Aminoglycoside Activity Against Carbapenem-Resistant Infections

Aminoglycosides are a class of rapidly bactericidal antibiotics that target the bacterial ribosome, disrupting protein synthesis. Despite historical concerns over nephrotoxicity and ototoxicity, renewed interest has emerged in their use against carbapenem-resistant Gram-negative pathogens. Resistance to carbapenems often coexists with mechanisms such as extended-spectrum β-lactamases and metallo-β-lactamases, severely limiting therapeutic options. Aminoglycosides retain activity against many such organisms, especially when used in optimised dosing regimens or in combination with β-lactam agents. Next-generation semisynthetic aminoglycosides, notably plazomicin, have been engineered to evade common enzymatic inactivation pathways and show potent activity against carbapenemase-producing Enterobacterales. Combination therapy with broad-spectrum β-lactams and aminoglycosides has demonstrated synergistic killing of metallo-β-lactamase producers in vitro, offering potential for clinical application. Ongoing pharmacokinetic and epidemiological studies continue to refine dosing strategies to maximise efficacy while minimising toxicity.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Aminoglycoside Activity Against Carbapenem-Resistant Infections publication trend

The graph below shows the total number of articles in aminoglycoside activity against carbapenem-resistant infections across all publications each year (not limited to Nature Index journals).

Technical terms

Aminoglycosides: A class of antibiotics that bind the 30S subunit of the bacterial ribosome, preventing protein synthesis.

Carbapenem-resistant Enterobacteriaceae (CRE): Gram-negative bacteria that produce enzymes (carbapenemases) rendering carbapenems ineffective.

Metallo-β-lactamase (MBL): A type of carbapenemase requiring zinc ions to hydrolyse β-lactam antibiotics, including carbapenems.

Aminoglycoside-modifying enzymes (AMEs): Bacterial enzymes that chemically modify aminoglycosides and inactivate their antibacterial activity.

Minimum inhibitory concentration (MIC): The lowest concentration of an antibiotic that prevents visible growth of a bacterium in vitro.

16S rRNA methylase: An enzyme that methylates the aminoglycoside binding site on the bacterial ribosome, conferring high-level resistance.

References

1. Aminoglycosides for the Treatment of Severe Infection Due to Resistant Gram-Negative Pathogens. Antibiotics (2023).
2. Comparing the activity of broad-spectrum beta-lactams in combination with aminoglycosides against VIM-producing Enterobacteriaceae. Microbiology Spectrum (2024).
3. Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance. BMC Infectious Diseases (2019).