Low plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to ...promote tailored treatments for both child and adult patients. The main aim of the study was to evaluate serum concentrations of isoniazid (INH) and rifampicin (RIF) and to investigate reasons for sub-therapeutic plasma concentrations in order to fix dosages. Children with TB were prospectively enrolled from January to August 2019. Two venous blood samples were collected (the first at least 15 days after the beginning of antitubercular treatment, and the second between 1 and 8 weeks later). Plasma concentrations were determined by a validated high-performance liquid chromatography method. In all, 45 children were included. Seventy blood samples for INH plasma concentration were collected between 120 and 240 min after drug intake. Adjusting for dose (mg/kg/day) and time of INH administration, when considering three different age groups (less than or equai to 2 years, 2-12 years, > 12 years), a statistically significant lower INH plasma concentration was observed in younger children compared to the older age groups in the multivariate analysis (p < 0.001 and p < 0.001). A total of 68 blood samples were evaluated for RIF concentrations. Both for INH and RIF a statistically significant lower plasma concentration was also observed in adolescents (p < 0.001). Fifteen children (15/45, 33%) presented drug concentrations under the referral therapeutic range. Based on our findings, monitoring patients' drug plasma concentrations in children under 2 years of age and in adolescents can make treatment more patient-tailored.
Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We ...retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.
In most countries, men seem to be more susceptible to tuberculosis (TB) than women, but only few studies have investigated the reasons of this gender incidence difference. The effect of sexual ...hormones on immunity is possible.
Data from children and adults, living in Tuscany, hospitalized for TB in all the thirty-one regional hospitals from January 1st 1997 to December 31st 2011, were analyzed using the International Classification of Disease, 9th Revision, Clinical Modification.
During the study period, 10,744 patients were hospitalized with TB diagnosis, precisely 279 (2.6%) children 0-14 years, 205 (1.9%) adolescents 15-18 years and 10,260 (95.5%) adults ≥ 18 years. The male population ranged from 249 patients (51.4%) in children and adolescents, to 6,253 (60.9%) in adults. Pulmonary TB was the most common form both in children and adults. Men were more likely than women to have pulmonary TB after puberty, while no significant differences were found between males and females in the hospitalized children. The male gender also resulted the most affected for the extra-pulmonary disease sites, excluding the lymphatic system, during the reproductive age.
Our findings suggest a possible role of sexual hormones in the development of TB. No significant male-female difference was found in TB incidence among children, while a sex ratio significantly different from 1:1 emerged among reproductive age classes. An increased incidence difference also persisted in older men, suggesting that male-biased risk factors could influence TB progression. Some limitations of the study are the sample size, the method of discharge diagnosis which could be deficient in accuracy in some cases, the increasing number of immigrants and the lack of possible individual risk factors (smoke and alcohol). Further studies are needed to investigate the possible hormone-driven immune mechanisms determining the sexual dimorphism in TB.
A group of Italian experts in impetigo medical care sought to define 10 statements to describe the ideal characteristics of the best local antibiotic treatments, and to provide relevant information ...re- garding their appropriate use and prescription that should be considered in clinical practice for impetigo management.
A group of Italian experts in impetigo medical care sought to define 10 statements to describe the ideal characteristics of the best local antibiotic treatments, and to provide relevant information regarding their appropriate use and prescription that should be considered in clinical practice for impetigo management.
A consensus on ideal features of antibiotic therapy for the treatment of impetigo was appraised by an online Delphi-based method, based on a panel of 61 infectious disease specialists, pediatricians, and dermatologists coordinated by a scientific committee of 5 experts specializing in impetigo management.
Full or very high consensus was reached on the 10 statements identified to describe the characteristics of the best hypothetic antibiotic therapy for impetigo together with indications for appropriate antibiotics use.
