table of contents - national foundation for infectious ... · stuart h. cohen, m.d. university of...

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Table of ContentsConference Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3

Conference Co-Chairs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4

Conference Organizing Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4

Scientific Program Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5

Executive Staff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5

Invited Presenters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6

General Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Americans with Disabilities Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Conference Information Desk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Conference Language . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Conference Location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Continuing Medical Education (CME) Accreditation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

No Smoking Policy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

Poster Session . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

Press Room . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

Program and Abstracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

Registration Fees and Hours . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

Speaker Ready Room and Audiovisual Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10

Verification of Attendance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10

Affiliated Events and Other Meetings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10

Hotel Floor Plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11

Program At-A-Glance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12

Final Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13

Abstracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

Abstracts of Invited Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

Abstracts of Submitted Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33

Abstracts of Submitted Poster Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37

Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43

Disclosure Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45

2005 Conference on Antimicrobial Resistance2

Conference ObjectivesAt the conclusion of this conference, participants should be able to meet the overall conference objectives andsession specific objectives:

Overall Conference Objectives:■ Discuss the science, prevention and control of antimicrobial resistance.

■ Define issues and potential solutions to the problem of antimicrobial resistance.

Session-Specific Objectives:Keynote Address■ Discuss choices and technical solutions humans deploy when population growth is constrained by limiting

conditions and contrast these strategies to those of bacteria when facing the same dilemma

New Technologies for Drug Discovery and Development■ Know the scope and extent of bacterial infections that are thought to be biofile-associated; outline the

mechanisms underlying the unresponsiveness of such infections to conventional antibiotic therapy; andacknowledge the ongoing efforts at Cumbre Inc. to implement a drug development platform to guide theoptimizations of agents with improved efficacy in killing bacteria grown in the biofilm state both in vitro andin vivo

■ Interpret novel approaches to antibiotic discovery currently being carried out at Cubist Pharmaceuticals

■ Describe strategies to combat bacterial antibiotic resistance

Animal Antibiotic Use: A Review of Recommendations, Actions and Results■ Learn what consensus recommendations have been made by various organizations to address the issue of

antibiotic resistance development in food animals and its potential impact on human antibiotic treatment offood borne disease, the progress that has been made to develop and implement the key recommendations forrisk assessment, regulation, responsible use, and research, as well as the results of some of those riskmanagement actions

■ Describe public health concerns about antibiotic resistance from an ecological perspective, and employ that lens to assess various actions and recommendations to lessen antibiotic use in food animals in the U.S. and Europe

■ Understand the distribution of bacterial pathogens producing human infections acquired in the community and during hospitalization.

Economics of Antimicrobial Resistance■ Acknowledge the strengths and limitations of estimates of costs attributable to antibiotic resistance

■ List key factors that drive the increased cost associated with infections due to resistant organisms

■ Compare and describe approaches to managing and reducing the cost associated with infections due toresistant organisms

S C I E N C E • P R E V E N T I O N • C O N T R O L 3

Antiviral Resistance■ Review the principles of HIV drug resistance and discuss the role of drug resistance testing in clinical

management■ Understand the risks of generation and transmission of resistant viruses; identify strategies to reduce the

risk of resistance; and define the roles of vaccination and antiviral strategies in pandemic planning

Gram-Negative Bacilli■ Understand the growing challenge that antimicrobial resistance in gram negative pathogens poses to

healthcare and be able to describe some of the measures that can be taken to confront this problem■ Analyze the complexities of susceptibility testing of gram negative bacilli, particularly multidrug-resistant

organisms, in patients with cystic fibrosis■ Explain the evolution of ESBLs and attendant clinical consequences■ Acknowledge the role and importance of gram negative pathogens as a cause of nosocomial infections and the

emergence of multidrug resistance in these pathogens and discuss potential control strategies

Defining Resistance in Vitro and In vivo: The Setting and Significance of Breakpoints■ Review how susceptibility data are presented to clinicians and the interfaces drawn from the data■ Explain how microbiologic, pharmacokinetic, pharmacodynamic, and clinical data (including microbiological

eradication) are all used to develop CLSI (NCCLS) breakpoints■ Discuss antimicrobial susceptibility testing breakpoint challenges and strategies for dealing with them in a

clinical laboratory■ Understand the impact of breakpoints on the safety and efficacy of antimicrobials and the effect on various

stakeholders including patients, clinicians, laboratories, drug sponsors, device manufacturers and governmentagencies.

Parasites■ Review the serious and widespread problem of drug resistance in veterinary helminthes■ Describe current issues in the treatment of human African typanosomiasis■ Explain the problems and mechanisms of drug resistance in parasites and list evolving molecular methods to

detect drug resistance in parasites■ Know the status of antileishmanial drugs in the treatment of visceral leishmaniasis

Acknowledgments (as of June 10, 2005)This conference is supported, in part, throughunrestricted educational grants from:

Advancis Pharmaceutical CorporationAdvanDx, Inc.AstraZeneca Pharmaceuticals LPBristol-Myers SquibbCubist Pharmaceuticals, Inc.Inhibitex, Inc.Janssen Ortho-McNeil Primary Care, Inc.Merck & Co., Inc.

