[Bacteriological evaluation of combined effects of vancomycin and beta-lactams. II. Results against gram-negative...

Evaluations were made for antibacterial activities of combination uses of flomoxef (FMOX) + vancomycin (VCM) against clinically isolated bacteria of family Enterobacteriaceae, and latamoxef (LMOX) + VCM, cefpirome (CPR) + VCM, and imipenem (IPM) + VCM against also clinically isolated Pseudomonas aeruginosa. The obtained results are summarized as follows. 1. FMOX and VCM appeared to act independently against Enterobacteriaceae without showing synergism or antagonism. 2. Regarding antibacterial effects of LMOX + VCM, or CPR + VCM against P. aeruginosa strains, MIC values under the combined uses were approximately 1 dilution (2 folds) higher than LMOX or CPR used alone, but we did not consider that these results meant the presence of antagonism between the beta-lactams and VCM. 3. Experimental results suggested that an antagonistic relationship was present between IPM and VCM against P. aeruginosa. The degree of the antagonism was dependent on VCM concentrations. In other words, when VCM is present at a concentration between 4 and 128 micrograms/ml, MIC values for IPM increased 2 to 4 dilutions (4 to 16 folds), whereas in the presence of 1 to 2 micrograms/ml VCM, MIC values for IPM were close to those of IPM alone. Further, some of this tendency was observed for FMOX against bacteria of family Enterobacteriaceae in the presence of VCM. 4. These results suggest that the dose level of VCM should be considered based on a low range when a combination therapy is considered between beta-lactams and VCM in the treatment of infections with MRSA alone or with Gram-negative rods with MRSA.