Antibiotic Synergism in Gram-Negative Infections
Summary
Antibiotic synergism refers to the situation in which two or more antimicrobial agents, when used in combination, produce a bactericidal effect greater than the sum of their individual activities. This strategy has become pivotal in tackling Gram-negative pathogens, notably those harbouring extended-spectrum β-lactamases, carbapenemases or multidrug-resistance mechanisms. Synergistic pairings may restore activity against resistant strains, suppress the emergence of further resistance and permit dose reduction to limit toxicity. Mechanisms underpinning synergy include complementary target inhibition (for example, cell-wall synthesis blockade by a β-lactam alongside protein synthesis disruption by an aminoglycoside), enzyme inhibition (as with β-lactamase inhibitors) and enhanced membrane permeability (seen when polymyxins disrupt outer membranes to facilitate penetration of co-administered drugs). Clinically, synergy has been applied to life-threatening infections caused by Pseudomonas aeruginosa, Acinetobacter baumannii and carbapenem-resistant Enterobacteriaceae. By integrating pharmacokinetic/pharmacodynamic principles with in vitro and in vivo models, recent efforts strive to optimise combination regimens, refine dosing schedules and translate synergistic interactions into improved patient outcomes.
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Antibiotic Synergism in Gram-Negative Infections publication trend
The graph below shows the total number of articles in antibiotic synergism in gram-negative infections across all publications each year (not limited to Nature Index journals).
Technical terms
Synergism: Enhanced antimicrobial effect when two or more agents are combined, exceeding individual activities.
β-lactamase inhibitor: Compound that binds and inactivates β-lactam‐hydrolysing enzymes, restoring β-lactam efficacy.
Minimum inhibitory concentration (MIC): Lowest antibiotic concentration that prevents visible bacterial growth in vitro.
Time-kill assay: Laboratory method quantifying bacterial viability over time in presence of antibiotics to assess synergy.
Pharmacokinetics/pharmacodynamics (PK/PD): The relationship between drug concentrations over time (PK) and their antimicrobial effects (PD).
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