Inhalation of macrolides: a novel approach to treatment of pulmonary infections.
Abstract
Systemic antibiotic treatment is established for many pulmonary diseases, e.g., cystic fibrosis (CF), bronchiectasis and chronic obstructive pulmonary disease (COPD) where recurrent bacterial infections cause a progressive decline in lung function. In the last decades inhalative administration of antibiotics was introduced into clinical routine, especially tobramycin, colistin, and aztreonam for treatment of CF and bronchiectasis. Even though they are important in systemic treatment of these diseases due to their antimicrobial spectrum and anti-inflammatory and immunomodulatory properties, macroli...
Source: Adv Data - March 19, 2015 Category: Epidemiology Authors: Siekmeier R, Hofmann T, Scheuch G Tags: Adv Exp Med Biol Source Type: research
Efficacy and side effects of antibiotics in the treatment of acute rhinosinusitis: a systematic review.
CONCLUSION: The usage of antibiotics in ARS is widespread and there seems to be only slight added benefit in the usage of antibi- otics over placebo in the treatment of ARS. Hence, larger scale studies should be done in the future to confirm the results of these studies.
PMID: 25756071 [PubMed - in process] (Source: Rhinology)
Source: Rhinology - March 12, 2015 Category: ENT & OMF Tags: Rhinology Source Type: research
Killing of by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin using drug minimum inhibitory concentrations and mutant prevention concentrations
Streptococcus pneumoniae is a prevalent cause of community-acquired upper and lower respiratory tract infections and spans all age groups. Drug-resistant pneumococcal strains have increased in prevalence, and numerous reports have documented the selection of drug-resistant strains during therapy—that is, the organism isolated from the patient was initially susceptible to the treatment antibiotic but resistance or reduced susceptibility developed during therapy [1,2]. (Source: International Journal of Antimicrobial Agents)
Source: International Journal of Antimicrobial Agents - February 16, 2015 Category: Drugs & Pharmacology Authors: J.M. Blondeau, S.D. Shebelski, C.K. Hesje Source Type: research
Genetic Diversity of Campylobacter jejuni Isolates from Korea and Travel-Associated Cases from East and Southeast Asian Countries.
Abstract
Forty domestic and travel-associated Campylobacter jejuni isolates were analyzed by profiling 7 pathogenic genes (cdtB, cadF, Cj0131, ciaB, racR, wlaN, and virB11) along with multilocus sequence typing (MLST) and antimicrobial susceptibility testing. cdtB, cadF, and Cj0131 were present in all isolates, whereas virB11 was not detected in either domestic or travel-associated isolates. ciaB was present in all domestic isolates and 94% of travel-associated isolates. The respective detection rates of racR and wlaN in domestic and travel-associated isolates were 94% and 71% and 35.3% and 23%, respective...
Source: Japanese Journal of Infectious Diseases - November 26, 2014 Category: Infectious Diseases Authors: Cha I, Kim NO, Nam JG, Choi ES, Chung GT, Kang YH, Hong S Tags: Jpn J Infect Dis Source Type: research
"First-Wave" Bias When Conducting Active Safety Monitoring of Newly Marketed Medications with Outcome-Indexed Self-Controlled Designs
Large health care databases are used extensively for pharmacoepidemiologic studies. Unique methodological issues arise when applying self-controlled designs (i.e., using within-person comparisons) for active surveillance of newly marketed drugs. We use 3 examples to illustrate bias related to population-level exposure time trends when using outcome-indexed self-controlled (i.e., case-crossover) designs for active surveillance and evaluate the ability of the case-time-control design to adjust for bias from population-level exposure time trends. We mimicked active surveillance by conducting sequential analyses after market e...
Source: American Journal of Epidemiology - September 8, 2014 Category: Epidemiology Authors: Wang, S. V., Schneeweiss, S., Maclure, M., Gagne, J. J. Tags: RESEARCH-ARTICLE Source Type: research
"First-Wave" Bias When Conducting Active Safety Monitoring of Newly Marketed Medications with Outcome-Indexed Self-Controlled Designs.
