Brian T. Tsuji PharmD, FCCP, FCCM, FIDSA
Brian T. Tsuji
PharmD, FCCP, FCCM, FIDSA
Professional Summary:
Our Interdisciplinary Laboratory is entirely dedicated to Clinical and Translational Approaches to Combat Antimicrobial Resistance. My team is focused PK/PD approaches to optimize antimicrobial dosing. With the recent emergence of multidrug-resistant Gram-negative bacteria, our independent, NIH-funded research program was one of the first to define and refine new exposure response relationships for the ‘last line’ polymyxin antibiotics (polymyxin B and colistin) and carbapenems. We were also one of the first laboratories to define key PK/PD relationships for a number of antibiotics that were crucial to guide dose selection in Phase 1, 2, and 3 clinical trials.
I have been very fortunate to be the Principal Investigator of R01AI111990, a $4.4M NIH grant which seeks to investigate the PK/PD of polymyxin combinations. We have published a series (n>39) of original manuscripts which have focused on innovative dosing strategies for polymyxin and β-lactam combinations. This allows our team to push the boundaries of knowledge in antimicrobial pharmacology and team science, and it is our clinical focus which allows us to provide insights into translating these scientific findings toward the care of critically ill patients who are infected with resistant Gram-negatives. I have been fortunate to be the mentor of 12 post-doctoral fellows who have gone on to successful careers. I also embrace my role as Associate Dean of Clinical and Translational Sciences in developing new and exciting programs and collaborations across the University for our faculty and students. A Past-President of the International Society of Anti-Infective Pharmacology, a member of the Antimicrobial Resistance Leadership Group and the Co-Chair of the International Consensus Guidelines for Optimal Polymyxin Use in collaboration with 6 international infectious diseases societies and organizations, I will leverage these experiences for our faculty and students at UB.
As Associate Dean for Clinical and Translational Sciences, I was honored to lead the Schools and UB‘s submission to build a New Masters of Science in Clinical and Therapeutics, to build teams in the PharmD Clinical Research Program, to foster NIH funded translational research, and to develop innovative experiences to train of the next generation of pharmacists and scientists.
Awards and Honors:
- Exceptional Scholar Young Investigator Award (2009)
Journal Articles:
- Bulman ZP, Satlin MJ, Chen L, Kreiswirth BN, Shin BS, Walsh TJ, Holden PN, Forrest A, Nation RL, Li J, Tsuji BT. Polymyxin B-Based Triple Combinations Wage War Against KPC-2-producing Klebsiella pneumoniae: New Dosing Strategies for Old Allies. Antimicrob Agents Chemother. 2017.
- Shafiq I, Bulman ZP, Spitznogle SL, Osorio JE, Reilly IS, Lesse AJ, Parameswaran GI, Mergenhagen KA, Tsuji BT. A combination of ceftaroline and daptomycin has synergistic and bactericidal activity in vitro against daptomycin nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA). Infect Dis (Lond). 2017.
- Bulman ZP, Ly NS, Lenhard JR, Holden PN, Bulitta JB, Tsuji BT. Influence of rhlR and lasR on Polymyxin Pharmacodynamics in Pseudomonas aeruginosa: Implications for Quorum Sensing Inhibition with Azithromycin. Antimicrob Agents Chemother. 2017.
- Lenhard JR, Smith NM, Bulman ZP, Tao X, Thamlikitkul V, Shin BS, Nation RL, Li J, Bulitta JB, Tsuji BT. High Dose Ampicillin/Sulbactam Combinations Combat Polymyxin-Resistant Acinetobacter baumannii in a Hollow-Fiber Infection Model. Antimicrob Agents Chemother. 2017.
- Soon RL, Lenhard JR, Bulman ZP, Holden PN, Kelchlin P, Steenbergen JN, Friedrich LV, Forrest A, Tsuji BT. In vitro pharmacodynamic evaluation of ceftolozane/tazobactam against β-lactamase-producing Escherichia coli in a hollow-fibre infection model. Int J Antimicrob Agents. 2017; 49(1).
- Lenhard JR, Bulitta JB, Connell TD, King-Lyons N, Landersdorfer CB, Cheah SE, Thamlikitkul V, Shin BS, Rao G, Holden PN, Walsh TJ, Forrest A, Nation RL, Li J, Tsuji BT. High-intensity meropenem combinations with polymyxin B: new strategies to overcome carbapenem resistance in Acinetobacter baumannii. J Antimicrob Chemother. 2017; 72(1).
