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Effect of meropenem on the vascular permeability factor produced by Acinetobacter baumannii
1Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic.
Abstract:
Eleven Acinetobacter baumannii strains produced a toxic substance--the vascular permeability factor--in the culture medium. Intradermal injection of this substance enhanced vascular permeability in the rabbit skin. The extent of permeability reactions varied from 0.28 cm2 to 1.61 cm2. Changes in the permeability factor activity of four A. baumannii strains after treatment with meropenem (CAS 96036-03-2) at suprainhibitory concentrations (2x, 4x or 8x) minimum inhibitory concentration (MIC) or supra-subinhibitory ones (2-8x MIC + 0.2x MIC) were tested in vitro. Meropenem at all suprainhibitory concentrations (with the exception of 8x MIC for one strain) was almost ineffective. Alterations in this activity were in the range of 93% to 106% of the control values. Supra-subinhibitory concentrations of meropenem significantly increased the permeability factor activity (to 150%-176% of the control values). These findings indicate that meropenem mainly at supra-subinhibitory concentrations can in vitro interfere with the vascular permeability factor produced by A. baumannii.
Insights
Meropenem at supra-subinhibitory concentrations significantly increased vascular permeability factor activity in Acinetobacter baumannii. This suggests meropenem may interfere with this toxin, impacting bacterial virulence.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Acinetobacter baumannii produces a vascular permeability factor (VPF) that enhances vascular permeability.
- The VPF's role in A. baumannii pathogenesis requires further investigation.
- Understanding factors that modulate VPF production is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the effect of meropenem on the production of vascular permeability factor by Acinetobacter baumannii.
- To determine if meropenem, at various concentrations, influences the VPF activity.
- To explore potential therapeutic implications of meropenem's interaction with VPF.
Main Methods:
- Eleven Acinetobacter baumannii strains were screened for VPF production.
- VPF activity was quantified by measuring enhanced vascular permeability in rabbit skin.
- Four A. baumannii strains were treated in vitro with meropenem at suprainhibitory (2x, 4x, 8x MIC) and supra-subinhibitory (2-8x MIC + 0.2x MIC) concentrations.
- Changes in VPF activity were assessed post-meropenem treatment.
Main Results:
- A. baumannii strains produced VPF, causing increased vascular permeability in rabbits.
- Meropenem at suprainhibitory concentrations was largely ineffective in altering VPF activity (93%-106% of control).
- Supra-subinhibitory concentrations of meropenem significantly increased VPF activity (150%-176% of control).
Conclusions:
- Meropenem, particularly at supra-subinhibitory concentrations, can interfere with the vascular permeability factor produced by A. baumannii in vitro.
- This interaction suggests a potential mechanism by which meropenem might modulate A. baumannii virulence.
- Further research is warranted to elucidate the clinical significance of this in vitro finding.