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121. Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases Full Text available with Trip Pro

Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases (...) . These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides-2'-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2'-desoxy molecule (GS-560660)-with significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and H. influenzae We tested their effects on efferocytosis, phagocytosis

2017 American Journal of Physiology - Lung Cellular and Molecular Physiology

122. Macrolide Resistance and Its Impacts on M. Pneumoniae Pneumonia in Children: Comparison of Two Recent Epidemics in Korea Full Text available with Trip Pro

Macrolide Resistance and Its Impacts on M. Pneumoniae Pneumonia in Children: Comparison of Two Recent Epidemics in Korea The aim of this study was to investigate the change in macrolide resistance rate in pediatric Mycoplasma pneumoniae pneumonia and to evaluate the influence of macrolide-resistant M. pneumoniae (MRMP) on the clinical course of disease, by comparing 2 recent, consecutive epidemics in Korea.A total of 250 patients with M. pneumoniae pneumonia admitted to a single tertiary (...) hospital were enrolled in this study. Detection of MRMP was based on specific point mutations in domain V of the 23S rRNA gene. The medical records of enrolled patients were reviewed retrospectively, and the clinical courses and laboratory data were compared.The macrolide resistance rate of M. pneumoniae was 51.1% (48/94) in the 2011 epidemic, and 87.2% (136/156) in the 2015 epidemic. All MRMP isolates had the A2063G point mutation. In comparison of 2 epidemics, the mean age of patients with M

2017 Allergy, asthma & immunology research

123. PharmGKB summary: macrolide antibiotic pathway, pharmacokinetics/pharmacodynamics Full Text available with Trip Pro

PharmGKB summary: macrolide antibiotic pathway, pharmacokinetics/pharmacodynamics 28146011 2018 07 09 2018 11 13 1744-6880 27 4 2017 04 Pharmacogenetics and genomics Pharmacogenet. Genomics PharmGKB summary: Macrolide antibiotic pathway, pharmacokinetics/pharmacodynamics. 164-167 10.1097/FPC.0000000000000270 Fohner Alison E AE Departments of aGenetics bBioengineering, School of Medicine, Stanford University, Stanford, California cDivision of Pharmaceutics, College of Pharmacy and Comprehensive (...) Cancer Center, The Ohio State University, Columbus, Ohio, USA. Sparreboom Alex A Altman Russ B RB Klein Teri E TE eng R24 GM061374 GM NIGMS NIH HHS United States Journal Article Research Support, N.I.H., Extramural United States Pharmacogenet Genomics 101231005 1744-6872 0 Anti-Bacterial Agents 0 Macrolides 63937KV33D Erythromycin 83905-01-5 Azithromycin H1250JIK0A Clarithromycin IM Anti-Bacterial Agents chemistry therapeutic use Azithromycin therapeutic use Bacteria drug effects pathogenicity

2017 Pharmacogenetics and genomics

124. The Berkeleylactones, Antibiotic Macrolides from Fungal Coculture Full Text available with Trip Pro

The Berkeleylactones, Antibiotic Macrolides from Fungal Coculture A carefully timed coculture fermentation of Penicillium fuscum and P. camembertii/clavigerum yielded eight new 16-membered-ring macrolides, berkeleylactones A-H (1, 4, 6-9, 12, 13), as well as the known antibiotic macrolide A26771B (5), patulin, and citrinin. There was no evidence of the production of the berkeleylactones or A26771B (5) by either fungus when grown as axenic cultures. The structures were deduced from analyses (...) of spectral data, and the absolute configurations of compounds 1 and 9 were determined by single-crystal X-ray crystallography. Berkeleylactone A (1) exhibited the most potent antimicrobial activity of the macrolide series, with low micromolar activity (MIC = 1-2 μg/mL) against four MRSA strains, as well as Bacillus anthracis, Streptococcus pyogenes, Candida albicans, and Candida glabrata. Mode of action studies have shown that, unlike other macrolide antibiotics, berkeleylactone A (1) does not inhibit

2017 Journal of natural products

125. Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control Full Text available with Trip Pro

Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual (...) rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1

2017 BMC microbiology

126. Examining the role of macrolides and host immunity in combatting filarial parasites Full Text available with Trip Pro

Examining the role of macrolides and host immunity in combatting filarial parasites Macrocyclic lactones (MLs), specifically the avermectins and milbemycins, are known for their effectiveness against a broad spectrum of disease-causing nematodes and arthropods in humans and animals. In most nematodes, drugs in this class induce paralysis, resulting in starvation, impaired ability to remain associated with their anatomical environment, and death of all life stages. Initially, this was also

