T-Cell Immune Responses in Newborns and Long-Term Sequelae in Congenital Cytomegalovirus Infection (CYTRIC Study).

OBJECTIVE: The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae. STUDY DESIGN: A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T lymphocytes (CMV-IFN-γ-CD8+/CD4+) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up. RESULTS: In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3 months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8+ or CD4+ lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study. CONCLUSIONS: CMV-specific IFN-γ-CD4+ and CD8+ T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae.

Benefits of a Pediatric Antimicrobial Stewardship Program in Antimicrobial Use and Quality of Prescriptions in a Referral Children's Hospital.

OBJECTIVES: To evaluate the results of the first 24 months of a postprescription review with feedback-based antimicrobial stewardship program in a European referral children's hospital. STUDY DESIGN: We performed a pre-post study comparing antimicrobial use between the control (2015-2016) and the intervention periods (2017-2018) expressed in days of therapy/100 days present. Quality of prescriptions was evaluated by quarterly cross-sectional point-prevalence surveys. Length of stay, readmission rates, in-hospital mortality rates, cost of systemic antimicrobial agents, and antimicrobial resistance rates were included as complementary outcomes. RESULTS: Total antimicrobial use and antibacterial use significantly decreased during the intervention period (P = .002 and P = .001 respectively), and total antifungal use remained stable. A significant decline in parenteral antimicrobial use was also observed (P < .001). In 8 quarterly point-prevalence surveys (938 prescriptions evaluated), the mean prevalence of use of any antimicrobial among inpatients was 39%. An increasing trend in the rate of optimal prescriptions was observed after the first point-prevalence survey (P = .0898). Nonoptimal prescriptions were more common in surgical than in medical departments, in antibacterial prescriptions with prophylactic intention, and in empirical more than in targeted treatments. No significant differences were observed in terms of mortality or readmission rates. Only minor changes in antimicrobial resistance rates were noted. CONCLUSIONS: Our antimicrobial stewardship program safely decreased antimicrobial use and expenditure, and a trend toward improvement in quality of prescription was also observed.