Epidemiology and outcomes of ventilator-associated events in critically ill children: Evaluation of three different definitions.

OBJECTIVE: Ventilator-associated pneumonia (VAP) is one of the most common healthcare-associated infections in pediatric intensive care units (PICUs), but its definite diagnosis remains controversial. The CDC Ventilator-Associated Event (VAE) module (validated in adults) constitutes a new approach for VAP surveillance. DESIGN: We described epidemiological characteristics of PICU VAE cases, investigated possible risk factors, and evaluated 3 different sets of diagnostic VAE criteria. SETTING: This study was conducted in a PICU in a tertiary-care general hospital in northern Greece during 2017-2019. PATIENTS: The study included patients aged 35 days-16 years who received mechanical ventilation. METHODS: From medical records, we retrieved epidemiological data, clinical data, and laboratory characteristics as well as ventilator settings for our analysis. We assessed "oxygen deterioration" for the tier 1 CDC VAE module using 3 sets of diagnostic criteria: (1) CDC adult VAE criteria [increase of daily minimum fraction of inspired oxygen (FiO2) ≥ 0.2 or positive end expiratory pressure (PEEP) ≥ 3 cmH2O for 2 days], (2) the US pediatric VAE criteria [increase of FiO2 ≥ 0.25 or mean airway pressure (MAP) ≥ 4 cmH2O for 2 days], and (3) the European pediatric VAE criteria (increase of FiO2 ≥ 0.2 or PEEP ≥ 2 cmH2O for 1 day or increase of FiO2 ≥ 0.15 and PEEP ≥ 1 cm H2O for 1 day). RESULTS: Among 326 children admitted to the PICU, 301 received mechanical ventilation. The incidence rate according to the CDC adult VAE criteria was 4.7 per 1,000 ventilator days. For the US pediatric VAE criteria the incidence rate was 6 per 1,000 ventilator days. For the European pediatric VAE criteria the incidence rate was 9.7 per 1,000 ventilator days. These results revealed statistically significant correlation of all 3 algorithms with adverse outcomes, including mortality. CONCLUSIONS: All VAE algorithms were associated with higher mortality rates. Our findings highlight the need for a unified pediatric VAE definition to improve preventive strategies.

Population Pharmacokinetics and Outcomes of Critically Ill Pediatric Patients Treated with Intravenous Colistin at Higher Than Recommended Doses.

Limited pharmacokinetic (PK) data suggest that currently recommended pediatric dosages of colistimethate sodium (CMS) by the Food and Drug Administration and European Medicines Agency may lead to suboptimal exposure, resulting in plasma colistin concentrations that are frequently <2 mg/liter. We conducted a population PK study in 17 critically ill patients 3 months to 13.75 years (median, 3.3 years) old who received CMS for infections caused by carbapenem-resistant Gram-negative bacteria. CMS was dosed at 200,000 IU/kg/day (6.6 mg colistin base activity [CBA]/kg/day; 6 patients), 300,000 IU/kg/day (9.9 mg CBA/kg/day; 10 patients), and 350,000 IU/kg/day (11.6 mg CBA/kg/day; 1 patient). Plasma colistin concentrations were determined using ultraperformance liquid chromatography combined with electrospray ionization-tandem mass spectrometry. Colistin PK was described by a one-compartment disposition model, including creatinine clearance, body weight, and the presence or absence of systemic inflammatory response syndrome (SIRS) as covariates (P < 0.05 for each). The average colistin plasma steady-state concentration (Css,avg) ranged from 1.11 to 8.47 mg/liter (median, 2.92 mg/liter). Ten patients had Css,avg of ≥2 mg/liter. The presence of SIRS was associated with decreased apparent clearance of colistin (47.8% of that without SIRS). The relationship between the number of milligrams of CBA per day needed to achieve each 1 mg/liter of plasma colistin Css,avg and creatinine clearance (in milliliters per minute) was described by linear regression with different slopes for patients with and without SIRS. Nephrotoxicity, probably unrelated to colistin, was observed in one patient. In conclusion, administration of CMS at the above doses improved exposure and was well tolerated. Apparent clearance of colistin was influenced by creatinine clearance and the presence or absence of SIRS.

Evaluation of continuous flash glucose monitoring in a pediatric ICU setting.

Glucose monitoring is of great importance among patients in intensive care units (ICU). The purpose of this study is to assess the performance of a new flash glucose monitoring (FGM) system in a pediatric ICU setting. Sixteen consecutive patients admitted in pediatric ICU aged > 4 years, expected length stay > 2 days and with no medication or existing diagnosis affecting glucose metabolism were enrolled. FreeStyle Libre sensor was applied to the upper arm of the patients (8 boys). FGM measurements were compared to 3 "references": arterial blood gas analysis, capillary blood analysis and biochemical serum analysis. Mean age of patients was 8.03 ± 2.91 years. Sensors remained in situ for a median of 9.71 ± 5.35 days. Removal of the sensor was mainly attributed to the completion of the predefine life-span of the sensor or discharge of the patient from the ICU. We compared 711 pairs of measurements between the sensor and other glucose measurement methods. Glucose values from the sensor were consistently lower with mean absolute relative difference (MARD) being 28.34%, 25.11% and 18.99% compared to the blood gas analyzer, capillary blood glucose meter, and biochemical serum analysis, respectively, but a wide interindividual variability. Significant linear correlations between age and MARD values were observed. Surveillance error grid (SEG) analysis showed 92.04%, 94.67% and 95.52% of the readings in the none or slight risk zone respectively. FreeStyle Libre is well tolerated although not adequately accurate with a tendency to underestimate glucose levels in critically ill pediatric patients.

