Hearing Following Prolonged and Delayed Ganciclovir Treatment in a Murine Cytomegalovirus Model

• Published in: The Laryngoscope 2024-01, Vol.134 (1), p.433-438
• Main Authors: Hillam, Katrina, Suarez, Daniel, Nielson, Christopher, Traxler, Abigail, Sommer, Elizabeth, Winslow, Anna, Holley, Anna, Huang, Emily, Hughes, Maura, Firpo, Matthew A., Rower, Joseph, Park, Albert H.
• Format: Article
• Language: English
• Subjects: Aged; Animals; Antiviral Agents - therapeutic use; Antiviral drugs; Child; congenital; Cytomegalovirus; Cytomegalovirus Infections - drug therapy; drug concentration; ganciclovir; Ganciclovir - therapeutic use; hearing loss; Humans; Mice; Mice, Inbred BALB C; Muromegalovirus; Otoacoustic Emissions, Spontaneous; sensorineural; valganciclovir
• ISSN: 0023-852X; 1531-4995; 1531-4995
• DOI: 10.1002/lary.30860

Objective Compare hearing outcomes utilizing standard, prolonged and delayed ganciclovir (GCV) therapy in a murine model of cytomegalovirus (CMV). Methods BALB/c mice were inoculated with mouse cytomegalovirus (mCMV) or saline via intracerebral injection on postnatal day 3 (p3). Intraperitoneal GCV or saline was administered at 12 h intervals for the duration of the standard (p3‐p17), delayed (p30‐p44), or prolonged treatment windows (p3‐p31). Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Blood and tissue samples were harvested from mice on p17 and p37 one hour after GCV administration, and their concentrations were assessed via liquid chromatography‐mass spectrometry. Results A delayed course of GCV improved ABR but not DPOAE thresholds in mCMV‐infected mice. A prolonged course of GCV did not provide better hearing thresholds than those administered standard treatment. The average GCV concentration in all 17‐day‐old mice tissue was significantly higher than those in older 37‐day‐old mice. Conclusion Delayed GCV treatment provided a hearing benefit on ABR over untreated mCMV infected mice. Prolonged CGV administration showed no benefit compared to a shorter duration GCV treatment. GCV drug concentrations both systemically and in the cochlea are much lower in older mice. These results have potential implications for the clinical management of cCMV infected children. Level of Evidence NA Laryngoscope, 134:433–438, 2024 In this paper we show that delayed ganciclovir (GCV) treatment provided improved auditory brainstem response (ABR) thresholds in mCMV infected mice. A prolonged course of GCV did not provide better hearing thresholds than those administered standard treatment. The average GCV concentration in younger 17‐day old mice was significantly higher than those in older 37‐day old mice. The results have important potential implications for the clinical management of cCMV infected children.