian, Carmen Filipescu, Daniela, Elena Predoi, Cornelia, Tomescu, Dana, Popescu, Mihai, Marcu, Alexandra, Grigoras, Ioana, Lungu, Olguta, Gritsan, Alexey, Anderzhanova, Anastasia, Meleshkina, Yulia, Magomedov, Marat, Zubareva, Nadezhda, Tribulev, Maksim, Gaigolnik, Denis, Eremenko, Aleksandr, Vistovskaya, Natala, Chukina, Maria, Belskiy, Vladislav, Furman, Mikhail, Ferrer Rocca, Ricard, Martinez, Maria, Casares, Vanessa, Mellado Artigas, Ricard, Vera, Paula, Flores, Matias, Amador Amerigo, Joaquin, Gracia Arnillas, Maria Pilar, Munoz Bermudez, Rosana, Armestar, Fernando, Catalan, Beatriz, Roig, Regina, Raguer, Laura, Dolores Quesada, María, Diaz Santos, Emilio, Gomà, Gemma, Ubeda, Alejandro, Salgado, Maria, Forcelledo Espina, Lorena, Garcia Prieto, Emilio, Asensio, Mj, Rodriguez, M., Maseda, Dr Emilio, Suarez De La Rica, Alejandro, Ignacio Ayestaran, J., Novo, Mariana, Blasco-Navalpotro, Miguel Angel, Orejas Gallego, Alberto, Sjovall, Fredrik, Sjövall, Fredrik, Spahic, Dzana, Johan Svensson, Carl, Haney, Michael, Edin, Alicia, Åkerlund, Joyce, De Geer, Lina, Prazak, Josef, Buetti, Niccolò, Jakob, Stephan, Pagani, Jl, Abed-Maillard, S., Akova, Murat, Tarık Aslan, Abdullah, Tarik Aslan, Abdullah, Timuroglu, Arif, Kocagoz, Sesin, Kusoglu, Hulya, Mehtap, Selcuk, Ceyhun, Solakoğlu, Altintas, Dr. Neriman Defne, Talan, Leyla, Kayaaslan, Bircan, Kaya Kalem, Ayşe, Kurt, Dr. Ibrahim, Telli, Murat, Ozturk, Barcin, Erol, Çiğdem, Dindar Demiray, Emine Kubra, Çolak, Sait, Akbas, Türkay, Dr. Kursat Gundogan, Sari, Ali, Agalar, Canan, Çolak, Onur, Baykam, Nurcan (N), Akdogan, Ozlem (O), Yilmaz, Mesut, Tunay, Burcu, Cakmak, Rumeysa, Saltoglu, Nese, Karaali, Ridvan, Iftihar Koksal, Firdevs Aksoy, Eroglu, Ahmet, Tolga Saracoglu, Kemal, Bilir, Yeliz, Guzeldag, Seda, Ersoz, Gulden, Evik, Guliz, Sungurtekin, Hulya, Ozgen, Cansu, Erdoğan, Cem, Gürbüz, Yunus, Altin, Nilgün, Bayindir, Yasar, Ersoy, Yasemin, Goksu, Senay, Akyol, Ahmet, Dr, Kartal, Batirel, Ayse, Cagan Aktas, Sabahat, Morris, Andrew Conway, Conway Morris, Andrew, Routledge, Matthew, Ercole, Ari, Antcliffe, David, Rojo, Roceld, Tizard, Kate, Faulkner, Maria, Cowton, Amanda, Kent, Melanie, Raj, Ashok, Zormpa, Artemis, Tinaslanidis, George, Khade, Reena, Torlinski, Tomasz, Mulhi, Randeep, Goyal, Shraddha, Bajaj, Manan, Soltan, Marina, Yonan, Aimee, Dolan, Rachael, Johnson, Aimee, Macfie, Caroline, Lennard, James, Templeton, Maie, Sousa Arias, Sonia, Franke, Uwe, Hugill, Keith, Angell, Hollie, Benjamin J Parcell, Cobb, Katherine, Cole, Stephen, Smith, Tim, Graham, Clive, Cerman, Jaroslav, Keegan, Allison, Ritzema, Jenny, Sanderson, Amanda, Roshdy, Ashraf, Szakmany, Tamas, Baumer, Tom, Longbottom, Rebecca, Hall, Daniel, Tatham, Kate, Loftus, S., Husain, A., Black, E., Jhanji, S., Rao Baikady, R., Mcguigan, Peter, Mckee, Rachel, Kannan, Santhana, Antrolikar, Supriya, Marsden, Nicholas, Della Torre, Valentina, Banach, Dorota, Zaki, Ahmed, Jackson, Matthew, Chikungwa, Moses, Attwood, Ben, Patel, Jamie, Rebecca E Tilley, Humphreys, Sally K., Jean Renaud, Paul, Sokhan, Anton, Burma, Yaroslava, Sligl, Wendy, Baig, Nadia, McCoshen, Lorena, Kutsogiannis, Demetrios J., Thompson, Patricia, Hewer, Tayne, Rabbani, Raihan, Huq, Shihan Mahmud Redwanul, Hasan, Rajib, Motiul Islam, Mohammad, Gurjar, Mohan, Baronia, Arvind, Kothari, Nikhil, Sharma, Ankur, Karmakar, Saurabh, Sharma, Priya, Nimbolkar, Janardan, Samdani, Pratit, Vaidyanathan, R., Ahmedi Rubina, Noor, Jain, Nikhilesh, Pahuja, Madhumati, Singh, Ritu, Shekhar, Saurav, Syed, Nabeel Muzaffar, Ozair, Ahmad, Sarwar Siddiqui, Suhail, Bose, Payel, Datta, Avijatri, Rathod, Darshana, Patel, Mayur, MK, Renuka, Sailaja, K Baby, Dsilva, Carol, Chandran, Jagadish, Ghosh, Pralay, Mukherjee, Sudipta, Sheshala, Kaladhar, Chandra Misra, Krushna, Adekola, Oyebola O., Yusuf Yakubu, Saidu, Mgbosoro Ugwu, Euphemia, Olatosi, John (O), Desalu, Ibironke, Asiyanbi, Gabriel, Oladimeji, Motunrayo, Idowu, Olusola, Adeola, Fowotade, Mer, Mervyn, Mc Cree, Melanie, El Sanousi, Dr. Bashir, Adil Ali Karar, Ali, Saidahmed, Elfayadh, Hamid, Hytham K.S., Loiodice, Ambre, Bailly, Sébastien, Ruckly, Stéphane, Buetti, Niccolò, Barbier, François, Staiquly, Quentin, and Timsit, Jean-François

Published
2024
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9. How to use biomarkers of infection or sepsis at the bedside: guide to clinicians

Author

Póvoa, Pedro, Coelho, Luís, Dal-Pizzol, Felipe, Ferrer, Ricard, Huttner, Angela, Conway Morris, Andrew, and Nobre, Vandack

Subjects
Infection -- Care and treatment -- Diagnosis, Medical colleges -- Health aspects -- Usage, C-reactive protein -- Health aspects -- Usage, Antibiotics -- Usage, Biological markers -- Health aspects -- Usage, Health care industry
Abstract

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In this context, biomarkers could be considered as indicators of either infection or dysregulated host response or response to treatment and/or aid clinicians to prognosticate patient risk. More than 250 biomarkers have been identified and evaluated over the last few decades, but no biomarker accurately differentiates between sepsis and sepsis-like syndrome. Published data support the use of biomarkers for pathogen identification, clinical diagnosis, and optimization of antibiotic treatment. In this narrative review, we highlight how clinicians could improve the use of pathogen-specific and of the most used host-response biomarkers, procalcitonin and C-reactive protein, to improve the clinical care of patients with sepsis. Biomarker kinetics are more useful than single values in predicting sepsis, when making the diagnosis and assessing the response to antibiotic therapy. Finally, integrated biomarker-guided algorithms may hold promise to improve both the diagnosis and prognosis of sepsis. Herein, we provide current data on the clinical utility of pathogen-specific and host-response biomarkers, offer guidance on how to optimize their use, and propose the needs for future research., Author(s): Pedro Póvoa [sup.1] [sup.2] [sup.3], Luís Coelho [sup.1] [sup.3], Felipe Dal-Pizzol [sup.4] [sup.5], Ricard Ferrer [sup.6] [sup.7], Angela Huttner [sup.8] [sup.9], Andrew Conway Morris [sup.10] [sup.11] [sup.12], Vandack Nobre [...]

Published
2023
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10. Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study

Author

Tabah, Alexis, Buetti, Niccolò, Staiquly, Quentin, Ruckly, Stéphane, Akova, Murat, Aslan, Abdullah Tarik, Leone, Marc, Conway Morris, Andrew, Bassetti, Matteo, Arvaniti, Kostoula, Lipman, Jeffrey, Ferrer, Ricard, Qiu, Haibo, Paiva, José-Artur, Povoa, Pedro, De Bus, Liesbet, De Waele, Jan, Zand, Farid, Gurjar, Mohan, Alsisi, Adel, Abidi, Khalid, Bracht, Hendrik, Hayashi, Yoshiro, Jeon, Kyeongman, Elhadi, Muhammed, Barbier, François, and Timsit, Jean-François

Published
2023
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11. Compartmentalisation of immune responses in critical illness: does it matter?

Author

Conway Morris, Andrew, Rynne, Jennifer, and Shankar-Hari, Manu

Subjects
Medical research, Medicine, Experimental, Inflammation, Immune response, Health care industry
Abstract

Author(s): Andrew Conway Morris [sup.1] [sup.2] [sup.3], Jennifer Rynne [sup.4], Manu Shankar-Hari [sup.4] Author Affiliations: (1) grid.5335.0, 0000000121885934, Division of Anaesthesia, Department of Medicine, University of Cambridge, Level 4 Addenbrooke's [...]

