Neurologic Outcomes and Quality of Life in Children After Extracorporeal Membrane Oxygenation.

RATIONALE: Use of life support with extracorporeal membrane oxygenation (ECMO) is associated with brain injury. However, the consequences of these injuries on subsequent neurologic development and health-related quality of life (HRQoL) are poorly described in children. OBJECTIVES: The aim of this preliminary study was to describe short- and long-term neurologic outcomes in survivors of ECMO, as well as their HRQoL. DESIGN: Retrospective identified cohort with contemporary evaluations. SETTING: Necker Children's Hospital academic PICU. PATIENTS: Forty survivors who underwent ECMO (October 2014 to January 2020) were included in follow-up assessments in May 2021. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We first reviewed the outcomes of ECMO at the time of PICU discharge, which included a summary of neurology, radiology, and Pediatric Overall/Cerebral Performance Category (POPC/PCPC) scores. Then, in May 2021, we interviewed parents and patients to assess HRQoL (Pediatric Quality of Life Inventory [PedsQL]) and POPC/PCPC for children 3 years old or older, and Denver II test (DTII) for younger children. An evaluation of DTII in the youngest patients 1 year after ECMO decannulation was also added. Median age at ECMO was 1.4 years (interquartile range [IQR], 0.4-6 yr). Thirty-five children (88%) underwent a venoarterial ECMO. At PICU discharge, 15 of 40 patients (38%) had neurologic impairment. Assessment of HRQoL was carried out at median of 1.6 years (IQR, 0.7-3.3 yr) after PICU discharge. PedsQL scores were over 70 of 100 for all patients (healthy peers mean results: 80/100), and scores were like those published in patients suffering with chronic diseases. In May 2021, seven of 15 patients had a normal DTII, and 36 of 40 patients had a POPC/PCPC score less than or equal to 3. CONCLUSIONS: None of our patients presented severe disability at long term, and HRQoL evaluation was reassuring. Considering the risk of neurologic impairment after ECMO support, a systematic follow-up of these high-risk survivor patients would be advisable.

Systemic corticosteroids for the treatment of acute episodes of rhabdomyolysis in lipin-1-deficient patients.

Mutations in the LPIN1 gene constitute a major cause of severe rhabdomyolysis (RM). The TLR9 activation prompted us to treat patients with corticosteroids in acute conditions. In patients with LPIN1 mutations, RM and at-risk situations that can trigger RM have been treated in a uniform manner. Since 2015, these patients have also received intravenous corticosteroids. We retrospectively compared data on hospital stays by corticosteroid-treated patients vs. patients not treated with corticosteroids. Nineteen patients were hospitalized. The median number of admissions per patient was 21 overall and did not differ when comparing the 10 corticosteroid-treated patients with the 9 patients not treated with corticosteroids. Four patients in the non-corticosteroid group died during a RM (mean age at death: 5.6 years). There were no deaths in the corticosteroid group. The two groups did not differ significantly in the number of RM episodes. However, for the six patients who had RM and occasionally been treated with corticosteroids, the median number of RM episodes was significantly lower when intravenous steroids had been administered. The peak plasma creatine kinase level and the area under the curve were or tended to be higher in patients treated with corticosteroids-even after the exclusion of deceased patients or focusing on the period after 2015. The median length of stay (10 days overall) was significantly longer for corticosteroid-treated patients but was similar after the exclusion of deceased patients. The absence of deaths and the higher severity of RM observed among corticosteroid-treated patients could suggest that corticotherapy is associated with greater survival.

Neuroinflammatory Disease following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children.