Abstract
Large health care databases are used extensively for pharmacoepidemiologic studies. Unique methodological issues arise when applying self-controlled designs (i.e., using within-person comparisons) for active surveillance of newly marketed drugs. We use 3 examples to illustrate bias related to population-level exposure time trends when using outcome-indexed self-controlled (i.e., case-crossover) designs for active surveillance and evaluate the ability of the case-time-control design to adjust for bias from population-level exposure time trends. We mimicked active surveillance by conducting sequenti...
Source: Am J Epidemiol - August 1, 2014 Category: Epidemiology Authors: Wang SV, Schneeweiss S, Gagne JJ, Maclure M Tags: Am J Epidemiol Source Type: research
Desmethyl Macrolides: Synthesis and Evaluation of
4-Desmethyl Telithromycin
ACS Medicinal Chemistry LettersDOI: 10.1021/ml5002097 (Source: ACS Medicinal Chemistry Letters)
Source: ACS Medicinal Chemistry Letters - July 22, 2014 Category: Chemistry Authors: Ian Glassford, Miseon Lee, Bharat Wagh, Venkata Velvadapu, Tapas Paul, Gary Sandelin, Charles DeBrosse, Dorota Klepacki, Meagan C. Small, Alexander D. MacKerell and Rodrigo B. Andrade Source Type: research
Involvement of intestinal permeability in the oral absorption of clarithromycin and telithromycin
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - May 1, 2014 Category: Drugs & Pharmacology Authors: Kohei Togami, Yoshiaki Hayashi, Sumio Chono, Kazuhiro Morimoto Tags: Original Paper Source Type: research
A modular, prospective, semi‐automated drug safety monitoring system for use in a distributed data environment
ConclusionsBeta‐testing across nine drug‐outcome examples demonstrated the feasibility of the proposed semi‐automated prospective monitoring approach. In retrospective assessments, the system identified an increased risk of myocardial infarction with rofecoxib and an increased risk of rhabdomyolysis with cerivastatin years before these drugs were withdrawn from the market. Copyright © 2014 John Wiley & Sons, Ltd. (Source: Pharmacoepidemiology and Drug Safety)
Source: Pharmacoepidemiology and Drug Safety - April 30, 2014 Category: Drugs & Pharmacology Authors: Joshua J. Gagne, Shirley V. Wang, Jeremy A. Rassen, Sebastian Schneeweiss Tags: Original Report Source Type: research
Pharmacokinetic modelling of serum and bronchial concentrations for clarithromycin and telithromycin, and site‐specific pharmacodynamic simulation for their dosages
This study aimed to describe in more detail the pharmacokinetics of the two macrolides in epithelial lining fluid (ELF) of human bronchi and to evaluate their pharmacodynamic target attainment at this site.
MethodsPreviously reported drug concentration data for serum and ELF were simultaneously fitted to a three‐compartment pharmacokinetic model using nonmem program. The model parameter estimates were used for site‐specific pharmacodynamic simulation.
Results and discussionPopulation mean parameters for clarithromycin were as follows: distribution volumes of central, peripheral and ELF compartments (V1/F, V2/F and V3/F...
Source: Journal of Clinical Pharmacy and Therapeutics - March 24, 2014 Category: Drugs & Pharmacology Authors: K. Ikawa, E. Kikuchi, J. Kikuchi, M. Nishimura, H. Derendorf, N. Morikawa Tags: Pharmacokinetics Source Type: research
A novel ketolide RBx 14255 with activity against multi-drug resistant Streptococcus pneumoniae.
