Reevaluating the FDA's warning against the use of probiotics in preterm neonates: A societal statement by ESPGHAN and EFCNI.

The recent advisory issued by the United States Food and Drug Administration, cautioning against the routine administration of probiotics in preterm neonates, has sparked a lively debate within the scientific community. This commentary presents a perspective from members of the Special Interest Group on Gut Microbiota and Modifications within the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and other authors who contributed to the ESPGHAN position paper on probiotics for preterm infants, as well as representatives from the European Foundation for the Care of Newborn Infants. We advocate for a more nuanced and supportive approach to the use of certain probiotics in this vulnerable population, balancing the demonstrated benefits and risks.

International Nosocomial Infection Control Consortium (INICC) report of health care associated infections, data summary of 45 countries for 2015 to 2020, adult and pediatric units, device-associated module.

BACKGROUND: Reporting on the International Nosocomial Infection Control Consortium study results from 2015 to 2020, conducted in 630 intensive care units across 123 cities in 45 countries spanning Africa, Asia, Eastern Europe, Latin America, and the Middle East. METHODS: Prospective intensive care unit patient data collected via International Nosocomial Infection Control Consortium Surveillance Online System. Centers for Disease Control and Prevention/National Health Care Safety Network definitions applied for device-associated health care-associated infections (DA-HAI). RESULTS: We gathered data from 204,770 patients, 1,480,620 patient days, 936,976 central line (CL)-days, 637,850 mechanical ventilators (MV)-days, and 1,005,589 urinary catheter (UC)-days. Our results showed 4,270 CL-associated bloodstream infections, 7,635 ventilator-associated pneumonia, and 3,005 UC-associated urinary tract infections. The combined rates of DA-HAIs were 7.28%, and 10.07 DA-HAIs per 1,000 patient days. CL-associated bloodstream infections occurred at 4.55 per 1,000 CL-days, ventilator-associated pneumonias at 11.96 per 1,000 MV-days, and UC-associated urinary tract infections at 2.91 per 1,000 UC days. In terms of resistance, Pseudomonas aeruginosa showed 50.73% resistance to imipenem, 44.99% to ceftazidime, 37.95% to ciprofloxacin, and 34.05% to amikacin. Meanwhile, Klebsiella spp had resistance rates of 48.29% to imipenem, 72.03% to ceftazidime, 61.78% to ciprofloxacin, and 40.32% to amikacin. Coagulase-negative Staphylococci and Staphylococcus aureus displayed oxacillin resistance in 81.33% and 53.83% of cases, respectively. CONCLUSIONS: The high rates of DA-HAI and bacterial resistance emphasize the ongoing need for continued efforts to control them.

Decreasing central line-associated bloodstream infections rates in intensive care units in 30 low- and middle-income countries: An INICC approach.

BACKGROUND: Central line (CL)-associated bloodstream infections (CLABSIs) occurring in the intensive care unit (ICU) are common and associated with a high burden. METHODS: We implemented a multidimensional approach, incorporating an 11-element bundle, education, surveillance of CLABSI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CLABSI rates and clinical outcomes, and performance feedback in 316 ICUs across 30 low- and middle-income countries. Our dependent variables were CLABSI per 1,000-CL-days and in-ICU all-cause mortality rates. These variables were measured at baseline and during the intervention, specifically during the second month, third month, 4 to 16 months, and 17 to 29 months. Comparisons were conducted using a two-sample t test. To explore the exposure-outcome relationship, we used a generalized linear mixed model with a Poisson distribution to model the number of CLABSIs. RESULTS: During 1,837,750 patient-days, 283,087 patients, used 1,218,882 CL-days. CLABSI per 1,000 CL-days rates decreased from 15.34 at the baseline period to 7.97 in the 2nd month (relative risk (RR) = 0.52; 95% confidence interval [CI] = 0.48-0.56; P < .001), 5.34 in the 3rd month (RR = 0.35; 95% CI = 0.32-0.38; P < .001), and 2.23 in the 17 to 29 months (RR = 0.15; 95% CI = 0.13-0.17; P < .001). In-ICU all-cause mortality rate decreased from 16.17% at baseline to 13.68% (RR = 0.84; P = .0013) at 17 to 29 months. CONCLUSIONS: The implemented approach was effective, and a similar intervention could be applied in other ICUs of low- and middle-income countries to reduce CLABSI and in-ICU all-cause mortality rates.

A Fatal Case of Opioid Intoxication After Raw Poppy Plant Ingestion.