Published
2022
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13. Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study

Author

Buetti, Niccolò, Tabah, Alexis, Loiodice, Ambre, Ruckly, Stéphane, Aslan, Abdullah Tarik, Montrucchio, Giorgia, Cortegiani, Andrea, Saltoglu, Nese, Kayaaslan, Bircan, Aksoy, Firdevs, Murat, Akova, Akdoğan, Özlem, Saracoglu, Kemal Tolga, Erdogan, Cem, Leone, Marc, Ferrer, Ricard, Paiva, José-Artur, Hayashi, Yoshiro, Ramanan, Mahesh, Conway Morris, Andrew, Barbier, François, and Timsit, Jean-François

Published
2022
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15. Neutrophil extracellular traps protect the kidney from ascending infection and are required for a positive leukocyte dipstick test.

Author

Stewart, Andrew P., Loudon, Kevin W., Routledge, Matthew, Lee, Colin Y. C., Trotter, Patrick, Richoz, Nathan, Gillman, Eleanor, Antrobus, Robin, Mccaffrey, James, Posner, David, Conway Morris, Andrew, Karet Frankl, Fiona E., and Clatworthy, Menna R.

Subjects
ARGININE deiminase, ESCHERICHIA coli, GENOME-wide association studies, URINARY organs, CLINICAL medicine, URINARY tract infections
Abstract

Lower urinary tract infection (UTI) is common but only rarely complicated by pyelonephritis. However, the mechanisms preventing extension to the kidney are unclear. Here, we identified neutrophil extracellular traps (NETs) in healthy human urine that provide an antibacterial defense strategy within the urinary tract. In both in vivo murine models of UTI where uropathogenic E. coli are inoculated into the bladder and ex vivo human urine models, NETs interacted with uromodulin to form large webs that entrapped the bacteria. Peptidyl arginine deiminase 4 (PADI4) inhibition in mice blocked NETosis and resulted in progression of cystitis into pyelonephritis, suggesting that NETosis of urinary neutrophils acts to prevent bacterial ascent into the kidney. Analysis of UK Biobank data revealed that genetic variants in PADI4 that associated with increased risk of rheumatoid arthritis in multiple genome-wide association studies were consistently associated with reduced susceptibility to UTI. Last, we showed that urine dipstick testing for leukocyte esterase was negative in the presence of intact blood neutrophils but became positive when neutrophils were stimulated to NET, and this could be prevented by selective PADI4 inhibition, demonstrating that this test does not detect absolute neutrophil count, as has long been assumed, but specifically detects neutrophils that have undergone NETosis. These findings highlight the role of NETosis in preventing ascending infections in the urinary tract and improve our understanding of one of the most common clinical tests in medicine. Editor's summary: Lower urinary tract infections (UTIs) rarely ascend to the kidney, but the mechanisms underlying this protection are not fully understood. Here, Stewart and colleagues identified neutrophil extracellular traps (NETs) in the urine of healthy individuals that interacted with uromodulin to form webs and entrap bacteria. Inhibition of peptidyl arginine deiminase type 4 (PADI4) reduced NETosis and increased pyelonephritis in mice challenged with uropathogenic E. coli, and an analysis of UK Biobank data revealed that variants in PADI4 were associated with reduced incidence of UTI. The authors also showed that the leukocyte esterase urine dipstick test specifically detects the presence of NETosing neutrophils, highlighting the importance of NETs in both the prevention and diagnosis of UTI. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Published
2024
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18. Post-mortem dissection of COVID-19: a pathogenic role for macrophages?

Author

Velu, Prasad P., Lucas, Christopher D., and Conway Morris, Andrew

Subjects
Medical research, Medicine, Experimental, Respiratory agents, Macrophages, Surgery, Health care industry
Abstract

Author(s): Prasad P. Velu [sup.1] [sup.2], Christopher D. Lucas [sup.1] [sup.2] [sup.3], Andrew Conway Morris [sup.4] [sup.5] Author Affiliations: (1) grid.4305.2, 0000 0004 1936 7988, Centre for Inflammation Research, Edinburgh [...]

Published
2021
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22. Contributors

Author

Amin, Pravin, primary, Aríztegui, Miguel Moreno, additional, Baldisseri, Marie R., additional, Beer, Natalia Largaespada, additional, Calgua, Erwin, additional, Delgado, María Cruz Martín, additional, Dias, Fernando Suparregui, additional, Díaz, Marilia, additional, Farmer, Drew, additional, Fernández, Patxi Pérez, additional, Godinez, Daniel, additional, Gotur, Deepa B., additional, Gurav, Sushma, additional, Hall, Erin, additional, Harahus, John M., additional, Hidalgo, Allyson, additional, Hidalgo, Benjamin, additional, Hidalgo, Jorge, additional, Hsu, Steven H., additional, Kaplan, Lewis J., additional, Logue, Ryan J., additional, Lynch, Deena, additional, MacDonald, Alexis U., additional, MacDonald, William G., additional, Marín-García, Gerald, additional, Mendes, Ciro Leite, additional, Conway Morris, Andrew, additional, Ogunbiyi, Obashina, additional, Pascual, Jose, additional, Pérez, Lorna, additional, Pérez-Fernández, Javier, additional, Reed, Mary Jane, additional, Rodríguez-Vega, Gloria, additional, Rosa, Regis Goulart, additional, Singh, Michael, additional, Steuer, Jacqueline Y., additional, Suresh, Rishi, additional, Taha, Ahmed Reda, additional, Tong, Allison, additional, Woc-Colburn, Laila, additional, Wu, Edwin, additional, and Zirpe, Kapil, additional

Published
2022
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23. Personal protective equipment and intensive care unit healthcare worker safety in the COVID-19 era (PPE-SAFE): An international survey

Author

Tabah, Alexis, Ramanan, Mahesh, Laupland, Kevin B., Buetti, Niccolò, Cortegiani, Andrea, Mellinghoff, Johannes, Conway Morris, Andrew, Camporota, Luigi, Zappella, Nathalie, Elhadi, Muhammed, Povoa, Pedro, Amrein, Karin, Vidal, Gabriela, Derde, Lennie, Bassetti, Matteo, Francois, Guy, Ssi yan kai, Nathalie, and De Waele, Jan J.

Published
2020
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24. Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2): a randomised controlled trial and process evaluation

Author

Hellyer, Thomas P, McAuley, Daniel F, Walsh, Timothy S, Anderson, Niall, Conway Morris, Andrew, Singh, Suveer, Dark, Paul, Roy, Alistair I, Perkins, Gavin D, McMullan, Ronan, Emerson, Lydia M, Blackwood, Bronagh, Wright, Stephen E, Kefala, Kallirroi, O'Kane, Cecilia M, Baudouin, Simon V, Paterson, Ross L, Rostron, Anthony J, Agus, Ashley, Bannard-Smith, Jonathan, Robin, Nicole M, Welters, Ingeborg D, Bassford, Christopher, Yates, Bryan, Spencer, Craig, Laha, Shondipon K, Hulme, Jonathan, Bonner, Stephen, Linnett, Vanessa, Sonksen, Julian, Van Den Broeck, Tina, Boschman, Gert, Keenan, DW James, Scott, Jonathan, Allen, A Joy, Phair, Glenn, Parker, Jennie, Bowett, Susan A, and Simpson, A John

Published
2020
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26. Obesity Is Associated with Attenuated Tissue Immunity in COVID-19

Author

Guo, Shuang A, Bowyer, Georgina S, Ferdinand, John R, Maes, Mailis, Tuong, Zewen K, Gillman, Eleanor, Liao, Mingfeng, Lindeboom, Rik GH, Yoshida, Masahiro, Worlock, Kaylee, Gopee, Hudaa, Stephenson, Emily, Gao, Catherine A, Lyons, Paul A, Smith, Kenneth GC, Haniffa, Muzlifah, Meyer, Kerstin B, Nikolić, Marko Z, Zhang, Zheng, Wunderink, Richard G, Misharin, Alexander V, Dougan, Gordon, Navapurkar, Vilas, Teichmann, Sarah A, Conway Morris, Andrew, Clatworthy, Menna R, Guo, Shuang A [0000-0002-1712-9180], Bowyer, Georgina S [0000-0002-2058-4045], Ferdinand, John R [0000-0003-0936-0128], Maes, Mailis [0000-0002-0266-6557], Tuong, Zewen K [0000-0002-6735-6808], Gillman, Eleanor [0000-0002-4221-7270], Lindeboom, Rik GH [0000-0002-3660-504X], Yoshida, Masahiro [0000-0002-3521-5322], Worlock, Kaylee [0000-0002-5656-7634], Gopee, Hudaa [0000-0001-8507-5682], Stephenson, Emily [0000-0002-4244-4019], Gao, Catherine A [0000-0001-5576-3943], Lyons, Paul A [0000-0001-7035-8997], Smith, Kenneth GC [0000-0003-3829-4326], Haniffa, Muzlifah [0000-0002-3927-2084], Meyer, Kerstin B [0000-0001-5906-1498], Nikolić, Marko Z [0000-0001-6304-6848], Zhang, Zheng [0000-0002-3544-1389], Wunderink, Richard G [0000-0002-8527-4195], Misharin, Alexander V [0000-0003-2879-3789], Dougan, Gordon [0000-0003-0022-965X], Navapurkar, Vilas [0000-0002-3610-3568], Teichmann, Sarah A [0000-0002-6294-6366], Conway Morris, Andrew [0000-0002-3211-3216], Clatworthy, Menna R [0000-0002-3340-9828], and Apollo - University of Cambridge Repository

Subjects
Adult, Pulmonary and Respiratory Medicine, obesity, Pediatric Obesity, SARS-CoV-2, COVID-19, Critical Care and Intensive Care Medicine, single-cell RNA sequencing, type-I interferon, Interferon Type I, Leukocytes, Mononuclear, bronchoalveolar lavage, Humans, Child, Lung
Abstract

Rationale: Obesity affects 40% of U.S. adults, is associated with a proinflammatory state, and presents a significant risk factor for the development of severe coronavirus disease (COVID-19). To date, there is limited information on how obesity might affect immune cell responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: To determine the impact of obesity on respiratory tract immunity in COVID-19 across the human lifespan. Methods: We analyzed single-cell transcriptomes from BAL in three ventilated adult cohorts with (n = 24) or without (n = 9) COVID-19 from nasal immune cells in children with (n = 14) or without (n = 19) COVID-19, and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (n = 42), comparing obese and nonobese subjects. Measurements and Main Results: Surprisingly, we found that obese adult subjects had attenuated lung immune or inflammatory responses in SARS-CoV-2 infection, with decreased expression of IFN-α, IFN-γ, and TNF-α (tumor necrosis factor α) response gene signatures in almost all lung epithelial and immune cell subsets, and lower expression of IFNG and TNF in specific lung immune cells. Peripheral blood immune cells in an independent adult cohort showed a similar but less marked reduction in type-I IFN and IFNγ response genes, as well as decreased serum IFNα, in obese patients with SARS-CoV-2. Nasal immune cells from obese children with COVID-19 also showed reduced enrichment of IFN-α and IFN-γ response genes. Conclusions: These findings show blunted tissue immune responses in obese patients with COVID-19, with implications for treatment stratification, supporting the specific application of inhaled recombinant type-I IFNs in this vulnerable subset.

