Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials

By Marc A Meier,  Angela Branche,  Olivia L Neeser,  Yannick Wirz,  Sebastian Haubitz, Lila Bouadma,  Michel Wolff,  Charles E Luyt,  Jean Chastre,  Florence Tubach, Mirjam Christ-Crain,  Caspar Corti,  Jens-Ulrik S Jensen,  Rodrigo O Deliberato, Kristina B Kristoffersen,  Pierre Damas,  Vandack Nobre,  Carolina F Oliveira, Yahya Shehabi,  Daiana Stolz,  Michael Tamm,  Beat Mueller,  Philipp Schuetz

Clinical Infectious Diseases, To be Published August 1, 2019


Whether procalcitonin (PCT)–guided antibiotic management in patients with positive blood cultures is safe remains understudied. We performed a patient-level meta-analysis to investigate effects of PCT-guided antibiotic management in patients with bacteremia.

We extracted and analyzed individual data of 523 patients with positive blood cultures included in 13 trials, in which patients were randomly assigned to receive antibiotics based on PCT levels (PCT group) or a control group. The main efficacy endpoint was duration of antibiotic treatment. The main safety endpoint was mortality within 30 days.

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Factors Associated With Antibiotic Prescribing and Outcomes for Pediatric Pneumonia in the Emergency Department.

By Matthew Lipshaw, Todd Florin, Sara Krueger, Michael Belsky, Thomas Epperson, Eric Crotty, Jessi Lipscomb, Judd Jacobs, Mantosh Rattan, Richard Ruddy, Samir Shah, Lilliam Ambroggio

Pediatric Emergency Care. July 8, 2019


Chest radiographs (CXRs) are often performed in children with respiratory illness to inform the decision to prescribe antibiotics. Our objective was to determine the factors associated with clinicians' plans to treat with antibiotics prior to knowledge of CXR results and the associations between preradiograph plans with antibiotic prescription and return to medical care.

Previously healthy children aged 3 months to 18 years with a CXR for suspected pneumonia were enrolled in a prospective cohort study in the emergency department. Our primary outcomes were antibiotic prescription or administration in the emergency department and medical care sought within 7 to 15 days after discharge. Inverse probability treatment weighting was used to limit bias due to treatment selection. Inverse probability treatment weighting was included in a logistic regression model estimating the association between the intention to give antibiotics and outcomes.

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Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial

By Prof Michael Levin, Aubrey J Cunnington, Clare Wilson, Prof Simon Nadel, Hans Joerg Lang, Nelly Ninis, Mignon McCulloch, Prof Andrew Argent, Heloise Buys, Christopher A Moxon, Abigail Best, Ruud G Nijman, Clive J Hoggart

The Lancet Respiratory Diseases, July 1, 2019


Fluid resuscitation is the recommended management of shock, but increased mortality in febrile African children in the FEAST trial. We hypothesised that fluid bolus-induced deaths in FEAST would be associated with detectable changes in cardiovascular, neurological, or respiratory function, oxygen carrying capacity, and blood biochemistry.

We developed composite scores for respiratory, cardiovascular, and neurological function using vital sign data from the FEAST trial, and used them to compare participants from FEAST with those from four other cohorts and to identify differences between the bolus (n=2097) and no bolus (n=1044) groups of FEAST. We calculated the odds of adverse outcome for each ten-unit increase in baseline score using logistic regression for each cohort. Within FEAST participants, we also compared haemoglobin and plasma biochemistry between bolus and non-bolus patients, assessed the effects of these factors along with the vital sign scores on the contribution of bolus to mortality using Cox proportional hazard models, and used Bayesian clustering to identify subgroups that differed in response to bolus. The FEAST trial is registered with ISRCTN, number ISRCTN69856593.

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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

By Yingfen Hsia, PhD,Brian R Lee, PhD, Ann Versporten, MPH, Yonghong Yang, PhD, Julia Bielicki, MD, Charlotte Jackson, PhD, Jason Newland, MD, Herman Goossens, PhD, Nicola Magrini, MD, Mike Sharland, MD on behalf of the GARPEC and Global-PPS networks

The Lancet Global Health. To be published July 2019


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.

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.

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.

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.

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.

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Management of ventilator-associated pneumonia (VAP) caused by resistant gram-negative bacteria: which is the best strategy to treat?

By Cristina Sarda, Farhan Fazal & Jordi Rello

Expert Review of Respiratory Medicine. June 24, 2019


Introduction: Treatment of ventilator-associated pneumonia (VAP) is a major challenge. The increase in multi-drug resistant bacteria has not been accompanied by the validation of new drugs, or by any new antimicrobial strategies to exploit the available agents. VAP due to Gram-negative bacteria has increased mortality, both due to the resistant pathogens themselves and due to inappropriate treatment. Local epidemiology, patients' characteristics and clinical responses provide the most important information for therapeutic decision-making. Moreover, data on VAP therapy due to resistant bacteria are lacking, and the choice of treatment is often based on clinical practice and individual experience. Areas covered: This review summarizes the strategies available for treating the three most prevalent resistant Gram-negative organisms causing VAP: Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae. The review covers the results of a Pubmed search, clinical practice guidelines and reviews, and the authors' experience. Expert opinion: The existing evidence focuses on bloodstream infections or other sites rather than pneumonia and there are no recommendations for the treatment of VAP by multi-drug resistant Gram-negative bacteria, especially for combination regimens. The approval of new drugs is needed to provide effective and safe alternatives for treating carbapenemase-producing strains. Precision medicine and personalized approach are also fundamental in future research.

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