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1,021 results on '"Sharland M."'

1. The burden of bacterial antimicrobial resistance in the WHO African region in 2019: a cross-country systematic analysis

Author

Sartorius, Benn, Gray, Authia P, Davis Weaver, Nicole, Robles Aguilar, Gisela, Swetschinski, Lucien R, Ikuta, Kevin S, Mestrovic, Tomislav, Chung, Erin, Wool, Eve E, Han, Chieh, Gershberg Hayoon, Anna, Araki, Daniel T, Abd-Elsalam, Sherief, Aboagye, Richard Gyan, Adamu, Lawan Hassan, Adepoju, Abiola Victor, Ahmed, Ayman, Akalu, Gizachew Taddesse, Akande-Sholabi, Wuraola, Amuasi, John H, Amusa, Ganiyu Adeniyi, Argaw, Ayele Mamo, Aruleba, Raphael Taiwo, Awoke, Tewachew, Ayalew, Melese Kitu, Azzam, Ahmed Y, Babin, Francois-Xavier, Banerjee, Indrajit, Basiru, Afisu, Bayileyegn, Nebiyou Simegnew, Belete, Melaku Ashagrie, Berkley, James A, Bielicki, Julia A, Dekker, Denise, Demeke, Dessalegn, Demsie, Desalegn Getnet, Dessie, Anteneh Mengist, Dunachie, Susanna J, Ed-Dra, Abdelaziz, Ekholuenetale, Michael, Ekundayo, Temitope Cyrus, El Sayed, Iman, Elhadi, Muhammed, Elsohaby, Ibrahim, Eyre, David, Fagbamigbe, Adeniyi Francis, Feasey, Nicholas A, Fekadu, Ginenus, Fell, Frederick, Forrest, Karen M, Gebrehiwot, Mesfin, Gezae, Kebede Embaye, Ghazy, Ramy Mohamed, Hailegiyorgis, Tewodros Tesfa, Haines-Woodhouse, Georgina, Hasaballah, Ahmed I, Haselbeck, Andrea Haekyung, Hsia, Yingfen, Iradukunda, Arnaud, Iregbu, Kenneth Chukwuemeka, Iwu, Chidozie C D, Iwu-Jaja, Chinwe Juliana, Iyasu, Assefa N, Jaiteh, Fatoumatta, Jeon, Hyonjin, Joshua, Charity Ehimwenma, Kassa, Gebrehiwot G, Katoto, Patrick DMC, Krumkamp, Ralf, Kumaran, Emmanuelle A P, Kyu, Hmwe Hmwe, Manilal, Aseer, Marks, Florian, May, Jürgen, McLaughlin, Susan A, McManigal, Barney, Melese, Addisu, Misgina, Kebede Haile, Mohamed, Nouh Saad, Mohammed, Mustapha, Mohammed, Shafiu, Mohammed, Shikur, Mokdad, Ali H, Moore, Catrin E, Mougin, Vincent, Mturi, Neema, Mulugeta, Temesgen, Musaigwa, Fungai, Musicha, Patrick, Musila, Lillian A, Muthupandian, Saravanan, Naghavi, Pirouz, Negash, Hadush, Nuckchady, Dooshanveer C, Obiero, Christina W, Odetokun, Ismail A, Ogundijo, Oluwaseun Adeolu, Okidi, Lawrence, Okonji, Osaretin Christabel, Olagunju, Andrew T, Olufadewa, Isaac Iyinoluwa, Pak, Gi Deok, Perovic, Olga, Pollard, Andrew, Raad, Mathieu, Rafaï, Clotaire, Ramadan, Hazem, Redwan, Elrashdy Moustafa Mohamed, Roca, Anna, Rosenthal, Victor Daniel, Saleh, Mohamed A, Samy, Abdallah M, Sharland, M, Shittu, Aminu, Siddig, Emmanuel Edwar, Sisay, Eskinder Ayalew, Stergachis, Andy, Tesfamariam, Wegen Beyene, Tigoi, Caroline, Tincho, Marius Belmondo, Tiruye, Tenaw Yimer, Umeokonkwo, Chukwuma David, Walsh, Timothy, Walson, Judd L, Yusuf, Hadiza, Zeru, Naod Gebrekrstos, Hay, Simon I, Dolecek, Christiane, Murray, Christopher J L, and Naghavi, Mohsen

Published
2024
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4. The methodology of surveillance for antimicrobial resistance and healthcare-associated infections in Europe (SUSPIRE): a systematic review of publicly available information

Author

Burkert, F., Carrara, E., von Cube, M., Drgona, L., Gilchrist, K., Goossens, H., Harbarth, S., Hequet, D., Jafri, H., Kahlmeter, G., Kuster, S., Luxemburger, C., McCarthy, M., Niks, M., Oualim, A., Poljak, M., Sandulescu, O., Schweiger, A., Vuong, C., Wiegand, I., Widmer, A., Witschi, A.T., Zanetti, G., Zingg, W., Núñez-Núñez, M., Navarro, M.D., Palomo, V., Rajendran, N.B., del Toro, M.D., Voss, A., Sharland, M., Sifakis, F., Tacconelli, E., and Rodríguez-Baño, J.

Published
2018
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15. Randomised controlled trial of fosfomycin in neonatal sepsis: pharmacokinetics and safety in relation to sodium overload

Author

Obiero, CW, Williams, P, Murunga, S, Thitiri, J, Omollo, R, Walker, AS, Egondi, T, Nyaoke, B, Correia, E, Kane, Z, Gastine, S, Kipper, K, Standing, JF, Ellis, S, Sharland, M, Berkley, JA, and NeoFosfo Study Group

Abstract

OBJECTIVE: To assess pharmacokinetics and changes to sodium levels in addition to adverse events (AEs) associated with fosfomycin among neonates with clinical sepsis. DESIGN: A single-centre open-label randomised controlled trial. SETTING: Kilifi County Hospital, Kenya. PATIENTS: 120 neonates aged ≤28 days admitted being treated with standard-of-care (SOC) antibiotics for sepsis: ampicillin and gentamicin between March 2018 and February 2019. INTERVENTION: We randomly assigned half the participants to receive additional intravenous then oral fosfomycin at 100 mg/kg two times per day for up to 7 days (SOC-F) and followed up for 28 days. MAIN OUTCOMES AND MEASURES: Serum sodium, AEs and fosfomycin pharmacokinetics. RESULTS: 61 and 59 infants aged 0-23 days were assigned to SOC-F and SOC, respectively. There was no evidence of impact of fosfomycin on serum sodium or gastrointestinal side effects. We observed 35 AEs among 25 SOC-F participants and 50 AEs among 34 SOC participants during 1560 and 1565 infant-days observation, respectively (2.2 vs 3.2 events/100 infant-days; incidence rate difference -0.95 events/100 infant-days (95% CI -2.1 to 0.20)). Four SOC-F and 3 SOC participants died. From 238 pharmacokinetic samples, modelling suggests an intravenous dose of 150 mg/kg two times per day is required for pharmacodynamic target attainment in most children, reduced to 100 mg/kg two times per day in neonates aged

Published
2022

18. The cascade of care for children and adolescents with HIV in the UK and Ireland, 2010 to 2016

Author

Chappell, Elizabeth, Lyall, Hermione, Riordan, Andrew, Thorne, Claire, Foster, Caroline, Butler, Karina, Prime, Katia, Bamford, Alasdair, Peters, Helen, Judd, Ali, Collins, Intira J., Doerholt, Katja, Klein, Nigel, Menson, Esse, Mcmaster, Paddy, Shackley, Fiona, Kenny, Julia, Shingadia, Delane, Storey, Sharon, Tudor?Williams, Gareth, Turkova, Anna, Welch, Steve, Cook, Claire, Crichton, Siobhan, Dobson, Donna, Fairbrother, Keith, Gibb, Diana M., Harper, Lynda, Le Prevost, Marthe, Van Looy, Nadine, Francis, Kate, Walsh, A, Thrasyvoulou, L, Welch, S, Laycock, N, Bernatoniene, J, Manyika, F, Sharpe, G, Lewis, P, Subramaniam, B, Hutchinson, L, Ward, P, Sloper, K, Fidler, K, Hague, R, Price, V, Clapson, M, Flynn, J, Cardoso, A, Abou, M, Klein, N, Shingadia, D, Ainsley?Walker, P, Tovey, P, Gurtin, D, Garside, Jp, Fall, A, Yeadon, S, Segal, S, Ball, C, Hawkins, S, Dowie, M, Bandi, S, Percival, E, Eisenhut, M, Roy, Pk, Kavanagh, C, Mcmaster, P, Murphy, C, Daniels, J, Lees, Y, Thompson, F, Williams, B, Cliffe, L, Myth, A, Southall, S, Freeman, H, Christie, S, Gordon, A, Rogahn, D, Harris, S, Collinson, A, Jones, L, Offerman, B, Greenberg, M, Benson, C, Riordan, A, O'Connor, R, Brown, N, Ibberson, L, Shackley, F, Faust, Sn, Hancock, J, Doerholt, K, Sharland, M, Storey, S, Gorman, S, Lyall, Egh, Monrose, C, Seery, P, Tudor?Williams, G, Menson, E, Broomhall, J, Scott, D, Stroobant, J, Bridgwood, A, Evans, J, Blake, E, Yannoulias, A, and O'Callaghan, M

Subjects
HIV infection in children -- Statistics -- Drug therapy, Continuum of care -- Statistics, Highly active antiretroviral therapy -- Statistics, Pediatric research, Health
Abstract

: Introduction: The UNAIDS 90‐90‐90 targets for the cascade of care are widely used to monitor the success of HIV care programmes but there are few studies in children. We assessed the cascade for children and adolescents living with HIV in the national Collaborative HIV Paediatric Study (CHIPS) in the UK and Ireland. Methods: Utilizing longitudinal data from CHIPS we compared the cascade of care for 2010, 2013 and 2016. Among children diagnosed with HIV and not known to be lost to follow‐up at the start of each calendar year, we summarized the proportion in active paediatric care during that year (defined as having ≥1 clinic visit, CD4 or viral load measurement, or change to antiretroviral therapy (ART) regimen), and of these, the proportion on ART at last visit in that year. Among those on ART, the proportion with viral suppression ( Results: Of children in paediatric HIV care at the start of 2010, 2013 and 2016 (n = 1249, 1157, 905 respectively), the proportion in active care during that calendar year was high throughout at 97 to 99%. Of those in active care, the proportion on ART increased from 79% to 85% and 92% respectively (p < 0.001). Among those on ART, the proportion with viral suppression and good immune status was stable at 83% to 86% and 85% to 88%, respectively, across the years. Among children in care in 2016, those aged ≥15 years were less likely to be virally suppressed (79% vs. 91%, p < 0.001) or to have good immune status (78% vs. 94%, p < 0.001) compared to younger children; there were no differences by place of birth or sex. Conclusions: Children and adolescents in the UK and Ireland national cohort had high retention in care. The proportion on ART increased significantly over time although there was no change in viral suppression or good immune status. Poorer outcomes among adolescents highlight the need for targeted support for this population., Introduction The HIV cascade of care is a model which outlines the steps from HIV infection that individuals must pass through to achieve viral suppression, with intermediate stages including diagnosis, [...]

