Antibiotic Resistance in Pediatric Infections: Global Emerging Threats, Predicting the Near Future.

Antibiotic resistance is a public health threat of the utmost importance, especially when it comes to children: according to WHO data, infections caused by multidrug resistant bacteria produce 700,000 deaths across all ages, of which around 200,000 are newborns. This surging issue has multipronged roots that are specific to the pediatric age. For instance, the problematic overuse and misuse of antibiotics (for wrong diagnoses and indications, or at wrong dosage) is also fueled by the lack of pediatric-specific data and trials. The ever-evolving nature of this age group also poses another issue: the partly age-dependent changes of a developing system of cytochromes determine a rather diverse population in terms of biochemical characteristics and pharmacokinetics profiles, hard to easily codify in an age- or weight-dependent dosage. The pediatric population is also penalized by the contraindications of tetracyclines and fluoroquinolones, and by congenital malformations which often require repeated hospitalizations and pharmacological and surgical treatments from a very young age. Emerging threats for the pediatric age are MRSA, VRSA, ESBL-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae and the alarming colistin resistance. Urgent actions need to be taken in order to step back from a now likely post-antibiotic era, where simple infections might cause infant death once again.

Long-term evaluation of glucose homeostasis in a cohort of HAART-treated HIV-infected children: a longitudinal, observational cohort study.

BACKGROUND AND OBJECTIVES: Few and mainly cross-sectional studies of glucose homeostasis are available in HIV-infected children treated with highly active antiretroviral therapy (HAART). The aim of the present study was to describe a 4-year course of glucose homeostasis in a cohort of HAART-treated children and adolescents, using glucose and insulin levels during an oral glucose tolerance test (OGTT) as outcome measures. In addition, we investigated possible risk factors, both related and unrelated to antiretroviral therapy, associated with insulin resistance. METHODS: We assessed glucose metabolism yearly for 4 consecutive years in 37 HIV-infected children receiving a protease inhibitor (PI)-based HAART regimen containing lamivudine/stavudine plus indinavir or ritonavir or nelfinavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen containing lamivudine/tenofovir/efavirenz. Generalized estimating equations were used to evaluate the relationship between the loge-transformed area under the serum concentration-time curve (AUC) of insulin during OGTT and antiretroviral therapy, controlling for time, sex, baseline age, puberty, body mass index and CD4+ T cells percentage. RESULTS: Ritonavir-unboosted PI-based HAART regimens were administered to most children at baseline; however, their use decreased during follow-up in favour of an NNRTI-based regimen. The nelfinavir/lamivudine/stavudine (regression coefficient=-0.69, p<0.05) and efavirenz/lamivudine/tenofovir (regression coefficient=-0.93, p<0.05) regimens, but not the ritonavir/lamivudine/stavudine regimen, were negatively associated with loge-transformed insulin AUC compared with indinavir/lamivudine/stavudine. Puberty was positively associated with loge-transformed insulin AUC. CONCLUSIONS: This 4-year prospective study of HAART-treated HIV-infected children shows that: (i) the nelfinavir/lamivudine/stavudine and the efavirenz/lamivudine/tenofovir regimens but not the ritonavir/lamivudine/stavudine regimen were associated with higher insulin sensivity, i.e. lower insulin AUC, compared with indinavir/lamivudine/stavudine; (ii) the treatment switched substantially in favour of NNRTI from the third year on and this change was associated with an improvement in insulin sensitivity compared with the previous HAART-based regimens; and (iii) puberty is a primary determinant of insulin sensitivity.

[Potential of three-dimensional brain ultrasonography in newborn: description of 3 case reports]. / Ruolo dell'ecografia cerebrale tridimensionale nel neonato: descrizione di 3 casi clinici.

Three neonates with enlargement of the lateral ventricle were evaluated with sonography. Two out of 3 patients had hydrocephalus and 1 an ischemic stroke. 3D US improved accuracy in diagnosing and following up hydrocephalus, while the diagnosis of arterial ischemic stroke was immediate. 3D US has the potential to become a valuable additional imaging tool for the evaluation of the paediatric neonatal brain, enabling an earlier diagnosis.

[Usefulness of the 5-6-yrs-old anthropometric health report for the evaluation of childhood overweight and obesity: pilot study in Lombardia (Italy)]. / Utilità della scheda bilancio di salute per la rilevazione di sovrappeso e obesità nei bambini tra 5 e 6 anni: esperienza pilota in Lombardia.

