Aminoglycosides for the Treatment of Severe Infection Due to Resistant Gram-Negative Pathogens

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2023 May 27

PMID 37237763

Authors

Michael Thy

Jean-Francois Timsit

Etienne de Montmollin

Affiliations

Soon will be listed here.

Abstract

Aminoglycosides are a family of rapidly bactericidal antibiotics that often remain active against resistant Gram-negative bacterial infections. Over the past decade, their use in critically ill patients has been refined; however, due to their renal and cochleovestibular toxicity, their indications in the treatment of sepsis and septic shock have been gradually reduced. This article reviews the spectrum of activity, mode of action, and methods for optimizing the efficacy of aminoglycosides. We discuss the current indications for aminoglycosides, with an emphasis on multidrug-resistant Gram-negative bacteria, such as extended-spectrum β-lactamase-producing , carbapenemase-producing Enterobacterales, multidrug-resistant , and carbapenem-resistant . Additionally, we review the evidence for the use of nebulized aminoglycosides.

Citing Articles

Recent advances and challenges in metal-based antimicrobial materials: a review of strategies to combat antibiotic resistance.

Zhu C, Diao Z, Yang Y, Liao J, Wang C, Li Y J Nanobiotechnology. 2025; 23(1):193.

PMID: 40059157 PMC: 11892188. DOI: 10.1186/s12951-025-03249-6.

Bibliometric analysis of global research on the clinical applications of aminoglycoside antibiotics: improving efficacy and decreasing risk.

Zhao T, Chen N, Zhang M, Lin L, Lin B, Fang Y Front Microbiol. 2025; 16:1532231.

PMID: 40046300 PMC: 11880276. DOI: 10.3389/fmicb.2025.1532231.

Preserving the antimicrobial arsenal: exploring alternatives to carbapenems in ESBL battles within the southeast of Ireland.

Ali S, Tobin A, Lapthorne S, Collison M, Murphy D, Chan G J Med Microbiol. 2025; 74(2).

PMID: 39907141 PMC: 11796091. DOI: 10.1099/jmm.0.001955.

Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies.

Rouby J, Xia J, Dhanani J, Li Bassi G, Monsel A, Torres A J Intensive Med. 2025; 5(1):12-22.

PMID: 39872832 PMC: 11764037. DOI: 10.1016/j.jointm.2024.07.006.

Effectiveness of a Novel Liposomal Methylglyoxal-Tobramycin Formulation in Reducing Biofilm Formation and Bacterial Adhesion.

Alluhaim W, Alkhulaifi M, Alzahrani R, Alrfaei B, Yassin A, Alghoribi M Antibiotics (Basel). 2025; 14(1).

PMID: 39858289 PMC: 11763214. DOI: 10.3390/antibiotics14010003.

References

Roberts J, Lipman J . Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009; 37(3):840-51. DOI: 10.1097/CCM.0b013e3181961bff. View

Durante-Mangoni E, Signoriello G, Andini R, Mattei A, De Cristoforo M, Murino P . Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin Infect Dis. 2013; 57(3):349-58. DOI: 10.1093/cid/cit253. View

Marcus R, Paul M, Elphick H, Leibovici L . Clinical implications of β-lactam-aminoglycoside synergism: systematic review of randomised trials. Int J Antimicrob Agents. 2011; 37(6):491-503. DOI: 10.1016/j.ijantimicag.2010.11.029. View

Moore R, Lietman P, Smith C . Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987; 155(1):93-9. DOI: 10.1093/infdis/155.1.93. View

Barza M, Ioannidis J, Cappelleri J, Lau J . Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ. 1996; 312(7027):338-45. PMC: 2350289. DOI: 10.1136/bmj.312.7027.338. View

Sirijatuphat R, Thamlikitkul V . Preliminary study of colistin versus colistin plus fosfomycin for treatment of carbapenem-resistant Acinetobacter baumannii infections. Antimicrob Agents Chemother. 2014; 58(9):5598-601. PMC: 4135862. DOI: 10.1128/AAC.02435-13. View

Zusman O, Altunin S, Koppel F, Dishon Benattar Y, Gedik H, Paul M . Polymyxin monotherapy or in combination against carbapenem-resistant bacteria: systematic review and meta-analysis. J Antimicrob Chemother. 2016; 72(1):29-39. DOI: 10.1093/jac/dkw377. View

