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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.
Mice selectively bred for hypersusceptibility to two-stage chemical skin carcinogenesis. They are also hypersusceptible to UV radiation tumorigenesis with single high-dose, but not chronic low-dose, exposures. SENCAR (SENsitive to CARcinogenesis) mice are used in research as an animal model for tumor production.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
The use of multiple drugs administered to the same patient, most commonly seen in elderly patients. It includes also the administration of excessive medication. Since in the United States most drugs are dispensed as single-agent formulations, polypharmacy, though using many drugs administered to the same patient, must be differentiated from DRUG COMBINATIONS, single preparations containing two or more drugs as a fixed dose, and from DRUG THERAPY, COMBINATION, two or more drugs administered separately for a combined effect. (From Segen, Dictionary of Modern Medicine, 1992)
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