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SOCIETY OF INFECTIOUS DISEASES PHARMACISTS

newsletter823 CONGRESS AVE., SUITE 230, AUSTIN, TX 78701

PRESIDENT’S COLUMN

WINTER 2015

Jason C. GallagherPharm.D., FCCP, FIDSA, BCPS Temple University

Another Annual Meeting has come and gone, and it is my pleasure to write you as the new President of our Society. I want to start by thanking Past-President Dave Bearden for his leadership last year, which after only two months I can already appreciate how much work he did as President. I would also like to thank outgoing members of the Board of Directors Joseph Kuti and P. David Rogers for their service to the Society over the past three and two years, respectively. It is an exciting time for SIDP, and I feel very fortunate to be serving in the role that I am for the Society right now. We are growing, evolving, leading, and infl uencing both practice and policy. How? I’m glad that you asked.

We are growing. SIDP’s growth has been fueled by several factors. Our Antimicrobial Stewardship Certifi cate program, led this year by Alan Gross, Jessica Robinson, and Kelly Harris, has trained many pharmacists to become more confi dent and knowledgeable stewards of antimicrobial use in their institutions. It is diffi cult to overstate the importance of this program to SIDP, and in my mind, to the infectious diseases community. Right now, the number of participants in our program outnumbers our membership total. Last year, the Board of Directors decided to reward those who have completed our certifi cate program with a year of free membership in SIDP so that they could experience the benefi ts of engaging in the infectious diseases pharmacy community. If even a small proportion of these members see value in their membership and join afterwards, our numbers will grow. Our growth is also sustained by the trend of increasing numbers of post-doctoral training programs in infectious diseases pharmacy, which increases the pool of ID pharmacists who can join

our Society. We represent the interests of all ID pharmacists and it is a goal to show this to both current and potential members. To meet this continued growth, we are investing signifi cantly in a new website to replace our archaic current site and help our members in many ways. Stay tuned!

We are evolving. As SIDP has grown, its membership has changed from one that was primarily researchers to one that is predominantly clinicians. This is again driven by the increased clinical post-doctoral training programs that are being created. This increase in ID pharmacists that are predominantly residency-trained does present an issue though in that it is likely that a lower proportion are trained to be researchers than have typically been in our membership. Here I believe SIDP serves an important role to facilitate networking opportunities at our Annual Meeting, via committee service, and in other ways to grow relationships between research- trained members and clinicians to grow the capabilities of both groups. Our research grants can also help facilitate continued growth of the research skills of new members.

We are leading. Anyone who attended the Annual Meeting, reads our newsletter, or has ever met them knows that Past-President Dave Bearden and member Kristi Kuper attended the White House forum on combatting antimicrobial resistance threats. However, we are doing much more than that. SIDP has been a member of the Infectious Diseases Society of America- led Stakeholder Forum on Antimicrobial Resistance (S-FAR) since its fi rst meeting at IDWeek 2014. This year, we joined the National Quality Form (NQF) and its subgroup on antimicrobial stewardship. Our Political Advocacy Committee, led by Emily Heil and Michael Nailor, has been very active and has turned the corner from endorsing policies, letters, and actions from other groups to creating position statements and letters to stakeholders of our own.

We are infl uencing. SIDP’s infl uence on other organizations is palpable. We have strengthened ties with the American Society for Microbiology (ASM) to guide the evolution of ASM Microbe into a meeting that meets the needs of ID pharmacists as ASM transitions from a fall ICAAC to a spring ASM Microbe. Dave Bearden and I met with ASM leadership at ICAAC and their interest in working with us is apparent. Currently, Amit Pai serves on the Planning Committee for Category A (PKPD, pharmacology) and it was just announced that, at our request, Conan MacDougall will be added for Category S (antimicrobial stewardship and quality of care) for the 2017 meeting. As this meeting evolves, we believe that it is in SIDP’s best interest to work with ASM to shape it into something that you will fi nd useful, and I hope that you will give ASM Microbe a try in June 2016. In addition to this, we are one of the sponsoring organizations for the petition to the Board of Pharmacy Specialties for the recognition of ID pharmacotherapy as its own specialty. I know this has been said before, but having

been involved in earlier attempts I can say that the eff ort is currently at a stage that has not been previously reached. I believe that it can move to completion rather easily.

I wish to close with a thanks for the enthusiastic sign-up that we received for volunteers for committee service. The fi rst thing I quickly learned when I began serving on the Board last year was that SIDP is a truly member-driven society, top-to-bottom. Our numbers and infl uence has grown, but our mechanism is the same – we exist to serve our members, and our members’ service allows us to do that. Almost 300 people signed up to serve on our committees (without those paper sheets, no less)! While not everyone was able to be placed on every requested committee, I am hopeful that most requests were able to be partially met. It is a tribute to the enthusiasm of our members that we had more volunteers than space for service. For that, I thank you.

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Special Recognition - Jeff rey Kuper, PharmD, BCPS

Dr. Jeff Kuper was a mentor of ours, a beloved professor at Rutgers University College of Pharmacy, and the creator of the infectious diseases pharmacy residency at Robert Wood Johnson University Hospital (RWJUH). He impacted the lives of many students during his many years at Rutgers and was one of the guiding infl uences that led us to careers in infectious diseases pharmacy (I still have his handouts on the antibiotic classes - Joe). His energy and enthusiasm for Infectious Diseases, combined with his ability to make a complex topic easy to understand without ‘dumbing it down’, made him a favorite among students. Dr. Kuper also taught students on the Infectious Diseases rotation at RWJUH. He was highly respected by the physicians and nurses. He was also a long-time member of the Society of Infectious Disease Pharmacists and served on a number of committees, including chair of the Annual Report Committee this past year.

Jeff did not have an easy life. He was born with cystic fi brosis and had associated type 1 diabetes for most of his life. Several years ago, he suff ered a hemorrhagic stroke, which he helped the EMS team diagnose when he called 911 with a crushing headache and said “I’m having a hemorrhagic stroke!” Aft er he recovered, he eventually moved from New Jersey back to his native South Dakota to be closer to family. It was at this point that his life improved.

Jeff was a bachelor at the time of his move, but he met his eventual wife Donna back home in South Dakota. While his recovery was diffi cult, we believe that he would not have traded circumstances with anyone. We believe that the happiest time in his life was that time. Unfortunately, his medical diffi culties continued and he passed away in 2015.

Dr. Kuper, thank you for your infl uence on our lives and our profession. You are missed.

Written by: Jason Gallagher and Joseph Kuti

Active

AssociateAbdel BendamkilaAbdullah Alosaimi

Adam BrothersAdam Utley

Amanda VolpeAmber SimpsonAmy HickmanAndrea ChbeirAndrew MelzakAngela Haskell

Ann LloydAnna KabakovAnthony Hall

Ardath MitchellArie Spitzfaden

Betsy LeeBobbie MasoudBrandi AcevedoBrian LaPlantBrianna Ho

Bryan KudlawiecBryce Lifer

Cara PhillipsCharity SchmidtChase CrawfordChee Lan Lau

Cheryl KimChia-Shan Tsai

Christine SoedelCristy Hodakowski

Crystal ChaDan FleischmanDana Woodall

Danielle SkoubyDavid MacMillanDeanna Buehrle

Delia CariasDennis Andrew AnchetaDiamantis Klimentidis

Divya SrinivasanDustyn WilliamsElizabeth Chung

Ariel MaBin Xiao

Erica HousmanJamie Borkowski

Joseph HongKari Furtek

Kimberly LeuthnerLori Gordon

Melanie NicolNour Baghdady

SIDP WELCOMES OUR NEWEST MEMBERS!

Ellen SandvigErin LockardFalguni Patel

Farhana AnsariFarrukh KhanFaryal QureshiFrank Wonka

Galen HamannGary BaileyGary Smith

Giselle ObrienGreg Nocito

Gwendolyn GarrorHamdi Elsoudi

Hannah YinglingHaoshu Yang

Heather HouseknechtHee Jung Kang

Herman MartinezHuei-Li BarkerHyeryeon Noh

Jack CrossJames BarlettJames Bird

Jamie GodinJane Irwin

Janelle CaruanoJean StoergerJeff rey Cies

Jeff rey YoungJen Sparks

Jenna PreuskerJennifer FlesnerJennifer WrightJessica Holland

Jill GossardJill MakowskiJill O’Donnell

Jim TurleyJohn Parker

Joseph ConoverJosephine ZepedaJudith Nwachukwu

Julie HallJulie Metcalfe

Justin SchmettererKareem Elfass

Karen BurkKarla SmtihKarolyn Hou

Kasey HickmanKatherine JamisonKatherine Renner

Katie GrittitbKatrina Truong

Kelli BellKersten Weber Tatarelis

Kiew Bing PauKiley Martin

Kimberly BelongieKirsty Cowles

Kristen BambergKristen Fuhrmann

Lan NguyenLarry ClemensLaura EnmanLaura Limburg

Laura RiceLauren Cavanaugh

Leanna LiuLeigh Ann Keeton

Leslie BarkerLillian Jandacek

Lisa TyjewskiLiza Vaezi

Louis PortasMannling HoMarc Meyer

Margaret HegerMaria WareMark Lesher

Marti HillsMegan JonsonMelinda CarterMelissa RohrMeng-lin LinMichael Holt

Michael WhippleMichelle Bundy

Mihail MihailescuMilda Monika TotoraitisMontgomery Williams

Nahla KandilNataly MeenesNathan FewelNick Hummel

Nina HullNita Roy

Noha HafezOhannes Kandilian

Omar MartinezOwoedimo UsoroPaige Anderson

Palak BhagatPamela Letzkus

Panit TaylorPatrick Ellis

Ralph Rivera Randi ConradRandy Seys

Robert BrummelRosita AminiRuston TaylorRyan Conrad

Sabbay MalvestiSandra EichSara AusmanSarah McCoy

Sarah MinorScott HarrisonShakeel Khan

Shalonda Barnes-Warren

Shue Hong KongSolomon Winans

Sparkle BoxStephen HuynhSteven DzierbaSteven Smoke

Thomas RiordanThomas Thomas

Tiff any DickeyTiff any Kan

Toni LeeToral Patel

Tracy WasemUkamaka Dike

Vikoriya MalamudWai Tak Vince Sung

Yamil Cabrera

Aaron WilsonAndrew ThompsonAnthony Casapao

Arnold DecanoAshley Besignano

Ashley GaleBethanne Carpenter

Brian BussCharity WilsonCristina Miglis

Derek Vander HorstDustin Carr

Elizabeth CadyEric LikarEris Cani

Esther FasanmiEthan SmithGary FongJanet Wu

Jeanne ForresterJennifer TieuJenny Shroda

Jessica MoralesJoshua WangKaitlyn RivardKellie GoodletKendall TuckerKristen Bunnell

Lindsay DonohueMadeline KingMallory Fowler

Trainee

Marguerite MonogueMark Mixon

Megan RusbyMelissa Santibanez

Naaseha RizviNancy Bui

Nicholas BrittNicole WilsonNicole WilsonOmar PerezPatrick Lake

Rachel FosterRachel MusgroveRand SulaimanRebecca Nolen

Rohini DaveSamuel BaynesSean AvedissianShaina DoyenShawn MazurTonya SmithTracy Trang

Tristan TimbrookVu Ta

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Clinical Pharmacy Manager, Infectious Diseases/Antimicrobial StewardshipLocation: NewYork-Presbyterian Hospital, New York, NYContact: Christine Kubin, PharmD, BCPS chk9005@nyp.orgDetails: Clinical Pharmacy Manager

Tele-Infectious Diseases/Antimicrobial Stewardship PharmacistLocation: Intermountain Healthcare, Salt Lake City, UTContact: Paul Wohlt - Paul.Wohlt@imail.orgDetails: Tele-ID

Clinical Pharmacy Specialist - Infectious DiseasesLocation: Los Angeles, CaliforniaContact: Bob Costa, CPC ; bob.costa@sierrastaffi ng.com Details: Clinical Pharmacy Specialist - Infectious Diseases

Assistant/Associate Professor of Pharmacy PracticeLocation: Pacifi c University, Hillsboro, OregonContact: Mark Della Paolera, PharmD, (dellapaolera@pacifi cu.edu)Details: Assistant/Associate Professor

Clinical Pharmacy Specialist - Infectious DiseasesLocation: University of Texas, MD AndersonContact: Brad Atkinson ; BJAtkins@mdanderson.orgDetails: Clinical Pharmacy Specialist - Infectious Diseases

Medical Aff airs ManagerLocation: Theravance, San Francisco, CA Contact: Christine Slover; cslover@theravance.comDetails: MAM

System Antimicrobial Stewardship PharmacistLocation: Carolinas HealthCare System, Charlotte, NCContact: Steven Jarrett – Steven.Jarrett@CarolinasHealthCare.orgDetails: System Antimicrobial Stewardship Pharmacist

Pharmaceutical Industry, Field-based Medical Aff airs – Hospital Infectious Diseases (Nationwide Opportunities)Company: The Medicines Company Contact: Mark Redell, PharmD, Mark.Redell@themedco.comDetails: Field-based Medical Aff airs

Clinical Pharmacist Infectious DiseasesLocation: Kaweah Delta Health Care District - CAContact: Pam Blackburn, pblackbu@kdhcd.orgDetails: Clinical Pharmacist ID

Medical Aff airs Director Company Name: MERCK & COMPANY INC. Location(s): Multiple locations, Multiple Locations, USDetails: Medical Aff airs Director

Assistant/Associate Professor Infectious DiseaseLocation: Univ. of Maryland School of Pharmacy, Rockville,MDContact: Health Congdon, PharmD, BCPS, CDE, hcongdon@rx.umaryland.eduDetails: Assistant/Associate Professor

Clinical Pharmacy Practitioner, Infectious DiseasesLocation: The Mount Sinai Hospital, New York, NYContact: Gina Caliendo, BS, PharmD, BCPS, Gina.caliendo@mountsinai.org Details: Clinical Pharmacy Practitioner

Pharmacist - Infectious Disease Specialty (ID)Location: Sutter Health- Roseville, CA Contact: Alfred Santos – santosa3@sutterhealth.orgDetails: Pharmacist

Infectious Disease Clinical PharmacistLocation: Community Regional Medical Center - Fresno, CA Contact: Stephanie Delgado, Recruiter – sdelgado3@communitymedical.orgDetails: ID Clinical Pharmacist

Medical Science Liaison – Hospital Infectious Diseases (Nationwide Opportunities) Locations: (MA, NH, VT), (KY, MD, OH), (NC, VA, DC), (LA, MS, TN), (AZ, CO, MT, NV, WY)Contact: Wendy Copley, wcopley@tmacmail.comDetails: Medical Science Liaison

