Pre-COVID-19-pandemic RSV epidemiology and clinical burden in pediatric primary care in Italy: a comparative analysis across two regions for the 2019/2020 season.

BACKGROUND: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season. METHODS: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations. RESULTS: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration. CONCLUSIONS: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures.

Epidemiology of respiratory syncytial virus in a large pediatric hospital in Central Italy and development of a forecasting model to predict the seasonal peak.

BACKGROUND: Respiratory Syncytial Virus (RSV) is responsible for the majority of acute lower respiratory infections in infants and can affect also older age groups. Restrictions linked to the emergence of the SARS-CoV-2 pandemic and their subsequent lifting caused a change in the dynamics of RSV circulation. It is therefore fundamental to monitor RSV seasonal trends and to be able to predict its seasonal peak to be prepared to the next RSV epidemics. METHODS: We performed a retrospective descriptive study on laboratory-confirmed RSV infections from Bambino Gesù Children's Hospital in Rome from 1st January 2018 to 31st December 2022. Data on RSV-positive respiratory samples (n = 3,536) and RSV-confirmed hospitalizations (n = 1,895) on patients aged 0-18 years were analyzed. In addition to this, a SARIMA (Seasonal AutoRegressive Integrated Moving Average) forecasting model was developed to predict the next peak of RSV. RESULTS: Findings show that, after the 2020 SARS-CoV-2 pandemic season, where RSV circulation was almost absent, RSV infections presented with an increased and anticipated peak compared to pre-pandemic seasons. While mostly targeting infants below 1 year of age, there was a proportional increase in RSV infections and hospitalizations in older age groups in the post-pandemic period. A forecasting model built using RSV weekly data from 2018 to 2022 predicted the RSV peaks of 2023, showing a reasonable level of accuracy (MAPE 33%). Additional analysis indicated that the peak of RSV cases is expected to be reached after 4-5 weeks from case doubling. CONCLUSION: Our study provides epidemiological evidence on the dynamics of RSV circulation before and after the COVID-19 pandemic. Our findings highlight the potential of combining surveillance and forecasting to promote preparedness for the next RSV epidemics.

Influenza viruses circulation in a tertiary care children hospital in Rome: a comparison between 2022 and the previous 5 years.

BACKGROUND: Influenza surveillance aims to determine onset, duration and intensity of the seasonal Influence-like Illness (ILI); data collection begins in the week 42 of a year and ends in the week 17 of the following year. In this observational study, we report the experience of a tertiary care children hospital in Rome about Influenza viruses circulation during the calendar year 2022 (January-December) in comparison with the previous five years (2017-2021), with a special focus on the weeks 18-41, usually not under surveillance. METHODS: This retrospective study involved 36782 respiratory samples referred to 21354 patients (pts), median age 2.63 years, admitted with respiratory symptoms at Bambino Gesù Children's Hospital in the years 2017-2022. Respiratory viruses were detected by molecular Allplex™ Respiratory Panel Assays (Seegene, Korea). RESULTS: Regarding the pre pandemic years, 2017-2019, distribution of Flu positive patients focused in the first weeks of the year (weeks 1-17). During the pandemic period, Flu was not detected. In 2022, 239 Flu viruses were identified: 37 FluA (weeks 1-17), 29 FluA (weeks 18-41) and 168 FluA and 5 FluB (weeks 42-52). For the year 2022, during the non-epidemic period, the number of Flu viruses detected corresponded to 12.1% of total Flu detected, respect to 0-1.7% for the previous five years (p < 0.001). CONCLUSIONS: When compared with pre SARS-CoV-2 pandemic years, our data show a significant increase in Influenza cases during weeks 18-41/2022 and reveal an unexpected summer circulation of these viruses: just weeks 26-30 showed to be influenza virus free. A national year-round Flu surveillance could be useful to understand if changing in influenza epidemiology is transitional or likely to persist in the following years.

Clonal Spread of Hospital-Acquired NDM-1-Producing Klebsiella pneumoniae and Escherichia coli in an Italian Neonatal Surgery Unit: A Retrospective Study.

