The re I ationships between serum protein bind I ng and the distribution of beta-I actam anfibiotics has been exfensively studied and reviewed over the past two decades. The differences in serum protein binding between ceftriaxone and cefotaxime have been esfablished. Methodology has been developed to compare the pharmacokinetics of antibiotics that differ in protein binding. Protein binding may be of importance in antibacterial chemotherapy because the bound antibiotic is essentially unavailable for anfibacterial acfivity. This effect should be reflected by an increase in mic and mbc under the in fluence of serum profein. The present study was not intended to quantify the total and free concentrations of ceftriaxone and cefotaxime in serum, but rather to evaluate the change in in vitro inhibitory and, more important, bactericidal activity of ceftriaxone, cefotaxime and ceftotaxime/desacetylcefotaxime (in 1:1 combination) against 121 nonpseudomonal Gram-negative bacferia in the presence of human serum protein. Since ceftriaxone is predominantly bound to albumin, the present investigation employed 48% and 95% equivalent levels (19 and 38 gm/L) of human serum albumin, instead of di I uting with 25% or 50% (volume/volume) of human serum as described by Jones and Barry.
We found that mic90 (1 mg/L) and mbc90 (2 mg/L) for ceftriaxone in the presence of 95% equiva I ent serum albumin increased eightfold and were at least a twofold di I ution lower than those of cefotaxime (0.25 and 1 mg/L) and cefotaxime/desacetylcefotaxime (0.5 and 1 mg/L), respectively. Because the mic90, a frequently used percentile to evaluate in vitro activity, is prone to error, even in symmetrical data distributions, and with nonsymmetrical or skewed distributions one should be caut ious of usi ng any percentile as an estimator of in vitro activity. We employed the natural logarithmic transformed measurements (ie, geometric means) of mics and mbcs to achieve a more accurate measure of central tendency. The geometric mean mic and mbc were the lowest for ceftriaxone indicating it had the best antimicrobial activity in broth only. However, based on the geometric means, activity of cefotaxime was superior in broth with serum albumin. Most advantageous shopping with best pharmacy you can choose in just a second: and find out exactly how little it could cost you to be getting your medications quick and easy.
Highly significant elevations in the geometric mean mics and mbcs of ceftriaxone were observed by two-way anova when in vitro test i ng was switched from 0% (broth only) to 95% equivalent serum albumin. There were also marked differences between cefotaxime and cefotaxime/desacetylcefotaxime. Cefotaxime proved more active than the 1:1 combination of cetotaxime and its metabolite, although an earlier report documented the advantages of antimicrobial agents that have active metabolites. Mandell and Afnan also reported synergistic activity of desacetylcefotaxime and its parent compound in the presence of neutrophils. The one-way anova of geometric mean mics and mbcs tested by Scheffe post-hoc showed that the inhibitory and bactericidal activities were greatest for cefotaxime followed by cefotaxime/desacetylcefotaxime and ceftriaxone.