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INVESTIGATOR PROFILES

Arnold Louie, M.D.

SENIOR SCIENTIST
Ordway Research Institute

DIRECTOR
Center for Biodefense
and Emerging Infections,
Ordway Research Institute

CO-CHIEF
 Bacterial and Fungal Emerging Infections and Pharmacodynamics Laboratory, Ordway Research Institute

CORE CHIEF
 Hollow Fiber Core,
Ordway Research Institute

SERVICE CHIEF
LC/MS/MS Analytical Services, Ordway Research Institute

CLINICAL ASSOCIATE PROFESSOR
 Department of Medicine,
Albany Medical College

STAFF PHYSICIAN,
 Medical Care Line,
Stratton Veterans Administration Medical Center, Albany, NY

CONTACT
Bacterial and Fungal Emerging Infections and Pharmacodynamics Laboratory
Phone: (518) 641-6463
Fax: (518) 641-6304
alouie@ordwayresearch.org


Arnold Louie, M.D.

Research Focus

The focus of the laboratory is to use cutting-edge, novel in-vitro hollow fiber pharmacodynamic and animal infection systems and mathematical models to define the dosage and frequency of administration of antibiotics that should be used clinically to optimize outcomes in human infections. While the members of the Bacterial and Fungal Emerging Infections and Pharmacodynamics Laboratory conduct studies using a diverse range of pathogens, Dr. Louie conducts studies primarily with the fungus Candida albicans and with the bacteria Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Mycobacterium tuberculosis, and multi-drug resistant Staphylococcus aureus. Candida albicans is associated with high morbidity and mortality in immunocompromised, hospitalized patients. The bacterial species of interest are increasingly resistant to an array of antibiotics.

Emergence of antibiotic resistance is a growing problem nationally and internationally. The laboratory is one of the few worldwide that uses infection and mathematical models to identify a minimum antibiotic exposure that should be used in order to prevent the selection of drug-resistant bacterial mutants during antibiotic therapy.

The laboratory is also actively conducting research to expand the selection of antibiotics that may be useful for the treatment of infections due to potential agents of bioterrorism and biowarfare, including Bacillus anthracis and Yersinia pestis, the bacteria that cause anthrax and plague, respectively. Using novel in-vitro pharmacokinetic/pharmacodynamic and mathematical models, the laboratory has defined the dosage and dosing frequency of a fluoroquinolone antibiotic that should be used to maximize the efficacy of this drug, while preventing these bacteria from developing resistance to the antibiotic during therapy. The use of other agents for the treatment of anthrax and plague are actively being sought as part of a five year $9.1 million program project grant, funded by the National Institutes of Health.

Dr. Louie has also developed a hollow fiber model of F. tularensis infection, another potential agent of bioterrorism and biowarfare. The laboratory is evaluating and optimizing candidate drugs for the treatment of infections due to this pathogen.

Furthermore, the laboratory is actively evaluating treatment strategies that are aimed at reducing the time needed to kill M. tuberculosis that are in a non-replicating persister state.  It is believed that the existence of non-replicating persisters in tuberculosis infections is the reason for why six months of combination antibiotic therapy is needed to cure people with active pulmonary tuberculosis.  Prolonged length of therapy is linked with reduced patient compliance with their drug regimens, resulting in emergence of multi-drug resistance by this microbe.  Decreasing the length of therapy while maintaining or improving treatment efficacy should result in improved patient compliance with their treatment regimens and, hence, reduction in emergence of drug resistant M. tuberculosis during therapy.

The group is actively exploring the value of using two or more antibiotics in combination for the treatment of serious bacterial and fungal infections, as well as the potential benefit of administering antibiotics in combination with compounds that augment the effectiveness of the infected host’s own immune defenses as additional methods for improving treatment outcomes.