Papaver somniferum contains many opioids and is frequently used in agriculture. Both the intoxication and the withdrawal of opioids have a wide range of symptoms such as coma, depressed respiration and agitation. Here, a fatal case of opioid intoxication will be presented. A four-year-old female patient was admitted to the pediatric intensive care unit after ingesting raw poppy plants. She had shallow respiration, tachycardia, hypertension and muscle cramps. A high plasma opioid level was measured and bolus intravenous naloxone was administered which resulted in a brief gain of consciousness. She was intubated after a sudden respiratory depression and loss of consciousness 10 hours later. Naloxone infusion was started and continued for two days. She developed disseminated intravascular coagulation and was lost on day twelve. Raw plant ingestion proves difficult to treat since there is less information about the ingredients. Having no consensus on naloxone dosage and intrinsic complications such as hypo- and hypertension, redistribution, rhabdomyolysis and dysmotility disrupts naloxone administration. Ingestion of opioids as plants brings out different complications for the treatment course while deciding on naloxone dosage proves opioid intoxication difficult to treat.

Daily Practice of Mechanical Ventilation and Weaning in Turkish PICUs: A Multicenter Prospective Survey.

OBJECTIVES: To investigate conventional mechanical ventilation weaning characteristics of patients requiring conventional mechanical ventilation support for greater than 48 hours within the PICU. DESIGN: The prospective observational multicenter cohort study was conducted at 15 hospitals. Data were being collected from November 2013 to June 2014, with two designated researchers from each center responsible for follow-up and data entry. SETTING: Fifteen tertiary PICUs in Turkey. PATIENTS: Patients between 1 month and 18 years old requiring conventional mechanical ventilation for greater than 48 hours were included. A single-center was not permitted to surpass 20% of the total sample size. Patients with no plans for conventional mechanical ventilation weaning were excluded. INTERVENTIONS: Conventional mechanical ventilation MEASUREMENTS AND MAIN RESULTS:: Pertinent variables included PICU and patient demographics, including clinical data, chronic diseases, comorbid conditions, and reasons for intubation. Conventional mechanical ventilation mode and weaning data were characterized by daily ventilator parameters and blood gases. Patients were monitored until hospital discharge. Of the 410 recruited patients, 320 were included for analyses. A diagnosis of sepsis requiring intubation and high initial peak inspiratory pressures correlated with a longer weaning period (mean, 3.65 vs 1.05-2.17 d; p < 0.001). Conversely, age, admission Pediatric Risk of Mortality III scores, days of conventional mechanical ventilation before weaning, ventilator mode, and chronic disease were not related to weaning duration. CONCLUSIONS: Pediatric patients requiring conventional mechanical ventilation with a diagnosis of sepsis and high initial peak inspiratory pressures may require longer conventional mechanical ventilation weaning prior to extubation. Causative factors and optimal weaning for this cohort needs further consideration.

Quadrivalent Influenza Vaccine Prevents Illness and Reduces Healthcare Utilization Across Diverse Geographic Regions During Five Influenza Seasons: A Randomized Clinical Trial.

BACKGROUND: We evaluated an inactivated quadrivalent influenza vaccine (IIV4) in children 6-35 months of age in a phase III, observer-blind trial. METHODS: The aim of this analysis was to estimate vaccine efficacy (VE) in preventing laboratory-confirmed influenza in each of 5 independent seasonal cohorts (2011-2014), as well as vaccine impact on healthcare utilization in 3 study regions (Europe/Mediterranean, Asia-Pacific and Central America). Healthy children were randomized 1:1 to IIV4 or control vaccines. VE was estimated against influenza confirmed by reverse transcription polymerase chain reaction on nasal swabs. Cultured isolates were characterized as antigenically matched/mismatched to vaccine strains. RESULTS: The total vaccinated cohort included 12,018 children (N = 1777, 2526, 1564, 1501 and 4650 in cohorts 1-5, respectively). For reverse transcription polymerase chain reaction confirmed influenza of any severity (all strains combined), VE in cohorts 1-5 was 57.8%, 52.9%, 73.4%, 30.3% and 41.4%, respectively, with the lower limit of the 95% confidence interval >0 for all estimates. The proportion of vaccine match for all strains combined in each cohort was 0.9%, 79.3%, 72.5%, 24.1% and 28.6%, respectively. Antibiotic use associated with influenza illness was reduced with IIV4 by 71% in Europe, 36% in Asia Pacific and 59% in Central America. CONCLUSIONS: IIV4 prevented influenza in children 6-35 months of age in each of 5 separate influenza seasons in diverse geographical regions. A possible interaction between VE, degree of vaccine match and socioeconomic status was observed. The IIV4 attenuated the severity of breakthrough influenza illness and reduced healthcare utilization, particularly antibiotic use.

Hemophagocytic Lymphohystiocytosis Associated With Type Ia Glycogen Storage Disease.