Roger C, Wallis S, Muller L, Saissi G, Lipman J, Lefrant J . Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy. Antimicrob Agents Chemother. 2016; 60(8):4901-9. PMC: 4958154. DOI: 10.1128/AAC.00828-16. View

Bliziotis I, Samonis G, Vardakas K, Chrysanthopoulou S, Falagas M . Effect of aminoglycoside and beta-lactam combination therapy versus beta-lactam monotherapy on the emergence of antimicrobial resistance: a meta-analysis of randomized, controlled trials. Clin Infect Dis. 2005; 41(2):149-58. DOI: 10.1086/430912. View

10.

Medeiros G, Rigatto M, Falci D, Zavascki A . Combination therapy with polymyxin B for carbapenemase-producing Klebsiella pneumoniae bloodstream infection. Int J Antimicrob Agents. 2019; 53(2):152-157. DOI: 10.1016/j.ijantimicag.2018.10.010. View

11.

Haidar G, Alkroud A, Cheng S, Churilla T, Churilla B, Shields R . Association between the Presence of Aminoglycoside-Modifying Enzymes and In Vitro Activity of Gentamicin, Tobramycin, Amikacin, and Plazomicin against Klebsiella pneumoniae Carbapenemase- and Extended-Spectrum-β-Lactamase-Producing Enterobacter.... Antimicrob Agents Chemother. 2016; 60(9):5208-14. PMC: 4997819. DOI: 10.1128/AAC.00869-16. View

12.

Cha M, Kang C, Kim S, Cho S, Ha Y, Wi Y . In vitro activities of 21 antimicrobial agents alone and in combination with aminoglycosides or fluoroquinolones against extended-spectrum-β-lactamase-producing Escherichia coli isolates causing bacteremia. Antimicrob Agents Chemother. 2015; 59(9):5834-7. PMC: 4538563. DOI: 10.1128/AAC.01121-15. View

13.

Johnston N, Mukhtar T, Wright G . Streptogramin antibiotics: mode of action and resistance. Curr Drug Targets. 2002; 3(4):335-44. DOI: 10.2174/1389450023347678. View

14.

Daikos G, Tsaousi S, Tzouvelekis L, Anyfantis I, Psichogiou M, Argyropoulou A . Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother. 2014; 58(4):2322-8. PMC: 4023796. DOI: 10.1128/AAC.02166-13. View

15.

Alevizakos M, Karanika S, Detsis M, Mylonakis E . Colonisation with extended-spectrum β-lactamase-producing Enterobacteriaceae and risk for infection among patients with solid or haematological malignancy: a systematic review and meta-analysis. Int J Antimicrob Agents. 2016; 48(6):647-654. DOI: 10.1016/j.ijantimicag.2016.08.021. View

16.

Hooton T, Blair A, Turck M, COUNTS G . Synergism at clinically attainable concentrations of aminoglycoside and beta-lactam antibiotics. Antimicrob Agents Chemother. 1984; 26(4):535-8. PMC: 179959. DOI: 10.1128/AAC.26.4.535. View

17.

Fishbain J, Peleg A . Treatment of Acinetobacter infections. Clin Infect Dis. 2010; 51(1):79-84. DOI: 10.1086/653120. View

18.

Gutierrez-Gutierrez B, Salamanca E, Cueto M, Hsueh P, Viale P, Pano-Pardo J . Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis. 2017; 17(7):726-734. DOI: 10.1016/S1473-3099(17)30228-1. View

19.

Makris D, Petinaki E, Tsolaki V, Manoulakas E, Mantzarlis K, Apostolopoulou O . Colistin versus Colistin Combined with Ampicillin-Sulbactam for Multiresistant Ventilator-associated Pneumonia Treatment: An Open-label Prospective Study. Indian J Crit Care Med. 2018; 22(2):67-77. PMC: 5842460. DOI: 10.4103/ijccm.IJCCM_302_17. View

20.

Degtyareva N, Gong C, Story S, Levinson N, Oyelere A, Green K . Antimicrobial Activity, AME Resistance, and A-Site Binding Studies of Anthraquinone-Neomycin Conjugates. ACS Infect Dis. 2017; 3(3):206-215. PMC: 5971063. DOI: 10.1021/acsinfecdis.6b00176. View