Medical Science Liaison - AntiviralLocation: West (CA) Territory: Midwest (Chicago), Southeast and Southwest (Texas)Details: Medical Science Liaison

Infectious Diseases PharmacistLocation: San Diego, CAContact: Mark Parmenter Parmenter.Mark@scrippshealth.orgDetails: ID Pharmacist

Infectious Infectious Disease Pharmacist for Teaching HospitalLocation: Pacifi c States, OR, WA, CAContact: Patty Wyatt, patty@clinipost.comID Pharmacist

Clinical Pharmacy Specialist, Infectious DiseaseLocation: Highland Hospital, Oakland, CAContact: Diana Thamrin dthamrin@alamedahealthsystem.orgDetails: Clinical Pharmacy Specialist – Infectious Disease

Antimicrobial Stewardship PharmacistLocation: Baltimore VA, Baltimore, MD Contact: Carol Rudo (carol.rudo@va.gov) Details: https://www.usajobs.gov/GetJob/ViewDetails/409549700

Clinical Pharmacy Specialist, Infectious DiseasesLocation: Prestigious Hospital System, South CarolinaContact: Bob Costa, bob.costa@sierrastaffi ng.com Details: Clinical Pharmacy Specialist

Infectious Diseases Pharmacy Specialist Location: Plaza Medical Center, Ft. Worth, TexasContact: Michael Lawless, Michael.lawless@hcahealthcare.com Details: ID Pharmacy Specialist

O P P O R T U N I T I E S F O R EM P L O Y M E N T

ID Job Listing (Please see the SIDP.org for complete details and hyperlinks to further descriptions)

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Pharmacist Clinical Staff Location: University of KentuckyContact: Scott Kincaid, seki232@uky.edu Details: Pharmacist Clinical Staff

Infectious Diseases Clinical Pharmacy Specialist Contact: Dr. Matt Goetz, Matt.Goetz@va.govDetails: https://www.usajobs.gov/GetJob/ViewDetails/401827200

Infectious Diseases Pharmacy Specialist Location: Medical City Dallas Hospital Contact: Michael Lawless, Michael.lawless@hcahealthcare.com Details: ID Pharmacy Specialist

Antimicrobial Stewardship Pharmacist Location: St. Mary's Medical Center, Grand Junction, CO Contact: Kate Christmas, 919-977-6186Details: ASP Pharmacist

Assistant Professor of Pharmacy Location: St. Louis College of Pharmacy Contact: Ryan Moenster, Pharm.D., BCPS (AQ-ID); Ryan.Moenster@stlcop.eduDetails: Assistant Professor

Project Director, Antibiotic Resistance ProjectLocation: Washington, DCContact: The Pew Charitable Trusts Details: Project Director

Medical Science Liaison - Infectious Disease/Anti-Infective (CO, NM, UT Region)on: CO, NM, UT Contact: Wendy Copley, wcopley@tmacmail.com Details: Infectious Diseases/Anti-Infective

Clinical Pharmacy Specialist Location: Maricopa Integrated Health System, Phoenix, Arizona Contact: http://jobs.mihs.org/clinical-pharmacy-specialist-pharma-cy-hospital/job/5146021 Details: Clinical Pharmacy Specialist

Senior Associate, Antibiotic Resistance Project Location: The Pew Charitable Trusts, Washington, DCDetails: Senior Associate

Clinical Pharmacist - Infectious Diseases Location: Southeast Missouri HospitalContact: Mandi R. Presser, MA, FASPR , apresser@sehealth.orgDetails: Clinical Pharmacist

Nationwide Opportunities for Medical Science Liaison - Infectious Diseases/Anti-InfectiveLocation: AZ/NV Contact: Wendy Copley, wcopley@tmacmail.com Details: Infectious Diseases/Anti-Infective

Clinical Pharmacist Specialist- Antimicrobial Stewardship & Infec-tious Diseases Location: National Institutes of HealthContact: Barry Goldspiel, PharmD , bgoldspiel@nih.gov Details: Clinical Pharmacist

Outpatient Infectious Diseases Clinical Pharmacy Specialist Location: Parkland Hospital & Health System, Dallas, texasContact: Steven S. Carlisle, BS.Pharm, R.Ph., Pharm.D., BCPS, Steven.Carlisle@phhs.org Details: Pharmacy Specialist

Sr Offi cer, Human Stewardship, Antibiotic Resistance Project Location: The Pew Charitable Trusts, Washington, DCDetails: Senior Offi cer

Assistant/Associate Professor - Infectious Disease Location: University of Maryland - Baltimore, MDContact: Heather Congdon, Pharm.D., BCPS, CDE, lcongdon@rx.umaryland.eduDetails: Assistant/Associate Professor

Clinical Pharmacy Specialist - Infectious DiseaseLocation: FloridaContact: Bob Costa, C.P.C., bob.costa@sierrastaffi ng.comDetails: Clinical Pharmacy Specialist

Assistant/Associate Professor - Internal Medicine/Pharmacotherapy Location: University of Maryland - Rockville, MDContact: Heather Congdon, Pharm.D., BCPS, CDE, lcongdon@rx.umaryland.eduDetails: Assistant/Associate Professor - Internal Medicine

Medical Science Liaison - Infectious Disease/Antimicrobial Location: Multiple TerritoriesContact: Theravance Biopharma - Karmon Johnson, Pharm.D., 501-626-8200Details: Medical Science Liaison- ID

Medical Liaison - Infectious DiseaseLocation: Multiple LocationsDetails: http://ejob.bz/ATS/jb.do?reqGK=839262

Location: The Pew Charitable Trusts, Washington, DCDetails: Director

Location: UCSF School of PharmacyDetails: Clinical Pharmacy Faculty

Clinical Pharmacy Specialist, Infectious Diseases Location: Prestigious Hospital System, PhiladelphiaContact: Bob Costa bob.costa@sierrastaffi ng.comDetails: Clinical Pharmacy Specialist

Pharmacist Location: San Francisco General Hospital - HIV/AIDS DivisionContact: Elena Jensen jensene@php.ucsf.eduDetails: Pharmacist

Location: Maine Medical CenterContact: Ned Asherman; Easherman@mmc.orgDetails: Clinical Pharmacy Specialist - ID

Location: Nationwide OpportunitiesContact: Lynette Lapola; LLAPOLA@judge.comDetails: MSL

Infectious Disease Clinical Specialist Location: Eastern Maine Medical CenterContact: Jamie L. Cronin, PharmD, BCPS; jcronin@emhs.orgDetails: Infectious Disease Clinical Specialist

Senior Manager/Field Trainer for Infectious Disease Medical Science Liaison TeamLocation: Candidate can live anywhere in the USContact: Theravance Biopharma - Karmon Johnson, Pharm.D., 501-626-8200Details: Senior Manager/Field Trainer

* All listed job opportunities have more extensive information listed on SIDP’s website.

To add or revise listings please email Stephanie Bulak at sbulak@eami.com.

Medical Science Liaison - Infectious Disease/Antimicrobial Location: Southeast Region: GA, AL, FL, NC, TN, SCContact: The Medical Aff airs CompanyDetails: Medical Science Liaison

Medical Science Liaison - Infectious Disease/Antimicrobial Location: West Region: CA, WA, AZ, NV, OR, COContact: The Medical Aff airs CompanyDetails: Medical Science Liaison

Clinical PharmacistLocation: Duke Antimicrobial Stewardship Outreach Network - Georgia/South CarolinaContact: Paul Thacker II, Paul.thacker@duke.edu, 919-684-4560Details: Clinical Pharmacist Clinical Pharmacy Specialist – Infectious DiseaseLocation: National Institutes of Health Clinical Center, Pharmacy Department, Bethesda, MDContact: Barry Goldspiel, PharmD, BCPS, BCOP, bgoldspiel@nih.gov, 301-496-5869Details: Clinical Pharmacy Specialist

Nationwide Opportunities for Medical Science Liaison - Infectious Disease/Anti-InfectiveLocation: NationwideContact: www.TheMedicalAff airsCompany.com; Wendy Copley; wcopley@tmacmail.com Details: Medical Science Liaison Clinical Pharmacy Specialist - Infectious Disease Location: Phoenix, ArizonaContact: Bob Costa, C.P.C., bob.costa@sierrastaffi ng.comDetails: Clinical Pharmacy Specialist

Medical Science Liaison Contact: TheravanceDetails: Medical Science Liaison

Director, Infectious Diseases, Global Health ScienceLocation: The Medicines Company, Several positions throughout the USA (Field-Based) for Qualifi ed Applicants; Immediate HiringContact: Jill Massey, PharmD, MBA, Jill.Massey@themedco.comDetails: Director, Infectious Diseases Outpatient Infectious Diseases Clinical Pharmacy SpecialistLocation: Parkland Health and Hospital System, Dallas, TXContact: Steven Carlisle, PharmD, BCPS steven.carlisle@phhs.orgDetails: Outpatient ID Clinical Pharmacy Specialist

Assistant Professor of Translational SciencesLocation: The University of Texas at Austin College of Pharmacy, San Antonio, TexasContact: Christopher Frei, Pharm.D., FCCP, freic@uthscsa.edu, 210-567-8371Details: Assistant Professor

Staff Pharmacist, Infectious Disease SpecialistLocation: Baptist Hospital East, Louisville, KYContact: Lindsey Higginbotham, Lindsey.higginbotham@bhsi.com Details: Staff Pharmacist

Infectious Diseases Medical Science Liaison - South Central Location: The Medical Aff airs CompanyContact: TMAC Career Center http://tmac.hodesiq.comDetails: ID Medical Science Liaison Tenure Track Assistant Professor Location: University of MinnesotaContact: Michael Kotlyar, PharmD kotly001@umn.eduDetails: Assistant Professor

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A n n u a l M e e t i n g s (January 2016 – December 2016 )

Date / Location Conference Name March 18–20, 2016 Washington, DC

April 13–17, 2016 Seattle, WA

April 18-20, 2016 Baltimore, MD

May 5-7, 2016 Orlando, FL

June 16, 2016Boston, MA

June 16-20, 2016 Boston, MA

July 17-22, 2016Durban, South Africa

July 31–August 3, 2016 Washington, DC

August 4–7, 2016 Washington, DC

September 9–12, 2016 Seattle, WA

October 24–27, 2016 Washington, DC

October 26-30, 2016New Orleans, LA

November 13-17, 2016Atlanta, GA

December 11–14, 2016 Washington, DC

@ASM Conference on The Individual Microbe: Single-cell Analysis and Agent-based Modelinghttp://conferences.asm.org/index.php/2012-02-09-21-04-52/asm-confer-ences-event-calendar/15-information/273-asm-conference-proposal-information-2

13th ASM Conference on Candida and Candidiasis*

2016 NFID Annual Conference on Vaccine Researchhttp://www.nfi d.org/acvr

19th Annual MAD-ID/NFID 2016 Joint Meeting(Champions Gate Hotel)

SIDP 2016 Annual Meeting

ICAAC 2016/ASM 2016 (ASM Microbe)http://www.asmmicrobe.org

AIDS 2016 (21st International AIDS Conference)http://www.aids2016.org/

ASM Conference on Streptococcal Genetics*

2nd ASM Conference on Experimental Microbial Evolution*

6th ASM Conference on Benefi cial Microbes*

ASM Conference on Infection and Cancer*

IDWeek 2016http://www.idweek.org

65th Annual American Society of Tropical Medicine and Hygiene Meetinghttp://www.astmh.org/Home.htm

ASM Conference on Antibacterial Development*

*Information on ASM Conferences can be located at http://conferences.asm.org/index.php/2012-02-09-21-04-52/asm-conferences-event-calendar

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Throughout our partnership with SIDP, ASM continues to recognize the importance of communication and collaboration among microbiologists, infectious diseases physicians and infectious diseases pharmacists and has incorporated this multidisciplinary approach into the new ASM Microbe. This new meeting, scheduled to take place on June 16-20, 2016 in Boston, Massachusetts, will be an integration of ASM’s two premier events, the General Meeting (GM) and ICAAC and will off er the superb programming previously associated with the GM and ICAAC, while also embracing the signifi cance of trans-disciplinary research and development.

Programming for ASM Microbe will feature issues of great interest and importance to the SIDP membership: antimicro-bial stewardship, antimicrobial resistance, molecular diagnostics, and new data from clinical trials. Specifi cally, ASM is pleased to partner with SIDP for joint workshops and symposia on:

- Clinical Tools to Individualize Antimicrobial Dosing; - Modeling Pediatric Anti-Infective Pharmacokinetics/Pharmacodynamics; - Basics of Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents; and - Decreased Antibiotic Effi cacy in Renal Impairment: Are We Getting the Dose Wrong?

Examples of other sessions of interest include: - Antimicrobial Stewardship in Hospitals - Modeling Pediatric Anti-Infective Pharmacokinetics/Pharmacodynamics - How to Use Behavioral Theories to Design an Eff ective Antimicrobial Stewardship Program - Predicting the Impact of Antibiotic Stewardship on AMR: Simulations Modeling - Controversies in Antimicrobial Stewardship - Antimicrobial Toxicodynamics

Additional details about the program can be found at asmmicrobe.org. Overall, ASM Microbe 2016 will feature nearly 200 substantive, thought-provoking sessions, more than 5,000 cutting-edge poster presentations and will be the preeminent meeting for learning about new antimicrobial agents in preclinical development.

As an added feature, ASM Microbe will also continue to follow in the ICAAC tradition of being the leading forum for net-working among ID pharmacists, practitioners, and investigators. There will be numerous opportunities for networking in Hubs throughout the convention center. These easy-access locations will include “bite-size” programming specifi c to a particular area of science, as well serving as a meeting spot for catching up with old friends and forming new collabora-tions with international colleagues.

In preparation for ASM Microbe, ASM has worked closely with SIDP leadership to ensure that there is adequate and ap-propriate representation of infectious diseases pharmacists on our planning committees. For 2016, we were honored to have Dr. Amit Pai serving on the planning committee and for 2017 we are pleased to announce the addition of Dr. Conan MacDougall. Their contributions are invaluable in developing content that is of interest to our respective memberships.

ASM Microbe 2016 will be an historical event for ASM and we hope you are able to join us in Boston to experience this prominent occasion.

We look forward to seeing you in Boston.

