Escherichia coli NDM-1 (CDC & FDA AR Isolate Bank #0055), UTI Model, CFU Data
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DOCUMENTS/REFERENCES
BIOLOGICAL INFORMATION
BACKGROUND INFORMATION
This model assesses the antimicrobial efficacy of test articles in an ascending urinary tract infection (UTI) model with a Tlr4Lps-d mouse lineage. Infection is established under conditions of diuresis, four days prior to treatment with an antimicrobial agent. Treatment is continued for three days prior to measuring microbial counts in kidney and bladder tissue.
ORGANISM
Gram-negative Bacteria
ASSAY INFORMATION
ASSAY TYPE
In Vivo
TESTING INFORMATION
PROCEDURE SUMMARY
Groups of 5-8 female specific-pathogen-free C3H-HeJ (Tlr4Lps-d) mice aged 7-8 weeks are used. Diuresis is induced by placing the mice on 5% glucose water for 6 days prior infection and for the study duration. Infection is established on day 0 in animals under pentobarbital anesthesia (80 mg/kg, intraperitoneal injection). A 50 µL suspension of E.coli (FDA-CDC AR-BANK#0055) is inoculated transurethrally into the bladder, 1 x 109 CFU/mouse, using a urinary catheter. On Day 4 (96 hr after infection), animals are randomly grouped then test substances and vehicle are administered. Recommended dosage is twice daily at 12-hour intervals for 3 sequential days by IV, IP, SC or PO administration (or per client’ request). On Day 7, 12 hr after the last dose, animals are humanely euthanized with CO2.asphyxiation, the bladder and kidneys are aseptically removed, and the tissue is homogenized in PBS pH 7.4. Serial dilutions of tissue homogenates are plated onto Nutrient Agar medium for bacterial enumeration (CFU/tissue). Bacterial counts in urine may be measured as an optional service.
CRITERIA FOR SIGNIFICANCE
Significant difference is determined at P < 0.05
TURNAROUND TIME
STANDARD
40 Days
EXPRESS
35 Days
CLINICAL RELEVANCE
THERAPEUTIC AREA
Infectious Disease
ADDITIONAL INFORMATION
BRAND
PDS
TESTING LOCATION
Taiwan - Taipei
OTHER INFORMATION
We will readily accommodate client-specified alterations. These studies are performed at our AAALAC accredited BSL-2 laboratory in Taipei, Taiwan. All aspects of this work are performed in general accordance with the Guide for the Care and Use of laboratory animals (National Academy Press, Washington, DC, 2011). The study protocol was approved by the Pharmacology Discovery Services IACUC and is performed with the oversight of veterinarians to assure the humane treatment of laboratory animals.
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