scholarly journals Determination of Antibiotic Effect in an In Vitro Pharmacodynamic Model: Comparison with an Established Animal Model of Infection

2002 ◽  
Vol 46 (11) ◽  
pp. 3574-3579 ◽  
Author(s):  
Charles R. Bonapace ◽  
Lawrence V. Friedrich ◽  
John A. Bosso ◽  
Roger L. White
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
In Vitro Model ◽  
Pharmacodynamic Model ◽  
Maximum Effect ◽  
Infection Model ◽  
Regression Equations ◽  
Antibiotic Effect ◽  
Vitro Model

ABSTRACT Animal infection models have historically been used to study pharmacodynamic relationships. Similar results could theoretically be produced by using an in vitro pharmacodynamic model as an alternative to animal models. We compared the antibiotic effects of ticarcillin administered in various doses and dosing regimens against Pseudomonas aeruginosa ATCC 27853 under conditions analogous to those previously employed in a neutropenic-mouse thigh infection model (B. Vogelman et al., J. Infect. Dis. 158:831-847, 1988). Ticarcillin dosages of either 96, 192, or 384 mg/day were administered at 1-, 2-, 3-, 4-, 8-, 12-, or 24-h intervals into a two-compartment model in order to duplicate the concentration-time profiles of the animal model. Colony counts were enumerated at 0 and 24 h. Linear regression and sigmoidal maximum-effect (Emax) model fitting were used to assess the relationship between the percentage of time that the concentration remained above the MIC (%T>MIC) or above four times the MIC (%T>4×MIC) and the change in the log10 CFU per milliliter (Δlog10 CFU/ml) in the central and peripheral compartments. Statistical analysis of the Δlog10 CFU/ml values was performed for matched regimens of the in vitro and animal models based on the %T>MICs. The slopes of the regression equations of %T>MICs relative to Δlog10 CFU/ml values were similar for the in vitro and animal models, but the y intercept was greater with the in vitro model. The Δlog10 CFU/ml values of the 0- to 24-h colony counts at equivalent %T>MICs in the two models were not statistically different (P = 0.087). Overall, the peripheral compartment of the in vitro model was a better predictor of effect than the central compartment. This study, which compares pharmacodynamic principles between an in vitro and an animal model, demonstrated similar relationships between %T>MICs and effects.

scholarly journals Activity of Telavancin against Staphylococcus aureus Strains with Various Vancomycin Susceptibilities in an In Vitro Pharmacokinetic/Pharmacodynamic Model with Simulated Endocardial Vegetations

2009 ◽  
Vol 53 (7) ◽  
pp. 2928-2933 ◽  
Author(s):  
Steven N. Leonard ◽  
Céline Vidaillac ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
In Vitro Model ◽  
Therapeutic Potential ◽  
Population Analysis ◽  
Pharmacodynamic Model ◽  
Bacterial Killing ◽  
Vitro Model

ABSTRACT We investigated the activity of telavancin, a novel lipoglycopeptide, alone and combined with gentamicin or rifampin (rifampicin) against strains of Staphylococcus aureus with various vancomycin susceptibilities. Strains tested included methicillin (meticillin)-resistant S. aureus (MRSA) 494, methicillin-sensitive S. aureus (MSSA) 1199, heteroresistant glycopeptide-intermediate S. aureus (hGISA) 1629, which was confirmed by a population analysis profile, and glycopeptide-intermediate S. aureus (GISA) NJ 992. Regimens of 10 mg/kg telavancin daily and 1 g vancomycin every 12 h were investigated alone and combined with 5 mg/kg gentamicin daily or 300 mg rifampin every 8 h in an in vitro model with simulated endocardial vegetations over 96 h. Telavancin demonstrated significantly greater killing than did vancomycin (P < 0.01) for all isolates except MRSA 494 (P = 0.07). Telavancin absolute reductions, in log10 CFU/g, at 96 h were 2.8 ± 0.5 for MRSA 494, 2.8 ± 0.3 for MSSA 1199, 4.2 ± 0.2 for hGISA 1629, and 4.1 ± 0.3 for GISA NJ 992. Combinations of telavancin with gentamicin significantly enhanced killing compared to telavancin alone against all isolates (P < 0.001) except MRSA 494 (P = 0.176). This enhancement was most evident against hGISA 1629, where killing to the level of detection (2 log10 CFU/g) was achieved at 48 h (P < 0.001). The addition of rifampin to telavancin resulted in significant (P < 0.001) enhancement of killing against only MSSA 1199. No changes in telavancin susceptibilities were observed. These results suggest that telavancin may have therapeutic potential, especially against strains with reduced susceptibility to vancomycin. Combination therapy, particularly with gentamicin, may improve bacterial killing against certain strains.

