Continuous infusion of beta-lactam antibiotics in pediatric intensive care unit: A monocenter before/after implementation study.

CONTEXT: Beta-lactam continuous infusion (CI) is currently recommended in adult intensive care units to achieve target concentrations. In pediatric intensive care (PICU), few studies suggest the value of Beta-lactam CI to achieve target concentration. Our objective was to analyze the impact of Beta-lactam CI protocolization on the achievement of target concentration in PICU patients. MATERIAL AND METHODS: We conducted a single-center retrospective study in patients with beta-lactam treatment for more than 2 days and at least one sample for therapeutic drug monitoring (TDM). From January 2018 to February 2022 (period 1, P1), BL were administered as an intermittent infusion with TDM upon request. From February to September 2022 (period 2, P2), Beta-lactam CI with TDM at day one was protocolized. The primary endpoint concerned achieving fT>4× Minimum Inhibitory Concentration = 100%. RESULTS: In P1, 214 assays involved 103 patients; in P2, 199 assays involved 72 patients. Target concentration achievement was more frequent in P2 (P2 = 73.7% vs. P1 = 29.1%; p < 0.001). At day 5/6 after Beta-lactam initiation, c-reactive protein concentrations were P1 = 84.9 ± 79.2 mg/L; P2 = 53.7±49.8 mg/L (p < 0.05). In the multivariable logistic regression model: P2, BSA, and albumin were positively associated with target achievement; urea, and male sex were negatively associated with target achievement. The daily average cost of beta-lactam vial consumption per child was: P1 = 5.04 ± 2.6 ; vs. P2 = 3.21 ± 2.7 ; (p-value < 0.001). The daily average reconstitution time of Beta-lactam syringes per child was: P1 = 23.5 ± 8.7 min, P2 = 13.9 ± 9.2 min (p-value < 0.001). CONCLUSION: Protocolization of Beta-lactam continuous infusion was associated with more frequent target concentration achievements in PICU. This implementation could be cost-effective and nurse time-saving.

Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children: results from the French pediatric national registry.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for an important mortality rate worldwide. We aimed to evaluate the actual imputability of SARS-CoV-2 on the mortality rate associated with SARS-CoV-2-related illnesses in the pediatric intensive care unit (PICU). Secondary objectives were to identify risk factors for death. METHODS: This national multicenter comparative study comprised all patients under 18 years old with positive SARS-CoV-2 polymerase chain reactions (PCRs) [acute corona virus disease 2019 (COVID-19) or incidental SARS-CoV-2 infection] and/or pediatric inflammatory multisystem syndrome (PIMS) recorded in the French PICU registry (PICURe) between September 1, 2021, and August 31, 2022. Included patients were classified and compared according to their living status at the end of their PICU stay. Deceased patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive care. The imputability of SARS-CoV-2 as the cause of death was classified into four categories: certain, very probable, possible, or unlikely, and was defined by any of the first three categories. RESULTS: There were 948 patients included of which 43 died (4.5%). From this, 26 deaths (67%) could be attributed to SARS-CoV-2 infection, with an overall mortality rate of 2.8%. The imputability of death to SARS-CoV-2 was considered certain in only one case (0.1%). Deceased patients suffered more often from comorbidities, especially heart disease, neurological disorders, hematological disease, cancer, and obesity. None of the deceased patients were admitted for pediatric inflammatory multisystem syndrome (PIMS). Mortality risk factors were male gender, cardiac comorbidities, cancer, and acute respiratory distress syndrome. CONCLUSIONS: SARS-CoV-2 mortality in the French pediatric population was low. Even though the imputability of SARS-CoV-2 on mortality was considered in almost two-thirds of cases, this imputability was considered certain in only one case.

Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.

In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.

Temporal Shift of the Respiratory Syncytial Virus Epidemic Peak for the Years 2020-2023 in Marseille, Southern France.

Respiratory syncytial virus is among the most common causes of respiratory infections. Typically, this viral infection has a seasonality during the cold months but with the SARS-CoV-2 pandemic this has been considerably modified. Here, we studied the epidemiology of this virus in university hospitals of Marseille, South of France, over the period 2020 to 2023. We tested in our laboratory from July 2020 to October 2021 16,516 nasopharyngeal swabs from 16,468 patients for RSV infection using different qPCR assays. We then analyzed data from previous and subsequent winters (from 2018 to 2023) and previous summers (from 2015 to 2021). A total of 676 patients were RSV-positive; their mean age was 3 years and 91 were under 5 years of age. We observed a delay of 4 months of the RSV epidemic's onset compared to other years with an epidemic that peaked in March 2021. We had significantly more RSV-positive cases during summer 2021 compared to previous summers, whereas the incidence of RSV infections was not significantly higher during winter 2022 versus previous winters. Moreover, 494 patients were diagnosed as RSV-positive in the emergency unit and 181 were subsequently hospitalized, and 34 patients were diagnosed RSV-positive while already in the intensive care unit. Over all the study periods, 38 patients diagnosed as RSV-positive died, the majority of whom (23/28) were over 65 years of age. These data show an atypical evolution of the incidence of RSV infections in our city and is another example of the unpredictability of infectious disease epidemiology.