2017 Parasites & vectors

127. French Prospective Clinical Evaluation of the Aptima Mycoplasma genitalium CE-IVD Assay and Macrolide Resistance Detection Using Three Distinct Assays Full Text available with Trip Pro

French Prospective Clinical Evaluation of the Aptima Mycoplasma genitalium CE-IVD Assay and Macrolide Resistance Detection Using Three Distinct Assays The aim of this study was to evaluate the clinical performance of the Aptima Mycoplasma genitalium transcription-mediated amplification (MG-TMA) CE-marked for in vitro diagnosis (CE-IVD) assay for the detection of Mycoplasma genitalium in male and female clinical samples in comparison with the in-house real-time PCR (in-house PCR) assay routinely (...) used in our laboratory. A total of 1,431 clinical specimens obtained from 1,235 patients were prospectively collected at the Bacteriology Department of Bordeaux University Hospital (France). Additional research-use-only Aptima M. genitalium transcription-mediated amplification (TMA) assays, Alt1-TMA and Alt2-TMA, were performed on discordant specimens to determine M. genitalium infection status. All confirmed M. genitalium-positive specimens were tested for macrolide resistance using three assays

2017 Journal of clinical microbiology

128. Mycoplasma genitalium Macrolide and Fluoroquinolone Resistance Detection and Clinical Implications in a Selected Cohort in New Zealand Full Text available with Trip Pro

Mycoplasma genitalium Macrolide and Fluoroquinolone Resistance Detection and Clinical Implications in a Selected Cohort in New Zealand Mycoplasma genitalium has been associated with infections of the genitourinary tract, and prevalence is secondary to Chlamydia trachomatis The clinical observation of increasing treatment failure indicating antibiotic resistance, especially in cases of recurrent urethritis, has been confirmed by molecular testing. Mutations in the 23S rRNA gene can cause (...) macrolide resistance, and topoisomerase/gyrase mutations can cause fluoroquinolone resistance. In this study, 115 M. genitalium DNA-positive samples were analyzed. Eighty-nine (77.4%) samples had a 23S rRNA mutation present, and 26 (22.6%) were wild type (no resistance mutation). Fluoroquinolone mutation screening was performed on 86 (74.8%) of the 115 samples, of which 20 (23.3%) samples had a mutation or mutations associated with increased resistance. This study shows the increasing antibiotic

2017 Journal of clinical microbiology

129. The macrolide antibiotic renaissance Full Text available with Trip Pro

The macrolide antibiotic renaissance Macrolides represent a large family of protein synthesis inhibitors of great clinical interest due to their applicability to human medicine. Macrolides are composed of a macrocyclic lactone of different ring sizes, to which one or more deoxy-sugar or amino sugar residues are attached. Macrolides act as antibiotics by binding to bacterial 50S ribosomal subunit and interfering with protein synthesis. The high affinity of macrolides for bacterial ribosomes (...) , together with the highly conserved structure of ribosomes across virtually all of the bacterial species, is consistent with their broad-spectrum activity. Since the discovery of the progenitor macrolide, erythromycin, in 1950, many derivatives have been synthesised, leading to compounds with better bioavailability and acid stability and improved pharmacokinetics. These efforts led to the second generation of macrolides, including well-known members such as azithromycin and clarithromycin. Subsequently

2017 British journal of pharmacology

130. Clinical Characteristics of Macrolide-Resistant Mycoplasma pneumoniae from Children in Jeju Full Text available with Trip Pro

Clinical Characteristics of Macrolide-Resistant Mycoplasma pneumoniae from Children in Jeju Mycoplasma pneumoniae is the major pathogen of community-acquired pneumonia in children. The prevalence of macrolide-resistant M. pneumoniae (MRMP) is important owing to the limited alternative therapies for children. We analyzed 111 M. pneumoniae obtained from 107 children admitted for lower respiratory tract infection at Jeju National University Hospital between 2010 and 2015. Macrolide resistance of M (...) . pneumoniae was searched for using polymerase chain reaction (PCR) and sequencing. Of 107 clinical M. pneumoniae, 11 (10.3%) carried macrolide resistance mutations in the 23S rRNA gene. All macrolide resistance mutations were A2063G transitions. We found an acquired A2063G mutation of M. pneumoniae from a patient during macrolide treatment. Patients' characteristics and clinical severity did not differ between those with MRMP and macrolide-sensitive M. pneumoniae, with the exception of frequent pleural

2017 Journal of Korean medical science

131. Additional corticosteroids or alternative antibiotics for the treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia Full Text available with Trip Pro

