In Vitro Activity of Aztreonam, Fosfomycin, Gentamicin or Levofloxacin against
Gram-Negative Bacteria in the Presence of the Cephalosporins RWJ-54428
(MC-02,479) or RWJ-333441 (MC-04,546)
B. FOLENO, E. WIRA, K. BUSH
The R. W. Johnson Pharmaceutical Res. Inst., Raritan, NJ
Presentation Number: 1075
Background: RWJ-54428 and RWJ-333441 are cephalosporins with targeted activity against
multi-drug resistant gram-positive pathogens, particularly MRSA. If either of these agents were to
be used for empiric therapy or in combination therapy for treatment of polymicrobial infections, it is
necessary to confirm that the in vitro activity of antibacterial agents with activity against
gram-negative bacteria is not altered by the presence of the cephalosporins. Methods: Each
cephalosporin was combined with aztreonam, fosfomycin, gentamicin or levofloxacin, and MICs
were determined using a checkerboard technique in agar dilution assays. Interaction of these
combinations was evaluated against 30 strains of enterobacteriaceae, 4 strains of Pseudomonas
aeruginosa and 2 strains of Moraxella catarrhalis. Fractional inhibitory concentrations were
determined using the criteria that an FIC £0.5 correlated with synergy and an FIC >4 with
antagonism. Results: Although an occasional strain exhibited synergy with each combination, no
consistent synergistic pattern was seen for any species with any of the four agents. Indifference
was seen for all four combinations in at least 24 of the 36 strains. No antagonism was observed for
any combination. Conclusion: On the basis of in vitro results, these two gram-positive
cephalosporins could be combined with any of these four gram-negative active agents for
successful empiric therapy. |
