Interest In Antibiotics Research Articles

New Insights into Pseudomonas spp.-Produced Antibiotics: Genetic Regulation of Biosynthesis and Implementation in Biotechnology.

Pseudomonas bacteria are renowned for their remarkable capacity to synthesize antibiotics, namely mupirocin, gluconic acid, pyrrolnitrin, and 2,4-diacetylphloroglucinol (DAPG). While these substances are extensively employed in agricultural biotechnology to safeguard plants against harmful bacteria and fungi, their potential for human medicine and healthcare remains highly promising for common science. However, the challenge of obtaining stable producers that yield higher quantities of these antibiotics continues to be a pertinent concern in modern biotechnology. Although the interest in antibiotics of Pseudomonas bacteria has persisted over the past century, many uncertainties still surround the regulation of the biosynthetic pathways of these compounds. Thus, the present review comprehensively studies the genetic organization and regulation of the biosynthesis of these antibiotics and provides a comprehensive summary of the genetic organization of antibiotic biosynthesis pathways in pseudomonas strains, appealing to both molecular biologists and biotechnologists. In addition, attention is also paid to the application of antibiotics in plant protection.

Trend of Changes in Chloramphenicol Resistance during the Years 2017–2020: A Retrospective Report from Israel

Resistant bacteria limit treatment options. This challenge has awakened interest in antibiotics that are no longer in use due to side effects, such as chloramphenicol. This work investigated trends in chloramphenicol resistance rates during 2017-2020 in bacteria isolated from diverse clinical samples at the Baruch Padeh Medical Center, Poriya, Israel. Bacteria were isolated from 3873 samples and identified using routine methods, including matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) technology. Chloramphenicol susceptibility was tested using a VITEK II instrument or by the Kirby-Bauer disk-diffusion test. The average chloramphenicol resistance rate was 24%, with no significant differences between study years. Chloramphenicol resistance was associated with sample origin (p < 0.001); isolates originating from sputum samples showed 49.8% resistance rate, compared to 2.3% of the body fluid isolates, 10.4% of the ear/eye isolates and 22.5% of the blood isolates. Furthermore, there was a significant decrease in chloramphenicol resistance among blood and ear/eye isolates during the study period (p = 0.01, p < 0.001, respectively). The highest resistance rate was among Pseudomonas aeruginosa isolates (50.5%). In conclusion, since chloramphenicol susceptibility seems to be retained, its comeback to the clinical world should be considered.

New insights about the EptA protein and its correlation with the pmrC gene in polymyxin resistance in Pseudomonas aeruginosa.

Nowadays, clinical and scientific interest in antibiotics, as polymyxin, has increased due to the large number of reports of multiresistant Gram-negative bacteria, as Pseudomonas aeruginosa. The aim of this study was to investigate a related group of proteins for resistance to polymyxins, encoded by P. aeruginosa genome, through in silico analysis. The mobilized colistin resistance 1 (MCR1) protein from Escherichia coli was used for comparison. Similar sequences to the protein MCR1 in P. aeruginosa were analysed for physicochemical properties. 31 protein isoforms in P. aeruginosa (EptA) were found able to confer resistance to polymyxin showing protein lengths between 551 and 572 amino acids, with molecular mass values between 61.36 - 62. 80kDa, isoelectric point between 6.10 to 7.17, instability index between 33.76 to 41.87, aliphatic index between 98.67 to 102.63 and the hydropathyindex between - 0.008 to 0.094. These proteins belong to the DUF1705 superfamily with bit-score values between 559.81 and 629.78. A high degree of similarity between EpTAs in P. aeruginosa was observed in relation to other proteins that confer resistance to polymyxins, present in Gram-negative bacteria species of clinical interest. Although, further studies are needed to identify the actual contribution of EptAs in P. aeruginosa species.

Screening acetylcholinesterase inhibitors from marine-derived actinomycetes by simple chromatography

Acetylcholinesterase (AchE) is an enzyme involved in the metabolism of Acetylcholine [Ach] cholinergic synapses in the central and peripheral nervous systems. As a result, AChE inhibitors promote an increase in the concentration and length of Ach synaptic activity. Acetylcholinesterase inhibitors (AchEIs) are currently considered the best therapeutic agents for Alzheimer’s patients. The potential sources of the current AChE inhibitors are predominantly plants. However, some of these drugs are known to have disadvantages such as limited half-life or side-effect such as hepatotoxicity. Marine microorganisms are a potential new source of the enzyme inhibitors. Since their rich and diverse metabolites have a wide range of biological activities, one of them is an actinomycetes of special interest in antibiotics. The purpose of this study was to screen AChE inhibitors from marine-derived actinomycetes using a simple method, thin layer chromatography (TLC). In addition, TLC was used for the determination of solvents for adsorption of actinomycetes AchE inhibitors. The results showed that the combination of chloroform/methanol = 80/20 had the best AchE inhibitor separation performance, while the combination of DCM/methanol = 90/10 should be considered if the gradient elution was selected during the separation process.