scholarly journals Towards an In Vitro Retinal Model to Study and Develop New Therapies for Age-Related Macular Degeneration

2021 ◽  
Vol 8 (2) ◽  
pp. 18
Author(s):  
Beatrice Belgio ◽  
Federica Boschetti ◽  
Sara Mantero
Keyword(s):  
Animal Models ◽  
Macular Degeneration ◽  
Tensile Testing ◽  
In Vitro Model ◽  
Age Related Macular Degeneration ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Age Related ◽  
Vitro Model

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly worldwide. So far, the etiology and the progression of AMD are not well known. Animal models have been developed to study the mechanisms involved in AMD; however, according to the “Three Rs” principle, alternative methods have been investigated. Here we present a strategy to develop a “Three Rs” compliant retinal three-dimensional (3D) in vitro model, including a Bruch’s membrane model and retina pigment epithelium (RPE) layer. First, tensile testing was performed on porcine retina to set a reference for the in vitro model. The results of tensile testing showed a short linear region followed by a plastic region with peaks. Then, Bruch’s membrane (BrM) was fabricated via electrospinning by using Bombyx mori silk fibroin (BMSF) and polycaprolactone (PCL). The BrM properties and ARPE-19 cell responses to BrM substrates were investigated. The BrM model displayed a thickness of 44 µm, with a high porosity and an average fiber diameter of 1217 ± 101 nm. ARPE-19 cells adhered and spread on the BMSF/PCL electrospun membranes. In conclusion, we are developing a novel 3D in vitro retinal model towards the replacement of animal models in AMD studies.

Three-dimensional microtissues as an in vitro model for personalized radiation therapy

The Analyst ◽  
2017 ◽  
Vol 142 (19) ◽  
pp. 3605-3612 ◽  
Author(s):  
Yuting Qiu ◽  
Dandan Ning ◽  
Peipei Zhang ◽  
Stephanie Curly ◽  
Yong Qiao ◽  
...  
Keyword(s):  
Cell Culture ◽  
Dna Damage ◽  
Animal Model ◽  
Radiation Therapy ◽  
In Vitro Model ◽  
Three Dimensional ◽  
Intermediate Model ◽  
Radiation Induced ◽  
Vitro Model

This paper describes the use of 3D microtissues as an intermediate model between the 2D cell culture and the animal model to assess radiation-induced cellular and DNA damage in the context of personalized radiation therapy.

scholarly journals Comparative Pharmacodynamics of Three Newer Fluoroquinolones versus Six Strains of Staphylococci in an In Vitro Model under Aerobic and Anaerobic Conditions

2002 ◽  
Vol 46 (5) ◽  
pp. 1561-1563 ◽  
Author(s):  
David H. Wright ◽  
Brent W. Gunderson ◽  
Laurie B. Hovde ◽  
Gigi H. Ross ◽  
Khalid H. Ibrahim ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Pharmacodynamic Model ◽  
Clinical Isolates ◽  
Anaerobic Conditions ◽  
Vitro Model ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

ABSTRACT Six strains of staphylococci were exposed to levofloxacin, moxifloxacin, or trovafloxacin in an in vitro pharmacodynamic model under both aerobic and anaerobic conditions. Each agent demonstrated a rapid 3-log10 kill versus susceptible isolates regardless of condition. Against clinical isolates with reduced susceptibility, regrowth occurred by 24 h and was frequently associated with further increases in MICs.

scholarly journals Fluoroquinolone Resistance in Anaerobic Bacteria following Exposure to Levofloxacin, Trovafloxacin, and Sparfloxacin in an In Vitro Pharmacodynamic Model

