Because the time-kill kinetic method is considered to be more sensitive than simple mic-mbc methodology for evaluating antimicrobial activity, it is possible to observe wide differences in the killing kinetics among strains with similar mics.
Since there was no difference in the extent of killing at 6 or 24 h, the extrapolated results from the convenience plot of 6 h time-kill tested at mbc levels of drugs were considered to be predictors of the bactericidal activity. All six strains tested resisted killing by ceftriaxone in broth with 95% serum albumin. A marked negative effect of serum albumin on the kill i ng by ceftriaxone was also demonstrated for four of six strains at a reduced, 48% equiva i ent serum albumin level in the test i ng broth. The killing rate was also slowed for two of six strains exposed to cefotaxime in broth with serum albumin.
The present study demonstrated a significant reduction in antimicrobial activity of ceftriaxone in the presence of human serum albumin (P=0.0001). In vivo animal model studies such as that of Tawara et al have shown that the therapeutic efficacy of cephem ant ibiotics including ceft riaxone in K pneumoniae-induced experimental pneumonia correlated with total drug level in se tum. However, in a rat model of K pneumoniae pneumonia described by Bakker-Woudenberg et al protein binding of these antimicrobial agents in serum adversely affected both drug penetration into lungs and therapeutic efficacy.
The clinical significance of the negative effect of ceftriaxone bind t ng to serum albumin remains controversial. While the pharmacokinetic and therapeutic efficacy data from the four clinical stud t es of ceftriaxone and cetotaxime are equivocal in showing a difference between the two agents, Mandell et al and Smith et al reported that the therapeutic efficacy of ceftriaxone (2 g every 24 h) was comparable with that of cefotaxime (2 g every 6 h) in treating serious nosocomial bacterial infections. You now have access to the best pharmacy that always does what it promises and sells finest quality drugs that you will benefit from: buy alesse and see for yourself how easy and convenient it could be to shop for your drugs online.
The results of our study suggest that there was a negative influence of serum albumin on the in vitro antimicrobial activity of ceftriaxone. The clinical importance of this has not been determined.