BACKGROUND: Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality after lung transplantation despite ganciclovir prophylaxis. The emergence of ganciclovir-resistant CMV in lung transplant patients has been reported, although the optimal strategy for the management of these infections remains uncertain. A review of the results of glanciclovir susceptibility testing in lung transplant recipients was performed. METHODS: We found 54% (113 of 210) of lung transplant patients developed CMV infection over a 4-year study period with ganciclovir-resistant CMV infection occurring in >5% of patients (6 of 113). The demographic and clinical characteristics of patients who developed ganciclovir-resistant vs -sensitive CMV infection were similar, although 50% (3 of 6) patients who developed resistance were CMV mismatched (D(+)/R(-) serology). All patients' CMV isolates had mutations in the UL97 gene. In addition, the 3 mismatch patients also had CMV with mutations in the UL54 gene. RESULTS: Treatment with a combination of foscarnet and ganciclovir or foscarnet alone for ganciclovir-resistant infection led to a significant reduction in virologic load in all patients (p = 0.03), although transient increases in viremia were observed in some patients early after treatment. Renal function worsened after treatment, but overall it was not significantly different from pre-treatment values (p = 0.07). CONCLUSIONS: Single or combination therapy with foscarnet is effective for treatment of ganciclovir-resistant isolates and excessive concern regarding toxicity should not preclude consideration of these treatments when clinically indicated.
BACKGROUND:Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality after lung transplantation despite ganciclovir prophylaxis. The emergence of ganciclovir-resistant CMV in lung transplant patients has been reported, although the optimal strategy for the management of these infections remains uncertain. A review of the results of glanciclovir susceptibility testing in lung transplant recipients was performed. METHODS: We found 54% (113 of 210) of lung transplant patients developed CMV infection over a 4-year study period with ganciclovir-resistant CMV infection occurring in >5% of patients (6 of 113). The demographic and clinical characteristics of patients who developed ganciclovir-resistant vs -sensitive CMV infection were similar, although 50% (3 of 6) patients who developed resistance were CMV mismatched (D(+)/R(-) serology). All patients' CMV isolates had mutations in the UL97 gene. In addition, the 3 mismatch patients also had CMV with mutations in the UL54 gene. RESULTS: Treatment with a combination of foscarnet and ganciclovir or foscarnet alone for ganciclovir-resistant infection led to a significant reduction in virologic load in all patients (p = 0.03), although transient increases in viremia were observed in some patients early after treatment. Renal function worsened after treatment, but overall it was not significantly different from pre-treatment values (p = 0.07). CONCLUSIONS: Single or combination therapy with foscarnet is effective for treatment of ganciclovir-resistant isolates and excessive concern regarding toxicity should not preclude consideration of these treatments when clinically indicated.
Authors: Katja Spiess; Mads G Jeppesen; Mikkel Malmgaard-Clausen; Karen Krzywkowski; Kalpana Dulal; Tong Cheng; Gertrud M Hjortø; Olav Larsen; John S Burg; Michael A Jarvis; K Christopher Garcia; Hua Zhu; Thomas N Kledal; Mette M Rosenkilde Journal: Proc Natl Acad Sci U S A Date: 2015-06-15 Impact factor: 11.205
Authors: Lucio 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 Journal: Antimicrob Agents Chemother Date: 2013-10-21 Impact factor: 5.191