Ceftazidime combined with mecillinam: serum bactericidal titres compared with in-vitro synergy against Gram-negative bacilli

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Abstract
In a study of the possible interaction between mecillinam and ceftazidime against Gram-negative bacilli, ten volunteers received on separate days: ceftazidime 20 mg/kg iv in 15 min, mecillinam 10 mg/kg iv in 15 min, or the combination. Blood samples were obtained before and 1 and 6 h after the end of the infusion. Ten strains each of Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Salmonella spp. and Yersinia spp. and nine strains each of Acinetobacter spp., and Pseudomonas aeruginosa were selected. Most of the strains were resistant to ampicillin and cefazolin. Serum levels of ceftazidime and mecillinam were measured by bioassay. Serum bacteriostatic (SBS) and bactericidal (SBA) titration was done in microtitre plates in cation supplemented Mueller-Hinton broth and 50% human serum. Chequerboard titration was also studied to assess in-vitro synergy between ceftazidime and mecillinam in Mueller-Hinton broth with or without 50% serum. The mean serum concentrations (SD) were for merillinam: 6·1 (1·7) at 1 h, and Acinetobacter spp. and Ps. aeruginosa, whereas it was observed in 37/60 (FIC and 33/60 (FBC) of the strains of other species in Mueller-Hinton; from the strains showing synergy, 28/37 (FIC and 30/33 (FBC) showed also synergy in Mueller-Hinton with 50% human serum. In SBS and SBA, on the other hand, the combination of mecillinam with ceftazidime showed an additive effect against most Enterobacteriaceae tested, synergy being shown for only 10–35% of tests. The very high activity of ceftazidime alone would probably prevent the addition of mecillinam from providing better clinical results.

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