Sepsis Guidelines

by Angela X Chen, M.B., B.S., M.P.H.; Steven Q. Simpson, M.D.; and Daniel J. Pallin, M.D., M.P.H.

Published in The New England Journal of Medicine, 04 April 2019. 

 

This interactive feature about the initial management of suspected sepsis offers a case vignette, accompanied by essays that either support or discourage the implementation of a 1-hour bundle for the management of sepsis and septic shock. Disclosure forms provided by the author are available with the full text of this article at NEJM.org.

 

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Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains

by van Dorp L, Wang Q, Shaw LP, Acman M, Brynildsrud OB, Eldholm V, Wang R, Gao H, Yin Y, Chen H, Ding C, Farrer RA, Didelot X, Balloux F, Wang H

Published in Microbial Genomics, 02 April 2019.

 

 

Carbapenem-resistant Klebsiella pneumoniae (CRKP) increasingly cause high-mortality outbreaks in hospital settings globally. Following a patient fatality at a hospital in Beijing due to a blaKPC-2-positive CRKP infection, close monitoring was put in place over the course of 14 months to characterize all blaKPC-2-positive CRKP in circulation in the hospital. Whole genome sequences were generated for 100 isolates from blaKPC-2-positive isolates from infected patients, carriers and the hospital environment. Phylogenetic analyses identified a closely related cluster of 82 sequence type 11 (ST11) isolates circulating in the hospital for at least a year prior to admission of the index patient. The majority of inferred transmissions for these isolates involved patients in intensive care units. Whilst the 82 ST11 isolates collected during the surveillance effort all had closely related chromosomes, researchers observed extensive diversity in their antimicrobial resistance (AMR) phenotypes. The study team was able to reconstruct the major genomic changes underpinning this variation in AMR profiles, including multiple gains and losses of entire plasmids and recombination events between plasmids, including transposition of blaKPC-2. They also identified specific cases where variation in plasmid copy number correlated with the level of phenotypic resistance to drugs, suggesting that the number of resistance elements carried by a strain may play a role in determining the level of AMR. Study findings highlight the epidemiological value of whole genome sequencing for investigating multi-drug-resistant hospital infections and illustrate that standard typing schemes cannot capture the extraordinarily fast genome evolution of CRKP isolates.

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Association between urinary community-acquired fluoroquinolone-resistant Escherichia coli and neighbourhood antibiotic consumption: a population-based case-control study

by Marcelo Low, MPH; Ami Neuberger, MD; Prof Thomas M Hooton, MD; Prof Manfred S Green, MBChB; Prof Raul Raz, MD; Prof Ran D Balicer, MD; et al.

Published in The Lancet Infectious Diseases, 01 April 2019. 

 

 

It is unknown whether increased use of antibiotics in a community increases the risk of acquiring antibiotic resistance by individuals living in that community, regardless of prior individual antibiotic consumption and other risk factors for antibiotic resistance. Researchers used a hierarchical multivariate logistic regression approach to evaluate the association between neighbourhood fluoroquinolone consumption and individual risk of colonisation or infection of the urinary tract with fluoroquinolone-resistant Escherichia coli. A population-based case-control study of adults (aged ≥22 years) living in 1733 predefined geographical statistical areas (neighbourhoods) in Israel was performed. A multilevel study design was used to analyse data derived from electronic medical records of patients enrolled in the Clalit state-mandated health service. 300,105 events with E coli growth and 1 899 168 cultures with no growth were identified from medical records and included in the analysis. 45 427 (16·8%) of 270 190 women and 8835 (29·5%) of 29 915 men had fluoroquinolone-resistant E coli events. The study team found an independent association between residence in a neighbourhood with higher antibiotic consumption and an increased risk of bacteriuria caused by fluoroquinolone-resistant E coli. Odds ratios (ORs) for the quintiles with higher neighbourhood consumption (compared with the lowest quintile) were 1·15 (95% CI 1·06–1·24), 1·31 (1·20–1·43), 1·41 (1·29–1·54), and 1·51 (1·38–1·65) for women, and 1·17 (1·02–1·35), 1·24 (1·06–1·45), 1·35 (1·15–1·59), and 1·50 (1·26–1·77) for men. Results remained significant when the analysis was restricted to patients who had not consumed fluoroquinolones themselves. These data suggest that increased use of antibiotics in specific geographical areas is associated with an increased personal risk of acquiring antibiotic-resistant bacteria, independent of personal history of antibiotic consumption and other known risk factors for antimicrobial resistance.  Article access can be found here.   
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Antibiotic prescription for febrile children in European emergency departments: a cross-sectional, observational study

by Josephine van de Maat, MD; Elles van de Voort, MD; Santiago Mintegi, PhD; Prof Alain Gervaix, PhD; Daan Nieboer; Prof Henriette Moll, PhD; et al.