Published
2019
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19. An optimised dosing regimen versus a standard dosing regimen of vancomycin for the treatment of late onset sepsis due to Gram-positive microorganisms in neonates and infants aged less than 90 days (NeoVanc): study protocol for a randomised controlled trial

Author

Hill, L. F., Turner, M. A., Lutsar, I., Heath, P. T., Hardy, P., Linsell, L., Jacqz-Aigrain, E., Roilides, E., Sharland, M., Giaquinto, C., Bilardi, D., Planche, T., Huertas, T. M., Hope, W., Zhao, W., Ghazal, P., Dotta, A., De La Cruz, J., Diaz, C. A., Conroy, S., Rawcliffe, L., Bonifazi, D., Manfredi, C., and Felisi, M.

Subjects
medicine.medical_specialty, medicine.drug_class, Antibiotics, Medicine (miscellaneous), Equivalence Trials as Topic, Loading dose, law.invention, Vancomycin, coagulase negative staphylococci, Non-inferiority, Study Protocol, 03 medical and health sciences, Neonate, Clinical Protocols, Randomized controlled trial, law, Vancomycin, Internal medicine, medicine, Clinical endpoint, Humans, coagulase negative staphylococci, Pharmacology (medical), Dosing, Gram-Positive Bacterial Infections, 030304 developmental biology, Randomised controlled trial, 0303 health sciences, lcsh:R5-920, Dose-Response Relationship, Drug, 030306 microbiology, business.industry, Infant, Newborn, Infant, Late-onset sepsis, Staphylococcal Infections, Anti-Bacterial Agents, 3. Good health, Regimen, Pharmacodynamics, Neonatal Sepsis, Safety, business, lcsh:Medicine (General), medicine.drug
Abstract

BackgroundVancomycin has been used in clinical practice for over 50 years; however, validated, pharmacokinetic (PK) data relating clinical outcomes to different dosing regimens in neonates are lacking. Coagulase negative staphylococci (CoNS) are the most commonly isolated organisms in neonatal, late-onset sepsis (LOS). Optimised use to maximise efficacy while minimising toxicity and resistance selection is imperative to ensure vancomycin’s continued efficacy.MethodsNeoVanc is a European, open-label, Phase IIb, randomised, controlled, non-inferiority trial comparing an optimised vancomycin regimen to a standard vancomycin regimen when treating LOS known/suspected to be caused by Gram-positive organisms (excludingStaphylococcus aureus) in infants aged ≤ 90 days. Three hundred infants will be recruited and randomised in a 1:1 ratio. Infants can be recruited if they have culture confirmed (a positive culture from a normally sterile site and at least one clinical/laboratory criterion) or clinical sepsis (presence of any ≥ 3 clinical/laboratory criteria) in the 24 h before randomisation.The optimised regimen consists of a vancomycin loading dose (25 mg/kg) followed by 5 ± 1 days of 15 mg/kg q12h or q8h, dependent on postmenstrual age (PMA). The standard regimen is a 10 ± 2 day vancomycin course at 15 mg/kg q24h, q12h or q8h, dependent on PMA.The primary endpoint is a successful outcome at the test of cure visit (10 ± 1 days after the end of vancomycin therapy). A successful outcome consists of the patient being alive, having successfully completed study vancomycin therapy and having not had a clinical/microbiological relapse/new infection requiring treatment with vancomycin or other anti-staphylococcal antibiotic for > 24 h.Secondary endpoints include clinical/microbiological relapse/new infection at the short-term follow-up visit (30 ± 5 days after the initiation of vancomycin), evaluation of safety (renal/hearing), vancomycin PK and assessment of a host biomarker panel over the course of vancomycin therapy.DiscussionBased on previous pre-clinical data and a large meta-analysis of neonatal, PK/pharmacodynamic data, NeoVanc was set up to provide evidence on whether a loading dose followed by a short vancomycin course is non-inferior, regarding efficacy, when compared to a standard, longer course. If non-inferiority is demonstrated, this would support adoption of the optimised regimen as a way of safely reducing vancomycin exposure when treating neonatal, Gram-positive LOS.Trial registrationClinicalTrials.gov,NCT02790996. Registered on 7 April 2016.EudraCT, 2015–000203-89. Entered on 18 July 2016.

Published
2020
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20. Antibiotic prescriptions patterns in the paediatric primary care setting before and after COVID-19 pandemic in Italy: an analysis using the AWaRe metrics

Author

Barbieri, E, Liberati, C, Cantarutti, A, Di Chiara, C, Lupattelli, A, Sharland, M, Giaquinto, C, Hsia, Y, Dona', D, Elisa Barbieri, Cecilia Liberati, Anna Cantarutti, Costanza Di Chiara, Angela Lupattelli, Michael Sharland, Carlo Giaquinto, Yingfen Hsia, Daniele Dona', Barbieri, E, Liberati, C, Cantarutti, A, Di Chiara, C, Lupattelli, A, Sharland, M, Giaquinto, C, Hsia, Y, Dona', D, Elisa Barbieri, Cecilia Liberati, Anna Cantarutti, Costanza Di Chiara, Angela Lupattelli, Michael Sharland, Carlo Giaquinto, Yingfen Hsia, and Daniele Dona'

Abstract

The containment measures following COVID-19 pandemic drastically reduced airway infections, but they also limited the access of patients to healthcare services. We aimed to assess the antibiotic prescription patterns in the Italian paediatric primary care setting before and after the containment measures implementation. For this retrospective analysis, we used a population database, Pedianet, collecting data of patients aged 0–14 years enrolled with family paediatricians (FP) from March 2019 to March 2021. Antibiotic prescriptions were classified according to WHO AWaRe classification. An interrupted time series evaluating the impact of the containment measures implementation on the monthly antibiotic index, on the access to watch index, and on the amoxicillin to co-amoxiclav index stratified by diagnosis was performed. Overall, 121,304 antibiotic prescriptions were retrieved from 134 FP, for a total of 162,260 children. From March 2020, the antibiotic index dropped by more than 80% for respiratory infections. The Access to Watch trend did not change after the containment measures, reflecting the propensity to prescribe more broad-spectrum antibiotics for respiratory infections even during the pandemic. Similarly, co-amoxiclav was prescribed more often than amoxicillin alone for all the diagnoses, with a significant variation in the trend slope for upper respiratory tract infections prescriptions.

Published
2022

22. Fosfomycin as a potential treatment for neonatal sepsis An open label randomised clinical trial evaluating safety and pharmacokinetics

Author

Obiero, C, Williams, P, Murunga, S, Thitiri, J, Omollo, R, Walker, AS, Egondi, T, Nyoake, B, Correia, E, Kane, Z, Gastine, S, Kipper, K, Standing, J, Ellis, S, Sharland, M, and Berkley, J

Abstract

Objective To assess pharmacokinetics and changes to sodium levels in addition to adverse events (AEs) associated with fosfomycin among neonates with clinical sepsis. Design A single-centre open-label randomised controlled trial. Setting Kilifi County Hospital, Kenya. Patients 120 neonates aged ≤28 days admitted being treated with standard-of-care (SOC) antibiotics for sepsis: ampicillin and gentamicin between March 2018 and February 2019. Intervention We randomly assigned half the participants to receive additional intravenous then oral fosfomycin at 100 mg/kg two times per day for up to 7 days (SOC-F) and followed up for 28 days. Main outcome(s) and measure(s) Serum sodium, AEs and fosfomycin pharmacokinetics. Results 61 and 59 infants aged 0–23 days were assigned to SOC-F and SOC, respectively. There was no evidence of impact of fosfomycin on serum sodium or gastrointestinal side effects. We observed 35 AEs among 25 SOC-F participants and 50 AEs among 34 SOC participants during 1560 and 1565 infant-days observation, respectively (2.2 vs 3.2 events/100 infant-days; incidence rate difference −0.95 events/100 infant-days (95% CI −2.1 to 0.20)). Four SOC-F and 3 SOC participants died. From 238 pharmacokinetic samples, modelling suggests an intravenous dose of 150 mg/kg two times per day is required for pharmacodynamic target attainment in most children, reduced to 100 mg/kg two times per day in neonates aged

