valganciclovir and Respiratory-Insufficiency

The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown.. To determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill.. Double-blind, placebo-controlled, randomized clinical trial (conducted March 10, 2011-April 29, 2016) with a follow-up of 180 days (November 10, 2016) that included 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States.. Patients were randomized (1:1) to receive either intravenous ganciclovir (5 mg/kg twice daily for 5 days), followed by either intravenous ganciclovir or oral valganciclovir once daily until hospital discharge (n = 84) or to receive matching placebo (n = 76).. The primary outcome was change in IL-6 level from day 1 to 14. Secondary outcomes were incidence of CMV reactivation in plasma, mechanical ventilation days, incidence of secondary bacteremia or fungemia, ICU length of stay, mortality, and ventilator-free days (VFDs) at 28 days.. Among 160 randomized patients (mean age, 57 years; women, 43%), 156 patients received 1or more dose(s) of study medication, and 132 patients (85%) completed the study. The mean change in plasma IL-6 levels between groups was -0.79 log10 units (-2.06 to 0.48) in the ganciclovir group and -0.79 log10 units (-2.14 to 0.56) in the placebo group (point estimate of difference, 0 [95% CI, -0.3 to 0.3]; P > .99). Among secondary outcomes, CMV reactivation in plasma was significantly lower in the ganciclovir group (12% [10 of 84 patients] vs 39% [28 of 72 patients]); absolute risk difference, -27 (95% CI, -40 to -14), P < .001. The ganciclovir group had more median VFDs in both the intention-to-treat (ITT) group and in the prespecified sepsis subgroup (ITT group: 23 days in ganciclovir group vs 20 days in the placebo group, P = .05; sepsis subgroup, 23 days in the ganciclovir group vs 20 days in the placebo group, P = .03). There were no significant differences between the ganciclovir and placebo groups in duration of mechanical ventilation (5 days for the ganciclovir group vs 6 days for the placebo group, P = .16), incidence of secondary bacteremia or fungemia (15% for the ganciclovir group vs 15% for the placebo group, P = .67), ICU length of stay (8 days for the ganciclovir group vs 8 days for the placebo group, P = .76), or mortality (12% for the ganciclovir group vs 15% for the placebo group, P = .54).. Among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir did not reduce IL-6 levels and the current study does not support routine clinical use of ganciclovir as a prophylactic agent in patients with sepsis. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression in this setting.. clinicaltrials.gov Identifier: NCT01335932.

Topics: Adult; Aged; Antiviral Agents; Critical Illness; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Female; Follow-Up Studies; Ganciclovir; Humans; Intention to Treat Analysis; Interleukin-6; Length of Stay; Male; Middle Aged; Respiration, Artificial; Respiratory Insufficiency; Sepsis; Treatment Outcome; Valganciclovir; Virus Activation; Wounds and Injuries

Cytomegalovirus (CMV) remains a significant contributor to morbidity and death after pediatric solid and stem cell transplantation. Decisions regarding prevention and treatment often lack pediatric-specific data to drive decision making. We present here a case-based discussion around some of these specific topics and focus on approaches to CMV prevention, post-CMV secondary prophylaxis options, and identification and treatment of resistant CMV infection, including emerging antiviral agents and the use of cytotoxic CMV-specific T-cells, in the setting of pediatric hematopoietic stem cell transplantation.

Topics: Antiviral Agents; Child; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Viral; Fatal Outcome; Foscarnet; Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation; Humans; Male; Recurrence; Respiratory Insufficiency; Risk Assessment; Secondary Prevention; T-Lymphocytes, Cytotoxic; Valganciclovir; Viral Load