5 logs CFU reduction at a drug(s) concentration of 64 μg/ml and showed no significant difference (P > 0.05). In contrast, a comparison of the effects of cefepime on P. aeruginosa monomicrobial (≈4.5 logs CFU reduction at a 64 μg/ml) and P. aeruginosa-A. fumigatus polymicrobial (≈1.5 selleck chemical logs CFU reduction at 64 μg/ml) biofilms (Panel B) showed that the polymicrobial biofilm is significantly less susceptible to cefepime (P < 0.0001). Similarly, a comparison of the effects of combination of
cefepime with posaconazole on monomicrobial biofilm of P. aeruginosa (≈4 logs CFU reduction at 64 μg/ml) with that obtained for polymicrobial biofilm (≈1.5 logs CFU reduction at 64 μg/ml) showed that polymicrobial biofilm is also significantly less susceptible to the combination of drugs (P = 0.0013). However, a comparison of the susceptibility of P. aeruginosa monomicrobial biofilm to cefepime alone (≈4.5 logs CFU reduction at a 64 μg/ml) and cefepime plus posaconazole (≈4 logs CFU reduction at 64 μg/ml) showed no significant difference (P = 0.4234) R428 chemical structure indicating that posaconazole has no detectable effect on the antibacterial activity of cefepime. Similarly, a comparison of the effect of cefepime selleck inhibitor on polymicrobial biofilm (≈1.5 logs CFU reduction at 64 μg/ml) with that of the combination of cefepime and posaconazole (≈1.5 logs CFU reduction
at 64 μg/ml) showed that the polymicrobial biofilm was almost equally susceptible (P = 0.4057) to the drug combination suggesting that the presence of posaconazole in the combination did not affect bioactivity of cefepime against polymicrobial biofilm. Figure 5 Biofilm inhibition by posaconazole and cefepime. A. Effects of posaconazole alone and in combination Glycogen branching enzyme with cefepime against A. fumigatus monomicrobial and A. fumigatus-P. aeruginosa polymicrobial biofilms. B. Effects of cefepime alone and in combination with posaconazole against P. aeruginosa monomicrobial and P. aeruginosa-A. fumigatus polymicrobial biofilms. Each experiment was performed two different times with the clinical isolates AF53470 and PA57402 using independently prepared conidial suspensions and bacterial cultures,
and one time with the laboratory isolates AF36607 and PA27853. Both clinical and laboratory isolates provided similar results. The data were analyzed by one-way and two-way ANOVA with Bonferroni’s multiple comparison test where each set of data is compared with all the other sets of data as well as by paired two-tailed Student’s t-test using Graphpad Prism 5.0. The vertical bar on each data point denotes standard error of the mean for two independent experiments performed with the clinical isolates. Legends: AF, A. fumigatus monomicrobial biofilm; PA, P. aeruginosa monomicrobial biofilm; PA + AF and AF + PA, polymicrobial biofilm; CEF, cefepime; PCZ, posaconazole. Since cefepime alone and in combination with posaconazole showed differential activity against P. aeruginosa monomicrobial and P.