Evaluation of the Bactericidal Activity of Fosfomycin in Combination with Selected Antimicrobial Comparison Agents Tested against Gram-Negative Bacterial Strains by Using Time-Kill Curves.
Robert K Flamm, Paul R Rhomberg, Jill M Lindley, Kim Sweeney, E J Ellis-Grosse, Dee Shortridge
Author Information
Robert K Flamm: JMI Laboratories, North Liberty, Iowa, USA robert-flamm@jmilabs.com.
Paul R Rhomberg: JMI Laboratories, North Liberty, Iowa, USA.
Jill M Lindley: JMI Laboratories, North Liberty, Iowa, USA.
Kim Sweeney: Zavante Therapeutics, Inc., San Diego, California, USA.
E J Ellis-Grosse: Zavante Therapeutics, Inc., San Diego, California, USA.
Dee Shortridge: JMI Laboratories, North Liberty, Iowa, USA.
The effects of combining fosfomycin with various antimicrobial agents were evaluated by broth microdilution checkerboard and time-kill kinetic studies. Checkerboard analyses were used to evaluate the following 30 Gram-negative isolates: 5 , 5 - species complex, and 20 isolates. No isolate exhibited antagonism when fosfomycin was tested in combination, and synergy was observed in more than 25% of the drug combinations tested. The most frequent instances of synergy occurred when testing fosfomycin with β-lactams. Two isolates of , 2 of , and 1 of the - species complex that exhibited synergy when fosfomycin was tested in combination were subjected to time-kill kinetic analyses for confirmation. Time-kill assays confirmed synergistic activity. These data indicated that combination therapy with fosfomycin may be beneficial.