Robin Patel, M.D. Chair, ICAAC Program Committee

David Aronoff , M.D. Chair, ICAAC Program Committee Vice-Chair, ICAAC Program Committee

ASM Microbe Abstract submission is currently openAbstract deadline: January 12, 2016 at 5:00 p.m. ET

Registration opens to everyone: January 7, 2016

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SIDP Member Publications

Congratulations to the following SIDP members for recent publications:

September 2015 update (includes April - June 2015 citations)

Aitken, SamuelAkins, RondaAllen, David

Argamany, JacquelineAvdic, Edina

Bachmeier, HarrisonBallow, CharlesBarber, Katie

Barriere, StevenBosso, John

Boucher, BradleyBowers, DanaBoyd, NatalieBrooks, Annie

Caplinger, ChristinaCarreno, Joseph

Casapao, AnthonyChilds-Kean, Lindsey

Cho, JonathanClaeys, Kimberly

Clay, PatrickCrandon, JaredCulshaw, DarrenDanziger, LarryDavis, Susan

Destache, ChristopherDrew, Richard

Durham, SpencerEaton, VaughnEstrada, Sandy

Figueroa, Deborah

Frei, ChristopherGarey, Kevin

Gauthier, TimothyGoff , Debra

Gubbins, PaulHall, Ronald

Hall Snyder, AshleyHayney, MaryHirsch, Betsy

Holtzman, CarolHong, JosephHurren, Jeff

Jankowski, ChristopherJimenez, Humberto

Johns, ScottJohnson, Melissa

Jung, RoseKashuba, Angela

Kays, MichaelKlepser, Michael

Krop, LynneKullar, RavinaKuper, KristiKuti, Joseph

Lamp, KennethLaPlante, Kerry

Le, JenniferLin, Yao Hua

Madaras-Kelly, KarlMaples, Holly

McLaughlin, Milena

Mohr, JohnMynatt, Ryan

Neuner, ElizabethNicolau, DavidO’Brien, Kristen

Oramasionwu, ChristinePatel, Hina

Pogue, JasonRaber, SusanReveles, Kelly

Rhodes, NathanielRodvold, KeithRose, Warren

Rybak, MichaelScarsi, KimberlyScheetz, MarcShah, DharaShields, RyanSmith, Jordan Stach, LeslieSuda, Katie

Swanson, JosephTam, Vincent

Tran, TrucTsuji, Brian

Townsend, Mary LouiseWeidle, PaulWerth, Brian

Wiederhold, NathanWood, Christopher

Yu, Diana

Stewardship

Garey KW, Aitken SL, Dima-Ala A, Beyda ND, Kuper K, Xie Y, Koo HL. Echinocandin use in hospitalized patients: a multi-institu-tional study. Am J Med Sci. 2015 Apr;349(4):316-20.

Goldman JL, Lee BR, Hersh AL, Yu D, Stach LM, Myers AL, Jackson MA, Day JC, McCulloh RJ, Newland JG. Clinical diagnoses and antimicrobials predictive of pediatric antimicrobial stewardship recommendations: a program evaluation. Infect Control Hosp Epidemiol. 2015 Jun;36(6):673-80.

Hicks LA, Bartoces MG, Roberts RM, Suda KJ, Hunkler RJ, Taylor TH Jr, Schrag SJ. US outpatient antibiotic prescribing variation according to geography, patient population, and provider specialty in 2011. Clin Infect Dis. 2015 May 1;60(9):1308-16.

Klepser ME, Adams AJ, Klepser DG. Antimicrobial stewardship in outpatient settings: leveraging innovative physician-pharmacist collaborations to reduce antibiotic resistance. Health Secur. 2015 May-Jun;13(3):166-73.

O'Brien KA, Zhang J, Mauldin PD, Gomez J, Hurst JM, Sean Boger M, Bosso JA. Impact of a stewardship-initiated restriction on empirical use of ciprofl oxacin on nonsusceptibility of Escherichia coli urinary isolates to ciprofl oxacin. Pharmacotherapy. 2015 May;35(5):464-9.

Santibañez M, Veulens MV, Jenistova T, Aragon L, Gauthier TP. Characteristics of primary literature in the fi eld of antimicrobial stewardship, 2000-2013. Infect Control Hosp Epidemiol. 2015 May;36(5):616-8.

Wenzler E, Rodvold KA, Danziger LH. Editorial commentary: improving prescribers to advance antimicrobial stewardship. Clin Infect Dis. 2015 Apr 15;60(8):1259-61.

11

PK/PD

Aitken SL, Altshuler J, Guervil DJ, Hirsch EB, Ostrosky-Zeichner LL, Ericsson CD, Tam VH. Cefepime free minimum concentra-tion to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneu-monia. Int J Antimicrob Agents. 2015 May;45(5):541-4.

Akins RL, Katz BD, Monahan C, Alexander D. Characterization of high-level daptomycin resistance in viridans group streptococci developed upon in vitro exposure to daptomycin. Antimicrob Agents Chemother. 2015 Apr;59(4):2102-12.

Berti AD, Baines SL, Howden BP, Sakoulas G, Nizet V, Proctor RA, Rose WE. Heterogeneity of genetic pathways toward dap-tomycin nonsusceptibility in Staphylococcus aureus determined by adjunctive antibiotics. Antimicrob Agents Chemother. 2015 May;59(5):2799-806.

Bowers DR, Cao H, Zhou J, Ledesma KR, Sun D, Lomovskaya O, Tam VH. Assessment of minocycline and polymyxin B combination against Acinetobacter baumannii. Antimicrob Agents Chemother. 2015 May;59(5):2720-5.

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 Apr;59(4):2315-27.

Casapao AM, Lodise TP, Davis S, Claeys KC, Kullar R, Levine DP, Rybak MJ. The association between the vancomycin day 1 exposure profi le and outcomes among patients with methicillin-resistant Staphylococcus aureus infective endocarditis. Antimicrob Agents Chemother. 2015 Jun;59(6):2978-85.

Crandon JL, Nicolau DP. In vivo activities of simulated human doses of cefepime and cefepime-AAI101 against multidrug-resistant Gram-negative Enterobacteriaceae. Antimicrob Agents Chemother. 2015 May;59(5):2688-94.

Guerra AD, Cantu DA, Vecchi JT, Rose WE, Hematti P, Kao WJ. Mesenchymal stromal/stem cell and minocycline-loaded hydrogels inhibit the growth of Staphylococcus aureus that evades immunomodulation of blood-derived leukocytes. AAPS J. 2015 May;17(3):620-30.

Hall RG 2nd, Michaels HN. Profi le of tedizolid phosphate and its potential in the treatment of acute bacterial skin and skin structure infections. Infect Drug Resist. 2015 Apr 22;8:75-82.

Hamada Y, Sutherland CA, Nicolau DP. Impact of revised cefepime CLSI breakpoints on Escherichia coli and Klebsiella pneumoniae susceptibility and potential impact if applied to Pseudomonas aeruginosa. J Clin Microbiol. 2015 May;53(5):1712-4.

Hong J, Krop LC, Johns T, Pai MP. Individualized vancomycin dosing in obese patients: a two-sample measurement approach improves target attainment. Pharmacotherapy. 2015 May;35(5):455-63.

Kuti JL, Nicolau DP. Presence of infection infl uences the epithelial lining fl uid penetration of oral levofl oxacin in adult patients. Int J Antimicrob Agents. 2015 May;45(5):512-8.

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: profi ling the time course of synergistic killing and prevention of resis-tance. J Antimicrob Chemother. 2015 May;70(5):1434-42.

Reyes J, Panesso D, Tran TT, Mishra NN, Cruz MR, Munita JM, Singh KV, Yeaman MR, Murray BE, Shamoo Y, Garsin D, Bayer AS, Arias CA. A liaR deletion restores susceptibility to daptomycin and antimicrobial peptides in multidrug-resistant Enterococcus faecalis. J Infect Dis. 2015 Apr 15; 211(8):1317-25.

Smith JR, Barber KE, Raut A, Aboutaleb M, Sakoulas G, Rybak MJ. β-Lactam combinations with daptomycin provide synergy against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium. J Antimicrob Chemother. 2015 Jun;70(6):1738-43.

Smith JR, Barber KE, Raut A, Rybak MJ. β-Lactams enhance daptomycin activity against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium in in vitro pharmacokinetic/pharmacodynamic models. Antimicrob Agents Chemother. 2015 May;59(5):2842-8.

Sutherland CA, Nicolau DP. Susceptibility profi le of ceftolozane/tazobactam and other parenteral antimicrobials against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa from US hospitals. Clin Ther. 2015 Jul 1;37(7):1564-71.

12

Tam VH, Ledesma KR, Bowers DR, Zhou J, Truong LD. Kidney injury associated with telavancin dosing regimen in an animal model. Antimicrob Agents Chemother. 2015 May;59(5):2930-3.

Tomaras AP, Crandon JL, McPherson CJ, Nicolau DP. Potentiation of antibacterial activity of the MB-1 siderophore-monobactam conjugate using an effl ux pump inhibitor. Antimicrob Agents Chemother. 2015 Apr;59(4):2439-42.

Wiederhold NP, Najvar LK, Matsumoto S, Bocanegra RA, Herrera ML, Wickes BL, Kirkpatrick WR, Patterson TF. Effi cacy of the investigational echinocandin ASP9726 in a guinea pig model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2015 May;59(5):2875-81.

Worboys PD, Wong SL, Barriere SL. Pharmacokinetics of intravenous telavancin in healthy subjects with varying degrees of renal impairment. Eur J Clin Pharmacol. 2015 Jun;71(6):707-14.

Clinical Research

Argamany JR, Aitken SL, Lee GC, Boyd NK, Reveles KR. Regional and seasonal variation in Clostridium diffi cile infections among hospitalized patients in the United States, 2001-2010. Am J Infect Control. 2015 May 1;43(5):435-40.

Arnold CJ, Johnson M, Bayer AS, Bradley S, Giannitsioti E, Miró JM, Tornos P, Tattevin P, Strahilevitz J, Spelman D, Athan E, Nacinovich F, Fortes CQ, Lamas C, Barsic B, Fernández-Hidalgo N, Muñoz P, Chu VH. Candida infective endocarditis: an observational cohort study with a focus on therapy. Antimicrob Agents Chemother. 2015 Apr;59(4):2365-73.

Bass SN, Lam SW, Bauer SR, Neuner EA. Comparison of oral vancomycin capsule and solution for treatment of initial episode of severe Clostridium diffi cile infection. J Pharm Pract. 2015 Apr;28(2):183-8.

Bassetti M, De Waele JJ, Eggimann P, Garnacho-Montero J, Kahlmeter G, Menichetti F, Nicolau DP, Paiva JA, Tumbarello M, Welte T, Wilcox M, Zahar JR, Poulakou G. Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria. Intensive Care Med. 2015 May;41(5):776-95.

Claeys KC, Lagnf AM, Patel TB, Jacob MG, Davis SL, Rybak MJ. Acute bacterial skin and skin structure infections treated with intravenous antibiotics in the emergency department or observational unit: experience at the Detroit Medical Center. Infect Dis Ther. 2015 Jun;4(2):173-86.

Claeys KC, Smith JR, Casapao AM, Mynatt RP, Avery L, Shroff A, Yamamura D, Davis SL, Rybak MJ. Impact of the combination of daptomycin and trimethoprim-sulfamethoxazole on clinical outcomes in methicillin-resistant Staphylococcus aureus infections. Antimicrob Agents Chemother. 2015 Apr;59(4):1969-76.

DiMondi VP, Townsend ML, Drew RH. Risk factors associated with unfavorable short-term treatment outcome in patients with documented Pseudomonas aeruginosa infection. Int J Clin Pharm. 2015 Apr;37(2):348-54.

Dubrovskaya Y, Prasad N, Lee Y, Esaian D, Figueroa DA, Tam VH. Risk factors for nephrotoxicity onset associated with polymyxin B therapy. J Antimicrob Chemother. 2015 Jun;70(6):1903-7.

Durham SH, Simmons ML, Mulherin DW, Foland JA. An evaluation of vancomycin dosing for complicated infections in pediatric patients. Hosp Pediatr. 2015 May;5(5):276-81.

Farmer AR, Murray CK, Driscoll IR, Wickes BL, Wiederhold N, Sutton DA, Sanders C, Mende K, Enniss B, Feig J, Ganesan A, Rini EA, Vento TJ. Combat-related Pythium aphanidermatum invasive wound infection: case report and discussion of utility of molecular diagnostics. J Clin Microbiol. 2015 Jun;53(6):1968-75.

Flannery AH, Bachmeier H. Vancomycin-associated nephrotoxicity: unintentional consequences of a loading dose? Crit Care Med. 2015 May;43(5):e154.

Gomes DM, Ward KE, LaPlante KL. Clinical implications of vancomycin heteroresistant and intermediately susceptible Staphylococcus aureus. Pharmacotherapy. 2015 Apr;35(4):424-32.

Le J, Capparelli EV, Wahid U, Wu YS, Romanowski GL, Tran TM, Nguyen A, Bradley JS. Bayesian estimation of vancomycin pharmacokinetics in obese children: matched case-control study. Clin Ther. 2015 Jun 1;37(6):1340-51.

Li C, Gubbins PO, Chen GJ. Prior pneumococcal and infl uenza vaccinations and in-hospital outcomes for community-acquired pneumonia in elderly veterans. J Hosp Med. 2015 May;10(5):287-93.

13

Long AJ, Worzella SL, Moran JJ, Hayney MS. Infl uenza vaccine antibody response and 6-Month persistence in lung transplant recipients using two defi nitions of seroprotection. Transplantation. 2015 Apr;99(4):885-9.

Madaras-Kelly K, Jones M, Remington R, Caplinger C, Huttner B, Samore M. Description and validation of a spectrum score method to measure antimicrobial de-escalation in healthcare associated pneumonia from electronic medical records data. BMC Infect Dis. 2015 Apr 25;15(1):197.

Maggio L, Nicolau DP, DaCosta M, Rouse DJ, Hughes BL. Cefazolin prophylaxis in obese women undergoing cesarean delivery: a randomized controlled trial. Obstet Gynecol. 2015 May;125(5):1205-10.

McClellan N, Swanson JM, Magnotti LJ, Griffi th TW, Wood GC, Croce MA, Boucher BA, Mueller EW, Fabian TC. Adjunctive intraventricular antibiotic therapy for bacterial central nervous system infections in critically ill patients with traumatic brain injury. Ann Pharmacother. 2015 May;49(5):515-22.

Morrill HJ, Pogue JM, Kaye KS, LaPlante KL. Treatment options for carbapenem-resistant Enterobacteriaceae infections. Open Forum Infect Dis. 2015 May 5;2(2):ofv050.