Systematic Endotracheal Aspiration in the Pediatric Intensive Care Unit Reduces Broad-spectrum Antibiotic Use for Ventilator-associated Pneumonia.

AIM: To determine the impact of a systematic endotracheal aspiration (ETA) sampling program for mechanically ventilated patients on initial antibiotic therapy for ventilator-acquired pneumonia (VAP). DESIGN: Retrospective cohort study; before-after study design. SETTING: Pediatric intensive care unit (PICU) with 16 medical and surgical beds in a tertiary teaching hospital. SUBJECTS: Patients <16 years of age hospitalized in the PICU who fulfilled VAP criteria. INTERVENTION: Biweekly systematic ETA sampling was conducted in mechanically ventilated patients. MEASUREMENTS: We retrospectively studied patients who received antibiotic therapy for suspected VAP 12 months before and after the initiation of systematic ETA (periods 1 and 2, respectively), evaluating the initial antibiotic therapy spectrum in both periods. RESULTS: During period 1, 56 patients developed VAP and 47 developed VAP during period 2. The incidence was 17 cases of VAP/1000 days of mechanical ventilation in both periods. Ideal antibiotic therapy was prescribed in 19.6% of cases for period 1 and 55.2% for period 2 (P = 0.001). Initial antibiotic therapy for VAP during period 2 had a significantly lower proportion of broad-spectrum antibiotics than therapy during period 1 (P = 0.01). CONCLUSION: In our PICU, knowledge of bronchial colonization reduced initial broad-spectrum antibiotic use for VAP.

Etiology and Epidemiology of Diarrhea in Hospitalized Children from Low Income Country: A Matched Case-Control Study in Central African Republic.

BACKGROUND: In Sub-Saharan Africa, infectious diarrhea is a major cause of morbidity and mortality. A case-control study was conducted to identify the etiology of diarrhea and to describe its main epidemiologic risk factors among hospitalized children under five years old in Bangui, Central African Republic. METHODS: All consecutive children under five years old hospitalized for diarrhea in the Pediatric Complex of Bangui for whom a parent's written consent was provided were included. Controls matched by age, sex and neighborhood of residence of each case were included. For both cases and controls, demographic, socio-economic and anthropometric data were recorded. Stool samples were collected to identify enteropathogens at enrollment. Clinical examination data and blood samples were collected only for cases. RESULTS: A total of 333 cases and 333 controls was recruited between December 2011 and November 2013. The mean age of cases was 12.9 months, and 56% were male. The mean delay between the onset of first symptoms and hospital admission was 3.7 days. Blood was detected in 5% of stool samples from cases. Cases were significantly more severely or moderately malnourished than controls. One of the sought-for pathogens was identified in 78% and 40% of cases and controls, respectively. Most attributable cases of hospitalized diarrhea were due to rotavirus, with an attributable fraction of 39%. Four other pathogens were associated with hospitalized diarrhea: Shigella/EIEC, Cryptosporidium parvum/hominis, astrovirus and norovirus with attributable fraction of 9%, 10%, 7% and 7% respectively. Giardia intestinalis was found in more controls than cases, with a protective fraction of 6%. CONCLUSIONS: Rotavirus, norovirus, astrovirus, Shigella/EIEC, Cryptosporidium parvum/hominis were found to be positively associated with severe diarrhea: while Giardia intestinalis was found negatively associated. Most attributable episodes of severe diarrhea were associated with rotavirus, highlighting the urgent need to introduce the rotavirus vaccine within the CAR's Expanded Program on Immunization. The development of new medicines, vaccines and rapid diagnostic tests that can be conducted at the bedside should be high priority for low-resource countries.

Vaginal metastasis of a Ewing Sarcoma five years after resection of the primary tumor.

A 35-year-old female presented with pain and swelling of the left wrist. A diagnosis of Ewing sarcoma was made and she underwent neoadjuvant chemotherapy and surgery. Macroscopic viable areas remained on the map of the surgical specimen; as such, she was classified as a poor responder and received high dose adjuvant chemotherapy. She remained disease-free for five years, until age 40. A vaginal polyp was then detected during a routine gynaecologic examination. It was removed and histopathology revealed metastatic Ewing sarcoma. To our knowledge, this is the first reported case of a vaginal metastasis of Ewing sarcoma.