Published
2023

27. Ventilator-associated pneumonia in critically ill patients with COVID-19

Author

Maes, Mailis, Higginson, Ellen, Pereira-Dias, Joana, Curran, Martin D., Parmar, Surendra, Khokhar, Fahad, Cuchet-Lourenço, Delphine, Lux, Janine, Sharma-Hajela, Sapna, Ravenhill, Benjamin, Hamed, Islam, Heales, Laura, Mahroof, Razeen, Soderholm, Amelia, Forrest, Sally, Sridhar, Sushmita, Brown, Nicholas M., Baker, Stephen, Navapurkar, Vilas, Dougan, Gordon, Bartholdson Scott, Josefin, and Conway Morris, Andrew

Published
2021
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28. Antimicrobial-associated harm in critical care: a narrative review

Author

Arulkumaran, Nishkantha, Routledge, Matthew, Schlebusch, Sanmarié, Lipman, Jeffrey, and Conway Morris, Andrew

Subjects
Methicillin -- Usage, Rationing -- Usage, Health care industry
Abstract

The belief that, for the individual patient, the benefit of prompt and continued use of antimicrobials outweighs any potential harm is a significant barrier to improved stewardship of these vital agents. Antimicrobial stewardship may be perceived as utilitarian rationing, seeking to preserve the availability of effective antimicrobials by limiting the development of resistance in a manner which could conflict with the immediate treatment of the patient in need. This view does not account for the growing evidence of antimicrobial-associated harm to individual patients. This review sets out the evidence for antimicrobial-associated harm and how this should be balanced with the need for prompt and appropriate therapy in infection. It describes the mechanisms by which antimicrobials may harm patients including: mitochondrial toxicity; immune cell toxicity; adverse drug reactions; selection of resistant organisms within a given patient; and disruption of the microbiome. Finally, the article indicates how the harms of antimicrobials may be mitigated and identifies areas for research and development in this field., Author(s): Nishkantha Arulkumaran [sup.1], Matthew Routledge [sup.2] [sup.3], Sanmarié Schlebusch [sup.4] [sup.5], Jeffrey Lipman [sup.4] [sup.6] [sup.7], Andrew Conway Morris [sup.8] [sup.9] Author Affiliations: (1) grid.83440.3b, 0000000121901201, Bloomsbury Institute for [...]

Published
2020
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29. Impact of supplementary air filtration on aerosols and particulate matter in a UK hospital ward: a case study

Author

Butler, Matthew B, Sloof, Darren, Peters, Christine, Conway Morris, andrew, Gouliouris, Theo, Thaxter, Rachel, Keevil, Victoria L, Beggs, Clive, Keevil, Victoria [0000-0001-6148-0640], and Apollo - University of Cambridge Repository

Subjects
Air filtration, Medicine for older people, Microbiology (medical), Cross Infection, SARS-CoV-2, HEPA filters, COVID-19, Respiratory Aerosols and Droplets, General Medicine, Carbon Dioxide, Hospitals, United Kingdom, Infectious Diseases, Air Pollution, Indoor, Airborne, Humans, Particulate Matter, Aged
Abstract

Background Aerosol spread of SARS-CoV-2 is a major problem in hospitals, leading to an increase in supplementary HEPA filtration aimed at reducing nosocomial transmission. We report a natural experiment that occurred when an air-cleaning unit (ACU) on a medicine for older people ward was accidentally switched off while being commissioned. Aim To assess aerosol transport within the ward and determine whether the ACU reduced airborne particulate matter (PM) levels. Methods An ACU was placed in a ward comprising two 6-bedded bays plus three single-bed isolation rooms, which had previously experienced several COVID-19 outbreaks. During commissioning, real-time measurements of key indoor air quality parameters (PM1-10, CO2, temperature and humidity) were collected from multiple sensors over two days. During this period, the ACU was accidentally switched off for approximately 7 hours, allowing the impact of the intervention on PM to be assessed. Findings The ACU greatly reduced PM counts (e.g. PM1: 65.5 – 78.2%) throughout the ward (p2m) transmission. The ACU greatly reduced PM levels throughout the ward space indicating its potential as an effective intervention to reduce the risk posed by infectious airborne particles.

Published
2023

31. Core Outcomes Set for Trials in People With Coronavirus Disease 2019

Author

Tong, Allison, Elliott, Julian H., Azevedo, Luciano Cesar, Baumgart, Amanda, Bersten, Andrew, Cervantes, Lilia, Chew, Derek P., Cho, Yeoungjee, Cooper, Tess, Crowe, Sally, Douglas, Ivor S., Evangelidis, Nicole, Flemyng, Ella, Hannan, Elyssa, Horby, Peter, Howell, Martin, Lee, Jaehee, Liu, Emma, Lorca, Eduardo, Lynch, Deena, Marshall, John C., Matus Gonzalez, Andrea, McKenzie, Anne, Manera, Karine E., McLeod, Charlie, Mehta, Sangeeta, Mer, Mervyn, Conway Morris, Andrew, Nseir, Saad, Povoa, Pedro, Reid, Mark, Sakr, Yasser, Shen, Ning, Smyth, Alan R., Snelling, Tom, Strippoli, Giovanni FM, Teixeira-Pinto, Armando, Torres, Antoni, Turner, Tari, Viecelli, Andrea K., Webb, Steve, Williamson, Paula R., Woc-Colburn, Laila, Zhang, Junhua, and Craig, Jonathan C.

Published
2020
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32. International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019

Author

Evangelidis, Nicole, Tong, Allison, Howell, Martin, Teixeira-Pinto, Armando, Elliott, Julian H., Azevedo, Luciano Cesar, Bersten, Andrew, Cervantes, Lilia, Chew, Derek P., Crowe, Sally, Douglas, Ivor S., Flemyng, Ella, Horby, Peter, Lee, Jaehee, Lorca, Eduardo, Lynch, Deena, Marshall, John C., McKenzie, Anne, Mehta, Sangeeta, Mer, Mervyn, Conway Morris, Andrew, Nseir, Saad, Povoa, Pedro, Reid, Mark, Sakr, Yasser, Shen, Ning, Smyth, Alan R., Snelling, Tom, Strippoli, Giovanni F. M., Torres, Antoni, Turner, Tari, Webb, Steve, Williamson, Paula R., Woc-Colburn, Laila, Zhang, Junhua, Baumgart, Amanda, Cabrera, Sebastian, Cho, Yeoungjee, Cooper, Tess, Guha, Chandana, Liu, Emma, Gonzalez, Andrea Matus, McLeod, Charlie, Natale, Patrizia, Saglimbene, Valeria, Viecelli, Andrea K., and Craig, Jonathan C.

Published
2020
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33. Complement-mediated neutrophil dysfunction in critical illness

Author

Conway Morris, Andrew

Subjects
616
Abstract

Critical illness, constituting an acute illness or injury resulting in organ dysfunction and failure, is associated with a profound, systemic activation of the immune system and inflammation-mediated organ damage. However, critically ill patients suffer a high rate of nosocomial infection with secondary sepsis being a common cause of death. This high prevalence of secondary infections argues for the influence of an immune suppression that may, at first glance, appear paradoxical in light of the pro-inflammatory nature of critical illness. Although immune cell hypo-function has been noted in clinical and experimental critical illness, the mediators of these effects remain poorly defined. In this thesis, neutrophil function was examined in the context of clinically suspected ventilator-associated pneumonia, a common and lethal intensive care acquired infection (ICU-AI), This demonstrated impaired bactericidal functions (phagocytosis and reactive oxygen species production) in neutrophils from both the peripheral and pulmonary compartments; however there was ample evidence of coexistent neutrophil activation (both cell surface markers and soluble mediators) and inflammation. An investigation of possible mediators of neutrophil dysfunction revealed a major role for C5a, the pro-inflammatory anaphylotoxin derived from complement C5. Recombinant C5a applied to healthy donor neutrophils was able to drive the defect in phagocytosis by phospho-inositol 3 kinase delta-mediated inhibition of RhoA and subsequent down regulation of actin polymerisation. The defects in RhoA and actin function were reversible with granulocyte-macrophage colony stimulating factor (GM-CSF) applied ex vivo, restoring phagocytic function to normal. Similar defects in RhoA and actin, and effective treatment with GMCSF, were found in neutrophils from critically ill patients. In a second cohort of critically ill adults recruited prior to developing any ICU-AI, C5a-mediated neutrophil dysfunction was an independent predictor of acquiring nosocomial infection, being associated with a 5.4 fold increased risk (95% Confidence interval 1.4-21.0). The same cohort of patients also displayed two other features of immune suppression, namely monocyte deactivation and elevated proportions of regulatory T-cells that were also associated with increased risk of infection (relative risk of infection 3 (95%CI1.3-6.9) and 2.4 (95%CI1.3-4.2) respectively). These measures acted additively with C5a-mediated dysfunction, those with no immune impairment having a zero rate of nosocomial infection with cumulative increases in impairments being associated with a progressive increase in risk of infection (p=0.0004 by Chi squared for trend). In conclusion, critical illness is characterised by a complex inflammatory state with features of simultaneous hyper- and hypoactivation. This remarkable duality is illustrated by the ability of a proinflammatory molecule, C5a, to drive neutrophil dysfunction, with this dysfunction being associated with a serious adverse event-nosocomial infection.