Pfizer, Inc.Presutti LaboratoriesOscient PharmaceuticalsRoche Laboratoriessanofi aventisSchering-Plough CorporationSTERIS CorporationTheravance, Inc.Vicuron Pharmaceuticals


Stuart H. Cohen, M.D.University of California, Davis Medical CenterSacramento, CA

Dennis M. Dixon, Ph.D.National Institute of Allergy and InfectiousDiseases/NIHBethesda, MD

Dale N. Gerding, M.D.Loyola University Medical SchoolHines, VA

Gayle K. Gilmore, RN, MA, MIS, CICAssociation for Professionals in Infection Control andEpidemiologyDuluth, MN

Susan Jennings, Ph.D.U.S. Environmental Protection AgencyWashington, DC

Stuart B. Levy, M.D.Tufts University School of MedicineBoston, MA

Marissa Miller, D.V.M., M.P.H.Conference Co-Chair

John H. Powers, M.D.Food and Drug AdministrationRockville, MD

Susan J. Rehm, M.D.Conference Co-Chair

Jane F. Robens, D.V.M.U.S. Department of AgricultureBeltsville, MD

David Ross, M.D. Ph.D.U.S. Food and Drug AdministrationRockville, MD

Katherine M. Shea, M.D., M.P.H.American Academy of PediatricsCommittee on Environmental HealthChapel Hill, NC

Paul L. Sundberg, D.V.M.American Veterinary Medical AssociationSchaumberg, IL

J. Todd Weber, M.D.Conference Co-Chair

Conference Co-ChairsMarissa Miller, D.V.M., M.P.H.

Department of Health and Human ServicesWashington, DC

Susan J. Rehm, M.D.National Foundation for Infectious Diseases

Bethesda, MD

J. Todd Weber, M.D.Centers for Disease Control and Prevention

Atlanta, GA

Former Conference Co-Chair and FounderWilliam J. Martone, M.D.Cubist Pharmaceuticals

Lexington, MA

Conference Organizing Committee

S C I E N C E • P R E V E N T I O N • C O N T R O L

Scientific Program Committee

5

Mitchell L. Cohen, M.D.Centers for Disease Control and PreventionAtlanta, GA

Stuart H. Cohen, M.D.Member, Conference Organizing Committee

Dennis M. Dixon, Ph.D.Member, Conference Organizing Committee

Barry I. Eisenstein, M.D.Cubist Pharmaceuticals, Inc.Lexington, MA

George M. Eliopoulos, M.D.Beth Israel Deaconess Medical CenterBoston, MA

Dale N. Gerding, M.D.Member, Conference Organizing Committee

Gayle K. Gilmore, RN, MAMember, Conference Organizing Committee

Frederick G. Hayden, M.D.University of Virginia Health Sciences CenterCharlottesville, VA

Susan Jennings, M.S.Member, Conference Organizing Committee

Mark Kunkel, M.D.Pfizer Global PharmaceuticalsNew York, NY

Elaine Larson, R.N., Ph.D.Columbia UniversitySchool of NursingNew York, NY

Stuart B. Levy, M.D.Member, Conference Organizing Committee

Marissa Miller, D.V.M., M.P.H.Conference Co-Chair

John H. Powers, M.D.Member, Conference Organizing Committee

Susan J. Rehm, M.D.Conference Co-Chair

John H. Rex, M.D.AstraZeneca PharmaceuticalsMacclesfield, Cheshire, United Kingdom

Jane Robens, D.V.M.Member, Conference Organizing Committee

David Ross, M.D., Ph.D.Member, Conference Organizing Committee

Merle A. Sande, M.D.University of Utah School of MedicineSalt Lake City, UT

Katherine M. Shea, M.D., M.P.H.Member, Conference Organizing Committee

Paul L. Sundberg, D.V.M.Member, Conference Organizing Committee

J. Todd Weber, M.D.Conference Co-Chair

Richard J. Whitley, M.D.Children’s HospitalBirmingham, AL

Executive StaffSharon Cooper-KerrDirector, Events PlanningNational Foundation for Infectious DiseasesBethesda, MD

Sheena L. MajetteDirector, Continuing Medical EducationNational Foundation for Infectious DiseasesBethesda, MD

Len NovickExecutive DirectorNational Foundation for Infectious DiseasesBethesda, MD


Richard Baltz, Ph.D.Scientific FellowCubist Pharmaceuticals, Inc.Lexington, MA

Henry M. Blumberg, M.D.Professor of MedicineProgram DirectorEmory University School of MedicineAtlanta, GA

George M. Eliopoulos, M.D.Chief, James L. Tullis FirmBeth Israel Deaconess Medical CenterBoston, MA

Mary Jane Ferraro, Ph.D., M.P.H.Associate Professor of PathologyHarvard Medical SchoolDirector, Microbiology LaboratoriesMassachusetts General HospitalBoston, MA

Donald A. Goldman, M.D.Professor of PediatricsHarvard Medical School, Children’s HospitalBoston, MA

Hajo Grundmann, M.D., M.Sc., D.T.M. & H.Project LeaderScientific CoordinatorInstitute for Public Health and the EnvironmentBilthoven, Netherlands

Roy M. Gulick, M.D., M.P.H.Associate Professor of MedicineWeill Medical College of Cornell UniversityNew York, NY

Anthony Harris, M.D., M.P.H.Associate ProfessorAssociate Hospital EpidemiologistsUniversity of MarylandBaltimore, MD

Janet A. Hindler, Ph.D.Senior SpecialistUCLA Medical CenterLos Angeles, CA

Ronald N. Jones, M.D.ProfessorTufts University School of MedicineBoston, MAPresident/CEOJMI LaboratoreiesNorth Liberty, IA

J. Kevin Judice, Ph.D.Chief Scientific OfficerAchaogen, Inc.South San Francisco, CA

Ray M. Kaplan, D.V.M., Ph.D.Associate ProfessorUniversity of GeorgiaAthens, GA

Daryl T.Y. Lau, M.D., M.Sc., M.P.H., F.R.C.P.(C)Assistant Professor of MedicineThe University of Texas Medical BranchGalveston, TX

