COMMENTARY

Can Ganciclovir Thwart CMV Reactivation in Critical Illness?

Greg Martin, MD

Disclosures

October 30, 2017

CMV Reactivation: Can It Be Reduced?

Cytomegalovirus (CMV) is a widely prevalent human herpes virus found in most healthy adults and causes lifelong latent infection in many organs, such as the lung. Latent CMV commonly reactivates during immunosuppression or critical illness, and research shows an association of CMV reactivation with worse clinical outcomes. In a recent study, Limaye and colleagues[1] sought to determine whether empiric ganciclovir would reduce plasma interleukin (IL)-6 levels in CMV-seropositive critically ill adults with respiratory failure due to either sepsis or severe traumatic injuries.

The Study

The study was a prospective, randomized controlled trial. Patients were randomly assigned 1:1 to receive either ganciclovir or placebo until hospital discharge. A total of 160 patients underwent randomization, and 132 completed the study. The mean change in IL-6 was not significantly different between groups, but CMV reactivation in plasma was significantly less in the ganciclovir group (12% vs 39%, P < .001). The ganciclovir group had more ventilator-free days in both the overall group and in the sepsis subgroup. There were no significant between-group differences in other secondary outcomes. The study authors concluded that among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir does not reduce IL-6 levels. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression.

Viewpoint

The past few years have seen a spate of studies documenting CMV reactivation in critically ill adults and associating CMV reactivation with worse clinical outcomes. It has been impossible to know with certainty whether the worse clinical outcomes were caused by CMV or whether the CMV was simply a marker of patients with worse critical illness and immune dysfunction. Sepsis, for example, is known to cause both an inflammatory and an anti-inflammatory response, and we increasingly are studying the immune paralysis that occurs with sepsis because of its potential to affect clinical outcomes. The ability to categorize patients with sepsis according to their immune phenotype, however, is not yet feasible in regular clinical settings.

This study sought to move the field forward by testing whether empiric CMV suppression (in CMV-seropositive adults) would improve clinical outcomes. Had this study demonstrated improved clinical outcomes, it would have helped to close the loop from confounded observational studies to show a causal relationship of CMV in critical illness outcomes. The study, however, failed to demonstrate even a change in the primary outcome of a biological inflammatory marker (IL-6) with ganciclovir therapy. That makes interpreting the differences in CMV reactivation and ventilator-free days more difficult, and it is impossible to recommend routine use of ganciclovir in critically ill patients.

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