Jürgen Bulitta, Ph.D.

Jürgen Bulitta

Associate Professor

Pharmaceutics

OFFICE: 6550 Sanger Road, Office 475, Orlando FL 32827

EMAIL: jbulitta@cop.ufl.edu

PHONE: 407-313-7010

CV: Link to CV

 

Education

  • Ph.D., Institute for Biomedical and Pharmaceutical Research in Germany and Julius-Maximilians-University of Würzburg, Germany
  • M.Sc., Chemistry, Friedrich-Alexander-University Erlangen-Nürnberg, Germany

Biographical Sketch

Jürgen Bulitta joined the Center for Pharmaco­metrics and Systems Pharmacology (CPSP) in the Department of Pharmaceutics at the College of Pharmacy as an Associate Professor in 2015. He is supported by the University of Florida’s preeminence program in Drug Discovery and Development. His laboratory is located at the UF Lake Nona campus in Orlando. His research program is supported by the NIH/NIAID, FDA and the state of Florida. (ORCID http://orcid.org/0000-0001-7352-3097)

Dr. Bulitta’s research focuses on multidrug-resistant bacterial ‘superbugs’ which present one of the three most serious threats to human health. To combat this global health crisis, his research goals are to develop and rationally optimize novel antibiotic combination dosing strategies and to discover and develop new antibiotics based on mechanistic biological insights which his group generated over the last decade.

Dr. Bulitta’s most significant scientific contributions are

  1. Identification and rational optimization of unique penicillin-binding protein (PBP) receptor occupancy patterns using double β-lactam antibiotic combinations (including β-lactamase inhibitors) to synergistically kill Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae and to minimize resistance, and
  2. Development and rational optimization of antibiotic combination dosage regimens against multidrug-resistant P. aeruginosa, A. baumannii, K. pneumoniae, and Escherichia coli,
  3. Discovery of the first antibiotics that eradicate non-replicating bacterial persisters at clinically relevant concentrations, and
  4. Pioneering the field of mechanism-based and QSP modeling of antibiotics.

Most recently, Dr. Bulitta’s team has made substantial progress to elucidating innovative combination dosing strategies against multidrug-resistant A. baumannii and K. pneumoniae (including carbapenem- and polymyxin-resistant isolates). His team has also developed enhanced assays to efficiently characterize the outer membrane permeability of β-lactam antibiotics and β-lactamase inhibitors. This ongoing research is generating the much-needed mechanistic understanding for synergistic antibiotic combinations to combat bacterial ‘superbugs’. These mechanistic insights hold excellent promise to provide guidance to clinicians in a timeline manner.

Dr. Bulitta’s group uses latest pharmacometrics methodology and dynamic in vitro infection models to develop systems pharmacology models that translate mechanistic research insights into innovative, clinically relevant dosage regimens. To date, he has significantly contributed to the translational development of beta-lactam antibiotics, beta-lactam / beta-lactamase inhibitor combinations, polymyxins, tedizolid (FDA approved in 2014), fusidic acid (in Phase III), and other antibiotics. He is an international leader in translational QSP modeling of antibiotics. His highly collaborative research involves an international network of academic, clinical and industry collaborators.

Dr. Bulitta’s second research stream focuses on human pharmacokinetics (PK), pharmacodynamics (PD), and complex oral or inhaled drug absorption. This includes a series of clinical studies on inhaled corticosteroids in fruitful collaboration with Dr. Guenther Hochhaus (COP, UF), FDA scientists and other collaborators. These FDA-funded clinical studies will inform future guidelines on the development and evaluation of generic formulations for inhaled drug products.

Dr. Bulitta is/has been funded by 22 peer-reviewed grants from the NIH-US, FDA, State of Florida, and the Australian equivalents of NIH and NSF ($19M; with $8.2M as PI). Additionally he led or significantly contributed to 23 collaborative projects with pharmaceutical industry (total: $2.4M). Dr. Bulitta published 120 peer-reviewed papers and contributed to over 95 phase I-IV clinical trials. He is the creator and developer of the SADAPT-TRAN facilitator package to develop systems pharmacology models in the S-ADAPT population modeling software package. He received the Giorgio Segré Prize 2010 for distinct contributions in the field of pharmacokinetics and pharmaco­dynamics by the European Federation for Pharmaceutical Sciences (EUFEPS) and the 2012 ASCEPT Denis Wade Johnson & Johnson New Investigators Award. He won the 2017 Teaching and Service Excellence Incentive Award from the UF College of Pharmacy.