Published in The Lancet Infectious Diseases, 01 April 2019. 

 

 

Prevalence of serious bacterial infections in children in countries in western Europe and the USA is low. Antibiotic stewardship aims at a more rational use of antibiotics but information on the frequency of antibiotic prescription to children in emergency departments is scarce. Researchers aimed to quantify and explain variability in antibiotic prescription in children attending European paediatric emergency departments. A cross-sectional, observational study of children aged between 1 month and 16 years who presented with fever to one of 28 European emergency departments on one random sampling day per month between Nov 1, 2014, and Feb 28, 2016 was performed. The surveyed sites were spread across 11 countries and included 17 academic hospitals with 3,000 to up to 80,000 annual visits to their paediatric emergency departments. Researchers determined the proportion of children without comorbidities who received antibiotic prescriptions by country, focus of infection, and type of antibiotic. Then, a detailed analysis of the same population, using a multilevel logistic regression analysis, into the variability in prescriptions across hospitals, focusing particularly on respiratory tract infections and correcting for a combination of result-dependent factors was done. Random group assignment was done by computer randomisation. Of 5,177 children in total, 617 children had comorbidities. Of the 4,560 children without comorbidities, 1454 (32%) received antibiotics. This percentage varied from 19% to 64% across countries. Of these 1454 prescriptions issued, 893 (61%) were second-line antibiotics. Antibiotic prescription for respiratory tract infections, the most common infection type, in children without comorbidities was most variable across countries (15–67% for upper respiratory tract infections and 24–87% for lower respiratory tract infections) and was associated with age (odds ratio [OR] 1·51, 95% CI 1·08–2·13), fever duration (OR 1·45, 1·01–2·07), blood concentrations of C-reactive protein (OR 2·31, 1·67–3·19), and chest x-ray results (OR 10·62, 5·65–19·94, for focal abnormalities; OR 3·49, 1·59–7·64, for diffuse abnormalities). After correcting for patient characteristics, diagnostic assessment, and hospital characteristics, antibiotic prescription for respiratory tract infections remained highly variable across emergency departments (standardised antibiotic prescription ratio 0·49–2·04). Antibiotic prescription in European emergency departments is highly variable, with frequent use of second-line antibiotics. To ensure successful antibiotic stewardship initiatives in Europe aimed at reducing unnecessary prescription of antibiotics, variability of prescription across hospitals should be considered, drivers of suboptimal antibiotic prescription at the local level need to be identified, and European guidelines need to be devised.

 

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Electronically delivered interventions to reduce antibiotic prescribing for respiratory infections in primary care: cluster RCT using electronic health records and cohort study

by Gulliford MC, Juszczyk D, Prevost AT, Soames J, McDermott L, Sultana K, Wright M, Fox R, Hay AD, Little P, Moore M, Yardley L, Ashworth M, Charlton J

Published in Health Technology Assessment, March 2019. 

 

Unnecessary prescribing of antibiotics in primary care is contributing to the emergence of antimicrobial drug resistance. The objective of this study was to develop and evaluate a multicomponent intervention for antimicrobial stewardship in primary care, and to evaluate the safety of reducing antibiotic prescribing for self-limiting respiratory infections (RTIs). A multicomponent intervention, developed as part of this study, including a webinar, monthly reports of general practice-specific data for antibiotic prescribing and decision support tools to inform appropriate antibiotic prescribing. A parallel-group, cluster randomised controlled trial was used for the study design. This study found evidence that, overall, general practice antibiotic prescribing for RTIs was reduced by this electronically delivered intervention. Antibiotic prescribing rates were reduced for adults aged 15-84 years, but not for children or the senior elderly.

 

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