The susceptibility data of the bacterial strains in broth and broth with serum albumin are shown in Table 1. A marked effect of serum albumin on the mic90 and mbc90 was noted. The ceftriaxone MIC90 and MBC90 increased eightfold in the presence of serum albumin. The mic90 of cefotaxime and cefotaxime/desacetylcefotaxime were virtually unaffected by the addition of serum albumin. There were minor differences in the MBC90 of cefotaxime and cefotaxime/desacetylcefotaxime in broth compared with broth with serum albumin.
Figure 1) Frequency distribution of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) (mg/L). All organisms were tested against ceftriaxone (MIC, MBC; a, b), cefotaxime (MIC, MBC; c, d), and cefotaxime/desacetylcefotaxime (MIC, MBC; e, f). Solid bars: in vitro testing in broth without serum albumin; hatched bars: in vitro testing in broth with 95% equivalent serum albumin
Figure 2) Killing curves for six selected strains of nonpseudomonal Gram-negative bacilli at an inoculum 3.5x10s colony-forming units (cfu)/mL. The antibiotic concentrations used were equal to the minimum bacterial concentrations in broth. Two Escherichia coli (a.b); two Enterobacter cloacae (c,d); and two Klebsiella pneumoniae (ef) strains were tested. Ceftriaxone without albumin. ceftriaxone with 48% equivalent serum albumin, and Ceftriaxone with 95% equivalent serum albumin; Cefotaxime without serum albumin, cefotaxime with 48% albumin, and cefotaxime with 95% albumin.
The frequency (number) distribution for the organisms inhibited (mic) or killed (mbc) at the antibiotic concentrations are shown in Figure 1. For cefotaxime and cefotaxime/desacetylcefotaxime, the maj ority of the mic results were clustered at the three drug concentrations (Figure 1c,e). For ceftriaxone mics (Figure 1a), the iso I ates were distributed over two clusters (0.03 to 0.06 mg/L in absence of albumin and 0.25 to 0.5 mg/L in presence of albumin). Simi I ar differences are observed for the mbc results of cefotaxime and cefotaxime/desacetylcefotaxime versus ceftriaxone (Figure 1d,f versus 1b). Since the disfributions of mic and mbc raw data were highly skewed, statistical analyses were performed on the geometric means. Two-way anova of mics and mbcs showed that there was a highly significant interaction between drug and serum albumin (P<0.0001). The extent of this effect was evaluated by one-way anova of mics tested with the Scheffe post-hoc comparison. There were significant differences in geometric mean mics and mbcs among the three drugs in broth only (P=0.05) and broth with 95% equivalent serum albumin (P=0.0001) (Table 2). The one-way anova of mics with the Scheffe post-hoc comparison definitively showed that cefotaxime and cefotaxime/ desaceytlcefotaxime were significantly more active than ceftriaxone when tested with albumin (P<0.01). Cefotaxime was found to be significantly more inhibitory than a 1:1 combination of cefotaxime and its desace-tyl mefabolite in broth without and with albumin (P<0.01). Even when serum albumin was added, cefotaxime had the most potent bactericidal activity (P<0.01). Cheapest online shopping is waiting for you to enjoy it as much as you wanted! This is the chance you were looking forward to, so why not go for it right now and finally buy at best fully-licensed pharmacy?
TABLE 1 Susceptibility of nonpseudomonal Gram-negative bacilli (n=121) to ceftriaxone (CAX), cefotaxime (CFT) and cefotaxime/desacetylcefotaxime (1:1; CFT/DACT) in broth only (0%) and broth with 95% equivalent human serum albumin
|Albumin concentration (%) MIC (mg/L): MIC90||CAX||CFT||CFT/DACT|
|MBC (mg/L): MBC90|
The effects of serum albumin on the bactericidal activity of ceftriaxone and cefotaxime were also assessed by the time-kill kinetic analysis. Any reduction in bactericidal activity was assessed by determination of the survival rate (log10 cfu/mL versus time [hours]) of bacferia when exposed to a drug in broth containing 48% and 95% equiva I ent concentrations of serum albumin. Six strains with elevated mbcs of ceftriaxone were tested: two E coli strains (Figure 2a,b) with ceftriaxone mbcs of 0.03 and 0.125 mg/L that increased to 0.5 and 2.0 mg/L, respectively, by addition of serum albumin; two E cloacae strains (Figure 2c,d) with ceftriaxone mbcs of 0.5 and 0.25 mg/L that rose to 2.0 mg/L in broth with serum albumin; and two Kpneumoniae strains (Figure 2e,f) with ceftriaxone mbcs of 0.06 and 0.125 mg/L that increased to 0.5 and 4.0 mg/L in serum albumin. Only one Kpneumoniae strain tested (Figure 2f) had an elevation in cefotaxime mbc (0.03 to 1.0 mg/L). Serum albumin at 48% or 95% equiva I ent serum levels did not overtly affect the bactericidal activity of cefotaxime based on 2log10 or greater increase in survival (cfu/mL) of bacteria at 6 h or 24 h. In contrast, a marked negative effect on the bactericidal activity of ceftriaxone was demonstrated for all six strains with the 95% equivalent serum albumin concentration and for four strains at the 48% equiva I ent concentration. There was no difference in the extent of killing at 6 h or 24 h, when the bactericidal activity of the antibiotics was compared in the presence of 48% or 95% equiva I ent serum albumin.
TABLE 2 Statistical analysis of raw data of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of ceftriaxone (CAX), cefotaxime (CFT) and cefotaxime/desacetylcefotaxime (1:1; CFT/ DACT) in broth only (0%) and broth with 95% equivalent human serum albumin
|Geometric mean CAX CFT CFT/DACT||P value*|