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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