Rubén López-Aladid1, Alba Guiu1, Gemma Sanclemente2, Francisco López-Medrano3, Frederic Cofán4, M Mar Mosquera1, Julián Torre-Cisneros5, Elisa Vidal5, Asunción Moreno2, Jose Maria Aguado3, Elisa Cordero6, Cecilia Martin-Gandul6, Pilar Pérez-Romero6, Jordi Carratalá7, Nuria Sabé7, Jordi Niubó8, Carlos Cervera9, Anna Cervilla1, Marta Bodro2, Patricia Muñoz10, Carmen Fariñas11, M Gemma Codina12, Maitane Aranzamendi13, Miguel Montejo14, Oscar Len15, M Angeles Marcos16. 1. Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona Institute for Global Health, Barcelona, (ISGlobal), Spain. 2. Department of Infectious Diseases, Hospital Clinic, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain. 3. Unit of Infectious Diseases, Instituto de Investigación Hospital 12 Octubre (i + 12) University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain. 4. Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain. 5. Clinical Unit of Infectious Diseases, Hospital Universitario Reina Sofia-IMIBIC-UCO, Córdoba, Spain. 6. Infectious Diseases Department, Hospital Universitario Virgen del Rocío, Sevilla, Instituto de Biomedicina de Sevilla (IBIS), Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Spain. 7. Department of Infectious Diseases, Bellvitge University Hospital, IDIBELL, Barcelona, Spain. 8. Department of Clinical Microbiology, Bellvitge University Hospital, IDIBELL, Barcelona, Spain. 9. Department of Medicine, Division of Infectious Diseases, University of Alberto, Edmonton, Canada. 10. Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitario Gregorio Marañón, Madrid, Spain. 11. Unidad de Enfermedades Infecciosas, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain. 12. Microbiology Service, Hospital Vall d'Hebron, Barcelona, Spain. 13. Servicio de Microbiología, Hospital Universitario de Cruces, Bilbao, Spain. 14. Unidad de Enfermedades Infecciosas, Hospital Universitario de Cruces, Bilbao, Spain. 15. Department of Infectious Diseases, Hospital Universitari Vall d'Hebrón, Uniiversitat Autónoma de Barcelona, Barcelona, Spain. 16. Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona Institute for Global Health, Barcelona, (ISGlobal), Spain. Electronic address: mmarcos@clinic.ub.es.
Abstract
BACKGROUND: Current guidelines recommend that treatment of resistant cytomegalovirus (CMV) in solid organ transplant (SOT) recipients must be based on genotypic analysis. However, this recommendation is not systematically followed. OBJECTIVES: To assess the presence of mutations associated with CMV resistance in SOT recipients with suspected resistance, their associated risk factors and the clinical impact of resistance. STUDY DESIGN: Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015. RESULTS: Of 39 patients studied, 9 (23%) showed resistance mutations. All had one mutation in the UL 97 gene and two also had one mutation in the UL54 gene. Resistance mutations were more frequent in lung transplant recipients (44% p=0.0068) and in patients receiving prophylaxis ≥6 months (57% vs. 17%, p=0.0180). The mean time between transplantation and suspicion of resistance was longer in patients with mutations (239 vs. 100days, respectively, p=0.0046) as was the median treatment duration before suspicion (45 vs. 16days, p=0.0081). There were no significant differences according to the treatment strategies or the mean CMV load at the time of suspicion. Of note, resistance-associated mutations appeared in one patient during CMV prophylaxis and also in a seropositive organ recipient. Incomplete suppression of CMV was more frequent in patients with confirmed resistance. CONCLUSIONS: Our study confirms the need to assess CMV resistance mutations in any patient with criteria of suspected clinical resistance. Early confirmation of the presence of resistance mutations is essential to optimize the management of these patients.
BACKGROUND: Current guidelines recommend that treatment of resistant cytomegalovirus (CMV) in solid organ transplant (SOT) recipients must be based on genotypic analysis. However, this recommendation is not systematically followed. OBJECTIVES: To assess the presence of mutations associated with CMV resistance in SOT recipients with suspected resistance, their associated risk factors and the clinical impact of resistance. STUDY DESIGN: Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015. RESULTS: Of 39 patients studied, 9 (23%) showed resistance mutations. All had one mutation in the UL 97 gene and two also had one mutation in the UL54 gene. Resistance mutations were more frequent in lung transplant recipients (44% p=0.0068) and in patients receiving prophylaxis ≥6 months (57% vs. 17%, p=0.0180). The mean time between transplantation and suspicion of resistance was longer in patients with mutations (239 vs. 100days, respectively, p=0.0046) as was the median treatment duration before suspicion (45 vs. 16days, p=0.0081). There were no significant differences according to the treatment strategies or the mean CMV load at the time of suspicion. Of note, resistance-associated mutations appeared in one patient during CMV prophylaxis and also in a seropositive organ recipient. Incomplete suppression of CMV was more frequent in patients with confirmed resistance. CONCLUSIONS: Our study confirms the need to assess CMV resistance mutations in any patient with criteria of suspected clinical resistance. Early confirmation of the presence of resistance mutations is essential to optimize the management of these patients.
Authors: Coretta C Van Leer Buter; Danielle W K de Voogd; Hans Blokzijl; Anoek A E de Joode; Stefan P Berger; Erik A M Verschuuren; Hubert G M Niesters Journal: J Antimicrob Chemother Date: 2019-08-01 Impact factor: 5.790
Authors: Marta Santos Bravo; Valentin Tilloy; Nicolas Plault; Sonsoles Sánchez Palomino; María Mar Mosquera; Mireia Navarro Gabriel; Francesc Fernández Avilés; María Suárez Lledó; Montserrat Rovira; Asunción Moreno; Laura Linares; Marta Bodro; Sébastien Hantz; Sophie Alain; María Ángeles Marcos Journal: Microbiol Spectr Date: 2022-03-28
Authors: Charlotte J Houldcroft; Sarah E Jackson; Eleanor Y Lim; George X Sedikides; Emma L Davies; Claire Atkinson; Megan McIntosh; Ester B M Remmerswaal; Georgina Okecha; Frederike J Bemelman; Richard J Stanton; Matthew Reeves; Mark R Wills Journal: Front Cell Infect Microbiol Date: 2020-06-26 Impact factor: 5.293