Several criteria have to be considered when selecting topical antibacterial therapy for impetigo. Beyond efficacy and safety, antimicrobial susceptibility and pharmacological characteristics of the agent are essential points. Formulation of the antimicrobial product is fundamental, as well as patient and caregiver preference, to facilitate therapeutic adherence, to achieve the infection control, and to obtain the best benefit from treatment (Curr Ther Res Clin Exp. 2023; 84:XXXXXX).
Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI).
Children with LTBI, ...active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB.
Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens.
Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs.
Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB.
Acute hematogenous osteomyelitis (AHOM) is a rare pathology in pediatric population. The aim of this study is to analyse the epidemiological data and the management, compared to European Society for ...Paediatric Infectious Disease (ESPID, European Society for Pediatric Infectious Diseases) guidelines 2017 of 216 children with AHOM, divided in three cohorts (neonatal-onset osteomyelitis, those with vertebral involvement and other types of osteomyelitis). We conducted a retrospective single center study, evaluating data from all the children (aged 0–18 years) consecutively admitted to the Meyer Children’s Hospital, during a period of ten years (1 January 2010–31 December 2019). Isolation of pathogen was possible in 65 patients and S. aureus was the most frequently involved (43/65 children). Magnetic Resonance Imaging (MRI, magnetic resonance imaging) was performed in 201/216 cases and was compatible with osteomyelitis in 185/201 of these children (92.03%). In the neonatal-onset osteomyelitis group the percentage of diagnostic ultrasound for osteomyelitis was 36.36% significantly higher than the other groups. The median duration of total antibiotic therapy was 37.5 days. In total, 186/199 children recovered without complications. The present study delineates three heterogeneous cohorts of patients. S. aureus is confirmed as the first pathogen for isolation in all three groups analysed. MRI represent a gold standard for diagnosis. Longer duration of antibiotics treatment was performed in neonatal and spondylodiscitis group, compared to the other types of osteomyelitis.
Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores ...are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale’s severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.
Fever phobia is still a major issue in paediatrics. We report knowledge of a sample of Italian paediatricians performed six years after the release of the Italian guidelines for the management of ...fever in children (IFG).
A questionnaire, developed following the IFG recommendations and previously administered to 300 paediatricians in 2012, was proposed to all the paediatricians attending the 2015 National Congress of Practice Paediatrics, held in Florence, Italy. Changes in answers over time were analyzed.
70.2% (562/800) paediatricians returned the questionnaire. The recommended site and device for body temperature measurement in children > 1 year was correctly chosen by 89.3% of participants (vs. 80.7% of 2012 participants; P < 0.001), but with children aged less than 1 year the correct answer was selected only by the 50.3% (vs. 39.3% of 2012 participants: P < 0.001). Use of physical methods was still incorrectly recommended by 51.6% of paediatricians (vs. 63.6% in 2012; P < 0.001). Use of antipyretics according to discomfort was adopted only by 38.2% of participants, while 12.2% of them recommended alternate use of antipyretics. These proportions were substantially stable since 2012 (45 and 11% respectively), rectal administration of antipyretics only in case of vomiting was correctly recommended by 86.8% of paediatricians vs. 74.7% in 2012 (P < 0.001).
Improvements in some pediatricians' misconceptions were observed over time. However, some incorrect habits persist. Further studies are needed to better understand the "weak points" of the communication between Scientific Societies and paediatricians in order to impact everyday clinical practice.
...the available literature on pediatric treatment strategies for SARS-CoV-2 infection in children was reviewed up to 10 March 2021 on PubMed, the website of national and international scientific ...societies and of clinical trials. In particular, for the age group 12–17 years, the risk factors are the following: body mass index > 95 percentile for age, sickle cell anemia, congenital or acquired cardiac disease, neurodevelopment disease, device carriers (tracheostomy, gastrostomy, etc.), asthma or other respiratory disorders requiring daily treatment 17, 18. ...the best treatment for pediatric COVID-19 is currently not well defined, because randomized trials in children are lacking.
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