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.