OBJECTIVE: To verify the possibility to use the Anthropometric Health Report (AHR), containing the BMI value, for overweight/obesity evaluation in 5-6-years-old children. DESIGN: Between January 2001 and December 2004, 4619 AHR had been examined. BMI values were compared with age and sex-specific BMI cutoffs, according to Cole, as well as with a single BMI value, calculated as the mean between boys and girls cutoff at 5.5 yrs of age. SETTING: 4619 children of ASL Provincia di Milano 2, aged 5-6 years were examined. PARTECIPANTS: 81 Family Pediatricians working in the area of Provincia di Milano 2. MAIN OUTCOME MEASURES: An easily available and low cost method for epidemiological studies on overweight and obesity in childhood. RESULTS: During the study period the number of examined children increased constantly (from 8% to 30% of the overall resident population). Also the correct compilation of the AHR raised (from 47% to 95%). The elevated percentage of overweight children (range 17-23%) and obese children (range 5-7%) in the study group confirms other published data in this age group. The use of a single BMI cutoff did not affect significantly (p > 0.05) the results with regard to the use ofage and sex-specific cut offs. Required time for carrying out the study was limited. Efficiency increased during the study: the number ofAHRs analyzed per hour increased from 37.5 in 2001 to 103.5 in 2004. Some critical points about current uses of AHR are discussed CONCLUSIONS: AHR could be used for epidemiological purposes. It could be considered an useful method in monitoring overweight/obesity in 5-6 years old children as well as in checking the efficacy of prevention and therapeutic strategies.

Infective Endocarditis in Children in Italy from 2000 to 2015.

OBJECTIVE: The Italian Society for Pediatric Infectious Diseases created a registry on children with infective endocarditis (IE) hospitalized in Italy. METHODS: A cross-sectional survey was conducted on patients hospitalized due to IE in Italian paediatric wards between January 1, 2000, and June 30, 2015. RESULTS: Over the 15-year study period, 47 IE episodes were observed (19 males; age range, 2-17 years). Viridans Streptococci were the most common pathogens among patients with predisposing cardiac conditions and Staphylococcus aureus among those without (37.9% vs. 5.5%, p = 0.018, and 6.9% vs. 27.8%, p = 0.089, respectively). Six of the 7 (85.7%) S. aureus strains were methicillin-resistant. The majority of patients with and without predisposing cardiac conditions recovered without any complications. CONCLUSION: In Italy, paediatric IE develops without any previous predisposing factors in a number of children, methicillin-resistant S. aureus has emerged as a common causative agent and the therapeutic approach is extremely variable.

[Intramedullary neuroenteric cyst simulating Sandifer's syndrome]. / Cisti neuroenteriche intramidollari che simulano la sindrome di Sandifer.

We report the case of a child with frequent episodes of arms and neck hypertonia and regurgitation. These characteristics, associated with an esophagitis, suggested the diagnosis of gastroesophageal reflux disease (Sandifer syndrome?). Because after an appropriate therapy the symptoms didn't disappear, a neurological disorder was suspected: MRI showed two bulky intramedullary cysts. After the removal of the cysts symptoms resolved.

Metabolic complications associated with antiretroviral therapy in HIV-infected and HIV-exposed uninfected paediatric patients.

IMPORTANCE OF THE FIELD: HIV-infection has become a chronic disease in paediatric patients with the potential for long-term survival and exposure to antiretroviral (ARV) therapies for 2 decades longer than HIV-infected adults. On the other hand, the administration of ARV to HIV-infected pregnant women has greatly increased both treatment of HIV infection and prevention of perinatal HIV transmission. Therefore, researches aiming to evaluate the safety of ARV therapies in HIV-infected children as well as in HIV-uninfected infants born to HIV-infected mothers are emerging as a new challenge and urgent priority. AREAS COVERED IN THIS REVIEW: The purpose of this review is to describe some of the more concerning metabolic complications associated with ARV in paediatric population: hyperlactataemia (HLA) syndromes, body shape abnormalities, disorders of glucose homeostasis and dyslipidaemia in HIV-infected children and adolescents. Frequency, risk factors, clinical findings, prevention and intervention strategies of the previously described abnormalities are discussed in depth. WHAT THE READER WILL GAIN: This review covers our current understanding of HLA syndromes in ARV-exposed uninfected infants born to HIV-infected mothers. TAKE HOME MESSAGE: Prevention of these metabolic complications should assume prominence and future researches should address several of the existing treatment gaps.

Applicability of quantitative ultrasonography of the radius and tibia in HIV-infected children and adolescents.

OBJECTIVE: To assess applicability of quantitative ultrasonography (QUS) for bone health assessment in HIV-infected youths. METHODS: QUS measurements of the radius and tibia and dual-energy x-ray absorptiometry (DXA) measurements of the lumbar spine and whole skeleton were obtained in 88 HIV-infected children and adolescents (aged 4.8-22.1 years, 43 boys and 45 girls). RESULTS: Radius speed of sound was significantly associated to lumbar spine and total body DXA measurements (R values from 0.57 to 0.60), after correction for differences in sex and anthropometry. Similarly, speed of sound of the tibia was associated to all DXA measurements (R from 0.58 to 0.66). The z scores calculated for lumbar spine DXA measurements were significantly lower (P < 0.0001) than those of QUS measurements, although no differences were observed between QUS and total body z scores. CONCLUSIONS: Our study shows that QUS of the peripheral skeleton is related to DXA. The ability to detect low values is similar to that of total body DXA. Our data suggest that QUS may be an additional diagnostic tool for the study of bone mass in HIV-infected youths.