Published
2011

35. Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study

Author

Shankar-Hari, Manu, Datta, Deepankar, Wilson, Julie, Assi, Valentina, Stephen, Jacqueline, Weir, Christopher J., Rennie, Jillian, Antonelli, Jean, Bateman, Anthony, Felton, Jennifer M., Warner, Noel, Judge, Kevin, Keenan, Jim, Wang, Alice, Burpee, Tony, Brown, Alun K., Lewis, Sion M., Mare, Tracey, Roy, Alistair I., Wright, John, Hulme, Gillian, Dimmick, Ian, Gray, Alasdair, Rossi, Adriano G., Simpson, A. John, Conway Morris, Andrew, and Walsh, Timothy S.

Published
2018
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36. Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study

Author

Rashidi, Mahboobeh, Hamid, Hytham K S, Saidahmed, Elfayadh, Karar, Ali Adil Ali, Mc Cree, Melanie, Adeola, Fowotade, Idowu, Olusola, Oladimeji, Motunrayo, Asiyanbi, Gabriel, Desalu, Ibironke, Olatosi, John O, Ugwu, Euphemia Mgbosoro, Yakubu, Saidu Yusuf, Misra, Krushna Chandra, Sheshala, Kaladhar, Mukherjee, Sudipta, Ghosh, Pralay, Chandran, Jagadish, Dsilva, Carol, Baby, Sailaja K, Renuka, M K, Patel, Mayur, Rathod, Darshana, Datta, Avijatri, Bose, Payel, Siddiqui, Suhail Sarwar, Ozair, Ahmad, Muzaffar, Syed Nabeel, Shekhar, Saurav, Singh, Ritu, Pahuja, Madhumati, Jain, Nikhilesh, Rubina, Noor Ahmedi, Vaidyanathan, R, Samdani, Pratit, Nimbolkar, Janardan, Sharma, Priya, Karmakar, Saurabh, Sharma, Ankur, Kothari, Nikhil, Baronia, Arvind, Gurjar, Mohan, Islam, Mohammad Motiul, Hasan, Rajib, Huq, Shihan Mahmud Redwanul, Rabbani, Raihan, Hewer, Tayne, Thompson, Patricia, Sligl, Wendy, Kutsogiannis, Demetrios J, McCoshen, Lorena, Baig, Nadia, Burma, Yaroslava, Sokhan, Anton, Renaud, Paul Jean, Humphreys, Miss Sally K, Tilley, Rebecca E, Patel, Jamie, Attwood, Ben, Chikungwa, Moses, Jackson, Matthew, Zaki, Ahmed, Banach, Dorota, Torre, Valentina Della, Marsden, Nicholas, Antrolikar, Supriya, Kannan, Santhana, Mckee, Rachel, Mcguigan, Peter, Baikady, R Rao, Jhanji, S, Black, E, Husain, A, Loftus, S, Tatham, Kate, Hall, Daniel, Longbottom, Rebecca, Baumer, Tom, Szakmany, Tamas, Roshdy, Ashraf, Sanderson, Amanda, Ritzema, Jenny, Keegan, Allison, Cerman, Jaroslav, Graham, Clive, Smith, Tim, Cole, Stephen, Cobb, Katherine, Parcell, Benjamin J, Angell, Hollie, Hugill, Keith, Franke, Uwe, Arias, Sonia Sousa, Templeton, Maie, Lennard, James, Macfie, Caroline, Johnson, Aimee, Dolan, Rachael, Yonan, Aimee, Soltan, Marina, Bajaj, Manan, Goyal, Shraddha, Mulhi, Randeep, Torlinski, Tomasz, Khade, Reena, Tinaslanidis, George, Zormpa, Artemis, Raj, Ashok, Kent, Melanie, Cowton, Amanda, Faulkner, Maria, Tizard, Kate, Rojo, Roceld, Antcliffe, David, Ercole, Ari, Morris, Andrew Conway, Routledge, Matthew, Aktas, Sabahat Cagan, Batirel, Ayse, Akyol, Ahmet, Goksu, Senay, Ersoy, Yasemin, Bayindir, Yasar, Altin, Nilgün, Gürbüz, Yunus, Erdoğan, Cem, Ozgen, Cansu, Sungurtekin, Hulya, Evik, Guliz, Ersoz, Gulden, Guzeldag, Seda, Bilir, Yeliz, Saracoglu, Kemal Tolga, Eroglu, Ahmet, Aksoy, Firdevs, Koksal, Iftihar, Karaali, Ridvan, Saltoglu, Nese, Cakmak, Rumeysa, Tunay, Burcu, Yilmaz, Mesut, Akdogan, Ozlem O, Baykam, Nurcan N, Çolak, Onur, Agalar, Canan, Sari, Ali, Gundogan, KÜRŞAT, Akbas, Türkay, Çolak, Sait, Demiray, Emine Kubra Dindar, Erol, Çiğdem, Ozturk, Barcin, Telli, Murat, Kurt, Ibrahim, Kalem, Ayşe Kaya, Kayaaslan, Bircan, Talan, Leyla, Altintas, Neriman Defne, Ceyhun, Solakoğlu, Mehtap, Selcuk, Kusoglu, Hulya, Kocagoz, Sesin, Timuroglu, Arif, Aslan, Abdullah Tarik, Akova, Murat, Abed-Maillard, S, Pagani, Jl, Jakob, Stephan, Prazak, Josef, De Geer, Lina, Åkerlund, Joyce, Edin, Alicia, Haney, Michael, Svensson, Carl Johan, Spahic, Dzana, Sjövall, Fredrik, Gallego, Alberto Orejas, Blasco-Navalpotro, Miguel Angel, Novo, Mariana, Ayestaran, J Ignacio, De La Rica, Alejandro Suarez, Maseda, Emilio, Rodriguez, Dra M, Asensio, Dra Mj, Prieto, Emilio Garcia, Espina, Lorena Forcelledo, Salgado, Dra Maria, Ubeda, Alejandro, Gomà, Gemma, Santos, Emilio Diaz, Quesada, María Dolores, Raguer, Laura, Roig, Regina, Catalan, Beatriz, Armestar, Fernando, Bermudez, Rosana Munoz, Arnillas, Maria Pilar Gracia, Amerigo, Joaquin Amador, Flores, Matias, Vera, Paula, Casares, Vanessa, Martinez, Maria, Rocca, Ricard Ferrer, Furman, Mikhail, Belskiy, Vladislav, Chukina, Maria, Vistovskaya, Natala, Eremenko, Aleksandr, Gaigolnik, Denis, Tribulev, Maksim, Zubareva, Nadezhda, Magomedov, Marat, Meleshkina, Yulia, Anderzhanova, Anastasia, Gritsan, Alexey, Lungu, Olguta, Grigoras, Ioana, Marcu, Alexandra, Popescu, Mihai, Tomescu, Dana, Predoi, Cornelia Elena, Filipescu, Daniela Carmen, Cobilinschi, Cristian, Grintescu, Ioana Marina, Bubenek-Turconi, Serban, Valeanu, Liana, Mendes, António Carvalho, Pereira, Énio, Moura, José Pedro, Nunes, Cristina, Pascoalinho, Dulce, Queiró, Joana, Ledo, Sara, da Costa, Tito, Molinos, Elena, Cunha, Rui Pedro, Costa, Vasco, Duarte, Tiago, Botelho, Isabel, de Figueiredo, António Manuel Pereira, Teresa, Ana, Krystopchuk, Andriy, Pinto, Ana Rios, Marques, Ana Josefina Pinheiro, Alves, Madalena, Guimarães, Nádia, Pereira, Tiago, Cartoze, Nuno, Bisanti, Alessandra, Martin-Loeches, Ignacio, Pietraszek-Grzywaczewska, Iwona, Peichota, Mariusz, Broda, Hanna, Nowakowski, Tomasz, Wasowska, Dominika, Walczak-Wieteska, Paulina, Kotkowska, Anna, Bojko, Jozef, Szczesniak, Anna, Komorowska, Irmina Kaptur, Tamowicz, Barbara, Mikstacki, Adam, Rizzo, Anna Chiara, Cotoia, Antonella, Fiorelli, Silvia, Rocco, Monica, Covotta, Marco, Pelagalli, Lorella, Di Guardo, Andrea, Bellina, Davide, Ippolito, Mariachiara, Cortegiani, Andrea, Battaglini, Denise, Pelosi, Paolo, Schlevenin, Maria Grazia, Zuccaro, Francesco, Lodi, Giovanni, Daroui, Ivan, Mirabella, Michele, Porcile, Elisa, Gratarola, Angelo, Giacobbe, Daniele Roberto, Di Gravio, Valentina, Vargas, Joel, Carelli, Simone, Montini, Luca Maria, De Pascale, Gennaro, Sales, Gabriele, Montrucchio, Giorgia, Papathanakos, Georgios, Kouroulas, Vasilios, Retselas, Ioannis, Theodorou, Vasiliki, Marouli, Diamantina, Malliotakis, Polychronis, Almiroudi, Mariota Panagiota, Dimopoulos, Georges, Ali, Fadi, Papageorgiou, Eirini, Athanasa, Zoi, Sakagianni, Aikaterini, Chantziara, Vasiliki, Efthymiou, Anna, Georgopoulou, Maria, Chatzis, Marinos, Sakkalis, Anastasios, Nikolaou, Charikleia, Kogkopoulos, Evangelos, Oikonomou, Marina, Kampolis, C, Papanikolaou, M, Marmanidou, Kyriaki, Paskalis, Harry, Karaiskos, Ilias, Moldovan, Leora, Matei, Mariana Kristina, Koutsoukou, Vasiliki, Romanou, Vasiliki, Vasileiou, Maria, Renta, Foteini, Papoti, Sofia, Iasonidou, Cristina, Kaimakamis, Evangelos, Soulountsi, Vasiliki, Fildisis, Georgios, Psallida, Vasiliki, Smyrniotis, Dimitrios, Arvaniti, Kostoula, Temirov, Talgat, Merenkov, Yevgeniy, Babashev, Baurzhan, Kaligozhin, Zhannur, Bazhykayeva, Yelena, Mugazov, Miras, Ymbetzhanov, Yerlan, Viderman, Dmitriy, Metz, Carlos, Lepper, Philippe, Wempe, Carola, Gottschalk, Antje, Schmidt, Karsten, Dubler, Simon, Pasieka, Bastian, Petros, Sirak, Thomas-Rueddel, Daniel, Bloos, Frank, Hoheisen, Sandra, Bracht, Hendrik, Klouche, Kada, Imzi, Nadia, Dahyot-Fizelier, Claire, Fartoukh, Muriel, Voiriot, Guillaume, Aparicio, Christelle, Siami, Shidasp, Le