Efficacy of Ceftobiprole and Daptomycin at Bone Concentrations Against Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm: Results of a Dynamic In Vitro PK/PD Model
<b>Background</b>: The presence of biofilms and low antimicrobial concentrations in bone tissue make prosthetic joint infections (PJI) difficult to treat. Ceftobiprole (CTO) has a potential role in MRSA PJI. This study evaluated the efficacy of ceftobiprole and daptomycin (DAP) alone and...
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MDPI AG
2025-04-01
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| author | Mikel Mancheño-Losa María Ángeles Meléndez-Carmona Carlos Lumbreras Jaime Lora-Tamayo |
| author_facet | Mikel Mancheño-Losa María Ángeles Meléndez-Carmona Carlos Lumbreras Jaime Lora-Tamayo |
| author_sort | Mikel Mancheño-Losa |
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| description | <b>Background</b>: The presence of biofilms and low antimicrobial concentrations in bone tissue make prosthetic joint infections (PJI) difficult to treat. Ceftobiprole (CTO) has a potential role in MRSA PJI. This study evaluated the efficacy of ceftobiprole and daptomycin (DAP) alone and in combination against MRSA biofilms at expected bone tissue concentrations. We assessed whether CTO-DAP outperformed DAP combined with a non-anti-MRSA beta-lactam (cefazolin [CZO]). <b>Methods</b>: A dynamic in vitro PK/PD biofilm model (CDC biofilm reactor) was used to simulate concentrations expected in cortical bone at a standard dosing of DAP (10 mg/kg/24 h), CTO (500 mg/8 h), and CZO (2 g/8 h), and assess performance against a 48-h MRSA biofilm from two clinical isolates that cause PJI (MRSA-1811 and MRSA-1733). Time–kill curves using the log change method (Δlog<sub>10</sub> CFU/cm<sup>2</sup>) assessed antimicrobial efficacy over 56 h. Resistance emergence was monitored. <b>Results:</b> Although both monotherapies were active, neither reached bactericidal levels nor was one superior to the other (Δlog<sub>10</sub> CFU/cm<sup>2</sup> CTO vs. DAP: −1.44 ± 0.25 vs. −1.50 ± 0.01 [<i>p</i> = 0.686] and −1.55 ± 0.74 vs. −0.56 ± 0.36 [<i>p</i> = 0.108] for MRSA-1811 and MRSA-1733, respectively). Only in the MRSA-1811 isolate did the CTO-DAP combination improve the activity of each monotherapy, without achieving a synergistic effect (Δlog<sub>10</sub> CFU/cm<sup>2</sup>: CTO-DAP −2.087 ± 0.048 vs. CTO −1.436 ± 0.249 [<i>p</i> = 0.013] and vs. DAP −1.503 ± 0.011 [<i>p</i> = 0.006]). No combination therapy (CTO-DAP vs. DAP-CZO) outperformed the other in either strain. No resistant bacterial subpopulations appeared with any antibiotic regimen. <b>Conclusions:</b> At clinically relevant concentrations, ceftobiprole and daptomycin showed similar activity against MRSA biofilms. The CTO-DAP combination showed comparable efficacy to DAP-CZO. |
| format | Article |
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| institution | OA Journals |
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| language | English |
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| spelling | doaj-art-4ca9f817d0e643ad84e87c7b02254a3a2025-08-20T02:17:25ZengMDPI AGAntibiotics2079-63822025-04-0114438610.3390/antibiotics14040386Efficacy of Ceftobiprole and Daptomycin at Bone Concentrations Against Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm: Results of a Dynamic In Vitro PK/PD ModelMikel Mancheño-Losa0María Ángeles Meléndez-Carmona1Carlos Lumbreras2Jaime Lora-Tamayo3Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación “i + 12” del Hospital 12 de Octubre, 28041 Madrid, SpainDepartment of Clinical Microbiology, Hospital Universitario 12 de Octubre, Instituto de Investigación “i + 12” del Hospital 12 de Octubre, 28041 Madrid, SpainDepartment of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación “i + 12” del Hospital 12 de