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Curriculum Vitae Alexander J. Lepak, M.D. Personal Data Office Infectious Disease Medical Foundation Centenial Building Room 5221 1685 Highland Ave Madison, WI 53705-2281 Phone 608-263-1545 Fax 608-263-4464 Email: [email protected] Laboratories Microbial Sciences Building Room 4465 1550 Linden Drive Madison WI 53706-1521 Phone 608-265-8578 William S. Middleton Memorial Veterans Hospital Room D2221 2500 Overlook Terrace Madison, WI 53705 Phone 608-265-1901 ext 17831 Education & Training 1995-99 Undergraduate: Bachelor of Science, University of Wisconsin-Madison 2000-05 Medical School: University of Wisconsin-Madison 2002-03 NIH-GCRC Mentored Medical Student Research Program – Mentor: David Andes 2005-08 Residency Training: University of Wisconsin Hospital and Clinics, Madison WI, Internal Medicine 2008-10 Clinical Fellowship: University of Wisconsin Hospital and Clinics, Madison WI, Infectious Disease 2010-2012 Research Fellowship: NRSA T32 Ruth L. Kirschstein National Research Service Award, PI: Bruce Klein, Mentors: David Andes and William Craig Board Certification: Internal Medicine: 2008 Infectious Diseases: 2010 Current Appointment Assistant Professor of Medicine Department of Medicine Division of Infectious Disease University of Wisconsin School of Medicine and Public Health Past Positions and Appointments 1998 Research Assistant, University of Wisconsin, Department of Veterinary Medicine, PI: Dr. Benjamin Darien, DVM 2000 Associate Research Specialisty, University of Wisconsin, Department of Pharmacology, PI: Bernard Weisblum, MD 2010-2012 Postdoctoral trainee, University of Wisconsin, Department of Medical Microbiology and Immunology 2010-2013 Clinical Instructor & Research Associate, University of Wisconsin School of Medicine and Public Health, Department of Medicine, Division of Infectious Disease Professional Societies Infectious Diseases Society of America American Society for Microbiology Honors/Awards: 1996-99 Dean’s List 1999 Phi Kappa Phi 1999 Graduated with Distinction, College of Letters & Science, University of Wisconsin-Madison 2002 NIH-GCRC Mentored Medical Student Clinical Research Grant Award 2009 . ICAAC Infectious Disease Fellows Grant Program Recipient 2010-2012 Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training (T32) Grant Award 2010 George McCracken Infectious Disease Fellow, American Society for Microbiology 2011-2013 National Institutes of Health, Division of Loan Repayment Program for Clinical Research Award Recipient, University of Wisconsin School of Medicine and Public Health, Madison, WI Published Peer Reviewed 1. Andes D, Lepak A, Pitula A, Marchillo K, Clark J. A simple approach for estimating gene expression in Candida albicans directly from a systemic infection site. J Infect Dis 2005;192(5):893-900. 2. Lepak A, Nett J, Lincoln L, Marchillo K, Andes D. Time course of microbiologic outcome and gene expression in Candida albicans during and following in vitro and in vivo exposure to fluconazole. Antimicrob Agents Chemother 2006;50(4):1311-19. 3. Andes D, Forrest A, Lepak A, Nett J, Marchillo K, Lincoln L. Impact of antimicrobial dosing regimen on evolution of drug resistance in vivo: fluconazole and Candida albicans. Antimicrob Agents Chemother 2006;50(7):2374-83. 4. Andes D, Lepak A, Nett J, Marchillo K, Lincoln L. In vivo fluconazole pharmacodynamics and resistance development in a previously susceptible Candida albicans population examined by microbiologic and transcriptional profiling. Antimicrob Agents Chemother 2006;50(7):2384-94. 