This article reports a rapid and unexpected spread of colonization cases of NDM-1 carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in a neonatal surgical unit (NSU) at Bambino Gesù Children's Hospital in Rome, Italy. Between the 16th of November 2020 and the 18th of January 2021, a total of 20 NDM-1 carbapenemase-producing K. pneumoniae (n = 8) and E. coli (n = 12) were isolated from 17 out of 230 stool samples collected from neonates admitted in the aforementioned ward and time period by an active surveillance culture program routinely in place to monitor the prevalence of colonization/infection with multidrug-resistant Gram-negative microorganisms. All strains were characterized by antimicrobial susceptibility testing, detection of resistance determinants, PCR-based replicon typing (PBRT) and multilocus-sequence typing (MLST). All isolates were highly resistant to most of the tested antibiotics, and molecular characterization revealed that all of them harbored the blaNDM-1 gene. Overall, IncA/C was the most common Inc group (n = 20/20), followed by IncFIA (n = 17/20), IncFIIK (n = 14/20) and IncFII (n = 11/20). MLST analysis was performed on all 20 carbapenemase-producing Enterobacterales (CPE) strains, revealing three different Sequence Types (STs) among E. coli isolates, with the prevalence of ST131 (n = 10/12; 83%). Additionally, among the 8 K. pneumoniae strains we found 2 STs with the prevalence of ST37 (n = 7/8; 87.5%). Although patient results were positive for CPE colonization during their hospital stay, infection control interventions prevented their dissemination in the ward and no cases of infection were recorded in the same time period.

Severe viral respiratory infections in the pre-COVID era: A 5-year experience in two pediatric intensive care units in Italy.

BACKGROUND: Viral respiratory infections are one of the main causes of hospitalization in children. Even if mortality rate is low, 2% to 3% of the hospitalized children need mechanical ventilation. Risk factors for admission to the pediatric intensive care unit (PICU) are well known, while few studies have described risk factors for invasive ventilator support and prolonged hospitalization. METHODS: A retrospective study including all patients aged between 2 and 18 months with a confirmed viral respiratory infection, requiring admission to PICU from September to March between 2015 and 2019, was conducted at Bambino Gesù Children's Hospital in Rome, Italy. RESULTS: One hundred ninety patients were enrolled, with a median age of 2.7 months; 32.1% had at least one comorbidity, mainly prematurity. The most frequent isolated viruses were RSV-B, rhinovirus, and RSV-A; 38.4% needed mechanical ventilation. This subgroup of patients had lower median birth weight compared with patients not requiring mechanical ventilation (2800 g vs. 3180 g, p = 0.02); moreover, comorbidities were present in 43.8% of intubated patients and in 24.8% of patients treated with non-invasive ventilation (p = 0.006). Viral coinfection did not result to be a risk factor for mechanical support, while virus-bacteria coinfection was significantly associated with mechanical ventilation (p < 0.001). Similar risk factors were identified for prolonged hospitalization. CONCLUSIONS: Early identification of patients who could have a sudden respiratory deterioration and need of mechanical ventilation is crucial to reduce complications due to orotracheal intubation and prolonged hospitalization in PICU. Further studies are needed to define high-risk group of patients and to design targeted interventions.

Hypoventilation and sleep hypercapnia in a case of congenital variant-like Rett syndrome.

BACKGROUND: Breathing disturbances are often a primary clinical concern especially during wakefulness of the classic form of Rett syndrome, but data for atypical forms are lacking. CASE PRESENTATION: We report the case of a 20-month-old female affected by Rett syndrome with congenital variant-like onset, characterized by severe hypotonia and neurodevelopment impairment. She presented hypoventilation, persistent periodic breathing, and sustained desaturation during sleep, without obstructive or mixed events. Pulse oximetry and capnography during wakefulness were strictly normal. To the best of our knowledge, this is the first case of a patient affected by a congenital variant of Rett syndrome presenting sleep hypercapnia. Hypotonia may play a major role in the genesis of hypoventilation and hypoxemia in our patient. Non-invasive ventilation led to quality-of-life improvements. CONCLUSIONS: Thus, we suggest screening patients with congenital-like Rett syndrome through transcutaneous bedtime carbon dioxide and oxygen monitoring. Moreover, assisted control mode was a breakthrough to achieve adequate ventilation in our case.

Escalation of care in children at high risk of clinical deterioration in a tertiary care children's hospital using the Bedside Pediatric Early Warning System.

