Antimicrobials

18

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.

5

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

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28

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.

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26

Apr, 2019

The use of polymyxins to treat carbapenem resistant infections in neonates and children

 

Authors: Thomas R, Velaphi S, Ellis S, et al.

Published in: Expert Opin Pharmacother. 2019;20(4):415-422. 

Introduction The incidence of healthcare-associated multidrug resistant bacterial infections, particularly due to carbapenem resistant organisms, has been on the rise globally. Among these are the carbapenem resistant Acinetobacter baumannii and Enterobacteriaceae, which have been responsible for numerous outbreaks in neonatal units. The polymyxins (colistin and polymyxin B) are considered to be the last resort antibiotics for treating such infections. However, pharmacokinetic and pharmacodynamic data on the use of polymyxins in neonates and children are very limited, and there are safety concerns.

Areas Covered In this review, the authors summarize the global burden of multidrug resistance, particularly carbapenem resistance, in the neonatal and paediatric population, and the potential wider use of polymyxins in treating these infections.

Expert Opinion Both colistin and polymyxin B have similar efficacy in treating multidrug resistant infections but have safety concerns. However, polymyxin B appears to be a better therapeutic option, with more rapid and higher steady state concentrations achieved compared to colistin and less reported nephrotoxicity. There is virtually no data in neonates and children currently; there is therefore an urgent need for pharmacokinetic and safety trials in these populations to determine the optimal drug and dosing regimens and provide recommendations for their use against carbapenem resistant infections.

26

Apr, 2019

Effects of an antimicrobial stewardship intervention on perioperative antibiotic prophylaxis in pediatrics

 

Authors: Donà D, Luise D, La Pergola E, et al.

Published in: Antimicrob Resist Infect Control. 2019;8:13. 

Purpose This study aims to determine the effectiveness of anAntimicrobial Stewardship Program based on a Clinical Pathway (CP) to improve appropriateness in perioperative antibiotic prophylaxis (PAP).

Materials and Methods This pre-post quasi-experimental study was conducted in a 12 month period (six months before and six months after CP implementation), in a tertiary Pediatric Surgical Centre. All patients from 1 month to 15 years of age receiving one or more surgical procedures were eligible for inclusion. PAP was defined appropriate according to clinical practice guidelines.

Results Seven hundred sixty-six children were included in the study, 394 in pre-intervention and 372 in post-intervention. After CP implementation, there was an increase in appropriate PAP administration, as well as in the selection of the appropriate antibiotic for prophylaxis, both for monotherapy (p = 0.02) and combination therapy (p = 0.004). Even the duration of prophylaxis decreased during the post-intervention period, with an increase of correct PAP discontinuation from 45.1 to 66.7% (p < 0.001). Despite the greater use of narrow-spectrum antibiotic for fewer days, there was no increase in treatment failures (10/394 (2.5%) pre vs 7/372 (1.9%) post, p = 0.54).

Conclusions CPs can be a useful tool to improve the choice of antibiotic and the duration of PAP in pediatric patients.

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26

Dec, 2018

High rates of prescribing antimicrobials for prophylaxis in children and neonates: results from the antibiotic resistance and prescribing in European children point prevalence survey

 

Authors: Hufnagel M, Versporten A, Bielicki J, et al.; for ARPEC Project Group.

Published in: J Pediatric Infect Dis Soc. 2018. doi: 10.1093/jpids/piy019.

Background This study was conducted to assess the variation in prescription practices for systemic antimicrobial agents used for prophylaxis among pediatric patients hospitalized in 41 countries worldwide.

Methods Using the standardized Antibiotic Resistance and Prescribing inEuropean Children Point Prevalence Survey protocol, a cross-sectional point-prevalence survey was conducted at 226 pediatric hospitals in 41 countries from October 1 to November 30, 2012.