Published
2022

23. Children living with HIV in Europe: do migrants have worse treatment outcomes?

Author

Chappell, E., Kohns Vasconcelos, M., Goodall, R. L., Galli, L., Goetghebuer, T., Noguera-Julian, A., Rodrigues, L. C., Scherpbier, H., Smit, C., Bamford, A., Crichton, S., Navarro, M. L., Ramos, J. T., Warszawski, J., Spolou, V., Chiappini, E., Venturini, E., Prata, F., Kahlert, C., Marczynska, M., Marques, L., Naver, L., Thorne, C., Gibb, D. M., Giaquinto, C., Judd, A., Collins, I. J., Goodall, R., Rodrigues, L., Duff, C., Gomezpena, D., Jackson, C., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., Le Chenadec, J., Ramos, E., Dialla, O., Wack, T., Laurent, C., Ait si Selmi, L., Leymarie, I., Ait Benali, F., Brossard, M., Boufassa, L., Floch-Tudal, C., Firtion, G., Hau, I., Chace, A., Bolot, P., Blanche, S., Granier, M., Labrune, P., Lachassine, E., Dollfus, C., Levine, M., Fourcade, C., Heller-Roussin, B., Runel-Belliard, C., Tricoire, J., Monpoux, F., Chirouze, C., Reliquet, V., Brouard, J., Kebaili, K., Fialaire, P., de Villeneuve, A., Lalande, M., de Flandres, J., Mazingue, F., Partisani, M. L., de Martino, M., Angelo Tovo, P., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona, D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Kinderziekenhuis, E., van der Kuip, M., Pajkrt, D., Scherpbier, H. J., de Boer, C., Weijsenfeld, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Henriet, S. S. V., van Aerde, M. K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Burger, D., Scholvinck, E. H., de Groot-de Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Loeffen, Y. G. T., Wolfs, T. F. W., Nauta, N., Schuurman, R., Hofstra, L. M., Wensing, A. M. J., Reiss, P., Zaheri, S., Boyd, A. C., Bezemer, D. O., van Sighem, A. I., Wit, F. W. M. N., Hillebregt, M. M. J., Woudstra, T. J., Bergsma, D., van de Sande, L., Rutkens, T., van der Vliet, S., Lelivelt, K. J., Scheijgrond, A., de Groot, L., van den Akker, M., Bakker, Y., EI Berkaoui, A., Bezemer, M., Bretin, N., Djoechro, E., Groters, M., Kruijne, E., Lodewijk, C., Lucas, E., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., Visser, K. M., Witte, E. C., Popielska, J., Pokorska-Spiewak, M., Oldakowska, A., Zawadka, K., Coupland, U., Doroba, M., Teixeira, C., Fernandes, A., Soler-Palacin, P., Antoinette Frick, M., Perez-Hoyos, S., Mur, A., Lopez, N., Mendez, M., Mayol, L., Vallmanya, T., Calavia, O., Garcia, L., Coll, M., Pineda, V., Rius, N., Rovira, N., Duenas, J., Fortuny, C., Jose Mellado, M., Escosa, L., Garcia Hortelano, M., Sainz, T., Gonzalez-Tome, M. I., Rojo, P., Blazquez, D., Prieto-Tato, L., Epalza, C., Tomas Ramos, J., Guillen, S., Saavedra, J., Santos, M., Santiago, B., de Ory, S. J., Carrasco, I., Munoz-Fernandez, M. A., Angel Roa, M., Penin, M., Martinez, J., Badillo, K., Onate, E., Pocheville, I., Garrote, E., Colino, E., Gomez Sirvent, J., Garzon, M., Roman, V., Angulo, R., Neth, O., Falcon, L., Terol, P., Luis Santos, J., Moreno, D., Lendinez, F., Peromingo, E., Uberos, J., Ruiz, B., Grande, A., Jose Romero, F., Perez, C., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Collado, P., Antonio Couceiro, J., Vila, L., Calvino, C., Isabel Piqueras, A., Oltra, M., Gavilan, C., Montesinos, E., Dapena, M., Alvarez, C., Jimenez, B., Gloria Andres, A., Marugan, V., Ochoa, C., Alfayate, S., Isabel Menasalvas, A., del Prado, Y. R., Navernaver, L., Soeria-Atmadja, S., Belfrage, E., Hagas, V., Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Crisinel, P. A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K. J., Muller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, C., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Sultan-Beyer, L., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Yerly, S., Lyall, H., Butler, K., Doerholt, K., Doherty, C., Foster, C., Harrison, I., Kenny, J., Klein, N., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Prime, K., Riordan, A., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Turkova, A., Welch, S., Cook, C., Dobson, D., Fairbrother, K., Prevost, M. L., Van Looy, N., Peters, H., Francis, K., Thrasyvoulou, L., Fidler, K., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Hague, R., Price, V., Flynn, J., Cardoso, A., Abou - Rayyah, M., Yeadon, S., Segal, S., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Anguvaa, L., Wren, L., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, A., Williams, B., Pope, S., Libeschutz, S., Cliffe, L., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Rosie Hague, D., Clarke, L., Jones, L., Brown, L., Greenberg, M., Benson, C., Ibberson, L., Patel, S., Hancock, J., Sharland, M., Lyall, E. G. H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Department of Sciences for Woman and Child's Health, Florence University, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam institute for Infection and Immunity, Infectious diseases, AII - Infectious diseases, Amsterdam Reproduction & Development (AR&D), Medical Microbiology and Infection Prevention, Gastroenterology and Hepatology, Global Health, APH - Aging & Later Life, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, 1, Elizabeth Chappell, 2 3 4, Malte Kohns Vasconcelo, L Goodall 1, Ruth, 5, Luisa Galli, 6, Tessa Goetghebuer, 9 10, Antoni Noguera-Julian 7 8, C Rodrigues 2, Laura, Scherpbier 11, Henriette, Smit 12, Colette, 1 13 14, Alasdair Bamford, 1, Siobhan Crichton, Luisa Navarro 10 15 16 17, Marissa, T Ramos 18, Jose, Warszawski 19 20, Josiane, Spolou 21, Vana, 5, Elena Chiappini, 5, Elisabetta Venturini, Prata 22, Filipa, Kahlert 23, Christian, Marczynska 24, Magdalena, Marques 25, Laura, Naver 26, Lar, Thorne 14, Claire, M Gibb 1, Diana, Giaquinto 27, Carlo, 1, Ali Judd, 1, Intira Jeannie Collin, Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC), European, Goodall, Ruth, Rodrigues, Laura, Duff, Charlotte, Gomezpena, Daniel, Jackson, Charlotte, Lundin, Rebecca, Mangiarini, Laura, Milanzi, Edith, Nardone, Alessandra, Hainaut, Marc, Van der Kelen, Evelyne, Delforge, Marc, Le Chenadec, Jerome, Ramos, Elisa, Dialla, Olivia, Wack, Thierry, Laurent, Corine, Ait Si Selmi, Lamya, Leymarie, Isabelle, Ait Benali, Fazia, Brossard, Maud, Boufassa, Leila, Floch-Tudal, Corinne, Firtion, Ghislaine, Hau, Isabelle, Chace, Anne, Bolot, Pascal, Blanche, Stéphane, Granier, Michèle, Labrune, Philippe, Lachassine, Eric, Dollfus, Catherine, Levine, Martine, Fourcade, Corinne, Heller-Roussin, Brigitte, Runel-Belliard, Camille, Tricoire, Joëlle, Monpoux, Fabrice, Chirouze, Catherine, Reliquet, Véronique, Brouard, Jacque, Kebaili, Kamila, Fialaire, Pascale, de Villeneuve, Arnaud, Lalande, Muriel, de Flandres, Jeanne, Mazingue, Françoise, Luisa Partisani, Maria, de Martino, Maurizio, Angelo Tovo, Pier, Gabiano, Clara, Carloni, Ine, Larovere, Domenico, Baldi, Francesco, Miniaci, Angela, Pession, Andrea, Badolato, Raffaele, Pantò, Grazia, Anastasio, Elisa, Montagnani, Carlotta, Bianchi, Leila, Allodi, Alessandra, Di Biagio, Antonio, Grignolo, Sara, Giacomet, Vania, Marchisio, Paola, Banderali, Giuseppe, Tagliabue, Claudia, Cellini, Monica, Bruzzese, Eugenia, DI COSTANZO, Pasquale, LO VECCHIO, Andrea, Donà, Daniele, Rampon, Osvalda, Romano, Amelia, Dodi, Icilio, Esposito, Susanna, Zuccaro, Valentina, Zanaboni, Domenico, Consolini, Rita, Bernardi, Stefania, Genovese, Orazio, Cristiano, Letizia, Mazza, Antonio, Garazzino, Silvia, Mignone, Federica, Silvestro, Erika, Portelli, Vincenzo, Pediatric surgery, Pediatrics, and Virology

Subjects
children, Europe, HIV, migrant, mortality, Adolescent, Child, Humans, Treatment Outcome, Viral Load, Anti-HIV Agents, HIV Infections, Transients and Migrants, medicine.medical_treatment, Human immunodeficiency virus (HIV), lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], medicine.disease_cause, 0302 clinical medicine, Medicine, Pharmacology (medical), 030212 general & internal medicine, health care economics and organizations, Health Policy, Hazard ratio, virus diseases, Immunosuppression, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, population characteristics, 0305 other medical science, Viral load, geographic locations, education, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, 030505 public health, business.industry, Proportional hazards model, medicine.disease, Confidence interval, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract

Contains fulltext : 249078.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. METHODS: Children aged

Published
2022
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24. Optimised versus standard dosing of vancomycin in infants with Gram-positive sepsis (NeoVanc): a multicentre, randomised, open-label, phase 2b, non-inferiority trial

Author

Hill, LF, Clements, MN, Turner, MA, Donà, D, Lutsar, I, Jacqz-Aigrain, E, Heath, PT, Roilides, E, Rawcliffe, L, Alonso-Diaz, C, Baraldi, E, Dotta, A, Ilmoja, M-L, Mahaveer, A, Metsvaht, T, Mitsiakos, G, Papaevangelou, V, Sarafidis, K, Walker, AS, Sharland, M, and NeoVanc Consortium

