Activities of 16-membered ring macrolides and telithromycin against different genotypes of erythromycin-susceptible and...
OBJECTIVES: To test four 16-membered macrolides (josamycin, spiramycin, midecamycin and rokitamycin) along with other compounds in the same class (erythromycin, clarithromycin, roxithromycin and azithromycin) plus clindamycin and telithromycin, against Streptococcus pyogenes and Streptococcus pneumoniae isolates with well-characterized resistance genotypes. METHODS: Four hundred and eighty-six isolates of S. pyogenes and 375 isolates of S. pneumoniae were assayed for their macrolide susceptibilities and investigated by PCR to detect their different erythromycin resistance genes. All strains had been isolated over the period 2002-2003 from specimens of different human origin obtained in 14 different Italian centres. RESULTS: All 16-membered macrolides showed very low MICs (MIC(50)s and MIC(90)s, , or =0.06-0.5 mg/L) for the erythromycin-susceptible isolates and for those with the M phenotype, but the ...https://pubblicazioni.unicam.it/handle/11581/235334
Resistance to Macrolides and Lincosamides | cmpt
Lincosamides specifically inhibit the peptidyl transferase reaction while macrolides block the exit tunnel inducing premature dissociation of peptidyl-tRNAs from the ribosome. (3,4). The binding sites for macrolides and lincosamide antibiotics lay in or near the active site of the peptide bond formation called peptidyl transferase center (PTC). (3) Because the binding sites for macrolides and lincosamides overlap, modification of any of these binding sites usually confers cross resistance to these antibiotics. (4,5). Spectrum of activity. Macrolides are active against gram positive bacteria and are effective against many of the pathogens associated with sexually transmitted diseases: Neisseria gonorrhoeae, Haemophilus ducreyi, Chlamydia trachomatis, and Ureaplasma urealyticum.. Gram negative bacilli are generally resistant; some exceptions ...http://cmpt.ca/resistance-to-macrolides-and-lincosamides/
Overview: Macrolides possess diverse natural activities and an capability to modulate - How NF-B is activated: the role of the...
90% after the widespread use of chronic erythromycin therapy (157). The characteristics of the clinical response to macrolide therapy are summarized as follows (71 157 202 258 (i) it takes up to 3 months of therapy for macrolides to show a significant effect; (ii) doses that are much lower than the MIC (i.e. low-dose macrolide therapy) are effective; (iii) the effect is seen even when patients are infected with macrolide-resistant bacteria such as (214) Mouse monoclonal to CD152(FITC). and (241 290 Clarithromycin has been shown to improve the transportability of secretions in human subjects (241 290 This mucoregulatory effect is seen even Aliskiren hemifumarate when hypersecretion is not induced by bacteria. Improved mucus transport may be associated with changes in the biophysical properties of secretions as well as with reduced inflammation. Ion transport. Tamaoki and coworkers (289) studied the effects of ...http://cancercurehere.com/?p=2115
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Antimicrobial drug use and macrolide-resistant **Streptococcus pyogenes**, Belgium - Institutional Repository University of...
In Belgium, decreasing macrolide, lincosamide, streptogramins B, and tetracycline use during 19972007 correlated significantly with decreasing macrolide-resistant Streptococcus pyogenes during 19992009. Maintaining drug use below a critical threshold corresponded with low-level macrolide-resistant S. pyogenes and an increased number of erm(A)-harboring emm77 S. pyogenes with low fitness costs. ...https://repository.uantwerpen.be/link/irua/101027
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Solithromycin is a novel ketolide antibiotic. Solithromycin (CAS 760981-83-7) can be used for anti-infection, and It is expected to be the first macrolide antibiotic available in intravenous, oral, and pediatric suspension formulations in over 20 years.http://www.adooq.com/solithromycin.html
Efficacy and Safety Study of Oral Solithromycin (CEM-101) Compared to Oral Moxifloxacin in Treatment of Patients With Community...
