Isothermal microcalorimetry versus checkerboard assay to evaluate in vitro synergism of meropenem-amikacin and meropenem-colistin combinations against multidrug-resistant Gram-negative pathogens

Elsevier

Available online 28 August 2022, 106668

International Journal of Antimicrobial AgentsHighlights•

Microcalorimetry is an accurate method to assess antimicrobial synergism

Microcalorimetry is faster than standard broth microdilution assays

Synergistic activity of meropenem-amikacin and -colistin against Gram-negatives

AbstractObjectives

: To evaluate the activity of meropenem-amikacin and meropenem-colistin combinations with checkerboard broth microdilution (CKBM) compared to isothermal microcalorimetry (ITMC) assays against a multicentric collection of multidrug-resistant Gram-negative (MDR-GN) clinical isolates, to compare the Fractional inhibitory concentration index (FICI) and time to results of CKBM and ITMC assays.

Methods

: A collection of 333 MDR-GNs showing reduced susceptibility to meropenem (121 Klebsiella pneumoniae, 14 Escherichia coli, 130 Pseudomonas aeruginosa and 68 Acinetobacter baumannii) isolated from different centres (Florence, Madrid, Rotterdam, and Stockholm) was included in the study. The antimicrobial activity of selected combinations was evaluated with CKBM and ITMC. FICI results were interpreted as synergistic/additive and indifferent for values ≤0.5/0.5<x≤1 and >1, respectively. WGS data in a subset of strains was used to evaluate their clonality.

Results

: A total of 254 and 286 strains were tested with meropenem-colistin and meropenem-amikacin combinations with ITMC and CKBM, respectively. Synergism/additive effects were observed with 46 strains (20 K. pneumoniae, 4 E. coli, 22 P. aeruginosa) and 20 strains (3 K. pneumoniae, 11 P. aeruginosa and 6 A. baumannii) with meropenem-amikacin and meropenem-colistin combination, respectively, with CKBM. ITMC showed a good concordance with CKBM with 89.5% and 92.2% of cases interpreted within the same FICI category for meropenem-amikacin and meropenem-colistin combinations, respectively. Most of the synergism/additivity effects were detected within 6 hours by ITMC.

Conclusions

: ITMC showed a very good concordance with CKBM against a large collection of MDR-GN and could be implemented for the rapid evaluation of in vitro activity of antimicrobial combinations.

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