Pharmacokinetics-pharmacodynamics of tazobactam in combination with cefepime in an in vitro infection model

We previously demonstrated that for tazobactam administered in combination with ceftolozane, the pharmacokinetic-pharmacodynamic (PK-PD) index that best described tazobactam efficacy was the percentage of the dosing interval that tazobactam concentrations were above a threshold (%T>threshold). Using data from studies of Enterobacteriaceae-producing ESBL, a relationship between tazobactam %T>threshold and reduction in log10 CFU from baseline, for which tazobactam threshold concentration was the product of the isolate's ceftolozane-tazobactam MIC value and 0.5, was identified. However, since the kinetics of cephalosporin hydrolysis vary among ESBLs and compounds, it is likely that the translational relationship to derive the tazobactam threshold concentration varies among enzymes and compounds. Using a one-compartment in vitro infection model, the PK-PD of tazobactam administered in combination with cefepime was characterized and a translational relationship across ESBL-producing Enterobacteriaceae was developed. Four clinical isolates, two Escherichia coli and two Klebsiella pneumoniae, known to produce CTX-M-15 β-lactamase enzymes and displaying cefepime MIC values of 2 to 4 mg/L in the presence of 4 mg/L tazobactam, were evaluated. Tazobactam threshold concentrations from 0.0625-1 times the tazobactam-potentiated cefepime MIC value were considered. The threshold that best described the relationship between tazobactam %T>threshold and change in log10 CFU from baseline was the product of 0.125 and the cefepime-tazobactam MIC (R2=0.813). The magnitude of %T>threshold associated with net bacterial stasis and a 1-log10 CFU/mL reduction from baseline at 24 hours was 21.9 and 52.8%, respectively. These data will be useful to support the identification of tazobactam dosing regimens in combination with cefepime for evaluation in future clinical studies

Correlation between gastroesophageal reflux and respiratory sounds in children.

irty-eight children (aged>24 months) with symptoms of gastroesophageal re ux and/or wheezing and cough were enrolled in this study. Patients underwent pH-impedance monitoring and recording of lung sounds (WHolter\uae). Results: e median number of cough events associated with weakly acid re ux in the group of patients with positive impedance monitoring was signi cantly higher than the median of cough associated with weakly acid and non-acid re ux in the group of patients with negative impedance monitoring (p = 0.003). e median number of events of wheezing 655% associated with an episode of acid re ux was signi cantly higher (p = 0.008) in the group of patients with positive 24-hr pH monitoring than those with negative 24-hr pH monitoring. Conclusion: In conclusion, we found a relationship between gastroesophageal re ux and respiratory symptoms: wheezing was associated mainly with acid re ux, whereas coughing was associated with weakly acid re ux

25-hydroxyvitamin D serum level in children of different ethnicity living in Italy

Several factors including ethnicity are known to influence 25(OH)D levels. The purpose of our study was to assess 25(OH)D levels among 1374 pediatric subjects of different ethnicity and to determine the prevalence of vitamin D deficiency and insufficiency among different ethnic groups. The prevalence of 25(OH)D a parts per thousand currency sign20 ng/ml was 44.2, 65.2, 69.2, 54.0, and 44.8 % among Caucasians, Africans, North Africans, Indians, and others, respectively (P < 0.001). The median of 25(OH)D was 21.0 ng/ml (IQR = 14.0-29.6 ng/ml) for the cohort. Season of blood sampling, age, ethnicity, gestational age, birth weight, and z-score BMI were associated with 25(OH)D levels. Caucasians had higher median 25(OH)D levels than sub-Saharan Africans (P < 0.001), North Africans (P < 0.001), and Indians (P < 0.001). There were no significant differences in the median 25(OH)D levels between ethnic groups among infants, whereas for children older than 1 year we found significant differences in 25(OH)D levels in the different ethnic groups, compared to Caucasians.Conclusion: Ethnicity was correlated with 25(OH)D levels among children older than 1 year. We found a high prevalence of vitamin D deficiency and insufficiency after the first year of life, and this was more remarkable in non-Caucasian children

Chronic urticaria and celiac disease: a case report.