- Soon RL, Lenhard JR, Reilly I, Brown T, Forrest A, Tsuji BT. Impact of Staphylococcus aureus accessory gene regulator (agr) system on linezolid efficacy by profiling pharmacodynamics and RNAIII expression. J Antibiot (Tokyo). 2017; 70(1).
- Tran TB, Velkov T, Nation RL, Forrest A, Tsuji BT, Bergen PJ, Li J. Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet? Int J Antimicrob Agents. 2016; 48(6).
- Lenhard JR, Gall JS, Bulitta JB, Thamlikitkul V, Landersdorfer CB, Forrest A, Nation RL, Li J, Tsuji BT. Comparative pharmacodynamics of four different carbapenems in combination with polymyxin B against carbapenem-resistant Acinetobacter baumannii. Int J Antimicrob Agents. 2016; 48(6).
- Lenhard JR, Nation RL, Tsuji BT. Synergistic combinations of polymyxins. Int J Antimicrob Agents. 2016; 48(6).
- Rees VE, Bulitta JB, Oliver A, Tsuji BT, Rayner CR, Nation RL, Landersdorfer CB. Resistance suppression by high-intensity, short-duration aminoglycoside exposure against hypermutable and non-hypermutable Pseudomonas aeruginosa. J Antimicrob Chemother. 2016; 71(11).
- Rao GG, Ly NS, Bulitta JB, Soon RL, San Roman MD, Holden PN, Landersdorfer CB, Nation RL, Li J, Forrest A, Tsuji BT. Polymyxin B in combination with doripenem against heteroresistant Acinetobacter baumannii: pharmacodynamics of new dosing strategies. J Antimicrob Chemother. 2016; 71(11).
- Brotzki CR, Mergenhagen KA, Bulman ZP, Tsuji BT, Berenson CS. Native valve Proteus mirabilis endocarditis: successful treatment of a rare entity formulated by in vitro synergy antibiotic testing. BMJ Case Rep. 2016; 2016.
- Rao GG, Ly NS, Diep J, Forrest A, Bulitta JB, Holden PN, Nation RL, Li J, Tsuji BT. Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii. Int J Antimicrob Agents. 2016; 48(3).
- Pettigrew MM, Tsuji BT, Gent JF, Kong Y, Holden PN, Sethi S, Murphy TF. Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease Antimicrob Agents Chemother. 2016; 60(7).
- Tsuji BT, Landersdorfer CB, Lenhard JR, Cheah SE, Thamlikitkul V, Rao GG, Holden PN, Forrest A, Bulitta JB, Nation RL, Li J. Paradoxical Effect of Polymyxin B: High Drug Exposure Amplifies Resistance in Acinetobacter baumannii. Antimicrob Agents Chemother. 2016; 60(7).
- Cheah SE, Li J, Tsuji BT, Forrest A, Bulitta JB, Nation RL. Colistin and Polymyxin B Dosage Regimens against Acinetobacter baumannii: Differences in Activity and the Emergence of Resistance. Antimicrob Agents Chemother. 2016; 60(7).
- Garonzik SM, Lenhard JR, Forrest A, Holden PN, Bulitta JB, Tsuji BT. Defining the Active Fraction of Daptomycin against Methicillin-Resistant Staphylococcus aureus (MRSA) Using a Pharmacokinetic and Pharmacodynamic Approach. PLoS One. 2016; 11(6).
- Cheah SE, Johnson MD, Zhu Y, Tsuji BT, Forrest A, Bulitta JB, Boyce JD, Nation RL, Li J. Polymyxin Resistance in Acinetobacter baumannii: Genetic Mutations and Transcriptomic Changes in Response to Clinically Relevant Dosage Regimens. Sci Rep. 2016; 6.
- Soon RL, Lenhard JR, Bulman ZP, Holden PN, Kelchlin P, Steenbergen JN, Friedrich LV, Forrest A, Tsuji BT. Combinatorial Pharmacodynamics of Ceftolozane-Tazobactam against Genotypically Defined β-Lactamase-Producing Escherichia coli: Insights into the Pharmacokinetics/Pharmacodynamics of β-Lactam-β-Lactamase Inhibitor Combinations. Antimicrob Agents Chemother. 2016; 60(4).
- Bergen PJ, Bulman ZP, Landersdorfer CB, Smith N, Lenhard JR, Bulitta JB, Nation RL, Li J, Tsuji BT. Optimizing Polymyxin Combinations Against Resistant Gram-Negative Bacteria. Infect Dis Ther. 2015; 4(4).
