{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:47:36Z","timestamp":1782125256673,"version":"3.54.5"},"reference-count":28,"publisher":"PAGEPress Publications","issue":"2","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Monaldi Arch Chest Dis"],"abstract":"<jats:p>Nafithromycin (WCK 4873) is a novel lactone ketolide antibiotic developed to address the critical issue of multidrug-resistant bacteria, especially those causing community-acquired pneumonia (CAP). Given the increasing prevalence of antibiotic resistance, there is a pressing need for new antibiotics with improved efficacy and safety profiles. This review synthesizes data from various in vitro studies and clinical trials to evaluate the pharmacological properties, mechanism of action, and clinical potential of nafithromycin. Key clinical trials assessed the drug\u2019s pharmacokinetics, safety, and efficacy in both healthy volunteers and patients with CAP. Nafithromycin exhibits strong in vitro antimicrobial activity against a broad spectrum of pathogens, including macrolide-resistant and telithromycin-insensitive strains. Clinical trials demonstrated that nafithromycin has a favorable pharmacokinetic profile, with high lung tissue concentrations and manageable side effects. Phase I studies confirmed its safety and tolerability in healthy adults, while Phase II trials showed its efficacy in treating CAP, with a 3-day treatment regimen proving comparable to a 7-day regimen of moxifloxacin. Nafithromycin holds significant promise as a therapeutic agent against respiratory infections caused by resistant bacteria. Its unique mechanism of action, high tissue penetration, and broad-spectrum activity position it as a valuable addition to the antimicrobial arsenal. Continued research and clinical trials are essential to further define its role in combating antibiotic resistance and ensuring effective treatment options.<\/jats:p>","DOI":"10.4081\/monaldi.2025.3340","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T14:25:25Z","timestamp":1754403925000},"source":"Crossref","is-referenced-by-count":0,"title":["Nafithromycin: advancements in antibiotic therapy against community-acquired pneumonia-resistant pathogens"],"prefix":"10.4081","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6421-5084","authenticated-orcid":false,"given":"Akshata","family":"Gore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agadi Hiremath","family":"Viswanatha Swamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5111-7685","authenticated-orcid":false,"given":"Sanatkumar","family":"Bharamu Nyamagoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2549","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"60754","doi-asserted-by":"publisher","DOI":"10.1086\/511159"},{"key":"60755","doi-asserted-by":"publisher","DOI":"10.1007\/s11696-023-02725-3"},{"key":"60756","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2020.1839983"},{"key":"60757","doi-asserted-by":"publisher","DOI":"10.4155\/bio-2019-0153"},{"key":"60758","unstructured":"National Center for Biotechnology Information. PubChem compound summary for CID 117587595, nafithromycin. 2025. Available from: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Nafithromycin."},{"key":"60759","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01994-13"},{"key":"60760","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2014.4887"},{"key":"60761","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01230-17"},{"key":"60762","unstructured":"U.S. National Library of Medicine. Available from: https:\/\/clinicaltrials.gov\/."},{"key":"60763","unstructured":"A phase 1 pharmacokinetic study of single-ascending doses of intravenous nafithromycin in healthy adult subjects. Available from: https:\/\/trial.medpath.com\/clinical-trial\/0f9f39a62bbd0dfb\/nct02770404-safety-tolerability-pharmacokinetic-study-nafithromycin."},{"key":"60764","unstructured":"The safety, tolerability and pharmacokinetics of single ascending doses and the effect of food on oral WCK 4873 in healthy adult volunteers. Available from: https:\/\/trial.medpath.com\/clinical-trial\/535bb7d742c42765\/double-blind-randomized-placebo-controlled-study-wck-4873."},{"key":"60765","unstructured":"Evaluate the safety, tolerability and pharmacokinetics of multiple ascending oral doses of WCK 4873 in healthy adult volunteers. Available from: https:\/\/trial.medpath.com\/clinical-trial\/3a58bf3c46f6e4d5\/double-blind-randomized-placebo-controlled-study-wck-4873."},{"key":"60766","unstructured":"Safety, tolerability, and pharmacokinetics of multiple doses of intravenous nafithromycin. Available from: https:\/\/trial.medpath.com\/clinical-trial\/1b0a74c0753f2ce4\/safety-tolerability-pharmacokinetics-nafithromycin."},{"key":"60767","unstructured":"Phase II study of oral nafithromycin in CABP. Available from: https:\/\/trial.medpath.com\/clinical-trial\/70788141238f88d4\/oral-nafithromycin-moxifloxacin-cabp-treatment."},{"key":"60768","doi-asserted-by":"crossref","unstructured":"Veeraraghavan B, Varghese R, Saigal K, et al. Activity of novel lactone ketolide nafithromycin against multicentric invasive and non-invasive pneumococcal isolates collected in India. JAC Antimicrob Resist 2021;3:dlab066.","DOI":"10.1093\/jacamr\/dlab066"},{"key":"60769","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02130-21"},{"key":"60770","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00585-21"},{"key":"60771","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlac103"},{"key":"60772","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01253-19"},{"key":"60773","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00682-18"},{"key":"60774","doi-asserted-by":"publisher","DOI":"10.2147\/JEP.S259286"},{"key":"60775","unstructured":"CDC. 2019 antibiotic resistance threats report. 2024. Available from: https:\/\/www.cdc.gov\/antimicrobial-resistance\/data-research\/threats\/index.html."},{"key":"60776","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201908-1581ST"},{"key":"60777","unstructured":"Solomon SL, Oliver KB. Antibiotic resistance threats in the United States: stepping back from the brink. Am Fam Physician 2014;89:938-41."},{"key":"60778","unstructured":"Khande H, Satav J, Kulkarni A, et al. WCK 4873 (nafithromycin): impact of hyper ermB induction in S. pneumoniae and S. aureus on the activity of ketolides. European Congress of Clinical Microbiology and Infectious Diseases, Vienna, Austria, 2017. Abstract P-1350."},{"key":"60779","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2020.155049"},{"key":"60780","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlab066"},{"key":"60781","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00972-17"}],"container-title":["Monaldi Archives for Chest Disease"],"original-title":[],"link":[{"URL":"https:\/\/www.monaldi-archives.org\/macd\/article\/download\/3340\/2118","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.monaldi-archives.org\/macd\/article\/download\/3340\/2118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T09:51:38Z","timestamp":1782121898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.monaldi-archives.org\/macd\/article\/view\/3340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,5,7]]}},"URL":"https:\/\/doi.org\/10.4081\/monaldi.2025.3340","relation":{},"ISSN":["2532-5264","1122-0643"],"issn-type":[{"value":"2532-5264","type":"electronic"},{"value":"1122-0643","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8,5]]}}}