How to measure the impacts of antibiotic resistance and antibiotic development on empiric therapy: new composite indices

Hughes, Judy; Hurford, Amy; Finley, Rita; Patrick, David M.; Wu, Jianhong; Morris, Andrew M.

doi:10.1136/bmjopen-2016-012040

Cited by 24 publications

(14 citation statements)

References 48 publications

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“…We model the effects of antimicrobial de-escalation on P. aeruginosa transmission, infection, and evolutionary dynamics in an intensive care unit, and consequences for patients. Specifically, we consider the effects of three therapy adjustment strategies on the evolution of P. aeruginosa resistance to piperacillin-tazobactam, which is often used for empiric therapy of severe infections in the ICU because it provides good coverage of common pathogens [ 19 – 21 ], and ciprofloxacin which is often used for definitive treatment of susceptible P. aeruginosa infections [ 22 – 27 ]. Ciprofloxacin is the preferred alternative because it provides poorer empiric coverage of common Gram-positive pathogens such as Staphylococcus aureus [ 21 ], and can be given orally.…”

Section: Methodsmentioning

confidence: 99%

Benefits and unintended consequences of antimicrobial de-escalation: Implications for stewardship programs

Hughes¹,

Xi²,

Falk³

et al. 2017

PLoS ONE

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Sequential antimicrobial de-escalation aims to minimize resistance to high-value broad-spectrum empiric antimicrobials by switching to alternative drugs when testing confirms susceptibility. Though widely practiced, the effects de-escalation are not well understood. Definitions of interventions and outcomes differ among studies. We use mathematical models of the transmission and evolution of Pseudomonas aeruginosa in an intensive care unit to assess the effect of de-escalation on a broad range of outcomes, and clarify expectations. In these models, de-escalation reduces the use of high-value drugs and preserves the effectiveness of empiric therapy, while also selecting for multidrug-resistant strains and leaving patients vulnerable to colonization and superinfection. The net effect of de-escalation in our models is to increase infection prevalence while also increasing the probability of effective treatment. Changes in mortality are small, and can be either positive or negative. The clinical significance of small changes in outcomes such as infection prevalence and death may exceed more easily detectable changes in drug use and resistance. Integrating harms and benefits into ranked outcomes for each patient may provide a way forward in the analysis of these tradeoffs. Our models provide a conceptual framework for the collection and interpretation of evidence needed to inform antimicrobial stewardship.

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Section: Methodsmentioning

confidence: 99%

Benefits and unintended consequences of antimicrobial de-escalation: Implications for stewardship programs

Hughes¹,

Xi²,

Falk³

et al. 2017

PLoS ONE

Self Cite

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“…The Empiric Coverage Index is a novel index proposed to evaluate the local impact of antibiotic resistance on empirical coverage. [9] So, the burning question that needs an answer is: What are the barriers to implementation of an ABS programme in your institution? This question was the focus of an Australian study that revealed interesting results after in-depth interviews were conducted with both doctors and nurses.…”

Section: Antibiotic Stewardship -It Starts With You! 'The Thoughtlessmentioning

confidence: 99%

Antibiotic stewardship – it starts with you!

Miller

2017

S Afr J Crit Care

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“…Unfortunately, many antibiotics are becoming less effective due to the selection and spread of antibiotic-resistant bacteria (2)(3)(4), resulting from antibiotic overuse (5). The increasing resistance to standard antibiotic therapy increases the risk of inappropriate empirical antibiotic therapy, treatment failure and mortality in critically ill patients (6). For example, in southern and eastern Europe carbapenem resistance in Enterobacteriales is approaching 50% incidence (7) (8).…”

Section: Introductionmentioning

confidence: 99%

A high-throughput fluidic chip for rapid phenotypic antibiotic susceptibility testing

Wistrand-Yuen

Malmberg

Fatsis-Kavalopoulos

et al. 2019

Preprint

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Many patients with severe infections receive inappropriate empirical treatment and rapid detection of bacterial antibiotic susceptibility can in this context improve clinical outcome and reduce mortality. We have to this end developed a high-throughput fluidic chip for rapid phenotypic antibiotic susceptibility testing of bacteria. A total of 21 clinical isolates of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were acquired from the EUCAST Development Laboratory and tested against amikacin, ceftazidime and meropenem (Gramnegative bacteria) or gentamicin, ofloxacin and tetracycline (Gram-positive bacteria). The bacterial samples were mixed with agarose and loaded in 8 separate growth chambers in the fluidic chip. The chip was thereafter connected to a reservoir lid containing different antibiotics and a pump used to draw growth media with or without antibiotics into the chip for generation of diffusion-limited antibiotic gradients in the growth chambers. Bacterial microcolony growth was monitored using darkfield time-lapse microscopy and quantified using a cluster image analysis algorithm. Minimum inhibitory concentration (MIC) values were automatically obtained by tracking the growth rates of individual microcolonies in different regions of antibiotic gradients. Stable MIC values were obtained within 2-4 hours and the results showed categorical agreement to reference MIC values as determined with broth microdilution in 86% of the cases. ImportancePrompt and effective antimicrobial therapy is crucial for the management of patients with severe bacterial infections but is becoming increasingly difficult to provide due to emerging antibiotic resistance. The traditional methods for antibiotic susceptibility testing (AST) used in most clinical laboratories are reliable but slow with turnaround times of 2-3 days, which necessitates the use of empirical therapy with broad-spectrum antibiotics. There is a great need for fast and reliable AST methods that enable start of targeted treatment within a few hours to improve patient outcome and reduce overuse of broad-spectrum antibiotics. The high-throughput fluidic chip for phenotypic AST described in the present study enables data on antimicrobial resistance within 2-4 hours allowing for an early initiation of appropriate antibiotic therapy.

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How to measure the impacts of antibiotic resistance and antibiotic development on empiric therapy: new composite indices

Cited by 24 publications

References 48 publications

Benefits and unintended consequences of antimicrobial de-escalation: Implications for stewardship programs

Benefits and unintended consequences of antimicrobial de-escalation: Implications for stewardship programs

Antibiotic stewardship – it starts with you!

A high-throughput fluidic chip for rapid phenotypic antibiotic susceptibility testing

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