Examining Neutropenia During Treatment of Cytomegalovirus Disease in Neonates.

Background: Congenital cytomegalovirus is the leading cause of nongenetic sensorineural hearing loss. Treatment with (val)ganciclovir improves audiologic outcomes. Neutropenia is a common adverse event, but correlates that predict who will develop neutropenia have not been identified.

Methods: Data from 3 National Institutes of Health-funded studies of intravenous ganciclovir or oral valganciclovir were evaluated. Baseline absolute neutrophil count (ANC) was defined as high (ANC >1000 cells/mm3) or low (ANC ≤1000 cells/mm3), and neutropenia was defined as ANC <800 cells/mm3. Mean 12-hour area under the curve (AUC12) ganciclovir values were analyzed as a function of degree of neutropenia using analysis of variance. AUC12 values ≥40 mgxhr/L were defined as high drug exposure and <40 mgxhr/L as low drug exposure.

Results: Of 134 subjects who had AUC12 values obtained during the first week of treatment, 61 (46%) developed neutropenia <800 cells/mm3. Infants with high drug exposure developed neutropenia more rapidly than subjects with low drug exposure (median of 28 vs. 216 days; P < 0.008). Although not significant, infants with a baseline ANC ≤1000 cells/mm3 were observed to develop neutropenia more rapidly compared with those with a high baseline ANC (estimated median of 69 vs. 216 days; P = 0.22) and in greater proportions, although not statistically significant [55.6% vs. 39.3%; P = 0.21; odds ratio, 1.9 (95% CI, 0.71-5.20)].

Conclusions: High AUC12 correlated with the development of neutropenia in infants treated for symptomatic congenital cytomegalovirus disease. Low baseline ANC also may contribute to the development of neutropenia.