Publications

PubMed Research Publications Feed

Affiliations

  • American Society for Microbiology (ASM)
  • American Society of Pharmacometrics (ASoP), founding member
  • American Association of Pharmaceutical Scientists (AAPS)
  • German Pharmaceutical Society (DPhG)
  • European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
  • German National Academic Foundation (“Studienstiftung des Deutschen Vokes”)

Research Interests

  • Drug discovery, development and optimal patient therapies
  • Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli
  • Pharmacokinetics, pharmacodynamics, translational pharmacology
  • Infectious diseases, multidrug-resistant bacteria, non-replicating persister phenotype
  • Beta-lactams, polymyxins, aminoglycosides and other antibiotics
  • Penicillin-binding proteins (PBPs)
  • Synergistic antibiotic combinations to maximize bacterial killing and minimize resistance
  • Dynamic infection models (including the hollow fiber system), emergence of resistance
  • Pharmacometrics, population modeling, and quantitative systems pharmacology
  • S-ADAPT and SADAPT-TRAN

Select Publications

Rationally Optimizing Antibiotic Combination Therapy

Yadav R, Bulitta JB, Wang J, Nation RL, Landersdorfer CB. Evaluation of PK/PD model-based optimized combination regimens against multidrug-resistant Pseudomonas aeruginosa in a murine thigh infection model using humanized dosing schemes. Antimicrob Agents Chemother. 2017. pii: AAC.01268-17. PMID: 28993331

Zavascki AP, Klee BO, Bulitta JB. Aminoglycosides against carbapenem-resistant Enterobacteriaceae in the critically ill: the pitfalls of aminoglycoside susceptibility. Expert Rev Anti Infect Ther. 2017; 15: 519-526. PMID: 28375030

Yadav R, Bulitta JB, Schneider E, Shin BS, Velkov T, Nation RL, Landersdorfer CB. Aminoglycoside concentrations required for synergy with carbapenems against Pseudomonas aeruginosa determined via mechanistic studies and modeling. Antimicrob Agents Chemother. 2017. pii: AAC.00722-17. PMID: 28893782

Yadav R, Landersdorfer CB, Nation RL, Boyce JD, Bulitta JB. Novel approach to optimising synergistic carbapenem plus aminoglycoside combinations against carbapenem-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2015; 59:2286-98. PMID: 25645842

Ly NS, Bulitta JB, Rao GG, Holden PN, Landersdorfer CB, Rao GG, Forrest A, Bergen PJ, Nation RL, Li J, Tsuji BT. Colistin and doripenem combinations against Pseudomonas aeruginosa: profiling the time-course of synergistic killing and resistance prevention. J Antimicrob Chemother. 2015; 70:1434-42. PMID: 25712313

Landersdorfer CB, Ly NS, Xu H, Tsuji BT, Bulitta JB. Quantifying subpopulation synergy for antibiotic combinations via mechanism-based modeling and a sequential dosing design. Antimicrob Agents Chemother. 2013; 57:2343-51. PMID: 23478962

Quantitative Modeling of the Mechanisms of Antibiotic Action and Prevention of Resistance

Rees V, Bulitta JB, Oliver A, Tsuji BT, Rayner C, Nation RL, Landersdorfer CB. Resistance suppression by high intensity, short duration aminoglycoside exposure against hypermutable and nonhypermutable Pseudomonas aeruginosa. J Antimicrob Chemother 2016; 71:3157-67. PMID: 27521357

Jacobs M, Grégoire N, Couet W, Bullitta JB. Distinguishing antimicrobial PK/PD models with different resistance mechanisms via Monte Carlo simulations and population modeling. PLoS Comput Biol. 2016; 12:e1004782. PMID: 26967893

Bulitta JB, Ly NS, Landersdorfer CB, Wanigaratne NA, Velkov T, Yadav R, Oliver A, Martin L, Shin BS, Forrest A, Tsuji BT. Two mechanisms of killing of Pseudomonas aeruginosa by tobramycin assessed at multiple inocula via mechanism-based modeling. Antimicrob Agents Chemother. 2015; 59:2315-27. PMID: 25645838

Bulitta JB, Yang JC, Yohonn L, Ly NS, Brown SV, RE D’Hondt, Jusko WJ, Forrest A, Tsuji BT. High inoculum Pseudomonas aeruginosa attenuates colistin bactericidal activity characterized by a mechanism-based population pharmacodynamic model. Antimicrob Agents Chemother 2010; 54:2051-62. PMID: 20211900

Bulitta JB, Ly NS, Yang JC, Forrest A, Jusko WJ, Tsuji BT. Development and Qualification of a Pharmacodynamic Model for the Pronounced Inoculum Effect of Ceftazidime Against Pseudomonas aeruginosa, Antimicrob Agents Chemother 2009; 53:46-56. PMID: 18852268

Human Population Pharmacokinetics, Pharmacodynamics and Toxicodynamics

Bulitta JB, Paik SH, Chi YA, Kim TH, Shin S, Landersdorfer CB, Jiao Y, Yadav R, Shin BS. Characterizing the Time-course of Antihypertensive Activity and Optimal Dose Range of Fimasartan via Mechanism-based Population Modeling. Eur J Pharm Sci. 2017; 107: 32-44. PMID: 28599987

De Miranda Silva C, Rocha A, Tozatto E, da Silva LM, Donadi EA, Dalla Costa T, Lanchote VL, Schmidt S, Bulitta JB. Development of an Enantioselective and Biomarker-Informed Translational Pharmacokinetic / Pharmacodynamic Model for Etodolac. AAPS J. Accepted Aug 19, 2017. PMID: 28875479