Octubre, 28041 Madrid, SpainDepartment of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación “i + 12” del Hospital 12 de Octubre, 28041 Madrid, Spain<b>Background</b>: The presence of biofilms and low antimicrobial concentrations in bone tissue make prosthetic joint infections (PJI) difficult to treat. Ceftobiprole (CTO) has a potential role in MRSA PJI. This study evaluated the efficacy of ceftobiprole and daptomycin (DAP) alone and in combination against MRSA biofilms at expected bone tissue concentrations. We assessed whether CTO-DAP outperformed DAP combined with a non-anti-MRSA beta-lactam (cefazolin [CZO]). <b>Methods</b>: A dynamic in vitro PK/PD biofilm model (CDC biofilm reactor) was used to simulate concentrations expected in cortical bone at a standard dosing of DAP (10 mg/kg/24 h), CTO (500 mg/8 h), and CZO (2 g/8 h), and assess performance against a 48-h MRSA biofilm from two clinical isolates that cause PJI (MRSA-1811 and MRSA-1733). Time–kill curves using the log change method (Δlog<sub>10</sub> CFU/cm<sup>2</sup>) assessed antimicrobial efficacy over 56 h. Resistance emergence was monitored. <b>Results:</b> Although both monotherapies were active, neither reached bactericidal levels nor was one superior to the other (Δlog<sub>10</sub> CFU/cm<sup>2</sup> CTO vs. DAP: −1.44 ± 0.25 vs. −1.50 ± 0.01 [<i>p</i> = 0.686] and −1.55 ± 0.74 vs. −0.56 ± 0.36 [<i>p</i> = 0.108] for MRSA-1811 and MRSA-1733, respectively). Only in the MRSA-1811 isolate did the CTO-DAP combination improve the activity of each monotherapy, without achieving a synergistic effect (Δlog<sub>10</sub> CFU/cm<sup>2</sup>: CTO-DAP −2.087 ± 0.048 vs. CTO −1.436 ± 0.249 [<i>p</i> = 0.013] and vs. DAP −1.503 ± 0.011 [<i>p</i> = 0.006]). No combination therapy (CTO-DAP vs. DAP-CZO) outperformed the other in either strain. No resistant bacterial subpopulations appeared with any antibiotic regimen. <b>Conclusions:</b> At clinically relevant concentrations, ceftobiprole and daptomycin showed similar activity against MRSA biofilms. The CTO-DAP combination showed comparable efficacy to DAP-CZO.https://www.mdpi.com/2079-6382/14/4/386biofilmMRSAprosthetic joint infectionceftobiproledaptomycin |
| spellingShingle | Mikel Mancheño-Losa María Ángeles Meléndez-Carmona Carlos Lumbreras Jaime Lora-Tamayo Efficacy of Ceftobiprole and Daptomycin at Bone Concentrations Against Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm: Results of a Dynamic In Vitro PK/PD Model Antibiotics biofilm MRSA prosthetic joint infection ceftobiprole daptomycin |
| title | Efficacy of Ceftobiprole and Daptomycin at Bone Concentrations Against Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm: Results of a Dynamic In Vitro PK/PD Model |
| title_full | Efficacy of Ceftobiprole and Daptomycin at Bone Concentrations Against Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm: Results of a Dynamic In Vitro PK/PD Model |
| title_fullStr | Efficacy of Ceftobiprole and Daptomycin at Bone Concentrations Against Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm: Results of a Dynamic In Vitro PK/PD Model |
| title_full_unstemmed | Efficacy of Ceftobiprole and Daptomycin at Bone Concentrations Against Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm: Results of a Dynamic In Vitro PK/PD Model |
| title_short | Efficacy of Ceftobiprole and Daptomycin at Bone Concentrations Against Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm: Results of a Dynamic In Vitro PK/PD Model |
| title_sort | efficacy of ceftobiprole and daptomycin at bone concentrations against methicillin resistant i staphylococcus aureus i biofilm results of a dynamic in vitro pk pd model |
| topic | biofilm MRSA prosthetic joint infection ceftobiprole daptomycin |
| url | https://www.mdpi.com/2079-6382/14/4/386 |
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