Increase in Incidence Rates and Risk Factors for Multidrug Resistant Bacteria in Septic Children: A Nationwide Spanish Cohort Study (2013-2019).

The emergence of multidrug-resistant (MDR) bacteria in children is a growing concern, particularly among septic patients, given the need for first-right dosing. Our aim was to determine the incidence rates and factors associated with MDR-sepsis in the pediatric intensive care unit (PICU), using data from the Spanish ENVIN-HELICS PICU registry between 2013 and 2019. The rate of MDR bacteria among septic children ranged between 5.8 and 16.2% throughout this study period, with a significant increase since 2015 (p = 0.013). MDR-gram-negative bacteria (92%), particularly EBL-Enterobacterales (63.7%), were the most frequent causative microorganisms of MDR-sepsis. During this study period, sixteen MDR-sepsis (32.6%) corresponded to intrahospital infections, and 33 (67.4%) had community-onset sepsis, accounting for 10.5% of the overall community-onset sepsis. Independent risk factors associated with MDR-sepsis were antibiotics 48 h prior to PICU admission (OR 2.38) and PICU onset of sepsis (OR 2.58) in >1 year-old children, and previous malnourishment (OR 4.99) in <1 year-old children. Conclusions: There was an alarming increase in MDR among septic children in Spain, mainly by gram-negative (ESBL-Enterobacterales), mostly coming from the community setting. Malnourished infants and children on antibiotics 48 h prior to PICU are at increased risk and therefore require closer surveillance.

Intestinal loads of extended-spectrum beta-lactamase and Carbapenemase genes in critically ill pediatric patients.

Introduction: Intestinal colonization by Multi-Drug Resistant Organisms (MDROs) can pose a threat on the health of critically ill patients. The extent of colonization by these organisms is related to previous antibiotic treatments and their ability to cause infections among adult patients. The aim of this study is to determine the relationship between the intestinal Relative Loads (RLs) of selected antibiotic resistance genes, antibiotic consumption and extra-intestinal spread among critically ill pediatric patients. Methods: RLs of bla CTX-M-1-Family, bla OXA-1, bla OXA-48 and bla VIM were determined in 382 rectal swabs obtained from 90 pediatric critically ill patients using qPCRs. The RLs were compared to the patients' demographics, antibiotic consumption, and detection of MDROs from extra-intestinal sites. 16SrDNA metagenomic sequencing was performed for 40 samples and clonality analyses were done for representative isolates. Results and discussion: 76 (74.45%) patients from which 340 (89.01%) rectal swabs were collected had at least one swab that was positive for one of the tested genes. Routine cultures did not identify carbapenemases in 32 (45.1%) and 78 (58.2%) swabs that were positive by PCR for bla OXA-48 and blaVIM, respectively. RLs of above 6.5% were associated with extra-intestinal spread of blaOXA-48-harboring MDROs. Consumption of carbapenems, non-carbapenem ß-lactams, and glycopeptides were statistically associated with testing negative for bla CTX-M-1-Family and bla OXA-1 while the consumption of trimethoprim/sulfamethoxazole and aminoglycosides was associated with testing negative for blaOXA-48 (P<0.05). In conclusion, targeted qPCRs can be used to determine the extent of intestinal dominance by antibiotic resistant opportunistic pathogens and their potential to cause extra-intestinal infections among a critically ill pediatric population.

Device Exposure and Patient Risk Factors' Impact on the Healthcare-Associated Infection Rates in PICUs.