Selected Publications (View)

  • Louie A, Heine HS, Kim K, Brown DL, VanScoy B, Liu W, Kinzig-Schippers M, Sorgel F, Drusano GL. Use of an In Vitro Pharmacodynamic Model to Derive a Linezolid Regimen that Optimizes Bacterial Kill and Prevents Emergence of Resistance in Bacillus anthracis.  Antimicrobial Agents and Chemotherapy  2008; 52: 2486-2496.
  • Louie A, Brown DL, Liu W, Kulawy RW, Deziel MR, Drusano GL.  In Vitro Infection Model Characterizing the Effect of Efflux Pump Inhibition on Prevention of Resistance to Levofloxacin and Ciprofloxacin in Streptococcus pneumoniae.  Antimicrobial Agents and Chemotherapy  2007; 51: 3988-4000.
  • Gumbo T, Louie A, Deziel MR, Liu W, Parsons LM, Salfinger M, Drusano GL.  Concentration-Dependent Mycobacterium tuberculosis Killing and Prevention of Resistance by Rifampin.  Antimicrobial Agents and Chemotherapy  2007; 51: 3781-3788
  • Louie A, Deziel MR, Liu W, Drusano GL.  Impact of Resistance Selection and Mutant Growth Fitness on the Relative Efficacies of Streptomycin and Levofloxacin for Plague Therapy.  Antimicrob Agents Chemother. 2007; 51: 2661-2667.
  • Heine HS, Louie A, Sorgel F, Bassett H, Miller L, Sullivan LJ, Kinzig-Schippers M, Drusano GL.  Comparison of Two Different Protein Synthesis Inhibitor Antibiotics for the Therapy of Yersinia pestis Delivered by Aerosol Challenge in a Mouse Model of Plague Pneumonia.  Journal of Infectious Diseases  2007; 196: 782-787.
  • Jumbe NL, Louie A, Miller MH, Liu W, Deziel MR, Tam VH, Bachhawat R, Drusano GL. Quinolone Efflux Pumps Play a Central Role in Emergence of Fluoroquinolone Resistance in Streptococcus pneumoniae. Antimicrobial Agents and Chemotherapy 2006; 50; 310-317.
  • Louie A, Deziel M, Liu W, Drusano MF, Gumbo T, Drusano GL. Pharmacodynamics of Caspofungin in a Murine Model of Systemic Candidiasis: Importance of Persistence of Caspofungin in Tissues to Understanding Drug Activity. Antimicrobial Agents and Chemotherapy 2005; 49: 5058-5068.
  • Gumbo T, Louie A, Deziel MR, Drusano GL. Pharmacodynamic Evidence that Ciprofloxacin Failure against Tuberculosis Is Not Due to Poor Microbial Kill But to Rapid Emergence of Resistance. Antimicrobial Agents and Chemotherapy 2005; 49: 3178-3181.
  • Tam VH, Louie A, Deziel MR, Liu W, Leary R, Drusano GL. Bacterial–Population Responses to Drug-Selective Pressure: Examination of Garenoxacin’s Effect on Pseudomonas aeruginosa. Journal of Infectious Diseases 2005; 192: 420-428.
  • Gumbo T, Louie A, Deziel MR, Parsons LM, Salfinger M, Drusano GL. Selection of a Moxifloxacin Dose that Suppresses Drug Resistance in Mycobacterium tuberculosis by Use of an In Vitro Pharmacodynamic Infection Model and Mathematical Modeling. Journal of Infectious Diseases  2004; 190: 1642-1651.
  • Jumbe N, Louie A, Leary R, Liu W, Deziel M, Tam V, Bachhawat R, Freeman C, Kahn J, Bush K, Dudley M, Miller M, Drusano G. Application of a Mathematical Model to Prevent In-vivo Amplification of Antibiotic-Resistant Bacterial Populations during Therapy. Journal of Clinical Investigation 2003; 112: 275-285.
  • Louie A, Kaw P, Banerjee P, Liu W, Chen G, Miller MH. Impact of the Order of Initiation of Fluconazole and Amphotericin B in Sequential or Combination Therapies on Killing of Candida albicans In Vitro and in a Rabbit Model of Endocarditis and Pyelonephritis. Antimicrobial Agents and Chemotherapy  2001; 45: 485-494.

 

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