Additional corticosteroids or alternative antibiotics for the treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia 29042865 2018 11 13 1738-1061 60 8 2017 Aug Korean journal of pediatrics Korean J Pediatr Additional corticosteroids or alternative antibiotics for the treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia. 245-247 10.3345/kjp.2017.60.8.245 Yang Eun-Ae EA Department of Pediatrics, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University

2017 Korean journal of pediatrics

132. Prevalence of Genotypes That Determine Resistance of Staphylococci to Macrolides and Lincosamides in Serbia Full Text available with Trip Pro

Prevalence of Genotypes That Determine Resistance of Staphylococci to Macrolides and Lincosamides in Serbia Macrolides, lincosamides, and streptogramins (MLS) resistance genes are responsible for resistance to these antibiotics in Staphylococcus infections. The purpose of the study was to analyze the distribution of the MLS resistance genes in community- and hospital-acquired Staphylococcus isolates. The MLS resistance phenotypes [constitutive resistance to macrolide-lincosamide-streptogramin B (...) (cMLSb), inducible resistance to macrolide-lincosamide-streptogramin B (iMLSb), resistance to macrolide/macrolide-streptogramin B (M/MSb), and resistance to lincosamide-streptogramin A/streptogramin B (LSa/b)] were determined by double-disc diffusion method. The presence of the MLS resistance genes (ermA, ermB, ermC, msrA/B, lnuA, lnuB, and lsaA) were determined by end-point polymerase chain reaction in 179 isolates of staphylococci collected during 1-year period at the Center for Microbiology

2017 Frontiers in public health

133. Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp. ZQ4BG Full Text available with Trip Pro

Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp. ZQ4BG Bioactive natural products from mangrove-derived actinomycetes are important sources for discovery of drug lead compounds. In this study, an extract prepared from culture of an actinomycete Streptomyces sp. ZQ4BG isolated from mangrove soils was found to have activity in inhibiting proliferation of glioma cells. Large culture of this mangrove actinomycete in Gause's liquid medium resulted in isolation of seven novel (...) polyene-polyol macrolides, named as flavofungins III-IX (3-9), together with known flavofungins I (1) and II (2) and spectinabilin (10). Structures of these isolated compounds were elucidated by extensive NMR analyses and HRESIMS data. The stereochemical assignments were achieved by a combination of NOE information, universal NMR database, and chemical reactions including preparation of acetonide derivatives and Mosher esters. Flavofungins IV-VIII (4-8) are rare 32-membered polyene-polyol macrolides

2017 Scientific reports

134. A Review Study on Macrolides Isolated from Cyanobacteria Full Text available with Trip Pro

A Review Study on Macrolides Isolated from Cyanobacteria Cyanobacteria are rich sources of structurally-diverse molecules with promising pharmacological activities. Marine cyanobacteria have been proven to be true producers of some significant bioactive metabolites from marine invertebrates. Macrolides are a class of bioactive compounds isolated from marine organisms, including marine microorganisms in particular. The structural characteristics of macrolides from cyanobacteria mainly manifest (...) in the diversity of carbon skeletons, complexes of chlorinated thiazole-containing molecules and complex spatial configuration. In the present work, we systematically reviewed the structures and pharmacological activities of macrolides from cyanobacteria. Our data would help establish an effective support system for the discovery and development of cyanobacterium-derived macrolides.

2017 Marine drugs

135. Prospective Evaluation of ResistancePlus MG, a New Multiplex Quantitative PCR Assay for Detection of Mycoplasma genitalium and Macrolide Resistance Full Text available with Trip Pro

Prospective Evaluation of ResistancePlus MG, a New Multiplex Quantitative PCR Assay for Detection of Mycoplasma genitalium and Macrolide Resistance Mycoplasma genitalium is a significant pathogen for which first-line treatment is becoming less effective due to increased resistance to macrolides. As conventional culture and antimicrobial susceptibility testing is not feasible for routine detection of this pathogen, molecular markers such as detection of mutations in the 23S rRNA gene have been (...) described to predict resistance. Recently, a novel multiplex quantitative PCR (qPCR) assay, ResistancePlus MG, has been described for the simultaneous detection of Mycoplasma genitalium and macrolide resistance. In the current study, the clinical performance of the assay was evaluated on 1,089 consecutive urine and anogenital swab samples in symptomatic and asymptomatic male and female patients. Overall, 6.0% were positive for M. genitalium, with 63.1% having macrolide resistance-associated mutations