A. Simon Lynch, Ph.D.Director of ResearchCumbre, Inc.Dallas, TX

Anne Moore, M.D., Ph.D.Chief, Parasitic Diseases Drug ServiceNational Center for Infectious DiseasesCenters for Disease Control and PreventionAtlanta, GA

Robert C. Owens, Jr., Pharm.D.Co-Director, Antimicrobial Stewardship ProgramMaine Medical CenterPortland, ME

Joseph M. Patti, Ph.D.Chief Scientific OfficerVice President, Preclinical DevelopmentInhibitex, Inc.Alpharetta, GA

John H. Powers, M.D.Lead Medical OfficerFood and Drug AdministrationRockville, MD

Roger K. Prichard, Ph.D.James McGill ProfessorMcGill UniversitySte. Anne de Bellevue, QC, Canada

Invited Presenters*

7S C I E N C E • P R E V E N T I O N • C O N T R O L

John P. Quinn, M.D.Professor of MedicineRush Medical SchoolChicago, IL

Lisa Saiman, M.D., M.P.H.Professor of Clinical PediatricsCollege of Physicians and Surgeons of ColumbiaUniversityNew York, NY

Thomas R. Shryock, Ph.D.Senior Microbiology Technical AdvisorElanco Animal HealthGreenfield, IN

Arjun Srinivasan, M.D.Medical EpidemiologistNational Center for Infectious DiseasesCenters for Disease Control and PreventionAtlanta, GA

Shyam Sundar, M.D., F.R.C.P., F.A.M.S.Professor of MedicineBanaras Hindu UniversityVaranasi, India

John Treanor, M.D.Associate Professor of Medicine, Microbiology andImmunologyUniversity of RochesterRochester, NY

David Wallinga, M.D., M.P.A.Director, Food and Health Program and AntibioticResistance ProjectInstitute for Agriculture and Trade PolicyMinneapolis, MN

*Speakers and presentations subject to change


General InformationAmericans with Disabilities ActThe Hyatt Regency Bethesda is fully accessible to the public in accordance with the Americans with DisabilitiesAct guidelines. If you have any special meeting needs or requirements, please contact either Sharon Cooper-Kerror a member of the hotel staff.

Conference Information DeskThe Conference Information Desk is located in the Waterford Lobby area outside the Crystal Ballroom.Conference staff will be available at the desk throughout the conference.

Conference LanguageThe official language for the conference is English.

Conference LocationAll sessions of the conference will be held at:

Hyatt Regency BethesdaOne Bethesda Metro CenterWisconsin Avenue at Old Georgetown RoadBethesda, Maryland 20814(301) 657-1234

Meeting rooms for specific sessions are listed in the Final Program (see Table of Contents).

Continuing Medical Education (CME) AccreditationGeneral CME InformationThe National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council forContinuing Medical Education (ACCME) to provide Continuing Medical Education (CME) for physicians. NFIDtakes responsibility for the content, quality, and scientific integrity of this CME activity.

NFID designates this CME activity for a maximum of 16 Category 1 Credits toward the AMA Physician’sRecognition Award. Each physician should claim only those hours of credit that he/she actually spent in theeducational activity.

Designated CME ActivitiesSessions designated with a symbol have been approved for CME Credit. No other sessions are eligible forCME credit hours.

CME


CME CertificatesIn order to ensure that you receive the CME credit hours to which you are entitled, please complete thefollowing:

1. Complete the CME Evaluation Form for credits located at the Conference Information Desk.

2. Return your completed evaluation to conference staff.

CME DisclosuresIn order for program sessions to be accredited, program presenters must disclose to the conference participantsany real or apparent conflict(s) of interest related to the content of their presentations. A summary of theseconflicts of interest is printed separately in this book under the heading Disclosure Index (see Table ofContents).

MessagesAll sleeping rooms in the Hyatt Regency Bethesda are equipped with a voice mail system. This system isaccessible via the hotel operator using the house phone. In case of emergencies requiring immediate attention,your party should call the general hotel number listed below and instruct the switchboard to deliver a message to Sharon Cooper-Kerr or Sheena Majette at the Conference Information Desk outside of the Crystal Ballroom.The general hotel number is 1-301-657-1234.

No Smoking PolicyThe Hyatt Regency Bethesda is a non-smoking facility. No smoking is allowed in any of the session rooms, coffee break area or in the foyer area adjoining the session rooms.

Poster SessionThe Poster Session/Reception will be held on Monday, June 27, 5:30 p.m. in the Waterford/Lalique Room.Presenters will be at their boards to answer questions and discuss their research. The Posters will continue to beon display throughout the conference.

Press RoomNFID will have a Press Room located in the Tiffany Salon. Press should sign in at the Conference InformationDesk during registration hours.

Program and AbstractsEach registered participant will receive one complimentary copy of the Final Program and Abstract Book as partof his/her registration fee. Additional copies, if available, can be purchased for $25. Orders for additional copiescan be taken at the Conference Information Desk and after the conference, by e-mail to [email protected], orby calling (301) 656-0003 x19.

Registration Fees and HoursThe onsite registration fee: US $450.00


The registration fee includes a program/abstract book, continental breakfast on each day of the conference, allscheduled coffee breaks, the reception on Monday, and the luncheon presentation on Tuesday. Accommodationsand additional meals are not included.

Individuals interested in registering onsite may do so at the Conference Information Desk between the followingtimes:

Sunday, June 26 7:00 p.m. – 9:00 p.m.

Monday, June 27 8:00 a.m. – 5:00 p.m.

Tuesday, June 28 7:00 a.m. – 5:00 p.m.

Wednesday, June 29 7:30 a.m. – 10:30 a.m.

