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Effects of linezolid on staphylococcal adherence versus time of treatment
Paul J Pagano1, Lewis V Buchanan, Charlene F Dailey
1Pfizer Kalamazoo, MI 49007, USA. paul.j.pagano@pfizer.com
Abstract:
Staphylococcus epidermidis has emerged as a major nosocomial pathogen that is often associated with infections of indwelling medical devices. Microbial adhesion to implanted foreign materials is a prerequisite for establishing infection. We studied the time-dependent anti-adhesion effects of linezolid and vancomycin on three S. epidermidis clinical isolates. Minimum inhibitory concentration (MIC) values were identical for both agents for all three isolates (2 mg/l). Bacterial suspensions were added to polystyrene wells and treated with 0.5-4 times the MIC of linezolid or vancomycin at 0, 2, 4 or 6 h post-inoculation. Supra-inhibitory (2 and 4 x MIC) and inhibitory (MIC) concentrations of linezolid demonstrated potent anti-adhesion activity following 2 and 4 h deferred treatments. Even at sub-inhibitory concentrations (0.5 x MIC), suppression of staphylococcal adherence to polystyrene was still evident in most cultures. Linezolid at two and four times the MIC also exerted significant inhibitory effects in cultures that had been treated with a 6-h delay. Supra-inhibitory and inhibitory concentrations of vancomycin administered 2 h post-infection appeared equally effective as linezolid. However, sub-inhibitory concentrations of vancomycin showed minimal or no activity against bacterial adhesion. When vancomycin treatments were delayed by 4 h, only concentrations above the MIC prevented adherence. Linezolid has promising in vitro anti-adhesion activity that merits further studies to determine its role in the management of foreign-body infections.
Insights
Linezolid shows strong anti-adhesion effects against Staphylococcus epidermidis, even at delayed or sub-inhibitory doses. This suggests potential for managing medical device infections caused by this common pathogen.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Staphylococcus epidermidis is a leading cause of nosocomial infections, particularly those involving indwelling medical devices.
- Microbial adhesion to foreign materials is a critical initial step in device-related infections.
Purpose of the Study:
- To investigate the time-dependent anti-adhesion efficacy of linezolid and vancomycin against clinical isolates of Staphylococcus epidermidis.
- To compare the anti-adhesion activity of these antibiotics at various concentrations and treatment delays.
Main Methods:
- Three clinical isolates of Staphylococcus epidermidis were used.
- Minimum inhibitory concentrations (MICs) for linezolid and vancomycin were determined.
- Bacterial suspensions were treated with 0.5-4 times the MIC of antibiotics at 0, 2, 4, or 6 hours post-inoculation.
- Adherence to polystyrene was quantified.
Main Results:
- Linezolid demonstrated potent anti-adhesion activity at inhibitory and supra-inhibitory concentrations, even with 2-6 hour treatment delays.
- Sub-inhibitory concentrations of linezolid also showed significant suppression of adherence.
- Vancomycin was effective at inhibitory and supra-inhibitory concentrations with a 2-hour delay, but less so with a 4-hour delay.
- Sub-inhibitory vancomycin concentrations had minimal effect on bacterial adhesion.
Conclusions:
- Linezolid exhibits promising in vitro anti-adhesion properties against Staphylococcus epidermidis.
- These findings suggest linezolid's potential role in managing infections associated with medical devices.
- Further research is warranted to explore linezolid's clinical utility in foreign-body infections.
