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Article

Itaconic Acid Increases the Efficacy of Tobramycin against Pseudomonas aeruginosa Biofilms

1
HIPS–Helmholtz Institute for Pharmaceutical Research Saarland, HZI—Helmholtz Center for Infection Research, D-66123 Saarbrücken, Germany
2
Department of Pharmacy, Saarland University, D-66123 Saarbrücken, Germany
*
Authors to whom correspondence should be addressed.
Current address: Department of Bioengineering, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Current address: Kusudama Therapeutics, Parque Científico y Tecnológico de Gipuzkoa, 20014 Donostia-San Sebastián, Spain.
Pharmaceutics 2020, 12(8), 691; https://doi.org/10.3390/pharmaceutics12080691
Received: 25 June 2020 / Revised: 17 July 2020 / Accepted: 20 July 2020 / Published: 22 July 2020
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
The search for novel therapeutics against pulmonary infections, in particular Pseudomonas aeruginosa (PA) biofilm infections, has been intense to deal with the emergent rise of antimicrobial resistance. Despite the numerous achievements in drug discovery and delivery strategies, only a limited number of therapeutics reach the clinic. To allow a timely preclinical development, a formulation should be highly effective, safe, and most importantly facile to produce. Thus, a simple combination of known actives that enhances the therapeutic efficacy would be a preferential choice compared to advanced drug delivery systems. In this study, we propose a novel combination of an anti-inflammatory agent—itaconic acid (itaconate, IA)—and an approved antibiotic—tobramycin (Tob) or ciprofloxacin (Cipro). The combination of Tob and IA at a molar ratio of 1:5 increased the biofilm eradicating efficacy in the strain PA14 wild type (wt) by ~4-fold compared to Tob alone. In contrast, such effect was not observed for the combination of IA with Cipro. Subsequent studies on the influence of IA on bacterial growth, pyocyanin production, and Tob biofilm penetration indicated that complexation with IA enhanced the transport of Tob through the biofilm. We recommend the simple and effective combination of Tob:IA for further testing in advanced preclinical models of PA biofilm infections. View Full-Text
Keywords: tobramycin; ciprofloxacin; itaconic acid; itaconate; Pseudomonas aeruginosa; biofilms; infections tobramycin; ciprofloxacin; itaconic acid; itaconate; Pseudomonas aeruginosa; biofilms; infections
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MDPI and ACS Style

Ho, D.-K.; De Rossi, C.; Loretz, B.; Murgia, X.; Lehr, C.-M. Itaconic Acid Increases the Efficacy of Tobramycin against Pseudomonas aeruginosa Biofilms. Pharmaceutics 2020, 12, 691. https://doi.org/10.3390/pharmaceutics12080691

AMA Style

Ho D-K, De Rossi C, Loretz B, Murgia X, Lehr C-M. Itaconic Acid Increases the Efficacy of Tobramycin against Pseudomonas aeruginosa Biofilms. Pharmaceutics. 2020; 12(8):691. https://doi.org/10.3390/pharmaceutics12080691

Chicago/Turabian Style

Ho, Duy-Khiet, Chiara De Rossi, Brigitta Loretz, Xabier Murgia, and Claus-Michael Lehr. 2020. "Itaconic Acid Increases the Efficacy of Tobramycin against Pseudomonas aeruginosa Biofilms" Pharmaceutics 12, no. 8: 691. https://doi.org/10.3390/pharmaceutics12080691

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