Effects of an Active Surveillance Program and Enhanced Infection Control Measures on Carbapenem-Resistant Gram-Negative Bacterial Carriage and Infections in Pediatric Intensive Care.

We evaluated the effects of enhanced infection control measures (ICMs) on carriage and infections of carbapenem-resistant Gram-negative bacteria (CRGNB) in a pediatric intensive care unit. We conducted a quasi-experimental study, including patients with infections of CRGNB retrospectively for 13 months and those participating in an active surveillance program prospectively for 22 months. Active surveillance (weekly rectal swabs) was implemented during a 63-week subperiod with standard ICMs and a subsequent 27-week subperiod with enhanced ICMs (intensified ICMs supplemented with audits and feedback). Prevalence, colonization pressure, incidence, and infections of CRGNB and compliance with ICMs and enhanced ICMs were recorded. Evaluation of results was performed using time series (TS) and interrupted TS. Compliance with hand hygiene improved during the second subperiod of active surveillance compared with the first; prevalence, colonization pressure, and incidence of CRGNB decreased significantly. The linear trend of centered moving average for carbapenem-resistant Klebsiella pneumoniae (CRKP) decreased from 1.2 to 0.1 infections/1,000 bed-days (IBD) (p = 0.046), while it remained unchanged for carbapenem-resistant Acinetobacter baumannii (CRAB) and increased for carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 0.0 to 2.1 IBD (p < 0.001). Enhanced ICMs can reduce CRKP infections in endemic units, in contrast to CRPA and CRAB infections, which are more difficult to eradicate.

Use of Ceftazidime-avibactam for the Treatment of Extensively drug-resistant or Pan drug-resistant Klebsiella pneumoniae in Neonates and Children <5 Years of Age.

BACKGROUND: Emergence of extensively drug-resistant (XDR) or pan drug-resistant (PDR) Enterobacteriaceae is a major public threat especially for young patients. Treatment options for these bacteria are extremely limited with no safety data existing for neonates and children. Ceftazidime-avibactam has activity against Gram-negative bacteria producing Klebsiella pneumoniae carbapenemase, but virtually no data exist on its use in neonatal and pediatric patients. METHODS: We present a single-center case series of neonates and children <5 years treated with ceftazidime-avibactam for XDR or PDR K. pneumoniae infections until August 2018. Medical records of patients who received ceftazidime-avibactam for at least 2 days (6 doses) were reviewed. Clinical, laboratory and microbiologic data were collected using a prestructured form. Adverse events and clinical/microbiologic responses and 15- and 30-day outcome were assessed. RESULTS: In our case series, 8 patients (median age 53 days, range from 13 days to 4.5 years) received 9 courses of ceftazidime-avibactam at a dose of 62.5 mg/kg q8h for suspected or proven XDR/PDR K. pneumoniae infections including bloodstream infections (8 courses), central nervous system infections (2 courses) and urinary tract infection (1 course). All patients were critically ill and received other antibiotics prior and concomitantly with the administration of ceftazidime-avibactam. There was no treatment discontinuation due to adverse events. Clinical and microbiologic responses occurred in all patients, and no patient died by day 30. CONCLUSIONS: Administration of ceftazidime-avibactam appears to be well tolerated and efficacious against in vitro susceptible XDR or PDR Enterobacteriaceae without being associated with significant adverse events.

Pharmacokinetics of Daptomycin in Critically Ill Pediatric Patients.

The pharmacokinetics of daptomycin (10 mg/kg once daily) was studied in 4 critically ill pediatric patients aged 8 to 14 yrs. The area under the concentration-time curve from time zero to infinity (AUC0-∞) of plasma concentrations on day 1 ranged between 123.8 to 663.9 µg · h/ml, with lower values observed in septic and burn patients; clearance ranged from 15.1 to 80.7 ml/h/kg. Higher-than-recommended doses of daptomycin may be needed in septic children to ensure optimal drug exposure. Interpatient variability may suggest a role for therapeutic drug monitoring.

Short-term and long-term mortality following pediatric intensive care.

BACKGROUND: The aim of the present study was to examine short-term and long-term mortality following discharge from the pediatric intensive care unit (PICU). METHODS: This was a prospective observational study. Data collected consisted of demographics, severity scores, procedures, treatment, need for and duration of mechanical ventilation (MV), length of PICU and hospital stay, and mortality at PICU and hospital discharge, at 3 and 6 months and at 1 and 2 years. RESULTS: A total of 300 patients (196 boys and 104 girls), aged 54.26 ± 49.93 months, were included in the study. Median (interquartile range) Pediatric Risk of Mortality (PRISM III-24) score was 7 (3-11) and predicted mortality rate was 11.16%. MV rate was 67.3% (58.3% at admission) for 6.54 ± 14.15 days, and length of PICU and hospital stay was 8.85 ± 23.28 days and 20.69 ± 28.64 days, respectively. Mortality rate at discharge was 9.7% and cumulative mortality rate thereafter was 12.7%, 15.0%, 16.7%, 19.0%, and 19.0% at hospital discharge, 3 months, 6 months, 1 year and 2 years, respectively. Significant risk factors of PICU mortality were inotrope use, PRISM III-24 score >8, MV, arterial and central venous catheterization, nosocomial infection, complications, and cancer. Independent predictors of mortality at discharge were inotrope use and PRISM III-24 score, whereas predictors of mortality at 2 years were comorbidity and cancer. CONCLUSIONS: A 2 year follow-up period seems sufficient for a comprehensive mortality analysis of PICU patients. Severity of critical illness is the key factor of short-term mortality, whereas comorbidity is the major determinant of long-term mortality.