title: Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance.
abstract: 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.
  
  
  
  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.
  
  
  
  Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona Institute for Global Health, Barcelona, (ISGlobal), Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: López-Aladid
authors.affiliation: Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona Institute for Global Health, Barcelona, (ISGlobal), Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Guiu
authors.affiliation: Department of Infectious Diseases, Hospital Clinic, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Sanclemente
authors.affiliation: Unit of Infectious Diseases, Instituto de Investigación Hospital 12 Octubre (i + 12) University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: López-Medrano
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Frederic
authors.initials: F
authors.lastname: Cofán
authors.affiliation: Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona Institute for Global Health, Barcelona, (ISGlobal), Spain.
authors.forename: M Mar
authors.initials: MM
authors.lastname: Mosquera
authors.affiliation: Clinical Unit of Infectious Diseases, Hospital Universitario Reina Sofia-IMIBIC-UCO, Córdoba, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Torre-Cisneros
authors.affiliation: Clinical Unit of Infectious Diseases, Hospital Universitario Reina Sofia-IMIBIC-UCO, Córdoba, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Vidal
authors.affiliation: Department of Infectious Diseases, Hospital Clinic, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Unit of Infectious Diseases, Instituto de Investigación Hospital 12 Octubre (i + 12) University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Aguado
authors.affiliation: 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.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cordero
authors.affiliation: 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.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martin-Gandul
authors.affiliation: 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.
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez-Romero
authors.affiliation: Department of Infectious Diseases, Bellvitge University Hospital, IDIBELL, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Carratalá
authors.affiliation: Department of Infectious Diseases, Bellvitge University Hospital, IDIBELL, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Sabé
authors.affiliation: Department of Clinical Microbiology, Bellvitge University Hospital, IDIBELL, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Niubó
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alberto, Edmonton, Canada.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cervera
authors.affiliation: Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona Institute for Global Health, Barcelona, (ISGlobal), Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Cervilla
authors.affiliation: Department of Infectious Diseases, Hospital Clinic, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bodro
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitario Gregorio Marañón, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fariñas
authors.affiliation: Microbiology Service, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: M Gemma
authors.initials: MG
authors.lastname: Codina
authors.affiliation: Servicio de Microbiología, Hospital Universitario de Cruces, Bilbao, Spain.
authors.forename: Maitane
authors.initials: M
authors.lastname: Aranzamendi
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario de Cruces, Bilbao, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Montejo
authors.affiliation: Department of Infectious Diseases, Hospital Universitari Vall d'Hebrón, Uniiversitat Autónoma de Barcelona, Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Len
authors.affiliation: Department of Clinical Microbiology, Hospital Clinic, Universidad de Barcelona, Barcelona Institute for Global Health, Barcelona, (ISGlobal), Spain. Electronic address: mmarcos@clinic.ub.es.
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Marcos
mesh_terms: D000328:Adult; D000368:Aged; D003587:Cytomegalovirus / Q000235:genetics* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000821:virology*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D066027:Transplant Recipients; D019737:Transplants
chemical_list: D004279:DNA, Viral
keywords: Cytomegalovirus; Genotypic analysis; Solid organ transplantation; Suspected resistance