|
|
| |
| |
 |
 |
Antimicrobial Susceptibility Testing
Broth-based assays are available for the routine determination of minimum inhibitory concentration (MIC) of antimicrobial compounds as specified by the Clinical Laboratory Standards Institute (CLSI, formerly the NCCLS). Complimentary studies such as mean bactericidal concentration (MBC) and kill-curve analyses can be used to determine bactericidal versus bacteriostatic mode-of-action as well as to provide an initial assessment of pharmacodynamic class. ImQuest maintains a broad collection of bacterial test strains (CLSI QC strains, recent clinical isolates, drug resistant strains, STI organisms) in addition to indication-specific panels (respiratory, pyogenic cocci, enteric, general spectrum, and yeast). Therapeutic efficacy in vivo is examined by using industry standard animal models such as the rodent neutropenic thigh, respiratory tract, groin abscess, and peritonitis infection models. These models can also provide important pharmacokinetic and pharmacodynamic parameters for dosing considerations, including dose-ranging, postantibiotic effect [PAE], and sub-MIC effect. Finally, ImQuest can custom configure in vitro pharmacodynamic models based on various published sources. These systems can provide important information regarding antimicrobial efficacy under dynamic situations where specific human serum half-life values are simulated.
 |
CLSI broth-based microdilution MIC and MBC determinations. |
|
Kill-curve analyses (for bactericidal versus bacteriostatic differentiation). |
|
In vivo therapeutic efficacy potential (neutropenic thigh, respiratory tract, peritonitis,
and groin abscess models with standard comparator drugs). |
|
Post-antibiotic effect in vivo and in vitro. |
|
Customized in vitro pharmacodynamic simulations. |
Whole-cell and genetic-based mode-of-action analysis, biochemical, and molecular studies that determine the mode-of-action (MOA) of new antimicrobial compounds are critical for late stage development and subsequent regulatory approval. Biosynthetic precursor incorporation assays are available that can place a compound's MOA into recognized metabolic pathways such as transcription/translation, DNA replication, and membrane or cell wall biosynthesis. Molecular genetic tools such as spontaneous mutant generation and sequence analysis as well as site-directed approaches are available to recover genes corresponding to potential new drug targets, or to track the dissemination of new or conventional resistance mechanisms. Transport assays and physicochemical analyses are available to address such issues as drug penetration, serum protein binding, and efflux mechanisms affecting efficacy and resistance potential. |
 |
Spectrum, Break-point, and Population Analysis
With our in-house strain collection and in collaboration with designated partners, ImQuest can provide a full range of spectrum sensitivities for key pathogens as well as population break-point analyses (MIC50 and MIC90 values). This information is critical for determination of spectrum coverage and labeling considerations. ImQuest also provides resistance surveillance both during clinical trials and the post-marketing period.
|
Spectrum analysis using general and indication-specific pathogen panels |
|
Population analysis for break-point determination and MIC50, MIC90 values |
|
Subsequent post marketing resistance surveillance |
|
|
Topical Microbicide Development
ImQuest has the capability to expand the development of antimicrobial agents to include topical microbicide formulations. Although ImQuest expertise resides in the development of microbicides to inhibit the sexual transmission of HIV and STI–causing pathogens, expanded microbicide capabilities includes the more traditional strains of non-STI bacteria.
Evaluations include efficacy and toxicity to define lead candidates, range and mechanism of action assays, combination microbicide therapy strategies, resistance, formulation development, and 3-dimensional tissue models. Importantly, these capabilities are optimized to define the efficacy of topical agents in the environment in which they are designed to act. |
|
Consulting Services
Antimicrobial compounds are a unique therapeutic class with development considerations unlike any other target space. While conventional drugs act directly on host tissues, antibiotics target microbial organisms within those tissues. This unique situation requires an appreciation for both the pharmacokinetic parameters of the host and pharmacodynamic parameters of the drug-microbe interaction. ImQuest fully augments assay services by providing preclinical oversight and consulting to assure success. |
|
|
| |
| |
| Copyright © 2006, ImQuest BioSciences. | | | |
| | | | | |
| | | | |
| |
|
|
