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Biofilm is an important virulence factor that allows bacteria to resist host responses and antibacterial agents. The aim of the study was to assess the in-vitro activity of several antimicrobials alone or in combination against two Staphylococcus aureus isolates using a novel pharmacokinetic/pharmacodynamic model of biofilm for three days. One methicillin-susceptible S. aureus (SH1000) and one methicillin-resistant S. aureus (N315) were evaluated in a modified biofilm reactor with polystyrene coupons. Simulated regimens included vancomycin (VAN) plus RIF, moxifloxacin (MOX) and high dose (10 mg/kg/day) daptomycin (DAP) alone and combined with rifampin (RIF) or clarithromycin (CLA). Against SH1000 viable planktonic (PB) and biofilm-embedded bacteria (BB), neither DAP nor MOX alone were bactericidal. In contrast, combination of DAP and MOX with CLA significantly increased the activity of the two agents against both PB and BB (p<0.01), and DAP+CLA reached the limit of detection at 72h. Against PB of N315, DAP alone briefly achieved bactericidal activity at 24h, whereas sustained cidal activity was observed at 32h with VAN+RIF. Overall, only minimal reduction was observed with both regimens against BB (< 2.8 log10 CFU/mL). Finally, combination of DAP+RIF was bactericidal against both PB and BB, achieving the limit of detection at 72h. In conclusion, we developed a novel in-vitro PK/PD model to assess the activity of antimicrobials against mature bacterial biofilm. Combinations of DAP or MOX with CLA were the most effective regimens and may represent promising options to treat persistent infections caused by S. aureus biofilms.
Wayne State University, Anti-Infective Research Laboratory, Detroit, MI USA; Infectious Diseases Unit, HU San Cecilio, Granada-Spain; University of Wisconsin, Madison, WI. USA.
This article was published in the following journal.
Name: Antimicrobial agents and chemotherapy
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The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.
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