Community-acquired bacterial pneumonia (CABP) is an acute infection of the pulmonary parenchyma with symptoms such as fever or hypothermia, chills, rigors, chest pain, and/or dyspnea. The widespread emergence of antibiotic resistant pathogens, including the macrolide-resistant Streptococcus pneumoniae, has resulted in a need for new and effective antibiotics that have activity against CABP pathogens. Solithromycin is a fourth generation macrolide antibiotic with excellent activity against resistant S. pneumoniae and other key typical and atypical bacterial respiratory pathogens. A completed Phase 2 study showed comparable efficacy to levofloxacin in adults with CABP ...https://clinicaltrials.gov/ct2/show/NCT01756339?cond=%22Pneumonia%2C+Bacterial%22&rank=11
Improving Glycosyltransferase by RACHITT Gene Shuffling | SBIR.gov
DESCRIPTION (provided by applicant): Glycosyltransferases involved in linking polyketide macrolactones with deoxysugars are key enzymes for combinatorial biosynthesis of novel macrolide anti-infective agents. In this proposal, a new gene shuffling technology, RACHITT, is applied to the desosarninyl transferase (Des VII) from the pikromycin biosynthetic pathway of Streptomyces venezuelae. Des VII is an enzyme with remarkable inherent substrate flexibility, and we expect to expand further its substrate spectrum to include 16-membered ring macrolactones. This technology is expected to provide glycosyltransferase enzymes that can catalyze the biosynthesis of 12-, 14-, and 16-membered ring macrolides. Moreover, we expect to generate a recombinant DesVII that has a higher enzymatic activity toward the 14-membered ring macrolactone narbonolide. This will be a key step in combinatorial biosynthesis of ketolide ...https://www.sbir.gov/sbirsearch/detail/69495
Lincomycin, And Clindamycin Azithromycin Clarithromycin Clindamycin Erythromycin Lincomycin The macrolides are similar in structure and activity. All the macrolides, lincomycin, and clindamycin are absorbed when taken orally, and erythromycin, lincomycin, azithromycin, and clindamycin can also be given parenterally. All are primarily bacteriostatic and bind to the 50S subunit of the ribosome, thus inhibiting bacterial protein synthesis. These drugs are active against aerobic and anaerobic gram-positive cocci, with the exception of enterococci, and against gram-negative anaerobes.. Pharmacology After oral or parenteral administration, these drugs diffuse well into body fluids, except CSF. Excretion is mainly in the bile, and dose adjustments are not required when renal failure is present.. Indications. Erythromycin is active against gram-positive cocci (including anaerobes), with the exception of enterococci; but many Staphylococcus aureus ...http://antibioticinformation.blogspot.com/2005/12/macrolides.html
Meta-analysis of bacterial resistance to macrolides : Journal of Antimicrobial Chemotherapy - oi
Objectives: Understanding changing resistance patterns is important in determining appropriate antibiotic treatments. This meta-analysis systematically evaluated resistance of Streptococcus pneumoniae and Streptococcus pyogenes to macrolide antibiotics among patients with community-acquired respiratory tract infections.. Methods: MEDLINE and EMBASE databases were searched and experts were consulted to identify published and unpublished literature reporting macrolide resistance rates. Identified studies were evaluated by two independent reviewers; those meeting a priori specified criteria (resistance by patient condition and strain, resistance thresholds, 1997-2003 isolates) were included. Data from included studies were abstracted by two independent reviewers using a standard review form. Discrepancies in abstracted data were resolved by the study investigator.. Results: Random-effects meta-analysis was performed for outcomes present in at ...http://oxfordindex.oup.com/view/10.1093/jac/dki060
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The Role of Macrolide Antibiotics in Increasing Cardiovascular Risk | JACC: Journal of the American College of Cardiology
