Open AccessFrom 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)
Author(s) -
Yiying Cai,
Nathalie Grace Sy Chua,
Tze-Peng Lim,
Jin Yao Teo,
Winnie Lee,
Asok Kurup,
Tse-Hsien Koh,
Thuan-Tong Tan,
Andrea Lay-Hoon Kwa
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0158740
Subject(s) - antibiotics , medicine , pneumonia , combination therapy , empiric therapy , regimen , antibiotic resistance , intensive care medicine , microbiology and biotechnology , biology
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 ( i ACT) 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 i ACT 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 i ACT for clinical management were included. The feasibility and role of the prospective i ACT 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 i ACT service was requested by Infectious Disease physicians for 39 cases (20 P . aeruginosa , 13 A . baumannii and 6 K . pneumoniae ). Bloodstream infection was the predominant infection (36%), followed by pneumonia (31%). All i ACT recommendations were provided within 48h from request for the service. Prior to i ACT-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 i ACT 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 i ACT service can be feasibly employed to guide the timely selection of rationally optimized combination regimens, and played a role in reducing indiscreet antibiotic use.