BL-P1654: a bacteriostatic penicillin?

In tube dilution studies, large discrepancies between inhibitory and bactericidal concentrations of BL-P1654 against Pseudomonas were observed. To explain these discrepancies which were not observed with carbenicillin, the kinetics of bacterial killing by these two penicillins were evaluated and compared. The kinetics of bacterial killing by both antimicrobial agents were characteristic of a penicillin, with killing initiating simultaneously with growth. Kill curves revealed the presence of a small number of cells resistant to BL-P1654 which were not detectable macroscopically. Studies on microbial resistance also showed the presence of a small but consistent number of cells resistant to BL-P1654 over a broad range of concentrations above its minimal inhibitory concentration. This pattern of resistance was not observed with carbenicillin. Thus, the discrepancies between inhibitory and bactericidal concentrations of BL-P1654 were not due to any unusual bacteriostatic activity but rather due to a small number of resistant cells whose presence could be detected only by sensitive subculturing techniques.