Speaker Ready Room and Audiovisual EquipmentA room has been set aside for speakers to preview their slides. All speakers should check in at the ConferenceInformation Desk to be directed to the ready room. The room will be open during the registration hours (seeGeneral Information-Registration Fees and Hours) and will be equipped with a laptop for preview of yourPowerPoint presentation.

Standard session room setup includes a PC, 250 zip drive, laser pointer, podium microphone, and aislemicrophones.

Verification of AttendanceAttendees may obtain a letter of attendance verification from the staff at the Conference Information Desk duringregistration hours.

Affiliated Events and Other MeetingsTuesday, June 28, 2005

Conference on Antimicrobial Resistance Organizing and Scientific Program Committee Meeting(Closed meeting)5:30 p.m. – 8:30 p.m., Ambassador/Diplomat Rooms

Wednesday, June 29, 2005Interagency Task Force on Antimicrobial Resistance1:30 – 5:00 p.m., Haverford/Baccarat Ballroom

PROGRAM-AT-A-GLANCE


SUNDAY, JUNE 26 MONDAY, JUNE 27 TUESDAY, JUNE 28 WEDNESDAY, JUNE 29

7:00 Registration Registration

7:30 Continental Breakfast Continental Breakfast

8:00 Registration Symposium 3: Symposium 6:Economics of Antimicrobial Defining Resistance in Vitro Resistance and In vivo: The Setting and

Significance of Breakpoints9:00 Continental Breakfast

9:30 Welcome and Introductions Coffee Break

9:35 Keynote Address

10:00 Symposium 4: Coffee BreakAntiviral Resistance

10:30 Coffee Break/Poster Set-up Symposium 7:Parasites

11:00 Symposium 1:New Technologies for Drug Discovery and Development

11:30 Luncheon Presentation

12:00

12:30 Adjournment/ParticipantEvaluation

1:00 Lunch (on your own) Submitted Presentations

1:30 Meeting—Interagency TaskForce on AntimicrobialResistance

2:15 Symposium 2:Animal Antibiotic Use: A Review of Recommendations, Actions and Results

2:30 Coffee Break

3:00 Symposium 5:Gram-Negative Bacilli

3:45 Coffee Break

4:15 Submitted Presentations

5:00 Adjournment

5:30 Poster Session and Reception

7:00 Registration

HOTEL FLOOR PLAN


FINAL PROGRAM


Sunday, June 26, 20057:00 p.m.–9:00 p.m. Registration Waterford Lobby

Monday, June 27, 20058:00 a.m.–5:00 p.m. Registration Waterford Lobby

9:00 a.m. Continental Breakfast Waterford Lobby

9:30 a.m. Opening Remarks Haverford/Baccarat Ballroom

Susan J. Rehm, M.D.National Foundation for Infectious DiseasesBethesda, MD

Keynote Address Haverford/Baccarat Ballroom

Moderator: J. Todd Weber, M.D.Centers for Disease Control and PreventionAtlanta, GA

9:35 a.m. 1. The Mathew Effect and the Tragedy of the Commons in Antimicrobial Resistance

Hajo Grundmann, M.D., M.Sc., D.T.M. & H.Institute for Public Health and the EnvironmentBilthoven, Netherlands

10:20 a.m. Questions and Answers

10:30 a.m. Poster Set-Up Waterford/Lalique Ballroom

10:30 a.m. Coffee Break Waterford Lobby

CME

FINAL PROGRAM

Monday, June 27, 2005 (continued)

Symposium 1.New Technologies for Drug Haverford/Baccarat Ballroom

Discovery and DevelopmentModerator: Barry I. Eisenstein, M.D.

Cubist Pharmaceuticals, Inc.Lexington, MA

11:00 a.m. 2. Immunologic Therapeutics for Gram-Positive Bacterial Infections

Joseph M. Patti, Ph.D.Inhibitex, Inc.Alpharetta, GA


11:30 a.m. 3. Natural Products Discovery: New Vistas Along Ancient Paths

Richard Baltz, Ph.D.Cubist Pharmaceuticals, Inc. Lexington, MA


12:00 p.m. 4. Preventing Expression of Chromosomal Resistance Determinates

J. Kevin Judice, Ph.D.Achaogen, Inc.South San Francisco, CA

12:25 p.m. Questions and Answers

12:30 p.m. 5. Development and Implementation of an Integrated Platform to Optimize Agents for Biofilm Activity

A. Simon Lynch, Ph.D.Cumbre, Inc.Dallas, TX


1:00 p.m. Lunch (on your own)


CME

Symposium 2. Animal Antibiotic Use: A Review of Haverford/Baccarat Ballroom

Recommendations, Actions, and ResultsModerator: Jane F. Robens, D.V.M.

U.S. Department of AgricultureBeltsville, MD

2:15 p.m. 6. Thomas R. Shryock, Ph.D.Elanco Animal HealthGreenfield, IN


2:40 p.m. 7. Ronald N. Jones, M.D.JMI LaboratoriesNorth Liberty, IA


3:05 p.m. 8. David Wallinga, M.D., M.P.A.Institute for Agriculture and Trade PolicyMinneapolis, MN


3:30 p.m. Panel Discussion

3:45 p.m. Coffee Break Waterford Lobby

Submitted Presentations 1: Resistance Mechanisms and Haverford/Baccarat Ballroom

Issues in Antibiotic UsageModerator: Elaine L. Larson, R.N., Ph.D.

Columbia University School of NursingNew York, NY

4:15 p.m. S1 Molecular Characterization and Kinetic Mechanism of Streptomycin Adenylyltransferase from a Recombinant Escherichia coliS. Jana, J. Deb Department of Biochemical Engineering and Biotechnology, Indian Institute ofTechnology-Delhi, New Delhi, INDIA.