2017 Journal of clinical microbiology

136. New Mandelalides Expand a Macrolide Series of Mitochondrial Inhibitors Full Text available with Trip Pro

New Mandelalides Expand a Macrolide Series of Mitochondrial Inhibitors Mandelalides A-D (1-4) are macrocyclic polyketides known to have an unusual bioactivity profile influenced by compound glycosylation and growth phase of cultured cells. The isolation and characterization of additional natural congeners, mandelalides E-L (5-12), and the supply of synthetic compounds 1 and 12, as well as seco-mandelalide A methyl ester (13), have now facilitated mechanism of action and structure-activity (...) relationship studies. Glycosylated mandelalides are effective inhibitors of aerobic respiration in living cells. Macrolides 1 and 2 inhibit mitochondrial function similar to oligomycin A and apoptolidin A, selective inhibitors of the mammalian ATP synthase (complex V). 1 inhibits ATP synthase activity from isolated mitochondria and triggers caspase-dependent apoptosis in HeLa cells, which are more sensitive to inhibition by 1 in the presence of the glycolysis inhibitor 2-deoxyglucose. Thus, mandelalide

2017 Journal of medicinal chemistry

137. A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity Full Text available with Trip Pro

A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity Broad-spectrum antibiotics are frequently prescribed to children. Early childhood represents a dynamic period for the intestinal microbial ecosystem, which is readily shaped by environmental cues; antibiotic-induced disruption of this sensitive community may have long-lasting host consequences. Here we demonstrate that a single pulsed macrolide antibiotic treatment (PAT) course early (...) in life is sufficient to lead to durable alterations to the murine intestinal microbiota, ileal gene expression, specific intestinal T-cell populations, and secretory IgA expression. A PAT-perturbed microbial community is necessary for host effects and sufficient to transfer delayed secretory IgA expression. Additionally, early-life antibiotic exposure has lasting and transferable effects on microbial community network topology. Our results indicate that a single early-life macrolide course can alter

2017 Nature communications

138. Outpatient Macrolide Antibiotic Prescribing in the United States, 2008–2011 Full Text available with Trip Pro

Outpatient Macrolide Antibiotic Prescribing in the United States, 2008–2011 National Ambulatory Medical Care Survey data were used to assess outpatient macrolide prescribing and selection. Conditions for which macrolides are firstline therapy represented 5% of macrolide prescribing. Family practitioners selected macrolides for children more frequently than pediatricians. Macrolides are an important antibiotic stewardship target.

2017 Open forum infectious diseases

139. Macrolide-resistant Mycoplasma pneumoniae prevalence and clinical aspects in adult patients with community-acquired pneumonia in China: a prospective multicenter surveillance study Full Text available with Trip Pro

Macrolide-resistant Mycoplasma pneumoniae prevalence and clinical aspects in adult patients with community-acquired pneumonia in China: a prospective multicenter surveillance study Drug resistant Mycoplasma pneumoniae (MP) is a rising issue in the management of community-acquired pneumonia (CAP). Epidemiological monitoring is essential for identifying resistant patterns of MP isolates against various antibiotics in adult CAP patients.This is a prospectively designed multicenter study conducted (...) and β-lactams plus quinolones. Macrolide resistance was as high as 80% and 72% against erythromycin (ERY) and azithromycin (AZM) respectively, which were associated with the A2063G transition mutation in domain V of the 23S ribosomal RNA (rRNA) gene. Six strains with mild to moderate ERY-resistant level were still susceptible to AZM. Tetracycline (TET), minocycline (MIN) and quinolones [moxifloxacin (MOX) and fluoroquinolones] had no signs of resistance.High resistance was observed with macrolides

2017 Journal of thoracic disease

140. Phenotypic and genotypic characterization of macrolide resistance among Staphylococcus aureus isolates in Isfahan, Iran Full Text available with Trip Pro

Phenotypic and genotypic characterization of macrolide resistance among Staphylococcus aureus isolates in Isfahan, Iran Macrolide, lincosamide and streptogramin B (MLS B) are noteworthy antibiotics for the treatment of Staphylococcus aureus infections. The purpose of this study, was to determine the phenotypic and genotypic characterization of macrolide resistance, among S. aureus, isolated from clinical samples and nasal swabs.Totally, 162 non-duplicate S. aureus isolates were collected from (...) B (iMLS B), macrolide-streptogramin B-resistant (MS B) and lincosamide-streptogramin-A resistance (LS A) phenotype was 32%, 6%, 6% and 2%, respectively. The most common erythromycin resistance genes, in S. aureus isolates were ermC (35.2%), followed by ermA (20.4%) and msrA (17.3%). Meanwhile, msrA was detected in 43.6% of MRSA isolates. The frequency of coexistence of ermA+ermC+msrA, in S. aureus isolates was 7% and it was only detected in MRSA isolates.In the current study, cMLS B phenotype

2017 Iranian journal of microbiology

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