Na X, Martin AJ, Sethi S, Kyne L, Garey KW, Flores SW, Hu M, Shah DN, Shields K, Leffl er DA, Kelly CP. A multi-center prospective derivation and validation of a clinical prediction tool for severe Clostridium diffi cile infection. PLoS One. 2015 Apr 23;10(4):e0123405.

Nichols KR, Karmire LC, Cox EG, Kays MB, Knoderer CA. Implementing extended-infusion cefepime as standard of care in a children's hospital: a prospective descriptive study. Ann Pharmacother. 2015 Apr;49(4):419-26.

Patel K, Crumby AS, Maples HD. Balancing vancomycin effi cacy and nephrotoxicity: Should we be aiming for trough or AUC/MIC? Paediatr Drugs. 2015 Apr;17(2):97-103.

Pollack CV Jr, Amin A, Ford WT Jr, Finley R, Kaye KS, Nguyen HH, Rybak MJ, Talan D.Acute bacterial skin and skin structure infections (ABSSSI): practice guidelines for management and care transitions in the emergency department and hospital. J Emerg Med. 2015 Apr;48(4):508-19.

Qureshi ZA, Hittle LE, O'Hara JA, Rivera JI, Syed A, Shields RK, Pasculle AW, Ernst RK, Doi Y. Colistin-resistant Acinetobacter baumannii: beyond carbapenem resistance. Clin Infect Dis. 2015 May 1;60(9):1295-303.

Rhodes NJ, Liu J, McLaughlin MM, Qi C, Scheetz MH. Evaluation of clinical outcomes in patients with Gram-negative blood-stream infections according to cefepime MIC. Diagn Microbiol Infect Dis. 2015 Jun;82(2):165-71.

Sakoulas G, Nonejuie P, Kullar R, Pogliano J, Rybak MJ, Nizet V. Examining the use of ceftaroline in the treatment of Streptococcus pneumoniae meningitis with reference to human cathelicidin LL-37. Antimicrob Agents Chemother. 2015 Apr;59(4):2428-31.

Sharpe JP, Magnotti LJ, Weinberg JA, Swanson JM, Wood GC, Fabian TC, Croce MA. Impact of pathogen-directed antimicrobial therapy for ventilator-associated pneumonia in trauma patients on charges and recurrence. J Am Coll Surg. 2015 Apr; 220(4):489-95.

Tamma PD, Han JH, Rock C, Harris AD, Lautenbach E, Hsu AJ, Avdic E, Cosgrove SE; Antibacterial Resistance Leadership Group. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia. Clin Infect Dis. 2015 May 1;60(9):1319-25.

Werth BJ, Carreno JJ, Reveles KR. Shifting trends in the incidence of Pseudomonas aeruginosa septicemia in hospitalized adults in the United States from 1996-2010. Am J Infect Control. 2015 May 1;43(5):465-8.

Wisdom A, Eaton V, Gordon D, Daniel S, Woodman R, Phillips C. INITIAT-E.D.: Impact of timing of INITIation of antibiotic therapy on mortality of patients presenting to an emergency department with sepsis. Emerg Med Australas. 2015 Jun;27(3):196-201.

Yu H, Chen K, Wu J, Yang Z, Shi L, Barlow LL, Aronoff DM, Garey KW, Savidge TC, von Rosenvinge EC, Kelly CP, Feng H. Identifi cation of toxemia in patients with Clostridium diffi cile infection. PLoS One. 2015 Apr 17;10(4):e0124235.

14

HIVAgot K, Taylor D, Corneli AL, Wang M, Ambia J, Kashuba AD, Parker C, Lemons A, Malahleha M, Lombaard J, Van Damme L. Accuracy of self-report and pill-count measures of adherence in the FEM-PrEP clinical trial: implications for future HIV-prevention trials. AIDS Behav. 2015 May;19(5):743-51.

Conrad C, Bradley HM, Broz D, Buddha S, Chapman EL, Galang RR, Hillman D, Hon J, Hoover KW, Patel MR, Perez A, Peters PJ, Pontones P, Roseberry JC, Sandoval M, Shields J, Walthall J, Waterhouse D, Weidle PJ, Wu H, Duwve JM; Centers for Disease Control and Prevention (CDC). Community outbreak of HIV infection linked to injection drug use of oxymorphone--Indiana, 2015. MMWR Morb Mortal Wkly Rep. 2015 May 1;64(16):443-4.

Date AA, Shibata A, Bruck P, Destache CJ. Development and validation of a simple and isocratic reversed-phase HPLC method for the determination of rilpivirine from tablets, nanoparticles and HeLa cell lysates. Biomed Chromatogr. 2015 May;29(5):709-15.

Holtzman CW, Brady KA, Yehia BR. Retention in care and medication adherence: current challenges to antiretroviral therapy success. Drugs. 2015 Apr;75(5):445-54.

Looney D, Ma A, Johns S. HIV therapy-the state of art. Curr Top Microbiol Immunol. 2015;389:1-29. Review.

Nicol MR, Fedoriw Y, Mathews M, Prince HM, Patterson KB, Geller E, Mollan K, Mathews S, Kroetz DL, Kashuba AD. Expression of six drug transporters in vaginal, cervical, and colorectal tissues: Implications for drug disposition in HIV prevention. J Clin Pharmacol. 2014 May;54(5):574-83.

McLaughlin MM, Ammar AT, Gerzenshtein L, Scarsi KK. Dosing nucleoside reverse transcriptase inhibitors in adults receiving continuous veno-venous hemofi ltration. Clin Drug Investig. 2015 Apr;35(4):275-80.

Nicol MR, Emerson CW, Prince HM, Nelson JA, Fedoriw Y, Sykes C, Geller EJ, Patterson KB, Cohen MS, Kashuba AD. Models for predicting eff ective HIV chemoprevention in women. J Acquir Immune Defi c Syndr. 2015 Apr 1;68(4):369-76.

Oramasionwu CU, Johnson TL, Zule WA, Carda-Auten J, Golin CE. Using pharmacies in a structural intervention to distribute low dead space syringes to reduce HIV and HCV transmission in people who inject drugs. Am J Public Health. 2015 Jun;105(6):1066-71.

Rahangdale L, De Paris K, Kashuba AD, Nelson JA, Cottrell M, Sykes C, Emerson C, Young SL, Stevens T, Patterson KB, Cohen MS. Immunologic, virologic, and pharmacologic characterization of the female upper genital tract in HIV-infected women. J Acquir Immune Defi c Syndr. 2015 Apr 1;68(4):420-4.

Sabo JP, Kort J, Ballow C, Kashuba AD, Haschke M, Battegay M, Girlich B, Ting N, Lang B, Zhang W, Cooper C, O'Brien D, Seibert E, Chan TS, Tweedie D, Li Y. Interactions of the hepatitis C virus protease inhibitor faldaprevir with cytochrome P450 enzymes: in vitro and in vivo correlation. J Clin Pharmacol. 2015 Apr;55(4):467-77.

Slim J, Jimenez H, Culshaw D, Patel H, Lamp KC. Daptomycin experience in patients with human immunodefi ciency virus and resistant gram-positive infections. J Int Assoc Provid AIDS Care. 2015 May;14(3):202-6.

Thompson CG, Bokhart MT, Sykes C, Adamson L, Fedoriw Y, Luciw PA, Muddiman DC, Kashuba AD, Rosen EP. Mass spectrometry imaging reveals heterogeneous efavirenz distribution within putative HIV reservoirs. Antimicrob Agents Chemother. 2015 May;59(5):2944-8.

Yehia BR, Stewart L, Momplaisir F, Mody A, Holtzman CW, Jacobs LM, Hines J, Mounzer K, Glanz K, Metlay JP, Shea JA. Barriers and facilitators to patient retention in HIV care. BMC Infect Dis. 2015 Jun 28;15:246.

OtherAllen D, Wilson D, Drew R, Perfect J. Azole antifungals: 35 years of invasive fungal infection management. Expert Rev Anti Infect Ther. 2015 Jun;13(6):787-98.

American College of Clinical Pharmacy, McBane SE, Dopp AL, Abe A, Benavides S, Chester EA, Dixon DL, Dunn M, Johnson MD, Nigro SJ, Rothrock-Christian T, Schwartz AH, Thrasher K, Walker S. Collaborative drug therapy management and comprehensive medication management-2015. Pharmacotherapy. 2015 Apr;35(4):e39-50.

15

Au TH, Destache CJ, Vivekanandan R. Hepatitis C therapy: looking toward interferon-sparing regimens. J Am Pharm Assoc (2003). 2015 Mar-Apr;55(2):e72-84.

Baek VS, Hurren J, Edwin SB. Evaluation of procedure-related bleeding risk in patients receiving bivalirudin during percutaneous coronary intervention. Ann Pharmacother. 2015 Apr;49(4):427-30.

Bader MS, Brooks AA, Srigley JA. Postexposure management of healthcare personnel to infectious diseases. Hosp Pract (1995). 2015 Apr;43(2):107-27.

Boddu SH, Bonam SP, Jung R. Development and characterization of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery. Drug Dev Ind Pharm. 2015 Apr;41(4):605-12.

Cho JC, Fiorenza MA, Estrada SJ. Ceftolozane/Tazobactam: a novel cephalosporin/β-lactamase inhibitor combination. Pharmacotherapy. 2015 Jul;35(7):701-15.

Cho JC, Armitstead JA. 30/60/10 Rule of eff ective performance planning. J Am Pharm Assoc (2003). 2015 Mar-Apr;55(2):120-2.

Clay PG. Caring for the boomers. J Am Pharm Assoc (2003). 2015 May-Jun;55(3):336.

Clay PG. Transitions of care programs with pharmacists continue to demonstrate benefi t. J Am Pharm Assoc (2003). 2015 Mar-Apr;55(2):224.

Donnelly K, Waltzek TB, Wellehan JF Jr, Sutton DA, Wiederhold NP, Stacy BA. Phaeohyphomycosis resulting in obstructive tracheitis in three green sea turtles Chelonia mydas stranded along the Florida coast. Dis Aquat Organ. 2015 Apr 8;113(3):257-62.

Enwere EN, Lin YH, Morell JA, Childs-Kean LM. ASHP Connect community. Am J Health Syst Pharm. 2015 Jun 15;72(12):1002-5.

Goff DA, Kullar R, Newland JG. Review of twitter for infectious diseases clinicians: useful or a waste of time? Clin Infect Dis. 2015 May 15;60(10):1533-40.

Hall Snyder A, Werth BJ, Barber KE, Sakoulas G, Rybak MJ. Comment on: Failure of combination therapy with daptomycin and synergistic ceftriaxone for enterococcal endocarditis. J Antimicrob Chemother. 2015 Apr; 70(4):1272-3.

Hammond DA, Smotherman C, Jankowski CA, Tan S, Osian O, Kraemer D, DeLosSantos M. Short-course of ranolazine prevents postoperative atrial fi brillation following coronary artery bypass grafting and valve surgeries. Clin Res Cardiol. 2015 May;104(5):410-7.

Khalil D, Boktor M, Mortensen EM, Frei CR, Mansi I. Comparison of frequency of infl ammatory bowel disease and noninfectious gastroenteritis among statin users versus nonusers. Am J Cardiol. 2015 May 15;115(10):1396-401.

Kilic A, Alam MJ, Tisdel NL, Shah DN, Yapar M, Lasco TM, Garey KW. Multiplex real-time PCR method for simultaneous identifi cation and toxigenic type characterization of Clostridium diffi cile from stool samples. Ann Lab Med. 2015 May;35(3):306-13.

Kremer JM, Kivitz AJ, Simon-Campos JA, Nasonov EL, Tony HP, Lee SK, Vlahos B, Hammond C, Bukowski J, Li H, Schulman SL, Raber S, Zuckerman A, Isaacs JD. Evaluation of the eff ect of tofacitinib on measured glomerular fi ltration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial. Arthritis Res Ther. 2015 Apr 6;17:95.

Maher JR, Chuchuen O, Henderson MH, Kim S, Rinehart MT, Kashuba AD, Wax A, Katz DF. Co-localized confocal Raman spectroscopy and optical coherence tomography (CRS-OCT) for depth-resolved analyte detection in tissue. Biomed Opt Express. 2015 May 8;6(6):2022-35.

Martinson JN, Broadaway S, Lohman E, Johnson C, Alam MJ, Khaleduzzaman M, Garey KW, Schlackman J, Young VB, Santhosh K, Rao K, Lyons RH Jr, Walk ST. Evaluation of portability and cost of a fl uorescent PCR ribotyping protocol for Clostridium diffi cile epidemiology. J Clin Microbiol. 2015 Apr;53(4):1192-7.

McLaughlin MM, Skoglund EW. Drug shortages and patient safety: an overview of essential information for the infusion nurse. J Infus Nurs. 2015 May-Jun;38(3):205-8.

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Mor V, Rella A, Farnoud AM, Singh A, Munshi M, Bryan A, Naseem S, Konopka JB, Ojima I, Bullesbach E, Ashbaugh A, Linke MJ, Cushion M, Collins M, Ananthula HK, Sallans L, Desai PB, Wiederhold NP, Fothergill AW, Kirkpatrick WR, Patterson T, Wong LH, Sinha S, Giaever G, Nislow C, Flaherty P, Pan X, Cesar GV, de Melo Tavares P, Frases S, Miranda K, Rodrigues ML, Luberto C, Nimrichter L, Del Poeta M. Identifi cation of a new class of antifungals targeting the synthesis of fungal sphingolipids. MBio. 2015 Jun 23;6(3):e00647.

Morrill HJ, LaPlante KL. Comment on: Overconsumption of antibiotics. Lancet Infect Dis. 2015 Apr;15(4):377-8.

O'Dowd H, Shannon DE, Chandupatla KR, Dixit V, Engtrakul JJ, Ye Z, Jones SM, O'Brien CF, Nicolau DP, Tessier PR, Crandon JL, Song B, Macikenas D, Hanzelka BL, Le Tiran A, Bennani YL, Charifson PS, Grillot AL. Discovery and characterization of a water-soluble prodrug of a dual inhibitor of bacterial DNA gyrase and topoisomerase IV. ACS Med Chem Lett. 2015 Jun 22;6(7):822-6.

Payk SL, Drew RH, Smith JD, Jiroutek MR, Holland MA. Sulfonylurea prescribing patterns after the introduction of DPP-4 inhibitors and GLP-1 receptor agonists. Clin Ther. 2015 Jul 1;37(7):1477-1482.e1.

