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Backbone structures of the aminoglycosides. 

Backbone structures of the aminoglycosides. 

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Since 1944, we have come a long way using aminoglycosides as antibiotics. Bacteria also have got them selected with hardier resistance mechanisms. Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance me...

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... aminoglycosides have a backbone structure consisting of an aminocyclitol ring saturated with amine and hydroxyl substitutions. In the majority of clinically useful aminoglycosides, this amino- cyclitol moiety is streptamine or 2-deoxystrepta- mine ( Figure 1). Streptomycin, possessing a streptidine molecule, is the only exception. ...

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... It also has bactericidal properties by disrupting the bacterial cell membranes. 21 This antibiotic is broad spectrum in action, and with high local concentrations, can be effective against gram-negative organisms and some gram-positive organisms such as Staphylococcus. 22 In 1970, Buchholz and Engelbrecht 23 reported that bone cement mixed with antibiotics was effective in the treatment and prophylaxis of infection in total hip arthroplasty. ...
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Aim The surgical management of chronic intramedullary osteomyelitis involves debridement of affected non-viable tissue and the use of antibiotics. Where surgery leaves a cavity, dead-space management is often through antibiotic-impregnated bone cement. These depots of local antibiotics are variable in elution properties and need removal. We review our unit's experience using a bioabsorbable synthetic calcium sulphate to deliver gentamicin as an adjunct in the treatment of osteomyelitis involving the medullary canal. Materials and methods We retrospectively reviewed 34 patients with chronic osteomyelitis who were treated using this method in our institute. Variables recorded included aetiology, previous interventions, diagnostic criteria, radiological features, serology, and microbiology. The Cierny–Mader system was used to classify. Follow-up involved a survival analysis to time to recurrence, clinical and functional assessment (AOFAS-Ankle/IOWA knee/Oxford Hip/DASH scores) and a general health outcome questionnaire (SF36). The primary outcome measure was clinical recurrence of infection. Results There were 24 male and 10 female patients. The mean age at presentation was 47 years (20–67). Clinical, laboratory, radiological, and patient reported outcomes were obtained at a median follow-up of 2.5 years (1.4–6.6 years). The bones involved were the femur (14, 41%), tibia (16, 47%), radius (1, 3%), and humerus (3, 9%). There were 13 cases classified as Cierny–Mader stage IV (diffuse with intramedullary osteomyelitis) and 21 cases as Cierny-Mader stage I. The median Oxford Hip score was 38 (11 patients, range 9–48). The median AOFAS score was 78 (14 patients, range 23–100). The median IOWA knee score was 71 (25 patients, range 22–95). The median DASH score was 33 (2 patients, range 1.7–64.2). There were two recurrences. The treatment success to date is 94%. Conclusion In our series of patients, bioabsorbable carriers of antibiotics appear to be effective adjuncts to surgical treatment of osteomyelitis and were associated with high clinical success rates. How to cite this article Selvaratnam V, Roche A, Narayan B, et al. Effectiveness of an Antibiotic-impregnated Bioabsorbable Carrier for the Treatment of Chronic Intramedullary and Diffuse Osteomyelitis. Strategies Trauma Limb Reconstr 2023;18(3):148–154.
... In summary, the antibiotics most frequently used in combinations with natural products were aminoglycosides, followed by beta-lactams and quinolones. Antibiotics of the aminoglycosides class act in the inhibition of protein synthesis such that bacterial resistance mechanisms mainly involve the activation of ef ux and target modi cation systems [128]. Thus, the synergistic effects that are generally obtained by the association of natural products with antibiotics are related to an increase in the in ux of the drug, which alters the permeability of the cell membrane, favoring the penetration of antibiotics and potentializing its effect [129]. ...