FINAL PROGRAM


CME

CME

FINAL PROGRAM


Monday, June 27, 2005 (continued)

4:30 p.m. S2 Antibiotic Resistance in Chlamydia spp.: Fitness Cost Associated with Spectinomycin Resistance due to Spontaneous Mutations in the 16S rRNA in C. psittaci 6BC.R. Binet, A. T. Maurelli Microbiology, USUHS, Bethesda, MD.

4:45 p.m. S3 Mechanisms of Acquired Microbial Resistance to Chlorine DioxideS. Powis, M. Riley, J. Hoying, S. K. Williams 1Biomedical Engineering, University of Arizona, Tucson, AZ

5:00 p.m. S4 Antibiotic Use and Beliefs in the Hispanic CommunityE. L. Larson1, M. Garcia2, J. Dilone1, J. Smolowitz1

1School of Nursing, Columbia University, New York, NY, 2Hispanic Research andRecruitment Center, Columbia University, New York, NY.

5:15 p.m. S5 Priorities for Controlling Antimicrobial Use: Linked Databases Can Show the WayD. M. Patrick, F. Marra, M. Chong, L. Lin, D. Roscoe, W. R. Bowie University of British Columbia, Vancouver, BC, CANADA.

5:30 p.m. Adjournment

5:30 p.m. Poster Session and Reception Waterford/Lalique Ballroom

Tuesday, June 28, 20057:00 a.m.–5:00 p.m. Registration Waterford Lobby

7:30 a.m. Continental Breakfast Waterford/Lalique Ballroom

Symposium 3: Economics of Antimicrobial Haverford/Baccarat Ballroom

ResistanceModerator: John Rex, M.D.

AstraZeneca PharmaceuticalsCheshire, United Kingdom

CME

FINAL PROGRAM


8:00 a.m. 9. Measuring Attributable Costs of Antibiotic Resistance

Anthony Harris, M.D., M.P.H.University of MarylandBaltimore, MD


8:30 a.m. 10. Cost Drivers of Infection Management: Why are Infections with Resistant OrganismsMore Costly and When Do Expensive Antimicrobials Save You Money?

Robert C. Owens, Jr., Pharm.D.Maine Medical CenterPortland, ME


9:00 a.m. 11. Pros and Cons of Strategics to Reduce Resistance

Donald A. Goldmann, M.D.Children’s HospitalBoston, MA


9:30 a.m. Coffee Break Waterford/Lalique Ballroom

Symposium 4. Antiviral Resistance Haverford/Baccarat Ballroom

Moderator: Stuart H. Cohen, M.D.University of California, Davis Medical CenterSacramento, CA

10:00 a.m. 12. The Role of Antiviral Resistance in the Treatment of Influenza

John Treanor, M.D.University of RochesterRochester, NY


10:30 a.m. 13. Resistance in the Management of Hepatitis B Infection

Daryl Ty Lau, M.D.University of Texas Medical BranchGalveston, TX

CME

FINAL PROGRAM


Tuesday, June 28, 2005 (continued)


11:00 a.m. 14. Antiretroviral Therapy: Resistance and the Role of Resistance Testing in ClinicalManagement

Roy M. Gulick, M.D.Weill Medical College & Cornell UniversityNew York, NY


11:30 a.m. Luncheon Presentation Waterford/Lalique BallroomManaging Serious Infections in an IncreasinglyComplex Environment

Submitted Presentations 2: Epidemiology and Clinical Haverford/Baccarat Ballroom

Aspects of ResistanceModerator: Jane F. Robens, D.V.M.

U.S. Department of AgricultureBeltsville, MD

1:00 p.m. S6 Characterization of Glycopeptide-Resistant Enterococcus faecium Isolated from a Semi-closed Vertically Integrated Population of Humans and Swine in the United States T. L. Poole1, M. E. Hume1, L. D. Campbell2, H. M. Scott2, W. Q. Alali2, R. B. Harvey1

1USDA, ARS, SPARC, College Station, TX, 2Veterinary Integrated Biosciences, Texas A&MUniversity, College Station, TX.

1:15 p.m. S7 Vancomycin-resistant Enterococci (VRE) from Human Stools in the CommunityA. May, K. Gay, K. Lewis, T. Barrett, T. Chiller, & NARMS Enterococci Working Group Centers for Disease Control and Prevention, Atlanta, GA.

1:30 p.m. S8 Nalidixic Acid Resistance in Salmonella Enteritidis, NARMS, 1996-2003F. Medalla, K. Gay, T. J. Barrett, T. M. Chiller, and the NARMS Working Group Centers for Disease Control and Prevention, Atlanta, GA.

1:45 p.m. S9 Effectiveness of Carbapenem in Infections Due to Extended Spectrum Beta Lactamase(ESBL) Producing OrganismsJ. L. Murillo, R. Elysee, M. HamraEpidemiology, Newark Beth Israel Medical Center, Newark, NJ.

CME

FINAL PROGRAM


2:00 p.m. S10 Epidemiology of Methicillin-resistant Staphylococcus aureus Infections at a Non-teaching Community HospitalA. Ramani1, M. Eckl2, M. Sweet 2

1Medicine, Columbia Memorial Hospital, Hudson, NY, 2Infection Control, ColumbiaMemorial Hospital, Hudson, NY.

2:15 p.m. S11 Developing Video Education on Methicillin-resistant Staphylococcus aureus for Correctional Facility Inmates: A Collaboration of Public Health and CorrectionalHealth Resources, New Jersey, 2004C. Robertson NJ Department of Health and Senior Services, Trenton, NJ.