OBJECTIVE: To describe neurologic, radiologic and laboratory features in children with central nervous system (CNS) inflammatory disease complicating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: We focused on CNS inflammatory diseases in children referred from 12 hospitals in the Paris area to Necker-Sick Children Reference Centre. RESULTS: We identified 19 children who had a history of SARS-CoV-2 infection and manifest a variety of CNS inflammatory diseases: encephalopathy, cerebellar ataxia, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, or optic neuritis. All patients had a history of SARS-CoV-2 exposure, and all tested positive for circulating antibodies against SARS-CoV-2. At the onset of the neurologic disease, SARS-CoV-2 PCR results (nasopharyngeal swabs) were positive in 8 children. Cerebrospinal fluid was abnormal in 58% (11/19) and magnetic resonance imaging was abnormal in 74% (14/19). We identified an autoantibody co-trigger in 4 children (myelin-oligodendrocyte and aquaporin 4 antibodies), representing 21% of the cases. No autoantibody was found in the 6 children whose CNS inflammation was accompanied by a multisystem inflammatory syndrome in children. Overall, 89% of patients (17/19) received anti-inflammatory treatment, primarily high-pulse methylprednisolone. All patients had a complete long-term recovery and, to date, no patient with autoantibodies presented with a relapse. CONCLUSIONS: SARS2-CoV-2 represents a new trigger of postinfectious CNS inflammatory diseases in children.

Therapeutic Drug Monitoring of Antibiotics in Critically Ill Children: An Observational Study in a Pediatric Intensive Care Unit.

BACKGROUND: Septic critically ill children are at a high risk of inadequate antibiotic exposure, requiring them to undergo therapeutic drug monitoring (TDM). The aim of this study was to describe the use of TDM for antibiotics in critically ill children. METHODS: The authors conducted a single-center observational study between June and December 2019, with all children treated with antibiotics in a pediatric intensive care unit located in a French university hospital. Standard clinical and laboratory data were recorded. Blood samples were collected for routine laboratory tests, and plasma antibiotic levels were assayed using validated analytical methods. RESULTS: A total of 209 children received antibiotics. TDM was performed in 58 patients (27.8%) who had a greater mean organ dysfunction (according to the International Pediatric Sepsis Consensus Conference) (3 versus 1 in the non-TDM group; P < 0.05) and were treated with antibiotics for longer. A total of 208 samples were analyzed. The median [interquartile range] assay turnaround time was 3 (1-5) days, and 48 (46.2%) of the 104 initial antibiotic concentration values were below the pharmacokinetic/pharmacodynamic targets. A total of 34 (46%) of the 74 off-target TDM measurements available before the end of the antibiotic treatment prompted dose adjustment. This dose adjustment increased the proportion of on-target TDM measurements (70% versus 20% without adjustment). Subsequent measurements of the minimum inhibitory concentration showed that the use of the European Committee on Antimicrobial Susceptibility Testing's epidemiological cutoff values led to underestimation of pharmacokinetic/pharmacodynamic target attainment in 10 cases (20%). CONCLUSIONS: TDM seems to be an effective means of optimizing antibiotic exposure in critically ill children. This requires timely plasma antibiotic assays and minimum inhibitory concentration measurements. It is important to define which patients should undergo TDM and how this monitoring should be managed.

Distinctive Features of Kawasaki Disease Following SARS-CoV-2 Infection: a Controlled Study in Paris, France.

BACKGROUND: An outbreak of multisystem inflammatory syndrome in children, including Kawasaki disease (KD), emerged during COVID-19 pandemic. We explored whether Kawasaki-like disease (KD), when associated with confirmed SARS-CoV-2 infection, has specific characteristics. METHODS: We included children and adolescents with KD criteria admitted in the department of general pediatrics of a university hospital in Paris, France, between January 1, 2018, and May 26, 2020. The incidence of KD was compared between the outbreak and a pre-outbreak control period (January 1, 2018, to April 25). Characteristics of patients with positive SARS-CoV-2 testing (KD-SARS-CoV-2) were compared to those of the pre-outbreak period (classic KD). RESULTS: A total of 30 and 59 children with KD were admitted during the outbreak and pre-outbreak periods, respectively (incidence ratio 13.2 [8.3-21.0]). During the outbreak, 23/30 (77%) children were diagnosed as KD-SARS-CoV-2. When compared with patients with classic KD, those with KD-SARS-CoV-2 were more frequently of sub-Saharan African ancestry (OR 4.4 [1.6-12.6]) and older (median 8.2 vs. 4.0 years, p < 0.001), had more often initial gastrointestinal (OR 84 [4.9-1456]) and neurological (OR 7.3 [1.9-27.7] manifestations, and shock syndrome (OR 13.7 [4.2-45.1]). They had significantly higher CRP and ferritin levels. Noticeably, they had more frequently myocarditis (OR 387 [38-3933]). CONCLUSIONS: Children and adolescents with KD-SARS-CoV-2 have specific features when compared with those with classic KD. These findings should raise awareness and facilitate the study of their pathogenesis.

