{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:26:37Z","timestamp":1792099597496,"version":"4.4.0"},"reference-count":19,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Macrolides inhibit biofilm formation in several Gram-negative, intrinsically-resistant bacterial species. However, the effect of macrolides upon biofilm formation by susceptible Gram-positive bacteria has been much less explored as such concentrations also inhibit cell growth. To circumvent this problem, the effect of macrolides (erythromycin, clarithromycin and azithromycin) at 0.5\u20132 \u00b5g\/mL, upon biofilm formation, was explored on macrolide-resistant Staphylococcus aureus isolates, using the crystal violet assay with 96-well plates. Early (4 h) biofilm formation by strains having constitutive target-modification resistance was consistently induced by all macrolides but not in azithromycin-treated cells in longer (8 and 12 h) incubation. In inducible-resistance isolates, early biofilm formation was enhanced by some macrolide treatments, compared to similar cell growth in the absence of antibiotics; but the typical decay of biofilms at longer incubation appeared prematurely in macrolide-treated cultures. Biofilm formation in an efflux-mediated resistant isolate was not affected by macrolides. These results indicate that macrolides induce the formation of biofilm by resistant S. aureus isolates, especially during the early stages. This suggests that the empirical use of macrolides against infections caused by resistant S. aureus strains could not only result in clinical failure but even in the enhancement of biofilms, making further treatment difficult.<\/jats:p>","DOI":"10.3390\/antibiotics12020187","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T05:36:55Z","timestamp":1673933815000},"page":"187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Macrolides at Clinically-Relevant Concentrations May Induce Biofilm Formation in Macrolide-Resistant Staphylococcus aureus"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-544X","authenticated-orcid":false,"given":"Carlos F.","family":"Am\u00e1bile-Cuevas","sequence":"first","affiliation":[{"name":"Fundacion Lusara, Mexico City 08810, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jac\/dkh309","article-title":"Macrolide activities beyond their antimicrobial effects: Macrolides in diffuse panbronchiolitis and cystic fibrosis","volume":"54","author":"Schultz","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1378\/chest.125.2_suppl.62S","article-title":"Effects of subinhibitory concentrations of macrolide antibiotics on Pseudomonas aeruginosa","volume":"125","author":"Wozniak","year":"2004","journal-title":"Chest"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Moshynets, O.V., Baranovskyi, T.P., Cameron, S., Iungin, O.S., Pokholenko, I., Jerdan, R., Kamyshnyi, A., Krikunov, A.A., Potochilova, V.V., and Rudnieva, K.L. (2022). Azithromycin possesses biofilm-inhibitory activity and potentiates non-bactericidal colistin methanesulfonate (CMS) and polymyxin B against Klebsiella pneumonia. PLoS ONE, 17.","DOI":"10.1101\/2022.02.17.480821"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.2220\/biomedres.41.259","article-title":"Direct anti-biofilm effects of macrolides on Acinetobacter baumannii: Comprehensive and comparative demonstration by a simple assay using microtiter plate combined with peg-lid","volume":"41","author":"Yamabe","year":"2020","journal-title":"Biomed. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1093\/jac\/dkg397","article-title":"Biofilm formation by Pseudomonas aeruginosa: Role of the C4-HSL cell-to-cell signal and inhibition by azithromycin","volume":"52","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Grayson, M.L. (2018). Azythromycin. Kucers\u2019 The Use of Antibiotics, CRC Press. [7th ed.].","DOI":"10.1128\/9781498747950"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Grayson, M.L. (2018). Erythromycin. Kucers\u2019 The Use of Antibiotics, CRC Press. [7th ed.].","DOI":"10.1128\/9781498747950"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Grayson, M.L. (2018). Clarithromycin. Kucers\u2019 The Use of Antibiotics, CRC Press. [7th ed.].","DOI":"10.1128\/9781498747950"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1128\/JCM.42.12.5842-5845.2004","article-title":"Azithromycin retards Pseudomonas aeruginosa biofilm formation","volume":"42","author":"Gillis","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00430-016-0479-5","article-title":"The anti-biofilm effect of macrolides in a rat model of S. aureus foreign-body infection: Might it be of clinical relevance?","volume":"206","author":"Murillo","year":"2017","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_11","first-page":"10","article-title":"Macrolides and staphylococcal biofilms","volume":"25","author":"Vidaillac","year":"2012","journal-title":"Rev. Esp. Quimioter."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1128\/AAC.01565-09","article-title":"Enhancement of biofilm formation by subinhibitory concentrations of macrolides in icaADBC-positive and -negative clinical isolates of Staphylococcus epidermidis","volume":"54","author":"Wang","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1099\/jmm.0.000893","article-title":"Adhesion and biofilm formation by Staphylococcus aureus clinical isolates under conditions relevant to the host: Relationship with macrolide resistance and clonal lineages","volume":"68","author":"Pompilio","year":"2019","journal-title":"J. Med. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1099\/jmm.0.052373-0","article-title":"SubMICs of penicillin and erythromycin enhance biofilm formation and hydrophobicity of Corynebacterium diphtheriae strains","volume":"62","author":"Gomes","year":"2013","journal-title":"J. Med. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"DiCicco, M., Neethirajan, S., Singh, A., and Weese, J.S. (2012). Efficacy of clarithromycin on biofilm formation of methicillin-resistant Staphylococcus pseudintermedius. BMC Vet. Res., 8.","DOI":"10.1186\/1746-6148-8-225"},{"key":"ref_16","unstructured":"CLSI (2020). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [30th ed.]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104","DOI":"10.7883\/yoken.JJID.2005.104","article-title":"Inducible clindamycin resistance in staphylococci isolated from clinical samples","volume":"58","author":"Delialioglu","year":"2005","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0147-619X(79)90010-6","article-title":"Penicillinase plasmids of Staphylococcus aureus: Restriction-deletion maps","volume":"2","author":"Novick","year":"1979","journal-title":"Plasmid"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0076-6879(99)10008-9","article-title":"Genetic approaches to study of biofilms","volume":"310","author":"Pratt","year":"1999","journal-title":"Meth. Enzymol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/2\/187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:08:09Z","timestamp":1760119689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/2\/187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,17]]},"references-count":19,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["antibiotics12020187"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12020187","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,17]]}}}