Jun, 2019

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.


Authors: Hsia Y, Lee BR, Versporten A, et al; GARPEC and Global-PPS networks.

Published in: Lancet Glob Health. 2019;7(7):e861-e871

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%). Accessantibiotic 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 antibioticuse 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.


Jun, 2019

Chronic Hepatites C in children in the Russian federation: a multicenter study


Authors: Volynets G, Skyortsowa TA, Ptapov AS, et al.

Published in: EASL, 19th – 23rd April 2017, Amsterdam




Jun, 2019

Treating hepatitis C virus in children: time for a new paradigm


Authors: Thorne C, Indolfi G, Turkova A, Giaquinto C, Nastouli E.

Published in: J Virus Erad. 2015 Jul 1;1(3):203-5.

Abstract Hepatitis C virus infection is a leading cause of liver-related morbidity and mortality. In the paediatric population, HCV infection is underdiagnosed and undertreated in the absence of robust screening policies worldwide, and a lack of tolerable, effective treatment. The recent advances in HCV drug development allow for optimism, a change in outcomes for the millions of children infected with this virus and a unique opportunity for strategies aiming at HCV eradication. The rapid development of the new compounds has been followed by a welcome shift in the regulatory processes; however, strategies aiming at improving diagnosis, selecting the best combinations and addressing mother-to-child transmission issues are required for the new therapeutic agents to be introduced safely and effectively in the paediatric population and to contribute to the goal of virus eradication.



Jun, 2019

Co-infection with HIV and HCV in 229 children and young adults living in Europe


Authors: Thorne C, Turkova A, Indolfi G, Venturini E, Giaquinto C

Published in: AIDS. 2017;31(1):127-135.

Objective To characterize children, adolescents and young adults infected with HIV/hepatitis C virus (HCV) vertically or before age of 18 years and living in Europe regarding mode of acquisition, HCV genotype, clinical status and treatment.

Design Retrospective, cross-sectional study using pooled data from 11 European paediatric HIV cohorts.

Methods Patients aged more than 18 months and less than 25 years, with HIV/HCV acquired vertically or in childhood, were included. Anonymized individual patient data were collected using a standard protocol and modified HIV Cohorts Data Exchange Protocol.

Results Of 229 patients included, 142 (62%) had vertically acquired infection. Median age at last follow-up was 16.2 years. Most children had HCV genotype 1 (101/184, 55%) or 3 (57/184, 31%). One-fifth (46/214) had a previous AIDS diagnosis (data missing on prior AIDS diagnoses for 15). At their last clinic visit, 70% (145/208) had no/mild immunosuppression (Centers for Disease Control and Prevention stage 1), and 131 of 179 on antiretroviral therapy had undetectable HIV RNA (assay thresholds varied from <20 to <150 copies/ml). Overall, 42% (86/204) had hepatomegaly in the previous year, and 55% (116/213) had alanine aminotransferase more than 40 IU/l at their last test. Of 97 patients with transient elastography, 12 had results more than 9 kPa; this was associated with duration of HCV infection (P = 0.033), but not with CD4 cell count, antiretroviral therapy use or sex in univariable analysis. Of 17 patients with liver biopsies, six had bridging fibrosis and one had cirrhosis. Twenty-five (11%) had been treated successfully for HCV.

Conclusion The high proportion of patients with progressive liver disease underscores the need for close monitoring and earlier and more effective HCV treatment.


Jun, 2019

Hepatitis C Co-Infection and CD4+ T Cell Recovery in HIV-Infected Children Receiving Anti-Retroviral Therapy.


Authors: Majekodunmi AO, Thorne C, Malyuta R, et al.

Published in: Pediatr Infect Dis J. 2017;36(5):e123-e129

Background The effect of hepatitis C virus (HCV) coinfection on CD4 T cell recovery in treated HIV-infected children is poorly understood.

Objective To compare CD4 T cell recovery in HIV/HCV coinfected children with recovery in HIV monoinfected children.

Method We studied 355 HIV monoinfected and 46 HIV/HCV coinfected children receiving antiretroviral therapy (ART) during a median follow-up period of 4.2 years (interquartile range: 2.7-5.3 years). Our dataset came from the Ukraine pediatric HIV Cohort and the HIV/HCV coinfection study within the European Pregnancy and Paediatric HIV Cohort Collaboration. We fitted an asymptotic nonlinear mixed-effects model of CD4 T cell reconstitution to age-standardized CD4 counts in all 401 children and investigated factors predicting the speed and extent of recovery.

Results We found no significant impact of HCV coinfection on either pre-ART or long-term age-adjusted CD4 counts (z scores). However, the rate of increase in CD4 z score was slower in HIV/HCV coinfected children when compared with their monoinfected counterparts (P < 0.001). Both monoinfected and coinfected children starting ART at younger ages had higher pre-ART (P < 0.001) and long-term (P < 0.001) CD4 z scores than those who started when they were older.

Conclusions HIV/HCV coinfected children receiving ART had slower CD4 T cell recovery than HIV monoinfected children. HIV/HCV coinfection had no impact on pre-ART or long-term CD4 z scores. Early treatment of HIV/HCV coinfected children with ART should be encouraged.


Jun, 2019

HCV treatment in children and young adults with HIV/HCV co-infection in Europe.