Boak LM, Rayner CR, Grayson ML, Paterson DL, Spelman D, Khumra S, Capitano B, Forrest A, Li J, Nation RL, Bulitta JB. Clinical population pharmacokinetics and toxicodynamics of linezolid. Antimicrob Agents Chemother 2014; 58:2334-4. PMID: 24514086

Bulitta JB, Okusanya OO, Forrest A, Bhavnani SM, Clark K, Still JG, Fernandes P, Ambrose PG. Population Pharmacokinetics of Fusidic Acid: Rationale for Front-loaded Dosing Regimens due to Auto-inhibition of Clearance. Antimicrob Agents Chemother. 2013; 57:498-507. PMID: 23147726

Prokocimer P, Bien P, Surber J, Mehra P, DeAnda C, Bulitta JB, Corey GR. Phase 2, randomized, double-blind, dose-ranging study evaluating the safety, tolerability, population pharmacokinetics, and efficacy of oral torezolid phosphate (tedizolid) in patients with complicated skin and skin structure infections. Antimicrob Agents Chemother 2011; 55:583-92. PMID: 21115795

Bulitta JB, Landersdorfer CB, Hüttner SJ, Drusano GL, Kinzig M, Holzgrabe U, Stephan U, Sörgel U. Population Pharmacokinetic Comparison and Pharmacodynamic Breakpoints of Ceftazidime in Cystic Fibrosis Patients and Healthy Volunteers. Antimicrob Agents Chemother 2010; 54:1275-82. PMID: 20065059

Bulitta JB, Duffull SB, Kinzig-Schippers M, Holzgrabe U, Stephan U, Drusano GL, Sörgel F. Systematic comparison of the population pharmacokinetics and pharmacodynamics of piperacillin in cystic fibrosis patients and healthy volunteers. Antimicrob Agents Chemother 2007; 51:2497-507. PMID: 17485505

Anti-Infective Pharmacodynamics – Experimental Models:

Rees VE, Bulitta JB, Nation RL, Tsuji BT, Sörgel F, Landersdorfer CB. Shape does matter: Short high-concentration exposure minimises resistance emergence for fluoroquinolones; J Antimicrob Chemother. 2015; 70:818-26. PMID: 25381167

Tsuji BT, Bulitta JB, Brown T, Forrest A, Kelchlin PA, Holden PN, Peloquin CA, Skerlos L, Hanna D. Pharmacodynamics of early, high-dose linezolid against vancomycin-resistant enterococci with elevated MICs and pre-existing genetic mutations. J Antimicrob Chemother 2012; 67:2182-90. PMID: 22685161

Tsuji BT, Brown T, Parasrampuria R, Brazeau D, Forrest A, Kelchlin P, Holden P, Peloquin C, Hanna D, Bulitta JB. Front-Loaded Linezolid Regimens Results in Increased Killing and Suppression of the Accessory Gene Regulator system of Staphylococcus aureus. Antimicrob Agents Chemother 2012; 56:3712-9. PMID: 22526313

Brown AN, Bulitta JB, McSharry JJ, Weng Q, Adams JR, Kulawy R, Drusano GL. The Effect of Effect of half-life on the pharmacodynamic index of zanamivir against influenza virus delineated by a mathematical model. Antimicrob Agents Chemother 2011; 55:1747-53. PMID: 21263045

Pharmacometric Approaches and Tools

Bulitta JB, Bingölbali A, Shin BS, Landersdorfer CB. Development of a new pre- and post-processing tool (SADAPT-TRAN) for nonlinear mixed-effects modeling in S-ADAPT. AAPS Journal 2011; 13:201-11. PMID: 21369876

Bulitta JB, Landersdorfer CB. Performance and robustness of the Monte Carlo importance sampling algorithm using parallelized S-ADAPT for basic and complex mechanistic models. AAPS Journal 2011; 13:212-26. PMID: 21374103

Bulitta JB, Landersdorfer CB, Kinzig M, Holzgrabe U, Sörgel F. A New Semi-Physiological Absorption Model to Assess the Pharmacodynamic Profile of Cefuroxime Axetil using Nonparametric and Parametric Population Pharmacokinetics, Antimicrob Agents Chemother 2009; 53:3462-71. PMID: 19528278

Landersdorfer CB, Kinzig M, Hennig FF, Bulitta JB, Holzgrabe U, Drusano GL, Sörgel F, Gusinde J. Penetration of moxifloxacin into bone evaluated by Monte Carlo simulation. Antimicrob Agents Chemother 2009; 53:2074-81. PMID: 19223648

Cheah S-E, Li J, Nation RL, Bulitta JB. Novel rate-area-shape modeling approach to quantify bacterial killing and regrowth for in vitro static time-kill studies. Antimicrob Agents Chemother 2015; 59:381-8. PMID: 25367905