BACKGROUND: Escalation and de-escalation are a routine part of high-quality care that should be matched with clinical needs. The aim of this study was to describe escalation of care in relation to the occurrence and timing of Pediatric Intensive Care Unit (PICU) admission in a cohort of pediatric inpatients with acute worsening of their clinical condition. METHODS: A monocentric, observational cohort study was performed from January to December 2018. Eligible patients were children: 1) admitted to one of the inpatient wards other than ICU; 2) under the age of 18 years at the time of admission; 3) with two or more Bedside-Paediatric-Early-Warning-System (BedsidePEWS) scores ≥ 7 recorded at a distance of at least one hour and for a period of 4 h during admission. The main outcome -the 24-h disposition - was defined as admission to PICU within 24-h of enrolment or staying in the inpatient ward. Escalation of care was measured using an eight-point scale-the Escalation Index (EI), developed by the authors. The EI was calculated every 6 h, starting from the moment the patient was considered eligible. Analyses used multivariate quantile and logistic regression models. RESULTS: The 228 episodes included 574 EI calculated scores. The 24-h disposition was the ward in 129 (57%) and the PICU in 99 (43%) episodes. Patients who were admitted to PICU within 24-h had higher top EI scores [median (IQR) 6 (5-7) vs 4 (3-5), p < 0.001]; higher initial BedsidePEWS scores [median (IQR) 10(8-13) vs. 9 (8-11), p = 0.02], were less likely to have a chronic disease [n = 62 (63%) vs. n = 127 (98%), p < 0.0001], and were rated by physicians as being at a higher risk of having a cardiac arrest (p = 0.01) than patients remaining on the ward. The EI increased over 24 h before urgent admission to PICU or cardiac arrest by 0.53 every 6-h interval (CI 0.37-0.70, p < 0.001), while it decreased by 0.25 every 6-h interval (CI -0.36-0.15, p < 0.001) in patients who stayed on the wards. CONCLUSION: Escalation of care was related to temporal changes in severity of illness, patient background and environmental factors. The EI index can improve responses to evolving critical illness.

Alert sign and symptoms for the early diagnosis of pulmonary tuberculosis: analysis of patients followed by a tertiary pediatric hospital.

BACKGROUND: Intercepting earlier suspected TB (Tuberculosis) cases clinically is necessary to reduce TB incidence, so we described signs and symptoms of retrospective cases of pulmonary TB and tried to evaluate which could be early warning signs. METHODS: We conducted a retrospective descriptive study of pulmonary TB cases in children in years 2005-2017; in years 2018-2020 we conducted a cohort prospective study enrolling patients < 18 years accessed to Emergency Department (ED) with signs/symptoms suggestive of pulmonary TB. RESULTS: In the retrospective analysis, 226 patients with pulmonary TB were studied. The most frequently described items were contact history (53.5%) and having parents from countries at risk (60.2%). Cough was referred in 49.5% of patients at onset, fever in 46%; these symptoms were persistent (lasting ≥ 10 days) in about 20%. Lymphadenopathy is described in 15.9%. The prospective study enrolled 85 patients of whom 14 (16.5%) were confirmed to be TB patients and 71 (83.5%) were non-TB cases. Lymphadenopathy and contact history were the most correlated variables. Fever and cough lasting ≥ 10 days were less frequently described in TB cases compared to non-TB patients (p < 0.05). CONCLUSIONS: In low TB endemic countries, pulmonary TB at onset is characterized by different symptoms, i.e. persistent fever and cough are less described, while more relevant are contact history and lymphadenopathy. It was not possible to create a score because signs/symptoms usually suggestive of pulmonary TB (considered in the questionnaire) were not significant risk factors in our reality, a low TB country.

Prevalence and Molecular Typing of Carbapenemase-Producing Enterobacterales among Newborn Patients in Italy.

