Point Prevalence Surveys of Antimicrobial Use among Hospitalized Children in Six Hospitals in India in 2016.

The prevalence of antimicrobial resistance in India is among the highest in the world. Antimicrobial use in inpatient settings is an important driver of resistance, but is poorly characterized, particularly in hospitalized children. In this study, conducted as part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) project, we examined the prevalence of and indications of antimicrobial use, as well as antimicrobial agents used among hospitalized children by conducting four point prevalence surveys in six hospitals between February 2016 and February 2017. A total of 681 children were hospitalized in six hospitals across all survey days, and 419 (61.5%) were prescribed one or more antimicrobials (antibacterials, antivirals, antifungals). Antibacterial agents accounted for 90.8% (547/602) of the total antimicrobial prescriptions, of which third-generation cephalosporins (3GCs) accounted for 38.9% (213/547) and penicillin plus enzyme inhibitor combinations accounted for 14.4% (79/547). Lower respiratory tract infection (LRTI) was the most common indication for prescribing antimicrobials (149 prescriptions; 24.8%). Although national guidelines recommend the use of penicillin and combinations as first-line agents for LRTI, 3GCs were the most commonly prescribed antibacterial agents (55/149 LRTI prescriptions; 36.9%). In conclusion, 61.5% of hospitalized children were on at least one antimicrobial agent, with excessive use of 3GCs. Hence there is an opportunity to limit their inappropriate use

Point prevalence surveys of antimicrobial use among eight neonatal intensive care units in India: 2016

BACKGROUND: Information about antimicrobial use is scarce and poorly understood among neonatal intensive care units (NICUs) in India. In this study, we describe antimicrobial use in eight NICUs using four point prevalence surveys (PPSs). METHODS: As part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) study, one-day, cross-sectional, hospital-based PPSs were conducted four times between 1 February 2016 and 28 February 2017 in eight NICUs. Using a standardized web-based electronic data entry form, detailed data were collected for babies on antimicrobials. RESULTS: A total of 403 babies were admitted to NICUs across all survey days, and 208 (51.6%) were prescribed one or more antimicrobials. Among 208 babies, 155 (74.5%) were prescribed antimicrobials for treatment of an active infection. Among 155 babies with an active infection, treatment was empiric in 109 (70.3%). Sepsis (108, 49.1%) was the most common reason for prescribing antimicrobials. Amikacin (17%) followed by meropenem (12%) were the two most commonly prescribed antimicrobials. For community-acquired sepsis, piperacillin-tazobactam (17.5%) was the most commonly prescribed drug. A combination of ampicillin and gentamicin was prescribed in only two babies (5%). CONCLUSIONS: The recommended first-line antimicrobial agents, ampicillin and gentamicin, were rarely prescribed in Indian NICUs for community acquired neonatal sepsis

Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm(3) and 2.83 mm(3), respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans

Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries

BACKGROUND: Improving the quality of hospital antibiotic use is a major goal of WHO's global action plan to combat antimicrobial resistance. The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate simple stewardship interventions that are widely applicable globally. We aimed to present data on patterns of paediatric AWaRe antibiotic use that could be used for local and national stewardship interventions. METHODS: 1-day point prevalence survey antibiotic prescription data were combined from two independent global networks: the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children and the Global Point Prevalence Survey on Antimicrobial Consumption and Resistance networks. We included hospital inpatients aged younger than 19 years receiving at least one antibiotic on the day of the survey. The WHO AWaRe classification was used to describe overall antibiotic use as assessed by the variation between use of Access, Watch, and Reserve antibiotics, for neonates and children and for the commonest clinical indications. FINDINGS: Of the 23 572 patients included from 56 countries, 18 305 were children (77·7%) and 5267 were neonates (22·3%). Access antibiotic use in children ranged from 7·8% (China) to 61·2% (Slovenia) of all antibiotic prescriptions. The use of Watch antibiotics in children was highest in Iran (77·3%) and lowest in Finland (23·0%). In neonates, Access antibiotic use was highest in Singapore (100·0%) and lowest in China (24·2%). Reserve antibiotic use was low in all countries. Major differences in clinical syndrome-specific patterns of AWaRe antibiotic use in lower respiratory tract infection and neonatal sepsis were observed between WHO regions and countries. INTERPRETATION: There is substantial global variation in the proportion of AWaRe antibiotics used in hospitalised neonates and children. The AWaRe classification could potentially be used as a simple traffic light metric of appropriate antibiotic use. Future efforts should focus on developing and evaluating paediatric antibiotic stewardship programmes on the basis of the AWaRe index. FUNDING: GARPEC was funded by the PENTA Foundation. GARPEC-China data collection was funded by the Sanming Project of Medicine in Shenzhen (SZSM2015120330). bioMérieux provided unrestricted funding support for the Global-PPS

