Comparison of the In Vitro Activity of BL-P1654 with Gentamicin and Carbenicillin Against Pseudomonas aeruginosa

The in vitro activity of 6-[d-alpha-(3 guanylureido)-phenylacetamido]-penicillanic acid (BL-P1654) was evaluated against 117 clinical isolates of Pseudomonas aeruginosa, many of which were known to be resistant to both gentamicin and carbenicillin. BL-P1654 was two to eight times more active than carbenicillin against P. aeruginosa. However, all 28 highly carbenicillin-resistant isolates (minimal inhibitory concentration [MIC] > 500 mug/ml) were also highly resistant to BL-P1654. When an MIC of 32 mug/ml or less and a zone of inhibition of 12 mm or more by a 10-mug disk were used as criteria indicating susceptibility to BL-P1654, the false-resistance rate by the disk test was 10.6% and the false-susceptibility rate was 4.2%. The combination of BL-P1654 and gentamicin was synergistic against 45 of 70 isolates of P. aeruginosa tested, but synergism was demonstrated against only 4 of 24 highly gentamicin-resistant (MIC > 63 mug/ml), 1 of 12 highly BL-P1654-resistant (MIC > 250 mug/ml) isolates, and none of nine isolates highly resistant to both of these antibiotics.