scholarly journals Systematic analysis of key parameters for genomics-based real-time detection and tracking of multidrug-resistant bacteria

2020 ◽  
Author(s):  
Claire L Gorrie ◽  
Anders Goncalves Da Silva ◽  
Danielle J Ingle ◽  
Charlie Higgs ◽  
Torsten Seemann ◽  
...  
Keyword(s):  
Medical Research ◽  
National Health ◽  
Research Council ◽  
Reference Genome ◽  
Medical Research Council ◽  
Sliding Window ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Variable Effect ◽  
The Impact

ABSTRACTBackgroundPairwise single nucleotide polymorphisms (SNPs) are a cornerstone for genomic approaches to multidrug-resistant organisms (MDROs) transmission inference in hospitals. However, the impact of key analysis parameters on these inferences has not been systematically analysed.MethodsWe conducted a multi-hospital 15-month prospective study, sequencing 1537 MDRO genomes for comparison; methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. We systematically assessed the impact of sample and reference genome diversity, masking of prophage and regions of recombination, cumulative genome analysis compared to a three-month sliding-window, and the comparative effects each of these had when applying a SNP threshold for inferring likely transmission (≤15 SNPs for S. aureus, ≤25 for other species).FindingsAcross the species, using a reference genome of the same sequence type provided a greater degree of pairwise SNP resolution, compared to species and outgroup-reference alignments that typically resulted in inflated SNP distances and the possibility of missed transmission events. Omitting prophage regions had minimal impacts, however, omitting recombination regions a highly variable effect, often inflating the number of closely related pairs. Estimating pairwise SNP distances was more consistent using a sliding-window than a cumulative approach.InterpretationThe use of a closely-related reference genome, without masking of prophage or recombination regions, and a sliding-window for isolate inclusion is best for accurate and consistent MDRO transmission inference. The increased stability and resolution provided by these approaches means SNP thresholds for putative transmission inference can be more reliably applied among diverse MDROs.FundingThis work was supported by the Melbourne Genomics Health Alliance (funded by the State Government of Victoria, Department of Health and Human Services, and the ten member organizations); an National Health and Medical Research Council (Australia) Partnership grant (GNT1149991) and individual grants from National Health and Medical Research Council (Australia) to NLS (GNT1093468), JCK (GNT1008549) and BPH (GNT1105905).

scholarly journals Effect of delays in concordant antibiotic treatment on mortality in patients with hospital-acquired Acinetobacter spp. bacteremia: a 13-year retrospective cohort

2020 ◽  
Author(s):  
Cherry Lim ◽  
Mo Yin ◽  
Prapit Teparrukkul ◽  
Maliwan Hongsuwan ◽  
Nicholas P.J. Day ◽  
...  
Keyword(s):  
Medical Research ◽  
Antibiotic Treatment ◽  
Research Council ◽  
Medical Research Council ◽  
Research Training ◽  
Absolute Increase ◽  
Immortal Time Bias ◽  
Training Fellowship ◽  
Hospital Acquired ◽  
The Impact

AbstractBackgroundTherapeutic options for multidrug-resistant Acinetobacter spp. are limited, and resistance to last resort antibiotics in hospitals is increasing globally. Quantifying the impact of delays in concordant antibiotic treatment on patient mortality is important for designing hospital antibiotic policies.MethodsWe included patients with Acinetobacter spp. hospital-acquired bacteremia (HAB) in a hospital in Thailand over a 13-year period. For each day of stay following the first positive blood culture we considered antibiotic treatment to be concordant if the isolated organism was susceptible to at least one antibiotic given. We used marginal structural models with inverse-probability weightings to determine the association between delays in concordant treatment and 30-day mortality.ResultsBetween January 2003 and December 2015, 1,203 patients had HAB with Acinetobacter spp., of which 682 patients (56.7%) had one or more days of delay in concordant treatment. These delays were associated with an absolute increase in 30-day mortality of 6.6% (95% CI 0.2%-13.0%), from 33.8% to 40.4%. Crude 30-day mortality was substantially lower in patients with three or more days of delays in concordant treatment compared to those with one to two days of delays. Accounting for confounders and immortal time bias resolved this paradox, and showed similar 30-day mortality for one, two and three or more days of delays.ConclusionsDelays in concordant antibiotic treatment were associated with a 6.6% absolute increase in mortality among patients with hospital-acquired Acinetobacter spp. bacteremia. If this association is causal, switching fifteen patients from discordant to concordant initial treatment would be expected to prevent one death.FundingThe Mahidol Oxford Tropical Medicine Research Unit (MORU) is funded by the Wellcome Trust [grant number 106698/Z14/Z]. CL is funded by a Wellcome Trust Research Training Fellowship [grant number 206736/Z/17/Z]. MY is supported by a Singapore National Medical Research Council Research Fellowship [grant number NMRC/Fellowship/0051/2017]. BSC is funded by the UK Medical Research Council and Department for International Development [grant number MR/K006924/1]. DL is funded by a Wellcome Trust Intermediate Training Fellowship [grant number 101103]. The funder has no role in the design and conduct of the study, data collection, or in the analysis and interpretation of the data.

scholarly journals Colorectal cancer screening:potential pitfalls

2001 ◽  
Vol 24 (1) ◽  
pp. 148 ◽  
Author(s):  
John Duggan
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Cost Effectiveness ◽  
Cancer Screening ◽  
Medical Research ◽  
Colorectal Cancer Screening ◽  
National Health ◽  
Research Council ◽  
Medical Research Council

The National Health and Medical Research Council has recently issued guidelines on colo-rectal cancer, and givensignificant support to Colorectal Cancer Screening. However, the evidence of cost-effectiveness is inconclusiveaccording to the Cochrane Centre.I argue that it would be wise to undertake trials that are appropriately funded. Otherwise, there is a risk that muchmoney will be spent that cannot subsequently be justified.

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