BACKGROUND: Hemophagocytic lymphohystiocytosis (HLH) is characterized by fever, splenomegaly, pancytopenia, and elevated levels of triglycerides and ferritin. These signs and symptoms are common to other metabolic diseases. OBSERVATION: A 5-month-old female infant, who presented with fever, respiratory distress, massive hepatomegaly, and bicytopenia, was diagnosed as having HLH and chemotherapy was initiated. The patient was negative for familial HLH gene mutations. Respiratory distress and laboratory findings improved rapidly after starting chemotherapy. However, there was no improvement in the massive hepatomegaly and she experienced hypoglycemic episodes. In addition, her family history included a cousin with glycogen storage disease (GSD). On the basis of the findings, the patient was diagnosed as having type Ia GSD. There are no previous reports of HLH secondary to GSD type Ia in the literature. CONCLUSIONS: Congenital metabolic diseases should be considered in the differential diagnosis of children with HLH.

Time Series Analysis of the Microbiota of Children Suffering From Acute Infectious Diarrhea and Their Recovery After Treatment.

Gut microbiota is closely related to acute infectious diarrhea, one of the leading causes of mortality and morbidity in children worldwide. Understanding the dynamics of the recovery from this disease is of clinical interest. This work aims to correlate the dynamics of gut microbiota with the evolution of children who were suffering from acute infectious diarrhea caused by a rotavirus, and their recovery after the administration of a probiotic, Saccharomyces boulardii CNCM I-745. The experiment involved 10 children with acute infectious diarrhea caused by a rotavirus, and six healthy children, all aged between 3 and 4 years. The children who suffered the rotavirus infection received S. boulardii CNCM I-745 twice daily for the first 5 days of the experiment. Fecal samples were collected from each participant at 0, 3, 5, 10, and 30 days after probiotic administration. Microbial composition was characterized by 16S rRNA gene sequencing. Alpha and beta diversity were calculated, along with dynamical analysis based on Taylor's law to assess the temporal stability of the microbiota. All children infected with the rotavirus stopped having diarrhea at day 3 after the intervention. We observed low alpha diversities in the first 5 days (p-value < 0.05, Wilcoxon test), larger at 10 and 30 days after probiotic treatment. Canonical correspondence analysis (CCA) showed differences in the gut microbiota of healthy children and of those who suffered from acute diarrhea in the first days (p-value < 0.05, ADONIS test), but not in the last days of the experiment. Temporal variability was larger in children infected with the rotavirus than in healthy ones. In particular, Gammaproteobacteria class was found to be abundant in children with acute diarrhea. We identified the microbiota transition from a diseased state to a healthy one with time, whose characterization may lead to relevant clinical data. This work highlights the importance of using time series for the study of dysbiosis related to diarrhea.

Early initiated feeding versus early reached target enteral nutrition in critically ill children: An observational study in paediatric intensive care units in Turkey.

AIM: Although early enteral nutrition (EN) is strongly associated with lower mortality in critically ill children, there is no consensus on the definition of early EN. The aim of this study was to evaluate our current practice supplying EN and to identify factors that affect both the initiation of feeding within 24 h after paediatric intensive care unit (PICU) admission and the adequate supply of EN in the first 48 h after PICU admission in critically ill children. METHODS: We conducted a prospective, multicentre, observational study in nine PICUs in Turkey. Any kind of tube feeding commenced within 24 h of PICU admission was considered early initiated feeding (EIF). Patients who received more than 25% of the estimated energy requirement via enteral feeding within 48 h of PICU admission were considered to have early reached target EN (ERTEN). RESULTS: Feeding was initiated in 47.4% of patients within 24 h after PICU admission. In many patients, initiation of feeding seems to have been delayed without an evidence-based reason. ERTEN was achieved in 43 (45.3%) of 95 patients. Patients with EIF were significantly more likely to reach ERTEN. ERTEN was an independent significant predictor of mortality (P < 0.001), along with reached target enteral caloric intake on day 2 associated with decreased mortality. CONCLUSIONS: There is a substantial variability among clinicians' perceptions regarding indications for delay to initiate enteral feeding in critically ill children, especially after the first 6 h of PICU admission. ERTEN, but not EIF, is associated with a significantly lower mortality rate in critically ill children.

Vaccine for prevention of mild and moderate-to-severe influenza in children.