The present meta-analysis, involving 20,819,622 individuals from 33 studies, found significantly increased risk of SCD or VTA, cardiovascular death, and MI in users of macrolides. This association with increased CV risk seemed to be present with current use of macrolides and disappeared for former use. In stratified analysis, azithromycin, clarithromycin, and erythromycin were associated with increased risk of SCD or VTA and azithromycin and clarithromycin with increased risk of CV death, but only clarithromycin was associated with increased risk of all-cause mortality. In terms of absolute risk, use of macrolides would account for an estimated 118.1 SCD or VTAs, 36.6 SCDs, and 38.2 cardiac deaths per 1 million courses.. Interpretation of the clinical importance of this finding is delicate. The estimates for additional SCDs and cardiac deaths per 1 million treatment courses are remarkably close, suggesting ...http://www.onlinejacc.org/content/66/20/2173
Notes from Dr. RW: Macrolides and mortality in critically ill patients with community acquired pneumonia
Conclusions:In observational studies of almost 10,000 critically ill patients with community-acquired pneumonia, macrolide use was associated with a significant 18% relative (3% absolute) reduction in mortality compared with nonmacrolide therapies. After pooling data from studies that provided adjusted risk estimates, an even larger mortality reduction was observed. These results suggest that macrolides be considered first-line combination treatment in critically ill patients with community-acquired pneumonia and support current guidelines ...http://doctorrw.blogspot.com/2014/08/macrolides-and-mortality-in-critically.html
Cempra Pharmaceuticals Presents New Data on Its Multi-Drug Resistant Anti-Infective Portfolio, Solithromycin (CEM-101) and...
Mechanism of telithromycin toxicity is proposed to be due to its inhibition of nicotinic acetylcholine receptors the novel fluoroketolide, solithromycin, like ohttps://www.drugs.com/clinical_trials/cempra-pharmaceuticals-presents-new-data-multi-resistant-anti-infective-portfolio-solithromycin-cem-10381.html
... can differ in their macrocyclic ring (modified to create clarithromycin (Biaxin©) and azithromycin (Zithromax©) with improved pharmacokinetic properties) and sugars. For telithromycin (Ketek®), the sugar at the 3-position was removed and replaced with a keto group - hence the class name of ketolides - and an additional modification allowed for binding to a secondary site on the bacterial ribosome, resulting in enhanced activity against resistant strains. ...http://www.aurametrix.com/topics/macrolides
Fidelta :: Novel Desosamine-Modified 14- and 15-membered Macrolides without Antibacterial Activity
Included was annelation of N-substituted 2-imino-1,3-oxazolidine 1 and 1,3-oxazolidin-2-one 2 moiety to the 2',3'-positions of desosamine ...http://fidelta.eu/resources/data-sheets/chemistry/novel-desosamine-modified-14-and-15-membered-macrolides-without-antibacterial-activity/
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Intravenous (IV) Administration of Cempra Pharmaceutical's Solithromycin (CEM-101) Demonstrates Excellent Systemic Tolerability...
Cempra Pharmaceuticals, a developer of differentiated antibiotics, today announced an oral presentation showing that intravenous (IV) solithromycin demonstrates excellent tolerabilityhttp://www.medindia.net/health-press-release/Intravenous-IV-Administration-of-Cempra-Pharmaceuticals-Solithromycin-CEM-101-Demonstrates-Excellent-Systemic-Tolerability-in-a-Phase-1-Clinical-Trial--102187-1.htm
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Macrolide Antibiotics - Health tips, Health care, Diseases treatment, Cancer, Blood Pressure
The Topic in which i am going to write today is a Topic on which you would have listen and read almost thousand of times because it is a ver ...http://health38.blogspot.com/2012/08/macrolide-antibiotics.html
Pharmacokinetics and Safety of Solithromycin Capsules in Adolescents - Full Text View - ClinicalTrials.gov
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...https://clinicaltrials.gov/ct2/show/NCT01966055?recr=Open&cond=%22Bacterial+Infections%22&rank=6
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