- Bulman ZP, Sutton MD, Ly NS, Bulitta JB, Holden PN, Nation RL, Li J, Tsuji BT. Emergence of polymyxin B resistance influences pathogenicity in Pseudomonas aeruginosa mutators. Antimicrob Agents Chemother. 2015; 59(7).
- Ly NS, Bulitta JB, Rao GG, Landersdorfer CB, Holden PN, 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 prevention of resistance. J Antimicrob Chemother. 2015; 70(5).
- 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(4).
- Rees VE, Bulitta JB, Nation RL, Tsuji BT, Sörgel F, Landersdorfer CB. Shape does matter: short high-concentration exposure minimizes resistance emergence for fluoroquinolones in Pseudomonas aeruginosa. J Antimicrob Chemother. 2015; 70(3).
- Lenhard JR, von Eiff C, Hong IS, Holden PN, Bear MD, Suen A, Bulman ZP, Tsuji BT. Evolution of Staphylococcus aureus under vancomycin selective pressure: the role of the small-colony variant phenotype. Antimicrob Agents Chemother. 2015; 59(2).
- Bergen PJ, Bulman ZP, Saju S, Bulitta JB, Landersdorfer C, Forrest A, Li J, Nation RL, Tsuji BT. Polymyxin combinations: pharmacokinetics and pharmacodynamics for rationale use. Pharmacotherapy. 2015; 35(1).
- Rao GG, Ly NS, Haas CE, Garonzik S, Forrest A, Bulitta JB, Kelchlin PA, Holden PN, Nation RL, Li J, Tsuji BT. New dosing strategies for an old antibiotic: pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease. Antimicrob Agents Chemother. 2013; 58(3).
- He H, Li JC, Nation RL, Jacob J, Chen G, Lee HJ, Tsuji BT, Thompson PE, Roberts K, Velkov T, Li J. Pharmacokinetics of four different brands of colistimethate and formed colistin in rats. J Antimicrob Chemother. 2013; 68(10).
- Soon RL, Turner SJ, Forrest A, Tsuji BT, Brown J. Pharmacokinetic/pharmacodynamic evaluation of the efficacy and safety of daptomycin against Staphylococcus aureus. Int J Antimicrob Agents. 2013; 42(1).
- 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(5).
- Takata T, Miyazaki M, Futo M, Hara S, Shiotsuka S, Kamimura H, Yoshimura H, Matsunaga A, Nishida T, Ishikura H, Ishikawa T, Tamura K, Tsuji BT. Presence of both heterogeneous vancomycin-intermediate resistance and ß-lactam antibiotic-induced vancomycin resistance phenotypes is associated with the outcome in methicillin-resistant Staphylococcus aureus bloodstream infection. Scand J Infect Dis. 2013; 45(3).
- Takata T, Miyazaki M, Futo M, Hara S, Shiotsuka S, Kamimura H, Yoshimura H, Matsunaga A, Nishida T, Ishikura H, Ishikawa T, Tamura K, Tsuji BT. Presence of both heterogeneous vancomycin-intermediate resistance and β-lactam antibiotic-induced vancomycin resistance phenotypes is associated with the outcome in methicillin-resistant Staphylococcus aureus bloodstream infection. Scand J Infect Dis. 2013; 45(3).
- Deris ZZ, Yu HH, Davis K, Soon RL, Jacob J, Ku CK, Poudyal A, Bergen PJ, Tsuji BT, Bulitta JB, Forrest A, Paterson DL, Velkov T, Li J, Nation RL. The combination of colistin and doripenem is synergistic against Klebsiella pneumoniae at multiple inocula and suppresses colistin resistance in an in vitro pharmacokinetic/pharmacodynamic model. Antimicrob Agents Chemother. 2012; 56(10).
- 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(9).
- Tsuji BT, Brown T, Parasrampuria R, Brazeau DA, Forrest A, Kelchlin PA, Holden PN, Peloquin CA, Hanna D, Bulitta JB. Front-loaded linezolid regimens result in increased killing and suppression of the accessory gene regulator system of Staphylococcus aureus. Antimicrob Agents Chemother. 2012; 56(7).
- Ly NS, Yang J, Bulitta JB, Tsuji BT. Impact of two-component regulatory systems PhoP-PhoQ and PmrA-PmrB on colistin pharmacodynamics in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012; 56(6).
