Antimicrobial Synergy in Multidrug-Resistant Acinetobacter baumannii
Summary
Acinetobacter baumannii has emerged as a formidable nosocomial pathogen owing to its capacity to acquire resistance to multiple antibiotic classes, including carbapenems, polymyxins and tetracyclines. The paucity of novel agents against these strains has driven interest in combination regimens that exploit synergistic interactions to restore bactericidal activity and minimise resistance emergence. Synergy may arise from enhanced drug uptake, sequential disruption of bacterial defences or complementary inhibition of vital pathways. Preclinical investigations span checkerboard and time-kill assays, pharmacokinetic/pharmacodynamic modelling and animal infection models, revealing promising pairings such as colistin with membrane-active or cell-wall inhibitors. Advances in whole-genome sequencing and resistance mechanism profiling inform rational selection of partners, while in vivo studies validate dose schedules that achieve therapeutic exposures without undue toxicity. An integrated approach, marrying genomic insight with robust in vitro and in vivo evaluation, underpins the path towards optimised synergistic therapies against multidrug-resistant A. baumannii.
Research from Nature Portfolio
Recent studies in a murine pneumonia model demonstrated that colistin combined with either fosfomycin or minocycline markedly reduced lung bacterial burden compared with monotherapy. Both combinations achieved bactericidal and synergistic effects at 24 and 48 hours, with significant reductions in colony counts relative to the most active single agent. These findings validate the in vitro synergy observed in checkerboard and time-kill experiments, support achievable pharmacodynamic targets in vivo and underscore the potential of these regimens as therapeutic options for carbapenem-resistant A. baumannii pneumonia.
Antimicrobial Synergy in Multidrug-Resistant Acinetobacter baumannii publication trend
The graph below shows the total number of articles in antimicrobial synergy in multidrug-resistant acinetobacter baumannii across all publications each year (not limited to Nature Index journals).
Technical terms
Minimum inhibitory concentration (MIC): The lowest concentration of an antimicrobial that prevents visible growth of a microorganism in vitro.
Fractional inhibitory concentration index (FICI): A metric calculated in checkerboard assays to quantify the extent of interaction between two antimicrobials (synergy, additivity or antagonism).
Checkerboard assay: An in vitro method that assesses antimicrobial combinations by testing serial dilutions of two drugs in a grid format to determine FICI values.
Time-kill assay: A dynamic in vitro experiment measuring bacterial viability over time in the presence of antimicrobial agents alone or in combination.
Synergy: A pharmacodynamic interaction in which the combined effect of two drugs exceeds the sum of their individual effects.
Multidrug-resistant (MDR): Refers to bacterial strains non-susceptible to at least one agent in three or more antimicrobial categories.
References
- In Vitro Synergistic Activity of Antimicrobial Combinations against Carbapenem- and Colistin-Resistant Acinetobacter baumannii and Klebsiella pneumoniae. Antibiotics (2023).
- Exploring Synergistic Combinations in Extended and Pan-Drug Resistant (XDR and PDR) Whole Genome Sequenced Acinetobacter baumannii. Microorganisms (2023).
- In vivo efficacy of combination of colistin with fosfomycin or minocycline in a mouse model of multidrug-resistant Acinetobacter baumannii pneumonia. Scientific Reports (2019).
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