Results Overall, 17693 pediatric patients were surveyed and 36.7% of them received antibiotics (n = 6499). Of 6818 inpatient children, 2242 (32.9%) received at least 1 antimicrobial for prophylactic use. Of 11899 prescriptions for antimicrobials, 3400 (28.6%) were provided for prophylactic use. Prophylaxis for medical diseases was the indication in 73.4% of cases (2495 of 3400), whereas 26.6% of prescriptions were for surgical diseases (905 of 3400). In approximately half the cases (48.7% [1656 of 3400]), a combination of 2 or more antimicrobials was prescribed. The use of broad-spectrum antibiotics (BSAs), which included tetracyclines, macrolides, lincosamides, and sulfonamides/trimethoprim, was high (51.8% [1761 of 3400]). Broad-spectrum antibiotic use for medical prophylaxis was more common in Asia (risk ratio [RR], 1.322; 95% confidence interval [CI], 1.202-1.653) and more restricted in Australia (RR, 0.619; 95% CI, 0.521-0.736). Prescription of BSA for surgical prophylaxis also varied according to United Nations region. Finally, a high percentage of surgical patients (79.7% [721 of 905]) received their prophylaxis for longer than 1 day.

Conclusions High proportion of hospitalized children received prophylactic BSAs. This represents a clear target for quality improvement. Collectively speaking, it is critical to reduce total prophylactic prescribing, BSA use, and prolonged prescription.

26

Dec, 2018

The impact of clinical pathways on antibiotic prescribing for acute otitis media and pharyngitis in the emergency department

 

Authors: Dona D, Baraldi M, Brigadoi G, et al.

Published in: Pediatr Infect Dis J. 2018;37(9):901-907.

Background Although Italian pediatric antimicrobial prescription rates are among the highest in Europe, little action has been taken to improve the appropriateness of antimicrobial prescriptions. The primary aim of this study was to assess changes in antibiotic prescription before and after acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis Clinical Pathway (CP) implementation; secondary aims were to compare treatment failures and to assess change in the total antibiotics costs before and after CP implementation.

Methods Pre-post quasi-experimental study comparing the 6-month period before CP implementation (baseline period: October 15, 2014, through April 15, 2015) to the 6 months after intervention (postintervention: October 15, 2015, through April 15, 2016).

Results Two hundred ninety-five pre- and 278 post intervention emergency department visits were associated with AOM. After CP implementation, there was an increase in “wait and see” approach and a decrease in overall prescription of broad-spectrum antibiotics from 53.2% to 32.4% (P < 0.001). One hundred fifty-one pre- and 166 post implementation clinic visits were associated with GAS pharyngitis, with a decrease in broad-spectrum prescription after CP implementation (46.4% vs. 6.6%; P < 0.001). For both conditions, no difference was found in treatment failure, and total antibiotics cost was significantly reduced after CP implementation, with a decrease especially in broad-spectrum antibiotics costs.

Conclusions A reduction in broad-spectrum antibiotic prescriptions and a reduction in the total cost of antibiotics for AOM and GAS pharyngitis along with an increase in “wait and see” prescribing for AOM indicate effectiveness of CP for antimicrobial stewardship in this setting.

26

Apr, 2018

Plasma and CSF pharmacokinetics of meropenem in neonates and young infants : results from the NeoMero studies

 

Authors: Germovesk E, Lutsar I, Kipepr K, et al.; for NeoMero Consortium

Published in: J Antimicrob Chemother. 2018;73(7):1908-1916

Background Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking.

Objectives To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS).

Methods Data were collected in two recently conducted studies, i.e. Neo-Mero-1 (neonatal LOS) and Neo-Mero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed.

Results A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome.

Conclusions Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.

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26

Apr, 2018

Surveillance for control of antimicrobial resistance

 

Authors: Tacconelli E, Sifakis F, Harbarth S, et al; for EPI-Net COMBACTE-MAGNET Group

Published in: Lancet Infect Dis. 2018;18(3):e99-e106.