Healthcare-associated infections related to device use (DA-HAIs) are a serious public health problem since they increase mortality, length of hospital stay and healthcare costs. We performed a multicenter, prospective study analyzing critically ill pediatric patients admitted to 26 Spanish pediatric intensive care units (PICUs) over a 3-month period each year from 2014 to 2019. To make comparisons and evaluate the influence of HAI Zero Bundles (care bundles that intend to reduce the DA-HAI rates to zero) on PICU HAI rates, the analysis was divided into two periods: 2014-2016 and 2017-2019 (once most of the units had incorporated all the Zero Bundles). A total of 11,260 pediatric patients were included. There were 390 episodes of HAIs in 317 patients and the overall rate of HAIs was 6.3 per 1000 patient days. The DA-HAI distribution was: 2.46/1000 CVC days for central-line-associated bloodstream infections (CLABSIs), 5.75/1000 MV days for ventilator-associated pneumonia (VAP) and 3.6/1000 UC days for catheter-associated urinary tract infections (CAUTIs). Comparing the two periods, the HAI rate decreased (p = 0.061) as well as HAI episodes (p = 0.011). The results demonstrate that exposure to devices constitutes an extrinsic risk factor for acquiring HAIs. The multivariate analysis highlights previous bacterial colonization by multidrug-resistant (MDR) bacteria as the most important extrinsic risk factor for HAIs (OR 20.4; 95%CI 14.3-29.1). In conclusion, HAI Zero Bundles have been shown to decrease HAI rates, and the focus should be on the prompt removal of devices, especially in children with important intrinsic risk factors.

Intestinal Dominance by Multidrug-Resistant Bacteria in Pediatric Liver Transplant Patients.

Pediatric liver transplantation (PLTx) is commonly associated with extensive antibiotic treatments that can produce gut microbiome alterations and open the way to dominance by multidrug-resistant organisms (MDROs). In this study, the relationship between intestinal Relative Loads (RLs) of ß-lactamase genes, antibiotic consumption, microbiome disruption, and the extraintestinal dissemination of MDROs among PLTx patients is investigated. 28 PLTx patients were included, from whom 169 rectal swabs were collected. Total DNA was extracted and blaCTX-M-1-Family, blaOXA-1, blaOXA-48, and blaVIM were quantified via quantitative polymerase chain reaction (qPCR) and normalized to the total bacterial load (16SrRNA) through LogΔΔCt to determine the RLs. 16SrRNA sequencing was performed for 18 samples, and metagenomic sequencing was performed for 2. Patients' clinical data were retrieved from the hospital's database. At least one of the genes tested were detected in all of the patients. The RLs for blaCTX-M-1-Family, blaOXA-1, blaOXA-48, and blaVIM were higher than 1% of the total bacterial population in 67 (80.73%), 56 (78.87%), 57 (77.03%) and 39 (61.9%) samples, respectively. High RLs for blaCTX-M-1-Family, blaOXA-1, and/or blaOXA-48, were positively associated with the consumption of carbapenems with trimethoprim-sulfamethoxazole and coincided with low diversity in the gut microbiome. Low RLs were associated with the consumption of noncarbapenem ß-lactams with aminoglycosides (P < 0.05). Extraintestinal isolates harboring the same gene(s) as those detected intraintestinally were found in 18 samples, and the RLs of the respective swabs were high. We demonstrated a relationship between the consumption of carbapenems with trimethoprim-sulfamethoxazole, intestinal dominance by MDROs and extraintestinal spread of these organisms among PLTx patients. IMPORTANCE In this study, we track the relative intestinal loads of antibiotic resistance genes among pediatric liver transplant patients and determine the relationship between this load, antibiotic consumption, and infections caused by antibiotic-resistant organisms. We demonstrate that the consumption of broad spectrum antibiotics increase this load and decrease the gut microbial diversity among these patients. Moreover, the high loads of resistance genes were related to the extraintestinal spread of multidrug-resistant organisms. Together, our data show that the tracking of the relative intestinal loads of antibiotic resistance genes can be used as a biomarker that has the potential to stop the extraintestinal spread of antibiotic-resistant bacteria via the measurement of the intestinal dominance of these organisms, thereby allowing for the application of preventive measures.

Antimicrobial Stewardship Improvement in Pediatric Intensive Care Units in Spain-What Have We Learned?