2001 ◽  
Vol 45 (7) ◽  
pp. 2136-2140 ◽  
Author(s):  
Gigi H. Ross ◽  
David H. Wright ◽  
Laurie Baeker Hovde ◽  
Marnie L. Peterson ◽  
John C. Rotschafer
Keyword(s):  
In Vitro Model ◽  
Anaerobic Bacteria ◽  
Pharmacodynamic Model ◽  
Fluoroquinolone Resistance ◽  
Time Curve ◽  
Development Of Resistance ◽  
Concentration Time ◽  
Vitro Model

ABSTRACT This investigation explored pharmacodynamic characteristics of fluoroquinolones against Bacteroides thetaiotamicron and the potential for development of resistance. An in vitro model was used to generate kill curves with three fluoroquinolones at various area under the concentration-time curve (AUC)/MIC ratios. Concentration-independent killing was observed. Increases in MICs were noted following exposure to fluoroquinolones at AUC/MIC ratios of 6 to 14.

scholarly journals Differentiated neuroblastoma F-11 cells as an alternative in-vitro model to dorsal root ganglion neurons

2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Stefania Blasa ◽  
Valentina Pastori ◽  
Alessia D’Aloia ◽  
Marzia M. Lecchi
Keyword(s):  
Animal Models ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
In Vitro Model ◽  
Dorsal Root Ganglion Neurons ◽  
Biomedical Field ◽  
Vitro Model ◽  
Ganglion Neurons

We induced differentiation in F-11 cells to verify if they could show similarities with sensory neurons, in order to develop an alternative to animal models for research studies in the biomedical field.

Impact of bacterial species and baseline resistance on fosfomycin efficacy in urinary tract infections

2019 ◽  
Vol 75 (4) ◽  
pp. 988-996 ◽  
Author(s):  
Iain J Abbott ◽  
Jordy Dekker ◽  
Elke van Gorp ◽  
Rixt A Wijma ◽  
Merel N Raaphorst ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Bacterial Species ◽  
Clinical Isolates ◽  
Infection Model ◽  
Limit Of Quantification ◽  
E Coli ◽  
Mutant Prevention Concentration ◽  
Vitro Model ◽  
Tract Infections

Abstract Objectives To assess the antibacterial effects of a single 3 g oral fosfomycin dose on Escherichia coli and Klebsiella pneumoniae clinical isolates within a dynamic bladder infection model. Methods An in vitro model simulating dynamic urinary fosfomycin concentrations was used. Target fosfomycin exposure (Cmax = 1984 mg/L and Tmax = 7.5 h) was validated by LC-MS/MS. Pharmacodynamic responses of 24 E. coli and 20 K. pneumoniae clinical isolates were examined (fosfomycin MIC ≤0.25–128 mg/L). Mutant prevention concentration (MPC), fosfomycin heteroresistance, fosfomycin resistance genes and fosA expression were examined. Pathogen kill and emergence of high-level resistance (HLR; MIC &gt;1024 mg/L) were quantified. Results Following fosfomycin exposure, 20 of 24 E. coli exhibited reductions in bacterial counts below the lower limit of quantification without regrowth, despite baseline fosfomycin MICs up to 128 mg/L. Four E. coli regrew (MIC = 4–32 mg/L) with HLR population replacement. At baseline, these isolates had detectable HLR subpopulations and MPC &gt;1024 mg/L. All E. coli isolates were fosA negative. In contrast, 17 of 20 K. pneumoniae regrew post exposure, 6 with emergence of HLR (proportion = 0.01%–100%). The three isolates without regrowth did not have a detectable HLR subpopulation after dynamic drug-free incubation. All K. pneumoniae had MPC &gt;1024 mg/L and were fosA positive. WGS analysis and fosA expression failed to predict fosfomycin efficacy. Conclusions E. coli and K. pneumoniae isolates demonstrate discrepant responses to a single fosfomycin dose in a dynamic bladder infection in vitro model. Treatment failure against E. coli was related to an HLR subpopulation, not identified by standard MIC testing. Activity against K. pneumoniae appeared limited, regardless of MIC testing, due to universal baseline heteroresistance.

Sign in / Sign up

Export Citation Format

Share Document