Abstract

BACKGROUND: Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms. METHODS: NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged 90 days or younger. Infants with at least three clinical or laboratory sepsis criteria or confirmed Gram-positive sepsis with at least one clinical or laboratory criterion were enrolled from 22 neonatal intensive care units in Greece, Italy, Estonia, Spain, and the UK. Infants were randomly assigned (1:1) to either the optimised regimen (25 mg/kg loading dose, followed by 15 mg/kg every 12 h or 8 h dependent on postmenstrual age, for 5 ± 1 days) or the standard regimen (no loading dose; 15 mg/kg every 24 h, 12 h, or 8 h dependent on postmenstrual age for 10 ± 2 days). Vancomycin was administered intravenously via 60 min infusion. Group allocation was not masked to local investigators or parents. The primary endpoint was success at the test of cure visit (10 ± 1 days after the end of actual vancomycin therapy) in the per-protocol population, where success was defined as the participant being alive at the test of cure visit, having a successful outcome at the end of actual vancomycin therapy, and not having a clinically or microbiologically significant relapse or new infection requiring antistaphylococcal antibiotics for more than 24 h within 10 days of the end of actual vancomycin therapy. The non-inferiority margin was -10%. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT02790996). FINDINGS: Between March 3, 2017, and July 29, 2019, 242 infants were randomly assigned to the standard regimen group (n=122) or the optimised regimen group (n=120). Primary outcome data in the per-protocol population were available for 90 infants in the optimised group and 92 in the standard group. 64 (71%) of 90 infants in the optimised group and 73 (79%) of 92 in the standard group had success at test of cure visit; non-inferiority was not confirmed (adjusted risk difference -7% [95% CI -15 to 2]). Incomplete resolution of clinical or laboratory signs after 5 ± 1 days of vancomycin therapy was the main factor contributing to clinical failure in the optimised group. Abnormal hearing test results were recorded in 25 (30%) of 84 infants in the optimised group and 12 (15%) of 79 in the standard group (adjusted risk ratio 1·96 [95% CI 1·07 to 3·59], p=0·030). There were six vancomycin-related adverse events in the optimised group (one serious adverse event) and four in the standard group (two serious adverse events). 11 infants in the intention-to-treat population died (six [6%] of 102 infants in the optimised group and five [5%] of 98 in the standard group). INTERPRETATION: In the largest neonatal vancomycin efficacy trial yet conducted, no clear clinical impact of a shorter duration of treatment with a loading dose was demonstrated. The use of the optimised regimen cannot be recommended because a potential hearing safety signal was identified; long-term follow-up is being done. These results emphasise the importance of robust clinical safety assessments of novel antibiotic dosing regimens in infants. FUNDING: EU Seventh Framework Programme for research, technological development and demonstration.

Published
2022

25. Clinical management of severe infections caused by carbapenem-resistant Gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations

Author

Carrara, E, Savoldi, A, Piddock, LJ, Franceschi, F, Ellis, S, Sharland, M, John Brink, A, Harris, PN, Levy-Hara, G, Rohit, A, Tsioutis, C, Zayyad, H, Giske, C, Chiamenti, M, Bragantini, D, Righi, E, and Gorska, A

Abstract

OBJECTIVES: Optimal treatment of carbapenem-resistant Gram-negative (CR-GNB) infections is uncertain due to the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. METHODS: A 36-items-questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball-sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. RESULTS: 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in High-Income-Countries vs 59% (194/283) in Upper-Medium-Income-Countries and 30% (118/196) in Lower-Middle-Income-Countries/Lower-Income-Countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of 'combination therapy' with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) of in vitro-synergism. CONCLUSIONS: Management of CR-GNB infections is far from being standardized. Strategic public health focussed randomised controlled trials are urgently required to inform evidence-based treatment guidelines.

Published
2022

29. Malignancies among children and young people with HIV in Western and Eastern Europe and Thailand the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) study group

Author

Chappell, E., Turkova, A., Goetghebuer, T., Jackson, C., Chiappini, E., Galli, L., Gingaras, C., Judd, A., Spoulou, V., Lisi, C., Ansone, S., Wolfs, T., Marczynska, M., Ene, L., Plotnikova, Y., Voronin, E., Samarina, A., Jourdain, G., Ngo-Giang-Huong, N., Fortuny, C., Navarro, M. L., Ramos, J. T., Naver, L., Crisinel, P. -A., Bailey, H., Malyuta, R., Volokha, A., Bamford, A., Crichton, S., Foster, C., Thorne, C., Collins, I. J., Giaquinto, C., Gibb, D. M., Critchton, S., Duff, C., Goodall, R., Gomezpena, D., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., de Martino, M., Tovo, P. A., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Venturini, E., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona', D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Pajkrt, D., Scherpbier, H. J., Weijsenfeld, A. M., de Boer, C. G., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E. G., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Henriet, S. S. V., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Scholvinck, E. H., de Groot-De Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Wolfs, T. F. W., Nauta, N., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Reiss, P., Zaheri, S., Bezemer, D. O., van Sighem, A. I., Smit, C., Wit, F. W. M. N., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Grivell, S., Meijering, R., Raethke, M., Rutkens, T., de Groot, L., van den Akker, M., Bakker, Y., Bezemer, M., El Berkaoui, A., Geerlinks, J., Koops, J., Kruijne, E., Lodewijk, C., Lucas, E., van der Meer, R., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., van de Sande, L., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Witte, E. C., Tuk, B., Popielska, J., Pokorska-Spiewak, M., Oldakowska, A., Zawadka, K., Coupland, U., Doroba, M., Miloenko, M., Labutina, S., Soler-Palacin, P., Frick, M. A., Perez-Hoyos, S., Mur, A., Lopez, N., Mendez, M., Mayol, L., Vallmanya, T., Calavia, O., Garcia, L., Coll, M., Pineda, V., Rius, N., Rovira, N., Duenas, J., Noguera-Julian, A., Mellado, M. J., Escosa, L., Hortelano, M. G., Sainz, T., Gonzalez-Tome, M. I., Rojo, P., Blazquez, D., Prieto, L., Guillen, S., Saavedra, J., Santos, M., Munoz, M. A., Ruiz, B., Fernandez, C., Phee, M., de Ory, S. J., Alvarez, S., Roa, M. A., Beceiro, J., Martinez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Sirvent, J. G., Garzon, M., Roman, V., Montesdeoca, A., Mateo, M., Munoz, M. J., Angulo, R., Neth, O., Falcon, L., Terol, P., Santos, J. L., Moreno, D., Lendinez, F., Grande, A., Romero, F. J., Perez, C., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Couceiro, J. A., Perez, A., Piqueras, A. I., Breton, R., Segarra, I., Gavilan, C., Jareno, E., Montesinos, E., Dapena, M., Alvarez, C., Andres, A. G., Marugan, V., Ochoa, C., Alfayate, S., Menasalvas, A. I., de Miguel, E., Soeria-Atmadja, S., Belfrage, E., Hagas, V., Aebi-Popp, K., Anagnostopoulos, A., Asner, S., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Grawe, C., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kahlert, C. R., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K. J., Muller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, Ch., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C. A., Yerly, S., Wannarit, P., Techakunakorn, P., Hansudewechakul, R., Wanchaitanawong, V., Theansavettrakul, S., Nanta, S., Ngampiyaskul, C., Phanomcheong, S., Hongsiriwon, S., Karnchanamayul, W., Kwanchaipanich, R., Kanjanavanit, S., Kamonpakorn, N., Nantarukchaikul, M., Layangool, P., Mekmullica, J., Lucksanapisitkul, P., Watanayothin, S., Lertpienthum, N., Warachit, B., Hanpinitsak, S., Potchalongsin, S., Thanasiri, P., Krikajornkitti, S., Attavinijtrakarn, P., Srirojana, S., Bunjongpak, S., Puangsombat, A., Na-Rajsima, S., Ananpatharachai, P., Akarathum, N., Lawtongkum, W., Kheunjan, P., Suriyaboon, T., Saipanya, A., Than-In-At, K., Jaisieng, N., Suaysod, R., Chailoet, S., Naratee, N., Kawilapat, S., Kaleeva, T., Baryshnikova, Y., Soloha, S., Bashkatova, N., Raus, I., Glutshenko, O., Ruban, Z., Prymak, N., Kiseleva, G., Lyall, H., Butler, K., Doerholt, K., Doherty, C., Harrison, I., Kenny, J., Klein, N., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Prime, K., Riordan, A., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Welch, S., Cook, C., Dobson, D., Fairbrother, K., Le Prevost, M., Van Looy, N., Peters, H., Francis, K., Thrasyvoulou, L., Fidler, K., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Hague, R., Price, V., Flynn, J., Cardoso, A., Abou-Rayyah, M., Yeadon, S., Segal, S., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Anguvaa, L., Wren, L., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, A., Williams, B., Pope, S., Libeschutz, S., Cliffe, L., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Hague, D. R., Clarke, L., Jones, L., Brown, L., Greenberg, M., Benson, C., Ibberson, L., Patel, S., Hancock, J., Sharland, M., Lyall, E. G. H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Chappell, E., Turkova, A., Goetghebuer, T., Jackson, C., Chiappini, E., Galli, L., Gingaras, C., Judd, A., Spoulou, V., Lisi, C., Ansone, S., Wolfs, T., Marczynska, M., Ene, L., Plotnikova, Y., Voronin, E., Samarina, A., Jourdain, G., Ngo-Giang-Huong, N., Fortuny, C., Navarro, M. L., Ramos, J. T., Naver, L., Crisinel, P. -A., Bailey, H., Malyuta, R., Volokha, A., Bamford, A., Crichton, S., Foster, C., Thorne, C., Collins, I. J., Giaquinto, C., Gibb, D. M., Critchton, S., Duff, C., Goodall, R., Gomezpena, D., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., de Martino, M., Tovo, P. A., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Venturini, E., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona, D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Pajkrt, D., Scherpbier, H. J., Weijsenfeld, A. M., de Boer, C. G., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E. G., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Henriet, S. S. V., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Scholvinck, E. H., de Groot-De Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Wolfs, T. F. W., Nauta, N., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Reiss, P., Zaheri, S., Bezemer, D. O., van Sighem, A. I., Smit, C., Wit, F. W. M. N., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Grivell, S., Meijering, R., Raethke, M., Rutkens, T., de Groot, L., van den Akker, M., Bakker, Y., Bezemer, M., El Berkaoui, A., Geerlinks, J., Koops, J., Kruijne, E., Lodewijk, C., Lucas, E., van der Meer, R., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., van de Sande, L., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Witte, E. C., Tuk, B., Popielska, J., Pokorska-Spiewak, M., Oldakowska, A., Zawadka, K., Coupland, U., Doroba, M., Miloenko, M., Labutina, S., Soler-Palacin, P., Frick, M. A., Perez-Hoyos, S., Mur, A., Lopez, N., Mendez, M., Mayol, L., Vallmanya, T., Calavia, O., Garcia, L., Coll, M., Pineda, V., Rius, N., Rovira, N., Duenas, J., Noguera-Julian, A., Mellado, M. J., Escosa, L., Hortelano, M. G., Sainz, T., Gonzalez-Tome, M. I., Rojo, P., Blazquez, D., Prieto, L., Guillen, S., Saavedra, J., Santos, M., Munoz, M. A., Ruiz, B., Fernandez, C., Phee, M., de Ory, S. J., Alvarez, S., Roa, M. A., Beceiro, J., Martinez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Sirvent, J. G., Garzon, M., Roman, V., Montesdeoca, A., Mateo, M., Munoz, M. J., Angulo, R., Neth, O., Falcon, L., Terol, P., Santos, J. L., Moreno, D., Lendinez, F., Grande, A., Romero, F. J., Perez, C., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Couceiro, J. A., Perez, A., Piqueras, A. I., Breton, R., Segarra, I., Gavilan, C., Jareno, E., Montesinos, E., Dapena, M., Alvarez, C., Andres, A. G., Marugan, V., Ochoa, C., Alfayate, S., Menasalvas, A. I., de Miguel, E., Soeria-Atmadja, S., Belfrage, E., Hagas, V., Aebi-Popp, K., Anagnostopoulos, A., Asner, S., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Grawe, C., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kahlert, C. R., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K. J., Muller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, Ch., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C. A., Yerly, S., Wannarit, P., Techakunakorn, P., Hansudewechakul, R., Wanchaitanawong, V., Theansavettrakul, S., Nanta, S., Ngampiyaskul, C., Phanomcheong, S., Hongsiriwon, S., Karnchanamayul, W., Kwanchaipanich, R., Kanjanavanit, S., Kamonpakorn, N., Nantarukchaikul, M., Layangool, P., Mekmullica, J., Lucksanapisitkul, P., Watanayothin, S., Lertpienthum, N., Warachit, B., Hanpinitsak, S., Potchalongsin, S., Thanasiri, P., Krikajornkitti, S., Attavinijtrakarn, P., Srirojana, S., Bunjongpak, S., Puangsombat, A., Na-Rajsima, S., Ananpatharachai, P., Akarathum, N., Lawtongkum, W., Kheunjan, P., Suriyaboon, T., Saipanya, A., Than-In-At, K., Jaisieng, N., Suaysod, R., Chailoet, S., Naratee, N., Kawilapat, S., Kaleeva, T., Baryshnikova, Y., Soloha, S., Bashkatova, N., Raus, I., Glutshenko, O., Ruban, Z., Prymak, N., Kiseleva, G., Lyall, H., Butler, K., Doerholt, K., Doherty, C., Harrison, I., Kenny, J., Klein, N., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Prime, K., Riordan, A., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Welch, S., Cook, C., Dobson, D., Fairbrother, K., Le Prevost, M., Van Looy, N., Peters, H., Francis, K., Thrasyvoulou, L., Fidler, K., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Hague, R., Price, V., Flynn, J., Cardoso, A., Abou-Rayyah, M., Yeadon, S., Segal, S., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Anguvaa, L., Wren, L., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, A., Williams, B., Pope, S., Libeschutz, S., Cliffe, L., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Hague, D. R., Clarke, L., Jones, L., Brown, L., Greenberg, M., Benson, C., Ibberson, L., Patel, S., Hancock, J., Sharland, M., Lyall, E. G. H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., and Yannoulias, A.

