8-Azatetracyclines: Synthesis and Evaluation of a Novel Class of Tetracycline Antibacterial Agents

bS Supporting Information ABSTRACT: A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds were identified that exhibit comparable efficacy to marketed tetracyclines in in vivo models of bacterial infection. The tetracycline class of antibacterial agents has seen wide-spread clinical use for over 50 years due to its broad spectrum anti-bacterial activity.1 Tetracyclines inhibit bacterial growth by prevent-ing protein biosynthesis through binding to the 30S ribosome

Comparison of experimental and operational modal analysis on a back to back planetary gear

Several modal analyse techniques are widely used to study the dynamic characteristics of a structure by identifying the modal parameters. This paper presents a comparison between an Experimental Modal Analysis (EMA) test, an Operational Modal Analysis (OMA) test and an Order Based Modal Analysis (OBMA) applied on a recirculating energy planetary gear. The OMA and OBMA offer a test of the planetary gear under its real boundary conditions, whereas the EMA is based on the frequency response function estimation. Using these different techniques, the back to back planetary gears modal parameters were identified. In a first step, the experimental results determined by EMA and OMA were correlated to the numerical results model obtained by a three-dimensional lumped parameter model. In a second step, the OBMA estimated modal parameters were compared to those of the EMA. According to the obtained results, OMA cannot excite all the modes. However, it was noticed that there is no significant difference between the modal parameters obtained by the EMA and the OBMA. The natural frequencies and damping ratios were deviating by 11% and 2.43%, respectively.This paper was financially supported by the Tunisian-Spanish Joint Project No. A1/037038/11. The authors would like also to acknowledge the help provided by the project “Dynamic behavior of gear transmissions in non-stationary conditions”, ref. DPI2017-85390, funded by the Spanish Ministry of Science and Technolog

In Vitro Activity of Eravacycline against Gram-Negative Bacilli Isolated in Clinical Laboratories Worldwide from 2013 to 2017

Eravacycline is a novel, fully synthetic fluorocycline antibiotic developed for the treatment of serious infections, including those caused by multidrug-resistant (MDR) pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a global collection of frequently encountered clinical isolates of Gram-negative bacilli. The CLSI broth microdilution method was used to determine MIC data for isolates of Enterobacterales (n\u2009=\u200913,983), Acinetobacter baumannii (n\u2009=\u20092,097), Pseudomonas aeruginosa (n\u2009=\u20091,647), and Stenotrophomonas maltophilia (n\u2009=\u20091,210) isolated primarily from respiratory, intra-abdominal, and urinary specimens by clinical laboratories in 36 countries from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. Multidrug-resistant (MDR) isolates were defined by resistance to agents from 653 different antimicrobial classes. The MIC90s ranged from 0.25 to 1\u2009\u3bcg/ml for Enterobacteriaceae and were 1\u2009\u3bcg/ml for A. baumannii and 2\u2009\u3bcg/ml for S. maltophilia, Proteus mirabilis, and Serratia marcescens Eravacycline's potency was up to 4-fold greater than that of tigecycline against genera/species of Enterobacterales, A. baumannii, and S. maltophilia The MIC90s for five of six individual genera/species of Enterobacterales and A. baumannii were within 2-fold of the MIC90s for their respective subsets of MDR isolates, while the MDR subpopulation of Klebsiella spp. demonstrated 4-fold higher MIC90s. Eravacycline demonstrated potent in vitro activity against the majority of clinical isolates of Gram-negative bacilli, including MDR isolates, collected over a 5-year period. This study further underscores the potential benefit of eravacycline in the treatment of infections caused by MDR Gram-negative pathogens

8-Azatetracyclines: Synthesis and Evaluation of a Novel Class of Tetracycline Antibacterial Agents

A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (<i>tet</i>(K)) and ribosomal protection (<i>tet</i>(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds were identified that exhibit comparable efficacy to marketed tetracyclines in in vivo models of bacterial infection