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Streptomyces: A Potential Source of Natural Antimicrobial Drug Leads
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Mahmoud A. Elfaky, Hanaa Nasr, Ilham Touiss, Mohamed L. Ashour
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.
Medicines in neonates
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Aminoglycosides need to enter the bacterial cell to inhibit protein synthesis. Uptake of aminoglycosides across the cytoplasmic membrane entails two energy-dependent phases, the former being driven by the transmembrane electrical potential. The second phase is stimulated by the binding of aminoglyco-side molecules to the ribosome process, which gives rise to the incorporation of defective proteins in the bacterial wall [48]. Their rapid killing effect is directly related to the maximum serum concentration (Cmax). A Cmax/MIC ratio of at least 8 is now recommended. The toxicity (nephro- and ototoxicity) of amino-glycosides is directly related to the total dose and the length of treatment [39]. It has been postulated that maximising Cmax should render these drugs more efficacious and could allow decreasing the length of treatment with the antibiotic combination (Table 2).
Investigational Nanomedicines in 2016: A Review of Nanotherapeutics Currently Undergoing Clinical Trials *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Joseph M. Caster, Artish N. Patel, Tian Zhang, Andrew Wang
Amikacin is a potent aminoglycoside antibiotic which is useful for the treatment of multidrug resistant Gram-negative bacteria as well as resistant strains of Mycobacterium tuberculosis [60, 61]. Like other aminoglycosides, significant toxicities include renal and neurologic toxicity. Amikacin is also limited by a relatively short half-life of 2–3 h [62]. Amikacin is generally reserved for the treatment of severe infections and requires frequent blood level monitoring. Arikayce is a liposomal formulation of amikacin designed as an inhaled medication for the treatment of drug resistant pseudomonal infections in patients with CF. Arikayce significantly improved the drug half-life and in a phase II trial, there was no notable difference in toxicity between the liposomal drug treatment and placebo [63]. The FDA has granted fast track designation to Arikace based on the results of a noninferiority phase 3 trial of 302 CF patients with chronic pseudamonal infections randomized to Arikace or inhaled tobramycin.
A nationwide evaluation of antibiotics consumption in Swedish intensive care units
Published in Infectious Diseases, 2022
Fredrik Sjövall, Morgan Edström, Sten Walther, Håkan Hanberger
Aminoglycosides are still widely used worldwide in combination therapy in patients with severe gram-negative sepsis [17]. They are still a recommended part of empirical antibiotic therapy in the most recent guidelines from the Society of Swedish infectious disease physicians (https://infektion.net/vardprogram/svar-sepsisseptisk-chock/#). However, aminoglycosides remain under debate as there is no definite evidence of improved outcomes and several studies report harmful side effects, especially renal toxicity [18–20]. In Sweden, aminoglycosides are usually administered as single dose in patients with sepsis [21]. The extreme variation in our study cannot be explained by case mix, disease severity or variation in microbial resistance patterns. Rather, it probably reflects the lack of firm evidence of efficacy, varying interpretation of published data, and local traditions [21].
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).
The war against bacteria, from the past to present and beyond
Published in Expert Review of Anti-infective Therapy, 2022
Lucrezia Bottalico, Ioannis Alexandros Charitos, Maria Assunta Potenza, Monica Montagnani, Luigi Santacroce
Mechanism of action – In position 5 of the 2-deoxyptreptamine ring they carry a hydroxyl, while in positions 4 and 6 they bind to amino sugars. The remaining positions of the ring carry free amino groups that bind with high affinity to the A-site on the 16S ribosomal RNA of the bacterial 30S ribosome. Because of this interaction, the antibiotics promote codon misreading on delivery of the aminoacyl transfer RNA and subsequent mistranslation. This results in error prone protein synthesis, incorrect amino acids assembly into a polypeptide and ultimately damage to the membrane and to other components of the bacterial cell. Because of their chemical structure and high surface charge, aminoglycosides are poorly absorbed via the gastrointestinal tract and are, thus, administered via the intravenous or intramuscular route for systemic infections.