Subjects
Adult, Male, Acquired Immunodeficiency Syndrome, Adolescent, Infant, HIV, HIV Infections, Eastern, Adolescents, Newborn, Thailand, Europe, malignancie, Neoplasms, malignancies, Humans, Children, Aged, Child, Europe, Eastern, Infant, Newborn
Abstract

Objectives: Investigate trends over time and predictors of malignancies among children and young people with HIV. Design: Pooled data from 17 cohorts in 15 countries across Europe and Thailand. Methods: Individuals diagnosed with HIV and presenting to paediatric care less than 18 years of age were included. Time at risk began at birth for children with documented vertically acquired HIV, and from first HIV-care visit for others. Children were followed until death, loss-to-follow-up, or last visit in paediatric or adult care (where data after transfer to adult care were available). Rates of reported malignancies were calculated overall and for AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (NADM) separately. Risk factors for any malignancy were explored using Poisson regression, and for mortality following a malignancy diagnosis using Cox regression. Results: Among 9632 individuals included, 140 (1.5%) were ever diagnosed with a malignancy, of which 112 (80%) were ADM. Overall, the rate of any malignancy was 1.18 per 1000 person-years; the rate of ADM decreased over time whereas the rate of NADM increased. Male sex, being from a European cohort, vertically acquired HIV, current severe immunosuppression, current viral load greater than 400 copies/ml, older age, and, for those not on treatment, earlier calendar year, were risk factors for a malignancy diagnosis. Fifty-eight (41%) individuals with a malignancy died, a median 2.4 months (IQR 0.6-8.8) after malignancy diagnosis. Conclusion: The rate of ADM has declined since widespread availability of combination ART, although of NADM, there was a small increase. Mortality following a malignancy was high, warranting further investigation.

