Center for Anti-Infective Research and Development (CAIRD) Capabilities

Key personnel:
Daniel V. Zurawski, Ph.D. – Director
Tomefa Asempa, PharmD - Associate Director, Clinical and Translational Infectious Diseases Research
Andrew Fratoni, PharmD - Associate Director, Clinical and Laboratory Studies
Aliaa Fouad, Ph.D. - Associate Director, Infectious Diseases Pharmacotherapy and Microbiology Research
Hanna Roenfanz, Ph.D. – Associate Director, Analytical Sciences

Bacteria of interest: The following bacterial species can be used in all the tests/animal models listed below. Laboratory strains and clinical isolates of all ESKAPEE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter, E. coli species) and Stenotrophomonas maltophilia. Also developing NTM and Neisseria gonorrhoeae models for future use so Mycobacterium abscessus and Mycobacterium avium and Neisseria gonorrhoeae laboratory strains and clinical isolates will also be available.

In vitro Antimicrobial Testing: CAIRD has a collection of over 6,000 bacterial isolates, including diverse sets of standard laboratory strains and clinical isolates. Using these strains, we offer the following in vitro experiments:

  1. Minimal Inhibitory Concentration (MIC) assays run at CLSI standards
  2. Disk Diffusion assays
  3. Disk broth elution assays
  4. Population Analysis Profile (PAP) for heteroresistance
  5. Static Time-Kill and Persister assays
  6. Chemostat in vitro Models

In vivo Antimicrobial Testing and Pharmacokinetic/Pharmacodynamic (PK/PD) Profiling: CAIRD is home to an AAALAC accredited full-service vivarium for use in the following pre-clinical murine studies:

  1. Sepsis Survival Model
    1. Efficacy studies may be evaluated using escalating or humanized dosing regimens
    2. Data Collection: Time to death, % survival, bacterial burden in kidney and/or spleen, histopathology, and clinical scoring
  2. Thigh Infection Model
    1. Efficacy and PK/PD studies may be evaluated using escalating or humanized dosing regimens
    2. Data Collection: Bacterial burden in thigh, histopathology, and clinical scoring
  3. Pulmonary Infection Model
    1. Survival/sepsis models for A. baumannii and K. pneumoniae models to evaluate initial efficacy.
    2. Additional efficacy and PK/PD studies based on plasma or pulmonary epithelial lining fluid (ELF) drug exposure may be evaluated using escalating or humanized dosing regimens
    3. Data Collection: Kaplan-Meier curves, bacterial burden in lung tissue, histopathology, and clinical scoring
  4. UTI Model - Pyelonephritis and cystitis
    1. Efficacy and PK/PD studies may be evaluated using escalating or humanized dosing regimens
    2. Data Collection: Bacterial burden in kidney and/or bladder, histopathology, and clinical scoring
  5. Wound Model
    1. Therapeutics may be evaluated systematically via escalating or humanized doses or topically
    2. Data collection: Time to close (wound area over time), bacterial burden in wound tissue, histopathology, gross pathology, and clinical scoring

Ex vivo Antimicrobial Testing:

  1. Pharmacokinetics and Dose Optimization using in-house Continuous Renal Replacement Therapy (CRRT) circuit
  2. Pharmacokinetics and Dose Optimization using in-house Extracorporeal Membrane Oxygenation (ECMO) circuit
  3. Intravenous compatibility via Y-site mixture with other clinical intravenous medications
  4. Drug stability (time, temperature, elastomeric pumps, etc.)

Phase I Pharmacokinetic Studies:

  1. Healthy volunteer studies in our Clinical Research Center
    1. Bronchoalveolar lavage (BAL) studies to determine pulmonary pharmacokinetics
    2. Microdialysis studies to determine subcutaneous & dermal pharmacokinetics
    3. Drug bioavailability and fed/fasted/tube-feed pharmacokinetic studies
  2. Phase Ib studies in hospitalized patients
    1. BAL studies in patients with pneumonia to determine pulmonary pharmacokinetics
    2. Microdialysis studies in patients with diabetic foot infections to determine subcutaneous & dermal pharmacokinetics at the margin of the wound

Population Pharmacokinetic Analyses, Monte Carlo Simulation, and Probability of Target Attainment (PTA) assessments can be applied to any of the models and studies listed above.

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) Analytical Services: In-house analytical services can be paired with any of the models listed above. Sampling may be performed over the course of the experiment to determine the pharmacokinetic profile of compound(s) of interest. Analysis is run on a Waters Acquity H-Class UPLC system coupled to a Xevo TQ-XS triple quadrupole mass spectrometer. All of our methods are validated and performed according to the FDA M10 Bioanalytical Method Development and Sample Analysis Guidance for Industry.

  1. Sample Analysis using methods previously validated at CAIRD
  2. Partial Validation for methods developed in other laboratories and in new matrices
  3. Method Development and Validation for compounds not previously analyzed at CAIRD

Research