Impact of public health measures on the post-COVID-19 respiratory syncytial virus epidemics in France.

Since the beginning of the COVID-19 pandemic, other respiratory illnesses decreased worldwide. This study described the consequences of public health measures on respiratory syncytial virus (RSV) severe infections in France, where an interseasonal resurgence of RSV occurred recently. All patients admitted to Necker Hospital (Paris) between August 2018 and April 2021 with a diagnosis of RSV-associated acute lung respiratory infection (ALRI) were enrolled. Characteristics of subjects with RSV-associated ALRI in 2020/2021 were compared to those infected during the two previous outbreaks. Overall, 664 inpatients were diagnosed with RSV-associated ALRI: 229, 183, and 252 during the 2018/2019, 2019/2020, and 2020/2021 outbreaks, respectively. During autumn 2020, a national lockdown began in France but schools remained open. A 3-month delayed RSV epidemic occurred at the end of this lockdown. Compared to previous outbreaks, the 2020/2021 epidemics involved more children aged 6 to 11 months (25.8% versus 13.1%, p < 0.0001), but less infants aged < 6 months (41.3% versus 56.6%, p < 0.0001) and less adults (0.0 versus 2.7%, p < 0.0001). Shorter length of stay at hospital, less frequent requirement of admission to intensive care unit, use of non-invasive ventilation, and/or high-flow nasal oxygen were observed in 2020/2021 than during previous epidemics (p < 0.0001). Delayed RSV outbreak was associated with more hospitalizations for ALRI, higher age of pediatric inpatients, but milder median clinical phenotype. Reinforced public health measures (even while keeping nurseries and schools open with mandatory face masks since six years of age) could impact, at least transiently, the burden of RSV-related hospitalizations.

Population pharmacokinetics of meropenem in critically ill children with different renal functions.

PURPOSE: We aimed to develop a meropenem population pharmacokinetic (PK) model in critically ill children and simulate dosing regimens in order to optimize patient exposure. METHODS: Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach. RESULTS: Forty patients with an age of 16.8 (1.4-187.2) months, weight of 9.1 (3.8-59) kg, and estimated glomerular filtration rate (eGFR) of 151 (19-440) mL/min/1.73 m2 were included. Eleven patients received continuous replacement renal therapy (CRRT). Concentration-time courses were best described by a two-compartment model with first-order elimination. Body weight (BW), eGFR, and CRRT were covariates explaining the between-subject variabilities on central/peripheral volume of distribution (V1/V2), inter-compartment clearance (Q), and clearance (CL): V1i = V1pop × (BW/70)1, Qi = Qpop × (BW/70)0.75, V2i = V2pop × (BW/70)1, CLi = (CLpop × (BW/70)0.75) × (eGFR/100)0.378) for patients without CRRT and CLi = (CLpop × (BW/70)0.75) × 0.9 for patients with CRRT, where CLpop, V1pop, Qpop, and V2pop are 6.82 L/h, 40.6 L, 1 L/h, and 9.2 L respectively normalized to a 70-kg subject. Continuous infusion, 60 and 120 mg/kg per day, is the most adequate dosing regimen to attain the target of 50% fT > MIC and 100% fT > MIC for patients infected by bacteria with high minimum inhibitory concentration (MIC) value (> 4 mg/L) without risk of accumulation except in children with severe renal failure. CONCLUSION: Continuous infusion allows reaching the fT > MIC targets safely in children with normal or increased renal clearance.