Published
2021

31. Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

Author

Chappell, E., Riordan, A., Jourdain, G., Soriano-Arandes, A., Ene, L., Scherpbier, H., Warszawski, J., Collins, I., Smit, C., Marques, L., Klein, N., Guillén, S., Judd, A., Thorne, C., Goodall, R., Königs, C., Spoulou, V., Prata, F., Goetghebuer, T., Chiappini, E., Galli, L., Naver, L., Giaquinto, C., Gibb, D., Marczynska, M., Okhonskaia, L., Klimkait, T., Lallemant, M., Ngo-Giang-Huong, N., Kiseleva, G., Malyuta, R., Volokha, A., Hainaut, M., Delforge, M., Le Chenadec, J., Ramos, E., Dialla, O., Wack, T., Laurent, C., Ait Si Selmi, L., Leymarie, I., Ait Benali, F., Brossard, M., Boufassa, L., Floch-Tudal, C., Firtion, G., Hau, I., Chace, A., Bolot, P., Blanche, S., Levine, M., Bicëtre, L., Fourcade, C., Heller-Roussin, B., Runel-Belliard, C., Tricoire, J., Chirouze, C., Reliquet, V., Brouard, J., Kebaili, K., Fialaire, P., Lalande, M., Schultze-Strasser, S., Baumann, U., Niehues, T., Neubert, J., Kobbe, R., Berlin, C., Feiterna-Sperling, C., Buchholz, B., Notheis, G., de Martino, M., Angelo Tovo, P., Patrizia, O., Larovere, D., Ruggeri, M., Faldella, G., Baldi, F., Badolato, R., Montagnani, C., Venturini, E., Lisi, C., Di Biagio, A., Taramasso, L., Giacomet, V., Erba, P., Esposito, S., Lipreri, R., Salvini, F., Tagliabue, C., Cellini, M., Bruzzese, E., Lo Vecchio, A., Rampon, O., Donà, D., Romano, A., Dodi, I., Maccabruni, A., Consolini, R., Bernardi, S., Tchidjou Kuekou, H., Genovese, O., Olmeo, P., Cristiano, L., Mazza, A., Gabiano, C., Garazzino, S., Pellegatta, A., Pajkrt, D., Weijsenfeld, A., de Boer CG, Jurriaans, S., Back, N., Zaaijer, H., Berkhout, B., Cornelissen, M., Schinkel, C., Wolthers, K., Fraaij, P., van Rossum AMC, van der Knaap LC, Visser, E., Koopmans, M., van Kampen JJA, Pas, S., Henriet, S., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F., Schölvinck, E., de Groot-de Jonge, H., Niesters, H., van Leer-Buter CC, Knoester, M., Bont, L., Geelen, S., Wolfs, T., Nauta, N., Ang, C., van Houdt, R., Pettersson, A., Vandenbroucke-Grauls, C., Reiss, P., Bezemer, D., van Sighem AI, Wit, F., Boender, T., Zaheri, S., Hillebregt, M., de Jong, A., Bergsma, D., Grivell, S., Jansen, A., Raethke, M., Meijering, R., de Groot, L., van den Akker, M., Bakker, Y., Claessen, E., El Berkaoui, A., Koops, J., Kruijne, E., Lodewijk, C., Munjishvili, L., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Rutkens, T., Schoorl, M., Timmerman, A., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Woudstra, T., Tuk, B., Popielska, J., Pokorska-Śpiewak, M., Ołdakowska, A., Zawadka, K., Coupland, U., DorobaLaura Marques, M., Teixeira, C., Fernandes, A., Voronin, E., Miloenko, M., Labutina, S., Tomás Ramos, J., Prieto, L., Luisa Navarro, M., Saavedra, J., Santos, M., Angeles Muñoz, M., Ruiz, B., Mc Phee CF, de Ory SJ, Alvarez, S., Ángel Roa, M., Beceiro, J., Martínez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Gómez Sirvent, J., Garzón, M., Román, V., Montesdeoca, A., Mateo, M., José Muñoz, M., Angulo, R., Neth, O., Falcón, L., Terol, P., Luis Santos, J., Moreno, D., Lendínez, F., Grande, A., José Romero, F., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Antonio Couceiro, J., Pérez, A., Isabel Piqueras, A., Bretón, R., Segarra, I., Gavilán, C., Jareño, E., Montesinos, E., Dapena, M., Álvarez, C., Gloria Andrés, A., Marugán, V., Ochoa, C., Alfayate, S., Isabel Menasalvas, A., de Miguel, E., Aebi-Popp, K., Asner, S., Aubert, V., Battegay, M., Baumann, M., Bernasconi, E., Böni, J., Brazzola, P., Bucher, H., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C., Grawe, C., Günthard, H., Haerry, D., Hasse, B., Hirsch, H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., de Tejada BM, Metzner, K., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Polli, C., Posfay-Barbe, K., Rauch, A., Rudin, C., Schmid, P., Scherrer, A., Speck, R., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C., Yerly, S., Techakunakorn, P., Hansudewechakul, R., Kham, C., Wanchaitanawong, V., Theansavettrakul, S., Sai, M., Nanta, S., Ngampiyaskul, C., Phanomcheong, S., Hongsiriwon, S., Karnchanamayul, W., Kwanchaipanich, R., Kanjanavanit, S., Kamonpakorn, N., Nantarukchaikul, M., Layangool, P., Mekmullica, J., Lucksanapisitkul, P., Watanayothin, S., Lertpienthum, N., Warachit, B., Hanpinitsak, S., Potchalongsin, S., Thanasiri, P., Krikajornkitti, S., Attavinijtrakarn, P., Srirojana, S., Bunjongpak, S., Puangsombat, A., Na-Rajsima, S., Ananpatharachai, P., Akarathum, N., Phuket, V., Lawtongkum, W., Kheunjan, P., Suriyaboon, T., Saipanya, A., Than-In-At, K., Jaisieng, N., Suaysod, R., Chailoet, S., Naratee, N., Kawilapat, S., Kaleeva, T., Baryshnikova, Y., Soloha, S., Bashkatova, N., Raus, I., Glutshenko, O., Ruban, Z., Prymak, N., Bailey, H., Bamford, A., Butler, K., Doerholt, K., Doherty, C., Foster, C., Francis, K., Harrison, I., Kenny, J., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Peters, H., Prime, K., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Turkova, A., Welch, S., Jeannie Collins, I., Cook, C., Crichton, S., Dobson, D., Fairbrother, K., M Gibb D, Harper, L., Le Prevost, M., Van Looy, N., Walsh, A., Thrasyvoulou, L., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Sloper, K., Fidler, K., Hague, R., Price, V., Clapson, M., Flynn, J., Cardoso, A., Abou-Rayyah, M., Gurtin, D., Yeadon, S., Segal, S., Ball, C., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Clough, S., Anguvaa, L., Conway, S., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, B., Pope, S., Cliffe, L., Smyth, A., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Rogahn, D., Clarke, L., Jones, L., Offerman, B., Greenberg, M., Benson, C., Ibberson, L., Faust, S., Hancock, J., Sharland, M., Lyall, H., Monrose, C., Seery, P., Menson, E., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Critchton, S., Duff, C., Gomezpena, D., Lundin, R., Mangiarini, L., Nardone, A., Posfay Barbe, Klara, Universidad de Alcalá - University of Alcalá (UAH), Department of Sciences for Woman and Child's Health, Università degli Studi di Firenze = University of Florence (UniFI), Épidémiologie clinique, santé mère-enfant et VIH en Asie du Sud-Est (IRD_PHPT), Harvard University-Chiang Mai University (CMU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Saint-Denis [Ile-de-France], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universitätsklinikum Frankfurt, Infectious Diseases, San Martino Hospital, Università degli studi di Genova = University of Genoa (UniGe), Department of Maternal and Pediatric Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Maternal-Infantile Department, Unit of Paediatrics and Oncohematology, University Hospital of Parma, Department of Infectious Diseases, IRCCS S. Matteo, Department of Paediatrics, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Dipartimento di Ingegneria [Benevento], Università degli Studi del Sannio, University of Twente, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Infectious Diseases and Perinatal Screening, Center for Infectious Disease Control, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Synthèse, Structure et Propriétés de Matériaux Fonctionnels (STEP), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Stichting HIV Monitoring, Universidade Federal do Ceará = Federal University of Ceará (UFC), Departamento de Química Orgánica, Universidade de Vigo, Polytechnical University of Valencia, Fac Biol, Dept Genet, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Service des maladies infectieuses, Hôpitaux Universitaires de Genève (HUG), University of Basel (Unibas), Dysfonctions métaboliques et diabètes: Mécanismes et approches thérapeutiques, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), University Heart Centre Freiburg - Bad Krozingen, Prapokklao Hospital [Chanthaburi, Thailand], Nakornping Hospital [Chiang Mai, Thailand], Samutsakhon Hospital [Samutsakhon, Thailand], Kalasin Hospital [Kalasin, Thailand], Sanpatong Hospital [Chiang Mai, Thailand], Chiang Mai University (CMU), Microbiology Department, St. Jame's Hospital, University of Edinburgh, Infectious Diseases and Microbiology Unit, Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, European Synchrotron Radiation Facility (ESRF), Centre for Ecology and Hydrology [Bangor] (CEH), Natural Environment Research Council (NERC), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), University of London [London], London South Bank University (LSBU), Dipartimento di Pediatria, Azienda Ospedaliera di Padova, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord, Florence University, Harvard University [Cambridge]-Chiang Mai University (CMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University of Genoa (UNIGE), Catholic University of Rome, University of Twente [Netherlands], Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), University of the Basque Country [Bizkaia] (UPV/EHU), Université Nice Sophia Antipolis (... - 2019) (UNS), Pediatrics, Virology, Chappell, Elizabeth, Riordan, Andrew, Jourdain, Gonzague, Soriano-Arandes, Antoni, Ene, Luminita, J Scherpbier, Henriette, Warszawski, Josiane, J Collins, Intira, Smit, Colette, Marques, Laura, Klein, Nigel, Guillén, Sara, Judd, Ali, Thorne, Claire, Goodall, Ruth, Königs, Christoph, Spoulou, Vana, Prata, Filipa, Goetghebuer, Tessa, Chiappini, Elena, Galli, Luisa, Naver, Lar, Giaquinto, Carlo, M Gibb, Diana, Marczynska, Magdalena, Okhonskaia, Liubov, Klimkait, Thoma, Lallemant, Marc, Ngo-Giang-Huong, Nicole, Kiseleva, Galyna, Malyuta, Ruslan, Volokha, Alla, Hainaut, Marc, Delforge, Marc, Le Chenadec, Jerome, Ramos, Elisa, Dialla, Olivia, Wack, Thierry, Laurent, Corine, Ait Si Selmi, Lamya, Leymarie, Isabelle, Ait Benali, Fazia, Brossard, Maud, Boufassa, Leila, Floch-Tudal, Corinne, Firtion, Ghislaine, Hau, Isabelle, Chace, Anne, Bolot, Pascal, Blanche, Stéphane, Levine, Martine, Kremlin Bicëtre, Le, Fourcade, Corinne, Heller-Roussin, Brigitte, Runel-Belliard, Camille, Tricoire, Joëlle, Chirouze, Catherine, Reliquet, Véronique, Brouard, Jacque, Kebaili, Kamila, Fialaire, Pascale, Lalande, Muriel, Schultze-Strasser, Stephan, Baumann, U, Niehues, T, Neubert, J, Kobbe, R, Berlin, Charite, Feiterna-Sperling, C, Königs, C, Buchholz, B, Notheis, G, de Martino, Maurizio, Angelo Tovo, Pier, Patrizia, Osimani, Larovere, Domenico, Ruggeri, Maurizio, Faldella, Giacomo, Baldi, Francesco, Badolato, Raffaele, Montagnani, Carlotta, Venturini, Elisabetta, Lisi, Catiuscia, Di Biagio, Antonio, Taramasso, Lucia, Giacomet, Vania, Erba, Paola, Esposito, Susanna, Lipreri, Rita, Salvini, Filippo, Tagliabue, Claudia, Cellini, Monica, Bruzzese, Eugenia, LO VECCHIO, Andrea, Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam institute for Infection and Immunity, AII - Infectious diseases, Amsterdam Reproduction & Development (AR&D), APH - Aging & Later Life, Infectious diseases, and Global Health

Subjects
0301 basic medicine, medicine.medical_treatment, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections, Rate ratio, Cohort Studies, 0302 clinical medicine, Pregnancy, Antiretroviral Therapy, Highly Active, Prevalence, 030212 general & internal medicine, Child, poor immune response, ddc:618, Immunosuppression, Viral Load, Hepatitis B, Thailand, 3. Good health, Europe, Thailand/epidemiology, Infectious Diseases, Cohort, Coinfection, Female, Cohort study, Adult, Microbiology (medical), viral suppression, medicine.medical_specialty, Adolescent, Anti-HIV Agents, antiretroviral therapy, 030106 microbiology, Europe/epidemiology, 03 medical and health sciences, children, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, HIV, Aged, Settore MED/38 - Pediatria Generale e Specialistica, business.industry, Immunity, medicine.disease, HIV Infections/drug therapy/epidemiology, CD4 Lymphocyte Count, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Anti-HIV Agents/therapeutic use, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children Results Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P < .001). Conclusions One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders.