Abstract Antimicrobial resistance poses a growing threat to public health and the provision of health care. Its surveillance should provide up-to-date and relevant information to monitor the appropriateness of therapy guidelines, antibiotic formulary, antibiotic stewardship programmes, public health interventions, infection control policies, and antimicrobial development. In Europe, although the European Antimicrobial Resistance Surveillance Network provides annual reports on monitored resistant bacteria, national surveillance efforts are still fragmented and heterogeneous, and have substantial structural problems and issues with laboratory data. Most incidence and prevalence data cannot be linked with relevant epidemiological, clinical, or outcome data. Genetic typing, to establish whether trends of antimicrobial resistance are caused by spread of resistant strains or by transfer of resistance determinants among different strains and species, is not routinely done. Furthermore, laboratory-based surveillance using only clinical samples is not likely to be useful as an early warning system for emerging pathogens and resistance mechanisms. Insufficient coordination of surveillance systems of human antimicrobial resistance with animal surveillance systems is even more concerning. Because results from food surveillance are considered commercially sensitive, they are rarely released publicly by regulators. Inaccurate or incomplete surveillance data delay a translational approach to the threat of antimicrobial resistance and inhibit the identification of relevant target microorganisms and populations for research and the revitalisation of dormant drug-discovery programmes. High-quality, comprehensive, and real-time surveillance data are essential to reduce the burden of antimicrobial resistance. Improvement of national antimicrobial resistance surveillance systems and better alignment between human and veterinary surveillance systems in Europe must become a scientific and political priority, coordinated with international stakeholders within a global approach to reduce the burden of antimicrobial resistance.

26

Apr, 2018

Effects of clinical pathway implementation on antibiotic prescription for pediatric community-acquired pneumonia

 

Authors: Donà D, Zingarella S, Gastaldi A, et al.

Published in: PLoS One. 2018;13(2):e0193581. 

Background Italian pediatric antimicrobial prescription rates are among the highest in Europe. As a first step in an Antimicrobial Stewardship Program, we implemented a Clinical Pathway (CP) for Community Acquired Pneumonia with the aim of decreasing overall prescription of antibiotics, especially broad-spectrum.

Materials and Methods The CP was implemented on 10/01/2015. We collected antibiotic prescribing and outcomes data from children aged 3 months-15 years diagnosed with CAP from 10/15/2014 to 04/15/2015 (pre-intervention period) and from 10/15/2015 to 04/15/2016 (post-intervention period). We assessed antibiotic prescription differences pre- and post-CP, including rates, breadth of spectrum, and duration of therapy. We also compared length of hospital stay for inpatients and treatment failure for inpatients and outpatients. Chi-square and Fisher’s exact test were used to compare categorical variables and Wilcoxon rank sum test was used to compare quantitative outcomes.

Results 120 pre- and 86 post-intervention clinic visits were identified with a diagnosis of CAP. In outpatients, we observed a decrease in broad-spectrum regimens (50% pre-CP vs. 26.8% post-CP, p = 0.02), in particular macrolides, and an increase in narrow-spectrum (amoxicillin) post-CP. Post-CP children received fewer antibiotic courses (median DOT from 10 pre-CP to 8 post-CP, p<0.0001) for fewer days (median LOT from 10 pre-CP to 8 post-CP, p<0.0001) than their pre-CP counterparts. Physicians prescribed narrow-spectrum monotherapy more frequently than broad-spectrum combination therapy (DOT/LOT ratio 1.157 pre-CP vs. 1.065 post-CP). No difference in treatment failure was reported before and after implementation (2.3% pre-CP vs. 11.8% post-CP, p = 0.29). Among inpatients we also noted a decrease in broad-spectrum regimens (100% pre-CP vs. 66.7% post-CP, p = 0.02) and the introduction of narrow-spectrum regimens (0% pre-CP vs. 33.3% post-CP, p = 0.02) post-CP. Hospitalized patients received fewer antibiotic courses post-CP (median DOT from 18.5 pre-CP to 10 post-CP, p = 0.004), while there was no statistical difference in length of therapy (median LOT from 11 pre-CP to 10 post-CP, p = 0.06). Days of broad spectrum therapy were notably lower post-CP (median bsDOT from 17 pre-CP to 4.5 post-CP, p <0.0001). No difference in treatment failure was reported before and after CP implementation (16.7% pre-CP vs. 15.4% post-CP, p = 1).

Conclusions Introduction of a CP for CAP in a Pediatric Emergency Department led to reduction of broad-spectrum antibiotic prescriptions, of combination therapy and of duration of treatment both for outpatients and inpatients.

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