Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

Assessing the resilience of HIV healthcare services provided to adolescents and young adults after the COVID-19 pandemic in the city of Beira (Mozambique): an interrupted time series analysis.

BACKGROUND: The COVID-19 pandemic has put the provision of health services globally at risk. In Sub-Saharan Africa, it had a major impact on HIV services. However, there is a lack of data on the post-pandemic period. This study aims to evaluate the resumption of HIV services and retention in care for adolescents and young people in the period following the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted using interrupted time series analysis. Three periods were considered: pre-pandemic (form June 2019 to March 2020), pandemic (form April 2020 to March 2022) post-pandemic (from April 2022 to March 2023). Six outcome measures were considered: number of outpatient visits, HIV tests, HIV positivity ratio, the antiretroviral treatment (ART) non-adherence ratio, recall ratio, and the return ratio for adolescent and young adults on ART. RESULTS: During the study period, 447,515 outpatient visits and 126,096 HIV tests were recorded. After a reduction at the beginning of the pandemic period, both visits and tests increased during the pandemic (p < 0.05) and decreased in the post-pandemic (p < 0.05), recovering the pre-pandemic trends. The HIV positivity ratio slightly decreased from 3.3% to 1.7% during the study period (p < 0.05). The ART non-adherence ratio decreased from 23.4% to 2.4% throughout the study period (p < 0.05), with a drop at the beginning of the post-pandemic period (p < 0.05). The recall ratio increased during the study period (p < 0.05) with a drop at the beginning of the pandemic and post-pandemic periods (p < 0.05). The return ratio decreased at the beginning of the pandemic (p < 0.05) but returned to the pre-pandemic ratio in the post-pandemic period. CONCLUSIONS: The post-pandemic values of the investigated outcomes were comparable to pre-pandemic period, or even improved. Differently from other services, such as the community activities, that have been severely affected by COVID-19 pandemic, the HIV service system has shown resilience following emergency situation.

Burden of Congenital CMV Infection: A Narrative Review and Implications for Public Health Interventions.

Cytomegalovirus causes the most common congenital infection worldwide. With most infants asymptomatic at birth, the few affected may present with variable clinical scenarios, from isolated hearing loss to severe neurologic impairment. Public health interventions include all actions at the health system, community, and individual levels that aim at reducing the burden of congenital Cytomegalovirus. This review examines the literature on maternal and neonatal screening programs in light of current evidence for treatment and the development of vaccines against Cytomegalovirus. Potential biases and benefits of these interventions are outlined, with the objective of increasing awareness about the problem and providing readers with data and critical tools to participate in this ongoing debate.

Assessing the impact of a community-based psychodrama intervention on mental health promotion of adolescents and young adults in Mozambique: A mixed-methods study.

Background: While mental health is an emerging issue in low-income countries, its promotion remains poor, with little context-oriented evidence available. Here we aimed to assess the impact and acceptability/feasibility of a community-based psychodrama intervention involving both adolescents and young adults (AYA) living with HIV (AYALHIV) and without HIV (AYAHIV-). Methods: We used a mixed-methods approach, where the quantitative part was based on pre/post questionnaires and the qualitative one on content analysis of semi-structured interviews. Trained community health care workers delivered psychodrama sessions involving AYAs aged 15-24 years once a week between July and August 2023 in Beira, Mozambique. The baseline assessment involved a sociodemographic and three mental health questionnaires: the Mental Health Knowledge Schedule (MAKS), Community Attitudes toward People with Mental Illness (CAMI27), and the Toronto Alexithymia Scale (TAS). We repeated all questionnaires after the intervention and conducted semi-structured interviews. Results: We enrolled 354 AYAs (50.8% female, 45.5% AYALHIV) at baseline; 315 (89.0%) attended the sessions, with a mean participation rate of 94.4%. Overall, 281 (89.2%) completed the post-intervention assessment. MAKS score improved from 44.5 (95% confidence interval (CI) = 44.0-45.0) to 47.1 (95% CI = 46.4-47.7, P < 0.001). Total CAMI27 score showed no significant variation (P = 0.855). Total TAS score decreased from 57.3 (95% CI = 56.1-58.5) to 54.3 (95% CI = 53.0-55.6, P < 0.001). We found no statistically significant interactions between time and sex, age, or HIV serostatus in all questionnaires. For the qualitative part of the study, we analysed 37 semi-structured interviews (43.2% with females, 40.5% with AYALHIV). We identified four areas of intervention impact: peer-to-peer support (30.3%), social empowerment (24.7%), resilience (23.0%), and emotional skills (21.9%). Regarding acceptability/feasibility, perceived scalability (37.2%) and affective attitude (34.5%) were the sub-areas most frequently retrieved in the SSIs. Conclusions: The community-based psychodrama intervention proved to be an effective tool in AYAs' mental health promotion, increasing knowledge and improving emotional awareness through group experience and interpersonal learning. The intervention also showed good acceptability and feasibility in the context of our study.