2:30 p.m. Coffee Break Waterford/Lalique Ballroom

Symposium 5. Gram-Negative Bacilli Haverford/Baccarat Ballroom

Moderator: Susan J. Rehm, M.D.National Foundation for Infectious DiseasesBethesda, MD

3:00 p.m. 15. Epidemiology of Antimicrobial Resistant Gram Negative Infections

Arjun Srinivasan, M.D.Centers for Disease Control and PreventionAtlanta, GA


3:30 p.m. 16. Mechanisms of Resistance in ESBL-Producing Organisms

John P. Quinn, M.D.Cook County HospitalChicago, IL


4:00 p.m. 17. Susceptibility Testing and Treatment of Gram Negative Infections in Cystic Fibrosis

Lisa Saiman, M.D., M.P.H.College of Physicians and Surgeons of Columbia UniversityNew York, NY


4:30 p.m. 18. Control of Multi-drug Resistant Gram Negative Infections in the Healthcare Setting

Henry M. Blumberg, M.D.Emory UniversityAtlanta, GA

CME

FINAL PROGRAM


Tuesday, June 28, 2005 (continued)


5:00 p.m. Adjournment

Wednesday, June 29, 20057:00 a.m.–10:30 a.m. Registration Waterford Lobby

7:30 a.m. Continental Breakfast Waterford/Lalique Ballroom

Symposium 6. Defining Resistance in Vitro Haverford/Baccarat Ballroom

And In vivo: The Setting andSignificance of Breakpoints

Moderator: John H. Powers, M.D.Food and Drug AdministrationRockville, MD

8:00 a.m. 19. Clinicians View of the Use of Breakpoints

George M. Eliopoulos, M.D.Beth Israel Deaconess Medical CenterBoston, MA


8:30 a.m. 20. Data Used in Selecting Breakpoints: A View from NCCLS

Mary Jane Ferraro, Ph.D.Massachusetts General HospitalBoston, MA


9:00 a.m. 21. Putting Breakpoints into Practice: A View from the Clinical Laboratory

Janet Hindler, M.C.L.S., M.T. (ASCP), F.(AAM)University of California, Los Angeles Medical CenterLos Angeles, CA

CME

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9:30 a.m. 22. Impact of Breakpoints on the Medical System: A View from a Regulatory Agency

John H. Powers, M.D.Food and Drug AdministrationRockville, MD


10:00 a.m. Coffee Break Waterford/Lalique Ballroom

Symposium 7. Parasites Haverford/Baccarat Ballroom

Moderator: J. Todd Weber, M.D.Centers for Disease Control and PreventionAtlanta, GA

10:30 a.m. 23. Molecular Methods to Detect Drug Resistance in Parasites

Roger Prichard, Ph.D.McGill UniversityQuebec, Canada


11:00 a.m. 24. African Trypanosomiasis

Anne Moore, M.D., Ph.D.Centers for Disease Control and PreventionAtlanta, GA


11:30 a.m. 25. Drug Resistance in Visceral Leishmaniasis

Shyam Sundar, M.D., F.R.C.P.Banaras Hindu UniversityVaranasi, India


12:00 p.m. 26. Veterinary Helminthes

Ray M. Kaplan, D.V.M., Ph.D.University of GeorgiaAthens, GA

CME

FINAL PROGRAM


Wednesday, June 29, 2005 (continued)


12:30 p.m. Adjournment/Participant Evaluation

1:30 p.m. Meeting-Interagency Task Force on Antimicrobial ResistanceSponsored by the Centers for Disease Control and Prevention

* Speakers and presentations are subject to change

Poster Session and Reception Monday, June 27, 2005, 5:30 p.m. – 6:30 p.m.Waterford/Lalique Ballroom(posters will be on display throughout the remainder of the conference in theWaterford/Lalique Ballroom)

P1 Complicated Skin and Skin Structure Infections (cSSSI) Treated withDaptomycin (DAP) in the Cubicin® Outcomes Registry and Experience (CORE)W. J. Martone, K. C. Lamp Medical Affairs, Cubist Pharmaceuticals, Lexington, MA.

P2 Animal Arm of NARMS Recovery of Salmonella Heidelberg from 1998–2003J. D. Tankson1, P. J. Fedorka-Cray1, M. Headrick2

1Bacterial Epidemiology and Antimicrobial Resistance Unit, USDA-ARS, Athens,GA, 2FDA-CVM, Rockville, MD.

P3 Perspective on Multi-Drug Resistant Salmonella enterica serotype TyphimuriumDefinitive Phage Type 104 from the Animal Arm of NARMSP. J. Fedorka-Cray1, N. Anandaraman2, D. A. Dargatz3, M. Headrick4

1BEAR, USDA-ARS-RRC, Athens, GA, 2OPHS, USDA-FSIS, Washington, DC, 3CEAH,USDA-APHIS-VS, Fort Collins, CO, 4OR, FDA-CVM, Laurel, MD.

P4 Assessment of Drug Resistance in Streptococcus ThermophilusL. Morelli, L. Tosi, G. BerrutiIstituto di Microbiologia, Facoltà di Agraria UCSC, Piacenza, ITALY.

P5 A USDA Multi-Agency Project: Collaboration In Animal Health, Food Safety &Epidemiology (CAHFSE): On-Farm UpdateJ. S. Bailey1, P. J. Fedorka-Cray1, N. E. Wineland2, D. A. Dargatz2, S. R. Ladely1, J. F. Robens3, R. R. Kraeling1

1Bacteriological Epidemiology and Antimicrobial Resistance, USDA, ARS, Athens,GA, 2USDA, APHIS, Fort Collins, CO, 3USDA, ARS, Beltsville, MD.