5. Lepak A, Andes D. Pharmacodynamics of Antifungal Drugs: A Strategy to Optimize Efficacy. Current Fungal Infection Reports 2008;2(1):12-19. 2 6. Nett JE, Lepak AJ, Marchillo K, Andes DR. Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis 2009;200(2):307-13. 7. Andes D, Diekema DJ, Pfaller MA, Bohrmuller J, Marchillo K, Lepak A. In vivo Comparison of the Pharmacodynamic Target Among Echinocandin Drugs and Candida species. Antimicrob Agents Chemother 2010;54(6):2497-506. 8. Lepak A, Andes D. Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting. Crit Care Clin 2011;27(1):123-47 9. Lepak A, Andes D. Antifungal PK/PD Considerations in Pulmonary Fungal Infections. Semin Respir Crit Care Med 2011;32(6):783-94 10. Andes D, Lepak A. Editorial Commentary: Antifungal Therapeutic Drug Monitoring Progress: Getting it Right the First Time. Clin Infect Dis 2012;55(3):391-93 11. Lepak AJ, Castanheira M, Diekema D, Pfaller M, Andes DR. Optimizing Echinocandin Dosing Regimen Design and Susceptibility Breakpoint Determination via Pharmacodynamic Evaluation of Three Echinocandins Against C. glabrata with and without Fks Mutations in an in vivo Disseminated Candidiasis Model. Antimicrob Agents Chemother 2012;56(11):5875-82 12. Lepak AJ, Marchillo K, Pichereau S, Craig WA, Andes DR. Comparative Pharmacodynamics of a new Oxazolidinone Tedizolid and Linezolid in a Neutropenic Murine Staphylococcus aureus Pneumonia Model. Antimicrob Agents Chemother 2012;56(11):5916-22 13. Lepak AJ, Marchillo K, Vanhecker J, Andes DR. Posaconazole Pharmacodynamic Target Determination against Wild-type and Cyp51 Mutant isolates of Aspergillus fumigatus in an in vivo model of Pulmonary Aspergillosis. Antimicrob Agents Chemother 2013;57(1):579-85 14. Lepak AJ, Marchillo K, VanHecker J, Forrest A, Andes DR. Impact of in vivo Triazole and Echinocandin Combination Therapy for Invasive Pulmonary Aspergillosis: Enhanced Efficacy against Cyp51 Mutant Isolates. Antimicrob Agents Chemother 2013;57(11):5438-47 15. Andes DR, Reynolds DK, Van Wart SA, Lepak AJ, Kovanda LL, Bhavnani SM. Clinical Pharmacodynamic Index Identification for Micafungin in Esophageal Candidiasis: Dosing Strategy Optimization. Antimicrob Agents Chemother 2013;57(11):5714-16 16. Lepak AJ, Marchillo K, VanHecker J, Diekema D, Andes DR. Isavuconazole Pharmacodynamic Target Determination for Candida species in an in vivo Murine Disseminated Invasive Candidiasis Model. Antimicrob Agents Chemother 2013;57(11):5642-48 17. Lepak AJ, Marchillo K, VanHecker J, Andes DR. Isavuconazole (BAL 4815) Pharmacodynamic Target Determination in an in vivo Murine Model of Invasive 3 18. Pulmonary Aspergillosis against Wild Type and Cyp51 Mutant Isolates of Aspergillus fumigatus. Antimicrob Agents Chemother, epub ahead of print Oct 2013 James S. Lewis II, Lepak AJ, Thompson GR, Craig WA, Andes DR, Sabol-Dzintars KE, Jorgensen JH. Failure of Clindamycin to Eradicate Infection with Beta-Hemolytic Streptococci Inducibly Resistant to Clindamycin in an Animal Model and in Human Infections. Submitted Clin Infect Dis, 2013 Book Chapters 1. Andes D, Lepak AJ. Antifungal Pharmacodynamics. In: Kauffman CA, Pappas PG, Sobel JD, and Dismukes WE (Eds) Essentials of Clinical Mycology, 2nd Edition. 2011 Springer Press. 