We present a novel ketolide RBx14255, a semi-synthetic macrolide derivative obtained by derivatization of clarithromycin, for its in vitro and in vivo activity against sensitive and macrolide-resistant S. pneumoniae. RBx 14255 showed excellent in vitro activity against macrolide-resistant S. pneumoniae including in-house generated telithromycin-resistant strain (S. pneumoniae 3390 NDDR). RBx 14255 showed potent protein synthesis inhibition against telithromycin-resistant S. pneumoniae 3390 NDDR. The binding affinity of RBx 14255 towards ribosome was found to be more than other tested drugs. The in vivo efficacy of RBx 1425...
Source: Antimicrobial Agents and Chemotherapy - February 18, 2014 Category: Microbiology Authors: Raj VS, Barman TK, Kalia V, Purnapatre K, Dube S, Ramkumar G, Bhateja P, Mathur T, Chaira T, Upadhyay DJ, Surase YB, Venkataramanan R, Chakrabarti A, Das B, Bhatnagar PK Tags: Antimicrob Agents Chemother Source Type: research
Insights into the mode of action of novel fluoroketolides, potent inhibitors of bacterial protein synthesis.
In this study, we present a series of novel ketolides carrying alkyl-aryl side chains at the C-6 position of the lactone ring and additionally, one or two fluorine atoms attached either directly to the lactone ring at the C-2 position or indirectly via the C-13 position. According to our genetic and biochemical studies, these novel ketolides occupy the known macrolide binding site at the entrance of the ribosomal tunnel and exhibit lower MIC values against wild type or mutant strains compared to erythromycin. In most cases, the ketolides display activities comparable to or better than the clinically used ketolide telithrom...
Source: Antimicrobial Agents and Chemotherapy - November 4, 2013 Category: Microbiology Authors: Krokidis MG, Márquez V, Wilson DN, Kalpaxis DL, Dinos GP Tags: Antimicrob Agents Chemother Source Type: research
Synthesis and antibacterial activity of novel modified 5-O-mycaminose 14-membered ketolides.
Abstract
A practicable method of introducing a side chain to the C-4' position of 5-O-desosamine in the 14-membered ketolides was developed. And using this method, a series of novel modified 5-O-mycaminose ketolides were synthesized. These ketolides containing 5-O-4'-carbamate mycaminose were evaluated for their in vitro antibacterial activities against some respiratory pathogens. 15b and 18e showed comparable activity to telithromycin and clarithromycin.
PMID: 24021890 [PubMed - as supplied by publisher] (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - August 23, 2013 Category: Chemistry Authors: Xu Y, Chen X, Zhu D, Liu Y, Zhao Z, Jin L, Liu C, Lei P Tags: Eur J Med Chem Source Type: research
The In Vitro Efficacy of Antimicrobial Agents Against the Pathogenic Free‐Living Amoeba Balamuthia mandrillaris
This article is protected by copyright. All rights reserved. (Source: The Journal of Eukaryotic Microbiology)
Source: The Journal of Eukaryotic Microbiology - June 20, 2013 Category: Microbiology Authors: Arine F Ahmad, Wayne Heaselgrave, Peter W Andrew, Simon Kilvington Tags: Short Communication Source Type: research
Impact of Ribosomal Modification on the Binding of the Antibiotic Telithromycin Using a Combined Grand Canonical Monte Carlo/Molecular Dynamics Simulation Approach
by Meagan C. Small, Pedro Lopes, Rodrigo B. Andrade, Alexander D. MacKerell
Resistance to macrolide antibiotics is conferred by mutation of A2058 to G or methylation by Erm methyltransferases of the exocyclic N6 of A2058 (E. coli numbering) that forms the macrolide binding site in the 50S subunit of the ribosome. Ketolides such as telithromycin mitigate A2058G resistance yet remain susceptible to Erm-based resistance. Molecular details associated with macrolide resistance due to the A2058G mutation and methylation at N6 of A2058 by Erm methyltransferases were investigated using empirical force field-based simulations. To ...
Source: PLoS Computational Biology - June 13, 2013 Category: Biology Authors: Meagan C. Small et al. Source Type: research
