In vitro interference of tigecycline at subinhibitory concentrations on biofilm development by Enterococcus faecalis.
ABSTRACT Since biofilm formation is the hallmark of Enterococcus faecalis isolates, the aim of this study was to quantify biofilm formation in the presence of subinhibitory concentrations of tigecycline.
Interference of tigecycline on biofilm formation was spectrophotometrically quantified using 20 biofilm-producing E. faecalis isolates with tigecycline MICs of 0.12 (8 strains) or 0.25 mg/L (12 strains). Biofilm production was measured in antibiotic-free tryptic soy broth supplemented with 1% glucose and compared with biofilm production in the same medium with tigecycline at subinhibitory concentrations (0.25× or 0.5× MIC, similar to trough concentrations in serum or concentrations in the colon after a standard dose) by reading the optical density at 450 nm (OD(450)) after staining with Crystal Violet.
In the presence of subinhibitory tigecycline concentrations, pooled OD(450) values for the 20 strains [median (IQR)] were significantly lower than those for controls: 0.468 (0.379-0.516) for antibiotic-free controls versus 0.295 (0.200-0.395) for 0.25× MIC tigecycline (P < 0.001) and 0.287 (0.245-0.479) for 0.5× MIC tigecycline (P < 0.001), with significant differences between pooled OD(450) values obtained with each concentration of tigecycline (P = 0.022). In 17 out of 20 (85%) strains the OD(450) obtained with 0.25× MIC tigecycline was significantly (P < 0.05) lower than the basal OD(450), while this occurred in 12 out of 20 (60%) strains with 0.5× MIC.
In vitro tigecycline subinhibitory concentrations were able to interfere with biofilm formation by E. faecalis.
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ABSTRACT: The aim of this study was to compare the activity of linezolid and vancomycin in an in vitro pharmacodynamic model to assess potential differences in activity against biofilm-embedded organisms. Single-lumen central venous catheters colonized with biofilm-embedded Staphylococcus aureus, Staphylococcus epidermidis or vancomycin-resistant Enterococcus faecium (VRE) were treated with simulated clinical dosing regimens of linezolid 600 mg every 12 h or vancomycin 1 g every 12 h in a one-compartment in vitro pharmacodynamic model. Quantitative cultures were sampled through the catheter and peripheral ports over 48 h to dynamically assess changes in the burden of catheter colonization and organism seeding, respectively. At 24 and 48 h catheters were removed, sonicated and cultured for adherent organisms. Both linezolid and vancomycin suppressed bacterial growth on the catheter and release of S. aureus and S. epidermidis into the model compared with controls (P < 0.05), while linezolid also suppressed counts compared with control and vancomycin versus VRE. Neither agent completely eradicated bacterial colonization of the catheters. MICs for the isolates recovered from the model did not increase over time with linezolid or vancomycin exposure. Lack of activity against biofilm-embedded organisms appeared to be the primary reason for microbiological failure of both drugs in the model.Journal of Antimicrobial Chemotherapy 05/2005; 55(5):792-5. · 5.34 Impact Factor
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ABSTRACT: Biofilm production was assessed in 52 Staphylococcus epidermidis isolates from the catheters of 52 patients with catheter-related bloodstream infections (CR-BSI) and compared with 14 isolates from the skin of healthy volunteers by spectrophotometry. The isolates were classified as non- (G1), weak- (G2) or strong- (G3) slime producers based on optical density, and as producers and non-producers based on the results of the Congo red agar test. Differences (p = 0.012) in the proportion of G1, G2 and G3 among the isolates were found between catheter and healthy skin strains: there was a higher percentage of G1 types among the healthy skin strains (35.7 vs. 11.5%; p = 0.046) and a higher percentage of G3 types among the catheter isolates (44.2 vs. 0%; p = 0.001). No significant differences were found with the Congo red agar test. G3 is a phenotypic marker for CR-BSI.European Journal of Clinical Microbiology 05/2008; 27(4):311-4. · 3.02 Impact Factor
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ABSTRACT: The objective of these analyses was to assess the penetration of tigecycline into colon wall tissue and epithelial lining fluid (ELF). The analyses included data from subjects without infection (phase 1) and patients with intra-abdominal infections (phase 2/3). Steady-state serum samples were collected from all subjects/patients (n = 577), while colon wall specimens (n = 23) and ELF specimens (n = 30) were obtained from subjects without infection. Tissue and serum data were simultaneously comodeled by using the BigNPAG program, and a four-compartment, open model with zero-order intravenous input and first-order elimination was employed. To examine the full range of tissue penetration and the associated probabilities of occurrence, a 9,999-subject Monte Carlo simulation was performed with two outputs, one for ELF penetration and one for colon wall tissue penetration. Data were well fit using models described above, with all r(2) values above 0.95. For subjects without infection, the median (5th and 95th percentiles) colon wall and ELF penetration ratios were 1.73 (0.160 and 199) and 1.15 (0.561 and 5.23), respectively. Simulation results predict that tissue penetration varies considerably and likely explain unexpected clinical outcomes for those patients infected with strains at margins of the MIC distribution.Antimicrobial Agents and Chemotherapy 12/2007; 51(11):4085-9. · 4.57 Impact Factor