Authors: Turkova A, Giacomet V, Goetghebuer T, et al

Published in: J Virus Erad. 2015;1(3):179-184

Objectives To describe use of treatment for chronic hepatitis C virus (HCV) infection in HIV/HCV co-infected children and young people living in Europe and to evaluate treatment outcomes.

Methods HCV treatment data on children and young people aged <25 years with HIV/HCV co-infection were collected in a cohort collaboration of 11 European paediatric HIV cohorts. Factors associated with receipt of HCV treatment and with sustained virological response 24 weeks after treatment completion (SVR24) were explored.

Results Of 229 HIV/HCV co-infected patients, 22% had a history of AIDS and of 55 who were treated for HCV, 47 (85%) were receiving combined antiretroviral therapy. The overall HCV treatment rate was 24% (n=55) but it varied substantially between countries, with the highest rate being in Russia at 61% (30/49). Other factors associated with treatment receipt were older age [adjusted odds ratio (AOR) 5.24, 95% confidence interval (CI) 1.9–14.4, for 18–24-year-olds vs 11–17-year-olds, P=0.001] and advanced fibrosis (AOR 5.5, 95% CI 1.3–23.7; for ≥9.6 vs ≤7.2 kPa, P=0.02). Of 50 patients with known treatment outcomes, 50% attained SVR24. Of these, 16 (80%) had genotype (GT) 2,3 and 8 (29%) had GT 1,4 (P<0.001). After adjusting for genotype (GT 1,4 vs GT 2,3), females (P=0.003), patients with non-vertical HCV acquisition (P=0.002) and those with shorter duration of HCV (P=0.009) were more likely to have successful treatment outcomes.

Conclusion Only half of the HIV/HCV co-infected youth achieved an HCV cure. HCV treatment success appears to be lower in the context of HIV co-infection than in HCV mono-infection, underscoring the urgent need to speed up approvals of new direct-acting antiviral combinations in children.



Jun, 2019

Highly active antiretroviral therapy started in infants under 3 months of age: 72-week follow-up for CD4 cell count, viral load and drug resistance outcome


Authors: Aboulker JP, Babiker A, Chaix ML, et al; Paediatric European Network for Treatment of AIDS.

Published in: AIDS. 2004.23;18(2):237-45

Objective To assess the feasibility and impact of highly active antiretroviral therapy (HAART) started in vertically HIV-1-infected infants less than 3 months of age.
Methods Adverse events, plasma HIV-1 RNA, CD4 cell counts, CD4 cell percentage (CD4%) and clinical progression were recorded at baseline and prospectively to 72 weeks in order to assess the toxicity, tolerability and efficacy of a combination of stavudine, didanosine and nelfinavir. Selection of genotypic resistance was also investigated.
Results Twenty infants, of whom only three had Centers for Disease Control and Prevention stage B, initiated HAART at median age 2.5 months (range, 0.9-4.7) with median HIV-1 RNA concentration 5.5 log10 copies/ml (range, 3.2-6.8) and CD4% 33% (range, 11-66). Median follow-up was 96 weeks (range, 60-144). At week 72, 11 infants were still taking the original treatment. Few adverse events were reported related to treatment, all minor and causing treatment interruption in only three infants. No AIDS-defining events occurred; one child died of non-HIV-related causes (prematurity). All but two had CD4% > 25% at 72 weeks; however, 14 infants had virological failure and six acquired resistance mutations.
Conclusions Early treatment with stavudine, didanosine and nelfinavir was well tolerated and associated with good clinical and immunological outcomes at week 72. However, a high rate of virological failure with emergence of genotypic resistance is of great concern. More palatable drug combinations for infants and closer drug monitoring are required.


Jun, 2019

Neurocognitive and Quality of Life Outcomes in Children after Planned Treatment Interruptions: the randomized PENTA 11 trial


Authors: T.Ramos J, Melvin D, Medin G, Compagnucci A, Bleier J, Boscolo V, Barclay L, de Ory S, Giaquinto C, Gibb D: on behalf of the PENTA Steering Committee

Published: 19th Conference on Retroviruses and Opportunistic Infections March 5th – 8th, 2012 – Seattle. Poster 963




Jun, 2019

Hard to study, hard to treat: putting children at the centre of antibiotic research and development


Authors: Balasegaram M, Pécoul B, Gray G, Sharland M, Swaminathan S.

Published in: Lancet Infect Dis. 2019;19(6):573-574

Abstract Newborn babies, infants, and children are substantially affected by antimicrobial resistance. Globally, infectious diseases remain a major cause of morbidity and mortality in children, and an estimated 214 000 newborn babies died from drug-resistant bacterial infections in 2015



May, 2019

R&D for children’s antibiotics – a wake-up call


Authors: O’Brien S, Sharland M, Zaoutis T

Published in: AMR CONTROL 2019-2020; online edition

Abstract It is time to prioritize children’s needs in the context of antimicrobial resistance (AMR). Children, especially babies and young infants, are particularly vulnerable to the rise in drug-resistant infection and need treatments that are adapted to their specific needs. Yet, there are almost no clinical trials looking into children’s antibiotics. This lack of prioritization threatens the attainment of the UN Sustainable Development Goals. The Global Antibiotic Research & Development Partnership (GARDP), Penta, St George’s, University of London and global partners are working together to tackle AMR in children. They call on governments, researchers, industry and more – to join them.