Critical Appraisal of Animal Models for Antibiotic Toxicity
Adorjan Aszalos in Modern Analysis of Antibiotics, 2020
Aminoglycosides represent an important class of antibiotics used clinically to treat gram-negative infections, often life-threatening in nature. This class includes such compounds as neomycin, gentamicin, tobramycin, amikacin, kanamycin, and netilmicin. Structurally, they consist of amino sugars linked to another moiety by a glycoside bond. Aminoglycoside-induced nephrotoxicity is well-documented in the human, with incidences ranging from 2 to 36% of patients receiving the drug [11–15]. In fact, aminoglycosides are the leading cause of antibiotic-induced acute renal failure [16]. Proximal tubule necrosis is a consistent feature of aminoglycoside nephrotoxicity in humans and experimental animals, primarily involving the pars convoluta of the proximal nephron [17–19].
Mechanisms of Chemically Induced Glomerular Injury
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
Aminoglycosides are poly cationic antibiotics used to control Gram-negative bacterial infections. Although proximal tubular necrosis is the major renal consequence of aminoglycoside nephrotoxicity, decreased GFR is the major cause for morbidity. While clinical manifestations such as enzymuria occur early in aminoglycoside-induced tubular damage,40 dysfunction of glomerular filtration occurs later in the clinical course of toxicity.41,42 GFR was reduced by aminoglycoside treatment in whole animal and isolated perfused rat kidney (Figures 5 and 6) as it was also shown in various reports.43–45 Since the decrease in GFR and SNGFR is dependent on the rate of glomerular plasma flow, the net transcapillary hydraulic pressure and the plasma oncotic pressure, as well as Kf,30,47 correlations between glomerular functional impairment and ultrastructural changes of the glomerulus were investigated.43,44,48
Streptomyces: A Potential Source of Natural Antimicrobial Drug Leads
Mahendra Rai, Chistiane M. Feitosa in Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Due to their broad range of action and potency, aminoglycosides are useful antibiotics. They are Actinomycetes-derived natural or hemi-synthetic heterosides. Aminoglycosides work by preventing bacteria from making proteins. They were started in 1944 with the isolation of streptomycin from Streptomyces griseus (Krause et al. 2016). It continues releasing a sequence of milestone compounds that have become a cornerstone in antibacterial chemotherapy. Additionally, aminoglycoside antibiotics share several characteristics due to their chemical similarity, including a broad antibacterial spectrum, partial or complete cross-resistance, potentiation of their bactericidal action in a slightly alkaline medium, poor gastrointestinal absorption, and weak glomerular filtration and ototoxicity. The diffusion potential of aminoglycosides into bone tissue is moderate.
Systematic review on activity of liposomal encapsulated antioxidant, antibiotics, and antiviral agents
Published in Journal of Liposome Research, 2022
Reshna K. R, Preetha Balakrishnan, Sreerag Gopi
Aminoglycosides are bactericidal antibiotics with a broad spectrum of activity which is primarily for infections caused by Gram-negative organisms. Gentamicin, amikacin, tobramycin, neomycin, and streptomycin are examples of aminoglycosides. Amikacin encapsulated in liposomes has recently begun to be tested in clinical trials. Aminoglycosides are being liposome-encapsulated to improve their therapeutic index. This is accomplished by boosting aminoglycoside concentrations at the site of infection and/or decreasing the toxicity of these medicines. To differentiate between the methods, three approaches can be distinguished: the use of conventional liposomes as a depot formulation for local drug administration; the targeting of (relatively) short circulating conventional liposomes to cells of the mononuclear phagocyte system (MPS) for the treatment of intracellular bacterial infections; and the targeting of long-circulating conventional liposomes to infectious foci located outside the MPS. By encapsulating aminoglycosides in liposomes, more of these antibiotics can be included in the therapeutic index. Liposomes may act as a reservoir for therapeutic medication concentrations at the infection site. This local administration could help affected tissues like the eye, wounds, and lungs (Raymond and Woudenberg 2001).
Impact of chronic medications in the perioperative period: mechanisms of action and adverse drug effects (Part I)
Published in Postgraduate Medicine, 2021
Ofelia Loani Elvir-Lazo, Paul F White, Hillenn Cruz Eng, Firuz Yumul, Raissa Chua, Roya Yumul
Aminoglycosides inhibit bacterial protein synthesis by binding to the 16S rRNA component of the 30S ribosome subunit [56]. Beta-lactams (e.g. penicillins, cephalosporins, and carbapenems) and glycopeptides (e.g. vancomycin) interfere with specific steps in bacterial cell wall biosynthesis, resulting in cell lysis. Beta-lactams block the cross-linking of peptidoglycan units by inhibiting the peptide bond formation reaction catalyzed by penicillin-binding proteins (PBP). Vancomycin achieves the same inhibition by blocking the transglucosylase and PBP activity [56]. Fluoroquinolones inhibit DNA synthesis by targeting the enzyme DNA gyrase, which is a topoisomerase, which prevents bacteria from replicating its DNA. Cyclic lipopeptides (daptomycin) also inhibit cell wall synthesis by altering the structural integrity of bacteria by inserting themselves into the cell membrane and inducing membrane depolarization [57]. Nitroimidazoles (metronidazole) inhibits protein synthesis by forming cytotoxic nitro-radical anions that result in DNA strand breakage [58].
Proteomics approach to understand bacterial antibiotic resistance strategies
Published in Expert Review of Proteomics, 2019
Bo Peng, Hui Li, Xuanxian Peng
Aminoglycoside antibiotics have continued to prove their clinical value in fighting infections with a broad spectrum of activity ranging from aerobic Gram-negative bacteria to mycobacteria. The commonly used aminoglycosides include gentamicin, kanamycin, amikacin, netilmicin, neomycin, framycetin, streptomycin, and plazomicin. These antibiotics share a common inositol moiety substituted with two amino or guanidino groups and with one or more sugars or aminosugars in the structure. Aminoglycosides hijack the function of bacterial ribosomes to inhibit protein synthesis through direct binding to the A- translational site of the 16S rRNA of the 30S ribosomal subunit. This binding event causes increased misreading of the mRNA and generates unfolded proteins. The accumulation of dysfunctional proteins induces a stress response and eventual death. Resistance to aminoglycosides is based on the following mechanisms: enzymatic modification and inactivation of the aminoglycosides by aminoglycoside acetyltransferases, nucleotidyltransferases, or phosphotransferases; decreased permeability; increased drug efflux; and modifications of the 30S ribosomal subunit that interfere with binding of the aminoglycosides [38].
Related Knowledge Centers
- Amino Sugar
- Antibiotic
- Bacilli
- Bacteriology
- Streptomycin
- Glycoside
- Medicinal Chemistry
- Gram-Negative Bacteria
- Medication
- Sugar