The spread of carbapenemase-producing Enterobacterales (CPE), especially Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli), is a serious public health threat in pediatric hospitals. The associated risk in newborns is due to their underdeveloped immune system and limited treatment options. The aim was to estimate the prevalence and circulation of CPE among the neonatal intensive units of a major pediatric hospital in Italy and to investigate their molecular features. A total of 124 CPE were isolated from rectal swabs of 99 newborn patients at Bambino Gesù Children's Hospital between July 2016 and December 2019. All strains were characterized by antimicrobial susceptibility testing, detection of resistance genes, and PCR-based replicon typing (PBRT). One strain for each PBRT profile of K. pneumoniae or E. coli was characterized by multilocus-sequence typing (MLST). Interestingly, the majority of strains were multidrug-resistant and carried the blaNDM gene. A large part was characterized by a multireplicon status, and FII, A/C, FIA (15%) was the predominant. Despite the limited size of collection, MLST analysis revealed a high number of Sequence Types (STs): 14 STs among 28 K. pneumoniae and 8 STs among 11 E. coli, with the prevalence of the well-known clones ST307 and ST131, respectively. This issue indicated that some strains shared the same circulating clone. We identified a novel, so far never described, ST named ST10555, found in one E. coli strain. Our investigation showed a high heterogeneity of CPE circulating among neonatal units, confirming the need to monitor their dissemination in the hospital also through molecular methods.

Health-related quality of life in Italian children and adolescents with congenital heart diseases.

BACKGROUND: Congenital heart disease (CHD) is the most common congenital anomaly at birth, affecting approximately 1% of live births. In recent decades great medical and surgical advances have significantly increased life expectancy, shifting healthcare professionals' and researchers' interests in patients' Quality of Life (QoL). The main aims of our study were to evaluate generic and condition-specific QoL in a group of Italian children and adolescents with CHD and their parents and examine the level of agreement and directional disagreement between child/adolescent and parents reports on generic and condition-specific QoL. METHODS: A cross-sectional study was designed with CHD children and adolescents and their parents referred to the Cardiology Department of "Bambino Gesù" Children's Hospital. The PedsQL scale was used, including generic (PedsQL 4.0) and cardiac-specific modules (PedsQL 3.0) were administered to patients and caregivers. A Kruskal-Wallis test was used to compare generic and cardiac module scores between patients with different ages, CHD diagnoses, and between patients who underwent surgery interventions and/or are currently taking cardiac medications. RESULTS: 498 families were enrolled in this study. On average, patients reported a good level of generic and condition-specific QoL, as well as their mothers and fathers. Children aged between 5-7 years old reported lower generic and cardiac-specific total QoL levels than children aged 8-12 years and adolescents (13-18 years). With regard to the agreement, patient-parent agreement on condition-specific QoL ranged from 25 to 75% while on generic QoL, it ranged from 19 to 76%. The highest percentage of disagreement between parents and children was found in patients aged 5-7 years old, both for condition-specific and generic QoL rates. CONCLUSIONS: Our study contributed to the growing body of knowledge on QoL in CHD, emphasizing the need for these families to receive support from multidisciplinary standardized care, including psychological consultations and support.

Hypoglycemia in a Pediatric Emergency Department: Single-Center Experience on 402 Children.

OBJECTIVES: This study aimed to establish the rate, etiology, and short-term outcome of hypoglycemia in infants and children accessing an emergency department of a tertiary care pediatric hospital. METHODS: The study was retrospectively conducted on the clinical records of children with hypoglycemia aged 15 days to 17 years who were admitted consecutively to the emergency department during a 6-year period for various clinical conditions. Hypoglycemia was defined as a venous plasma glucose level lower than 45 mg/dL. RESULTS: Hypoglycemia was detected in 402 patients (female-to-male ratio, 1.26; mean age, 2.6 ± 1.8 years), with a rate of 0.99 per 1000 children. Plasma glucose levels ranged from 3 to 45 (mean, 37.48 ± 7.44) mg/dL. Hypoglycemia was associated with gastroenteritis or other infectious diseases causing protracted fasting in 86.32% of cases, whereas hypoglycemia related to a different etiology (HDE) was observed in 13.68% of hypoglycemic children. Most HDE patients had a final diagnosis of ketotic hypoglycemia, whereas metabolic defects were a rare (1.49%) but nonnegligible etiologic cause. A severe triage code was more frequent in the HDE group (P < 0.001). Factors significantly and independently associated with HDE were impaired level of consciousness, assessed with the AVPU scale (A, alert; V, responding to verbal; P, responding to pain; U, unresponsive; adjusted odds ratio, 2.50; P = 0.025) and clinical onset within 12 hours (adjusted odds ratio, 3.98; P < 0.001). CONCLUSIONS: In a nonnegligible number of critically ill children, hypoglycemia can be detected. In a minority of cases, hypoglycemia was due to metabolic disorders that should be suspected on the basis of the severity of hypoglycemia, and the recent onset and the presence of neuroglycopenic symptoms.