Philip A, Gessner-Wharton M, Birney P, Blee J, Desai A, Gorbach C, Karralli R, Lorimer D, Munch K, Nweke G, Parekh S, Puebla M, Cox R, Pitman EP, Garey KW. Pharmacy Practice Model Initiative task force report: improving participation in a survey on hospital pharmacy practices in Texas. Am J Health Syst Pharm. 2015 Jun 15;72(12):1053-7.

Philip A, Green M, Hoff man T, Gautreaux S, Wallace D, Roux R, Garey KW. Expansion of clinical pharmacy through increased use of outpatient pharmacists for anticoagulation services. Am J Health Syst Pharm. 2015 Apr 1;72(7):568-72.

Potashman MH, Formella DN, Hamed K, Mohr JF. Comment on: Effi cacy and safety of daptomycin for the treatment of infectious disease: a meta-analysis based on randomized controlled trials. J Antimicrob Chemother. 2015 Apr;70(4):1274-5.

Raber S, Mandema JW, Li H, Nickens DJ. A model-based dose-response meta-analysis of ocular hypotensive agents as a drug development tool to evaluate new therapies in glaucoma. J Ocul Pharmacol Ther. 2015 May;31(4):189-97.

Raub JN, Thurston TM, Fiorvento AD, Mynatt RP, Wilson SS. Implementation and outcomes of a pharmacy residency mentorship program. Am J Health Syst Pharm. 2015 Jun 1;72(11 Suppl 1):S1-5.

Sandoval-Denis M, Gené J, Sutton DA, Wiederhold NP, Guarro J. Acrophialophora, a poorly known fungus with clinical signifi cance. J Clin Microbiol. 2015 May;53(5):1549-55.

Schumock GT, Li EC, Suda KJ, Wiest MD, Stubbings J, Matusiak LM, Hunkler RJ, Vermeulen LC. National trends in prescription drug expenditures and projections for 2015. Am J Health Syst Pharm. 2015 May 1;72(9):717-36.

Tran TT, Palmer HR, Weimar MR, Arias CA, Cook GM, Murray BE. Oral bacitracin: A consideration for suppression of intestinal vancomycin-resistant enterococci (VRE) and for VRE bacteremia from an apparent gastrointestinal tract source. Clin Infect Dis. 2015 Jun 1;60(11):1726-8.

17

DG, a 62 year old female, has an extensive past medical history notable for metastatic esthesio-neuroblastoma (diagnosed in 1998), recurrent chronic sinusitis, seizures attributed to beta-lactam antibiotic exposure, chronic thrombotic thrombocytopenic purpura, migraines, and chronic dip-loplia. Since the time of neuroblastoma diagnosis, the patient has undergone multiple neurosur-gical procedures and sinus cavity operations, and experienced subsequent episodes of sinusitis and meningitis. She was hospitalized approximately two weeks prior to this currently discussed admission, and diagnosed with a severe sinus infection and meningitis. Cultures obtained from the patient’s sinus cavity demonstrated Pseudomonas aeruginosa and she was treated with mero-penem (minimum inhibitory concentration [MIC] unknown from outside hospital). DG was stable enough to be discharged but then was quickly re-admitted to an outside hospital with increasing confusion; meropenem was restarted.

After two days at the outside hospital, DG was transferred to our hospital where meropenem treatment was continued. An MRI of the brain revealed structural changes noting that the midface/paranasal sinus cavity was now directly contiguous with intracranial compartment secondary to bone erosion, as well as rim-enhancing fl uid collections in the left frontal lobe which were sugges-tive of an intracranial abscess. Neurosurgery performed a bifrontal craniotomy with reconstruction of the anterior fossa fl oor and left frontal abscess evacuation. Initial gram stain of the brain tissue specimen revealed Gram-positive cocci and Gram-negative rods, and vancomycin was added to the antimicrobial regimen. Final brain tissue cultures revealed moderate multi-drug resistant Pseudomonas aeruginosa (Table 1) and moderate Staphylococcus epidermidis.

Page CrewPharmDPGY-2 ID ResidentMidwestern University, Chicago College of PharmacyNorthwestern Memorial Hospital Elise GilbertPharmD, BCPSAssistant ProfessorChicago State UniversityID Clinical PharmacistNorthwestern Memorial Hospital Viktorija BarrPharmD, BCPSAssistant ProfessorRosalind Franklin UniversityID Clinical PharmacistNorthwestern Memorial Hospital

Ceftolozane/Tazobactam For CNS Infection

Pseudomonas aeruginosa

Antimicrobial Agent MIC in mcg/mL Kirby-Bauer

Amikacin 8

Aztreonam R

Cefepime ≥ 64

Ceftazidime R

Ciprofl oxacin 2

Colistin 3 (E-test)

Gentamicin 8

Meropenem ≥ 16

Minocycline R

Piperacillin/tazobactam R

Tobramycin ≤ 1

Table 1 Brain Tissue Culture and Sensitivity Results of Pseudomonas aeruginosa isolate

+MICs determined using Vitek II unless otherwise noted

Following evaluation of the culture and susceptibilities, DG’s regimen was modifi ed to include meropenem and tobramycin for P. aeruginosa, and vancomycin for S. epidermidis. Although tobra-mycin CNS penetration is suboptimal with reported CSF/blood penetration of 0 to 30%, tobramycin was selected as part of the multi-drug regimen due to the favorable MIC.1 While the MIC for colistin suggests potential intermediate susceptibility, penetration of colistin in the CSF is approximately

18

5% thus precluding its use in this setting.2 In light of the resistance profi le of the P. aeruginosa isolate, and the patient’s history of treatment failure with meropenem, susceptibilities for ceftolozane/tazobactam were requested. The MIC for ceftolozane/tazobact-am was determined using an experimental E-test. The MIC was reported as 2 mcg/mL (breakpoint < or equal to 4/4 mcg/mL for P. aeruginosa).3

At Northwestern Memorial Hospital, ceftolozane/tazobactam has been approved onto formulary under restriction. Use is restricted to non-cystic fi brosis patients who have cultures demonstrating defi nitive multidrug resistant Pseudomonas aerugino-sa with known resistance to all available antibiotics and known susceptibility to ceftolozane/tazobactam. It is also approved for infection with defi nitive extended spectrum beta-lactamase (ESBL) producing organisms where there is known susceptibility to ceftolozane/tazobactam. Antimicrobial stewardship program (ASP) pharmacists are responsible for reviewing each request for ceftolozane/tazobactam and approving its use in appropriate clinical scenarios.

Currently, there are no published studies evaluating the CNS penetration of ceftolozane/tazobactam. While cephalosporins typically display poor CSF penetration, the minimum inhibitory concentrations are generally low enough that it is possible to achieve eff ective concentrations in CSF.4 Thus, in an eff ort to successfully treat this multi-drug resistant Pseudomonas infection, the ASP pharmacist recommended the use of ceftolozane/tazobactam 1.5 grams every 8 hours in combination with tobramycin.3

Ultimately, the patient was discharged on a defi nitive regimen of ceftolozane/tazobactam, tobramycin, and vancomycin for a 7 week course of therapy with planned reimaging after antibiotics were completed. About 1.5 weeks after all antibiotics were discon-tinued, the patient had an MRI which demonstrated a large left frontal lobe fl uid cavity with surrounding enhancement. She was readmitted to our institution, and had an abscess evacuation two days later. Intra-operative fl uid cultures did not show growth of any organisms. The patient was re-started on ceftolozane/tazobactam (as the single antimicrobial agent), this time at a higher dose of 3 grams every 8 hours, which is currently being studied for the treatment of pneumonia.5 At this time, the patient continues to receive ceftolozane/tazobactam, and will be treated for an indeterminate duration of time.

References:

1. Gilbert DN, Moellering RC Jr, Eliopoulos GM, Chambers HF, Saag MS, eds. The Sanford Guide to Antimicrobial Therapy, 39th ed. Sperryville, VA: Antimicrobial Therapy; 2009.

2. Markantonis SL, Markou N, Fousteri M, et al: Penetration of colistin into cerebrospinal fl uid. Antimicrob Agents Chemother 2009; 53(11):4907-4910.

3. Zerbaxa [package insert]. Lexington, MA: Cubist Pharmaceuticals; 2015.4. Lutsar I, Friedland IR. Pharmacokinetics and pharmacodynamics of cephalosporins in cerebrospinal fl uid. Clin Pharma-

cokinet. 2000 Nov; 39(5):335-43.5. Xiao AJ, Miller BW, Huntington JA, Nicolau DP. Ceftolozane/tazobactam pharmacokinetic/pharmacodynamics-derived

dose justifi cation for phase 3 studies in patients with nosocomial pneumonia. J Clin Pharmacol. 2015 Jun 10. doi: 10.1002/jcph.566. [Epub ahead of print]

Ceftolozane-tazobactam (Zerbaxa™, Merck & Co, Inc.) and ceftazidime-avi-bactam (Avycaz™, Actavis, Inc.) are beta-lactam/beta-lactamase inhibitor combinations recently approved by the U.S. FDA. Both are indicated as monotherapy for complicated urinary tract infections (cUTI), including py-elonephritis, and in combination with metronidazole for complicated intra-ab-dominal infections (cIAI).

Ceftolozane-tazobactam is a nov-el third-generation cephalosporin combined with tazobactam.1 Versus ceftazidime, it has increased activity against AmpC beta-lactamases, ex-tended-spectrum beta-lactamases (ES-BLs), and Pseudomonas aeruginosa, including multi-drug resistant (MDR) strains.2 It has no activity against car-bapenemases. Gram-positive and anaerobic activity is lim-ited.1,2 The normal dose is 1.5 g (1 g of ceftolozane and 0.5 g of tazobactam) is administered intravenously (IV) over 1 hour, every 8 hours. Dosage adjustment is required for cre-atinine clearance (ClCr) < 50 mL/min. Product information includes a warning regarding decreased clinical response in ClCr of 30-50 mL/min based on subgroup analyses of Phase III trials in cUTI and cIAI.3 Therapy duration is 7 days for cUTI and 4-14 days for cIAI. Adverse eff ects are similar to other cephalosporins and include nausea, diarrhea, head-ache, and pyrexia. It is listed in Pregnancy Category B.

In terms of clinical and microbiologic response, ceftolozane-tazobactam demonstrated non-inferiority and superiority compared to levofl oxacin in a Phase III trial of cUTI in 800 patients.4 Escherichia coli was the predomi-nant uropathogen and 82% of patients had pyelonephritis. Clinical cure rates for ESBLs were 90.2% and 73.7% for ceftolozane-tazobactam and levofl oxacin, respectively. In terms of clinical cure overall, ceftolozane-tazobactam plus metronidazole demonstrated non-inferiority compared to meropenem in a Phase III trial of cIAI in 806 patients.5 The appendix was the most common infection origin and E. coli was the predominant pathogen. Clinical cure rates for ES-BLs were 95.8% for ceftolozane-tazobactam plus metroni-dazole and 88.5% for meropenem. Clinical cure rates for P. aeruginosa were 100% and 93.1% for ceftolozane-tazobact-am plus metronidazole and meropenem, respectively.

Ceftazidime-avibactam is a combination of ceftazidime with a novel beta-lactamase inhibitor. Avibactam expands ceftazi-

dime’s spectrum to include many AmpC beta-lactamases, ESBLs, and Klebsiella pneumoniae carbapenemases (KPCs).6 The combination also demonstrated activity against meropenem non-suscep-tible Enterobacteriaceae. Compared to ceftazidime, increased activity against Pseudomonas aeruginosa has been shown, but is variable.7 It has no appre-ciable activity against anaerobic bacteria and Gram-positive activity is limited.6 Dosage adjustment is required for creat-inine clearance (ClCr) < 50 mL/min. The product information includes a warning regarding decreased clinical response in patients with ClCr of 30-50 mL/min based on results from a Phase III cIAI trial.8 The normal dose is 2.5 g (2 g of ceftazidime and 0.5 g of avibactam) administered IV over 2 hours, every 8 hours. Therapy duration is 7 to 14 days for cUTI and 5 to

14 days for cIAI. It is well-tolerated, with the most common adverse eff ects being nausea, vomiting, constipation, and anxiety. It is listed in Pregnancy Category B.

Phase III trials evaluating ceftazidime-avibactam have not yet been published. In a Phase II cUTI trial in 62 patients, a microbiological response was seen in 70.4% and 71.4% of patients in the ceftazidime-avibactam and imipen-em-cilastatin arms, respectively.9 Over half of patients had pyelonephritis and E. coli was the predominant uropatho-gen. Ceftazidime-avibactam eradicated 85.7% of ceftazi-dime-resistant pathogens isolated. In a Phase II cIAI study in 144 patients, clinical response was observed in 91.2% and 93.4% of patients in the ceftazidime-avibactam plus metronidazole and meropenem arms, respectively.10 The appendix was the most common infection origin and E. coli was the predominant pathogen. A microbiological response to ceftazidime-avibactam was observed in 96.2% of ceftazi-dime non-susceptible isolates.

Ceftolozane-tazobactam and ceftazidime-avibactam are useful additions to the Gram-negative antimicrobial ar-mamentarium. Both are eff ective for cUTI and cIAI; and, each has activity against certain resistant Gram-negative bacteria. Ceftolozane-tazobactam appears to be useful for MDR P. aeruginosa and many ESBLs. Ceftazidime-avibac-tam appears to be useful for ESBLs and KPCs. Questions remain regarding the impact of renal impairment on their effi cacy. Trials evaluating both in pediatrics, cystic fi brosis, and ventilator-associated pneumonia are in progress.

New Beta-Lactam/Beta-Lactamase Inhibitor Combina ons: ce olozane-tazobactam (Zerbaxa™)

and ce azidime-avibactam (Avycaz™)Winter J. Smith, Pharm.D., BCPS

18

References

1. Cho JC, Fiorenza MA, Estrada S. Ceftolozane/tazobactam: a novel cephalosporin/beta-lactamase inhibitor combination. Pharmacotherapy 2015;35(7):701-15.

2. Zhanel GG, Chung P, Adam H, et al. Ceftolozane/tazobactam: a novel cephalosporin/beta-lactamase inhibitor combination with activity against multidrug-resistant Gram-negative bacilli. Drugs 2014;74:31-51.

3. Merck & Co., Inc. Zerbaxa™ (ceftolozane/tazobactam) prescribing information. Whitehouse Station, NJ, 2015.

4. Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO. Ceftolozane-tazobactam compared with levofl oxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomized, double-blind, phase 3 trial (ASPECT-cUTI). Lancet 2015;385:1949-56.

5. Solomkin J, Hershberger E, Miller B, et al. Ceftolozane/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: results from a randomized, double-blind, Phase 3 trial (ASPECT-cIAI). Clin Infect Dis 2015;60(10):1462-71.