Global Internet Data on the Interest in Antibiotics and Probiotics Generated by Google Trends.

Data from the Google search engine enables the assessment of Google users’ interest in a specific topic. We analyzed the world trends in searches associated with the topics “antibiotics” and “probiotics” from January 2004 to June 2019, using Google Trends. We analyzed the yearly trends and seasonal variation. We performed an R-Spearman rank correlation analysis of the relative search volume (RSV) of the topics in 2015 with antibiotic consumption, health expenditure per capita, and the 2015 Human Development Index (HDI) of the country. The mean interest in the topic of antibiotics was equal to RSV = 57.5 ± 17.9, rising by 3.7 RSV/year (6.5%/year), while that of probiotics was RSV = 14.1 ± 7.9, which rose by 1.7 RSV/year (12.1%). The seasonal amplitude of antibiotics was equal to RSV = 9.8, while probiotics was RSV = 2.7. The seasonal peaks for both topics were observed in the cold months. The RSV of probiotics, but not antibiotics, was associated with antibiotic consumption (Rs = 0.35; p < 0.01), health expenditure (Rs = 0.41; p < 0.001), and HDI (Rs = 0.44; p < 0.001). Google users’ interest in antibiotic- and probiotic-related information increases from year to year, and peaks in cold months. The interest in probiotic-related information might be associated with antibiotic consumption, health expenditure, and the development status of the Google users’ country.

Reductions in parent interest for antibiotics following a 2-minute tablet-delivered intervention in pediatric outpatient clinics.

Purpose Approximately 11.4 million or 29% of prescriptions given to children with acute upper respiratory tract infections (ARTIs) annually in outpatient pediatric care are unnecessary. Providers consistently report pressure from parents as a contributing factor. While decreases in parental desire for antibiotics have been documented, some parents still harbor misconceptions that contribute to high interest in antibiotics. Enhancing parents’ understanding of appropriate antibiotic use may reduce their interest in antibiotics and support better parent-provider communication. Methods We investigated the impact of a 90 second gain-framed (i.e., emphasizing the positive aspects of a decision) animated, educational video promoting cautious …

1886. Provider’s Close Approximation of Parental Desire for Antibiotics Does Not Diminish Concern of Anticipated Conflict

BackgroundPediatric providers cite parental pressure as a reason for antibiotic overprescribing for acute respiratory tract infections (ARTI). Previous work indicates providers overestimate parental desire for antibiotics. We examined providers’ beliefs about parental interest in antibiotics, their comfort explaining denial and their concerns about parents’ response.MethodsProviders and parents of children aged 1–5 years with ARTI were enrolled from an academic and private practice clinic in a RCT testing interventions to improve appropriate antibiotic prescribing. At baseline, providers rated their belief of how often parents want antibiotics for their children in the context of a viral illness (never/rarely/sometimes/often/always), comfort explaining denial of antibiotics, and concern about parental disagreement about antibiotic necessity (not at all/ somewhat/mostly/completely). Prior to intervention, parents rated their interest for an antibiotic for their child on a 1–100 visual analog scale; low (≤39), neutral (40–59) or high (≥60).Results41 providers [66% physicians/34% APN, 78% female, median 8 (IQR 4, 12) years in practice] and 1,051 parents [mean age 31.5(SD = 6.0), 83.8% female, 26.0% ≤ high school degree, 80.0% White] were surveyed. Providers reported that parents sometimes (58%) or rarely/never (15%) want antibiotics. Similarly, the majority of parents’ interest was neutral (61.3%) or low (10.4%). Although 98% of providers reported being mostly/completely comfortable explaining denial of antibiotics, 56% were concerned that parents would disagree and feared parental push back (74%) or lack of satisfaction with the visit (82%).ConclusionFindings suggest that provider perceptions of parental desire for antibiotics are more tempered than previous reports and similar to what parents actually report. Nevertheless, despite high reported comfort explaining antibiotic denial, many providers still anticipate conflict when they tell parents that an antibiotic is not necessary.Disclosures B. R. Lee, Pfizer: Investigator, Research grant. Merck: Investigator, Research grant. J. Newland, Merck: Investigator, Research grant. C. Bickford, Teva: Spouse’s contract, Consulting fee.

Distinct tRNA Accommodation Intermediates Observed on the Ribosome with the Antibiotics Hygromycin A and A201A

The increase in multi-drug-resistant bacteria is limiting the effectiveness of currently approved antibiotics, leading to a renewed interest in antibiotics with distinct chemical scaffolds. We have solved the structures of the Thermus thermophilus 70S ribosome with A-, P-, and E-site tRNAs bound and in complex with either the aminocyclitol-containing antibiotic hygromycin A (HygA) or the nucleoside antibiotic A201A. Both antibiotics bind at the peptidyl transferase center and sterically occlude the CCA-end of the A-tRNA from entering the A site of the peptidyl transferase center. Single-molecule Förster resonance energy transfer (smFRET) experiments reveal that HygA and A201A specifically interfere with full accommodation of the A-tRNA, leading to the presence of tRNA accommodation intermediates and thereby inhibiting peptide bond formation. Thus, our results provide not only insight into the mechanism of action of HygA and A201A, but also into the fundamental process of tRNA accommodation during protein synthesis.

155 3D QSAR and protein–protein interaction studies on neuraminidase against Clostridium perfringens: An approach toward target identification using structure-based drug designing

The rapid onset of resistance to new drugs and emergence of antibiotic resistant bacteria has led to resurgence in life-threatening bacterial infections. These problems have revitalized interest in antibiotics and lead to new research. To gain further insight between structural and biological activity of Clostridium perfringens, a gram-positive anaerobe responsible for food poisoning, mynecrosis in wound infections, and enterotoxemia in humans. We have considered various in silico approaches for developing new drug leads, based on small ligand structure. The importance of neuraminidases in the virulence of C. perfringens makes it a potent target for the studies of drug designing against this microbe. Natural products or their direct derivatives play crucial roles in many diseases. In the present study, 3D QSAR analysis using kNN-MFA method was performed on a series of pterocarpan derivatives as Clostridial neuraminidase inhibitors. Twenty-five compounds using random selection and sphere exclusion method for the division of dataset into training and test set were chosen. kNN-MFA methodology with stepwise, simulated annealing and genetic algorithm was used for model building and four predictive models have been generated. The most significant model has a high internal predictivity of 64.80% (q 2 = 0.6480) and an external predictivity of 95.46% (r 2 = 0.9546). Model showed that electrostatic and steric interactions play important role in determining neuraminidase inhibitory activity. The kNN-MFA plots provide further understanding of the relationship between structural features of substituted pterocarpan derivatives and their activities which were applied for designing new compounds as inhibitors. The drug likeliness of these compounds was checked through ADME property prediction and their interaction with the neuraminidase was checked by molecular docking studies. Moreover, analysis of protein–protein interaction network of NanI in C. perfringens was done.

Antibiotics and muscle relaxation

Anesthesiologists use quite a few medications during anesthesia of a patient. Those include inhaled anesthetics, intravenous anesthetics, opioids, muscle relaxants, cholinesterase inhibitors, anticholinergic drugs, adrenergic agonists and antagonists, hypotensive agents, local anesthetics, and several adjunct drugs. We are usually well-trained in the administration of these drugs and aware of their actions and side effects. How about antibiotics? The anesthesiologists do not seem to have as much interest in antibiotics as their own favorite drugs. Antimicrobial agents can be used for prophylaxis to reduce the incidence of postoperative infections or for treatment of obvious preexisting infection. It is frequently requested to the anesthetic part to administer the prescribed antibiotics perioperatively. Many institutions have much debate as to the actual administration of the antibiotics, as well as the responsibility for their actions and side effects between anesthesiologists and surgeons. The truth is, each institution has its own protocol for antibiotic administration for the prophylaxis of surgical site infections and updates the protocol occasionally according to the rapid change of the drugs and information. There are potential difficulties that anesthesiologists be made aware of in association with the use of antibiotics, such as allergic reactions, end-organ damage and prolongation of neuromuscular block [1]. Most antibiotics can cause neuromuscular blockade alone and also potentiate blockade when combined with neuromuscular blockers. These can happen by the two different mechanisms, including inhibition of the prejunctional acetylcholine release and depression of postjunctional nicotinic acetylcholine receptor sensitivity to acetylcholine. Because gentamicin covers gram-negative organisms, and clindamycin covers gram-positive and anaerobic organisms, the combination therapy of those is a common treatment for postpartum endometritis. There are few reports about the effect of gentamicin and clindamycin on neuromuscular blockade caused by rocuronium. In this edition of the Journal, Lee et al. [2] studied about the effect of gentamicin and clindamycin to rocuronium-induced neuromuscular blockade in rat phrenic nerve-hemidiaphragm preparations. So far, the authors have succeeded in finding out the effect of a variety of drugs on neuromuscular blockade in a series of in vitro studies. They have presented us with beautiful sigmoid curves to show a relationship between drug concentration and response on the single twitch and tetanic fade in their articles. Their consecutive findings are as follows: 1. Clindamycin and gentamicin interfere with neuromuscular transmission. Neostigmine and calcium antagonize the neuromuscular blockade caused by gentamicin, but augment that caused by clindamycin [3]. 2. Neostigmine partially antagonizes the neuromuscular blockade that is induced by a combination of clindamycin and rocuronium [4]. 3. Bupivacaine inhibits neuromuscular conduction and enhances rocuronium-induced neuromuscular blockade [5]. 4. Gentamicin or a combination of gentamicin and clindamycin enhances rocuronium-induced neuromuscular blockade [2]. All the above laboratory results can be applied clinically in the operating room and intensive care unit. Since anesthesiologists will perhaps not be able to avoid a responsibility in administration of antibiotic regimen as time goes on, we should have the latest knowledge concerning antibiotics, including the interaction with the muscle relaxants.