Guennec, Loïc, Demeret, Sophie, Silva, Stein, Sarton, Benjamine, Roger, Claire, Lefrant, Jean-Yves, Larcher, Romaric, Badre, Gaëtan, Kalfon, Pierre, Razazi, Keyvan, Dessap, Armand Mekonted, Baudry, Thomas, Argaud, Laurent, Smonig, Roland, Louis, Guillaume, Bourenne, Jérémy, Gainnier, Marc, Barbier, François, Djanikian, Flora, Perrigault, Pierre-François, Foucrier, Arnaud, Janny, Sylvie, Weiss, Emmanuel, Bruel, Cédric, Tran, Marc, Philippart, François, Paulet, Rémi, Thyrault, Martial, Duprey, Matthieu, Garcon, Pierre, Mira, Jean-Paul, Le Souhaitier, Mathieu, Bortolotti, Perrine, Kipnis, Eric, Duburcq, Thibault, Coupez, Elisabeth, Souweine, Bertrand, Nica, Alexandru, Alfandari, Serge, Leroy, Olivier, Rosman, Jérémy, Mateu, Philippe, Escudier, Etienne, Guesdon, Charlotte, Massri, Alexandre, Beuzelin, M, Marchalot, A, Le Meur, Anthony, Auchabie, Johann, Castanera, Jérémy, Dulac, Thierry, Montravers, P, Zappela, N, Patrier, Juliette, Timsit, Jean-François, Arbelot, Charlotte, Leone, Marc, Lasic, Hrvoje, Nikolic, Mario, Sakan, Sanja, Persec, Jasminka, Brajkovic, Ana Vujaklija, Radonic, Radovan, Filipovic-Grcic, Ina, Custovic, Aida, Zlojutro, Biljana, Kovacevic, Pedja, Opdenacker, Godelive, De Waele, Elisabeth, Wittebole, Xavier, Serck, Nicolas, De Schryver, Nicolas, Misset, Benoît, Layos, Nathalie, Noel, Cindérella, Biston, Patrick, Haentjens, Lionel, Henin, Pierre, Mesland, Jean-Baptiste, Vanderhaeghen, Sofie F M, Bourgeois, Marc, Denys, Wouter, Hollevoet, Isabelle, De Waele, Jan, De Bus, Liesbet, Tomas, Ernesto Deloya, Perez-Nieto, Orlando R, Tejeda-Huezo, Brigitte, Sánchez-Hurtado, Luis, Ñamendys-Silva, Silvio A, Davalos-Alvarez, Adrian, Dominguez-Cherit, Jose G, Lomeli-Teran, Manuel, Villafuerte, Missael Vladimir Espinoza, Herrera, Mara Ocotlan Gonzalez, Aguilar, Candy Garcia, Leal, Jesús Nicolás Pantoja, Castillo, Roberto Alejandro, Hermosillo, Mariana, Romero-Gonzalez, Juan P, Reyes, Luis Felipe, Montefiore, Pablo, Nuccetelli, Yanina, Alonzo, Microbiologa Irene, Aparicio, Dra Marta, Segura, Matías, Fernández, Rubén, Lopez, Patricia Mabel, Acevedo, José Oscar, Morvillo, Lic Natalia, Centeno, Pablo, Sellami, Walid, Turki, Olfa, Bouaziz, Mounir, Bakr, Lubna, Al-Jadaan, Mohammad, Abu-Sayf, Natalia, Chaaban, Mohammad Karam, Aljabbary, Ahmed, Awad, Maher, Almekhlafi, Ghaleb A, Elrabi, Omar, Sallam, Hend, Nissar, Shaikh, Lance, Marcus, Karic, Edin, Elbuzidi, Abdurahaman, Hssain, Ali Ait, Jayyab, Mustafa Abu, Amro, Sarah, Belkhadir, Z, Ghannam, A, Hachimi, Abdelhamid, Younes, Oujidi, Housni, Brahim, Zeggwagh, Amine Ali, Dendane, Tarek, Wajdi, Maazouzi Ahmed, Mouhssine, Doumiri, Kanjaa, Nabil, Boukatta, Brahim, Seddiki, Rachid, Serghini, Issam, Hasan, Rabab Shaban Ben, Hasan, Hayat Ben, Jobran, Rania, Hdada, Aisha Khaled, Abousnina, Fathi A, Abdulwahed, Eman, Taher, Ahmed Sa, Bouhuwaish, Ahmad, Bilkhayr, Hala, Almiqlash, Bushray, Homaidan, Ahmed Gaber Sadik, AliAli, Almajdoub Mohammed, Aqeelah, Ahmed, Gamra, Marwa, Buimsaedah, Ahmad, Fares, Aya, Ibrahim, Rebecca, Abilama, Fayez, Diab, Adei, Harara, Belal, Levin, Phillip, Belman, Daniel, Rigler, Merav, Kagan, Ilya, Singer, Pierre, Ahmed, Abdullah Khudhur, Tabatabaei, Seyed Mohammad Nasirodin, Tajvidi, Ramin, Masjedi, Mansoor, Sarshad, Hakimeh, Sabetian, Golnar, Dabiri, Gholamreza, Aalinezhad, Fatemeh, Mahmoodpoor, Ata, Zargar, Mohammad Amin, Kiani, Arash, Amiri, Fereshteh, Javaherforoosh, Fatemeh, Baghbanian, Reza, Soltani, Farhad, Savaie, Mohsen, Ahmadi, Fatemeh, Kashipazha, Davood, Mehraban, Zahra, Borsi, Seyed Hamid, Ouhadian, Maryam, Zand, Farid, Hemead, Hanan M, Awad, Ahmed K, Elbadawy, Merihan A, Elsayed, Ahmed, Elmandouh, Omar, Aldhalia, Amer, Saber, Ahmed, Elbahnasawy, Mohamed, Mostafa, Tarek, Osman, Nermin, Barsoum, Mina, Elhadidy, Amr, Alsisi, Adel, Houfi, Ashraf El, Nadeem, Rashid, Chiewroongroj, Supattra, Apichatbutr, Yutthana, Wongsurakiat, Phunsup, Ku, Shih-Chi, Kuo, Li-Kuo, Hu, Ting-Yu, Cia, Cong-Tat, Chou, Nai-Kuan, Yeh, Yu Chang, Ng, Louis Xiang Long, Ng, Kangqi, Quah, Jessica Lishan, Lim, Jia Yan, Ong, Caroline Yu Ming, Li, Andrew Yunkai, Goh, Ken Junyang, Kwa, Andrea Lay Hoon, Lie, Sui An, Ng, Shin Yi, Goh, Qing Yuan, Lim, Sung Yoon, Park, Seung Yong, Park, Sunghoon, Lee, Sang-Min, Jeon, Kyeongman, Ali, Saedah, Mazlan, Mohd Zulfakar, Azman, Abd Hamid, Tong, Lee Kok, Noor, Zuraini Md, Rahman, Hamizah Bt Abdul, Fong, Kean Khang, Wong, Siong Ling Danny, Liew, Mun Thing, Visvalingam, Sheshendrasurian, Pheng, Lee See, Jamaluddin, Muhamad Fadhil Hadi, Hasan, M Shahnaz, Takaki, Shunsuke, Kato, Hideaki, Atobe, Kaori, Saito, Hiroki, Rinka, Hiroshi, Omori, Koichiro, Fujitani, Shigeki, Yoshida, Hideki, Nagashima, Michio, Mishima, Yuka, Shigemitsu, Hidenobu, Kuriyama, Akira, Matsuyoshi, Takeo, Makino, Jun, Hosokawa, Koji, Hashimoto, Satoru, Yamasaki, Masaki, Karumai, Toshiyuki, Hayashi, Yoshiro, Geng, Nan, Peije, Li, Weifeng, Xie, Ye, Ling, Qin, Bingyu, Wang, Yan, Yan, Jing, Huang, Min, Zhou, Suming, Hu, Chungfang, Ye, Jilu, Zhang, Min, Yin, Yongjie, Wang, Jinfeng, Wang, Ruilan, Yin, Chengfen, Xu, Lei, Mingmin, Chen, Wusi, Qiu, Zhao, Juan, Zhao, Peng, Wang, Hao, Chen, Xiaomei, Luo, Jili, Qian, Chuanyun, Zhen, Wang, Wei-Hua, Lu, Jianfeng, Xie, Haibo, Qiu, Sridharan, Dhadappa Damodar, Sudhirchandra, Shah, Moorthi, P Dhakshina, Mon, Tomas, Walid, Haji Adi Muhamad Ibnu, Tabah, Alexis, Buetti, Niccolò, Staiquly, Quentin, Ruckly, Stéphane, Conway Morris, Andrew, Bassetti, Matteo, Lipman, Jeffrey, Ferrer, Ricard, Qiu, Haibo, Paiva, José-Artur, Povoa, Pedro, Abidi, Khalid, Elhadi, Muhammed, Pollock, Hamish, Margetts, Ben, Young, Meredith, Bhadange, Neeraj, Tyler, Steven, Ledtischke, Anne, Finnis, Mackenzie, Dwivedi, Jyotsna, Saxena, Manoj, Biradar, Vishwanath, Soar, Natalie, Sarode, Vineet, Brewster, David, Regli, Adrian, Weeda, Elizabeth, Ahmed, Samiul, Fourie, Cheryl, Laupland, Kevin, Ramanan, Mahesh, Walsham, James, Meyer, Jason, Litton, Edward, Palermo, Anna Maria, Yap, Timothy, Eroglu, Ege, Attokaran, Antony George, Jaramillo, C'havala, Nafees, Khalid Mahmood Khan, Rashid, Nurhikmahtul Aqilah Haji Abd, Tabah, Alexi, Buetti, Niccolò, Staiquly, Quentin, Ruckly, Stéphane, Akova, Murat, Aslan, Abdullah Tarik, Leone, Marc, Conway Morris, Andrew, Bassetti, Matteo, Arvaniti, Kostoula, Lipman, Jeffrey, Ferrer, Ricard, Qiu, Haibo, Paiva, José-Artur, Povoa, Pedro, De Bus, Liesbet, De Waele, Jan, Zand, Farid, Gurjar, Mohan, Alsisi, Adel, Abidi, Khalid, Bracht, Hendrik, Hayashi, Yoshiro, Jeon, Kyeongman, Elhadi, Muhammed, Barbier, Françoi, Timsit, Jean-Françoi, EUROBACT-2 Study Group, ESICM, ESCMID ESGCIP and the OUTCOMEREA Network including, Andrea Cortegiani, and Mariachiara Ippolito