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Natural products derived from plants play an important role in the development of antimicrobial agents. Antimicrobials are of interest both in the pharmaceutical industry to prevent or fight infections, and in the food industry for their ability to extend the shelf life of food. Although numerous plant extracts and their natural products (metabolites) have demonstrated antimicrobial potential, they still have numerous limitations for being used as antimicrobials. Among them is the genetic variability of the plants, which can be influenced by soil conditions; the difficulty to isolate biocompounds; the low yield of the extract or natural product; the low stability and poor water solubility; and, finally, the weak antimicrobial potency compared to commercial antimicrobials. Due to the great biodiversity and the growing problem of microbial resistance to current drugs, numerous research groups are seeking to improve the antimicrobial activity of plant extracts or their metabolites by means of different techniques. Some of the techniques are the combination of antimicrobial substances in search of synergy, the formation of inclusion complexes with cyclodextrins, and the elaboration of polymeric or solid lipidic nanoparticles, nanoemulsions. Several antimicrobial combinations, as well as different formulations, have proven useful in enhancing the proven biological activity of natural products. This chapter will discuss the main results obtained, the natural products studied in recent years, the field of application, as well as the difficulties and prospects for this field of research.KeywordsAntimicrobial synergismHybrid combinationsNatural antimicrobialsPhytochemicals nanoencapsulated
... Aminoglycoside inhibits peptide elongation at 30S ribosomal subunit, resulting in inaccurate mRNA translation which can halt protein synthesis or alter amino acid compositions at certain points [59]. However, when some mutations occur in the 30S ribosomal subunit, aminoglycosides no longer interact with the target [60]. In all the microbiome samples, the AMR genes conferring resistance to aminoglycoside were the most prevalent (Figure 3a). ...
Article
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Rapid and accurate pathogen identification is crucial in effectively combating infectious diseases. However, the current diagnostic tools for bacterial infections predominantly rely on century-old culture-based methods. Furthermore, recent research highlights the significance of host–microbe interactions within the host microbiota in influencing the outcome of infection episodes. As our understanding of science and medicine advances, there is a pressing need for innovative diagnostic methods that can identify pathogens and also rapidly and accurately profile the microbiome landscape in human samples. In clinical settings, such diagnostic tools will become a powerful predictive instrument in directing the diagnosis and prognosis of infectious diseases by providing comprehensive insights into the patient’s microbiota. Here, we explore the potential of long-read sequencing in profiling the microbiome landscape from various human samples in terms of speed and accuracy. Using nanopore sequencers, we generate native DNA sequences from saliva and stool samples rapidly, from which each long-read is basecalled in real-time to provide downstream analyses such as taxonomic classification and antimicrobial resistance through the built-in software (
... They work by preventing the production of proteins in bacteria by binding to the amino group site of 16S RNAs found inside subunits of the 30S ribosome. This location may make it harder to be coded by the genes, prevent them from being read, and prevent translocation [9,10]. The most well-known method of resistance to aminoglycosides in these bacteria is inhibiting the development of enzymes [10]. ...
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Since the peak of the coronavirus disease 2019 (COVID-19) pandemic, concerns around multidrug-resistant (MDR) bacterial pathogens have increased. This study aimed to characterize aminoglycoside resistance genes in MDR Klebsiella pneumoniae (K. pneumoniae) collected during the COVID-19 pandemic. A total of 220 clinical isolates of gram-negative bacteria were collected from tertiary hospitals in Makkah, Saudi Arabia, between April 2020 and January 2021. The prevalence of K. pneumoniae was 40.5%; of the 89 K. pneumoniae isolates, MDR patterns were found among 51 (57.3%) strains. The MDR isolates showed elevated resistance rates to aminoglycoside agents, including amikacin (100%), gentamicin (98%), and tobramycin (98%). PCR assays detected one or more aminoglycoside genes in 42 (82.3%) MDR K. pneumoniae strains. The rmtD gene was the most predominant gene (66.7%; 34/51), followed by aac(6 0)-Ib and aph(3 0)-Ia (45.1%; 23/51). The aac(3)-II gene was the least frequent gene (7.8%; 4/51) produced by our isolates. The rmtC gene was not detected in the studied isolates. Our findings indicated a high risk of MDR bacterial infections through the COVID-19 outbreak. Therefore, there is a need for continuous implementation of effective infection prevention control (IPC) measures to monitor the occurrence of MDR pathogens and the emergence of MDR bacterial infections through the COVID-19 outbreak.
... They work by preventing the production of proteins in bacteria by binding to the amino group site of 16S RNAs found inside subunits of the 30S ribosome. This location may make it harder to be coded by the genes, prevent them from being read, and prevent translocation [9,10]. The most well-known method of resistance to aminoglycosides in these bacteria is inhibiting the development of enzymes [10]. ...