Severe and invasive bacterial infections in infants aged less than 90 days with and without SARS-CoV-2 infection.

BACKGROUND: Fever in children represents one of the most common causes of medical evaluation. Infants younger than 90 days of age are at higher risk of severe and invasive bacterial infections (SBI and IBI). However, clinical signs and symptoms of viral and bacterial infections in young infants are frequently similar, and several studies have shown that the risk of SBIs remains non-negligible even in the presence of a positive point-of-care viral test. Our study aims to evaluate whether the proportion of SBIs and IBIs in febrile infants younger than 90 days during the COVID-19 pandemic was higher than that in the pre-pandemic period, and to describe the proportion of SBIs and IBIs in infants with and without SARS-CoV-2 infection. METHODS: This was a retrospective single-center cohort study conducted at the Children's Hospital of the University of Padua in Italy, involving febrile young infants evaluated in the Pediatric Emergency Department (PED) and admitted to Pediatric Acute Care Unit (PACU) between March 2017 to December 2022. Infants admitted before the COVID-19 pandemic were compared to infants admitted during the pandemic period and SARS-CoV-2 positive patients to the negative ones. RESULTS: 442 febrile infants younger than 90 days were evaluated in Padua PED and admitted to the wards. The proportion of SBIs and IBIS did not significantly change over the study periods, ranging between 10.8% and 32.6% (p = 0.117) and between 0% and 7.6%, respectively (p = 0.367). The proportion of infants with a diagnosis of SBIs and IBIs was higher in the SARS-CoV-2 negative group (30.3% and 8.2%, respectively) compared to the positive group (8.5% and 2.8%, respectively) (p < 0.0001). The most common diagnosis in both groups was UTI, mainly caused by E. coli. A similar proportion of blood and urine cultures were performed, whereas lumbar puncture was more frequently performed in SARS-CoV-2 negative infants (40.2% vs 16.9%, p = 0.001). CONCLUSIONS: Although the risk of concomitant serious bacterial infection with SARS-CoV-2 is low, it remains non-negligible. Therefore, even in SARS-CoV-2-positive febrile infants, we suggest that the approach to screening for SBIs remains cautious.

Comparison between the Viral Illness Caused by SARS-CoV-2, Influenza Virus, Respiratory Syncytial Virus and Other Respiratory Viruses in Pediatrics.

Respiratory tract infections (RTIs) are the most common infectious syndromes, primarily caused by viruses. The primary objective was to compare the illness courses between historical RTIs and recent SARS-CoV-2 infections. The study cohort consisted of RTI cases evaluated at the Pediatric Emergency Departments of Padua and Bologna, discharged or admitted with microbiologically confirmed viral RTI between 1 November 2018 and 30 April 2019 (historical period) and 1 March 2020 and 30 April 2021 (recent period). We evaluated the risk of oxygen or respiratory support, hospitalization, antibiotic therapy, and complications among different viral infections. The odds ratio (OR) and the 95% confidence intervals (CIs) were estimated through mixed-effect logistic regression models, including a random intercept on the individual and hospital. We identified 767 RTIs: 359 in the historical period compared with 408 SARS-CoV-2 infections. Infections of SARS-CoV-2 had a lower risk of being admitted (OR 0.04, 95% CI 0.03-0.07), receiving respiratory support (OR 0.19, 95% CI 0.06-0.58), needing antibiotic therapy (OR 0.35, 95% CI 0.22-0.56) and developing complications (OR 0.27, 95% CI 0.14-0.51) compared to all other viral RTIs. COVID-19 in children is clinically similar to other viral RTIs but is associated with a less severe infection course. Thus, most prevention strategies implemented for SARS-CoV-2 should still be considered during RSV and Influenza epidemics.