Antibiotic misuse in pediatric intensive care units (PICUs) can lead to increased antimicrobial resistance, antibiotic-triggered side effects, hospital costs, and mortality. We performed a multicenter, prospective study, analyzing critically ill pediatric patients (≥1 month to ≤18 years) admitted to 26 Spanish PICUs over a 3-month period each year (1 April−30 June) from 2014−2019. To make comparisons and evaluate the influence of AMS programs on antibiotic use in PICUs, the analysis was divided into two periods: 2014−2016 and 2017−2019 (once 84% of the units had incorporated an AMS program). A total of 11,260 pediatric patients were included. Total antibiotic prescriptions numbered 15,448 and, overall, 8354 patients (74.2%) received at least one antibiotic. Comparing the two periods, an increase was detected in the number of days without antibiotics in patients who received them divided by the number of days in PICUs, for community-acquired infections (p < 0.001) and healthcare-associated infections (HAIs) acquired in PICUs (p < 0.001). Antibiotics were empirical in 7720 infections (85.6%), with an increase in appropriate antibiotic indications during the second period (p < 0.001). The main indication for antibiotic adjustment was de-escalation, increasing in the second period (p = 0.045). Despite the high rate of antibiotic use in PICUs, our results showed a significant increase in appropriate antibiotic use and adjustment following the implementation of AMS programs.

Ventilator-associated events in children: A multicentre prospective cohort study.

BACKGROUND: The Centres for Disease Control and Prevention (CDC) broadened the focus of surveillance from ventilator-associated pneumonia to ventilator-associated event (VAE) for quality purposes. No paediatric definition of VAE (PaedVAE) has been accurately validated. We aimed to analyse the incidence and impact on patient outcomes resulting from the application of the adult and two paediatric VAE (PaedVAE) criteria. SECONDARY OBJECTIVE: to evaluate VAE/PaedVAE as factors associated with increased duration of mechanical ventilation (MV) and Paediatric Intensive Care Unit (PICU) stay. METHODS: Multicentre observational prospective cohort study in 15 PICUs in Spain. VAEs were assessed using the 2013/2015 CDC classification. PaedVAE were assessed using the CDC definition based on mean airway pressure (MAP-PaedVAE) versus a paediatric definition based on positive end-expiratory pressure (PEEP-PaedVAE). Children who underwent MV ≥ 48 h were included. RESULTS: A total of 3626 ventilator-days in 391 patients were analysed. The incidence of VAE, MAP-PaedVAE and PEEP-PaedVAE was 8.55, 5.24 and 20.96 per 1000 ventilator-days, respectively. The median time [IQR] for VAE, MAP-PaedVAE and PEEP-PaedVAE development from the MV onset was 4 [3-12.5], 4 [3-14], and 5 [3-7.75] days, respectively. Among survivors, all three were associated with increased MV duration (> 7 days) and PICU stay (> 10 days) at univariate analysis. Multivariate analysis showed that PEEP-PaedVAE was the only definition independently associated with MV above 7 days [OR = 4.86, 95% CI (2.41-10.11)] and PICU stay [OR = 3.49, 95% CI (1.68-7.80)] above ten days, respectively. CONCLUSIONS: A VAE definition based on slight PEEP increases should be preferred for VAE surveillance in children.

Diaphragm Ultrasonography to Predict Noninvasive Respiratory Treatment Failure in Infants With Severe Bronchiolitis.

BACKGROUND: Noninvasive respiratory support is commonly used in treatment of bronchiolitis. Determinants of failure are needed to prevent delayed intubation. METHODS: We conducted a prospective observational pilot study in infants admitted to a pediatric ICU. Diaphragmatic excursion (dExc), diaphragmatic inspiratory/expiratory time, and diaphragmatic thickening fraction (dTF) were recorded at admission, 24 h, and 48 h in both hemidiaphragms. RESULTS: Twenty-six subjects were included (14 on HFNC and 12 on NIV) with a total of 56 ultrasonographic evaluations. Three subjects required invasive ventilation. Sixty-four percent of the subjects on HFNC required NIV as rescue therapy and 2/14 invasive ventilation (14.2%). In the HFNC group there were no differences in dExc between those who required escalation to NIV or invasive ventilation and those who didn't. Left dTF was higher in subjects on HFNC requiring invasive ventilation versus those needing NIV (left dTF 47% vs 22% [13-30]; P = .046, r = 0.7). Diaphragmatic I:E ratios were higher in infants on HFNC requiring invasive ventilation and diaphragmatic expiratory time was shorter (left P = .038; right P = .02). In the NIV group there were no differences in dExc, I:E ratios, or dTF between subjects needing escalation to invasive ventilation and those who didn't. We found no correlation between a clinical work of breathing score and echographic dTF. CONCLUSIONS: In infants with moderate or severe bronchiolitis receiving HFNC, the use of ultrasonographic left dTF could help predict respiratory treatment failure and need for invasive ventilation. The use of ultrasonographic dExc is of little help to predict both.

