Antimicrobial Therapy for Multidrug-Resistant Gram-Negative Infections
Summary
Multidrug-resistant Gram-negative bacteria pose a mounting challenge across clinical settings worldwide, driven by the proliferation of β-lactamases, carbapenemases and efflux mechanisms that undermine traditional antibiotic classes. Treatment now centres on novel β-lactam/β-lactamase inhibitor combinations such as ceftazidime–avibactam, ceftolozane–tazobactam and meropenem–vaborbactam, alongside emerging siderophore cephalosporins like cefiderocol. Polymyxins and fosfomycin retain value against carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, albeit hampered by toxicity concerns. Optimising dosing through pharmacokinetic/pharmacodynamic modelling and therapeutic drug monitoring is crucial to maintain effective drug exposures and prevent resistance amplification. In parallel, stewardship programmes and rapid diagnostic platforms guide early targeted therapy, reducing reliance on broad-spectrum empiric regimens. The evolving landscape demands integration of global surveillance data, local resistance profiles and clinical outcome studies to refine algorithms for severe infections such as ventilated hospital-acquired pneumonia, complicated urinary tract infections and neonatal sepsis. Collaborative efforts between clinicians, microbiologists and pharmacologists are essential to preserve the utility of existing agents while advancing next-generation therapies.
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Antimicrobial Therapy for Multidrug-Resistant Gram-Negative Infections publication trend
The graph below shows the total number of articles in antimicrobial therapy for multidrug-resistant gram-negative infections across all publications each year (not limited to Nature Index journals).
Technical terms
Multidrug-Resistant (MDR): Bacteria resistant to at least one agent in three or more antimicrobial categories.
Gram-Negative Bacteria: Organisms characterised by an outer membrane that often contains porins and efflux pumps, making them inherently less permeable to many antibiotics.
β-Lactamase Inhibitor: A compound that binds to and deactivates β-lactamases, enzymes that hydrolyse β-lactam antibiotics.
Carbapenemase: A subclass of β-lactamases capable of hydrolysing carbapenems, often conferring extensive resistance.
Minimum Inhibitory Concentration (MIC): The lowest antimicrobial concentration that prevents visible bacterial growth in vitro.
Pharmacokinetics (PK): The study of drug absorption, distribution, metabolism and excretion over time.
Pharmacodynamics (PD): The relationship between drug concentration and its antimicrobial effect, often expressed as time- or concentration-dependent killing.
References
- Outcomes in participants with ventilated nosocomial pneumonia and organ failure treated with ceftolozane/tazobactam versus meropenem: a subset analysis of the phase 3, randomized, controlled ASPECT-NP trial. Annals of Intensive Care (2023).
- New Antimicrobials for the Treatment of Neonatal Sepsis Caused by Multi-Drug-Resistant Bacteria: A Systematic Review. Antibiotics (2023).
- Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: A Multicenter Study. Open Forum Infectious Diseases (2018).
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