BACKGROUND: Commonly used trivalent vaccines contain one influenza B virus lineage and may be ineffective against viruses of the other B lineage. We evaluated the efficacy of a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages. METHODS: In this multinational, phase 3, observer-blinded study, we randomly assigned children 3 to 8 years of age, in a 1:1 ratio, to receive the QIV or a hepatitis A vaccine (control). The primary end point was influenza A or B confirmed by real-time polymerase chain reaction (rt-PCR). Secondary end points were rt-PCR-confirmed, moderate-to-severe influenza and rt-PCR-positive, culture-confirmed influenza. The vaccine efficacy and the effect of vaccination on daily activities and utilization of health care resources were assessed in the total vaccinated cohort (2584 children in each group) and the per-protocol cohort (2379 children in the QIV group and 2398 in the control group). RESULTS: In the total vaccinated cohort, 62 children in the QIV group (2.40%) and 148 in the control group (5.73%) had rt-PCR-confirmed influenza, representing a QIV efficacy of 59.3% (95% confidence interval [CI], 45.2 to 69.7), with efficacy against culture-confirmed influenza of 59.1% (97.5% CI, 41.2 to 71.5). For moderate-to-severe rt-PCR-confirmed influenza, the attack rate was 0.62% (16 cases) in the QIV group and 2.36% (61 cases) in the control group, representing a QIV efficacy of 74.2% (97.5% CI, 51.5 to 86.2). In the per-protocol cohort, the QIV efficacy was 55.4% (95% CI, 39.1 to 67.3), and the efficacy against culture-confirmed influenza 55.9% (97.5% CI, 35.4 to 69.9); the efficacy among children with moderate-to-severe influenza was 73.1% (97.5% CI, 47.1 to 86.3). The QIV was associated with reduced risks of a body temperature above 39°C and lower respiratory tract illness, as compared with the control vaccine, in the per-protocol cohort (relative risk, 0.29 [95% CI, 0.16 to 0.56] and 0.20 [95% CI, 0.04 to 0.92], respectively). The QIV was immunogenic against all four strains. Serious adverse events occurred in 36 children in the QIV group (1.4%) and in 24 children in the control group (0.9%). CONCLUSIONS: The QIV was efficacious in preventing influenza in children. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT01218308.).

Pharmacoeconomic evaluation of voriconazole vs. liposomal amphotericin B in empiric treatment of invasive fungal infections in Turkey.

BACKGROUND: Invasive fungal infections (IFI) are associated with considerable expense and mortality on healthcare systems. There is a need to provide evidence of both clinical efficacy and value for money with any health technology. The current pharmacoeconomic evaluation investigated the use of liposomal amphotericin B (LAmB) and voriconazole for the empiric treatment of IFI in the Turkish setting. METHODS: Decision analytic modelling was used to create a pathway for patient treatment with a 5-point composite outcome measure. The data was obtained from a major non-inferiority multicentre randomised controlled study, with an expert panel of clinicians in Turkey providing transition probabilities and cost not available in the literature. Sensitivity analyses were performed on the inputs from the clinical trial and the expert panel. RESULTS: As per the base case analysis, voriconazole was preferred by Turkish Lira (TL) 2,523 per patient treated and TL2,520 per surviving patient. LAmB was the preferred alternative by TL5,362 per successfully treated patient. Removing fever resolution as part of the composite outcome measure resulted in voriconazole being the preferred alternative per successfully treated patient. Univariate sensitivity analysis highlighted that increasing the duration of voriconazole by >1.2 days or decreasing LAmB by >1.0 days changes the result. Monte Carlo Simulation resulted in 69.4% of simulations favouring voriconazole per patient treated. CONCLUSION: There is a strong likelihood that voriconazole is economically more favourable than LAmB in the empiric treatment of IFI in Turkey.

Clinical efficacy comparison of Saccharomyces boulardii and yogurt fluid in acute non-bloody diarrhea in children: a randomized, controlled, open label study.

The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 +/- 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, although these differences were not significant. However, diarrhea had resolved in significantly more children on day 3 in the S. boulardii group (48.5% versus 25.5%; P < 0.05). In outpatient cases, yogurt treatment was cheaper than S. boulardii whereas in hospitalized patients, treatment cost was similar. In conclusion, the effect of daily freshly prepared YF was comparable to S. boulardii in the treatment of acute non-bloody diarrhea in children. The duration of diarrhea was shorter in the S. boulardii group, expressed as a significantly higher number of patients with normal stools on day 3.

Clinical efficacy of Saccharomyces boulardii and metronidazole compared to metronidazole alone in children with acute bloody diarrhea caused by amebiasis: a prospective, randomized, open label study.

The aim was to evaluate the efficacy of Saccharomyces boulardii (Sb) in addition to metronidazole in amebiasis. A prospective, randomized, open clinical trial was performed in 50 children presenting with acute bloody diarrhea caused by Entameba histolytica. Group A and B (each N = 25) was treated with metronidazole, but Sb (250 mg, twice daily) during the 7 days was added to Group B patients who were re-evaluated 2, 3, 5, 10, and 30 days after diagnosis. Duration of bloody diarrhea was significantly longer in Group A (72.0 +/- 28.5 versus 42.2 +/- 17.4 hours, P < 0.001). On day 5, amebic cysts had disappeared in all children in Group B, whereas in Group A, amebic cysts were still present in 6 children (P < 0.05). On day 10, all children were cured and cysts had disappeared in all. The addition of Sb to metronidazole in amebiasis significantly decreases duration of (bloody) diarrhea and enhances clearance of cysts.