We describe a case of a 9-year-old girl who presented chronic urticaria associated with celiac disease. The prevalence of the manifestation of chronic urticaria in celiac disease is unknown but increase in atopic immunologic disorders has been reported in the setting of gluten enteropathy. Relationship between the clinical manifestations is not clear. The present case of subclinical celiac disease diagnosis in an otherwise asymptomatic child with chronic urticaria further reinforces the evidence that differential for celiac disease warrants to be always considered in children with refractory urticaria

SLEEP-DISORDERED BREATHING IN CHILDREN WITH RECURRENT WHEEZING/ASTHMA: A SINGLE CENTRE STUDY

The main findings of the present study were that children with recurrent wheezing/asthma showed an increased Central Apnea Index than unaffected children. Recurrent wheezing/asthma can affect Central Apnea Index in these children. The selection of a sample of affected and unaffected children, balanced for age and Sleep Disordered Breathing severity, may confirm this observation. This data may suggest a dysfunction of the breathing control in the central nervous system during sleep. Systemic or central inflammation may take a role

Serum and exhaled breath condensate leptin levels in asthmatic and obesity children: a pilot study.

BACKGROUND: Recent studies have highlighted the possible involvement of leptin in inflammation. The leptin receptor is also expressed by alveolar macrophages, T lymphocytes and bronchial epitelial cells, suggesting a possible role in the cascade of airway inflammation. OBJECTIVES: The aim of the study was to evaluate the levels of leptin in exhaled breath condensate (EBC) from asthmatic, normal- and overweight children, in relationship with airway inflammation. METHODS: 15 asthmatic non-obese children, 15 healthy non-asthmatic non-obese children, 11 obese children with asthma (OA) and 20 obese children without asthma (ONA) were enrolled. Body impedance of body weight, EBC collection, FeNO, spirometry and a blood sampling for serum leptin were assessed. RESULTS: Leptin EBC levels were significantly higher (3.9 ng ml(-1) ± 1.3) in overweight children than those obese with asthma (3.6 ng ml(-1) ± 1.6; p = 0.97), non-owerweight asthmatics (2.2 ng ml(-1) ± 1.2; p < 0.0001) and in healthy children (0.9 ng ml(-1) ± 0.6; p < 0.001). Leptin EBC levels in asthmatic children were significantly higher than in healthy children (p = 0.05). Leptin serum levels were significantly higher in the overweight children compared with the asthmatics (12.7 ng ml(-1) ± 13.2; p < 0.001) and the healthy group (11.1 ng ml(-1) ± 11.2; p < 0.001). We observed a significant correlation between EBC-leptin levels and the serum-leptin levels (p = 0.001). No correlations were found between EBC-leptin levels, FeNO and lung function. CONCLUSIONS: This study shows that leptin is measurable in EBC in children and that EBC-leptin levels are significantly higher in the obese subjects and in asthmatic ones compared with healthy subjects. Leptin may therefore represent a non-invasive marker of non-specific airway inflammation in children

Different Levels of Exhaled Nasal Nitric Oxide in Patients Diagnosed with Primary Dyskinesia

Background:Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormally beating cilia. In&nbsp; these patients levels of nasal nitric oxide (nNO) are lower than those observed in healthy subjects.&nbsp; Objectives:We recorded the nNO levels in PCD patients in order to use those nNO measurements in the screening and identification of patients with symptoms suggestive of disease PCD disease.Methods:We measured nasal NO in 36 PCD patients (3 uncooperative younger children and 33 cooperative adult patients) and did a nNO re-evaluation after 12 months in patients with higher levels of nNO.Results:Twenty-seven PCD patients showed very low nNO levels (29.1 ppb) and nine cooperative patients had high nNO levels (583.3 ppb, p&lt;0.001) (T0); the PCD patients with high nNO levels were re-evaluated after 12 months (T1). The median T0 and T1 nNO values of the seven PCD patients were 360 ppb and 324&nbsp; ppb(p=0.0180), respectively; in 6 patients with high levels of nNO the diagnosis of PCD was confirmed byelectron microscopy, and in one subject the diagnosis was confirmed for secondary ciliary dyskinesia.Conclusions:Low levels of&nbsp; nNO remain&nbsp; indicative of&nbsp; PCD&nbsp; disease; high levels of nNO are supportive of PCD, but cannot be used to exclude diagnosis.These results suggest that repeated measures are warranted when nNO is occasionally high inpatients with symptoms suggestive of PCD disease, and at present electron microscopy is still the only valid evaluation tool in unclear cases of PCD.</p