Ganciclovir-resistant cytomegalovirus infections among lung transplant recipients are associated with poor outcomes despite treatment with foscarnet-containing regimens.

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
  • 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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: