Search

Introduction: Chronic obstructive pulmonary disease (COPD) is a common syndrome associated with smoking and environmental exposures coupled with genetic susceptibility. Recent major advancements in the treatment of COPD patients have become available. Areas covered: New data on the role of classic bronchodilators, including short-acting and long-acting beta2-agonists and anti-muscarinic antagonists, in the treatment of COPD patients are discussed. Data promoting a more targeted approach to inhaled and systemic corticosteroid use in COPD are reviewed. Phosphodiesterase (PDE) inhibitors, including the recently approved PDE 3/4 inhibitor inhaled ensifentrine, are noted. Selective use of antibiotics can play a role in complex COPD patients. COPD patients with evidence of asthma-COPD overlap syndrome and type-two lymphocytic inflammatory-mediated airway constriction appear to respond to biologics, particularly the anti-IL-4/IL-3 antagonist monoclonal antibody, dupilumab. Expert opinion: New therapeutic options have made the approach and treatment of the COPD patient much more complicated. These options tend to be very expensive. Attention to identifying the endotype and phenotype will help direct the pharmacotherapy. [ABSTRACT FROM AUTHOR]

AbstractBovine mastitis is a mammary gland inflammation that can occur due to infectious pathogens, Staphylococcus aureus and Escherichia coli, which are, respectively, the most prevalent Gram-positive and Gram-negative bacteria associated with this disease. Currently, antibiotic treatment has become more complicated due to the presence of resistant pathogens. This review, therefore, aims to identify the most common resistance genes reported for these strains in the last four years. During the review, it was noted that blaZ, blaSHV, blaTEM, and blaampC are the most reported genes for S. aureus and E. coli, associated with drug inactivation, mainly β-lactamases. They are characterized by generating bacterial resistance to β-lactam antibiotics, the most common treatment in animal and human bacterial treatments (penicillins and cephalosporins, among others). Genes associated with efflux systems were also present in the two strains and included norA, tetA, tetC, and tetK, which generate resistance to macrolide and tetracycline antibiotics. Additionally, the effects of spreading resistance between animals and humans through direct contact (such as consumption of contaminated milk) or indirect contact (through environmental contamination) has been deeply discussed, emphasizing the importance of having adequate sanitation and antibiotic control and administration protocols. [ABSTRACT FROM AUTHOR]

Antibiotic residues and antibiotic resistance genes (ARGs) in sludge pose high risks to human health and the ecological environment. Hyper-temperature aerobic bio-drying system (HTAB) has the potential for higher degradation efficiency of antibiotics and ARGs due to high-temperature and rapid organic matter degradation. This study firstly reports two sludge HTAB processes, hyperthermophilic aerobic bio-drying (HAB) and electro-assisted heating bio-drying (EHAB), for the removal efficiency of four types of antibiotics, quinolones, tetracyclines, macrolides, and sulfonamide antibiotics, and ARGs, as well as the relationship between antibiotics and ARGs. The microbial communities of the two HTAB processes showed significant differences compared to the conventional bio-drying process (CAB). Compared to the CAB, the HTAB significantly improved the removal efficiency of antibiotics and ARGs and shortened the half-life of antibiotics. In the two HTAB processes, the total antibiotic removal of the HAB and EHAB processes was 78.11 and 74.15%, respectively. Compared with the EHAB process, the HAB process had higher removal for all four types of antibiotics, especially significantly improving the removal efficiency of tetracyclines. Compared to the CAB, both HTAB processes significantly enhanced the removal efficiency of ARGs and mobile genetic elements (MGEs). In the two HTAB processes, the HAB showed a higher removal efficiency of ARGs and MGEs compared to the EHAB. The relevant mechanisms indicated that temperature and changes in microbial communities jointly affected the removal efficiency of antibiotics and ARGs. [ABSTRACT FROM AUTHOR]

This review investigates the potential of natural compounds obtained from marine sources for the treatment of cancer. The oceans are believed to contain physiologically active compounds, such as alkaloids, nucleosides, macrolides, and polyketides, which have shown promising effects in slowing human tumor cells both in vivo and in vitro. Various marine species, including algae, mollusks, actinomycetes, fungi, sponges, and soft corals, have been studied for their bioactive metabolites with diverse chemical structures. The review explores the therapeutic potential of various marine-derived substances and discusses their possible applications in cancer treatment. [ABSTRACT FROM AUTHOR]

Nowadays, incorrect apply of antibiotics to treat infections in honey has led to health risks for humans and antibiotic resistance. Current systematic review and meta-analysis conducted to study antibiotic residues in honey. Data were obtained through searching the databases, including Scopus, Web of Science, PubMed, and other internal databases. The pooled concentration of antibiotic residues was 5.032 (µg/kg) that ranged from 4.72 to 5.33 (µg/kg). The ranking of antibiotics concentration was found in order of fluoroquinolone (8.59 µg/kg) > tetracycline (5.68 µg/kg) > sulfonamides (5.54 µg/kg) > macrolides (4.19µg/kg), respectively. Liquid chromatography–mass spectrometry (LC–MS) method (37.9.7%), high-performance liquid chromatography (HPLC) method (34.4%), and enzyme-linked immunosorbent assay (ELISA) method (27.5.8%) were the most used methods in various studies. In order to avoid contamination, proper use of antibiotics, placement of hives at a suitable distance from agricultural environment, and regular control of antibiotic residues in honey seems to be necessary. [ABSTRACT FROM AUTHOR]

Throughout the COVID-19 pandemic, public officials in the United States – from the President to governors, mayors, lawmakers, and even school district commissioners – touted unproven treatments for COVID-19 alongside, and sometimes as opposed to, mask and vaccine mandates. Utilising the framework of ‘pharmaceutical messianism’, our article focuses on three such cures – hydroxychloroquine, ivermectin, and monoclonal antibodies – to explore how pharmaceuticals were mobilised within politicised pandemic discourses. Using the states of Utah, Texas, and Florida as illustrative examples, we make the case for paying attention to pharmaceutical messianism at the subnational and local levels, which can very well determine pandemic responses and outcomes in contexts such as the US where subnational governments have wide autonomy. Moreover, we argue that aside from the affordability of the treatments being studied and the heterodox knowledge claiming their efficacy, the widespread uptake of these cures was also informed by popular medical (including immunological) knowledge, pre-existing attitudes toward ‘orthodox’ measures like vaccines and masks, and mistrust toward authorities and institutions identified with the ‘medical establishment’. Taken together, our case studies affirm the recurrent nature of pharmaceutical messianism in times of health crises – while also refining the concept and exposing its limitations. [ABSTRACT FROM AUTHOR]

Clarithromycin as a macrolide antibiotic and zinc oxide (ZnO) nanoparticles with antibacterial and anti-inflammatory properties was incorporated into the chitosan/gelatin/polyurethane (PU) core-shell nanofibers prepared by the coaxial electrospinning method. The morphology and structure of nanofibers were characterized using SEM, FTIR, water contact angle, degradation rate, and swelling tests. The mean fiber diameters of the chitosan/gelatin/PU (CGP), CGP containing 1000 lM clarithromycin, CGP containing 2000 lM clarithromycin, CGP containing 0.5% ZnO, CGP containing 1 wt% ZnO, CGP containing 1000 lM clarithromycin, and 0.5 wt% ZnO and CGP containing 2000 lM clarithromycin, and 1 wt% ZnO were 210 ± 110 nm, 235 ± 100 nm, 250 ± 120 nm, 300 ± 120 nm, 360 ± 130 nm, 410 ± 130 nm, and 460 ± 140 nm, respectively. The gradual faster release of ZnO nanoparticles from core-shell nanofibers was obtained within 24 h; whereas, the sustained release of clarithromycin was achieved during 120 h. Loading of clarithromycin and ZnO nanoparticles into the nanofibers resulted in 100% bactericidal activity of core-shell nanofibers against both Escherichia coli and Staphylococcus aureus. The cell viability results indicated that loading of 0.5 wt% ZnO nanoparticles and 2000 lM clarithromycin was suitable for the development of the synthesized core-shell nanofibers as a potential wound dressing. [ABSTRACT FROM AUTHOR]

Rapamycin is a macrolide antibiotic with antifungal, immunosuppressive, antitumor, and lifespan-extension activities etc. In order to increase its structural diversity, microbial transformation of rapamycin was conducted. More than 3 converted compounds were shown in the microbial conversion culture of rapamycin by Bacillus subtilis CGMCC7764. By extensive NMR and MS spectroscopic analyses, the major compound was identified as 43-O-(β-D-glucoside)-rapamycin. This compound has an inhibitory effect on tumour growth, and its activity is similar to rapamycin. [ABSTRACT FROM AUTHOR]

The post-treatment of recycling the fine photocatalyst nanoparticles restricts their application. In this study, a new photocatalytic material was synthesized by immobilizing the N-doped TiO2 and graphene oxide (GO) composite on polypropylene (PP) (N–TiO2/GO/PP) fibre sheet, and characterized based on X-ray diffraction spectroscopy (XRD), Raman spectroscopy and Scanning Electron Microscope (SEM). The photocatalytic activity was evaluated using roxithromycin (ROX) as a typical antibiotic pollutant. XRD, Raman spectra and SEM images proved that N–TiO2/GO/PP fibre sheet was successfully synthesized. The photocatalytic degradation of 10 mg L−1 ROX can reach up to 90% and the degradation rate constant was 0.2299 h−1 in surface water with the application amount of TiO2/GO/PP fibre sheet of 24.6 cm × 2.7 cm and reaction time of 9 h under the irradiation of simulated sunlight. The application amount of TiO2/GO/PP fibre sheet, initial concentration of ROX and water matrix significantly affect the degradation of ROX. A low concentration of natural organic matter (NOM) slightly promoted the degradation of ROX, while a high concentration of NOM significantly inhibited the degradation of ROX. Alkaline condition (pH 8–9) is favourable for the photocatalytic degradation of ROX by TiO2/GO/PP fibre sheet. The photocatalytic reactivity of the TiO2/GO/PP fibre sheet showed no significant decrease after three runs. Two primary degradation products of ROX were identified and they showed lower ecotoxicity than ROX. The results demonstrate that the new synthesized TiO2/GO/PP fibre sheet shows promising application prospects in the treatment of antibiotics in wastewater and surface waters. [ABSTRACT FROM AUTHOR]

In this study, an immunochromatographic test (using the Charm QUAD2® Test) was used to screen for residual macrolides and lincosamides in raw cow's milk. The validation parameters (selectivity/specificity, detection capability (CCβ), and ruggedness) were in agreement with the requirements of[EC] 2021. The selectivity of the immunochromatographic test was verified by the negative results of microbiological tests. The false-positive rate was 0%. The CCβ values of the immunochromatographic test for various antibiotics in milk were as follows: erythromycin 0.02 mg/kg, spiramycin 0.1 mg/kg, tilmicosin 0.025 mg/kg, tylosin 0.05 mg/kg, lincomycin 0.15 mg/kg, and pirlimycin 0.15 mg/kg. The determined CCβ values were lower than the respective maximum residue limits (MRLs; regulatory limits in Japan) for milk, except for lincomycin (equal to the MRL). The presence of antibiotic groups other than macrolides and lincosamides did not interfere with the specificity of the test. It showed no significant difference in lot-to-lot repeatability. The results obtained by the two researchers showed no significant differences. Finally, the test was applied to milk samples obtained from a tylosin-treated cow. The outcome was positive and in agreement with the results of the chemical analytical and microbiological methods. Therefore, this validated immunochromatographic test is expected to be suitable for routine analysis to ensure milk safety. [ABSTRACT FROM AUTHOR]

The misuse of antibiotics in the animal sector is the main driver of antibiotic resistance. More than 80% of Italian beef cattle imported from France are Charolais, which undergo a commingling procedure before reaching Italian fattening farms. The aim of this study was to evaluate the effect of commingling Charolais cattle in France on antibiotic use (AMU) and animals' performances in Italy. A total of 19,756 young bulls from 449 batches transported to Italy between 2016 and 2018 were considered. Carcase weight (CW), slaughter age (SA), antibiotic treatments, vaccinations information and the French department of origin were available for each animal. Also, treatment incidence 100 (TI100it) and average daily carcase gain (ADCG) were calculated. Three classes of commingling were assigned to each animal according to the French department of origin. A linear mixed model was used to investigate sources of variation of CW, SA, ADCG and TI100it. Respiratory diseases were the main reasons for treatment and macrolides were the most used class of antibiotics. The TI100it decreased by 11% from 2016 to 2018 (p <.05). Animals that went through the highest level of commingling had lighter CW, lower ADCG and greater TI100it than animals subjected to lower commingling (p <.05). Younger animals reached higher TI100it than older ones (p <.05). Younger and highly commingled animals had higher TI100it (p <.001) than older animals equally commingled. This first-of-its-kind study showed that commingling procedures increase the risk of AMU and affect the performances of Charolais cattle. Commingling procedures increase the use of antibiotics and penalise animals' performances. Younger and highly commingled animals are at greater risk of being treated. Reducing commingling levels can be an effective strategy to reduce antibiotic use in beef cattle. [ABSTRACT FROM AUTHOR]

In their roles as nurses, data collectors, or other, fieldworkers undertake myriad tasks working intimately with and on the bodies of others – a type of work called 'body work'. This work further includes the micro-political relations shaping these interactions, and studies have shown the importance of these relationships in the success of clinical trials, particularly in the Gambia. This study seeks to expand the concept of body work to understand the roles and interactions of fieldworkers within the trial community, and the effect on a mass drug administration (MDA) clinical trial. We conducted a mixed-methods social science study alongside the MDA in 2018–2019, including in-depth interviews, focus group discussions, and semi-structured observations with the population involved (and not) in the MDA, as well as the MRC fieldworkers. We found that fieldworkers participated in what we call 'reciprocity work'. Through their regular tasks and interactions, they necessarily showed respect and established trust in a way that formed and contributed to reciprocal relationships, the results of which impacted the trial and individuals' autonomy in the decision-making process. Understanding the role of fieldworkers and their reciprocity work is a vital component in comprehending how research ethics are made and conducted in global health research. [ABSTRACT FROM AUTHOR]

The intensification of aquaculture in Cameroon requires efficient screening methods to control veterinary drug residues in fish. This is why the charm II radio receptor technique for the detection of antimicrobial residues in aquaculture fish initiated in Belgium was transferred to Cameroon according to Commission Decision 2002/657/EC. The validation parameters included the following tests: repeatability, reproducibility and robustness in addition to the mandatory characteristics, detection capability and specificity. Selected veterinary drug-free fish samples of tilapia (Oreochromis niloticus), catfish (Clarias gariepinus), carp (Cyprinus Carpio) and kanga (Heterotis niloticus) were spiked at different target concentrations with different antimicrobials (β-lactams, tetracycline, sulfonamides, macrolides and chloramphenicol). The detection capabilities (CCβ) were at MRPL (0.3 µg/kg for chloramphenicol), or below the regulatory limits in a range of 0.25–0.5 MRL with 0% false-negative results. β-lactams (penicillin G), tetracyclines (tetracycline, chloretetracycline and oxytetracycline) and macrolides (erythromycine A) were detected at half MRL (25, 50 and 100 µg/kg respectively), while sulfonamides (sulfamethazine) was detected at 25 µg/kg (0.25 MRL). The detection capabilities (CCβ) obtained were satisfactory as the cut-off factors (Fm) were less than the mean values of blank fish readings (B) (Fm < B). Furthermore, the method was applicable since the cut-off factor was less than the positivity threshold (Fm < T). The variability of the data under repeatability and reproducibility conditions was acceptable, with a relative standard deviation less than 15%. Results were unaffected by delaying the reading time from 0 h to 24 h after the addition of scintillation fluid, with a precision below 16%. Likewise, non-target drugs were not detected even at high concentrations (100 MRL) in a cross-reactivity study. From the overall results, the performance characteristics (detection capabilities, precision, robustness and specificity) were suitable and comparable to the initial validation results, indicating that the transfer to Cameroon laboratory was valid, the method was reliable and could be used in aquaculture fish quality monitoring programs in Cameroon. [ABSTRACT FROM AUTHOR]

Neonatal sepsis is a major cause of morbidity and mortality in preterm infants. Chorioamnionitis is an important risk factor for the development of sepsis, therefore neonates born to mothers developing signs of amnionitis need to be treated with antibiotics immediately after birth. Ureaplasma spp can be a causative agent of vaginal or intra amniotic infection needing antibiotic treatment. Macrolides are frequently used to treat maternal intrauterine infection, but antibiotic treatment of the neonate should be consciously chosen with consideration of potential side effects. Indeed, macrolides are great purveyors of heart rhythm disorders. We describe the case of a 29 weeks preterm infant born to a mother with Ureaplasma spp infection. The baby was treated with erythromycin immediately after birth. During the second day of life, the baby presented some episodes of tachyarrhythmia with premature ventricular beats (PVBs) that were followed by a non-sustained ventricular tachycardia as high as 270 bpm leading to a cardiac arrest. After resuscitation, tachycardia resolved but the rhythm was characterised by numerous PVBs and an electrocardiogram (ECG) diagnosed a Long QT Syndrome (LQTS). Erythromycin was discontinued, and the rhythm normalised a few days after withdrawal. Erythromycin should be administered in neonates only if no other choice is available, as although generally well tolerated, its administration can be associated with QTc interval prolongation. When no other option is available, paediatricians should be aware to perform cardiac monitoring or at least serial ECGs before and during erythromycin administration. [ABSTRACT FROM AUTHOR]

Adverse drug reactions represent a major public health problem, both from an economic point of view and, mainly, from the point of view of the induced pathology (iatrogenic diseases), being difficult to differentiate from other pathological conditions or even from the treated disease. Thus, these aspects prevent the use of the first-choice drugs needed for a particular treatment, in different therapeutic classes: beta-lactam antibiotics; sulfonamides; macrolide antibiotics; quinolones; non-steroidal anti-inflammatories; corticosteroids; Angiotensin converting enzyme (ACE) inhibitors; general anesthetics; biological drugs; antiepileptic drugs etc. On the other hand, adverse drug reactions represent a major problem for both clinical practice and preclinical research, in order to develop new drugs. Hypersensitivity reactions mainly refer to the adverse effects that can be harmful, disturbing, and sometimes fatal, that appear under the conditions of a normal immune system, including allergies and autoimmune reactions, both triggered by an immunological-allergic mechanism. The main purpose of this paper is to review the main classes of drugs involved in inducing hypersensitivity reactions. [ABSTRACT FROM AUTHOR]

This review aimed to explore and summarise available cases of delirium suspected to be associated with the use of macrolide antibiotics reported in the literature and the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) database. Electronic searches of the literature were conducted in four online databases: PubMed/MEDLINE, Scopus, Web of Science and Serbian Citation Index (SCIndeks). A search of FAERS database was also conducted to supplement the findings of the literature search. Descriptive statistics, narrative summation and tabulation of the extracted data were made. Cases of delirium which satisfied inclusion criteria were found for clarithromycin, azithromycin, erythromycin and telithromycin. Delirium was described in patients of various age groups, including children. Drug-drug interactions may have contributed to its occurrence in some of the cases. Average time to onset of delirium was 2.5 days for azithromycin and 3.3 days for clarithromycin. Considering that these drugs may be a possible cause of delirium, clinicians should be aware that timely recognition of this possible side effect can lead to earlier discontinuation of the culprit drug, reduce time spent in a delirious state and improve patients' outcomes. Cases of delirium which satisfied inclusion criteria were found for clarithromycin, azithromycin, erythromycin and telithromycin. Cases of delirium were described in patients of various age groups, including children. Drug-drug interactions may have contributed to the occurrence of delirium in some of the cases. Time to onset of delirium ranged from 2 to 3.5 days (mean: 2.5 days) for azithromycin and from 1 to 7 days (mean: 3.3 days) for clarithromycin. Cessation of the macrolide antibiotic seems to be the best management strategy, although some of the patients may, in addition, require antipsychotics. [ABSTRACT FROM AUTHOR]

The new natural products reported in 2020 in peer-reviewed articles in journals with good reputations were reviewed and analyzed. The advances made by Asian research groups in the field of natural products chemistry in 2020 were summarized. Compounds with unique structural features and/or promising bioactivities originating from Asian natural sources were discussed based on their structural classification. [ABSTRACT FROM AUTHOR]

Macrolides are critically important antimicrobials for both human and animal health and should be prioritized in risk assessments, as inappropriate use may result in antimicrobial resistance. The antimicrobials erythromycin, oleandomycin, spiramycin, tilmicosin and tylosin were analysed in infant formula samples by HPLC-MS/MS using a validated analytical method based on a modified QuEChERS extraction. The results of the occurrence study were employed to perform a dietary exposure assessment of infants to residues. In a total of 30 analysed samples, 73% contained spiramycin residues and 27%, tilmicosin residues. Calculated daily intakes ranged from 1.47 × 10−6 to 2.71 × 10−4 mg kg−1 body weight considering all analytes, representing 0.01–0.59% of acceptable daily intakes. The results of the dietary exposure assessment were all below acceptable daily intakes, indicating low potential health concerns. However, according to Brazilian regulations, infant formulas containing residues of one or more of the investigated analytes were deemed as non-compliant. [ABSTRACT FROM AUTHOR]

To study antibiotic prescriptions among 0- to 4-year-old children before and after implementing a quality project on prudent prescribing of antibiotics in primary healthcare in the capital region of Iceland. An observational, descriptive, retrospective study using quantitative methodology. Primary healthcare in the Reykjavik area with a total population of approximately 220,000. A total of 6420 children 0–4 years of age presenting at the primary healthcare centres in the metropolitan area over three years from 2016 to 2018. Reduction of antibiotic prescriptions and change in antibiotic profile. Data on antibiotic prescriptions for children 0–4 years of age was obtained from the medical records. Out-of-hours prescriptions were not included in the database. The number of prescriptions during the study period ranged from 263.6 to 289.6 prescriptions/1000 inhabitants/year. A reduction of 9% in the total number of prescriptions between 2017–2018 was observed. More than half of all prescriptions were for otitis media, followed by pneumonia and skin infections. Amoxicillin accounted for over half of all prescriptions, increasing between 2016 and 2018 by 51.3%. During this period, the prescribing of co-amoxiclav and macrolides decreased by 52.3% and 40.7%, respectively. These changes were significant in all cases, p < 0.0001. The results show an overall decrease in antibiotic prescribing concurrent with a change in the choice of antibiotics prescribed and in line with the recommendations presented in the prescribing guidelines implemented by the Primary Healthcare of the Capital Area, and consistent with the project's goals. A substantial proportion of antibiotic prescribing can be considered inappropriate and the antibiotic prescription rate is highest in Iceland of the Nordic countries. After implementing guidance on the treatment of common infections together with feedback on antibiotic prescribing, a decrease in the total number of prescriptions accompanied by a shift in the antibiotic profile was observed. [ABSTRACT FROM AUTHOR]

At present, the distribution of antibiotics in wastewater is mainly concentrated in municipal sewage treatment plants, and little attention is paid to the distribution and removal of antibiotics in landfill leachate. The concentrations of five sulfonamide, three tetracycline, and two macrolide antibiotics in leachate from a solid waste incineration plant were measured and the efficiency of the leachate treatment process in removing them was investigated. All target antibiotics were detected in the raw leachate samples. The total sulfonamide, tetracycline, and macrolide concentrations in the raw leachate ranged from 0.98 to 90.25, 1.90 to 50.64, and 146.41 to 382.90 ng/L, respectively. The leachate treatment process simultaneously removed all ten antibiotics with high removal efficiencies ranged from 96.0% to 100%. Biological and physical processes affected the removal of different types of antibiotics differently, with macrolides being more difficult for microorganisms to degrade than the other two categories. Leachate contaminants correlated to antibiotics suggesting environmental factors impact the removal of antibiotics. The accumulation of antibiotics in the leachate treatment process may create environmental problems. [ABSTRACT FROM AUTHOR]

It is important to predict drug-drug interactions via inhibition of intestinal cytochrome P450 3A (CYP3A) which is a determinant of bioavailability of orally administered CYP3A substrates. However, inhibitory effects of macrolide antibiotics on CYP3A-mediated metabolism are not entirely identical between humans and rodents. We investigated the effects of macrolide antibiotics, clarithromycin and erythromycin, on in vitro and in vivo metabolism of triazolam, a CYP3A substrate, in CYP3A-humanised mice generated by using a mouse artificial chromosome vector carrying a human CYP3A gene. Metabolic activities of triazolam were inhibited by macrolide antibiotics in liver and intestine microsomes of CYP3A-humanised mice. The area under the plasma concentration-time curve ratios of 4-hydroxytriazolam to triazolam after oral dosing of triazolam were significantly decreased by multiple administration of macrolide antibiotics. The plasma concentrations ratios of α-hydroxytriazolam and 4-hydroxytriazolam to triazolam in portal blood were significantly decreased by multiple administration of clarithromycin in CYP3A-humanised mice. These results suggest that intestinal CYP3A activity was inhibited by macrolide antibiotics in CYP3A-humanised mice in vitro and in vivo. The plasma concentrations of triazolam and its metabolites in the portal blood of CYP3A-humanised mice would be useful for direct evaluation of intestinal CYP3A-mediated drug-drug interactions. [ABSTRACT FROM AUTHOR]

Two new milbemycin derivatives, milbemycin M (1) and milbemycin N (2), were isolated from the culture of a genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were elucidated through the interpretation of NMR and HR-ESI-MS spectroscopic data, as well as comparison with previous reports. The acaricidal and nematicidal activities of them against Tetranychus cinnabarinus and Bursaphelenchus xylophilus were tested. The results showed that compounds 1–2 possessed potent acaricidal and nematocidal activities. [ABSTRACT FROM AUTHOR]

Nafithromycin is a next generation lactone ketolide antibiotic slated to enter phase III clinical development in India for the treatment of CABP as a shorter 800 mg-OD X3 day therapeutic regimen. Nafithromycin exhibits potent activity against MDR Streptococcus pneumoniae including erythromycin and telithromycin-resistant resistant strains. Older macrolides/ketolides are reported to be potent inhibitors of CYP3A4/5. To facilitate comparative assessment of drug–drug interaction potential, CYP inhibitory activities of nafithromycin was evaluated in comparison with clarithromycin, telithromycin, cethromycin and solithromycin. CYP inhibitory activities were assessed against key CYP isoforms (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and CYP3A4/5) using human liver microsomes. Additionally, time-dependent inhibition (TDI), metabolism-based inhibition (MBI) and kinact/KI activities were also investigated for CYP3A4/5. Nafithromycin did not inhibit key CYP enzymes and was found to be a weak inhibitor of CYP3A4/5. Comparator antibiotics were found to be potent inhibitors with 2- to 50-fold leftward shifts in CYP3A4/5 IC50 values, while such shift was not noted for nafithromycin. kinact/KI ratio of nafithromycin was 3- to 153-fold lower than comparator drugs, further substantiating its lower affinity for CYP3A4/5. In sum, weaker inhibition and lower kinact/KI ratio for CYP3A4/5, points towards nafithromycin's lower propensities towards clinical drug–drug interactions as compared to other macrolides/ketolides antibiotics. [ABSTRACT FROM AUTHOR]

Due to their antimicrobial activity Enterococcus faecium strains have a growing record of use as beneficial adjunct cultures in animal nutrition or components of probiotic preparations for humans. However, safety concerns accompany the application of enterococci, as clinical strains associated with infection have been isolated, especially antibiotic resistant cultures. With the increasing availability of whole genome sequencing (WGS), valuable safety data can be extracted in the early phase of development of the probiotic dossier of an E. faecium strain. Here we report the results of initial safety assessment of E. faecium LBB.E81 by selecting accessible commercial antibiotic susceptibility test and WGS. Testing against a panel of antibiotic substances showed that E. faecium LBB.E81 was susceptible to all antimicrobials with the exception of its intrinsic, non-transferable resistance to nitrofurantoin. The identified antibiotic resistance genes of E. faecium LBB.E81 aac(6')-Ii, msrC and efmA belonged to a group of intrinsic non-transferable factors contributing to the lower susceptibility of the E. faecium species to aminoglycoside and macrolide antibiotics but with minimal inhibitory concentrations for E. faecium LBB.E81 below the threshold values determined for resistant strains. The only potential virulence factor genes found in the genome of E. faecium LBB.E81 were a defective acm (collagen-binding adhesin) and efaAfm (antigen A – like protein) without any evidence for its involvement in pathogenicity. Other hospital associated virulence factor genes of E. faecium such as IS16, hyl, asa-type genes, cyl; gelE and fsr, sprE and esp(fm) were found to be absent in E. faecium LBB.E81. [ABSTRACT FROM AUTHOR]

The new natural products reported in 2019 in peer-reviewed articles in journals with good reputations were reviewed and analyzed. The advances made by Asian research groups in the field of natural products chemistry in 2019 were summarized. Compounds with unique structural features and/or promising bioactivities originating from Asian natural sources were discussed based on their structural classification. [ABSTRACT FROM AUTHOR]

Purpose: Erythromycin is an effective topical antibiotic for treating mild-to-moderate inflammatory acne vulgaris, especially papules acne during puberty as well as papules - pustular acne in adult women. Erythromycin is a macrolide antibiotic that has long been used as a topical dosage form to treat acne. It has favorable effects in resolving inflammatory acne lesions not only by reducing Propioni bacterium acnes density, but also by directly inhibiting neutrophil chemotactic factors and reactive oxygen species (ROS) production. Zinc, a metallic element has bacteriostatic activity against Propioni bacterium acnes. Combining zinc with antibiotic (erythromycin) can reduce antibiotic resistance and increase antibiotic absorption in-to the skin. Material and methods: In the present study, erythromycin (2% w/v) with zinc acetate (1.2% w/v) as 'topical gel' and erythromycin (2% w/v) gel alone were evaluated for treating mild to moderate inflammatory acne vulgaris. This double-blind study was carried out on 102 patients 13–25 years of age, divided into two groups. The group A received erythromycin and group B received erythromycin with zinc acetate topical gels during 3 weeks. Acne grading and lesion counts for comedones, papules and pustules were performed during each visit zero, first, second and third weeks. Results: Erythromycin treatment (with zinc acetate) gel showed to be more effective than erythromycin (alone) gel with respect to reducing the number of acne lesions and severity grade of acne.Number of lesions and severity of acne were significantly reduced at the end of 3rd week in both groups (p <.001). Conclusions: In conclusion, it can be stated that erythromycin with and without zinc acetate was clinically effective, and both formulations produced a significant reductions in acne grading as well as inflamed and noninflamed lesion counts (p <.000). Statistically, there was no significant difference between formulation A and B. [ABSTRACT FROM AUTHOR]

Two new sixteen-membered macrolides, Δ2,3-tenvermectin A (1) and 13α-hydroxy milbemycin β11 (2), were isolated from the fermentation broth of the genetically engineered strain Streptomyces avermitilis MHJ1011. Their structures were determined based on extensive spectroscopic analysis and comparison with related known compounds. Compounds 1 and 2 exhibited potent acaricidal activity against Tetranychus cinnabarinus. [ABSTRACT FROM AUTHOR]

Tylosin fermentation dregs (TFDs) are biosolid waste of antibiotics tylosin production process which contain nutritious components and may be recycled as soil amendments. However, the specific ecological safety of TFDs from the perspective of bacterial resistance in soil microenvironment is not fully explored. In the present study, a series of replicated lab-scale work were performed using the simulated fertilization to gain insight into the potential environmental effects and risks of macrolide antibiotic resistance genes (ARGs) and the soil microbial communities composition via quantitative PCR and 16S rRNA sequencing following the TFDs land application as the soil amendments. The results showed that bio-processes might play an important role in the decomposition of tylosin which degraded above 90% after 20 days in soil. The application of TFDs might induce the development of antibiotic-resistant bacteria, change soil environment and reduce the microbial diversity. Though the abundances of macrolide ARGs exhibited a decreasing trend following the tylosin degradation, other components in TFDs may have a lasting impact on both macrolide ARGs abundance and soil bacterial communities. Thus, this study pointed out the fate of TFDs on soil ecological environment when directly applying into soil, and provide valuable scientific basis for TFDs management. [ABSTRACT FROM AUTHOR]

Recent studies have shown azithromycin-specific clinical efficacy against macrolide-resistant strains of Streptococcus pneumoniae, despite the low susceptibility of the bacteria in vitro. This discrepancy complicates dosing and selection for treatment of macrolide-resistant strains. Although phagocyte delivery of azithromycin to inflamed tissues is considered a possible factor for clinical efficacy, there is a lack of sufficient evidence, and other pharmacokinetic factors under systemic inflammation may contribute. The concentrations of azithromycin, clarithromycin and erythromycin in the plasma and buffy coat were determined in normal and sepsis model rats. Furthermore, we compared the transport of the drug into the lung. The levels of all three macrolides in the buffy coat were higher than the levels in the plasma, and lower leukocyte counts in plasma were observed in septic rats, suggesting accumulation of the drugs per leukocyte was increased. The concentrations in the lung tissue of septic rats at each sampling time were the same as those in normal rats, and azithromycin-specific long-term stasis in the lung was evident. These results suggest that both the phagocyte delivery and the stasis of azithromycin in the lung could contribute to its clinical efficacy in treating infections caused by macrolide-resistant strains. [ABSTRACT FROM AUTHOR]

