Screening for synergistic activity of antimicrobial combinations against carbapenem-resistant Enterobacteriaceae using inkjet printer-based technology

The Journal of Antimicrobial Chemotherapy
Thea Brennan-KrohnJames E Kirby

Abstract

Synergistic combination antimicrobial therapy may provide new options for treatment of MDR infections. However, comprehensive in vitro synergy data are limited and facile methods to perform synergy testing in a clinically actionable time frame are unavailable. To systematically investigate a broad range of antibiotic combinations for evidence of synergistic activity against a collection of carbapenem-resistant Enterobacteriaceae (CRE) isolates. We made use of an automated method for chequerboard array synergy testing based on inkjet printer technology in the HP D300 digital dispenser to test 56 pairwise antimicrobial combinations of meropenem, aztreonam, cefepime, colistin, gentamicin, levofloxacin, chloramphenicol, fosfomycin, trimethoprim/sulfamethoxazole, minocycline and rifampicin, as well as the double carbapenem combination of meropenem and ertapenem. In a screening procedure, we tested these combinations against four CRE strains and identified nine antibiotic combinations that showed potential clinically relevant synergy. In confirmatory testing using 10 CRE strains, six combinations demonstrated clinically relevant synergy with both antimicrobials at the minimum fractional inhibitory concentration (FICI-MIN) in the susc...Continue Reading

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Citations

Aug 1, 2018·Antimicrobial Agents and Chemotherapy·Thea Brennan-KrohnJames E Kirby
Jul 17, 2019·Antimicrobial Agents and Chemotherapy·Thea Brennan-Krohn, James E Kirby
Oct 1, 2019·Current Opinion in Infectious Diseases·Matteo BassettiDaniele Roberto Giacobbe
Feb 14, 2020·Journal of Clinical Microbiology·Eric RansomMaria Karlsson
Aug 25, 2020·Advanced Intelligent Systems·Dean Ho
Nov 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·Katelyn E Zulauf, James E Kirby

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