Human Cord Blood Serum-Derived APP α-Secretase Cleavage Activity is Mediated by C1 Complement

Alzheimer’s Disease (AD) is the leading cause of dementia in the elderly. In healthy individuals, amyloid precursor protein (APP) is cleaved by α-secretase, generating soluble α-amyloid precursor protein (sAPPα), which contributes neuroprotective functions in the neuronal environment. In contrast, in the neurodegenerative environment of AD patients, amyloid-β-peptide (Aβ) of either 40 or 42 residues are generated by increased activity of β- and γ-secretase. These proteins amalgamate in specific regions of the brain, which disrupts neuronal functions and leads to cognitive impairment. Human umbilical cord blood cells (HUCBC) have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases, including AD. Our most recent work studied the impact of umbilical cord blood serum (CBS) on modulation of sAPPα production. Heat-sensitive CBS significantly promoted sAPPα production, indicating that heat-sensitive factor(s) play(s) a role in this process. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to determine the molecular source of α-secretase in purified CBS and aged blood serum (AgBS) fraction. Of the proteins identified, the subunits of C1 complex (C1q, C1r, and C1s) and alpha-2-macroglobulin showed significantly greater levels in purified α-CBS fraction (α-CBSF) compared with the AgBS fraction (AgBSF). Specifically, C1 markedly increased sAPPα and alpha-carboxyl-terminal fragment (α-CTF) production in a dose-dependent fashion, whereas C1q alone only minimally increased and C3 did not increase sAPPα production in the absence of sera. Furthermore, C1q markedly increased sAPPα and α-CTF, while decreasing Aβ, in CHO/APPwt cells cultured in the presence of whole sera. These results confirm our initial assumption that APP α-secretase activity in human blood serum is mediated by complement C1, opening a potential therapeutic modality for the future of AD

Human Cord Blood Serum-Derived APP α-Secretase Cleavage Activity is Mediated by C1 Complement

Alzheimer’s Disease (AD) is the leading cause of dementia in the elderly. In healthy individuals, amyloid precursor protein (APP) is cleaved by α-secretase, generating soluble α-amyloid precursor protein (sAPPα), which contributes neuroprotective functions in the neuronal environment. In contrast, in the neurodegenerative environment of AD patients, amyloid-β-peptide (Aβ) of either 40 or 42 residues are generated by increased activity of β- and γ-secretase. These proteins amalgamate in specific regions of the brain, which disrupts neuronal functions and leads to cognitive impairment. Human umbilical cord blood cells (HUCBC) have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases, including AD. Our most recent work studied the impact of umbilical cord blood serum (CBS) on modulation of sAPPα production. Heat-sensitive CBS significantly promoted sAPPα production, indicating that heat-sensitive factor(s) play(s) a role in this process. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to determine the molecular source of α-secretase in purified CBS and aged blood serum (AgBS) fraction. Of the proteins identified, the subunits of C1 complex (C1q, C1r, and C1s) and alpha-2-macroglobulin showed significantly greater levels in purified α-CBS fraction (α-CBSF) compared with the AgBS fraction (AgBSF). Specifically, C1 markedly increased sAPPα and alpha-carboxyl-terminal fragment (α-CTF) production in a dose-dependent fashion, whereas C1q alone only minimally increased and C3 did not increase sAPPα production in the absence of sera. Furthermore, C1q markedly increased sAPPα and α-CTF, while decreasing Aβ, in CHO/APPwt cells cultured in the presence of whole sera. These results confirm our initial assumption that APP α-secretase activity in human blood serum is mediated by complement C1, opening a potential therapeutic modality for the future of AD