Tylosin A is a macrolide antibiotic used in beekeeping. The aim of the study was to characterise the behaviour of tylosin A in honey after heating and during storage, and to identify its degradation products using a non-targeted approach. In addition, the possibility of a semi-quantification of tylosin B using tylosin A was assessed as a case study for the semi-quantification of degradation products using the parent compounds. The results showed significant degradation of tylosin A in aqueous solution (~96%) as well as in spiked and incurred honey dissolved in water (~50% and ~29%, respectively) after heating at 100°C for 90 min. However, at a lower heating temperature of 70°C, degradation was only observed in water (~31%). When stored at room temperature (27°C) for one year, tylosin A degraded significantly (~47%) in an incurred honey sample. Tylosin B, the only reported degradation product of tylosin A in honey so far, increased significantly in aqueous solution under all treatments, but it only increased in spiked water-honey mixture after heating at 100°C. Two new degradation products, namely 5-O-mycaminosyltylonolide (OMT) and lactenocin, were tentatively identified in water and spiked honey after heating at 100°C. The results of the present study reinforce the conclusion that relying only on the water model or spiked food matrix is not sufficient to understand the thermal degradation of antibiotics in food matrices. Finally, a semi-quantification of tylosin B with a relative error of 20% in an incurred honey sample was possible using the response factor of tylosin A, its parent compound. The results of this study prove that a semi-quantification using the parent compound to quantify its degradation compound can provide satisfactory results, but this will be analyte-dependent. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of Mycobacterium avium complex (MAC) pulmonary disease is increasing worldwide. We conducted a systematic review and meta-analysis to determine the treatment success rate of antibiotic therapy in MAC pulmonary disease and evaluate the effectiveness of aminoglycoside-containing regimens.Methods: We searched literature between 1 January 1980 to 19 June 2019. Studies with diagnosis criteria based on the current guidelines that reported treatment outcomes were included. We defined treatment success as the achievement of culture conversion and completion of the planned treatment without relapse while on treatment.Results: We retrieved 45 studies including 3862 patients. The estimated pooled treatment success rate was 68.1% [95% confidence interval (CI) 64.7-71.4%]. Based on the Cochrane tool, the included studies had a low risk of bias. Forty-two studies reported macrolide-containing regimens, while 6 studies included aminoglycoside-containing regimens. Macrolide-containing regimens led to better treatment success rates comparing to non-macrolide-containing regimens; 69% vs 58.5%, respectively. Treatment duration of 12 months or more showed better results.Conclusion: Poor treatment success rate of MAC pulmonary disease calls for more randomized clinical trials designed based on consensus definitions of the disease diagnosis and treatment. New drugs with a better adherence rate need to be developed.Systematic Review Registration: PROSPERO (pending registration ID: 151674). [ABSTRACT FROM AUTHOR]

The correlation between the allocation of trisoxazole macrolides in the capitums, appendages, and bases of the sponge Penares cf. nux and the surface-attached bacteria on the corresponding parts was examined. The kabiramide contents were highest in the capitums, followed by the appendages and bases. Conversely, direct counts of cultivable surface-attached bacteria showed that the bacteria aggregate more densely on the surfaces of the bases. This suggested the repelling effects of the kabiramides against the fouling bacteria, particularly on the capitums and appendages. Twenty-two bacterial strains were isolated and identified to 15 species; however, none has shown the potentials as a producer of any secondary metabolites in the sponge P. nux. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is affected by many environmental factors, including infections and antibiotics. However, the relationship between antibiotics and psoriasis is inadequately studied. Some antibiotics were listed as triggering factors; others showed benefit for psoriasis control. The aim of this article is to review current evidence that may help identify appropriate antibiotics for patients with psoriasis. Areas covered: The PubMed, Embase, Clinicalkey databases, and google scholar were searched for relevant articles published up to May 2019. Literature regarding antibiotics and psoriasis were included. Six randomized controlled trials and four controlled or cohort studies were identified in 13 kinds of antibiotics. Expert opinion: Macrolides and rifampin showed decrease of psoriasis area and severity index score in plaque-type psoriasis, while penicillin revealed no statistically significant improvement in guttate psoriasis. Previously tetracyclines were considered as triggering factors, but data were found only in cases or retrospective studies. Mechanisms were thought to be related to immunomodulation rather than bacteria inhibition. Research gap in the influence of genetic susceptibility, the impact on microbiota, and the mode of actions remain to be investigated. [ABSTRACT FROM AUTHOR]

A method was established for coupled solid phase extraction-ultra performance liquid chromatography and mass spectrometry, to simultaneously detect 12 common antibiotics belonging to 4 types (sulfonamides, macrolides, fluoroquinolones and cephalosporins) in the Harbin section of the Songhua River basin, Northeastern China. The results showed that the 12 antibiotics monitored were all detected to varying degrees, with 100% detection rates for sulfamethoxazole (SMX), cefazolin (CFZ), ofloxacin (OFL), flumequine (FLU), azithromycin (AZI) and roxithromycin (ROX), and the highest levels were in winter, the lowest in summer. The total concentrations of all 12 antibiotics in spring, summer, autumn and winter, were 39.7, 9.6, 27.5 and 136.2 ng L−1, respectively. Seasonality was also observed in antibiotic distribution along the riverbank, with winter concentrations of all antibiotics detected upstream of the Harbin section being lower than the downstream section; in summer, except for CFZ, the concentrations of all antibiotics detected were higher upstream, than downstream of the Harbin section. Finally, the health risks to people of different ages caused by residual antibiotic contamination in the Songhua River were evaluated, and the results showed that the risk of antibiotics was far lower than 1, with no direct threat to human health established. [ABSTRACT FROM AUTHOR]

Two new polyketide metabolites, the 12-membered macrolides 4-hydroxy-12-methyloxacyclododecane-2,5,6-trione (1) and 12-methyloxacyclododecane-2,5,6-trione (2), were isolated from the endophytic fungal strain Cladosprium colocasiae A801 of the plant Callistemon viminalis, together with five known derivatives. Their structures were fully characterized by means of detailed spectroscopic analysis for new structures, and in comparison with published data for known compounds. The antibacterial, cytotoxic, and α-glucosidase inhibitory activities of the new compounds 1 and 2 were evaluated. [ABSTRACT FROM AUTHOR]

A series of novel 4″-O-desosaminyl clarithromycin derivatives with 11, 12-arylalkyl side chains was synthesized by coupling 6-deoxy-desosamine donors (18, 19) with 4″-OH of compounds 5a–c. The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive and resistant pathogens, and compounds 21d and 21e displayed significant improvement of activities against resistant pathogens. [ABSTRACT FROM AUTHOR]