Validation of Administrative Data and Timing of Point Prevalence Surveys for Antibiotic Monitoring.

Importance: Point prevalence surveys (PPSs) are used globally to collect data on antibiotic prescriptions. However, the optimal frequency for data collection to ensure comprehensive understanding of antibiotic use and to target and monitor stewardship interventions remains unknown. Objective: To identify the optimal frequency for collecting data on antibiotic use among the pediatric population through PPSs leveraging administrative data. Design, Setting, and Participants: This prognostic study used a cross-sectional validation approach and was conducted in pediatric outpatient and inpatient settings in the Veneto region of Italy. Antibiotics were classified according to the World Health Organization Access, Watch and Reserve criteria. Prescribing rates of access antibiotics were analyzed for pediatric inpatients with records dated between October 1, 2014, and December 31, 2022, and outpatients with records dated between January 1, 2010, and December 31, 2022. The study included children younger than 15 years with an antibiotic prescription who were admitted to the pediatric acute care unit or evaluated by a primary care pediatrician. Data analysis was performed from October 2023 to January 2024. Main Outcomes and Measures: An algorithm was developed to identify optimal time frames for conducting PPSs. This approach sought to minimize the discrepancy between quarterly and yearly PPS results, aiming to accurately estimate annual antibiotic prescribing rates in both inpatient and outpatient settings (primary outcome). External validity of the optimal PPS time frames derived from outpatient data when applied to the inpatient setting was also investigated. Validation involved assessing the effectiveness of administrative data in identifying strategic PPS periods for capturing inpatient antibiotic use patterns (secondary outcome). Results: This analysis included 106 309 children: 3124 were inpatients (1773 males [56.8%]) and 103 185 were outpatients (53 651 males [52.0%]). A total of 5099 and 474 867 antibiotic prescriptions from inpatients and outpatients were analyzed, respectively. Outpatients tended to be older than inpatients, with a median age of 3.2 (IQR, 1.3-6.3) years vs 2.6 (IQR, 0.6-6.6) years, respectively, and with a lower burden of clinical comorbidities (≥1 comorbidity: 6618 [6.4%] vs 1141 [36.5%], respectively). The algorithm successfully identified distinct time frames within the calendar year from inpatient and outpatient records optimized for PPS data collection. Rates obtained from the quarterly PPS during these identified periods exhibited greater agreement with annual antibiotic prescribing rates (inpatient: r = 0.17, P < .001; and outpatient: r = 0.42, P < .001) than those derived from the yearly PPS (inpatient: r = 0.04, P = .58; and outpatient: r = 0.05, P = .34), with a Δ reduction of up to 89.8% (where Δ represents the percentage point change in antibiotic prescribing rates). Furthermore, the optimal PPS time frames gleaned from the outpatient data demonstrated robust applicability to the inpatient setting, yielding comparable results in both scenarios. Conclusions and Relevance: This study evaluated the potential of administrative data in determining the optimal timing of PPS implementation. The quarterly PPS balanced precision and sustainability, especially when implemented during strategically selected periods across different seasons. Further studies are needed to validate the algorithm used in this study, especially in post-COVID-19 pandemic years and different settings.

The impact of Antimicrobial Stewardship Programmes in paediatric emergency departments and primary care: a systematic review.

