Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid-organ Transplant Recipients on Continuous Veno-venous Hemodialysis.

BACKGROUND: Optimal valganciclovir dosing for cytomegalovirus (CMV) prophylaxis in solid-organ transplant (SOT) patients on continuous veno-venous hemodialysis (CVVHD) is not known. Ganciclovir trough concentrations ≥0.60 µg/mL have been suggested for CMV prophylaxis. This study was conducted to determine if valganciclovir 450 mg enterally every 24 hours achieves ganciclovir trough concentrations ≥0.60 µg/mL in patients on CVVHD. METHODS: This single-center, prospective, open-label, pharmacokinetic study included adult SOT patients admitted to an intensive care unit from March 2018 to June 2019 on CVVHD. All patients were receiving valganciclovir 450 mg enterally every 24 hours for CMV prophylaxis prior to enrollment. Each patient had a peak and trough sample drawn at steady state. RESULTS: Ten SOT patients were included in the study (6 liver, 1 simultaneous liver-kidney, 2 bilateral lung, 1 heart). The mean ± SD age was 51.8 ± 14.0 years, and average body mass index was 27 ± 6.9 kg/m2. Ganciclovir trough concentrations ranged from 0.31 to 3.16 µg/mL, and 80% of participants have trough concentrations ≥0.60 µg/mL. No patients had documented neutropenia while on valganciclovir and CVVHD; 60% of patients had significant thrombocytopenia. CONCLUSIONS: Valganciclovir 450 mg enterally every 24 hours achieved ganciclovir trough concentrations ≥0.60 µg/mL in most patients on CVVHD, similar to those reported with intravenous ganciclovir for prophylaxis in this population. Based on these data, valganciclovir may require dosing every 24 hours to achieve concentrations equivalent to ganciclovir. Neutropenia did not occur in the study period. Thrombocytopenia was common and likely multifactorial.

Influenza infection in neutropenic adults.

While lymphopenia is a well-defined risk factor for severe influenza, the effect of neutropenia is unknown. This was a retrospective single centre study of adult patients with documented neutropenia and influenza between 2005 and 2013. Forty patients were included with a median follow-up of 2 years (IQR 0.8-4.0). Median ANC at influenza diagnosis was 0.3 × 109/L (IQR 0.1-0.4 × 109/L). Outcomes included hospitalization (N = 28, 70%), pneumonia (N = 9, 23%), ICU admission (N = 9, 23%) and mechanical ventilation (N = 7, 18%). Three deaths (7.5%) were attributed to influenza, all of whom had lower respiratory tract infection (LRTI). Patients with LRTI (N = 18, 45%) also had a higher 30-day mortality (37 versus 0%) and 90-day mortality (42 versus 0%) than those with upper respiratory tract infection. In summary, neutropenic patients have high rates of influenza complications. Our study highlights the need for early diagnosis and aggressive management of influenza in this population.