6. Zasowski EJ, Rybak JM, Rybak MJ. The beta-lactams strike back: ceftazidime-avibactam. Pharmacotherapy 2015;35(8):755.70.

7. Zhanel GG, Lawson CD, Adam H, et al. Ceftazidime-avibactam: a novel cephalosporin/beta-lactamase inhibitor combina-tion. Drugs 2013;73:159-77.

8. Forest Pharmaceuticals, Inc. Avycaz™ (ceftazidime/avibactam) prescribing information. Cincinnati, OH, 2015.

9. Vazquez JA, Gonzalez Patzan LD, Duttaroy DD, Kreidly Z, Sable C, Lipka J. Effi cacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospi-talized adults: results of a prospective, investigator-blinded, randomized study. Curr Med Res Opin 2012;28:1921-31.

10. Lucasti C, Popescu I, Ramesh MK, Lipka J, Sable C. Comparative study of the effi cacy and safety of ceftazidime/avi-bactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized double-blind, Phase II trial. J Antimicrob Chemother 2013; 68(5):1183-92.

19

Antibiotics in Agriculture: a Danger to Human Health and a Call to Action from the Society of Infectious Diseases Pharmacists

20

Samuel L. Aitken, Pharm.D.1, Thomas J. Dilworth, Pharm.D.2, Emily L. Heil, Pharm.D.3, and Michael D. Nailor, Pharm.D.4*1. Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX2. Department of Pharmacy, Wheaton Franciscan Healthcare – St. Francis, Milwaukee, WI

3. Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD4. Department of Pharmacy Services, Hartford Hospital, Hart-ford, CT and Department of Pharmacy Practice, University of Connecticut, Storrs, CT

Keywords: antifungals, growth promotion, resistance, farming, horticulture, aquaculture, antimicrobial stewardship

Running Head: Antibiotics in agriculture

Corresponding Author:*Michael D. NailorUniversity of Connecticut School of Pharmacy69 North Eagleville Rd, Unit 3092Storrs, CT 06269-3092Department of Pharmacy ServicesHartford Hospital80 Seymour StreetHartford CT 06102Phone: 860-972-2961Michael.Nailor@hhchealth.org

AbstractThe use of antibiotics in agriculture, particularly in food-pro-ducing animals, is pervasive and represents the overwhelming majority of antibiotic use worldwide. The link between antibiotic use in animals and antibiotic resistance in humans is unequiv-ocal. Transmission can occur through ingesting undercooked meats harboring resistant bacteria, be introduced through direct contact of animals by animal handlers, as well as other means. Antibiotics in aquaculture and antifungals in horticulture also represent an evolving threat. Regulations aimed at decreasing the amount of antibiotics used in food production in order to lim-it the development of antibiotic resistance have recently been implemented. However, further action is needed to minimize antibiotic use in agriculture. This manuscript describes the ex-tent of this current problem and serves as the offi cial position of the Society of Infectious Diseases Pharmacists on this urgent threat to human health.

A AThe introduction of antibiotics revolutionized modern medicine. Antibiotics not only provide a treatment option for patients with an active infection but also allow modern medical techniques with frequent infectious complications to be safely performed. Without eff ective antibiotics myelosuppressive chemotherapy, organ transplantation, basic surgery, and invasive techniques ( e.g. endotracheal intubation or implantation of cardiac devic-es) would not be feasible.1 Thus, the growing rate of antibiotic resistance has been cited as a top threat to global health with almost all facets of medical care potentially aff ected. Eff orts to bring novel antibiotics to the market, increase infection control eff orts, and enhance antimicrobial stewardship eff orts have so far not turned the tide. Unfortunately, the majority of antibiot-ic use falls outside the purview of medical care, and instead occurs overwhelmingly in agriculture and aquaculture and thus requires increased attention.

In the early twentieth century, farmers struggled to meet dra-matically increasing consumer demands for meat and meat products. In 1950, a study performed by American Cyanamid found that adding antibiotics to livestock feed accelerated ani-mal growth rates and “[blew] the lid clear off the realm of animal nutrition” per the editors of Successful Farming magazine.2 Shortly after this publication antibiotics started to be used more widespread for growth promotion and routine disease pre-vention. Notably absent was a corresponding editorial on the impact of this practice could have on antibiotics used in human medicine.

More than a decade after antibiotics began to be used in ag-riculture for non-therapeutic purposes, an editorial in the New England Journal of Medicine in 1966 warned of the reality of antibiotic resistance and the Swann Report of 1969 brought to light the possible dangers to the human population stemming from the use of antibiotics in food animal production.3, 4 Over the years, data linking routine, non-therapeutic use of antibi-otics in agriculture to antibiotic resistance has accumulated. A key turning point occurred in 2010, when the United States (U.S.) Food and Drug Administration (FDA), U.S. Department of Agriculture (USDA), and the Centers for Disease Control and Prevention (CDC) all testifi ed before the U.S. Congress that there is a defi nitive link between this non-therapeutic use of an-tibiotics in food animal production and the antibiotic resistance crisis in humans.5

Despite signifi cant warnings and evidence of harm, antibiot-ics continue to be used routinely in animal agriculture for the purposes of growth promotion, feed effi ciency, and disease prevention. Moreover, current antibiotic use in agriculture dra-matically exceeds antibiotic use in humans, with approximately

21

80% of antibiotics consumed annually in the U.S. being used for agricultural purposes (see Figure 1).6 The Animal Drug User Fee Amendments of 2008 (ADUFA 105) requires the FDA to issue an annual report of sales and distribution data for anti-microbials used in food-producing animals. Sales and distri-bution of medically important antimicrobials increased in the U.S. by 20% from 2009 to 2013 with over 9 million kilograms of medically important antimicrobial drugs sold in 2013. The vast majority, an estimated 95%, of these antibiotics was for use in food animals’ feed and water. Furthermore, the majority of sales of medically important antimicrobials (Table 1) were sold over-the-counter without any veterinary oversight.7

Our interconnected society and health system facilitates the global spread of resistance mechanisms and antibiotic resistant organisms originating from agricultural practice. An understand-ing of these interactions can improve patient care by reducing infections caused by these organisms and guide consumers and policy makers to minimize non-therapeutic uses of these important agents. This review highlights evidence supporting the harm of non-therapeutic use of antibiotics in agriculture and serves as an offi cial position statement of the Society of Infectious Diseases Pharmacists on antibiotic use in agriculture (Table 2). Specifi cally, this review will describe the nature of common mechanisms of antibiotic resistance, how resistance mechanisms can move from animals to humans, links between animal antibiotic resistance and human health, and the poten-tial eff ects of antibiotics used in animals on human health out-side of antibiotic resistance. Lastly, the review will discuss how antimicrobials currently being used in non-animal agriculture may also be aff ecting human health. For update information re-garding public policy and action both within the US and globally, please see Table 3.

T I A H – R U CAntibiotics used in animal feed can be generally classifi ed into two categories – ionophore and non-ionophore antibiotics. The ionophore antibiotics have no current use in human medicine and are mainly used to increase feed effi ciency, a measure of how well animals convert feed into body mass or milk. Mecha-nistically they can transport cations and amines across biologi-cal membranes which disrupts cellular cation gradients, arrest-ing bacterial and fungal cell growth and inducing cell death. 8 The non-ionophore antibiotics, which are often the same antibiotics used in human medicine, improve feed effi ciency through a number of mechanisms including changes in volatile fatty acid ratios, changes in ammonia digestion, and by inhibit-ing lactic acid-producing bacteria with a subsequent decrease in the energy-intensive production of methane.8

While the exact mode of action for antibiotics in growth promo-tion is unknown, when given in subtherapeutic doses, antibi-otics can increase the feed effi ciency and promote growth via alterations of the animal’s microfl ora. Suppressing commensal bacteria that would otherwise divert nutrition from the animal maintains a more eff ective and absorptive gut lining, allowing for greater returns in weight gain without providing any addition-al feed for the animals.3 Additionally, non-ionophore antibiotics have been used to increase feed effi ciency by maintaining ani-mal health by preventing infection in the intensive farm systems commonly seen in poultry and swine production. The extent to which antibiotics increase food production is dependent on a

number of variables including the diet which is fed to the ani-mals and the conditions in which the animal is raised.8 Changes in animal feed during the last few decades calls into question the extrapolation of early studies demonstrating a benefi t of antibiotics on food effi ciency. Contemporary studies have found only minimal eff ects of antibiotics on food effi ciency and poten-tially economically harmful after including the purchase price of the antimicrobial.9

To assess the potential impact of veterinary antimicrobial use on human health, an understanding of the medical importance of any antimicrobial that might be used in animals is of critical importance. In its Guidance for Industry (GFI) #152, “Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Eff ects on Bacteria of Human Health Con-cern” published in 2003, the FDA established classifi cations of the medical importance of diff erent antibiotics, classifying each agent as “important”, “highly important”, and “critically import-ant”.9 These categorizations take into account their therapeutic uses in humans, whether alternatives exist, cross-resistance both within drug classes and with other drug classes, and the relative diffi culty of the transmission of resistance elements. Additionally, this document provides a framework for assessing the overall risk to humans for each antimicrobial through qual-itative assessments of the risk of resistant bacteria developing in treated animals, the likelihood that humans would ingest the resistant bacteria, and, fi nally, the clinical consequences of hu-man exposure to resistant bacteria. Table 1 summarizes these antibiotic classifi cations.

Despite this framework, antibiotics deemed to be “critically important” for humans continue to be used as feed additives. Currently, antibiotics used as feed additives account for greater than 80% of all veterinary use of medically important antibiotics in the U.S.7 Furthermore, a 2014 study released by the National Resources Defense Council (NRDC) found of the 30 antibiotic feed additives currently marketed, none would be approved under current FDA guidance. Of these 30, 18 were classifi ed as “high risk” for the transmission of antibiotic resistance to humans.10 Additionally, resistance to certain antibiotics in one category may lead to cross-resistance with antibiotics in other categories as described below.

A , A R , A RRecognizing the structural similarity that exists between many antibiotics used in both agriculture and human health is funda-mental to understanding how resistance can spread from ani-mals to humans. Antibiotics in human medicine have tradition-ally been grouped into classes based on molecular similarity and mechanism of action. Many of these classes have at least one drug registered in the U.S. for use in animal feed while still other antibiotics and classes are used in other countries.11 Anti-biotic resistance mechanisms can also be grouped together. An initial classifi cation fi rst separates resistance into either intrinsic or acquired. As it relates to antibiotic resistance development in the animal food industry, acquired antibiotic resistance is a more concerning problem. Acquired resistance can be further divided into four fundamental categories: 1) preventing anti-biotic access to the target 2) modifying the antibiotic target 3) protecting the target site from interaction with the antibiotic, and 4) modifi cation of the antibiotic.12

22

The fi rst mechanism of resistance, preventing antibiotic ac-cess to the target, is achieved through two methods. The fi rst, reduced permeability of the drug into the cell, generally results from reduction in the number of outer-membrane porins, which act as channels for antibiotics to pass into the cell. This mech-anism can produce non-susceptibility by itself or it can combine with other resistance mechanism(s) to produce signifi cant re-sistance.13 An example of this is the combination of decreased porin expression with β-lactamases leading to carbapenem resistance in Enterobacteriaceae. As porins may facilitate the entry of multiple classes of antibiotics into the cell, decreased porin expression can result in cross-class resistance, such as combined fl uoroquinolone and carbapenem resistance. The second mechanism that results in decreased antibacterial ac-cess to the target are changes in effl ux pump selectivity and ac-tivity.13 Although many bacterial species express effl ux pumps as intrinsic resistance mechanisms, plasmids may also carry genes encoding for the effl ux of numerous antibiotics leading to multi-drug resistance. Expression of a variety of diff erent pumps can be regulated by various stress factors, including low-level antibiotic exposure.14

The second major mechanism of acquired drug resistance, modifying the antibiotic target, leads to some of the most im-portant examples of antibacterial resistance in Streptococcus pneumoniae and Staphylococcus aureus. The mecA gene, for example, encodes for a penicillin binding protein (PBP-2a) that has dramatically reduced binding to most β-lactam antibiotics and leads to methicillin-resistance in staphylococci.13 A recently discovered variant of mecA, mecC, has been identifi ed. mecC produces a broad-spectrum β-lactam resistance phenotype as well as a diagnostic challenge as mecC is not detected by mecA PCR or mecA PBP-2a latex agglutination assays.15 This resistance element was fi rst described in milk samples from cattle with mastitis in England. Subsequently, over half of MRSA isolates from human sources in Denmark, Scotland, and England that did not harbor mecA were found to carry mecC.16

The third major mechanism of acquired resistance is the protection of the target site from the antibiotic. As with the mechanisms discussed above, many of these clinically relevant examples have been known to be transferred across species. Resistance to macrolides, lincosamides (including clindamycin), and streptogramins can be produced through acquisition of the erythromycin ribosomone methylase (erm). This mechanism alters the bacterial ribosome preventing binding of these three drug classes. Fluoroquinolone resistance can be produced by qnr resistance genes. This mechanism produces pentapeptide repeat proteins (PRPs) on topoisomerase IV that promotes the release of the bound fl uoroquinolone.13

Lastly, direct modifi cation of antibiotics has been demonstrat-ed to occur to several diff erent antibiotic classes. Perhaps the most important example of antibiotic modifi cation though is hydrolysis of β-lactam antibiotics by β-lactamase enzymes. Numerous classes of β-lactamases have described that have a variety of affi nities for medically important β-lactams. Over the last decade, β-lactamases have proliferated that encode for resistance to 3rd generation cephalosporins, β lactam-β lact-amase inhibitors, and carbapenems through numerous genet-ically diverse enzymes. These agents have traditionally been the last line of defense against gram-negative bacteria. Many of these resistant genes are now encoded on plasmids and able

to transfer between species.13

Bacteria have developed resistance mechanisms over thou-sands of millennia as they have competed against naturally produced antibiotics from other species or microorganisms to control their own ecological niches.17 Importantly, many of these mechanisms may confer resistance to synthetic antibiotic classes such as the fl uoroquinolones or oxazolidinones, without prior exposure.18 The genes that encode for these resistance mechanisms may then transfer via plasmids and spread among many species of bacteria.19 This transferable pool of resistance is called the antibiotic resistome and has important implications for human health.20 Given the non-specifi c mechanism of a number of resistance mechanisms such as effl ux pumps and reduced cell entry, resistance to one antibiotic class may lead to resistance to another, unrelated class. Additionally, since the resistance genes are already dispersed, it is unlikely that eradication will occur.

