title: Use of high-dose ganciclovir for the treatment of cytomegalovirus replication in solid organ transplant patients with ganciclovir resistance-inducing mutations.
abstract: BACKGROUND
  Experience with high-dose ganciclovir for the management of resistant cytomegalovirus (CMV) replication in transplant patients is limited despite its adoption as an effective therapy by some consensus documents.
  
  
  METHODS
  We studied six cases of CMV replication in solid organ transplant patients whose genotypic testing showed mutations associated with different levels of resistance to ganciclovir. All were treated with high-dose intravenous ganciclovir (7.5-10 mg/kg/12 hr) or oral valganciclovir (1350-1800 mg/12 hr) corrected according to creatinine clearance. The virologic response was considered positive if the CMV plasma viral load was undetectable. Safety was evaluated by clinical assessment, including the review of vital signs and laboratory tests.
  
  
  RESULTS
  All patients had asymptomatic replication, except one who had digestive disease. Four patients received universal prophylaxis with valganciclovir. Two patients received preemptive therapy with valganciclovir for individual episodes of replication. Two of the six patients received steroid boluses before the episode of replication by resistant CMV. All patients responded to treatment, including those with mutations associated with a high level of ganciclovir resistance. Four patients had neutropenia (<1.5 × 10/L), but only one received treatment.
  
  
  CONCLUSIONS
  High-dose ganciclovir/valganciclovir can be an option in the treatment of resistant CMV replication and could be considered an alternative treatment in nonsevere patients for whom the use of foscarnet should be avoided. The toxicity of this regimen does not appear to limit its use.
authors: Clinical Microbiology Unit, IMIBIC-Reina Sofía University Hospital-University of Córdoba, Córdoba, Spain.
authors: Irene
authors: I
authors: Gracia-Ahufinger
authors: Juan
authors: J
authors: Gutiérrez-Aroca
authors: Elisa
authors: E
authors: Cordero
authors: Elisa
authors: E
authors: Vidal
authors: Sara
authors: S
authors: Cantisán
authors: Domingo
authors: D
authors: del Castillo
authors: Cecilia
authors: C
authors: Martín-Gandul
authors: Antonio
authors: A
authors: Rivero
authors: Julián
authors: J
authors: Torre-Cisneros
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D003587:Cytomegalovirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control / Q000821:virology; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage* / Q000031:analogs & derivatives; D005814:Genes, Viral; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016377:Organ Transplantation / Q000009:adverse effects*; D000077562:Valganciclovir; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir