Comparison of methods for detection of in vitro synergy in multidrug-resistant Gram-negative bacteria

Abstract

The use of combined antibiotic therapy has become an option for infections caused by multidrug-resistant (MDR) bacteria. Time-kill (TK) assay is considered the gold standard method for evaluation of in vitro synergy; moreover, it is time-consuming and an expensive method. The purpose of this study was to evaluate in vitro synergy using the disk diffusion method through disk approximation (DA), and agar gradient diffusion method by MIC:MIC ratio, as both can be used routinely in clinical microbiology laboratories. Sixty-two MDR Gram-negative clinical isolates (28 Pseudomonas aeruginosa , 20 Acinetobacter baumannii and 14 Serratia marcescens ) were submitted to TK, DA, and MIC:MIC ratio synergy methods. Overall, the agreement between the DA and TK assays ranged from 20 to 93%. As the isolates of A. baumannii showed variable results of synergism according to TK, the calculated agreement was statistically significant in this species against fosfomycin with meropenem, including colistin-resistant isolates. MIC: MIC ratio method showed agreement range from 35 to 71% with TK assays. The kappa test showed a good agreement for the combination of colistin with amikacin (K = 0.58; P = 0.04) among the colistin-resistant A. baumannii isolates. The DA and MIC:MIC ratio methods are easier to perform and may be a more viable tool for clinical microbiology laboratories.

Antibacterial activity and carbapenem re‐sensitizing ability of 1,10‐phenanthroline‐5,6‐dione and its metal complexes against KPC‐producingKlebsiella pneumoniaeclinical strains

“…The current findings provide strong evidence of the beneficial effects rendered by drug combinations, since a time‐kill assay is considered to be the gold standard for such evaluations as it is known to produce consistent results across different studies (Gaudereto et al . 2020).…”