Article
Full-text available
Since the peak of the coronavirus disease 2019 (COVID-19) pandemic, concerns around multidrug-resistant (MDR) bacterial pathogens have increased. This study aimed to characterize aminoglycoside resistance genes in MDR Klebsiella pneumoniae (K. pneumoniae) collected during the COVID-19 pandemic. A total of 220 clinical isolates of gram-negative bacteria were collected from tertiary hospitals in Makkah, Saudi Arabia, between April 2020 and January 2021. The prevalence of K. pneumoniae was 40.5%; of the 89 K. pneumoniae isolates, MDR patterns were found among 51 (57.3%) strains. The MDR isolates showed elevated resistance rates to aminoglycoside agents, including amikacin (100%), gentamicin (98%), and tobramycin (98%). PCR assays detected one or more aminoglycoside genes in 42 (82.3%) MDR K. pneumoniae strains. The rmtD gene was the most predominant gene (66.7%; 34/51), followed by aac(60)-Ib and aph(30)-Ia (45.1%; 23/51). The aac(3)-II gene was the least frequent gene (7.8%; 4/51) produced by our isolates. The rmtC gene was not detected in the studied isolates. Our findings indicated a high risk of MDR bacterial infections through the COVID-19 outbreak. Therefore, there is a need for continuous implementation of effective infection prevention control (IPC) measures to monitor the occurrence of MDR pathogens and the emergence of MDR bacterial infections through the COVID-19 outbreak.
... The FICI values of combinations were found to be 0.5 to 0.1562 (Table 1). Although several mechanism-based studies were performed earlier on the interaction of antibiotics with specific markers using biophysical and biochemical approaches [14][15][16]. Antibiotic combination therapy with ceftazidime/avibactam (CAZ/AVI) and aztreonam (ATM) was previously investigated for the treatment of infection with NDM producer Enterobacterales. The majority of Enterobacterales that are ATM resistant and NDM positive shows significant efficacies of the CAZ/AVI+ATM combination against them [17]. ...
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The emergence of multidrug-resistance (MDR)—New Delhi metallo-beta-lactamase (NDM)-producing microorganisms—has become a serious concern for treating such infections. Therefore, we investigated the effective antimicrobial combinations against multidrug-resistant New Delhi metallo-beta-lactamase-producing strains of Enterobacterales. The tests were carried out using the 2D(two-dimensional) checkerboard method. Of 7 antimicrobials, i.e., doripenem (DRP), streptomycin (STR), cefoxitin (FOX), imipenem (IPM), cefotaxime (CTX), meropenem (MER), and gentamicin (GEN), 19 different combinations were used, and out of them, three combinations showed synergistic effects against 31 highly drug-resistant strains carrying blaNDM and other associated resistance markers. Changes in the minimum inhibitory concentration (MIC) values were interpreted using the test fractional inhibitory concentration index (FIC Index). The FIC Index values of these combinations were found in the range of 0.1562 to 0.5, which shows synergy, whereas no synergism was observed in the remaining antimicrobial combinations. We conclude that these antibiotic combinations can be analyzed in in vivo and pharmacological studies to establish an effective therapeutic approach.
... Estos datos se asemejan a los resultados del presente estudio. La sensibilidad de este microorganismo podría deberse según mencionado por Shakil et al. (2008), los aminoglucósidos como la gentamicina matan a las bacterias mediante la inhibición de la síntesis de proteínas adhiriéndose al 16S rANR y mediante la interrupción de la integridad de la membrana celular bacteriana. ...
Article
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En una clínica veterinaria ubicada en la ciudad de Fernando de la Mora en el año 2020, fueron examinados 48 caninos que presentaron uno o más signos clínicos de otitis, sin distinción de sexo ni raza, con el objetivo de determinar la frecuencia de bacterias aisladas en otitis, su sensibilidad y resistencia a los antimicrobianos en pacientes caninos. Se extrajeron las muestras por medio de hisopados óticos para realizar el cultivo, aislamiento, identificación y posterior antibiograma. Los resultados obtenidos fueron los siguientes: 38 muestras, presentaron crecimiento bacteriano correspondio al 78%. En 19 (45%) muestras se aisló al Staphylococcus spp, en 11 (26%) muestras Pseudomona spp, 5 (12%) muestras presentaron Streptococcus spp, 4 (10%) correspondieron a Proteus spp, 2 (5%) Escherichia coli y de 1(2%) se aisló Citrobacter koseri. Los resultados del antibiograma indicaron, el Staphylococcus spp resultó sensible a: enrofloxacina en el (100%), clindamicina (94,7%), cefalexina (94,4%), oxacilina (89,4%), eritromicina (76,4%). La Pseudomona spp. sensible a: gentamicina (en el 81,8%), ciprofloxacina (81,2%). El Streptococcus spp sensible a: ampicilina (100%), penicilina (100%), eritromicina (100%), cloranfenicol (100%), cefpodoxima (100%), enrofloxacina (100%). Por último, se halló al Staphylococcus spp resistente a penicilina (100%), la Pseudomona spp. resistente a cotrimoxazol en el (100%) y el Streptococcus spp no presentó ninguna resistencia.