F –

The animal-to-human transfer of antibiotic resistant bacteria to humans through the consumption of contaminated food prod-ucts or by direct contact with animals or animal waste harboring antibiotic resistance are a signifi cant threat to human health. As such, human omnivores and vegetarians alike are susceptible to acquiring agriculture-developed antibiotic resistance. The fol-lowing summarizes highlights major antibiotic resistance trans-mission mechanisms and is graphically presented in Figure 221.

Direct transmissionIn the most straightforward cases, antibiotic resistance may be directly transmitted from farm animals to farmers and other an-imal handlers. The transmission of drug-resistant enterococci, including vancomycin-resistant enterococci (VRE), from broiler (i.e., domesticated chickens for meat production) hens to broiler farmers has been clearly documented in the Netherlands.22 Similar studies have documented the transmission of fl uoro-quinolone-resistant E. coli to poultry farmers23 and methicil-lin-resistant Staphylococcus aureus (MRSA) to pig farmers and their close contacts.24 Analogously to the spread of antibiotic resistance from human to human, antibiotic resistant bacteria may spread clonally from animal to handler or resistance genes may be horizontally transferred by mobile genetic elements. Additionally, several studies have demonstrated that generally uncommon bacterial strains or antibiotic resistance patterns, such as tetracycline-resistant S. aureus, may be highly preva-lent in farm animals and farm workers, but not the community at large.11, 25 These fi ndings suggest a strong epidemiologic link between antibiotic resistance in farm animals and transmission to humans with subsequent colonization.

Environmental contaminationIn addition to direct transmission from farm animals to their han-dlers, antibiotic resistant bacteria may spread beyond the farm animals and into the surrounding environment with a signifi cant impact on human health. Environmental sampling around a broiler farm, a large industrial farm for growing chickens, in Ger-many showed that extended-spectrum β-lactamase (ESBL) or AmpC-producing E. coli could be found in 86% of waste slurry samples and 7.5% of samples taken of ambient air.26Antibiotic resistant bacteria have also been shown to be more prevalent downwind, rather than upwind, of cattle feed yards.27 Further-

23

more, an estimated 2-3% of fl ies sampled at poultry farms in the Netherlands are carriers of ESBL E. coli¸ indicating the potential risk for vector-based dissemination of antibiotic-resis-tant bacteria.28 While most of the evidence regarding the harms to the surrounding community of antibiotic use in agriculture is largely theoretical, a population-based study conducted in cen-tral Pennsylvania linked proximity to high-intensity pig-farming to an increased risk of community-acquired MRSA infections.29

Additionally, the antibiotics used on farms may enter the sur-rounding environment through contaminated wastewater and persist indefi nitely, leading to natural selection pressure for anti-biotic resistance.30 A comprehensive literature review found that of the 61 most commonly recovered pharmaceutical products recovered from freshwater ecosystems worldwide, 24 (39%) were antibiotics.9 The highest median concentration of any drug examined in this review belonged to ciprofl oxacin; the median ciprofl oxacin concentration was 0.164 mg/L and the highest recorded ciprofl oxacin concentration was 6.5 mg/L, within the range expected of patients receiving therapeutic ciprofl oxacin.10 Among all antibiotics studied, the overall median concentration was 0.008 mg/L. While there are other more important sourc-es of antibiotic residues in the environment, including hospital wastewater and sewage, farm runoff remains a contributing factor to antibiotics in the environment.31

The spillover of antibiotic resistance into the surrounding en-vironment may also have unexpected eff ects. While antibiotic resistant pathogens can be identifi ed in agricultural soil sam-ples from diverse sources, multidrug resistance and high-lev-el antibiotic resistance are found almost exclusively in soil samples that have been exposed to manure originating from animals that have received antibiotics.32 In turn, certain antibiot-ic resistance elements may be found more frequently in vege-tables grown in the presence of manure.33 Although antibiotic resistance in manure has been linked to animals exposed to antibiotics, resistance has also been shown to bloom in manure derived from animals that have never been exposed to antibiot-ics, highlighting the complex interplay between natural resis-tance presence in the environment and selection by antibiotic pressure.34

The commercial food supplyAntibiotic resistance among classic foodborne illnesses, such as Salmonella and Campylobacter species, is a signifi cant threat to human health.35 Data from the U.S. and Europe strongly link the use of fl uoroquinolones in animals with fl uoro-quinolone resistance in Campylobacter spp. isolates obtained from animal and human sources.36, 37 In contrast, Australia has a long-standing policy banning the agricultural use of fl uoro-quinolones with correspondingly low fl uoroquinolone resistance rates.38 One period-prevalence study surveyed the susceptibil-ity of C. jejuni isolates from 585 patients in 5 Australian states and found that only 2% of isolates were resistant to ciprofl ox-acin.39 A second surveillance study identifi ed fl uoroquinolone resistance in only 12 of 370 Australian human Campylobacter isolates, with 10 of these isolates having a proven travel asso-ciation.38

The use of antibiotics in agriculture has also been linked to the development of resistance in Salmonella enterica. In New England, the prevalence of multidrug resistance among hu-man-origin S. enterica serotype Newport isolates rose from 0%

to 53% between 1998 and 2001, coinciding with the emergence of the same multidrug resistant strains in livestock in the same area.40 Similar rises among S. enterica serotype typhimurium have been noted among humans and livestock in both the U.S. and U.K.41

Antibiotic resistance in pathogens not considered to be strictly foodborne has also been identifi ed. Resistance to quinupris-tin-dalfopristin, a drug in the same class as the widely used feed additive virginiamycin, occurred in 18-54% of enterococci identifi ed in retail meat.42 Clostridium diffi cile has also been identifi ed in retail meat, and molecular analysis found that isolates identifi ed in patients and retail meat samples were of similar ribotypes.43 A more in depth analysis demonstrated that farm animals and farmers shared identical strains.43, 44

The transmission of antibiotic resistance in E. coli deserves special consideration. A molecular-epidemiologic comparison in Barcelona, Spain analyzed 117 E. coli isolates of human or chicken origin with varying ciprofl oxacin resistance profi les. The resistant isolates of human origin were epidemiologically distinct from susceptible human isolates, but indistinguishable from the resistant isolates from chicken, indicating that cip-rofl oxacin-resistant E. coli may be transmitted to humans via food supply.45 Studies conducted in the U.S. have shown that contamination of meat in retail settings with antibiotic resistant E. coli is frequent, with as many as 94% of E. coli samples displaying resistance to clinically important antibiotics, including resistance to third generation cephalosporins in up to 26%.46,

47 While relatively few studies have linked the onset of human infections to antibiotic resistance in the food supply, a recent review of the published literature indicates that a substantial proportion of infections due to ESBL E. coli may originate from food production animals, particularly from poultry.48 Further-more, the prevalence of fl uoroquinolone resistance in Australian human-origin E. coli isolates is low and stable, providing addi-tional supporting evidence of the link between low agricultural use of fl uoroquinolones and corresponding low levels of human resistance.49

A R M , M , E P H C

In addition to antibiotic resistant bacteria, antibiotics themselves can appear in the commercial food supply as a result of agricul-tural antibiotic use. There is a paucity of literature on how these antibiotic residues may aff ect human health, although there have been rare reports of allergic reactions following consump-tion of meat contaminated with antibiotics.50, 51 Additionally, antibiotic residues may have other less obvious consequences, such as disruption of the human microbiota and its own antibi-otic resistome. It has been hypothesized that subtherapeutic antibiotic exposure, including exposure through our food supply, may lead to deleterious metabolic eff ects, including obesity.52, 53

As a result of these and other concerns, the U.S. has enacted regulations to limit these exposures.54

The U.S. National Residue Program (NRP) for Meat, Poultry, and Egg Products, administered by the USDA Food Safety and Inspection Service (FSIS), sets acceptable daily intake (ADI) and maximum residue limits (MRL) based on antibiotic-specifi c pharmacokinetics, pharmacodynamics, and toxicodynamics. These ADI and MRL are then reviewed to inform the selection of a withdrawal time; the period of time for which an animal can

24

receive no antibiotic(s) prior to its meat or milk being delivered for human consumption. The FSIS tests meat, milk, and eggs destined for human consumption; however, these inspections happen only sporadically. Currently in the U.S., testing for antibiotic residues is performed on random samples from each major class of production animal as well as eggs.55 Targeted sampling by FSIS may also be performed when there is sus-picion of disease or antibiotic use within an animal population. FSIS currently tests for the following antibiotics: aminoglyco-sides, β-lactams, fl uoroquinolones, macrolides, tetracyclines, and sulfonamides. In 2011, FSIS tested 5,006 samples for antibiotic residues of which 47 samples (0.94%) had detectable levels of antibiotic residues; 8 (0.16%) samples had antibiot-ic residue levels above the maximum allowable level.55 Few non-governmental studies have evaluated the presence of antibiotic residues in meat, milk, or eggs destined for human consumption and there is signifi cant heterogeneity between studies with respect to antibiotics studied, analytical methodol-ogy, and geographic location. Additionally, most studies were published more than 15 years ago when regulations were less strict and analytical technologies were less robust. Recently, tetracyclines have been recovered from milk and pork destined for human consumption, despite having passed the mandated 4-day withdrawal time.56, 57

A U AThe use of antibiotics in aquaculture, or the farming of aquat-ic organisms, is pervasive and less regulated than the use of antibiotics milk and meat-producing animals. Additionally, approximately 90% of global aquaculture comes from Asia where the use of antibiotics in aquaculture is not tightly regu-lated.58 The presence of antibiotic residuals in aquatic products of South Asian source and destined for South Asian markets is correspondingly high.59 While strict regulations in the U.S. and European Union theoretically limit the presence of antibiotic re-siduals in imported fi sh products, this is not always the case. A recent study of seafood purchased in the southwestern U.S. but originating from 11 diff erent countries found that 5 antibiotics were routinely detectable in various sources, including “antibiot-ic free” salmon.60 Of note, none of the antibiotics exceeded the federally-determined MRL. A number of diff erent classes of anti-biotics were detected, although tetracyclines were found at the highest concentrations in all samples in line with aquaculture usage patterns. Not unexpectedly, tetracycline resistance in E. coli originating from commercial seafood exceeds 30%.61

Furthermore, regulations limiting antibiotic use in aquaculture are not universally followed. A recent global survey of aquacul-ture professionals found that use of fl uoroquinolones in aqua-culture was reported by 70% of respondents from the U.S., a rate similar to other countries worldwide.62 These results are remarkable given that the FDA has banned fl uoroquinolone use in aquaculture destined for human consumption, unless a sponsor obtains an approval for such use; extra-label use of fl uoroquinolones in food producing animals is prohibited by the FDA.63

A U HThe agricultural use of antibiotics extends beyond meat and fi sh production and into crop management. In the U.S., an estimated 36 metric tons of antibiotics were used in crop pro-duction in 2011. This is in contrast to the 14,900 metric tons sold as animal feed additive. While the percentage of overall

antibiotic use is small, any antibiotic use in crop production is nevertheless concerning. Streptomycin accounts for the vast majority of tonnage used, and is generally used as a topical spray to prevent the spread of the bacteria Erwinia amylovora, (the causative agent of fi re blight, in apple and pear orchards. Several studies have noted that the use of streptomycin does not alter the environmental prevalence of antibiotic resistant bacteria or resistance genes, but studies on the impact of this practice on farm workers or the community at large are lacking and no systematic surveillance mechanisms are in place.64, 65

Of additional concern is the widespread use of azole and sterol demethylation inhibitor (DMI) fungicides in horticulture in order to limit the development of fungal plant infections. In the Neth-erlands, a country with relatively high use of DMI fungicides, 6 – 13% of Aspergillus fumigatus isolates from patients with invasive aspergillosis are resistant to azole antifungals.66 In the U.S., DMI fungicide use is lower than in Europe or Asia. A re-cent surveillance study of clinical Aspergillus isolates conducted by the CDC found that 5% were above the epidemiologic cutoff value for resistance to itraconazole and that mutations in the cyp51a gene, which are associated with reduced susceptibility to azole antifungals, were more common in these isolates than those with lower MICs.67 During this time, 381,018 kilograms of DMI fungicides were used by states providing the clinical iso-lates.67 While a fi rm link between environmental DMI fungicide use and azole resistance in clinical Aspergillus isolates has not been established, no mandatory surveillance mechanisms are in place to ensure the necessary study of this important ques-tion. Furthermore, the use of these fungicides falls outside the purview of the FDA.

CDespite substantial eff orts in antibiotic development, infection control, and human antibiotic stewardship, antibiotic resistance continues to propagate. Given that the vast majority of antibiot-ics used worldwide are for non-therapeutic agricultural purpos-es and that the transfer of antibiotic resistance to humans is a well-documented consequence, an increased eff ort to curb antibiotic use in agriculture is critical to a national and global strategy of combating antibiotic resistance. Antibiotic steward-ship eff orts to date have focused on increasing appropriate antibiotic use in humans, however, these eff orts fail to address over 80% of inappropriate antibiotic use nationwide. Healthcare providers, policy makers, and consumers must understand the clear link between antibiotic use in agriculture and antibiotic-re-sistant bacteria in humans in order to inform discussion and policies aimed at combating the antibiotic resistance epidemic.

25

REFERENCES1. Spellberg B. The future of antibiotics. Crit Care 2014;3:228.

2. Ogle M. In Meat We Trust: An Unexpected History of Carnivore America. New York, NY: Houghton Miffl in Harcoury Publishing Company, 2013:111.

3. Infectious drug resistance. N Engl J Med 1966;5:277.

4. Soulsby L. Antimicrobials and animal health: a fascinating nexus. J Antimicrob Chemother 2007;i77-8.

5. Antibiotic Resistance and the Use of Antibiotics in Animal Agriculture: Hearing Before the Subcommittee on Health of the Committee on Ener-gy and Commerce of the 111th Congress, 2nd Session (July 14, 2010).

6. Hollis A, Ahmed Z. Preserving antibiotics, rationally. N Engl J Med 2013;26:2474-6.

7. Food and Drug Administration. 2013 Summary Report on Antimicrobials Sold or Distributed for Use in Food-Producing Animals. Available from http://www.fda.gov/downloads/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/UCM440584.pdf. Accessed July 7, 2015

8. Hall JO. Ionophore use and toxicosis in cattle. Vet Clin North Am Food Anim Pract 2000;3:497-509, vii.

9. Food and Drug Administration. 2003 Guidance for Industry #152. Evaluating the safety of antimicrobial new animal drugs with regard to their microbiological eff ects on bacteria of human health concern. Available from http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplian-ceEnforcement/GuidanceforIndustry/UCM052519.pdf. Accessed July 9, 2015

10. Natural Resources Defence Council. 2014 Playing chicken with antibiotics: previously undisclosed FDA documents show antibiotic feed additives don't meet the agency's own safety standards. Available from http://www.nrdc.org/food/saving-antibiotics/fi les/antibiotic-feed-fda-docu-ments-IB.pdf. Accessed July 9, 2015

11. Stobberingh E, van den Bogaard A, London N, Driessen C, Top J, Willems R. Enterococci with glycopeptide resistance in turkeys, turkey farmers, turkey slaughterers, and (sub)urban residents in the south of The Netherlands: evidence for transmission of vancomycin resistance from animals to humans? Antimicrob Agents Chemother 1999;9:2215-21.