Sulfur mustard (SM) is a blistering chemical warfare agent that was used during the World War I and in the Iraq–Iran conflict. The aim of this paper is to discuss and critically review the published results of experiments on the treatment of SM poisoning based on our clinical and research experience. The victims must remove from the contaminated zone immediately. The best solution for decontamination is large amounts of water, using neutral soap and 0.5% sodium hypochlorite. Severely intoxicated patients should be treated according to advanced life support protocols and intensive care therapy for respiratory disorders and the chemical burn. Sodium thiosulfate infusion (100–500 mg/kg/min) should be started up to 60 min after SM exposure. However, N-acetyle cysteine (NAC) is recommended, none of them acts as specific or effective antidote. The important protective and conservative treatment of SM-induced pulmonary injuries include humidified oxygen, bronchodilators, NAC as muculytic, rehydration, mechanical ventilation, appropriate antibiotics and respiratory physiotherapy as clinically indicated. Treatment of acute SM ocular lesions start with topical antibiotics; preferably sulfacetamide eye drop, continue with lubricants, and artificial tears. Treatment for cutaneous injuries include: moist dressing; preferably with silver sulfadiazine cream, analgesic, anti-pruritic, physically debridement, debridase, Laser debridement, followed by skin autologous split-thickness therapy as clinically indicated. The new suggested medications and therapeutic approaches include: anti-inflammatory agents, Niacinamide, Silibinin, Calmodulin antagonists, Clobetasol, full-thickness skin grafting for skin injuries; Doxycycline; Bevacizumab, and Colchicine for ocular injuries. Recommended compounds based on animal studies include Niacinamide, Aprotinin, des-aspartate-angiotensin-I, Gamma-glutamyltransferase, vitamin E, and vitamin D. In vitro studies revealed that Dimethylthiourea, L-nitroarginine, Methyl-ester, Sodium pyruvate, Butylated hydroxyanisole, ethacrynic acid, and macrolide antibiotics are effective. However, none of them, except macrolide antibiotics have been proved clinically. Avoidance of inappropriate polypharmacy is advisable. [ABSTRACT FROM AUTHOR]

The total syntheses of four polyketides, surinone B (1), alatanones A-B (2-3), and trineurone A (4) were accomplished through an efficient and unified strategy via one-pot C-acylation reaction coupling 1,3-cyclohexadiones with EDC-activated acids under mild conditions. Alatanone A (2) was found to be a potent anti-microbial agent against Gram-positive and Gram-negative bacteria with MIC 31.25 μg/ml while alatanone B (3) was found to be a potent anti-fungal agent against Cladosporium cladosporioides with MIC 62.5 μg/ml compared to cycloheximide MIC 125 μg/ml. Our methodology allows performing kilogram scale of these scarce polyketides for the development of new antimicrobials. [ABSTRACT FROM AUTHOR]

Antibiotics, primarily doxycycline and azithromycin, make up most oral prescriptions Since 2014, the 15 most frequently prescribed oral medications represented 83 per cent of all prescribed oral medications and belonged to eight unique classes of medicine. Keywords: Drugs; dry eye; legislation; oral medications EN Drugs dry eye legislation oral medications 425 427 3 04/12/21 20210501 NES 210501 Optometry in New Zealand has evolved from a focus on clinical optics and refraction when it was first offered as a three-year Diploma by the University of Auckland in 1965, to the five-year Bachelor Honours degree now on offer. SP 1 sp While the original I Medicines Act 1981 i allowed an optometrist to 'sell or supply a medicine for use in cleaning, soaking, or lubricating contact lenses', the legislation permitting therapeutic medication use by optometrists came through as an amendment to the I Optometrists and Dispensing Opticians Act i in 1996. Left: the total number of prescriptions by optometrists in New Zealand, broken down into topical (ocular) medications in blue, and oral medications in orange, since optometrists were permitted to prescribe them in 2014. [Extracted from the article]

Background: Shigella remains the primary cause of diarrhoea in paediatric patients worldwide and accounts for up to 40,000 deaths per year. Current guidelines for the treatment of shigellosis are based on data which are over a decade old. In an era of increasing antimicrobial resistance, an updated review of the appropriate empirical therapy for shigellosis in children is necessary, taking into account susceptibility patterns, cost and the risk of adverse events. Methods: A systematic review of the current published literature on the treatment of shigella dysentery was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: The initial search produced 131 results, of which nine studies met the inclusion criteria. The quality of the studies was assessed as per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. International guidelines were also reviewed. There is a lack of current research regarding the clinical treatment of shigellosis in paediatric and adult patients, despite rising antimicrobial resistance worldwide. In particular, there is a lack of studies assessing the non-susceptibility of community-acquired strains, with almost all published research pertaining to microbiological data from hospital-based settings. Discussion: Current WHO guidelines support the use of fluoroquinolones (first-line), β-lactams (second-line) and cephalosporins (second-line) which accords with currently available evidence and other international guidelines, and there is no strong evidence for changing this guidance. Azithromycin is appropriate as a second-line therapy in regions where the rate of non-susceptibility of ciprofloxacin is known to be high, and research suggests that, from a cardiac point of view, azithromycin is safer than other macrolide antibiotics. Cefixime is also a reasonable alternative, although its use must be weighed against the risk of dissemination of extended-spectrum β-lactamase-producing organisms. [ABSTRACT FROM AUTHOR]

Purpose: Aldosterone-producing adenoma (APA) is the main curable cause of endocrine hypertension cause of primary aldosteronism (PA) and it is in up to 66% of all cases investigated with adrenal vein sampling (AVS). Mutations in the KCNJ5 potassium channel involve up to 70% of APA and cause the most florid PA phenotypes. The recent finding that macrolide antibiotics specifically inhibit in vitro the altered function of mutated KCNJ5 channels has opened new horizons for the diagnosis and treatment of APA with KCNJ5 mutations in that it can allow identification and target treatment of PA patients harbouring a mutated APA. Thus, we aimed at investigating if clarithromycin and roxithromycin, two macrolides that potently blunt mutated Kir3.4 channel function in vitro, affect plasma aldosterone concentration in adrenal vein blood during AVS and in peripheral blood, respectively, in PA patients with a mutated APA. Methods and design: We designed two proof of concept studies. In study A: consecutive patients with an unambiguous biochemical evidence of PA will be exposed to a single dose of 250 mg clarithromycin during AVS, to assess its effect on the relative aldosterone secretion index in adrenal vein blood from the gland with and without APA. In study B: consecutive hypertensive patients submitted to the work-up for hypertension will receive a single oral dose of 150 mg roxithromycin. The experimental endpoints will be the change induced by roxithromycin of plasma aldosterone concentration and other steroids, direct active renin concentration, serum K+, systolic and diastolic blood pressure. Discussion: We expect to prove that: (i) clarithromycin allows identification of mutated APA before adrenalectomy and sequencing of tumour DNA; (ii) the acute changes of plasma aldosterone concentration, direct active renin concentration, and blood pressure in peripheral venous blood after roxithromycin can be a proxy for the presence of an APA with somatic mutations. [ABSTRACT FROM AUTHOR]

The total synthesis of an 18-membered polyhydroxylated macrolide (+)-Aspicilin was accomplished starting from commercially available enantiopure propylene oxide and D-(+)-gluconolactone by asymmetric synthetic approach. The key reactions involved are Witttig reaction, Sharpless asymmetric dihydroxylation, and Yamaguchi macrolactonization. [ABSTRACT FROM AUTHOR]