Eosinopenia as a marker of diagnosis and prognostic to distinguish bacterial from aseptic meningitis in pediatrics.

Procalcitonin (PCT) has proven its efficacy to distinguish bacterial from aseptic meningitis in children. Nevertheless, its use in routine is limited by its cost and availability, especially in low- and middle-income countries. It is now acknowledged that eosinopenia is a marker of infection and/or severity of the systemic inflammatory response. Although no study ever demonstrated that eosinopenia could differentiate bacterial from viral infection, we decided to conduct a study concerning meningitis in children. This bicentric and retrospective study was conducted between January 2012 and October 2018, in children hospitalized for meningitis. The white blood cell was systematically gathered at the admission to evaluate the eosinophil count. Characteristic data were compared between 2 groups: documented bacterial meningitis (DBP) and aseptic meningitis which includes documented viral meningitis (DVM) and non-documented meningitis (ND). Among 190 patients admitted for meningitis, 151 were analyzed, including DBM (n = 45), DVM (n = 73), and ND (n = 33) meningitis. Groups were comparable. Mean age was 33 ± 48 months with a sex ratio of 1.6. Mean of eosinophil count was 15 ± 34/mm3 in the DBM group versus 132 ± 167/mm3 for the aseptic meningitis group (p < 0.0001). Best threshold for the diagnosis of bacterial meningitis was an eosinophil count < 5/mm3 with a sensitivity of 80% and specificity of 73% and a likelihood ratio of 2.9. Eosinopenia seems to be a reliable and non-invasive marker of bacterial meningitis in pediatrics. The absence of extra cost makes it very interesting in low- and middle-income countries or when usual biomarkers such as PCT are unavailable.

Fulminant arterial vasculitis as an unusual complication of disseminated staphylococcal disease due to the emerging CC1 methicillin-susceptible Staphylococcus aureus clone: a case report.

BACKGROUND: Staphylococcus aureus has emerged as a leading cause of invasive severe diseases with a high rate of morbidity and mortality worldwide. The wide spectrum of clinical manifestations and outcome observed in staphylococcal illness may be a consequence of both microbial factors and variability of the host immune response. CASE PRESENTATION: A 14-years old child developed limb ischemia with gangrene following S. aureus bloodstream infection. Histopathology revealed medium-sized arterial vasculitis. The causing strain belonged to the emerging clone CC1-MSSA and numerous pathogenesis-related genes were identified. Patient's genotyping revealed functional variants associated with severe infections. A combination of virulence and host factors might explain this unique severe form of staphylococcal disease. CONCLUSION: A combination of virulence and genetic host factors might explain this unique severe form of staphylococcal disease.

Achievement of Therapeutic Vancomycin Exposure With Continuous Infusion in Critically Ill Children.

OBJECTIVE: Describe and assess a continuous infusion dosing scheme of vancomycin therapy in critically ill children. DESIGN: Retrospective single-center study, January to June 2015. SETTING: PICU located within a French tertiary academic pediatric hospital. PATIENTS: All children admitted in the PICU from January 2015 to June 2015, receiving continuous infusion of vancomycin therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and biological data, vancomycin dosing information, and plasma concentrations were recorded. Using a previously published population pharmacokinetics model, pharmacokinetic parameters were derived for each patient and vancomycin concentrations described after the loading dose. Areas under the curve were estimated for each patient, and an initial covariate-adjusted dose was calculated for every patient. A total of 87 vancomycin concentrations were analyzed from 28 patients between 1 month and 17 years old. The median (range) loading dose was 14.8 (12-16) mg/kg followed by a continuous infusion of vancomycin of 44 (35-61) mg/kg/d. On their first sample, 12 patients (43%) had a concentration between 15 and 30 mg/L. On day 1, the median (range) estimated area under the curve was 349 (201-1,001) mg/L × hr, and seven patients (25%) had an area under the curve greater than 400 mg/L × hr. Using the pharmacokinetics model, the median (range) calculated initial daily dose, taking into account age, bodyweight, and serum creatinine concentration, was 53 (36-69) mg/kg/d resulting in a simulated day 1 area under the curve of 409 (341-593) mg/L × h with a theoretical pharmacokinetic target attainment of 57%. CONCLUSIONS: The current continuous infusion of vancomycin dosing scheme used in our population was inappropriate and led to underexposure. Using pharmacokinetic approaches such as covariate-adjusted initial dosing and Bayesian estimation of exposure should prove useful for achieving the pharmacokinetic target.