No evidence of SARS-CoV-2 in hospitalized patients with severe acute respiratory syndrome in five Italian hospitals from 1st November 2019 to 29th February 2020.

BACKGROUND: On 9th January 2020, China CDC reported a novel coronavirus (later named SARS-CoV-2) as the causative agent of the coronavirus disease 2019 (COVID-19). Identifying the first appearance of virus is of epidemiological importance to tracking and mapping the spread of SARS-CoV-2 in a country. We therefore conducted a retrospective observational study to detect SARS-CoV-2 in oropharyngeal samples collected from hospitalized patients with a Severe Acute Respiratory Infection (SARI) enrolled in the DRIVE (Development of Robust and Innovative Vaccine Effectiveness) study in five Italian hospitals (CIRI-IT BIVE hospitals network) (1st November 2019 - 29th February 2020). OBJECTIVES: To acquire new information on the real trend in SARS-CoV-2 infection during pandemic phase I and to determine the possible early appearance of the virus in Italy. MATERIALS AND METHODS: Samples were tested for influenza [RT-PCR assay (A/H1N1, A/H3N2, B/Yam, B/Vic)] in accordance with the DRIVE study protocol. Subsequently, swabs underwent molecular testing for SARS-COV-2. [one-step real-time multiplex retro-transcription (RT) PCR]. RESULTS: In the 1683 samples collected, no evidence of SARS-CoV-2 was found. Moreover, 28.3% (477/1683) of swabs were positive for influenza viruses, the majority being type A (358 vs 119 type B). A/H3N2 was predominant among influenza A viruses (55%); among influenza B viruses, B/Victoria was prevalent. The highest influenza incidence rate was reported in patients aged 0-17 years (40.3%) followed by those aged 18-64 years (24.4%) and ≥65 years (14.8%). CONCLUSIONS: In Italy, some studies have shown the early circulation of SARS-CoV-2 in northern regions, those most severely affected during phase I of the pandemic. In central and southern regions, by contrast no early circulation of the virus was registered. These results are in line with ours. These findings highlight the need to continue to carry out retrospective studies, in order to understand the epidemiology of the novel coronavirus, to better identify the clinical characteristics of COVID-19 in comparison with other acute respiratory illnesses (ARI), and to evaluate the real burden of COVID-19 on the healthcare system.

Highly Specific Memory B Cells Generation after the 2nd Dose of BNT162b2 Vaccine Compensate for the Decline of Serum Antibodies and Absence of Mucosal IgA.

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.

Sars-Cov2 Not Detected in a Pediatric Population With Acute Respiratory Infection in Primary Care in Central and Southern Italy From November 2019 to Early March 2020.

Background: In December 2019, a novel coronavirus named SARS-CoV-2 started circulating in China and this led to a major epidemic in Northern Italy between February and May 2020. Young children (aged <5 years) seem to be less affected by this coronavirus disease (COVID-19) compared to adults, although there is very little information on the circulation of this new virus among children in Italy. We retrospectively tested nasopharyngeal swabs for SARS-CoV-2 in samples collected in young children between November, 2019 and March, 2020 in the context of the RSV ComNet study. Methods: Two networks of primary care pediatricians in Lazio (Central Italy) and Puglia (Southern Italy) collected nasopharyngeal swabs from children, aged <5 years, presenting with symptoms for an acute respiratory infection (ARI). The RSV ComNet study is a multicenter study implemented to estimate the burden of RSV in young children (aged <5 years) in the community. Swabs were sent to a central reference laboratory and tested for 14 respiratory viruses through RT-PCR. All collected samples were retrospectively tested for SARS-CoV-2 using RT-PCR (Istituto Superiore di Sanità protocol). Results: A total of 293 children with ARI were identified in the two participating networks. The highest number of cases were recruited in weeks 51/2019 and 3/2020. The majority of patients (57%) came from the Lazio region. All of the 293 samples tested negative for SARS-Cov2. Rhinovirus was the most frequently detected virus (44%), followed by RSV (41%) and influenza viruses (14%). Conclusions: Our study shows that in Lazio (a region of intermediate SARS-COV-2 incidence) and Puglia (a region of low incidence), the SARS-Cov2 virus did not circulate in a sample of ARI pediatric cases consulting primary care pediatricians between November 2019 and March 2020.

