Implementation of a Vancomycin Dose-Optimization Protocol in Neonates: Impact on Vancomycin Exposure, Biological Parameters, and Clinical Outcomes.

Vancomycin dosing used in neonates results frequently in insufficient concentrations. A vancomycin dose-optimization protocol consisting of an individualization of loading and maintenance doses (administered during continuous infusion) through a previously validated pharmacokinetic model was implemented in our center. This monocenter retrospective study aimed to compare vancomycin average concentration (Cavg) in the therapeutic range (15 to 25 mg/L) and biological and clinical parameters before and after implementation of this protocol. A total of 60 and 59 courses of vancomycin treatment in 45 and 49 patients were analyzed in groups before and after implementation, respectively. Initial vancomycin Cavg were more frequently in the therapeutic range in the group after implementation (74.6% versus 28.3%, P < 0.001), with 1.6-fold higher Cavg (20.3 [17.0-22.2] mg/L versus 12.9 [11.3-17.0] mg/L, P < 0.001). Considering all Cavg during longitudinal therapeutic drug monitoring (TDM), the frequency of therapeutic Cavg was higher in the group after implementation (74.8% [n = 103] versus 31% [n = 116], P < 0.001). The dose optimization protocol was also associated with a reduced time to obtain a negative blood culture (P < 0.001) and fewer antibiotic switches (P = 0.025), without increasing the frequency of nephrotoxicity. Clinical outcomes also appeared to be improved, with less periventricular leukomalacia (P = 0.021), trended toward less respiratory instability (P = 0.15) and a shorter duration of vasoactive drug use (P = 0.18) for neonates receiving personalized doses of vancomycin. This personalized vancomycin dose protocol improves vancomycin exposure in neonates, with good safety, and suggests an improvement in biological and clinical outcomes.

Antimicrobial stewardship programs in European pediatric intensive care units: an international survey of practices.

Antibiotic therapy represents one of the most common interventions in pediatric intensive care units (PICUs). This study aims to describe current antimicrobial stewardship programs (ASP) in European PICUs. A cross-sectional survey distributed to European pediatric intensive care physicians through the European Society of Neonatal and Pediatric Intensive Care (ESPNIC) Infection, Inflammation, and Sepsis Section, to members of the Spanish Society of Pediatric Intensive Care, of the Pediatric Reanimation and Emergency Care French Group, and to European physicians known to be involved in antimicrobial stewardship programs. Responses from 60 PICUs across 12 countries were analyzed. Fifty three (88%) stated that ASP was implemented. The main interventions considered as ASP were the pharmacokinetic monitoring of antimicrobials (n = 41, 77%) and the development of facility-specific clinical practice guidelines (n = 40, 75%). The most common team composition of antimicrobial stewardship program included a pediatric infectious disease physician, a pharmacist, and a microbiologist (n = 11, 21%). CONCLUSION:  Although ASP practices were reported to be widely implemented across European PICUs, this survey observed a large heterogeneity in terms of activities and modalities of intervention. WHAT IS KNOWN: • Antibiotic therapy represents one of the most common interventions in pediatric intensive care units. • The role and subsequent success of antimicrobial stewardship programs has largely been reported in the adult population but scarcely in the pediatric population. WHAT IS NEW: • Antimicrobial stewardship programs were reported to be widely implemented across European pediatric intensive care units. • We observed a large heterogeneity in terms of activities and modalities of intervention.

Chronic Granulomatous Disease in Patients Reaching Adulthood: A Nationwide Study in France.

Background: Although prognosis of Chronic Granulomatous Disease (CGD) has greatly improved, few studies have focused on its long-term outcome. We studied the clinical course and sequelae of CGD patients diagnosed before age 16, at various adult time points. Method: Cross-sectional French nationwide retrospective study of patients screened through the National Reference Center for Primary Immunodeficiencies (CEREDIH) registry. Results: Eighty CGD patients (71 males [88.7%], 59 X-linked [73.7%], median age 23.9 years [minimum, 16.6; maximum, 59.9]) were included, Median ages at diagnosis and last follow-up were 2.52 and 23.9 years, respectively. Seven patients underwent hematopoietic stem cell transplantation. A total of 553 infections requiring hospitalization occurred in 2017 patient-years. The most common site of infection was pulmonary (31%). Aspergillus spp. (17%) and Staphylococcus aureus (10.7%) were the commonest pathogens. A total of 224 inflammatory episodes occurred in 71 patients, mainly digestive (50%). Their characteristics as well as their annual frequency did not vary before and after age 16. Main sequelae were a small adult height and weight and mild chronic restrictive respiratory failure. At age 16, only 53% of patients were in high school. After age 30 years, 9/13 patients were working. Ten patients died during adulthood. Conclusions: Adult CGD patients displayed similar characteristics and rates of severe infections and inflammatory episodes that those of childhood. The high rate of handicap has become a matter of medical and social consideration. Careful follow-up in centers of expertise is strongly recommended and an extended indication of curative treatment by HSCT should be considered.

