Background: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy. Methods: We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV^®) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables. Results: We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22–0.84), with significantly higher rates (2.1%, 95% CI 0.58–5.3) in the high-risk group (p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers (p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31–4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23–37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83). Conclusions: For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings.

Palabras clave: Enfermedad fúngica invasora; antifúngicos; antifungal stewardship; impacto económico

Invasive fungal disease (IFD) is one of the leading causes of morbidity and mortality in immunocompromised pediatric patients. This is a multicenter prospective cohort study with a nested retrospective analysis aimed at identifying risk factors for IFD in immunocompromised children with cancer and episodes of persistent high-risk febrile neutropenia (HRFN). One hundred and seventy-four episodes of persistent HRFN were analyzed, of which 34 (19.5%) were confirmed as IFD, 52.9% were caused by filamentous fungi, and 47.1% by yeasts. Logistic regression and survival analyses identified the following significant risk factors for IFD: male sex (OR 4.04), adolescence (OR 4.65), C-reactive protein ≥ 90 mg/L at admission (OR 3.13), and transfer to a critical care unit (OR 10.73). The predictive model demonstrated strong discriminatory capacity (AUC 0.84), with 79.4% sensitivity and 82.1% specificity. These findings highlight that adolescents, particularly males with severe clinical conditions and elevated inflammatory markers, are at the highest risk for IFD during episodes of HRFN. The proposed risk factor-based model may support early risk stratification and guide targeted antifungal prophylaxis or therapy, potentially improving outcomes in this population. Validation an external cohort is required to confirm these results and optimize clinical applicability.

Palabras clave: voriconazol; aspergilosis; concentración plasmática; monitorización terapéutica de fármacos

Background/Objectives: The objective of this study is to evaluate the efficacy and safety of maintaining antimicrobial (AM) therapy or adjusting AM therapy during episodes of febrile neutropenia (FN) catalogued as a fever of unknown origin (FUO) in children with cancer. Methods: This is a prospective, multicenter, noninferiority, randomized study, approved by ethics committee, in children with episodes of FN in eight hospitals in Chile. Microbiological and molecular samples were drawn at admission. Patients with FUO (negative bacterial and viral study with no clinical focus suggesting infection) and favorable evolution during the first 48–72 h of AM therapy were randomized 1:1 to maintain or adjust treatment, reducing the number and spectrum of AMs. The primary endpoint was the percentage of episodes with an uneventful resolution; the secondary endpoints were the re-adjustment of AM therapy, days of fever/hospitalization/AM therapy, days of vancomycin and meropenem per 1000 days of neutropenia, number of AMs after randomization, pediatric intensive care unit (PICU) admission, sepsis, and death. Results: A total of 266 of 939 FN episodes recruited between March 2021 and January 2024 were catalogued as FUO, of which 231 had a favorable evolution at 48–72 h and were randomized, 111 to maintain and 120 to adjust AM therapy. Both groups presented the same percentage of uneventful resolution, with 106 (96%) in the group that maintain AM therapy and 114 (95%) in the adjusted group (p = 1.00); relative risk 1.01, (95%CI 0.95–1.06); absolute risk difference 0.01, (95%CI −0.05–0.06). Conclusions: The main finding of this study demonstrates that adjusting antimicrobial therapy appears safe in carefully selected FUO cases with a favorable early evolution, during episodes of FN catalogued as FUO in children with cancer. These findings open an opportunity to new AM stewardship strategies in this population, with a possible future impact on AM resistance.

Invasive fungal disease (IFD) is one of the leading causes of morbidity and mortality in immunocompromised pediatric patients. This is a multicenter prospective cohort study with a nested retrospective analysis aimed to identify risk factors for IFD in immunocompromised children with cancer and episodes of persistent high-risk febrile neutropenia (HRFN). One hundred and seventy-four episodes of persistent HRFN were analyzed, of which 34 (19.5%) were confirmed as IFD, 52.9% caused by filamentous fungi and 47.1% by yeasts. Logistic regression and survival analyses identified the following significant risk factors for IFD: male sex (OR 4.04), adolescence (OR 4.65), C-reactive protein ≥ 90 mg/L at admission (OR 3.13), and transfer to a critical care unit (OR 10.73). The predictive model demonstrated strong discriminatory capacity (AUC 0.84), with 79.4% sensitivity and 82.1% specificity. These findings highlight that adolescent, particularly males with severe clinical conditions and elevated inflammatory markers, are at highest risk for IFD during episodes of HRFN. The proposed risk factors-based model may support early risk stratification and guide targeted antifungal prophylaxis or therapy, potentially improving outcomes in this population. Validation in external cohort is required to confirm these results and optimize clinical applicability.