Twenty-eight years of intestinal transplantation in Paris: experience of the oldest European center.

Our aim was to describe our achievements in pediatric intestinal transplantation (ITx) and define areas for improvement. After a period (1987-1990) of nine isolated small bowel transplants (SBTx) where only one patient survived with her graft, 110 ITx were performed on 101 children from 1994 to 2014: 60 SBTx, 45 liver-small bowel, four multivisceral (three with kidneys), and one modified multivisceral. Indications were short bowel syndrome (36), motility disorders (30), congenital enteropathies (34), and others (1). Induction treatment was introduced in 2000. Patient/graft survival with a liver-containing graft or SBTx was, respectively, 60/41% and 46/11% at 18 years. Recently, graft survival at 5/10 years was 44% and 31% for liver-containing graft and 57% and 44% for SBTx. Late graft loss occurred in 13 patients, and 7 of 10 retransplanted patients died. The main causes of death and graft loss were sepsis and rejection. Among the 55 currently living patients, 21 had a liver-containing graft, 19 a SBTx (17 after induction), and 15 were on parenteral nutrition. ITx remains a difficult procedure, and retransplantation even more so. Over the long term, graft loss was due to rejection, over-immunosuppression was not a significant problem. Multicenter studies on immunosuppression and microbiota are urgently needed.

Preoperative risk factors for intra-operative bleeding in pediatric liver transplantation.

This study analyzes the preoperative risk factors for intra-operative bleeding in our recent series of pediatric LTs. Between November 2009 and November 2014, 84 consecutive isolated pediatric LTs were performed in 81 children. Potential preoperative predictive factors for bleeding, amount of intra-operative transfusions, postoperative course, and outcome were recorded. Cutoff point for intra-operative HBL was defined as intra-operative RBC transfusions ≥1 TBV. Twenty-six patients (31%) had intra-operative HBL. One-year patient survival after LT was 66.7% (CI 95%=[50.2-88.5]) in HBL patients and 83.8% (CI 95%=[74.6-94.1]) in the others (P=.054). Among 13 potential preoperative risk factors, three of them were identified as independent predictors of high intra-operative bleeding: abdominal surgical procedure(s) prior to LT, factor V level ≤30% before transplantation, and ex situ parenchymal transsection of the liver graft. Based on these findings, we propose a simple score to predict the individual hemorrhagic risk related to each patient and graft association. This score may help to better anticipate intra-operative bleeding and improve patient's management.

Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016.

We report 59 cases of severe paediatric conditions linked with enterovirus (EV)-A71 and EV-D68 in France between May and October 2016. Fifty-two children had severe neurological symptoms. EV sequence-based typing for 42 cases revealed EV-A71 in 21 (18 subgenotype C1, detected for the first time in France) and EV-D68 in eight. Clinicians should be encouraged to obtain stool and respiratory specimens from patients presenting with severe neurological disorders for EV detection and characterisation.

Prevention of infections during primary immunodeficiency.

Because infectious diseases are a major source of morbidity and mortality in the majority of patients with primary immunodeficiencies (PIDs), the application of a prophylactic regimen is often necessary. However, because of the variety of PIDs and pathogens involved, and because evidence is scarce, practices are heterogeneous. To homogenize practices among centers, the French National Reference Center for PIDs aimed at elaborating recommendations for anti-infectious prophylaxis for the most common PIDs. We performed a literature review of infectious complications and prophylactic regimens associated with the most frequent PIDs. Then, a working group including different specialists systematically debated about chemoprophylaxis, immunotherapy, immunization, and recommendations for patients. Grading of prophylaxis was done using strength of recommendations (decreasing from A to D) and evidence level (decreasing from I to III). These might help infectious diseases specialists in the management of PIDs and improving the outcome of patients with PIDs.

Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule.

PURPOSE: Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection. MATERIALS AND METHODS: We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals. RESULTS: A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47). CONCLUSIONS: A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.

Case Report: Cerebrovascular Events Associated With Bacterial and SARS-CoV-2 Infections in an Adolescent.

Neurologic manifestations associated with Covid-19 are increasingly reported, especially stroke and acute cerebrovascular events. Beyond cardiovascular risk factors associated with age, some young adults without medical or cardiovascular history had stroke as a presenting feature of Covid-19. Suggested stroke mechanisms in this setting are inflammatory storm, subsequent hypercoagulability, and vasculitis. To date, a handful of pediatric stroke cases associated with Covid-19 have been reported, either with a cardioembolic mechanism or a focal cerebral arteriopathy. We report the case of an adolescent who presented with febrile meningism and stupor. Clinical, biological, and radiological features favored the diagnosis of Lemierre syndrome (LS), with Fusobacterium necrophorum infection (sphenoid sinusitis and meningitis) and intracranial vasculitis. The patient had concurrent SARS-CoV-2 infection. Despite medical and surgical antimicrobial treatment, stroke prevention, and venous thrombosis prevention, he presented with severe cerebrovascular complications. Venous thrombosis and stroke were observed, with an extension of intracranial vasculitis, and lead to death. As both F. necrophorum and SARS-CoV-2 enhance inflammation, coagulation, and activate endothelial cells, we discuss how this coinfection may have potentiated and aggravated the usual course of LS. The potentiation by SARS-CoV-2 of vascular and thrombotic effects of a bacterial infection may represent an underreported cerebrovascular injury mechanism in Covid-19 patients. These findings emphasize the variety of mechanisms underlying stroke in this disease. Moreover, in the setting of SARS-CoV-2 pandemic, we discuss in what extent sanitary measures, namely, lockdown and fear to attend medical facilities, may have delayed diagnosis and influenced outcomes. This case also emphasizes the role of clinical assessment and the limits of telemedicine for acute neurological condition diagnosis.

Assessment of the Effects of a High Amikacin Dose on Plasma Peak Concentration in Critically Ill Children.

OBJECTIVES: This study aimed to assess the incidence of amikacin plasma peak concentration (Cmax) below 60 mg·L-1 in critically ill children receiving an amikacin dosing regimen of 30 mg kg-1·day-1. Secondary objectives were to identify factors associated with low Cmax and to assess the incidence of acute kidney injury (AKI). METHODS: A retrospective observational study was performed in two French pediatric intensive care units. All admitted children who received 30 mg·kg-1 amikacin and had a Cmax measurement were eligible. Clinical and biological data, amikacin dose, and concentrations were collected. RESULTS: In total, 30 patients were included, aged from 3 weeks to 7 years. They received a median amikacin dosage of 30 mg kg-1·day-1 (range 29-33) based on admission body weight (BW), corresponding to 27 mg kg-1·day-1 (range 24-30) based on actual BW. Cmax was < 60 mg·L-1 in 21 (70%) children and none had a Cmax ≥ 80 mg·L-1. Among the 15 patients with a measured minimum inhibitory concentration (MIC), 13 (87%) had a Cmax/MIC ratio > 8. Univariate analysis showed that factors associated with Cmax < 60 mg·L-1 were high estimated glomerular filtration rate (p = 0.015) and low blood urea concentration (p = 0.001). AKI progression or occurrence was observed after amikacin administration in two (7%) and six (21%) patients, respectively. CONCLUSIONS: Despite the administration of the maximal recommended amikacin dose, Cmax was below the pharmacokinetic target in 70% of our pediatric population. Further studies are needed to develop a pharmacokinetic model in a population of critically ill children to optimize target attainment.