title: Ganciclovir-resistant cytomegalovirus infections among lung transplant recipients are associated with poor outcomes despite treatment with foscarnet-containing regimens.
abstract: Ganciclovir-resistant cytomegalovirus (CMV) infections are reported infrequently among lung transplant recipients receiving extended valganciclovir prophylaxis. We performed a single-center, retrospective review of ganciclovir-resistant CMV infections in a program that employed valganciclovir prophylaxis for ≥6 months after lung transplant. CMV infections were diagnosed in 28% (170/607) of patients. UL97 mutations were detected in 9.4% (16/170) of CMV-infected patients at a median of 8.5 months posttransplant (range, 5 to 21) and despite prophylaxis for a median of 7 months (range, 4 to 21). UL97 mutations were canonical; 25% (4/16) of strains carried concurrent UL54 mutations. Ganciclovir-resistant CMV was more likely with breakthrough infections (75% [12/16] versus 19% [30/154]; P = 0.00001) and donor positive/recipient negative (D+/R-) serostatus (75% versus 45% [69/154]; P = 0.03). The median whole-blood CMV load was 4.13 log10 copies/cm(3) (range, 2.54 to 5.53), and 93% (14/15) of patients had low-moderate immune responses (Cylex Immunoknow). Antiviral therapy was successful, failed, or eradicated viremia followed by relapse in 12% (2/16), 31% (5/16), and 56% (9/16) of patients, respectively. Eighty-seven percent (14/16) of patients were treated with foscarnet-containing regimens; toxicity developed in 78% (11/14) of these. Median viral load half-life and time to viremia eradication among foscarnet-treated patients were 2.6 and 23 days, respectively, and did not correlate with protection from relapse. Sixty-nine percent (11/16) of patients developed CMV pneumonitis, and 25% (4/16) died of it. Serum viral load was independently associated with death among foscarnet-treated patients (P = 0.04). In conclusion, ganciclovir-resistant CMV infections remained a major cause of morbidity and mortality following lung transplantation. Foscarnet-based regimens often eradicated viremia rapidly but were ineffective in the long term and limited by toxicity.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Lucio R
authors.initials: LR
authors.lastname: Minces
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Dimitra
authors.initials: D
authors.lastname: Mitsani
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Shields
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Kwak
authors.forename: Fernanda P
authors.initials: FP
authors.lastname: Silveira
authors.forename: Rima
authors.initials: R
authors.lastname: Abdel-Massih
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Pilewski
authors.forename: Maria M
authors.initials: MM
authors.lastname: Crespo
authors.forename: Christian
authors.initials: C
authors.lastname: Bermudez
authors.forename: Jay K
authors.initials: JK
authors.lastname: Bhama
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005260:Female; D017245:Foscarnet / Q000627:therapeutic use*; D015774:Ganciclovir / Q000627:therapeutic use*; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014766:Viremia / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D017245:Foscarnet; D015774:Ganciclovir