Subjects
antibiotic resistance, bloodstream infection, hospital-acquired, bacteremia, Critical Care and Intensive Care Medicine
Abstract

Purpose: In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. Methods: We carried out a prospective international cohort study of adult patients (≥ 18years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. Results: 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) waspresent in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alivefrom hospital by day-28. Conclusions: HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.

Published
2023

37. A qualitative investigation of paediatric intensive care staff attitudes towards the diagnosis of lower respiratory tract infection in the molecular diagnostics era

Author

Clark, John A., primary, Conway Morris, Andrew, additional, Kanaris, Constantinos, additional, Inwald, David, additional, Butt, Warwick, additional, Osowicki, Joshua, additional, Schlapbach, Luregn J., additional, Curran, Martin D., additional, White, Deborah, additional, Daubney, Esther, additional, Agrawal, Shruti, additional, Navapurkar, Vilas, additional, Török, M. Estée, additional, Baker, Stephen, additional, and Pathan, Nazima, additional

Published
2023
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38. Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia

Author

Navapurkar, Vilas, Bartholdson Scott, Josefin, Maes, Mailis, Hellyer, Thomas P, Higginson, Ellen, Forrest, Sally, Pereira-Dias, Joana, Parmar, Surendra, Heasman-Hunt, Emma, Polgarova, Petra, Brown, Joanne, Titti, Lissamma, Smith, William Pw, Scott, Jonathan, Rostron, Anthony, Routledge, Matthew, Sapsford, David, Török, M Estée, McMullan, Ronan, Enoch, David A, Wong, Vanessa, VAP-Rapid Investigators, Curran, Martin D, Brown, Nicholas M, Simpson, A John, Herre, Jurgen, Dougan, Gordon, Conway Morris, Andrew, Bartholdson Scott, Josefin [0000-0003-3380-4446], Brown, Joanne [0000-0001-7111-6439], Routledge, Matthew [0000-0003-0423-6857], Brown, Nicholas M [0000-0002-6657-300X], Conway Morris, Andrew [0000-0002-3211-3216], and Apollo - University of Cambridge Repository

Subjects
Molecular pathology, Critical Care, Pneumonia, Antimicrobial stewardship
Abstract

Funder: Addenbrooke’s Charitable Trust, Funder: Academy of Medical Sciences and the Health Foundation, Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.

Published
2022
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39. Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study

Author

Conway Morris, Andrew, Datta, Deepankar, Shankar-Hari, Manu, Stephen, Jacqueline, Weir, Christopher J., Rennie, Jillian, and Antonelli, Jean

Subjects
Medical research -- Health aspects, Medicine, Experimental -- Health aspects, T cells -- Health aspects, Infection -- Care and treatment, Health care industry
Abstract

Purpose Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients. Methods Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (T.sub.regs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections. Results A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of T.sub.regs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00-4.74), 3.44 (1.58-7.47) and 2.41 (1.14-5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9. Conclusions This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies. Trial registration The study was registered with clinicaltrials.gov (NCT02186522)., Author(s): Andrew Conway Morris [sup.1] [sup.2], Deepankar Datta [sup.2] [sup.3], Manu Shankar-Hari [sup.4], Jacqueline Stephen [sup.5], Christopher J. Weir [sup.5], Jillian Rennie [sup.2], Jean Antonelli [sup.5], Anthony Bateman [sup.6], Noel [...]

Published
2018
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40. A qualitative investigation of paediatric intensive care staff attitudes towards the diagnosis of lower respiratory tract infection in the molecular diagnostics era

Author

Clark, John A; https://orcid.org/0000-0001-6916-9195, Conway Morris, Andrew; https://orcid.org/0000-0002-3211-3216, Kanaris, Constantinos; https://orcid.org/0000-0002-4017-4553, Inwald, David; https://orcid.org/0000-0001-9518-7821, Butt, Warwick; https://orcid.org/0000-0003-3543-1014, Osowicki, Joshua; https://orcid.org/0000-0002-9432-6700, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Curran, Martin D; https://orcid.org/0000-0002-1589-5850, White, Deborah; https://orcid.org/0000-0002-9254-996X, Daubney, Esther; https://orcid.org/0000-0003-1206-0169, Agrawal, Shruti; https://orcid.org/0000-0001-8695-1314, Navapurkar, Vilas; https://orcid.org/0000-0002-3610-3568, Török, M Estée; https://orcid.org/0000-0001-9098-8590, Baker, Stephen; https://orcid.org/0000-0003-1308-5755, Pathan, Nazima; https://orcid.org/0000-0002-9447-4252, Clark, John A; https://orcid.org/0000-0001-6916-9195, Conway Morris, Andrew; https://orcid.org/0000-0002-3211-3216, Kanaris, Constantinos; https://orcid.org/0000-0002-4017-4553, Inwald, David; https://orcid.org/0000-0001-9518-7821, Butt, Warwick; https://orcid.org/0000-0003-3543-1014, Osowicki, Joshua; https://orcid.org/0000-0002-9432-6700, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Curran, Martin D; https://orcid.org/0000-0002-1589-5850, White, Deborah; https://orcid.org/0000-0002-9254-996X, Daubney, Esther; https://orcid.org/0000-0003-1206-0169, Agrawal, Shruti; https://orcid.org/0000-0001-8695-1314, Navapurkar, Vilas; https://orcid.org/0000-0002-3610-3568, Török, M Estée; https://orcid.org/0000-0001-9098-8590, Baker, Stephen; https://orcid.org/0000-0003-1308-5755, and Pathan, Nazima; https://orcid.org/0000-0002-9447-4252

Abstract

Background In the past decade, molecular diagnostic syndromic arrays incorporating a range of bacterial and viral pathogens have been described. It is unclear how paediatric intensive care unit (PICU) staff diagnose lower respiratory tract infection (LRTI) and integrate diagnostic array results into antimicrobial decision-making. Methods An online survey with eleven questions was distributed throughout paediatric intensive care societies in the UK, continental Europe and Australasia with a total of 755 members. Participants were asked to rate the clinical factors and investigations they used when prescribing for LRTI. Semi-structured interviews were undertaken with staff who participated in a single-centre observational study of a 52-pathogen diagnostic array. Results Seventy-two survey responses were received; most responses were from senior doctors. Whilst diagnostic arrays were used less frequently than routine investigations (i.e. microbiological culture), they were of comparable perceived utility when making antimicrobial decisions. Prescribers reported that for arrays to be clinically impactful, they would need to deliver results within 6 h for stable patients and within 1 h for unstable patients to inform their immediate decision to prescribe antimicrobials. From 16 staff interviews, we identified that arrays were helpful for the diagnosis and screening of bacterial LRTI. Staff reported it could be challenging to interpret results in some cases due to the high sensitivity of the test. Therefore, results were considered within the context of the patient and discussed within the multidisciplinary team. Conclusions Diagnostic arrays were considered of comparable value to microbiological investigations by PICU prescribers. Our findings support the need for further clinical and economic evaluation of diagnostic arrays in a randomised control trial. Trial registration Clinicaltrials.gov, NCT04233268. Registered on 18 January 2020.