Published
2020
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32. Variation in paediatric hospital antibiotic guidelines in Europe

Author

Spyridis, N, Syridou, G, Goossens, H, Versporten, A, Kopsidas, J, Kourlaba, G, Bielicki, J, Drapier, N, Zaoutis, T, Tsolia, M, Sharland, M, Vergison, A, Léon, V, Delestrait, M, Huza, C, Lepage, P, Mahieu, L, Boy, T, Jansens, H, Van der Linden, D, Briquet, C, Allegaert, K, Smits, A, Gabriels, P, Vuye, A, Lutsar, I, Tamm, E, Larionova, A, Laan, D, Orbach, M, Lorrot, M, Angoulvant, F, Prot-Labarthe, S, Dubos, F, Lagree, M, Hufnagel, M, Schuster, K, Henneke, P, Roilides, E, Iosifidis, E, Corovessi, V, Michos, A, Galanakis, E, Gkentzi, D, Giacquinto, C, Longo, G, Dona, D, Mion, T, DʼArgenio, P, Degli, ML Ciofi, De Luca, M, Ciliento, G, Esposito, S, Danieli, E, Montinaro, V, Tenconi, R, Nicolini, G, Sviestina, C I Montagnani, Pavare, J, Rasnaca, K, Gardovska, D, Grope, I, Usonis, V, Gurksniene, V, Eidukaite, A, Biver, A, Brett, A, Esteves, I, Cambrea, SC, Craiu, M, Tomescu, E, Cizman, M, Babnik, J, Kenda, R, Vidmar, I, Nunez-Cuadros, E, Rojo, P, Lopez-Varela, E, Ureta, N, Mosqueda, R, Perez-Lopez, A, Orta, L, Santos, M, Navarro, M, Santiago, B, Hernandez-Sampelaya, T, Saavedra, J, Pineiro, R, Torel, P, Mate Cano, I, Baumann, P, Berger, C, Menson, E, Botgros, A, Doerholt, K, Drysdale, S, Makwana, N, McCorry, A, Garbash, EM, Chetcutiganado, C, McLeod, M, Caldwell, N, Nash, C, McCullagh, B, Sharpe, D, Tweddell, L, Liese, JG, Aston, J, Gallagher, A, Satodia, P, Howard-Smith, N, Korinteli, I, Tavchioska, G, Jensen, L, Trethon, A, Unuk, S, Childs, N, and Canlas, J

Published
2016
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36. Global Divergence of Antifungal Prescribing Patterns: Data From the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children Surveys

Author

Ferreras-Antolin, L, Bielicki, J, Warris, A, Sharland, M, Hsia, Y, and GARPEC Network

Abstract

BACKGROUND: Globally, invasive fungal diseases (IFDs) have a significant impact in human health. With an increasing pediatric population at risk of IFD, effective antifungal drugs access and affordability should be ensured universally. The aim of our study was to characterize the global antifungal drug use in neonates and children and its variability between countries in different income groups. METHODS: Data were extracted from the Global Antimicrobial Resistance, Prescribing and Efficacy in Neonates and Children Point Prevalence Survey project, consisting in 1 pilot and four 1-day Point Prevalence Survey between 2015 and 2017. The data had been entered through a study-specific web-based data collection tool. RESULTS: From a total of 13,410 children included, 7.8% (1048/13,410) received at least 1 systemic antifungal drug: 9.5% (95% confidence interval: 8.9%-10.1%) in high income countries (HIC) versus 5.0% (95% confidence interval: 4.4%-5.6%) in low-middle income countries (LMIC) (P < 0.01). A significant proportion of patients on antifungals belonged to high-risk group for IFD (67.4%; 706/1048); most of these were managed in HIC (72.8%, P < 0.01). The likelihood of receiving antifungals being in high-risk group was higher in HIC compared with LMIC (ratio of 5.8 vs. 3.4, P < 0.01). Antifungal prophylaxis was more likely prescribed in HIC (67.2% vs. 30.4%, P < 0.01). Fluconazole was the most frequently prescribed drug. The proportional use of fluconazole was higher in LMIC compared with HIC. CONCLUSIONS: A significant variability of antifungal prescribing patterns was observed. The proportional use of systemic antifungals was twice as high in HIC compared with LMIC. More detailed data on access and antifungal use in limited-resource settings should be explored.

Published
2021

37. Enhanced surveillance of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in children in the UK and Ireland

Author

Johnson, A.P., Sharland, M., Goodall, C.M., Blackburn, R., Kearns, A.M., Gilbert, R., Lamagni, T.L., Charlett, A., Ganner, M., Hill, R., Cookson, B., Livermore, D., Wilson, J., Cunney, R., Rossney, A., and Duckworth, G.

Subjects
Staphylococcus aureus infections -- Demographic aspects, Staphylococcus aureus infections -- Distribution, Staphylococcus aureus infections -- Reports, Sentinel health events -- Demographic aspects, Sentinel health events -- Reports, Company distribution practices
Published
2010

39. Changes in clinical indications for community antibiotic prescribing for children in the UK from 1996 to 2006: will the new NICE prescribing guidance on upper respiratory tract infections just be ignored?

Author

Thompson, P.L., Spyridis, N., Sharland, M., Gilbert, R.E., Saxena, S., Long, P.F., Johnson, A.P., and Wong, I.C.K.

Subjects
Respiratory tract infections -- Care and treatment, Drug therapy -- Standards, Practice guidelines (Medicine) -- Usage, Drugs -- Prescribing, Drugs -- Standards
Published
2009

40. Tuberculosis in the United Kingdom and Republic of Ireland

Author

Teo, S.S.S., Riordan, A., Alfaham, M., Clark, J., Evans, M.R., Sharland, M., Novelli, V., Watson, J.M., Sonnenberg, P., Hayward, A., Moore-Gillon, J., and Shingadia, D.

Subjects
Tuberculosis -- Distribution, Tuberculosis -- Demographic aspects, Tuberculosis -- Research, Pediatric respiratory diseases -- Distribution, Pediatric respiratory diseases -- Research, Tuberculosis in children -- Distribution, Tuberculosis in children -- Demographic aspects, Tuberculosis in children -- Research, Company distribution practices
Published
2009

41. Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe-results from the PED-MERMAIDS multicentre case-control study

Author

Vasconcelos, M.K. Loens, K. Sigfrid, L. Iosifidis, E. Epalza, C. Donà, D. Matheeussen, V. Papachristou, S. Roilides, E. Gijon, M. Rojo, P. Minotti, C. Da Dalt, L. Islam, S. Jarvis, J. Syggelou, A. Tsolia, M. Nyang'wa, M.N. Keers, S. Renk, H. Gemmel, A.-L. D'Amore, C. Atti, M.C.D. Sánchez, C.R.-T. Martinón-Torres, F. Burokiene, S. Goetghebuer, T. Spoulou, V. Riordan, A. Calvo, C. Gkentzi, D. Hufnagel, M. Openshaw, P.J. De Jong, M.D. Koopmans, M. Goossens, H. Ieven, M. Fraaij, P.L.A. Giaquinto, C. Bielicki, J.A. Horby, P. Sharland, M.

Subjects
viruses, respiratory tract diseases
Abstract

Background Both pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation. Methods 349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets. Results RSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses. Conclusion RSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent. © 2016 Georg Thieme Verlag. All rights reserved.

Published
2021

42. β-Lactam antimicrobial pharmacokinetics and target attainment in critically ill patients aged 1 day to 90 years: the ABDose study

Author

Lonsdale, DO, Kipper, K, Baker, EH, Barker, CIS, Oldfield, I, Philips, BJ, Johnston, A, Rhodes, A, Sharland, M, and Standing, JF

Abstract

Background\ud The pharmacokinetics of β-lactam antibiotics in critical illness remain poorly characterized, particularly in neonates, children and the elderly. We undertook a pharmacokinetic study of commonly used β-lactam antibiotics in critically ill patients of all ages. The aims were to produce a whole-life β-lactam pharmacokinetic model and describe the extent to which standard doses achieve pharmacokinetic/pharmacodynamic targets associated with clinical cure.\ud \ud Patients and methods\ud A total of 212 critically ill participants with an age range from 1 day (gestational age 24 weeks) to 90 years were recruited from a UK hospital, providing 1339 pharmacokinetic samples. Population pharmacokinetic analysis was undertaken using non-linear mixed-effects modelling (NONMEM) for each drug. Pooled data were used to estimate maturation and decline of β-lactam pharmacokinetics throughout life.\ud \ud Results\ud Pharmacokinetic models for eight drugs were described, including what is thought to be the first benzylpenicillin model in critically ill adults. We estimate that 50% of adult β-lactam clearance is achieved by 43 weeks post-menstrual age (chronological plus gestational age). Fifty percent of decline from peak adult clearance occurs by 71 years. Paediatric participants were significantly less likely than adults to achieve pharmacokinetic/pharmacodynamic targets with standard antibiotic doses (P

Published
2020

43. The current state of immunization against Gram-negative bacteria in children: a review of the literature

Author

Broad, J, Le Doare, K, Heath, P, Hallchurch, P, Whelan, I, Boyd, H, Carruthers, E, Sharland, M, and Ladhani, S

Abstract

Purpose of review \ud Gram-negative bacteria (GNB) are a major cause of infection worldwide and multidrug resistance in infants and children. The major pathogens include Klebsiella pneumoniae, Escherichia coli, Enterobacter spp., Pseudomonas aeruginosa and Acinetobacter baumannii. With new antibiotic options limited, immunization is likely to play a critical role in prevention. This review discusses their epidemiology, the current state of vaccine research and potential immunization strategies to protect children. A comprehensive review of the literature, conference abstracts along with web searches was performed to identify current and investigational vaccines against the major GNB in children.\ud \ud Recent findings \ud Phase I--III vaccine trials have been undertaken for the major Gram-negative bacteria but not in infants or children. E. coli is a common infection in immune-competent children, including neonatal sepsis. Several vaccines are in late-phase clinical trials, with some already licensed for recurrent urinary tract infections in women. Klebsiella spp. causes community-acquired and hospital-acquired infections, including sepsis in neonates and immunocompromised children although no vaccine trials have extended beyond early phase 2 trials. P. aeruginosa is a common pathogen in patients with cystic fibrosis. Phase 1--3 vaccine and monoclonal antibody trials are in progress, although candidates provide limited coverage against pathogenic strains. Enterobacter spp. and A. baumannii largely cause hospital-acquired infections with experimental vaccines limited to phase 1 research.\ud \ud Summary \ud The current immunization pipelines for the most prevalent GNB are years away from licensure. Similar to incentives for new antibiotics, global efforts are warranted to expedite the development of effective vaccines.

