Bactericidal activity of bound ceftriaxone against Streptococcus pneumoniae

Abstract Objectives – Ceftriaxone is a semi-synthetic cephalosporin with a high level of protein binding to albumin. The authors wanted to determine whether the bound fraction was actively bactericidal. Material and method – The bactericidal activity of 3 ceftriaxone concentrations (5, 50, and 200 mg/L) in a brain-heart broth with and without human serum albumin, and in human serum, was evaluated by the time-kill technique on 3 S. pneumoniae strains with varying degree of susceptibility to penicillin G. Results – The low concentration (5 mg/L) exhibits a slightly better bactericidal activity on the penicillin G susceptible strain without albumin than with albumin, in the earlier contact phase. A similar bactericidal activity occurs in both media at the 6 th hour and up to the late phase of bactericidal activity. Concerning the strains with an intermediate or total resistance to penicillin G, the bactericidal activity is identical in the three media. This implies that bound ceftriaxone has a bactericidal activity. Only the 5 mg/L concentration doesn't seem to exhibit any activity on the strain with decreased susceptibility. This may be explained by the existence of two binding-sites of ceftriaxone on serum albumin: a high-affinity, low-capacity site, and a low-affinity, high-capacity site. At low concentrations, only the high-affinity sites are bound and thus, the bound ceftriaxone is inactive. At high concentrations, the part of ceftriaxone mainly bound to the low-affinity sites is much more labile, and may thus interact with the PBPs having a higher affinity for ceftriaxone. Conclusion – This study demonstrates that bound ceftriaxone has a bactericidal activity against S. pneumoniae.