Vidmantas Petraitis, M.D.
Associate Member, CDI
Director, Pharmacology Core, CDI
The primary objective of Dr. Petraitis lab is to advance, explore, and apply state-of-the-art technologies in the development of novel immunotherapeutics, antimicrobial agents, and molecular detection systems. Our focus is on diagnosing, treating, and preventing life-threatening infections through translational research that bridges the gap between experimental findings and practical application. The Pharmacology Program at CDI has implemented an advanced technique for drug quantification in dosed animal tissue. Through the integration of laser capture microdissection (LCM) with liquid chromatography/mass spectrometry (LC/MS) analysis, we can achieve precise measurement of drug levels in specific cells or tissues, yielding valuable insights into the drug's distribution, metabolism, and pharmacokinetics within the animal model. This combined approach of LCM and LC/MS analysis offers a robust and comprehensive method for drug quantification, enabling us to investigate the pharmacokinetics and tissue-specific effects of drugs. The knowledge gained from this technique contributes to the development and optimization of therapeutic targets, as well as the establishment of appropriate therapeutic levels. Understanding the disposition of drugs in various organs and tissues is of paramount importance in the design of clinical trials, making this approach particularly valuable for guiding the development of effective and safe treatments. The lab's translational research approach has gained international recognition within the scientific community.
For decades, Dr. Petraitis laboratory has achieved remarkable success and productivity in working with rabbit models to study pneumonia, CNS, and disseminated infections. These models have proven to be highly indicative of human infections, as they accurately replicate the progression of diseases from initial colonization to well-established infection. With 28 years of direct laboratory experience in experimental pharmacology, the lab is actively involved in developing innovative strategies for the effective administration of existing antibacterial and antifungal agents, as well as new compounds under development. In addition, to better understand drug penetration and improve dosing regimens, we have extensively studied tissue penetration of antimicrobial agents. We are focused on creating predictive in vitro and in vivo preclinical systems utilizing various animal models to gain a better understanding of pathophysiology, microbiology, and pharmacology. These findings are then translated into practical therapeutic applications, clinical trials, and standards of care for antimicrobial therapy in immunocompromised patients.
Dr. Petraitis's research focuses on antifungal pharmacology and experimental therapeutics. We have methodically investigated the pharmacokinetics and pharmacodynamics of all the major classes of antifungal agents (polyenes, lipid formulations, triazoles, and echinocandins), as well as numerous experimental classes. The models of primary pulmonary aspergillosis, fusariosis, mucormycosis, Exserohilum rostratum meningitis, as well as disseminated, CNS, and catheter related models of invasive candidiasis, are microbiologically, histologically, immunologically, and radiologically highly predictive of the conditions observed in patients. The antifungal activities in these novel model systems have laid the foundation for numerous clinical trials, which in turn have significantly impacted antifungal therapy over the past couple decades.
In the last decade we have expanded our focus to the rapidly emerging public health threat of multidrug resistant (MDR) Gram-negative bacterial infections. Using highly predictive rabbit model systems and mouse models of Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Klebsiella pneumoniae (KPC) pneumonia, we are investigating new antimicrobial agents in the battle against MDR organisms.
In addition, our laboratory has developed a small molecule platform used for the discovery of new antimicrobial and anticancer candidates, the identification and validation of new targets, and preclinical evaluation of activity.
Dr Petraitis laboratory has extensive administrative experience in reporting, fulfilling goals, meeting milestones, and achieving objectives under multiple contract mechanisms. Our previous or current contracting collaborations include preclinical studies model developments with Allergan Inc., Amplyx Pharmaceuticals, Cubist Pharmaceuticals Inc., Leadiant Biosciences, The Medicines Company, Merck & Co., Novartis Pharmaceuticals Co., Scynexis Inc., Shionogi Inc., Tetraphase Pharmaceuticals Inc., Viosera Therapeutics, and FDA.
As result of these collaborations, Dr. Petraitis and his team through their translational research efforts have contributed to the preclinical and clinical pharmacology of multiple antimicrobial agents from bench to bedside such as: amphotericin B, amphotericin B lipid complex, liposomal amphotericin B, flucytosine, caspofungin, micafungin, anidulafungin, fluconazole, itraconazole, voriconazole, posaconazole, ravuconazole, isavuconazole, ibrexafungerp, fosmanogepix, trimethoprim/sulfamethoxazole, ceftazidime, ceftazidime/avibactam, and ceftolozane/tazobactam.