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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.
AuthorsLucio R Minces, M Hong Nguyen, Dimitra Mitsani, Ryan K Shields, Eun J Kwak, Fernanda P Silveira, Rima Abdel-Massih, Joseph M Pilewski, Maria M Crespo, Christian Bermudez, Jay K Bhama, Yoshiya Toyoda, Cornelius J Clancy
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 58 Issue 1 Pg. 128-35 ( 2014) ISSN: 1098-6596 [Electronic] United States
PMID24145525 (Publication Type: Journal Article)
Chemical References
  • Antiviral Agents
  • Foscarnet
  • Ganciclovir
Topics
  • Adult
  • Aged
  • Antiviral Agents (therapeutic use)
  • Cytomegalovirus Infections (drug therapy)
  • Drug Resistance, Viral (drug effects)
  • Female
  • Foscarnet (therapeutic use)
  • Ganciclovir (therapeutic use)
  • Humans
  • Lung Transplantation
  • Male
  • Middle Aged
  • Retrospective Studies
  • Viremia (drug therapy)
  • Young Adult

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