Congenitally acquired cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide and the most frequent cause of acquired sensorineural hearing loss. The burden of the disease is even more important in premature and very low birth weight infants. However, few data exist on the treatment with intravenous ganciclovir and oral valganciclovir in this vulnerable population. We report the case of twins congenitally infected with CMV and born prematurely at 27 weeks' gestation. Treatment regimens were initially individualized for their prematurity and renal function, and then adjusted with therapeutic drug monitoring (TDM) to adapt to their continuously evolving physiologic maturation. As infants were aging, the plasmatic half-life of ganciclovir slowly decreased to term infant values around 10 weeks of chronological age, or 37 weeks of postmenstrual age. Results for blood polymerase chain reaction tests became negative and long-term follow-ups were satisfactory in both twins. The limited data for infants born before 32 weeks of gestation or at less than 1200 g and evolution of ganciclovir pharmacokinetic parameters justify the use of TDM in these settings.

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