The infectious disease challenges of our time

The infectious disease challenges of our time

Development and Validation of Micellar Liquid Chromatographic Methods for the Determination of Antibiotics in Different Matrixes

Antibiotics are the most important bioactive and chemotherapeutic compounds to be produced by microbiological synthesis, and they have proved their worth in a variety of fields, such as medicinal chemistry, agriculture, and the food industry. Interest in antibiotics has grown in parallel with an increasingly high degree of productivity in the field of analytical applications. Therefore, it is necessary to develop chromatographic procedures capable of determining various drugs simultaneously in the shortest possible time. Micellar liquid chromatography (MLC) is an RP-HPLC technique that offers advantages over conventional HPLC as far as sample preparation, selectivity, and versatility are concerned. Its main advantage is that samples can be injected directly into the chromatographic system with no previous preparation step. This paper mainly focuses on the results of the authors' own recent research and reports the chromatographic conditions for determination of various antibiotics (penicillins, quinolones, and sulfonamides) in different matrixes (pharmaceuticals, biological fluids, and food). The work of other authors on MLC-based antibiotic determination has been included.

Future antibiotics scenarios: is the tide starting to turn?

The fight against multidrug-resistant (MDR) pathogens continues. This article discusses the gap between the need for new antibiotics and lean research and development (R&D) pipelines. Many large pharmaceutical companies have terminated their antibacterial research programmes as they focus on potentially more lucrative therapeutic areas. At the same time, an increasingly dry funding situation hampers smaller start-up companies. Antibacterial innovation proceeds in waves. Following a wave of broad-spectrum antibiotics in the 1980s and 1990s, many companies focused on the development of small-spectrum antibiotics targeted at Gram-positive bacteria. In recent years, MDR Gram-negative bacteria have emerged and spread rapidly. The resulting intensified need for new therapeutic options against Gram-negative bacteria appears to promise financially rewarding return on investment for pharmaceutical companies within this small market niche. Thus, interest in antibiotics, particularly in drugs effective against MDR Gram-negative bacteria, is back. We appear to be at the start of a new wave of antibacterial drug R&D that will hopefully yield new therapeutic options in the future (10–15 years). Until then, the problem of MDR Gram-negative bacteria must continue to be addressed with a multifaceted set of solutions based on currently available tools.

Effects of Terramycin Antibiotic and Apistan Acaricide on Colonies of Honey Bees (Hymenoptera: Apidae) Infested with Varroa jacobsoni (Parasitiformes: Varroidae)

The effects of the antibiotic Terramycin and the acaricide Apistan were tested on colonies of honey bees, Apis mellifera L., infested with the parasitic mite Varroa jacobsoni Oudemans. Interest in antibiotics stems from the possibility that V. jacobsoni vectors pathogens. Each of 20 colonies randomly received 1 of 4 treatments : (1) 7 applications (28.3 g, 198.1 g total) of a standard Terramycin and powdered sucrose mixture, (2) 2 Apistan strips, (3) Terramycin and Apistan, or (4) no treatment as an experimental control. Terramycin increased the body weight of hive bees of mixed ages and of newly emerged adult bees. Apistan increased the body weight of hive bees of mixed ages, maintained colony population size during a period of apiary-wide decline, decreased the number of V. jacobsoni per newly emerged bee, and decreased the incidence of misshapen newly emerged bees. Overall, the effects of Terramycin antibiotic and Apistan acaricide on V. jacobsoni-infested colonies were favorable or neutral, and no interactions between the 2 products were detected.