Abstract
BackgroundThe use of combined antibiotic therapy has become an option for infections caused by multidrug-resistant (MDR) bacteria. The time-kill (TK) assay is considered the gold standard method for the evaluation of in vitro synergy, but it is a time-consuming and expensive method.The purpose of this study was to evaluate two methods for testing in vitro antimicrobial combinations: the disk diffusion method through disk approximation (DA) and the agar gradient diffusion method via the MIC:MIC ratio. The TK assay was included as the gold standard. MDR Gram-negative clinical isolates (n = 62; 28 Pseudomonas aeruginosa, 20 Acinetobacter baumannii, and 14 Serratia marcescens) were submitted to TK, DA, and MIC:MIC ratio synergy methods.ResultsOverall, the agreement between the DA and TK assays ranged from 20 to 93%. The isolates of A. baumannii showed variable results of synergism according to TK, and the calculated agreement was statistically significant in this species against fosfomycin with meropenem including colistin-resistant isolates. The MIC:MIC ratiometric agreed from 35 to 71% with TK assays. The kappa test showed good agreement for the combination of colistin with amikacin (K = 0.58; P = 0.04) among the colistin-resistant A. baumannii isolates.ConclusionsThe DA and MIC:MIC ratiometric methods are easier to perform and might be a more viable tool for clinical microbiology laboratories.
Highlights
The use of combined antibiotic therapy has become an option for infections caused by multidrugresistant (MDR) bacteria
All A. baumannii isolates were resistant to meropenem (MIC ranging from 16 to 128 μg/mL) and fosfomycin (MIC ranged from 64 to 128 μg/mL); 19/20 (95%) were resistant to amikacin
Pseudomonas aeruginosa isolates were susceptible to colistin and resistant to meropenem (MIC ranged from 16 to 512 μg/mL)
Summary
The use of combined antibiotic therapy has become an option for infections caused by multidrugresistant (MDR) bacteria. The time-kill (TK) assay is considered the gold standard method for the evaluation of in vitro synergy, but it is a time-consuming and expensive method. The purpose of this study was to evaluate two methods for testing in vitro antimicrobial combinations: the disk diffusion method through disk approximation (DA) and the agar gradient diffusion method via the MIC:MIC ratio. MDR Gram-negative clinical isolates (n = 62; 28 Pseudomonas aeruginosa, 20 Acinetobacter baumannii, and 14 Serratia marcescens) were submitted to TK, DA, and MIC:MIC ratio synergy methods. Combined antimicrobial therapy is a promising strategy for treating infections caused by MDR pathogens and can further extend antimicrobial lifespan and minimize the evolution of resistance [3, 4]. Despite the importance of in vitro testing, methods that are accessible to Gaudereto et al BMC Microbiology (2020) 20:97 clinical microbiology laboratories for testing synergism in a clinically actionable period are not available
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