Published
2020

44. Appropriateness of Antibiotic Prescribing in United States Children’s Hospitals: A National Point Prevalence Survey

Author

Tribble, AC, Lee, BR, Flett, KB, Handy, LK, Gerber, JS, Hersh, AL, Kronman, MP, Terrill, CM, Sharland, M, and Newland, JG

Abstract

BACKGROUND: Studies estimate that 30-50% of antibiotics prescribed for hospitalized patients are inappropriate, but pediatric data are limited. Characterization of inappropriate prescribing practices for children are needed to guide pediatric antimicrobial stewardship. METHODS: Cross-sectional analysis of antibiotic prescribing at 32 US children's hospitals. Subjects included hospitalized children with ≥1 antibiotic order at 0800 on one day per calendar quarter, over six quarters (Quarter 3 2016 - Quarter 4 2017). Antimicrobial stewardship program (ASP) physicians and/or pharmacists used a standardized survey to collect data on antibiotic orders and evaluate appropriateness. The primary outcome was the percentage of antibiotics prescribed for infectious use that were classified as suboptimal, defined as inappropriate or needing modification. RESULTS: Of 34 927 children hospitalized on survey days, 12 213 (35.0%) had ≥1 active antibiotic order. Among 11 784 patients receiving antibiotics for infectious use, 25.9% were prescribed ≥1 suboptimal antibiotic. Of the 17 110 antibiotic orders prescribed for infectious use, 21.0% were considered suboptimal. Most common reasons for inappropriate use were bug-drug mismatch (27.7%), surgical prophylaxis >24 hours (17.7%), overly broad empiric therapy (11.2%), and unnecessary treatment (11.0%). The majority of recommended modifications were to stop (44.7%) or narrow (19.7%) the drug. ASPs would not have routinely reviewed 46.1% of suboptimal orders. CONCLUSIONS: Across 32 children's hospitals, approximately 1 in 3 hospitalized children are receiving one or more antibiotics at any given time. One quarter of these children are receiving suboptimal therapy, and nearly half of suboptimal use is not captured by current ASP practices.

Published
2020

45. Understanding antibiotic availability and use in low and middle income countries: Insights from health facility surveys

Author

Knowles, R, Sharland, M, Hsia, Y, Magrini, N, Moja, L, Siyam, A, and Tayler, E

Abstract

Objective To assess antibiotic availability and use in health facilities in low- and middle-income countries, using the service provision assessment and service availability and readiness assessment surveys. Methods We obtained data on antibiotic availability at 13 561 health facilities in 13 service provision assessment and 8 service availability and readiness assessment surveys. In 10 service provision assessment surveys, child consultations with health-care providers were observed, giving data on antibiotic use in 22 699 children. Antibiotics were classified as access, watch or reserve, according to the World Health Organization’s AWaRe categories. The percentage of health-care facilities across countries with specific antibiotics available and the proportion of children receiving antibiotics for key clinical syndromes were estimated. Findings The surveys assessed the availability of 27 antibiotics (19 access, 7 watch, 1 unclassified). Co-trimoxazole and metronidazole were most widely available, being in stock at 89.5% (interquartile range, IQR: 11.6%) and 87.1% (IQR: 15.9%) of health facilities, respectively. In contrast, 17 other access and watch antibiotics were stocked, by fewer than a median of 50% of facilities. Of the 22 699 children observed, 60.1% (13 638) were prescribed antibiotics (maostly co-trimoxazole or amoxicillin). Children with respiratory conditions were most often prescribed antibiotics (76.1%; 8972/11 796) followed by undifferentiated fever (50.1%; 760/1518), diarrhoea (45.7%; 1293/2832) and malaria (30.3%; 352/1160). Conclusion Routine health facility surveys provided a valuable data source on the availability and use of antibiotics in low- and middle-income countries. Many access antibiotics were unavailable in a majority of most health-care facilities.

Published
2020
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46. Evaluation of the coverage of three antibiotic regimens for neonatal sepsis in the 1 hospital setting across Asian countries

Author

Bielicki, JA, Sharland, M, Heath, PT, Walker, AS, Agarwal, R, Turner, P, and Cromwell, DA

Abstract

Importance High levels of antimicrobial resistance in neonatal bloodstream isolates are being reported globally, including in Asia. Local hospital antibiogram data may include too few isolates to meaningfully examine the expected coverage of antibiotic regimens. Objective To assess the coverage offered by 3 antibiotic regimens for empirical treatment of neonatal sepsis in Asian countries. Design, Setting, and Participants A decision analytical model was used to estimate coverage of 3 prespecified antibiotic regimens according to a weighted-incidence syndromic combination antibiogram. Relevant data to parameterize the models were identified from a systematic search of Ovid MEDLINE and Embase. Data from Asian countries published from 2014 onward were of interest. Only data on blood culture isolates from neonates with sepsis, bloodstream infection, or bacteremia reported from the relevant setting were included. Data analysis was performed from April 2019 to July 2019. Exposures The prespecified regimens of interest were aminopenicillin-gentamicin, third-generation cephalosporins (cefotaxime or ceftriaxone), and meropenem. The relative incidence of different bacteria and their antimicrobial susceptibility to antibiotics relevant for determining expected concordance with these regimens were extracted. Main Outcomes and Measures Coverage was calculated on the basis of a decision-tree model incorporating relative bacterial incidence and antimicrobial susceptibility of relevant isolates. Data on 7 bacteria most commonly reported in the included studies were used for estimating coverage, which was reported at the country level. Results Data from 48 studies reporting on 10 countries and 8376 isolates were used. Individual countries reported 51 (Vietnam) to 6284 (India) isolates. Coverage varied considerably between countries. Meropenem was generally estimated to provide the highest coverage, ranging from 64.0% (95% credible interval [CrI], 62.6%-65.4%) in India to 90.6% (95% CrI, 86.2%-94.4%) in Cambodia, followed by aminopenicillin-gentamicin (from 35.9% [95% CrI, 27.7%-44.0%] in Indonesia to 81.0% [95% CrI, 71.1%-89.7%] in Laos) and cefotaxime or ceftriaxone (from 17.9% [95% CrI, 11.7%-24.7%] in Indonesia to 75.0% [95% CrI, 64.8%-84.1%] in Laos). Aminopenicillin-gentamicin coverage was lower than that of meropenem in all countries except Laos (81.0%; 95% CrI, 71.1%-89.7%) and Nepal (74.3%; 95% CrI, 70.3%-78.2%), where 95% CrIs for aminopenicillin-gentamicin and meropenem were overlapping. Third-generation cephalosporin coverage was lowest of the 3 regimens in all countries. The coverage difference between aminopenicillin-gentamicin and meropenem for countries with nonoverlapping 95% CrIs ranged from −15.9% in China to −52.9% in Indonesia. Conclusions and Relevance This study’s findings suggest that noncarbapenem antibiotic regimens may provide limited coverage for empirical treatment of neonatal sepsis in many Asian countries. Alternative regimens must be studied to limit carbapenem consumption.

Published
2020

47. Association of Empiric Antibiotic Regimen Discordance with 30-Day Mortality in Neonatal and Pediatric Bloodstream Infection - A Global Retrospective Cohort Study.

Author

Cook A., Hsia Y., Russell N., Sharland M., Cheung K., Grimwood K., Cross J., Cotrim Da Cunha D., Magalhaes G.R., Renk H., Hindocha A., McMaster P., Okomo U., Darboe S., Alvarez-Uria G., Jinka D.R., Murki S., Kandraju H., Dharmapalan D., Esposito S., Bianchini S., Fukuoka K., Aizawa Y., Jimenez-Juarez R.N., Ojeda-Diezbarroso K., Pirs M., Rozic M., Anugulruengkitt S., Jantarabenjakul W., Cheng C.-L., Jian B.-X., Spyridakis E., Zaoutis T., Bielicki J., Cook A., Hsia Y., Russell N., Sharland M., Cheung K., Grimwood K., Cross J., Cotrim Da Cunha D., Magalhaes G.R., Renk H., Hindocha A., McMaster P., Okomo U., Darboe S., Alvarez-Uria G., Jinka D.R., Murki S., Kandraju H., Dharmapalan D., Esposito S., Bianchini S., Fukuoka K., Aizawa Y., Jimenez-Juarez R.N., Ojeda-Diezbarroso K., Pirs M., Rozic M., Anugulruengkitt S., Jantarabenjakul W., Cheng C.-L., Jian B.-X., Spyridakis E., Zaoutis T., and Bielicki J.

Abstract

Background: While there have been studies in adults reporting discordant empiric antibiotic treatment associated with poor outcomes, this area is relatively unexplored in children and neonates despite evidence of increasing resistance to recommended first-line treatment regimens. Method(s): Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children <18 years with blood-culture-confirmed bacterial bloodstream infections (BSI) were collected anonymously using REDCapTM through the Global Antibiotic Prescribing and Resistance in Neonates and Children network from February 2016 to February 2017. Concordance of early empiric antibiotic treatment was determined using European Committee on Antimicrobial Susceptibility Testing interpretive guidelines. The relationship between concordance of empiric regimen and 30-day mortality was investigated using multivariable regression. Result(s): Four hundred fifty-two children with blood-culture-positive BSI receiving early empiric antibiotics were reported by 25 hospitals in 19 countries. Sixty percent (273/452) were under the age of 2 years. S. aureus, E. coli, and Klebsiella spp. were the most common isolates, and there were 158 unique empiric regimens prescribed. Fifteen percent (69/452) of patients received a discordant regimen, and 7.7% (35/452) died. Six percent (23/383) of patients with concordant regimen died compared with 17.4% (12/69) of patients with discordant regimen. Adjusting for age, sex, presence of comorbidity, unit type, hospital-acquired infections, and Gram stain, the odds of 30-day mortality were 2.9 (95% confidence interval: 1.2-7.0; P = 0.015) for patients receiving discordant early empiric antibiotics. Conclusion(s): Odds of mortality in confirmed pediatric BSI are nearly 3-fold higher for patients receiving a discordant early empiric antibiotic regimen. The impact of improved concordance of early empiric treatment on mortality, particularly in critically ill patie

Published
2021

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