Knowledge and Perception of COVID-19 Pandemic during the First Wave (Feb-May 2020): A Cross-Sectional Study among Italian Healthcare Workers.

Italy was the first country in Europe to face the coronavirus pandemic. The aim of the study was to analyze healthcare workers' (HCWs) level of information, practice, and risk perception towards COVID-19. We set up a cross-sectional study through SurveyMonkey® and distributed the link through Facebook and Whatsapp closed groups. The research instrument was a 31 items questionnaire distributed using Facebook and Whatsapp. It was conducted in Italy from February to May 2020. The study participants were general practitioners, pediatricians and other health professionals. A total of 958 participants were included: 320 (33.4%) general practitioners, 248 (25.9%) pediatricians and 390 (40.7%) other health professionals. The highest response rate was from Northern Italy (48.1%), followed by Central Italy (29.9%) and Southern Italy (22.0%). Less than a half (46%) of respondents felt they had a good level of information of COVID-19 case definition and of national prevention guidelines. Respondents reported to have changed their clinical practice; particularly, they increased the use of masks (87.1%, p < 0.001), disinfection and sanitization of doctors' offices (75.8%, p < 0.001), the use of protective glasses (71.2%, p < 0.001), alcoholic hand solution (71.2%, p < 0.001), and hand washing (31.8%, p = 0.028). HCWs are at high risk of infection; less than a half of them felt adequately prepared to face COVID-19 pandemic, so they need extensive information and awareness of the disease to take adequate precautionary measures, and they are crucial to disseminate good practices.

Use of multiple metrics to assess antibiotic use in Italian children's hospitals.

Quantification of antibiotic utilization is an essential component of antibiotic stewardship programs. In this multicentric study, we used different metrics to evaluate inpatient antibiotic use in children. The study objectives were to describe point prevalence of antibiotic use by indication and patient characteristics, to evaluate DOTs, LOTs and PDDs, and to compare PDDs to DDDs, which assume average maintenance dose per day in adults. All children hospitalized on the days of the study were included. Trained personnel collected demographic and clinical data from patients' clinical records. We recorded information about antibiotics administered on the date of data collection, and in the previous 30 days of hospitalization. Of 810 patients, 380 (46.9%; CI 95%: 43.4-50.4) received one or more antibiotics; prevalence of use was 27.0% for prophylaxis (219/810), and 20.7% (168/810) for treatment. Overall, 587 drugs were issued to the 380 patients receiving antibiotics (1.5 antibiotic per patient). When considering treatments, DOT and LOT per 100 patient-days were 30.5 and 19.1, respectively, resulting in a DOT/LOT ratio of 1.6. PDDs increased with age and approached DDDs only in children aged ≥ 10 years; the ratio between PDDs estimated in children aged ≥ 10 years and in 0-11 month-old infants ranged from 2 for sulfamethoxazole and trimethoprim, to 25 for meropenem. Our results confirm that DOT, LOT and PDD are better alternatives to DDD in children.

Impact of the COVID-19 pandemic on the Emergency Department of a tertiary children's hospital.

