Use of high-dose ganciclovir for the treatment of cytomegalovirus replication in solid organ transplant patients with ganciclovir resistance-inducing mutations

• Published in: Transplantation Vol. 95; no. 8; pp. 1015 - 1020
• Main Authors: Gracia-Ahufinger, Irene, Gutiérrez-Aroca, Juan, Cordero, Elisa, Vidal, Elisa, Cantisán, Sara, del Castillo, Domingo, Martín-Gandul, Cecilia, Rivero, Antonio, Torre-Cisneros, Julián
• Format: Journal Article
• Language: English
• Published: United States 27-04-2013
• Subjects: Adoption; Adult; Antiviral Agents - administration & dosage; Cytomegalovirus; Cytomegalovirus - drug effects; Cytomegalovirus - genetics; Cytomegalovirus - physiology; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - etiology; Cytomegalovirus Infections - prevention & control; Cytomegalovirus Infections - virology; Drug Resistance, Viral - genetics; Female; Ganciclovir - administration & dosage; Ganciclovir - analogs & derivatives; Genes, Viral; Humans; Male; Middle Aged; Mutation; Organ Transplantation - adverse effects; Viral Load - drug effects; Virus Replication - drug effects
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/TP.0b013e31828555ac

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.
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.
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.
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.