- Sakoulas G, Bayer AS, Pogliano J, Tsuji BT, Yang SJ, Mishra NN, Nizet V, Yeaman MR, Moise PA. Ampicillin enhances daptomycin- and cationic host defense peptide-mediated killing of ampicillin- and vancomycin-resistant Enterococcus faecium. Antimicrob Agents Chemother. 2012; 56(2).
- Butterfield JM, Tsuji BT, Brown J, Ashley ED, Hardy D, Brown K, Forrest A, Lodise TP. Predictors of agr dysfunction in methicillin-resistant Staphylococcus aureus (MRSA) isolates among patients with MRSA bloodstream infections. Antimicrob Agents Chemother. 2011; 55(12).
- Bergen PJ, Tsuji BT, Bulitta JB, Forrest A, Jacob J, Sidjabat HE, Paterson DL, Nation RL, Li J. Synergistic killing of multidrug-resistant Pseudomonas aeruginosa at multiple inocula by colistin combined with doripenem in an in vitro pharmacokinetic/pharmacodynamic model. Antimicrob Agents Chemother. 2011; 55(12).
- Bulitta JB, Landersdorfer CB, Forrest A, Brown SV, Neely MN, Tsuji BT, Louie A. Relevance of pharmacokinetic and pharmacodynamic modeling to clinical care of critically ill patients. Curr Pharm Biotechnol. 2011; 12(12).
- Bergen PJ, Forrest A, Bulitta JB, Tsuji BT, Sidjabat HE, Paterson DL, Li J, Nation RL. Clinically relevant plasma concentrations of colistin in combination with imipenem enhance pharmacodynamic activity against multidrug-resistant Pseudomonas aeruginosa at multiple inocula. Antimicrob Agents Chemother. 2011; 55(11).
- Tsuji BT, Okusanya OO, Bulitta JB, Forrest A, Bhavnani SM, Fernandez PB, Ambrose PG. Application of pharmacokinetic-pharmacodynamic modeling and the justification of a novel fusidic acid dosing regimen: raising Lazarus from the dead. Clin Infect Dis. 2011; 52 Su.
- Okusanya OO, Tsuji BT, Bülitta JB, Forrest A, Bulik CC, Bhavnani SM, Fernandes P, Ambrose PG. Evaluation of the pharmacokinetics-pharmacodynamics of fusidic acid against Staphylococcus aureus and Streptococcus pyogenes using in vitro infection models: implications for dose selection. Diagn Microbiol Infect Dis. 2011; 70(1).
- Lim LM, Ly N, Anderson D, Yang JC, Macander L, Jarkowski A, Forrest A, Bulitta JB, Tsuji BT. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy. 2010; 30(12).
- Bergen PJ, Bulitta JB, Forrest A, Tsuji BT, Li J, Nation RL. Pharmacokinetic/pharmacodynamic investigation of colistin against Pseudomonas aeruginosa using an in vitro model. Antimicrob Agents Chemother. 2010; 54(9).
- Bulitta JB, Yang JC, Yohonn L, Ly NS, Brown SV, D'Hondt RE, Jusko WJ, Forrest A, Tsuji BT. Attenuation of colistin bactericidal activity by high inoculum of Pseudomonas aeruginosa characterized by a new mechanism-based population pharmacodynamic model. Antimicrob Agents Chemother. 2010; 54(5).
- Bulitta JB; Yang JC; Yohonn L; Ly NS; Brown SV; D'Hondt RE; Jusko WJ; Forrest A; Tsuji BT. Attenuation of Colistin Bactericidal Activity by High Incoulum of Pseudomonas Aeruginosa Characterized by a New Mechanism-Based Population Pharmacodynamic Model. Antimicrobial Agents and Chemotherapy. 2010; 54.
- Wu M, von Eiff C, Al Laham N, Tsuji BT. Vancomycin and daptomycin pharmacodynamics differ against a site-directed Staphylococcus epidermidis mutant displaying the small-colony-variant phenotype. Antimicrob Agents Chemother. 2009; 53(9).
- Begic D; Tsuji BT. Daptomycin pharmacodynamics against Staphylococcus aureus hemB mutants displaying the small colony variant phenotype. Journal Antimicrobial Chemotherapy. 2009; 2009.
- Tsuji BT. Loss of vancomycin bactericidal activity against accessory gene regulator (agr) dysfunctional Staphylococcus aureus under conditions of high bacterial density.. Diagn Microbiol Infect Dis. 2009; Diagn.