BACKGROUND: Italy was the first country in Europe affected by COVID-19: the emergency started on February 20, 2020, culminating with national lockdown on March 11, which terminated on May 4, 2020. We describe how the pandemic affected Emergency Department (ED) accesses in a tertiary children's hospital, composed by two different pediatric centers, one located in Rome's city center and the second, Palidoro (regional COVID-19 center), in its surrounding metropolitan area, both in the Lazio region, analyzing the profile of admitted patients during the pandemic period in terms of their general characteristics (at presentation in the ED's) and urgent hospitalizations compared to prepandemic period. METHODS: The study compare the period between the 21st of February and the 30th of April 2020, covering the three phases of the national responses (this period will be referred to as the pandemic period) with the same period of 2019 (prepandemic period). The study analyzes the number of ED visits and urgent hospitalizations and their distribution according to selected characteristics. RESULTS: The reduction of ED visits was 56 and 62%, respectively in Rome and Palidoro centers. The higher relative decline was encountered for Diseases of Respiratory System, and for Diseases of the Nervous System and Sense Organs. A doubling of the relative frequency of hospitalizations was observed, going from 14.2 to 24.4% in Rome and from 6.4 to 10.3% in Palidoro. In terms of absolute daily numbers the decrease of urgent hospitalizations was less sharp than ED visits. For pathologies such as peritonitis, tumors or other possible life-treathening conditions we did not observe a significative increase due to delayed access. CONCLUSIONS: In the pandemic period there was a general reduction in the number of children referred to ED, such reduction was greater in low-acuity levels. The reduction for respiratory tract infections and other communicable diseases during school closure and the national lockdown must make us reflect on the possible impact that these conditions may have on the health system, in particular the ED, at the reopening of schools. The major problem remains the fear for possible diagnostic delays in life-threatening or crippling diseases; our study doesn't demonstrate an increase in number or significant delay in some serious conditions such as tumors, peritonitis, diabetic ketoacidosis, ileo-colic intussusception and testis/ovary torsion. A continuous, deep re-organizational process step by step of the ED is nececessary in the present and upcoming pandemic situation.

Impact and Sustainability of Antibiotic Stewardship in Pediatric Emergency Departments: Why Persistence Is the Key to Success.

Antibiotic stewardship programs proved to be effective in improving prescribing appropriateness. This multicenter quasi-experimental study, aimed to assesses the stewardship impact on antibiotics prescribing in different semesters from 2014 to 2019 in three pediatric emergency departments (Center A, B, and C) in Italy. All consecutive patients diagnosed with acute otitis media or pharyngitis were evaluated for inclusion. Two different stewardship were adopted: for Center A and B, clinical pathways were implemented and disseminated, and yearly lectures were held, for Center C, only pathways were implemented. Broad-spectrum prescription rates decreased significantly by 80% for pharyngitis and 29.5 to 55.2% for otitis after the implementation. In Center C, rates gradually increased from the year after the implementation. Amoxicillin dosage adjusted to pharyngitis recommendations in Center C (53.7 vs. 51.6 mg/kg/die; p = 0.011) and otitis recommendations in Center A increasing from 50.0 to 75.0 mg/kg/die (p < 0.001). Days of therapy in children < 24 months with otitis increased from 8.0 to 10.0 in Center A, while in older children decreased in Center A (8.0 vs. 7.0; p < 0.001) and Center B (10.0 vs. 8.0; p < 0.001). Clinical pathways combined with educational lectures is a feasible and sustainable program in reducing broad-spectrum antibiotic prescribing with stable rates over time.

Management of Enteral Nutrition in the Pediatric Intensive Care Unit: Prokinetic Effects of Amoxicillin/Clavulanate in Real Life Conditions.

PURPOSE: Malnutrition is a common feature in critically ill children. Enteral nutrition (EN) is the main strategy to nutritionally support critical ill children, but its use can be hindered by the development of intolerance. The study aimed to assess the effectiveness and safety of amoxicillin/clavulanate (A/C) to treat EN intolerance. METHODS: We retrospectively evaluated patients admitted to the pediatric intensive care unit from October 2018 to October 2019. We conducted a case-control study: in the first 6 months (October 2018-April 2019) we implemented the nutritional protocol of our Institution with no drug, whereas in the second half (May 2019-October 2019) we employed A/C for 1 week at a dose of 10 mg/kg twice daily. RESULTS: Twelve cases were compared with 12 controls. At the final evaluation, enteral intake was significantly higher than that at baseline in the cases (from 2.1±3.7 to 66.1±27.4% of requirement, p=0.0001 by Wilcoxon matched-pairs signed rank test) but not in the controls (from 0.2±0.8 to 6.0±14.1% of the requirement, p=NS). Final gastric residual volume at the end of the observation was significantly lower in the cases than in the controls (p=0.0398). The drug was well tolerated as shown by the similar safety outcomes in both cases and controls. CONCLUSION: Malnutrition exposes critically ill children to several complications that affect the severity of disease course, length of stay, and mortality; all may be prevented by early EN. The development of intolerance to EN could be addressed with the use of A/C. Future prospective clinical trials are needed to confirm these conclusions.