12. Li XZ, Nikaido H. Effl ux-mediated drug resistance in bacteria: an update. Drugs 2009;12:1555-623.

13. Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol 2015;1:42-51.

14. Li XZ, Plesiat P, Nikaido H. The challenge of effl ux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev 2015;2:337-418.

15. Paterson GK, Harrison EM, Holmes MA. The emergence of mecC methicillin-resistant Staphylococcus aureus. Trends Microbiol 2014;1:42-7.

16. Garcia-Alvarez L, Holden MT, Lindsay H, et al. Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bo-vine populations in the UK and Denmark: a descriptive study. Lancet Infect Dis 2011;8:595-603.

17. D'Costa VM, King CE, Kalan L, et al. Antibiotic resistance is ancient. Nature 2011;7365:457-61.

18. Schwarz S, Werckenthin C, Kehrenberg C. Identifi cation of a plasmid-borne chloramphenicol-fl orfenicol resistance gene in Staphylococcus sciuri. Antimicrob Agents Chemother 2000;9:2530-3.

19. Allen HK, Donato J, Wang HH, Cloud-Hansen KA, Davies J, Handelsman J. Call of the wild: antibiotic resistance genes in natural environ-ments. Nat Rev Microbiol 2010;4:251-9.

20. Andersson DI, Hughes D. Persistence of antibiotic resistance in bacterial populations. FEMS Microbiol Rev 2011;5:901-11.

21. U.S. Centers for Disease Control and Prevention. Antibiotic Use in Food-Producing Animals: Tracking and Reducing the Public Health Im-pact, Available from http://www.cdc.gov/narms/animals.html. Accessed 9/16/2015,

22. van den Bogaard AE, Willems R, London N, Top J, Stobberingh EE. Antibiotic resistance of faecal enterococci in poultry, poultry farmers and poultry slaughterers. J Antimicrob Chemother 2002;3:497-505.

23. van den Bogaard AE, London N, Driessen C, Stobberingh EE. Antibiotic resistance of faecal Escherichia coli in poultry, poultry farmers and poultry slaughterers. J Antimicrob Chemother 2001;6:763-71.

24. Voss A, Loeff en F, Bakker J, Klaassen C, Wulf M. Methicillin-resistant Staphylococcus aureus in pig farming. Emerg Infect Dis 2005;12:1965-6.

26

25. Oppliger A, Moreillon P, Charriere N, Giddey M, Morisset D, Sakwinska O. Antimicrobial resistance of Staphylococcus aureus strains ac-quired by pig farmers from pigs. Appl Environ Microbiol 2012;22:8010-4.

26. Laube H, Friese A, von Salviati C, Guerra B, Rosler U. Transmission of ESBL/AmpC-producing Escherichia coli from broiler chicken farms to surrounding areas. Vet Microbiol 2014;3-4:519-27.

27. McEachran AD, Blackwell BR, Hanson JD, et al. Antibiotics, bacteria, and antibiotic resistance genes: aerial transport from cattle feed yards via particulate matter. Environ Health Perspect 2015;4:337-43.

28. Blaak H, Hamidjaja RA, van Hoek AH, de Heer L, de Roda Husman AM, Schets FM. Detection of extended-spectrum beta-lactamase (ES-BL)-producing Escherichia coli on fl ies at poultry farms. Appl Environ Microbiol 2014;1:239-46.

29. Casey JA, Curriero FC, Cosgrove SE, Nachman KE, Schwartz BS. High-density livestock operations, crop fi eld application of manure, and risk of community-associated methicillin-resistant Staphylococcus aureus infection in Pennsylvania. JAMA Intern Med 2013;21:1980-90.

30. Martinez JL. Environmental pollution by antibiotics and by antibiotic resistance determinants. Environ Pollut 2009;11:2893-902.

31. Brown KD, Kulis J, Thomson B, Chapman TH, Mawhinney DB. Occurrence of antibiotics in hospital, residential, and dairy effl uent, municipal wastewater, and the Rio Grande in New Mexico. Sci Total Environ 2006;2-3:772-83.

32. Popowska M, Rzeczycka M, Miernik A, Krawczyk-Balska A, Walsh F, Duff y B. Infl uence of soil use on prevalence of tetracycline, streptomy-cin, and erythromycin resistance and associated resistance genes. Antimicrob Agents Chemother 2012;3:1434-43.

33. Marti R, Tien YC, Murray R, Scott A, Sabourin L, Topp E. Safely coupling livestock and crop production systems: how rapidly do antibiotic resistance genes dissipate in soil following a commercial application of swine or dairy manure? Appl Environ Microbiol 2014;10:3258-65.

34. Udikovic-Kolic N, Wichmann F, Broderick NA, Handelsman J. Bloom of resident antibiotic-resistant bacteria in soil following manure fertiliza-tion. Proc Natl Acad Sci U S A 2014;42:15202-7.

35. White DG, Zhao S, Simjee S, Wagner DD, McDermott PF. Antimicrobial resistance of foodborne pathogens. Microbes Infect 2002;4:405-12.

36. Wegener HC. The consequences for food safety of the use of fl uoroquinolones in food animals. N Engl J Med 1999;20:1581-2.

37. Engberg J, Aarestrup FM, Taylor DE, Gerner-Smidt P, Nachamkin I. Quinolone and macrolide resistance in Campylobacter jejuni and C. coli: resistance mechanisms and trends in human isolates. Emerg Infect Dis 2001;1:24-34.

38. Unicomb L, Ferguson J, Riley TV, Collignon P. Fluoroquinolone resistance in Campylobacter absent from isolates, Australia. Emerg Infect Dis 2003;11:1482-3.

39. Unicomb LE, Ferguson J, Staff ord RJ, et al. Low-level fl uoroquinolone resistance among Campylobacter jejuni isolates in Australia. Clin Infect Dis 2006;10:1368-74.

40. Gupta A, Fontana J, Crowe C, et al. Emergence of multidrug-resistant Salmonella enterica serotype Newport infections resistant to expand-ed-spectrum cephalosporins in the United States. J Infect Dis 2003;11:1707-16.

41. Glynn MK, Bopp C, Dewitt W, Dabney P, Mokhtar M, Angulo FJ. Emergence of multidrug-resistant Salmonella enterica serotype typhimurium DT104 infections in the United States. N Engl J Med 1998;19:1333-8.

42. Hayes JR, English LL, Carter PJ, et al. Prevalence and antimicrobial resistance of enterococcus species isolated from retail meats. Appl Environ Microbiol 2003;12:7153-60.

43. Rodriguez C, Taminiau B, Avesani V, Van Broeck J, Delmee M, Daube G. Multilocus sequence typing analysis and antibiotic resistance of Clostridium diffi cile strains isolated from retail meat and humans in Belgium. Food Microbiol 2014;166-71.

44. Knetsch CW, Connor TR, Mutreja A, et al. Whole genome sequencing reveals potential spread of Clostridium diffi cile between humans and farm animals in the Netherlands, 2002 to 2011. Euro Surveill 2014;45:20954.

45. Johnson JR, Kuskowski MA, Menard M, Gajewski A, Xercavins M, Garau J. Similarity between human and chicken Escherichia coli isolates in relation to ciprofl oxacin resistance status. J Infect Dis 2006;1:71-8.

46. Johnson JR, Kuskowski MA, Smith K, O'Bryan TT, Tatini S. Antimicrobial-resistant and extraintestinal pathogenic Escherichia coli in retail foods. J Infect Dis 2005;7:1040-9.

47. Schroeder CM, White DG, Ge B, et al. Isolation of antimicrobial-resistant Escherichia coli from retail meats purchased in Greater Washing-ton, DC, USA. Int J Food Microbiol 2003;1-2:197-202.

48. Lazarus B, Paterson DL, Mollinger JL, Rogers BA. Do human extraintestinal Escherichia coli infections resistant to expanded-spectrum cephalosporins originate from food-producing animals? A systematic review. Clin Infect Dis 2015;3:439-52.

49. Collignon P, Angulo FJ. Fluoroquinolone-resistant Escherichia coli: food for thought. J Infect Dis 2006;1:8-10.

27

50. Dayan AD. Allergy to antimicrobial residues in food: assessment of the risk to man. Vet Microbiol 1993;3-4:213-26.

51. Dewdney JM, Edwards RG. Penicillin hypersensitivity--is milk a signifi cant hazard?: a review. J R Soc Med 1984;10:866-77.

52. Cox LM, Blaser MJ. Antibiotics in early life and obesity. Nat Rev Endocrinol 2015;3:182-90.

53. Riley LW, Raphael E, Faerstein E. Obesity in the United States - dysbiosis from exposure to low-dose antibiotics? Front Public Health 2013;69.

54. Donoghue DJ. Antibiotic residues in poultry tissues and eggs: human health concerns? Poult Sci 2003;4:618-21.

55. National Residue Program for Meat Poultry and Egg Products. 2011 Residue Sample Results. Available from http://www.fsis.usda.gov/wps/wcm/connect/f511ad0e-d148-4bec-95c7-22774e731f7c/2011_Red_Book.pdf?MOD=AJPERES. Accessed July 8, 2015

56. Baron PA, Love DC, Nachman KE. Pharmaceuticals and personal care products in chicken meat and other food animal products: a mar-ket-basket pilot study. Sci Total Environ 2014;296-300.

57. Lindquist D, Wu H, Mason S, et al. Tetracycline residues in porcine stomach after administration via drinking water on a swine farm. J Food Prot 2014;1:122-6.

58. Thuy HT, Nga le P, Loan TT. Antibiotic contaminants in coastal wetlands from Vietnamese shrimp farming. Environ Sci Pollut Res Int 2011;6:835-41.

59. Pham DK, Chu J, Do NT, et al. Monitoring Antibiotic Use and Residue in Freshwater Aquaculture for Domestic Use in Vietnam. Ecohealth 2015.

60. Done HY, Halden RU. Reconnaissance of 47 antibiotics and associated microbial risks in seafood sold in the United States. J Hazard Mater 2015;10-7.

61. Ryu SH, Park SG, Choi SM, et al. Antimicrobial resistance and resistance genes in Escherichia coli strains isolated from commercial fi sh and seafood. Int J Food Microbiol 2012;1-2:14-8.

62. Tusevljak N, Dutil L, Rajic A, et al. Antimicrobial use and resistance in aquaculture: fi ndings of a globally administered survey of aquacul-ture-allied professionals. Zoonoses Public Health 2013;6:426-36.

63. United States Food and Drug Administration Center for Food Safety and Applied Nutrition. 2011 Fish and Fishery Products - Hazards and Controls Guidance. Available from http://www.fda.gov/downloads/Food/GuidanceRegulation/UCM251970.pdf. Accessed July 8, 2015

64. Duff y B, Holliger E, Walsh F. Streptomycin use in apple orchards did not increase abundance of mobile resistance genes. FEMS Microbiol Lett 2014;2:180-9.

65. Walsh F, Smith DP, Owens SM, Duff y B, Frey JE. Restricted streptomycin use in apple orchards did not adversely alter the soil bacteria communities. Front Microbiol 2013;383.

66. Verweij PE, Snelders E, Kema GH, Mellado E, Melchers WJ. Azole resistance in Aspergillus fumigatus: a side-eff ect of environmental fungi-cide use? Lancet Infect Dis 2009;12:789-95.

67. Pham CD, Reiss E, Hagen F, Meis JF, Lockhart SR. Passive surveillance for azole-resistant Aspergillus fumigatus, United States, 2011-2013. Emerg Infect Dis 2014;9:1498-503.

28

Table 1. Antibiotic importance categories according to FDA Guidance for Industry #152

Risk Category Antibiotic Classes

Critically important 3rd generation cephalosporins, fl uoroquinolones, macrolides, trimetho-

prim/sulfamethoxazole

Highly important Natural penicillins and semisynthetic penicillins, 4th gen. cephalosporins,

carbapenems, clindamycin, aminoglycosides, tetracyclines, strepto-

gramins, glycopeptides, oxazolidinones, rifamycins, chloramphenicol,

metronidazole, polymyxin B

Important 1st generation cephalosporins, 2nd generation cephalosporins, mono-

bactams

Table 2: Position Statements from the Society of Infectious Diseases Pharmacists on Antibiotics in Agriculture

1. The agricultural industry should minimize agricultural consumption of all antibiotics that the

FDA has deemed important to human health

2. The agricultural industry should be required to report what antibiotics are being utilized, in

which settings they are being used, and for what purposes.

3. The FDA should require mandatory, rather than voluntary, changes in the labeling of

antibiotics used in agriculture to prevent their use as growth promoters.

4. Funding should be established to further investigate the magnitude of the interaction

between antibiotics used in agriculture and human health.

5. Funding should be established to investigate alternative agriculture practices that optimize

food production without utilizing antibiotics that have important public health risks.

6. Antifungal and antibacterial agents used in horticulture may also be impacting human

health and should receive similar attention as antibacterial usage in animals.

Table 3: Websites Describing Public Policy and Actions Steps Enacted Regarding Antibiotics in Agriculture

- Pew Research Center: http://www.pewtrusts.org/en/projects/antibiotic-resistance-project/about/antibiotic-use-in-food-animals

- Center for Global Development: http://www.cgdev.org/

- United States President’s Council of Advisors on Science and Technology: http://www.whitehouse.gov/ostp/pcast

- One Health: http://www.cdc.gov/onehealth/

- European Medicines Agency: http://www.ema.europa.eu/ema

Figure 1: United States Antibiotic Consumption, Estimated

Estimated antibiotic consumption in the United States, adopted from Hollis et al.6

0

2000000

4000000

6000000

8000000

10000000

12000000

14000000

Livestock Humans Aquaculture Pets Crops

Killo

gram

s of A

ntib

iotic

Figure 2: Resistant Organism Transfer from Animals to Humans

Depiction of varying methods of transfer of resistant organisms to humans from food producing animals. Used with permission from www.cdc.gov

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