2. Lepak A, Andes D. Antifungal Pharmacodynamics. Fundamentos de Medicina: Enfermedades Infecciosas*. Translated: Fundamentals in Medicine: Infectious Diseases. Edition: 7th. Pubisher: Corporacion para Investigaciones Biologicas. In press 3. O’reilly T, Andes D, Lepak A, Frimodt-Moller N. Evaluation of Antimicrobials in Experimental Animal Infections. In: Lorian V (Ed). Antibioitcs in Laboratory Medicine. In Press Abstracts 1. D. Andes, A. Lepak, A. Pitula, J. Smith. In Vitro Fluconazole Pharmacodynamic Impact on the Transcription of Genes Associated with C. albicans Drug Resistance. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2003 2. D. Andes, A. Lepak. Relationship Between Fluconazole Pharmacodynamic Exposure In Vitro and S. cerevisiae Genome Expression. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2003 3. D. Andes, A. Lepak, K. Marchillo, A. Pitula. Impact of fluconazole postantifungal effect on mRNA abundance of CDR1 and CDR2 efflux pumps in a murine infection model. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2004 4. D. Andes, A. Lepak, K. Marchillo, J. Nett, A.Pitula, J. Smith. Fluconazole pharmacodynamics and the emergence of Candida albicans resistance in an in vivo infection model. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2004 5. A. Lepak, Andes D. Candida albicans Global Transcriptional Profile During and Following Fluconazole Exposure – Gene Expression PAE. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2005 6. L. Lincoln, J. Nett, A. Lepak, M. Van Handel, D. Andes. Analysis of the global transcriptional profile of C. albicans cells from an in vivo catheter biofilm model. Candida and Candidiasis, American Society for Microbiology, 2006 4 7. D. Andes, A. Lepak, D. Diekema, M. Pfaller, K. Marchillo, J. Bohrmuller. Identification of the In Vivo Pharmacodynamic (PD) Target for Echinocandins against C. albicans (CA), C. glabrata (CG), and C. parapsilosis (CG) in the Neutropenic Murine Disseminated Candidiasis Model. Abstract A1-419. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, 2009 8. A. Lepak, H. Sanchez, K. Marchillo, D. R. Andes. Comparative Pharmacodynamics (PD) of a Triazole and Echinocandin for Invasive Pulmonary Aspergillosis (IPA). Abstract A1-040. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Boston, MA, 2010 9. N. W. Moore, A. J. Lepak, T. D. Moon. Infectious Complications Following Transrectal Prostate Biopsy at a Single Institution. 84th Annual Meeting of the North Central Section of the American Urological Association, 2010. Selected for presentation at the national meeting, the 107th Annual Meeting of the American Urological Association, 2011 10. M. C. Arendrup, A. Lepak, W. Hope, D. R. Andes. Comparison of the in vivo Pharmacodynamics (PD) of An Echinocandin and Triazole Based Upon Use of Clsi and Eucast Susceptibility Methods. Abstract A2-578. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Chicago, IL, 2011 11. A. Lepak, A. Forrest, K. Marchillo, D. R. Andes. Dose Ranging Pharmacodynamics (PD) of Echinocandin (E) and Triazole (T) Combination Antifungal Therapy in an In Vivo Pulmonary Aspergillosis (IPA) Model. Abstract A2-580. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Chicago, IL, 2011 12. A. Lepak, K. Marchillo, D. R. Andes. In Vivo Pharmacodynamics (PD) Characterization of the Novel Lantabiotic, Nai-107 in the Neutropenic Murine Thigh Model Against S. aureus. Abstract F1-751. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Chicago, IL, 2011 13. D. R. Andes, A. Lepak, K. Marchillo. In-vivo Pharmacodynamic (PD) Target for the Oral Glucan Synthase Inhibitor (GSI), MK-3118 (MK) Against C. albicans (CA), C. glabrata (CG), and C. parapsilosis (CP) in the Neutropenic Murine Disseminated Candidiasis Model. Abstract A2-579. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Chicago, IL, 2011 14. A. Lepak, K. Marchillo, W. Craig, D. R. Andes. In vivo Evaluation of a Novel Carbapenemase Inhibitor (CPI), Rpx7009, in Combination with the Carbapenem Rpx2003 against 2 KPC Producing K. pneumoniae (KP) in a Neutropenic Murine Thigh Model. Abstract F-857. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, CA, 2012 15. C. C. Bulik, O. O. Okusanya, S. M. Bhavnani, A. Lepak, P. G. Ambrose, J.L. Hoover, D. R. Andes. Evaluation of the Pharmacokinetics/Pharmacodynamics (PK/PD) of GSK2251052 (GSK052) against Gram-Negative Bacilli (GNB) in a Murine-Thigh Infection Model. Abstract A-1270. 52nd Interscience Conference on Antimicrobial 5 Agents and Chemotherapy, American Society for Microbiology, San Francisco, CA, 2012 16. D. R. Andes, O. O. Okusanya, C. C. Bulik, A. Lepak, S. M. Bhavnani, A. Forrest, J. L. Hoover, P. G. Ambrose. Evaluation of the Pharmacokinetics/Pharmacodynamics (PK/PD) of GSK2251052 (GSK052) against Gram-Negative Bacilli (GNB) Using Data from a Neutropenic Murine-Pneumonia Infection Model. Abstract A-1271. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, CA, 2012 17. A. J. Lepak, W. A. Craig, D. R. Andes, K. Marchillo, J. van Hecker. Reduced Activity of Clindamycin against Various Streptococci with Clindamycin-Inducible Resistance in the Neutropenic Thigh Infection Model. Abstract D-1431. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, CA, 2012 18. A. Lepak, M. Castanheira, M. Pfaller, D. Diekema, D. R. Andes. Pharmacodynamic (PD) Evaluation of 3 Echinocandins (E) against C. glabrata (CG) with and without Fks Mutations in the Neutropenic Disseminated Candidiasis Model. Abstract A-1929. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, CA, 2012 19. A. Lepak, D. R. Andes, A. Forrest. In Vivo Pharmacodynamic (PD) Evaluation of Combination Triazole (T) and Echinocandin (E) Therapy against Susceptible and Resistant A. fumigatus (AF). Abstract A-1930. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, CA, 2012 20. A. Lepak, K. Marchillo, J. Cabezas, D. R. Andes. Isavuconazole (ISA) Pharmacodynamic (PD) Target Determination C. albicans (CA) in an In Vivo Neutropenic Murine Model of Invasive Candidiasis (IC). Abstract A-1931. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, CA, 2012 21. A. Lepak, K. Marchillo, J. VanHecker, D. R. Andes. Pharmacodynamics (PD) of Posaconazole (P) in a Murine Invasive Pulmonary Aspergillosis (IPA) model against Wild Type and Cyp51 Mutant isolates. Abstract A-1932. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, CA, 2012 22. A. Lepak, K. Marchillo, J. Cabezas, W. Craig, D. R. Andes. In Vivo Pharmacodynamic (PD) Characterization of a New Fluoroquinolone (FQ) Antibiotic, Kpi-10, against GramPositive (GP) and Gram-Negative (GN) bacteria. Abstract A-1947. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, CA, 2012 23. A. Lepak, K. Marchillo, J. vanHecker, D. Andes. Pharmacodynamics (PD) of Isavuconazole (Isav) in a Murine Invasive Pulmonary Aspergillosis (IPA) Model Against Wild type (WT) and Cyp51 Mutants. Abstract A-291. Selected for oral presentation at 6 the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Denver, CO, 2013 24. A. Lepak, K. Marchillo, J. vanHecker, D. Diekema, D. Andes. Impact of Candida species on the Isavuconazole (ISA) Pharmacodynamic (PD) Target in an in vivo Neutropenic Murine Model of Invasive Candidiasis (IC). Abstract A-451. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Denver, CO, 2013 25 D. Andes, D. K. Reynolds, S. A. Van Wart, A. Lepak, L. L. Kovanda, S. M. Bhavnani. Clinical Pharmacodynamic (PD) Index Identification for Micafungin in Esophageal Candidiasis: Dosing Strategy Optimization. Abstract A-452. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Denver, CO, 2013 26 A. Lepak, A. Reda, K. Marchillo, J. VanHecker, D. Andes. In vivo Pharmacodynamic Target Evaluation of Ceftolozane against Streptococcus and Pseudomonas in a Neutropenic Murine Thigh Infection Model. Submitted, 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Barcelona, Spain, 2014 Invited Research Presentations Years Location UNIVERSITY OF WISCONSIN 2007 Department of Medicine Advances in Medicine Seminar 2008 Deparment of Medicine Advances in Medicine Seminar 2011 Microbes in Health and Disease Seminar 2012 Microbes Seminar in Health and Title Antifungal Prophylaxis in Hematological Malignancy Antifungal Pharmacodynamics, Optimizing Therapy Old Dog New Tricks: Use of Pharmacodynamic Approaches to Optimize Aspergillus Therapy Disease Invasive Fungal Infections and Drug Resistance: In vivo Pharmacodynamic Models to Optimize Therapy Research Support/Grants NIH/GCRC: Mentored Medical Student Clinical NIH GCRC M01 RR03186 Sponsor: NIH-GCRC 2002-2003 Investigator-Initiated Studies Program: Identification of the pharmacodynamic target for caspofungin and posaconazole used alone and in combination against drug susceptible and drug resistant Aspergillus fumigatus strains in a murine model of Invasive Pulmonary Aspergillosis (IPA). Sponsor: Merck PI: David Andes 2010-2011 Ruth L. Kirschstein National Research Service Award (NRSA) Training Grant 7 Sponsor: NIH 5 T32 AI 55397-08 PI: Bruce Klein 2010-2012 National Institutes of Health Loan Repayment Program Sponsor: NIH 2011-2013 Research Mentoring Anne Reda Stuart Burke Journal Review Antimicrobial Agents and Chemotherapy (ad hoc) Journal of Antimicrobial Chemotherpay (ad hoc) Diagnostic Microbiology and Infectious Disease (ad hoc) Service/Committees Years Service/Role 2008-10 UWHC Infection Control Committee 2008-10 VAH Infection Control Committee 2008-present UWHC Antimicrobial Use Subcommittee, Pharmacy and Therapeutics Committee 2008-10 UW Infectious Disease Fellowship Education Committee 2012-present 2010-present UW Internal Medicine Residency applicant interviewer 2010-present UW Infectious Disease Fellowship applicant interviewer 2012-present UWHC Antimicrobial Stewardship Physician 2012-present UW Infectious Disease Fellowship Clinical Compentency Committee Teaching Activities Years Location UNIVERSITY OF WISCONSIN 2009 Internal Medicine Resident Seminar 2009 2010 2011 2012 2013 University of Wisconsin Physician Assistant Program Invited Seminar University of Wisconsin Physician Assistant Program Invited Seminar Title Antibiotic review: Bug-Drug and difficult to treat microorganisms Antibiotic Review for the Physician Assistant in Training Antibiotic Review and Management Pearls for Commonly Encountered Outpatient Infectious Diseases Enteric Viral Infections Small Group Leader University of Wisconsin School of Medicine and Public Health, 2nd Year Medical School Foundations in Medicine Course University of Wisconsin Infectious Malaria Disease Fellowship Curriculum Internal Medicine Resident Lecture Guidelines: Procalcitonin, Beta-lactam series: Guidance and Implementation Allergy, SSTI, and UTI 8 of UWHC Guidelines Infectious Disease 9