... This implies that layer thickness and roughness can slightly depend on the deposition conditions (temperature and humidity of the laboratory, as well as on the operator). leading eventually to a complete lack of protein turnover, 60 while the latter permits to achieve the same result by preventing the elongation of the peptide chain on the 50S subunit of ribosomes. 61 It is thus expected that, in this case, the interaction between bacteria and silver cannot occur effectively due to the excessively low viability of the cell population. ...
Article
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The incorporation of responsive elements into photonic crystals is an effective strategy for fabricating active optical components to be used as sensors, actuators, and modulators. In particular, the combination of simple multilayered dielectric mirrors with optically responsive plasmonic materials has proven to be successful. Recently, Tamm plasmon (TP) modes have emerged as powerful tools for these purposes. These modes arise at the interface between a distributed Bragg reflector (DBR) and a plasmonic layer and can be excited at a normal incidence angle. Although the TP field is located usually at the DBR/metal interface, recent studies have demonstrated that nanoscale corrugation of the metal layer permits access to the TP mode from outside, thus opening exciting perspectives for many real-life applications. In this study, we show that the TP resonance obtained by capping a DBR with a nanostructured layer of silver is responsive to Escherichia coli. Our data indicate that the modification of the TP mode originates from the well-known capability of silver to interact with bacteria, within a process in which the release of Ag+ ions leaves an excess of negative charge in the metal lattice. Finally, we exploited this effect to devise a case study in which we optically differentiated between the presence of proliferative and nonproliferative bacteria using the TP resonance as a read-out. These findings make these devices promising all-optical probes for bacterial metabolic activity, including their response to external stressors.
... Aminoglycoside inhibits peptide elongation at 30S ribosomal subunit, resulting in inaccurate mRNA translation which can halt protein synthesis or alter amino acid compositions at certain points [59]. However, when some mutations occur in the 30S ribosomal subunit, aminoglycosides no longer interact with the target [60]. In all the microbiome samples, the AMR genes conferring resistance to aminoglycoside were the most prevalent ( Figure 3). ...
Preprint
Full-text available
Rapid and accurate pathogen identification is crucial in effectively combating infectious diseases. However, the current diagnostic tools for bacterial infections predominantly rely on century-old culture-based methods. Furthermore, recent research highlights the significance of host-microbe interactions within the host microbiota in influencing the outcome of infection episodes. As our understanding of science and medicine continues to advance, there is a pressing need for innovative diagnostic methods that can identify pathogens and also rapidly and accurately profile the microbiome landscape in human samples. In clinical settings, such diagnostic tools will become a powerful predictive instrument in directing the diagnosis and prognosis of infectious diseases by providing comprehensive insights into the patient’s microbiota. Here, we explore the potential of long-read sequencing in profiling the microbiome landscape from various human samples in terms of speed and accuracy. Using nanopore sequencers, we generate native DNA sequences from saliva and stool samples rapidly, from which each long-read is basecalled in real-time to provide downstream analyses such as taxonomic classification and antimicrobial resistance through the built-in software (< 12 hours). Subsequently, we utilize the nanopore sequence data for in-depth analysis of each microbial species in terms of host-microbe interaction types and deep learning-based classification of unidentified reads. We find that the nanopore sequence data encompass complex information regarding the microbiome composition of the host and its microbial communities, and also shed light on the unexplored human mobilome including bacteriophages. In this study, we use two different systems of long-read sequencing to give insights into human microbiome samples in the ‘slow’ and ‘fast’ modes, which raises additional inquiries regarding the precision of this novel technology and the feasibility of extracting native DNA sequences from other human microbiomes.
... Furthermore, aminoglycosides including gentamicin have the ability to suppress bacteria cells regrowth a few hours after antibiotic concentration falls below the minimum inhibitory concentration (MIC), which is a key point in biofilm prevention which occurs in a short-time period after implantation. As far as Gram (+) bacteria are concerned, synergistic effects of aminoglycosides with other medications against Gram (+)were observed, but the mechanism remained unknown [77,[80][81][82][83]. Therefore, the sudden decrease in the number of viable S.aureus cells may be related to the synergistic effect of chitosan and gentamicin. ...