- 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. Ag. Chemother.. 2009; 53.
- Tsuji BT. In vitro pharmacodynamics of novel rifamycin ABI-0043 against Staphylococcus aureus.. Journal Antimicrobial Agents and Chemotherapy. 2008.
- von Eiff C; Kelchlin PA; Forrest A; Smith P; Tsuji BT. Attenuated vancomycin bactericidal activity against Staphylococcus aureus hemB mutants expressing the small-colony-variant phenotype. Antimicrob Agents Chemother. 2008; 52.
- Tsuji BT; Rhomberg PR; Jones RN; Rybak MJ. Evaluation of daptomycin, telavancin, teicoplanin, and vancomycin activity in the presence of albumin or serum. Diagn Microbiol Infect Dis. 2008; 60.
- Yang JC; Forrest A; Tsuji BT. Optimizing use of quinolones in the critically ill. Semin Respir Crit Care Med. 2007; 28.
- Yang JC, Tsuji BT, Forrest A. Optimizing use of quinolones in the critically ill. Semin Respir Crit Care Med. 2007; 28(6).
- Rose WE, Rybak MJ, Tsuji BT, Kaatz GW, Sakoulas G. Correlation of vancomycin and daptomycin susceptibility in Staphylococcus aureus in reference to accessory gene regulator (agr) polymorphism and function. J Antimicrob Chemother. 2007; 59(6).
- Tsuji BT, Rybak MJ, Lau KL, Sakoulas G. Evaluation of accessory gene regulator (agr) group and function in the proclivity towards vancomycin intermediate resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 2007; 51(3).
- Tsuji BT, Rybak MJ. Etest synergy testing of clinical isolates of Staphylococcus aureus demonstrating heterogeneous resistance to vancomycin. Diagn Microbiol Infect Dis. 2006; 54(1).
- Tsuji BT, Rybak MJ. Short-course gentamicin in combination with daptomycin or vancomycin against Staphylococcus aureus in an in vitro pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother. 2005; 49(7).
Abstracts:
- McClain R; Tsuji BT. Canadian Community- and Healthcare-Associated Methicillin-Resistant Staphylococcus aureus (MRSA): An Evaluation of Accessory Gene Regulator (agr) Function and Vancomycin (V) Pharmacodynamics. 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy October 25 - 28, 2008, Washington, DC. 2008.
- Begic D; Tsuji BT. Comparative Daptomycin (DAP) and Vancomycin (VAN) Activity Against Staphylococcus aureus hemB Mutants Expressing the Small-Colony-Variant (SCV) Phenotype in an In Vitro Pharmacodynamic Model (IVPM). 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy October 25 - 28, 2008, Washington, DC. 2008.
- Bulitta J; Tsuji BT. Inverse Inoculum Effect of Ciprofloxacin (CIP) and Imipenem (IMI) Against Pseudomonas aeruginosa (Pa) Characterized by New Mechanism-Based Pharmacodynamic (PD) Models. 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy October 25 - 28, 2008, Washington, DC. 2008.
- Ly N; Tsuji BT. Mechanism-Based Pharmacokinetic / Pharmacodynamic Model for the Inverse Inoculum Effect of Imipenem against Pseudomonas aeruginosa. 2008 AAPS Annual Meeting, Atlanta, GA, USA; November 16 - 20, 2008.. 2008.
- Takata T; Tsuji BT. Relationship Between Accessory Gene Regulator Locus with Vancomycin Bactericidal Activity and Efficacy in Methicillin-Resistant Staphylococcus aureus Bacteremia. 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy October 25 - 28, 2008, Washington, DC. 2008.
- Wu M; Tsuji BT. Vancomycin and Daptomycin Pharmacodynamics Differ Against a Site-Directed Staphylococcus epidermidis Mutant Displaying the Small Colony Variant Phenotype. 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy October 25 - 28, 2008, Washington, DC. 2008.
Evaluative Studies and Case Reports:
- Narita M, Tsuji BT, Yu VL. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy. 2007; 27(8).
Presentations:
- "http://www.buffalo.edu/news/releases/2017/05/032.html" . (2009)
- "Mechanism-Based Pharmacokinetic Pharmacodynamic (PKPD) Model for the Inverse Inoculum Effect of Imipenem Against Psedomonas Aeruginosa" American Association of Pharmaceutical Sciences Meeting (2008)