Genetic Characterization of Multidrug-Resistant Acinetobacter baumannii and Synergy Assessment of Antimicrobial Combinations

<b>Background/Objectives</b>: <i>A. baumannii</i> is a prominent nosocomial pathogen due to its drug-resistant phenotype, representing a public health problem. In this study, the aim was to determine the effect of different antimicrobial combinations against selected multidrug-resistant (MDR) or extensive drug-resistant (XDR) isolates of <i>A. baumannii</i>. <b>Methods</b>: MDR or XDR <i>A. baumannii</i> isolates were characterized by assessing genes associated with drug resistance, efflux pumps, porin expression, and biofilm formation. The activities of antimicrobial combinations including tigecycline, ampicillin/sulbactam, meropenem, levofloxacin, and colistin were evaluated using checkerboard and time-to-kill assays on isolates with different susceptibility profiles and genetic characteristics. <b>Results</b>: Genetic characterization of MDR/XDR strains (<i>n</i> = 100) included analysis of OXA-24/40 gene carbapenemase (98%), genes encoding aminoglycoside-modifying enzymes (44%), and <i>parC</i> gene mutations (10%). AdeIJK, AdeABC, and AdeFGH efflux pumps were overexpressed in 17-34% of isolates. Omp33-36, OmpA, and CarO membrane porins were under-expressed in 50-76% of isolates; CarO was overexpressed in 22% of isolates. Isolates showed low biofilm production (11%). Synergistic activity was observed with levofloxacin-ampicillin/sulbactam and meropenem-colistin, which were able to inhibit bacterial growth. <b>Conclusions</b>: Genetic characteristics of <i>A. baumannii</i> were highly variable among the strains. Synergistic activity was observed with meropenem-colistin and levofloxacin-ampicillin/sulbactam combinations in the checkerboard method, but not in the time-to-kill assays. These discrepancies among both methods indicate that further studies are needed to determine the best therapeutic combination for treating infections by <i>A. baumannii</i>.

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Publication Details

Journal
Antibiotics
Published
2024-11-13
DOI
https://doi.org/10.3390/antibiotics13111079
Citations
2
Primary Topic
Antibiotic Resistance in Bacteria
Type
article
Field-Weighted Citation Impact
0.34

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article

Genetic Characterization of Multidrug-Resistant Acinetobacter baumannii and Synergy Assessment of Antimicrobial Combinations

Juan Francisco Contreras‐Cordero, Paola Bocanegra‐Ibarias, Adrián Camacho-Ortíz, Samantha Flores-Treviño et al.
2 citations
Antibiotics
Antibiotic Resistance in Bacteria
0.34
article

Genetic Characterization of Multidrug-Resistant Acinetobacter baumannii and Synergy Assessment of Antimicrobial Combinations

Juan Francisco Contreras‐Cordero, Paola Bocanegra‐Ibarias, Adrián Camacho-Ortíz, Samantha Flores-Treviño, Aurora Luna-De-Alba
article en
2 citations

Abstract

<b>Background/Objectives</b>: <i>A. baumannii</i> is a prominent nosocomial pathogen due to its drug-resistant phenotype, representing a public health problem. In this study, the aim was to determine the effect of different antimicrobial combinations against selected multidrug-resistant (MDR) or extensive drug-resistant (XDR) isolates of <i>A. baumannii</i>. <b>Methods</b>: MDR or XDR <i>A. baumannii</i> isolates were characterized by assessing genes associated with drug resistance, efflux pumps, porin expression, and biofilm formation. The activities of antimicrobial combinations including tigecycline, ampicillin/sulbactam, meropenem, levofloxacin, and colistin were evaluated using checkerboard and time-to-kill assays on isolates with different susceptibility profiles and genetic characteristics. <b>Results</b>: Genetic characterization of MDR/XDR strains (<i>n</i> = 100) included analysis of OXA-24/40 gene carbapenemase (98%), genes encoding aminoglycoside-modifying enzymes (44%), and <i>parC</i> gene mutations (10%). AdeIJK, AdeABC, and AdeFGH efflux pumps were overexpressed in 17-34% of isolates. Omp33-36, OmpA, and CarO membrane porins were under-expressed in 50-76% of isolates; CarO was overexpressed in 22% of isolates. Isolates showed low biofilm production (11%). Synergistic activity was observed with levofloxacin-ampicillin/sulbactam and meropenem-colistin, which were able to inhibit bacterial growth. <b>Conclusions</b>: Genetic characteristics of <i>A. baumannii</i> were highly variable among the strains. Synergistic activity was observed with meropenem-colistin and levofloxacin-ampicillin/sulbactam combinations in the checkerboard method, but not in the time-to-kill assays. These discrepancies among both methods indicate that further studies are needed to determine the best therapeutic combination for treating infections by <i>A. baumannii</i>.

AntibioticsVol. 13(11)
Universidad Autónoma de Nuevo León (MX)
Consejo Nacional de Ciencia y Tecnología
Openalex Percentile: Top 46%
Antibiotic Resistance in Bacteria
0.34
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