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Title: From Bench-Top to Bedside: A prospective In vitro Antibiotic Combination Testing (iACT) service to guide the selection of rationally optimized antimicrobial combinations against Extensively Drug Resistant (XDR) Gram Negative Bacteria (GNB)
Authors: Cai Y.
Chua N.G.
Lim T.-P. 
Teo J.Q.-M.
Lee W.
Kurup A. 
Koh T.-H. 
Tan T.-T. 
Kwa A.L. 
Keywords: antibiotic resistance
bloodstream infection
clinical feature
controlled study
drug screening
drug selectivity
extensively drug resistant gram negative bacteria
feasibility study
Gram negative bacterium
in vitro antibiotic combination testing
outcome assessment
process optimization
retrospective study
combination drug therapy
dose response
drug effects
Gram-Negative Bacterial Infections
hospital mortality
microbial sensitivity test
middle aged
multidrug resistance
prospective study
translational research
antiinfective agent
Anti-Bacterial Agents
Dose-Response Relationship, Drug
Drug Resistance, Multiple, Bacterial
Drug Therapy, Combination
Gram-Negative Bacterial Infections
Hospital Mortality
Microbial Sensitivity Tests
Middle Aged
Prospective Studies
Translational Medical Research
Issue Date: 2016
Publisher: Public Library of Science
Citation: Cai Y., Chua N.G., Lim T.-P., Teo J.Q.-M., Lee W., Kurup A., Koh T.-H., Tan T.-T., Kwa A.L. (2016). From Bench-Top to Bedside: A prospective In vitro Antibiotic Combination Testing (iACT) service to guide the selection of rationally optimized antimicrobial combinations against Extensively Drug Resistant (XDR) Gram Negative Bacteria (GNB). PLoS ONE 11 (7) : e0158740. ScholarBank@NUS Repository.
Abstract: Introduction Combination therapy is increasingly utilized against extensively-drug resistant (XDR) Gram negative bacteria (GNB). However, choosing a combination can be problematic as effective combinations are often strain-specific. An in vitro antibiotic combination testing (iACT) service, aimed to guide the selection of individualized and rationally optimized combination regimens within 48 hours, was developed. We described the role and feasibility of the iACT service in guiding individualized antibiotic combination selection in patients with XDR-GNB infections. Methods A retrospective case review was performed in two Singapore hospitals from April 2009-June 2014. All patients with XDR-GNB and antibiotic regimen guided by iACT for clinical management were included. The feasibility and role of the prospective iACT service was evaluated. The following patient outcomes were described: (i) 30-day in-hospital all-cause and infection-related mortality, (ii) clinical response, and (iii) microbiological eradication in patients with bloodstream infections. Results From 2009-2014, the iACT service was requested by Infectious Disease physicians for 39 cases (20 P. aeruginosa, 13A. baumannii and 6 K. pneumoniae). Bloodstream infection was the predominant infection (36%), followed by pneumonia (31%). All iACT recommendations were provided within 48h from request for the service. Prior to iACT-guided therapy, most cases were prescribed combination antibiotics empirically (90%). Changes in the empiric antibiotic regimens were recommended in 21 (54%) cases; in 14 (36%) cases, changes were recommended as the empiric regimens were found to be non-bactericidal in vitro. In 7 (18%) cases, the number of antibiotics used in combination empirically was reduced by the iACT service. Overall, low 30-day infection-related mortality (15%) and high clinical response (82%) were observed. Microbiological eradication was observed in 79% of all bloodstream infections. Conclusions The iACT service can be feasibly employed to guide the timely selection of rationally optimized combination regimens, and played a role in reducing indiscreet antibiotic use. © 2016 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0158740
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