The total synthesis of 14-membered resorcylic acid macrolide, β-zearalenol, was accomplished starting from commercially available enantiomerically pure propylene oxide and methyl 2,4-dihydroxy-6-methylbenzoate using Grignard reaction, asymmetric dihydroxylation, Yamaguchi macrolactonization, and ring-closing metathesis as key steps. [ABSTRACT FROM AUTHOR]

Chagas disease is a neglected tropical disease; the only viable drugs are outdated and produce frequent side effects, and the overwhelming majority of cases are undiagnosed and untreated. Globally, people encounter numerous impediments to accessing biomedical treatment for Chagas disease. However, little is known about how people with Chagas disease manage their health outside the biomedical system. In this article, I discuss knowledge of ethnomedical treatments among marginalized patients in an endemic area of Bolivia. I interviewed 68 patients, 63 (93 percent) of whom had positive diagnoses for Chagas disease. Participants free listed 66 ethnomedical remedies either for Chagas disease (n = 39) or its cardiac symptoms. Participants stressed the accessibility of ethnomedical remedies in contrast to the multiple barriers to accessing biomedical treatment. Far from eroding in the face of globalization and sociopolitical marginalization, ethnomedical knowledge in the study area is dynamic and flexible, communicated through various channels. [ABSTRACT FROM AUTHOR]

A confirmatory HPLC-MS/MS method for the determination of residues of 11 antibacterial substances from different therapeutic class (β-lactams, lincosamides, fluoroquinolones, macrolides, pleuromutilins and sulfonamides) in animal feeds has been developed. The sample preparation is based on extraction with 0.1% formic acid in acetonitrile. Separation of the analytes was performed on biphenyl column with a gradient of 0.1% formic acid in acetonitrile and 0.1% formic acid in Milli-Q water. The developed method was validated following the guidelines included in the European Union Commission Decision 2002/657/EC. Limits of detection ranging from 79.22 to 193.60 µg/kg; instrumental and analytical linearity coefficients were above 0.99 for matrix-match calibration; and relative recoveries ranging from 76.04% to 117.39%. Repeatability of the method was in the range of 2.41-19.76% (CV, %), whereas reproducibility ranged from 6.52 to 28.40% (CV %). The method shown to be efficient and precise for quantification of the 11 antibacterial substances in animal feed. The results demonstrate the feasibility of the method for routine use to monitor these substances in feed. The validated method was successfully applied to eight suspect feed samples collected from the Association of American Feed Control Officials (AFFCO) and feed manufactures from Galicia (Spain) in June and July 2017. Of these 8 non-target feeds, 5 were positive for the presence of tiamulin, tylosin and sulfadiazine. [ABSTRACT FROM AUTHOR]

Introduction:Until recently considered as a minor health problem, the role of bronchiectasis is now increasingly recognized. New specific drugs are being approved for treatment of bronchiectasis. Possibly they will offer better perspectives to bronchiectatic subjects with evolving course. Areas covered:We provide an overview of aetiopathogenesis, clinics and non-pharmacological management, extending the topic of pharmacological treatment. Present therapies were extrapolated from other chronic lung diseases, but newer promising specific drugs are being awaited. Therapy aims at improving mobilisation of bronchial secretions and, if any, reversing airflow obstruction. Antibiotics are indicated to treat exacerbations, eradicate or reduce sputum bacterial load. Expert commentary:Over the last years evidence is mounted that bronchiectatic subjects with accelerated course of disease should be referred to secondary and tertiary centres. This requires increased awareness on the role and the frequency of bronchiectasis in primary care. Long-term continuous or cyclical use of antibiotics is recommended to stabilize or improve the course of evolving disease. Macrolides are a currently preferred option. Inhaled antibiotics are gaining importance and are the object of ongoing research interest. Practical challenges of inhaled antibiotic treatment remain the need of defining the best therapeutic regimen and optimizing true adherence. [ABSTRACT FROM PUBLISHER]

Background:The beneficial effect of macrolides for the treatment of community-acquired pneumonia (CAP) in combination with beta-lactams may be due to their anti-inflammatory activity. In patients with pneumococcal meningitis, the use of steroids improves outcomes only if they are administered before beta-lactams. The objective of this study was to compare outcomes in hospitalized patients with CAP when macrolides were administered before, simultaneously with, or after beta-lactams. Methods:Secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study database. Study groups were defined based on the sequence of administration of macrolides and beta-lactams. The study outcomes were time to clinical stability (TCS), length of stay (LOS) and in-hospital mortality. Accelerated failure time models were used to evaluate the adjusted impact of sequential antibiotic administration and time-to-event outcomes, while a logistic regression model was used to evaluate their adjusted impact on mortality. Results:A total of 99 patients were included in the macrolide before group and 305 in the macrolide after group. Administration of a macrolide before a beta-lactam compared to after a beta-lactam reduced TCS (3 vs. 4 days,p = .011), LOS (6 vs. 7 days,p = .002) and mortality (3 vs. 7.2%,p = .228). Conclusions:The administration of macrolides before beta-lactams was associated with a statistically significant decrease in TCS and LOS and a non-statistically significant decrease in mortality. The beneficial effect of macrolides in hospitalized patient with CAP may occur only if administered before beta-lactams. [ABSTRACT FROM AUTHOR]

The present study was designed to develop a concise synthetic route for macrolide, with the purpose of confirming the absolute configuration of natural dihydroresorcylide (1) and making it more easily accessible for biological evaluation. The absolute configuration of C-3 in natural 1 was revised to beRby comparison of the rotation sign of synthetic (R)-and (S)-1. The synthetic (R)-1was found to be a novel highly specific PTP1B inhibitor with an IC50value of 17.06 μM. [ABSTRACT FROM PUBLISHER]

Macrolide antibiotic roxithromycin was evaluated in terms of its genotoxic, cytotoxic and oxidative stress effects. For this purpose; 25, 50, 100 and 200 μg/mL concentrations of roxithromycin were dissolved in dimethyl sulfoxide and treated to human peripheral blood lymphocytes for two different treatment periods (24 and 48 h). In chromosome aberration (CA) and micronucleus (MN) tests, roxithromycin did not show genotoxic effect. But it induced sister chromatid exchange (SCE) at the highest concentration (200 μg/mL) for the 24-h treatment period and at all concentrations (except 25 μg/mL) for the 48-h treatment period. Looking at cytotoxic effect of roxithromycin, statistically insignificant decreases on mitotic index and proliferation index were observed. Roxithromycin decreased nuclear division index (NDI) at highest two concentrations (100 and 200 μg/mL) for the 24-h treatment period and at all concentrations (expect 25 μg/mL) for the 48-h treatment period. Total oxidant values, total antioxidant values and oxidative stress index did not change with roxithromycin treatment. Eventually, roxithromycin did not have genotoxic and oxidative stress effects in human-cultured lymphocytes. [ABSTRACT FROM AUTHOR]