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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EAminoglycosides are a well-known class of drugs with proven efficacy; however, they are being used less frequently because of resistance, nephrotoxicity, and ototoxicity. This article discusses plazomicin (formerly ACHN-490), a new aminoglycoside that is used to treat gram-negative infections.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EBacterial Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDrug Resistance\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPneumonia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEmerging Therapies\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EAminoglycosides are a well-known class of drugs with proven efficacy; however, they are being used less frequently because of resistance, nephrotoxicity, and ototoxicity. George Zhanel, PhD, University of Manitoba, Winnipeg, Manitoba, Canada, discussed plazomicin (formerly ACHN-490), a new aminoglycoside that is used to treat gram-negative infections, which was evaluated against gentamicin, tobramycin, and amikacin. Dr. Zhanel believes plazomicin is a next-generation aminoglycoside that retains its activity against multidrug-resistant gram-negative and gram-positive bacterial strains that express all clinically relevant aminoglycoside-modifying enzymes. It is not active against organisms that harbor rRNA methyltransferases. Plazomicin is synergistic with daptomycin and ceftobiprole against a variety of MRSA phenotypes and with a variety of \u03b2-lactams (eg, cefepime, doripenem, imipenem, and piperacillin-tazobactam) and against \u003Cem\u003EP. aeruginosa\u003C\/em\u003E (\u003Cem\u003Ein vitro\u003C\/em\u003E). At 15 mg\/kg IV, plazomicin has a C\u003Csub\u003Emax\u003C\/sub\u003E of 113 \u03bcg\/mL, an AUC\u003Csub\u003E0\u201324\u003C\/sub\u003E of 239 h\u00b7\u03bcg\/mL, t\u003Csub\u003E1\/2\u003C\/sub\u003E of 3.0 hr, and V\u003Csub\u003Ess\u003C\/sub\u003E of 0.24 L\/kg. Animal and human studies have not reported nephrotoxicity or ototoxicity [Zhanel G et al. \u003Cem\u003EExpert Rev Anti Infect Ther\u003C\/em\u003E 2011. Submitted; Zhanel G et al. IDSA 2011]. Plazomicin is currently being investigated in a Phase 2 study to treat complicated urinary tract infections and acute pyelonephritis [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01096849\u0026amp;atom=%2Fspmdc%2F11%2F12%2F25.atom\u0022\u003ENCT01096849\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EPrabhavathi Fernandes, PhD, Cempra Pharmaceuticals, Chapel Hill, North Carolina, USA, presented information on macrolides and ketolides with improved antibacterial properties. Dr. Fernandes discussed several investigational programs: a novel series of azetidinyl ketolides that mitigate hepatotoxicity by minimizing hepatic turnover and time-dependent inactivation of CYP3A isoforms in the liver [Magee TV et al. \u003Cem\u003EJ Med Chem\u003C\/em\u003E 2009]; cethromycin, a ketolide antibiotic that has shown potent activity (similar to telithromycin) against macrolide-resistant bacterial strains but failed to obtain United States Food and Drug Administration approval for community-acquired bacterial pneumonia (CABP) and is now being pursued in superiority trials in simple drug-resistant respiratory infections; and modithromycin, a bridged bicyclic macrolide that is also similar in potency to telithromycin that is active against pneumococcal strains with \u003Cem\u003Eerm\u003C\/em\u003E and \u003Cem\u003Emef\u003C\/em\u003E resistance but has a relatively high (8 \u03bcg\/mL) MIC\u003Csub\u003E90\u003C\/sub\u003E for \u003Cem\u003EH. influenzae\u003C\/em\u003E and a very long half-life. Dr. Fernandes concluded her presentation with solithromycin (CEM-101), an oral (Phase 2) and intravenous (Phase 1) fluoroketolide that is being evaluated for the treatment of CABP that has shown activity against \u003Cem\u003ES. pneumoniae\u003C\/em\u003E, CA-MRSA, \u003Cem\u003EEnterococci\u003C\/em\u003E, and \u003Cem\u003EM. avium\u003C\/em\u003E and in animal models of malaria. MICs are similar to azithromycin for gram-negatives, but on average, solithromycin is 8 to 16 times more active for the gram-positive organisms and is active against azithromycin-resistant strains. Solithromycin has 67% oral bioavailability, as compared with 38% for azithromycin; is well distributed into tissues and cells; has a plasma half-life of approximately 7 hours; shows no significant effect against nACH receptors; and has been shown to be safe and well tolerated in Phase 1 studies [Still JG et al. \u003Cem\u003EAntimicrob Agents Chemother\u003C\/em\u003E 2011]. In the recently completed Phase 2 trials, it has shown noninferiority to levofloxacin, with favorable safety and tolerability. Plans are underway for a Phase 3 oral trial and Phase 2 intravenous-oral trial in CABP in 2012.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EKelly Aubart, PhD, GlaxoSmithKline, Collegeville, Pennsylvania, USA, discussed GSK1322322, a novel peptide deformylase inhibitor that is in development for hospitalized CABP, acute bacterial skin, and skin structure infections. The new agent has good activity against gram-positive pathogens, including those that infect the skin and soft tissue, as well as the respiratory tract. It is potent \u003Cem\u003Ein vivo\u003C\/em\u003E and \u003Cem\u003Ein vitro\u003C\/em\u003E against a range of pathogens, including MRSA. GSK1322322 was safe and well tolerated in Phase 1 studies. A Phase 2 study in skin and soft tissue infections has recently been completed [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01209078\u0026amp;atom=%2Fspmdc%2F11%2F12%2F25.atom\u0022\u003ENCT01209078\u003C\/a\u003E].\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/12\/25.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmxdp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}