Mosaic Variegated Aneuploidy syndrome 2 caused by biallelic variants in CEP57, two new cases and review of the phenotype.

Mosaic Variegated Aneuploidy Syndrome 2 (MVA2; MIM 614114) is a rare autosomal recessive disorder, characterized by mosaic aneuploidies involving multiple chromosomes and tissues, caused by biallelic pathogenic variants in the CEP57 gene. Only 10 patients have been reported to date. We report two additional non related cases born to Moroccan consanguineous parents, carrying the previously described c.915_925dup11 CEP57 homozygous variant. Common features of these 12 cases include growth retardation, typically of prenatal onset, distinctive facial features, endocrine, cardiovascular and skeletal, abnormalities while malignancies have not been reported. This report describes the phenotypical spectrum of MVA2.

Utility of FilmArrayⓇ ME panel for prompt Neisseria meningitidis detection in non-cerebrospinal fluid samples- A case report.

The FilmArrayⓇ Meningitis/Encephalitis Panel detects the 14 most frequent pathogens causing meningitis and/or encephalitis. The use of FilmArray ME with non-validated samples is seldom published in the literature. We describe the case of a 3-year-old child, diagnosed with acute meningoencephalitis, in whom the FilmArrayⓇ ME technique successfully identified Neisseria meningitidis in both skin biopsy and whole blood samples.

Asynchrony, neural drive, ventilatory variability and COMFORT: NAVA versus pressure support in pediatric patients. A non-randomized cross-over trial.

PURPOSE: To determine if neurally adjusted ventilatory assist (NAVA) improves asynchrony, ventilatory drive, breath-to-breath variability and COMFORT score when compared to pressure support (PS). METHODS: This is a non-randomized short-term cross-over trial in which 12 pediatric patients with asynchrony (auto-triggering, double triggering or non-triggered breaths) were enrolled. Four sequential 10-min periods of data were recorded after 20 min of ventilatory stabilization (wash-out) at each of the following settings: baseline PS with the ventilator settings determined by the attending physician (1-PS(b)); PS after optimization (2-PS(opt)); NAVA level set so that maximum inspiratory pressure (P(max)) equaled P(max) in PS (3-NAVA); same settings as in 2-PS(opt) (4-PS(opt)). RESULTS: The median asynchrony index was significantly lower during NAVA (2.0%) than during 2-PS(opt) (8.5%, p = 0.017) and 4-PS(opt) (7.5%, p = 0.008). In NAVA mode, the NAVA trigger accounted on average for 66% of triggered breaths. The median trigger delay with respect to neural inspiratory time was significantly lower during NAVA (8.6%) than during 2-PS(opt) (25.2%, p = 0.003) and 4-PS(opt) (28.2%, p = 0.0005). The median electrical activity of the diaphragm (EAdi) change during trigger delay normalized to maximum inspiratory EAdi difference was significantly lower during NAVA (5.3%) than during 2-PS(opt) (21.7%, p = 0.0005) and 4-PS(opt) (24.6%, p = 0.001). The coefficient of variation of tidal volume was significantly higher during NAVA (44.2%) than during 2-PS(opt) (19.8%, p = 0.0002) and 4-PS(opt) (23.0%, p = 0.0005). The median COMFORT score during NAVA (15.0) was lower than that during 2-PS(opt) (18.0, p = 0.0125) and 4-PS(opt) (17.5, p = 0.039). No significant changes for any variable were observed between 1-PS(b) and 2-PS(opt). CONCLUSIONS: Neurally adjusted ventilatory assist as compared to optimized PS results in improved synchrony, reduced ventilatory drive, increased breath-to-breath mechanical variability and improved patient comfort.