FINAL PROGRAM


P6 Cephalosporin Susceptibility of Amoxi-R Salmonella Typhimurium Isolated fromCattle in the UK.V. Thomas1, M. Rose2, C. Wilhelm1, R. Davis3; 1Profiling, Intervet Innovation GmbH, Schwabenheim, GERMANY, 2ProductDevelopment, Intervet Innovation GmbH, Schwabenheim, GERMANY, 3Food andEnvironmental Safety Department, Veterinary Laboratories Agency, Weybridge,UNITED KINGDOM.

P7 In-vitro Susceptibility of E. coli Isolated from Feces of US Feedlot Cattle toCephalosporinsM. Rose1, C. Wilhelm2, G. Martin3;1Product Development, Intervet Innovation GmbH, Schwabenheim, GERMANY,2Product Profiling, Intervet Innovation GmbH, Schwabenheim, GERMANY,3Product Development, Intervet Inc., Millsboro, DE.

P8 Effects of Enrofloxacin Treatment in Intestinal Bacteria of ChickenJ. M. Miranda, C. M. Franco, C. A. Fente, B. I. Vazquez, A. CepedaQuÃmica AnalÃtica, NutriciÃ_n y BromatologÃa, Universidad de Santiago deCompostela, Lugo, SPAIN.

P9 Effects of Sulfonamides Treatment in Intestinal Bacteria of ChickenJ. M. Miranda, C. M. Franco, C. A. Fente, B. I. Vazquez, A. Cepeda QuÃmica AnalÃtica, NutriciÃ_n y BromatologÃa, Universidad de Santiago deCompostela, Lugo, SPAIN.

P10 Effects of Doxicyclyne Treatment in Intestinal Bacteria of ChickenJ. M. Miranda, C. M. Franco, C. A. Fente, B. I. Vazquez, A. Cepeda QuÃmica AnalÃtica, NutriciÃ_n y BromatologÃa, Universidad de Santiago deCompostela, Lugo, SPAIN.

P11 A Cationic Steroid Antibiotic Active Against Vancomycin-resistant Staphylococciand EnterococciP. B. Savage1, T. Bogdanovich2, P. C. Appelbaum2; 1Chemistry and Biochemistry, Brigham Young University, Provo, UT, 2Pathology,Milton S. Hershey Medical Center, Hershey, PA.

P12 A Cationic Steroid Antibiotic Active Against Highly Tobramycin-resistantPseudomonas AeruginosaP. B. Savage1, T. Orsak1, J. L. Burns2

1Chemistry and Biochemistry, Brigham Young University, Provo, UT, 2Pediatrics,University of Washington, Seattle, WA.

P13 The Use of Fluoroquinolones as Second-line Agents in the Treatment of Multi-drug Resistant TuberculosisD. Seyoum The United States Pharmacopial Convention, Inc., Rockville, MD.

FINAL PROGRAM


P14 Antibiotic Resistance in Chlamydia spp.: Fitness Cost Associated withSpectinomycin Resistance due to Spontaneous Mutations in the 16S rRNA in C. psittaci 6BC.R. Binet, A. T. Maurelli Microbiology, USUHS, Bethesda, MD.

P15 Availability of Antibiotics Without Prescription in New York CityE. LarsonSchool of Nursing, Columbia University, New York, NY.

P16 Effectiveness of Carbapenem in Infections Due to Extended Spectrum BetaLactamase (ESBL) Producing OrganismsJ. L. Murillo, R. Elysee, M. HamraEpidemiology, Newark Beth Israel Medical Center, Newark, NJ.

P17 Mechanisms of Acquired Microbial Resistance to Chlorine DioxideS. Powis1, M. Riley2, J. Hoying1, S. K. Williams1

1Biomedical Engineering, University of Arizona, Tucson, AZ, 2Agricultural andBiosystems Engineering, University of Arizona, Tucson, AZ.

P18 Vancomycin-resistant Enterococci (VRE) from Human Stools in the CommunityA. May, K. Gay, K. Lewis, T. Barrett, T. Chiller, &. NARMS Enterococci WorkingGroup CDC, Atlanta, GA.

P19 Nalidixic Acid Resistance in Salmonella Enteritidis, NARMS, 1996-2003F. Medalla, K. Gay, T. J. Barrett, T. M. Chiller, and the NARMS Working Group Centers for Disease Control and Prevention (CDC), Atlanta, GA.

ABSTRACTS OF INVITED PRESENTATIONS


ABSTRACTS OFINVITED

PRESENTATIONS



The Mathew Effect and the Tragedy of the Commons in Antimicrobial ResistanceH. GrundmannInstitute for Public Health and the EnvironmentBilthoven, Netherlands

Failure to invest in commons can be explained by game theory and commonlyresults from rational market decisions. The loss of effectiveness of antimicrobialcompounds (antimicrobcrobial resistance) is a classic example for his type of socialdilemma. Tyically, these tragedies lack a technical solutions. Four aspects of thedilemma of antimicrobial resistance shall be illustrated and the strategies ofmicroorganisms, which globally solve their own dilemma through clonal andcumulative evolution will be discussed.