Disseminated rhinovirus C8 infection with infectious virus in blood and fatal outcome in a child with repeated episodes of bronchiolitis.

We report a fatal case of acute lower respiratory tract disease with human rhinovirus C (HRV-C) as the unique cause in a 19-month-old girl with a history of repeated episodes of bronchiolitis. HRV-C type 8 nucleic acids were observed in respiratory, stool, and cerebrospinal fluid samples, and infectious virions were isolated from patient serum after inoculation onto reconstituted airway epithelia.

Carbapenem prescriptions: Compliance with guidelines in a pediatric hospital.

BACKGROUND: This study aimed to describe the use of carbapenems in a pediatric tertiary center and to assess its compliance with national and local guidelines. METHODS: This retrospective study focused on children who received at least one dose of carbapenems in a tertiary university hospital over a 1-year period (2019). The appropriateness of each prescription was assessed. RESULTS: In total, 96 prescriptions were collected for 75 patients (median age 3 years [interquartile range, IQR: 0-9]). Most prescriptions were empirical (n = 77, 80%) and mainly concerned nosocomial infections (n = 69, 72%). At least one risk factor for extended-spectrum beta-lactamases was found in 48% (n = 46) of cases. The median duration of treatment with carbapenems was 5 days and it was over 7 days in 38% (n = 36) of cases. The use of carbapenems was considered appropriate in 95% (18/19) and 70% (54/77) of cases when therapy was guided by culture results or was empirical, respectively. De-escalation of carbapenem treatment within 72 h occurred in 31% (n = 30) of cases. CONCLUSION: The use of carbapenems can be optimized in the pediatric population, even when the initial prescription for a carbapenem is considered appropriate.

Evaluation of Microbiological Performance and the Potential Clinical Impact of the ePlex® Blood Culture Identification Panels for the Rapid Diagnosis of Bacteremia and Fungemia.

Molecular rapid diagnostic assays associated with antimicrobial stewardship have proven effective for the early adaptation of empiric therapy in bloodstream infections. The ePlex® BCID (GenMark Diagnostics) Panels allow identification of 56 bacteria and fungi and 10 resistance genes in 90 min directly from positive blood cultures. We prospectively evaluated 187 sepsis episodes at Grenoble University Hospital and retrospectively analyzed the cases to measure the potential clinical impact of the ePlex BCID results. Identification of all pathogens was obtained for 164/187 (88%) bloodstream infections with 100% detection of antimicrobial resistance genes (17 blaCTX-M , 1 vanA, and 17 mecA genes). Only 15/209 (7%) strains were not covered by the panels. Sensitivity for detection of micro-organisms targeted by the RUO BCID-GP, BCID-GN, and BCID-FP Panels was respectively 84/84 (100%), 103/107 (96%), and 14/14 (100%). Interestingly, accurate identification of all pathogens was achieved in 15/17 (88%) polymicrobial samples. Retrospective analysis of medical records showed that a modification of antimicrobial treatment would have been done in 45% of the patients. Treatment modifications would have been an optimization of empiric therapy, a de-escalation or an escalation in respectively 16, 17, and 11% of the patients. Moreover, 11% of the samples were classified as contaminants or not clinically relevant and would have led to early de-escalation or withdrawal of any antibiotic. Detection of resistance genes in addition to identification alone increased escalation rate from 4 to 11% of the patients. Absence of the ePlex result was considered a lost opportunity for therapy modification in 28% of patients.

Evaluation of the social bond: a new method tested in Mus spicilegus.

Innovative and fruitful studies of social bonds have been developed in recent years, although the methods used to establish the existence of a social bond between two individuals have not evolved significantly. Two types of paradigms have been currently used: the separation-reunion paradigm, which evaluates the distress caused by the disruption of the social bond, and choice paradigms, which test the specificity of the bond to a given individual. We have developed a new paradigm based on the idea that the cost an individual was ready to pay in order to gain access to a conspecific depended on the strength of the social bond between the two individuals. To test our paradigm we used mound-building mice, Mus spicilegus that present, in both males and females, a level of tolerance that differs greatly according to the degree of familiarity between the individuals. Our new method for testing social bond revealed unsuspected differences between males and females. Our results suggested that, at least in Mus spicilegus, strong social bonds were not necessary to the development of a high level of tolerance between individuals.