Journalartikel

Jahr der Veröffentlichung: 2018

Seiten: 422-426

Zeitschrift: International Journal of Antimicrobial Agents

Bandnummer: 51

Heftnummer: 3

ISSN: 0924-8579

eISSN: 1872-7913

DOI Link: https://doi.org/10.1016/j.ijantimicag.2017.11.004

Verlag: Elsevier

Abstract: 
Oral antibiotics for the treatment of urinary tract infections are scarce. In this ex vivo phase 1 annex study, the clinical safety, urinary concentrations and bactericidal activity of a new formulation for improved oral absorption of tobramycin (Tobrate (TM)) were evaluated. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of five test strains, one reference strain and four clinical uropathogenic strains were determined in cation-adjusted Mueller-Hinton broth (CA-MHB) and in pooled antimicrobial agent-free subjects' urine at different pH values (5.5, 6.5, 7.5 and 8.5). Urinary concentrations and urinary bactericidal titres (UBTs) following single oral administration of 600 mg Tobrate (TM) were measured in nine healthy volunteers up to 24 h. The MIC/MBC values in CA-MHB were 2-4/24 mg/L for two Escherichia coli strains, 2/2 mg/L for Klebsiella pneumoniae, 0.5/1 mg/L for Pseudomonas aeruginosa and 8/1 mg/L for Proteus mirabilis. MBCs in pooled alkaline urine were significantly lower than those in acidic urine. The mean maximum urinary concentration following 600 mg tobramycin was 83.9 mg/L (2-4 h collection period). The highest reciprocal median UBT values for each test strain were between 2 and 4 during the collection periods 2-4 h and 4-8 h, respectively. The new enteric oral tobramycin formulation significantly improved the very poor oral absorption of standard tobramycin salt. For all pathogens tested, maximum urinary concentrations of tobramycin were at least two times above the urinary MBC. A twice-or three-times daily dosage regimen and alkalising co-medication may further improve urinary bactericidal activity. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Harvard-Zitierstil: Loose, M., Naber, K., Shields, P., Reinhart, H. and Wagenlehner, F. (2018) Urinary concentrations and antimicrobial activity of tobramycin in healthy volunteers receiving a single oral dose of a novel formulation for improved absorption, International Journal of Antimicrobial Agents, 51(3), pp. 422-426. https://doi.org/10.1016/j.ijantimicag.2017.11.004

APA-Zitierstil: Loose, M., Naber, K., Shields, P., Reinhart, H., & Wagenlehner, F. (2018). Urinary concentrations and antimicrobial activity of tobramycin in healthy volunteers receiving a single oral dose of a novel formulation for improved absorption. International Journal of Antimicrobial Agents. 51(3), 422-426. https://doi.org/10.1016/j.ijantimicag.2017.11.004