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The significant reduction of new antibiotics development can be overcome by complementing with alternative therapies, such as antimicrobial photodynamic therapy (aPDI). Through photosensitizer (PS) compounds, aPDI produces local oxidative stress-activated by light (photooxidative stress), nonspecifically killing bacteria. Methodology: Bimetallic Re(I)-based compounds, PSRe-\u00b5L1 and PSRe-\u00b5L2, were tested in aPDI and compared with a Ru(II)-based PS positive control. The ability of PSRe-\u00b5L1 and PSRe-\u00b5L2 to inhibit K. pneumoniae was evaluated under a photon flux of 17 \u00b5W\/cm2. In addition, an improved aPDI effect with imipenem on KPC+ bacteria and a synergistic effect with cefotaxime on ESBL producers of a collection of 118 clinical isolates of K. pneumoniae was determined. Furthermore, trypan blue exclusion assays determined the PS cytotoxicity on mammalian cells. Results: At a minimum dose of 4 \u00b5g\/mL, both the PSRe-\u00b5L1 and PSRe-\u00b5L2 significantly inhibited in 3log10 (&gt;99.9%) the bacterial growth and showed a lethality of 60 and 30 min of light exposure, respectively. Furthermore, they were active on clinical isolates of K. pneumoniae at 3\u20136 log10. Additionally, a remarkably increased effectiveness of aPDI was observed over KPC+ bacteria when mixed with imipenem, and a synergistic effect from 3 to 6log10 over ESBL producers of K. pneumoniae clinic isolates when mixed with cefotaxime was determined for both PSs. Furthermore, the compounds show no dark toxicity and low light-dependent toxicity in vitro to mammalian HEp-2 and HEK293 cells. Conclusion: Compounds PSRe-\u00b5L1 and PSRe-\u00b5L2 produce an effective and synergistic aPDI effect on KPC+, ESBL, and clinical isolates of K. pneumoniae and have low cytotoxicity in mammalian cells.<\/jats:p>","DOI":"10.3390\/pharmaceutics13111889","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T22:08:41Z","timestamp":1636409321000},"page":"1889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effective Treatment against ESBL-Producing Klebsiella pneumoniae through Synergism of the Photodynamic Activity of Re (I) Compounds with Beta-Lactams"],"prefix":"10.3390","volume":"13","author":[{"given":"Iv\u00e1n A.","family":"Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias Naturales, Matem\u00e1tica y del Medio Ambiente, Universidad Tecnol\u00f3gica Metropolitana, Las Palmeras 3360, \u00d1u\u00f1oa, Santiago 7800003, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annegrett","family":"Palavecino","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda Celular, Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Lord Cochrane 418, Santiago 8330546, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanza","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda Celular, Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Lord Cochrane 418, Santiago 8330546, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Dreyse","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidad T\u00e9cnica Federico Santa Mar\u00eda, Av. Espa\u00f1a 1680, Casilla, Valpara\u00edso 2390123, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Melo-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Molecular y Microbiolog\u00eda, Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330025, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7551-8088","authenticated-orcid":false,"given":"Susan M.","family":"Bueno","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Molecular y Microbiolog\u00eda, Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330025, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-7327","authenticated-orcid":false,"given":"Christian Erick","family":"Palavecino","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda Celular, Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Lord Cochrane 418, Santiago 8330546, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S1473-3099(15)00424-7","article-title":"Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study","volume":"16","author":"Liu","year":"2016","journal-title":"Lancet Infect. 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