Background: Antibiotics remain the most prescribed medicine in children worldwide, but half of the prescriptions are unnecessary or inappropriate, leading to an increase in antibiotic resistance. This study aims to systemically review the effects of different Antimicrobial Stewardship Programmes (ASPs) on reducing the rates of both antibiotic prescriptions and changes in antimicrobial resistance, and on the economic impact in paediatric emergency departments (PED) and primary care settings. Materials and methods: Embase, MEDLINE, and Cochrane Library were systematically searched, combining Medical Subject Heading and free-text terms for 'children' and 'antimicrobial' and 'stewardship'. The search strategy involved restrictions on dates (from 1 January 2007 to 30 December 2020) but not on language. Randomized controlled trials, controlled and non-controlled before and after studies, controlled and non-controlled interrupted time series, and cohort studies were included for review. The review protocol was registered at the PROSPERO International Prospective Register of Systematic Reviews: Registration Number CRD42021270630. Results: Of the 47,158 articles that remained after removing duplicates, 59 were eligible for inclusion. Most of the studies were published after 2015 (37/59, 62.7%) and in high-income countries (51/59, 86.4%). Almost half of the studies described the implementation of an ASP in the primary care setting (28/59, 47.5%), while 15 manuscripts described the implementation of ASPs in EDs (15/59, 25.4%). More than half of the studies (43/59, 72.9%) described the implementation of multiple interventions, whereas few studies considered the implementation of a single intervention. Antibiotic prescriptions and compliance with guidelines were the most frequent outcomes (47/59, 79.7% and 20/59, 33.9%, respectively). Most of the articles reported an improvement in these outcomes after implementing an ASP. Meanwhile, only very few studies focused on health care costs (6/59, 10.2%) and antimicrobial resistance (3/59 5.1%). Conclusion: The implementation of ASPs has been proven to be feasible and valuable, even in challenging settings such as Emergency Departments and Primary care.

Point-of-Care and Rapid Tests for the Etiological Diagnosis of Respiratory Tract Infections in Children: A Systematic Review and Meta-Analysis.

Fever is one of the most common causes of medical evaluation of children, and early discrimination between viral and bacterial infection is essential to reduce inappropriate prescriptions. This study aims to systematically review the effects of point-of-care tests (POCTs) and rapid tests for respiratory tract infections on changing antibiotic prescription rate, length of stay, duration of therapy, and healthcare costs. Embase, MEDLINE, and Cochrane Library databases were systematically searched. All randomized control trials and non-randomized observational studies meeting inclusion criteria were evaluated using the NIH assessment tool. A meta-analysis was performed to assess the effects of rapid influenza diagnostic tests and film-array respiratory panel implementation on selected outcomes. From a total of 6440 studies, 57 were eligible for the review. The analysis was stratified by setting and POCT/rapid test type. The most frequent POCTs or rapid tests implemented were the Rapid Influenza Diagnostic Test and film-array and for those types of test a separate meta-analysis assessed a significant reduction in antibiotic prescription and an improvement in oseltamivir prescription. Implementing POCTs and rapid tests to discriminate between viral and bacterial infections for respiratory pathogens is valuable for improving appropriate antimicrobial prescriptions. However, more studies are needed to assess these findings in pediatric settings.

The Impact of Clinical Pathways on Antibiotic Prescribing for Acute Otitis Media and Pharyngitis in the Emergency Department.

BACKGROUND: Although Italian pediatric antimicrobial prescription rates are among the highest in Europe, little action has been taken to improve the appropriateness of antimicrobial prescriptions. The primary aim of this study was to assess changes in antibiotic prescription before and after acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis Clinical Pathway (CP) implementation; secondary aims were to compare treatment failures and to assess change in the total antibiotics costs before and after CP implementation. METHODS: Pre-post quasi-experimental study comparing the 6-month period before CP implementation (baseline period: October 15, 2014, through April 15, 2015) to the 6 months after intervention (postintervention: October 15, 2015, through April 15, 2016). RESULTS: Two hundred ninety-five pre- and 278 postintervention emergency department visits were associated with AOM. After CP implementation, there was an increase in "wait and see" approach and a decrease in overall prescription of broad-spectrum antibiotics from 53.2% to 32.4% (P < 0.001). One hundred fifty-one pre- and 166 postimplementation clinic visits were associated with GAS pharyngitis, with a decrease in broad-spectrum prescription after CP implementation (46.4% vs. 6.6%; P < 0.001). For both conditions, no difference was found in treatment failure, and total antibiotics cost was significantly reduced after CP implementation, with a decrease especially in broad-spectrum antibiotics costs. CONCLUSIONS: A reduction in broad-spectrum antibiotic prescriptions and a reduction in the total cost of antibiotics for AOM and GAS pharyngitis along with an increase in "wait and see" prescribing for AOM indicate effectiveness of CP for antimicrobial stewardship in this setting.