{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:52:14Z","timestamp":1791845534426,"version":"4.3.4"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n As we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n . MIC values against\n Streptococcus pneumoniae<\/jats:named-content>\n ,\n Streptococcus pyogenes<\/jats:named-content>\n ,\n Staphylococcus aureus<\/jats:named-content>\n , and\n Haemophilus influenzae<\/jats:named-content>\n strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible\n erm<\/jats:italic>\n genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds.\n In vivo<\/jats:italic>\n efficacy was assessed in a murine model of\n S. pneumoniae<\/jats:named-content>\n -induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. The\n in vitro<\/jats:italic>\n antibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducible\n erm<\/jats:italic>\n genes. They acted as typical protein synthesis inhibitors in an\n Escherichia coli<\/jats:named-content>\n transcription\/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against an\n S. pneumoniae<\/jats:named-content>\n strain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in good\n in vivo<\/jats:italic>\n efficacy.\n <\/jats:p>","DOI":"10.1128\/aac.00524-16","type":"journal-article","created":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T17:07:56Z","timestamp":1467220076000},"page":"5337-5348","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory Pathogens\n In Vitro<\/i>\n and\n In Vivo<\/i>"],"prefix":"10.1128","volume":"60","author":[{"given":"Hana","family":"\u010cip\u010di\u0107 Paljetak","sequence":"first","affiliation":[{"name":"GlaxoSmithKline Research Centre Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Verbanac","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research Centre Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasna","family":"Padovan","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research Centre Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslava","family":"Dominis-Kramari\u0107","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research Centre Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljko","family":"Kelneri\u0107","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research Centre Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Peri\u0107","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research Centre Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihailo","family":"Banjanac","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research Centre Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrijela","family":"Ergovi\u0107","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research Centre Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerrisa","family":"Simon","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Broskey","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Holmes","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Erakovi\u0107 Haber","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research Centre Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1202937"},{"key":"e_1_3_3_3_2","first-page":"494","article-title":"The incidence rate and economic burden of community-acquired pneumonia in a working-age population","volume":"6","author":"Broulette J","year":"2013","unstructured":"Broulette J, Yu H, Pyenson B, Iwasaki K, Sato R. 2013. 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