Published
2023

41. Exchange protein directly activated by cyclic AMP (EPAC) activation reverses neutrophil dysfunction induced by β2-agonists, corticosteroids, and critical illness

Author

Scott, Jonathan, Harris, Graham J., Pinder, Emma M., Macfarlane, James G., Hellyer, Thomas P., Rostron, Anthony J., Conway Morris, Andrew, Thickett, David R., Perkins, Gavin D., McAuley, Daniel F., Widdrington, John D., Wiscombe, Sarah, Baudouin, Simon V., Roy, Alistair I., Linnett, Vanessa C., Wright, Stephen E., Ruchaud-Sparagano, Marie-Hélène, and Simpson, A. John

Published
2016
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42. Role of immunosuppression in an antibiotic stewardship intervention and its association with clinical outcomes and antibiotic use: protocol for an observational study (RISC-sepsis)

Author

Scott, Jonathan, primary, Trevi, Loredana, additional, McNeil, Hannah, additional, Ewen, Tom, additional, Mawson, Phil, additional, McDonald, David, additional, Filby, Andrew, additional, Lall, Ranjit, additional, Booth, Katie, additional, Boschman, Gert, additional, Melkebeek, Vesna, additional, Perkins, Gavin, additional, McMullan, Ronan, additional, McAuley, Daniel F, additional, McCullagh, Iain J, additional, Walsh, Timothy, additional, Rostron, Anthony, additional, Shankar-Hari, Manu, additional, Dark, Paul, additional, Simpson, A John, additional, Conway Morris, Andrew, additional, and Hellyer, Thomas P, additional

Published
2022
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44. guide to clinicians

Author

Póvoa, Pedro, Coelho, Luís, Dal-Pizzol, Felipe, Ferrer, Ricard, Huttner, Angela, Conway Morris, Andrew, Nobre, Vandack, Ramirez, Paula, Rouze, Anahita, Salluh, Jorge, Singer, Mervyn, Sweeney, Daniel A., Torres, Antoni, Waterer, Grant, Kalil, Andre C., and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)

Subjects
Antibiotic stewardship, Sepsis, Diagnosis, Intensive care unit, Critical Care and Intensive Care Medicine, Biomarkers
Abstract

Funding This work received an unrestricted grant from GSK Portugal and was supported by Sociedade Portuguesa de Ginecologia (SPG). Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In this context, biomarkers could be considered as indicators of either infection or dysregulated host response or response to treatment and/or aid clinicians to prognosticate patient risk. More than 250 biomarkers have been identified and evaluated over the last few decades, but no biomarker accurately differentiates between sepsis and sepsis-like syndrome. Published data support the use of biomarkers for pathogen identification, clinical diagnosis, and optimization of antibiotic treatment. In this narrative review, we highlight how clinicians could improve the use of pathogen-specific and of the most used host-response biomarkers, procalcitonin and C-reactive protein, to improve the clinical care of patients with sepsis. Biomarker kinetics are more useful than single values in predicting sepsis, when making the diagnosis and assessing the response to antibiotic therapy. Finally, integrated biomarker-guided algorithms may hold promise to improve both the diagnosis and prognosis of sepsis. Herein, we provide current data on the clinical utility of pathogen-specific and host-response biomarkers, offer guidance on how to optimize their use, and propose the needs for future research. publishersversion epub_ahead_of_print

Published
2023

45. Addenbrooke’s Air Disinfection Study - Implementation of air disinfection to prevent hospital acquired infections on inpatient wards for older people: A pragmatic controlled before-and-after study

Author

Keevil, Victoria, Goudie, Robert, Butler, Matthew, Conway-Morris, Andrew, Beggs, Clive, Peters, Christine, Gouliouris, Theodore, Navapurkar, Vilas, Illingworth, Chris, Thaxter, Rachel, and Baker, Stephen

Subjects
Geriatrics, Medicine and Health Sciences, Medical Specialties, Diseases, Infectious Disease
Abstract

The proposed study will be a controlled before and after study involving inpatient wards for older people, all designated as green (non-COVID-19 cohort) wards. The study has a quasi-experimental design but is entirely observational, and no intervention other than routine clinical care is proposed. We are utilising routinely collected healthcare data, available for large scale retrospective analysis due to implementation of an electronic health record (EHR) at our hospital, and taking advantage of the limited availability of air cleaning units (ACUs) currently in operation. Prior to this study air cleaning units were commissioned and installed on some inpatient wards. Thus, some of our wards for older people currently have ACUs installed, and others do not. Installation of ACUs is based on the availability of machines, locations most suited to their installation, and considering clinical need. All aspects of routine healthcare will remain the same and will not be affected by the study. Data to support our analytical approach will be extracted from the EHR. This records all aspects of patient care and will be used to identify our study population and ascertain co-variable and outcome information, primarily cases of ward acquired infection on wards with and without ACU technology. Despite this opportunistic design, we believe that this study can yield important insights. The study will involve assessment of the impact of ACUs on respiratory and other infections associated with problematic nosocomial pathogens, including Clostridioides difficile (C. difficile), Staphylococcus aureus (S. aureus - methicillin-resistant and susceptible strains); as well as the SARS-CoV-2 virus, norovirus, influenza, and other respiratory viruses. Alongside this clinical evaluation, the study will also enable the environmental impact of the ACUs to be assessed, in terms of both markers of air quality e.g., humidity and particulate count, and the ward microbiome. Sensors will be placed on intervention and control wards to monitor air quality and air and surface microbiological sampling will be performed. As such, it will represent the first comprehensive study of its kind in an inpatient setting for older people.

Published
2022
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46. A multinational Delphi consensus to end the COVID-19 public health threat

