Klebsiella pneumoniae KPC-2 (CDC & FDA AR Isolate Bank #0098), Thigh Infection Model, CFU Data

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BIOLOGICAL INFORMATION
BACKGROUND INFORMATION
This model assesses the antimicrobial efficacy of test articles in a tissue infection model with a KPC-2 carbapenem resistant Klebsiella pneumoniae clinical isolate. Microbial counts in thigh tissue are measured. K. pneumoniae can cause life-threatening infections such as bacteremia, peritonitis, lung, and urinary tract infections. This KPC-2 beta-lactamase producing organism is resistant to many antibiotics including aminoglycosides, quinolones, beta-lactam antibiotics, and trimethoprim/sulfamethoxazole. It is susceptible to tigecycline, and colistin.
SPECIES
Klebsiella pneumoniae
STRAIN COMMON NAME
(#0098)
ORGANISM
Gram-negative Bacteria
INCUBATION CONDITIONS
Aerobic
NOTABLE ANTIBIOTIC RESISTANCE GENE
KPC-2
ANTIBIOTIC RESISTANCE GENES
aph(4)-Ia,catA1,cmlA1,dfrA12,KPC-2,mph(A),OmpK35,oqxA,oqxB,OXA-9,sul1,sul3,TEM-1A
SOURCE
STRAIN SOURCE
CDC & FDA AR Isolate Bank
STRAIN SOURCE ID
AR Bank #0098
ASSAY INFORMATION
ASSAY TYPE
In Vivo
TESTING INFORMATION
PROCEDURE SUMMARY
Groups of 5 male or female specific-pathogen-free ICR (CD-1) mice weighing 22 ± 2 g are used. Animals are immunosuppressed by two intraperitoneal injections of cyclophosphamide, the first at 150 mg/kg 4 days before infection (Day –4) and the second at 100 mg/kg 1 day before infection (Day –1). On Day 0, animals are inoculated intramuscularly (0.1 ml/thigh) into the right thigh with 0.5-1 x 10e5 CFU/mouse of K. pneumoniae KPC-2 FDA-CDC AR-BANK#0098. Vehicle and/or test substances are then administered 2 and 14 hours later (BID) or per client’s specifications. Standard dose routes are IV, IP, SC or PO. At 26 hours after inoculation, animals are humanely euthanized with carbon dioxide asphyxiation and then the muscle of the right thigh is harvested from each test animal. The removed muscle tissue is homogenized in 3 ml of PBS, pH 7.4, with a Polytron homogenizer. Homogenates, 0.1 ml, are used for serial 10-fold dilutions and plated onto nutrient agar medium for colony count (CFU/g) determination.
CRITERIA FOR SIGNIFICANCE
Significant difference is determined at ≥ 2-log or P < 0.05
TURNAROUND TIME
STANDARD
20 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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