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      Potentiation effects of amikacin and fosfomycin against selected amikacin-nonsusceptible Gram-negative respiratory tract pathogens.

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          Abstract

          The amikacin-fosfomycin inhalation system (AFIS) is a combination of 2 antibiotics and an in-line nebulizer delivery system that is being developed for adjunctive treatment of pneumonia caused by Gram-negative organisms in patients on mechanical ventilation. AFIS consists of a combination of amikacin and fosfomycin solutions at a 5:2 ratio (amikacin, 3 ml at 100 mg/ml; fosfomycin, 3 ml at 40 mg/ml) and the PARI Investigational eFlow Inline System. In this antibiotic potentiation study, the antimicrobial activities of amikacin and fosfomycin, alone and in a 5:2 combination, were assessed against 62 Gram-negative pathogens from a worldwide antimicrobial surveillance collection (SENTRY). The amikacin MICs for 62 isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were ≥32 μg/ml (intermediate or resistant according to the Clinical and Laboratory Standards Institute [CLSI]; resistant according to the European Committee on Antimicrobial Susceptibility Testing [EUCAST]). Each isolate was tested against amikacin (0.25 to 1,024 μg/ml), fosfomycin (0.1 to 409.6 μg/ml), and amikacin-fosfomycin (at a 5:2 ratio) using CLSI reference agar dilution methods. The median MIC values for amikacin and fosfomycin against the 62 isolates each decreased 2-fold with the amikacin-fosfomycin (5:2) combination from that with either antibiotic alone. Interactions between amikacin and fosfomycin differed by isolate and ranged from no detectable interaction to high potentiation. The amikacin-fosfomycin (5:2) combination reduced the amikacin concentration required to inhibit all 62 isolates from >1,024 to ≤ 256 μg/ml and reduced the required fosfomycin concentration from 204.8 to 102.4 μg/ml. These results support continued development of the amikacin-fosfomycin combination for aerosolized administration, where high drug levels can be achieved.

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          Author and article information

          Journal
          Antimicrob. Agents Chemother.
          Antimicrobial agents and chemotherapy
          1098-6596
          0066-4804
          Jul 2014
          : 58
          : 7
          Affiliations
          [1 ] Cardeas Pharma, Seattle, Washington, USA Bruce.Montgomery@CardeasPharma.com.
          [2 ] JMI Laboratories, North Liberty, Iowa, USA.
          [3 ] Cardeas Pharma, Seattle, Washington, USA.
          Article
          AAC.02780-13
          10.1128/AAC.02780-13
          4068521
          24752275
          Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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