Author

Lazarus, Jeffrey V., Romero, Diana, Kopka, Christopher J., Karim, Salim Abdool, Abu-Raddad, Laith J., Almeida, Gisele, Baptista-Leite, Ricardo, Barocas, Joshua A., Barreto, Mauricio L., Bar-Yam, Yaneer, Bassat, Quique, Batista, Carolina, Bazilian, Morgan, Chiou, Shu-Ti, del Rio, Carlos, Dore, Gregory J., Gao, George F., Gostin, Lawrence O., Hellard, Margaret, Jimenez, Jose L., Kang, Gagandeep, Lee, Nancy, Matičič, Mojca, McKee, Martin, Nsanzimana, Sabin, Oliu-Barton, Miquel, Pradelski, Bary, Pyzik, Oksana, Rabin, Kenneth, Raina, Sunil, Rashid, Sabina Faiz, Rathe, Magdalena, Saenz, Rocio, Singh, Sudhvir, Trock-Hempler, Malene, Villapol, Sonia, Yap, Peiling, Binagwaho, Agnes, Kamarulzaman, Adeeba, El-Mohandes, Ayman, Barreto, Mauricio, Abdulla, Salim, Addleman, Sarah, Aghayeva, Gulnara, Agius, Raymond, Ahmed, Mohammed, Ramy, Mohamed Ahmed, Aide, Pedro, Aleman, Soo, Alfred, Jean-Patrick, Ali, Shamim, Aliaga, Jorge, Aloudat, Tammam, Alqahtani, Saleh A., Al-Salman, Jameela, Amuasi, John H., Agrawal, Anurag, Anwar, Wagida, Araujo-Jorge, Tania, Artaza, Osvaldo, Asadi, Leyla, Awuku, Yaw, Baker, Michael, Barberia, Lorena, Bascolo, Ernesto, Belcher, Paul, Bell, Lizett, Benzaken, Adele, Bergholtz, Emil, Bhadelia, Nahid, Bhan, Anant, Bilodeau, Stephane, Bitrán, Ricardo, Bluyssen, Philomena, Bosman, Arnold, Bozza, Fernando A., Brinkmann, Melanie M., Brown, Andrew, Mellado, Bruce, Bukusi, Elizabeth, Bullen, Chris, Buonanno, Giorgio, Burgess, Rochelle, Butler, Matthew, Byakika-Kibwika, Pauline, Cabieses, Baltica, Carlsson, Gunilla, Cascini, Fidelia, Chabala, Chishala, Chakroun, Mohamed, Cheng, null, Chetty, Agnes, Chumachenko, Dmytro, Consalves, Gregg, Conway Morris, Andrew, Cordie, Ahmed, Corrah, Tumani, Crabtree-Ramírez, Brenda, Dashdorj, Naranjargal, Davidovitch, Nadav, de Souza, Luis Eugenio, Dhariwal, Akshay Chand, Druică, Elena, Ergonul, Onder, Erondu, Ngozi A., Essar, Mohammad Yasir, Ewing, Andrew, Fanjul, Gonzalo, Feierstein, Daniel, Feigl-Ding, Eric, Figueroa, Ramon, Figueroa, John Peter, Fisher, Dale, Flores, Walter, Forero-Peña, David A., Frumkin, Howard, Gamkrelidze, Amiran, Gandhi, Monica, Garcia, Patricia, Garcia-Basteiro, Alberto L., García-Sastre, Adolfo, Garg, Suneela, Gbeasor-Komlanvi, null, Gershenson, Carlos, Gilada, Ishwar, Giovanella, Ligia, González, Marino, Green, Manfred S., Greenhalgh, Trisha, Griffin, Paul, Griffin, Stephen, Grinsztejn, Beatriz, Anand, Tanu, Guerra, Germán, Guinto, Renzo, Gujski, Mariusz, Guner, Rahmet, Hamdy, Adam, Hâncean, Marian-Gabriel, Haniffa, Abusayeed, Hartigan-Go, Kenneth Y., Hassan, Hoda K., Hay, Simon I., Heino, Matti T. J., Hel, Zdenek, Hotez, Peter, Hu, Jia, Hukić, Mirsada, IJsselmuiden, Carel, Iroko, Davidson, Iskarous, Maged, Izugbara, Chimaraoke, Jacobs, Choolwe, Jadad, Alejandro R., Jehan, Fyezah, Jordan, Ayana, Jroundi, Imane, Kain, Kevin, Kamberi, Fatjona, Karamov, Eduard, Karan, Abraar, Katz, Rebecca, Katzourakis, Aris, Kazembe, Abigail, Khamis, Faryal, Khamzayev, Komiljon, Khanyola, Judy, Khunti, Kamlesh, Kiguli-Malwadde, Elsie, Kim, Woo Joo, Kirenga, Bruce J., Klimovský, Daniel, Kmush, Brittany L., Knaul, Felicia, Kogevinas, Manolis, Kristensen, Frederik, Kumar, Dinesh, Kumar, Raman, Kvalsvig, Amanda, Lacerda, Marcus V., Lal, Arush, Lawton, Tom, Lemery, Jay, Leonardi, Anthony J., Li, Yuguo, Löttvall, Jan, Lounis, Mohamed, Maceira, Daniel, MacIntyre, C. Raina, Madani, Azzeddine, Magiorkinis, Gkikas, Malekzadeh, Reza, Choisy, Marc, Marcelin, Jasmine R., Marks, Guy B., Marr, Linsey, Marrazzo, Jeanne, Martina, Antonieta, Martín-Moreno, José M., Mateos, Carlos, Mayxay, Mayfong, Mazarati, Jean Bapiste, Mboup, Souleymane, McDonald, Jennifer, McMillan, Faye, Mechili, Enkeleint, Medici, Andre, Davis, Sarah L. M., Meier, Petra, Memish, Ziad A., Menon, Jaideep, Menon, Purnima, Mesiano-Crookston, Jonathan, Michie, Susan, Mikolasevic, Ivana, Milicevic, Ognjen, Mishra, Asit Kumar, Mohamed, Rahma, Mokdad, Ali H., Monroy-Valle, Michele, Morawska, Lidia, Moschos, Sterghios A., Motawea, Karam, Mousavi, Sayed Hamid, Mumtaz, Ghina, Munene, Peter K., Muñoz Almagro, Carmen, Muriuki, Janet, Muyingo, Sylvia, Naniche, Denise, Naylor, C. David, Ndembi, Nicaise, Nemec, Juraj, Nesteruk, Igor, Ngaruiya, Christine, Nguyen, Hung, Nikolova, Dafina, Nitzan, Dorit, Norheim, Ole, Noushad, Mohammed, Ntoumi, Francine, Nyborg, Gunhild Alvik, Ochodo, Eleanor, Odabasi, Zekaver, Okwen, Mbah Patrick, Olivia, Keiser, Ong, David S. Y., Opara, Ijeoma, Orozco, Miguel, Oshitani, Hitoshi, Pagel, Christina, Pai, Madhukar, Pálsdóttir, Björg, Papatheodoridis, Georgios, Paraskevis, Dimitrios, Leigh, Jeanna Parsons, Pécoul, Bernard, Peichl, Andreas, Perez-Then, Eddy, Duc, Phuc Pham, Philippe, Cécile, Pineda Rojas, Andrea, Pladsen, Courtney, Pozniak, Anton, Quiroga, Rodrigo, Qureshi, Huma, Rampal, Sanjay, Ranney, Megan, Rathe, Laura, Ratzan, Scott, Raventos, Henriette, Rees, Helen, Reis, Renata, Ricciardi, Walter, Rizk, Nesrine, Robalo, Magda, Robertson, Eleanor, Robinson, Leanne, Rokx, Casper, Ros, Tamsin, Røttingen, John-Arne, Rubin, Meir, Ruxrungtam, Kiat, Sadirova, Shakhlo, Saha, Senjuti, Salgado, Nelly, Sanchez, Lizet, Sangaramoorthy, Thurka, Santamaria-Ulloa, Carolina, Santos, Renata, Sawaf, Bisher, Schneider, Matthias F., Schooley, Robert T., Sener, Alper, Sepulveda, Jaime, Shah, Jaffer, Shibani, Mosa, Shoib, Sheikh, Sikazwe, Izukanji, Šimaitis, Aistis, Gill, Amandeep Singh, Skhvitaridze, Natia, Sokolović, Milka, Solomon, Roma, Solórzano, Xavier, Springer, Sandra A., Šrol, Jakub, Staines, Anthony, Stelfox, Henry T., Strathdee, Steffanie, Sulaiman, Lokman Hakim, Sutton, Brett, Svanæs, Dag, Swed, Sarya, Sypsa, Vana, Sørensen, Kristine, Tajudeen, Raji, Tan, Amy, Tang, Julian, Tanner, Marcel, Sethi, Tavpritesh, Temmerman, Marleen, Than, Kyu Kyu, Tinto, Halidou, Tomètissi, Sênoudé Pacôme, Torres, Irene, Tshering, null, Tsiodras, Sotirios, Tsofa, Benjamin, Vahlne, Anders, Vargas, Juan Rafael, Bernal, Ivan Dario Velez, Ventura, Deisy, Vilasanjuan, Rafael, Vipond, Joe, Wamala-Andersson, Sarah, Wargocki, Pawel, West, Robert, Weyand, Angela, White, Trenton M., Wolff, Guntram, Yao, Maosheng, Yates, Christian A., Yeboah, Georgina, Yee-Sin, Leo, Yi, Siyan, Teo, Yik-Ying, Yong, Poovorawan, Zamora-Mesía, Victor, Øvrehus, Anne, 0000-0001-9618-2299, 0000-0002-4832-9564, 0000-0002-4986-2133, 0000-0003-0790-0506, 0000-0003-0875-7596, 0000-0002-6994-1891, 0000-0002-3869-615X, 0000-0001-5286-4044, 0000-0001-6203-1847, 0000-0002-0121-9683, 0000-0003-1793-6350, 0000-0003-2418-0037, 0000-0002-5095-748X, 0000-0003-4492-3256, 0000-0002-5964-8210, 0000-0002-6779-3151, 0000-0002-8074-4450, Lazarus, Jeffrey V [0000-0001-9618-2299], Romero, Diana [0000-0002-4832-9564], Karim, Salim Abdool [0000-0002-4986-2133], Abu-Raddad, Laith J [0000-0003-0790-0506], Bassat, Quique [0000-0003-0875-7596], Chiou, Shu-Ti [0000-0002-6994-1891], Gao, George F [0000-0002-3869-615X], Gostin, Lawrence O [0000-0001-5286-4044], Jimenez, Jose L [0000-0001-6203-1847], McKee, Martin [0000-0002-0121-9683], Oliu-Barton, Miquel [0000-0003-1793-6350], Pradelski, Bary [0000-0003-2418-0037], Rathe, Magdalena [0000-0002-5095-748X], Trock-Hempler, Malene [0000-0003-4492-3256], Yap, Peiling [0000-0002-5964-8210], Binagwaho, Agnes [0000-0002-6779-3151], Kamarulzaman, Adeeba [0000-0002-8074-4450], Apollo - University of Cambridge Repository, Helsinki Collegium for Advanced Studies, Research Group of Nelli Hankonen, Doctoral Programme in Social Sciences, Academic Disciplines of the Faculty of Social Sciences, RS: CAPHRI - R2 - Creating Value-Based Health Care, International Health, Performance analysis and optimization of LARge Infrastructures and Systems (POLARIS), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Internal Medicine, Medical Microbiology & Infectious Diseases, Veritati - Repositório Institucional da Universidade Católica Portuguesa, and Lazarus J. V., Romero D., Kopka C. J., Karim S. A., Abu-Raddad L. J., Almeida G., Baptista-Leite R., Barocas J. A., Barreto M. L., Bar-Yam Y., et al.

Subjects
Pandemics/economics, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, COVID-19 Vaccines, Delphi Technique, General Science & Technology, International Cooperation, Temel Bilimler (SCI), ÇOK DİSİPLİNLİ BİLİMLER, Public Health/economics, [SHS]Humanities and Social Sciences, SDG 3 - Good Health and Well-being, RA0421 Public health. Hygiene. Preventive Medicine, Medicine and Health Sciences, Humans, prevention and control, human, Settore MED/42 - IGIENE GENERALE E APPLICATA, Health Education, Pandemics, Multidisipliner, Organizations, Multidisciplinary, MULTIDISCIPLINARY SCIENCES, COVID-19/economics, Temel Bilimler, pandemic, Communication, Health Policy, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Doğa Bilimleri Genel, COVID-19, 3142 Public health care science, environmental and occupational health, Delphi study, NATURAL SCIENCES, GENERAL, N/A, Public Opinion, Government, Natural Sciences (SCI), Public Health, Natural Sciences
Abstract

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic . Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches , while maintaining proven prevention measures using a vaccines-plus approach that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Published
2022

47. New Movement in Sepsis Immunotherapeutics-A Role for Prokineticin 2?

Author

Conway Morris, Andrew, Conway Morris, Andrew [0000-0002-3211-3216], and Apollo - University of Cambridge Repository

Subjects
Sepsis, Neuropeptides, Humans, Signal Transduction
Abstract

The human proteome is estimated to consist of around 78,000 proteins, the majority of which are splice variants of the ~20,000 ‘master proteins’ encoded in the human genome. Blood plasma, the most widely used biological fluid for both discovery and investigation in patients, has a reported 10,546 species of protein (1). With this diversity of protein content it is unsurprising that, when confronted with a systemic insult such as sepsis, the concentrations of many proteins are perturbed. The question for critical care physicians and researchers is whether these pertubations are mechanistically important for the diseases we treat or are simply epiphenomena of critical illness syndromes, organ failure and our therapeutic interventions.

Published
2022

48. Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia [version 3; peer review: 2 approved]

Author

Navapurkar, Vilas, Bartholdson Scott, Josefin, Maes, Mailis, Hellyer, Thomas P, Higginson, Ellen, Forrest, Sally, Pereira-Dias, Joana, Parmar, Surendra, Heasman-Hunt, Emma, Polgarova, Petra, Brown, Joanne, Titti, Lissamma, Smith, William Pw, Scott, Jonathan, Rostron, Anthony, Routledge, Matthew, Sapsford, David, Török, M Estée, McMullan, Ronan, Enoch, David A, Wong, Vanessa, Curran, Martin D, Brown, Nicholas M, Simpson, A John, Herre, Jurgen, Dougan, Gordon, and Conway Morris, Andrew

Subjects
Molecular pathology, Critical Care, Pneumonia, Antimicrobial stewardship
Abstract

Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing.Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable.Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.

Published
2022

49. Response

Author

Hamed, Islam, Shaban, Nesreen, Nassar, Marwan, Cayir, Dilek, Love, Sam, Navapurkar, Vilas, Mahroof, Razeen, Curran, Martin D, Webb, Stephen, Yang, Huina, Conway Morris, Andrew, Watson, Katherine, and Rostron, Anthony

Subjects
3201 Cardiovascular Medicine and Haematology, 32 Biomedical and Clinical Sciences, 3202 Clinical Sciences
Published
2022
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50. Co-infection and ICU-acquired infection in COIVD-19 ICU patients

Author

Conway Morris, Andrew, Kohler, Katharina, De Corte, Thomas, Ercole, Ari, De Grooth, Harm Jan, Elbers, Paul W.G., Povoa, Pedro, Morais, Rui, Koulenti, Despoina, Jog, Sameer, Nielsen, Nathan, Jubb, Alasdair, Cecconi, Maurizio, De Waele, Jan, and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)

Subjects
Critical Care and Intensive Care Medicine
Abstract

Funding European Society of Intensive Care Medicine. ACM is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/V006118/1). BACKGROUND: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients. METHODS: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method. RESULTS: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO. CONCLUSIONS: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021). publishersversion published

Published
2022

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