Immunologic Therapeutics for Gram-Positive Bacterial InfectionsJ. PattiInhibitex, Inc.Alpharetta, GA

Microbial adhesion is the first crucial step in a series of events that often leads toinfection in humans. Staphylococci express MSCRAMM® proteins, a family of cellsurface adhesins that facilitate adherence and colonization by attaching toextracellular matrix components of host tissues or serum-conditioned implantedbiomaterials. Using genomic and proteomic tools, we have identified a number ofhuman antibodies targeting these proteins. The MSCRAMM® protein antibodiesinhibit staphylococci from attaching or recolonizing host tissues or implanted medicaldevices, as well as promote clearance by the immune system. We currently have threeprograms focused on developing human antibodies for the prevention and treatment ofstaphylococcal infections. Veronate®, a human polyclonal immunoglobulincontaining elevated levels of antibodies to both S. aureus and S. epidermidisMSCRAMM® proteins, is being developed for the prevention of infections in very lowbirth weight infants. Veronate® has enrolled over 1,100 neonates in a pivotal Phase IIIclinical trial. Aurexis®, a humanized monoclonal antibody, has recently completed aPhase II trial in patients with S. aureus bacteremia. In addition, we are developing avaccine that will prevent both S. aureus and coagulase-negative staphylococciinfections. Data supporting all three approaches will be the topic of discussion.

Natural Products Discovery: New Vistas Along Ancient PathsR. BaltzCubist Pharmaceuticals, Inc.Lexington, MA

Natural products produced by actinomycetes and fungi have been rich sources ofantibacterial agents. Over the past fifty years, at least 10 million strains ofactinomycetes and fungi have been screened by the pharmaceutical industry, and all ofthe commonly produced antibiotics have undoubtedly been discovered. The morecommon antibiotics pose problems for the discovery of rarer antibiotics because ofrediscovery and dereplication issues. The discovery rate of truly novel antibacterialagents has declined in recent years, partly because the pharmaceutical industry has notdeveloped robust methods to discover rare antibiotic producers. We have addressed thisissue by miniaturizing the fermentation by ~ 1000-fold using Ca++ alginatemacrodroplets, and screening for broad spectrum antibacterial activities on geneticallyengineered Escherichia coli strains resistant to many common antibiotics. Byencapsulating actinomycete spores extracted directly from pooled soil samples, we canscreen ~ 1000 times as many strains per year (>10 million) as by traditionalfermentation methodology.

In addition to our macrodroplet screening technology, we have developed moleculargenetic methods for natural product lead optimization. Traditionally, thepharmaceutical industry has used chemical modifications to optimize thepharmaceutically relevant characteristics of lead molecules. There are significantlimitations to this approach for complex natural products assembled by polyketidesynthase (PKS) and nonribosomal peptide synthetase (NRPS) mechanisms. Wedeveloped combinatorial biosynthesis methodology to modify the core peptide structureof daptomycin, a lipopeptide antibiotic produced by Streptomyces roseosporus andmarketed as Cubicin® by Cubist Pharmaceuticals. Combinatorial biosynthesis has beencoupled with medicinal chemistry to generate large numbers of daptomycin derivativeswith antibacterial activities.

Preventing Expression of Chromosomal Resistance DeterminatesJ. JudiceAchaogen, Inc.South San Francisco, CA

The emergence of drug-resistant bacteria poses a serious threat to human health. Inthe case of several antibiotics, including those of the quinolone and rifamycin classes,bacteria rapidly acquire resistance through mutation of chromosomal genes duringtherapy. In this work, we show that preventing induction of the SOS response byinterfering with the activity of the protease LexA renders pathogenic Escherichia coliunable to evolve resistance in vivo to ciprofloxacin or rifampicin, important quinoloneand rifamycin antibiotics. We show in vitro that LexA cleavage is induced duringRecBC-mediated repair of ciprofloxacin-mediated DNA damage and that this results inthe derepression of the SOS-regulated polymerases Pol II, Pol IV and Pol V, whichcollaborate to induce resistance conferring mutations. Our findings indicate that theinhibition of mutation could serve as a novel therapeutic strategy to combat theevolution of antibiotic resistance.

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Development and Implementation of an Integrated Platform to Optimize Agents for Biofilm ActivityA. LynchCumbre, Inc.Dallas, TX

Biofilms are glycocalyx-encased communities of microorganisms that grow attachedto solid surfaces, and have been associated with a wide variety of infections in patientswith indwelling medical devices. During the first part of his presentation, Dr. Lynchwill summarize the current state of knowledge regarding the scope and extent ofbacterial infections that are thought to be biofilm-associated and the mechanismsunderlying the unresponsiveness of such infections to conventional antibiotic therapy.Dr. Lynch will then outline alternate experimental strategies that have proposed orattempted in efforts to improve the therapeutic treatment of biofilm-associatedinfections. Dr. Lynch will then devote the remainder of his presentation to describingongoing efforts at Cumbre Inc. in the development and implementation of an integratedplatform of in vitro and in vivo assays to guide the development of chemotherapeuticagents with enhanced efficacy against biofilms formed by Staphylococcus aureus andepidermidis, the major causative pathogens of medical device-related infections. In thislast section of the presentation, validation of the Cumbre approach will be demonstratedby reference to the optimization of a novel agent with in vitro and in vivo biofilmactivity that is superior to currently approved antibiotics.

Animal Antibiotic Use: A Review of Recommendations, Actions, and ResultsT. ShryockElanco Animal HealthGreenfield, IN

Since 1997, the concern that the use of same-class antibiotics in food animalproduction can select for resistant bacteria that compromise human treatment has leadto numerous meetings and reports (e.g. the US Public Health Action Plan, WHO and OIEreports) that have similar recommendations to minimize and contain antibiotic resistantfood borne bacteria. For example, risk assessment, risk management (includingresponsible use programs, resistance monitoring, regulatory evaluations, replacementwith alternatives or discontinuation of certain uses) and research were consistent themes.In a short span of time in the U.S., the veterinary medical community, animal healthpharmaceutical industry, producer organizations, public health agencies, regulatoryauthorities, USDA researchers, consumer groups and many other stakeholders haveworked to develop and implement new regulatory guidance for microbial food safetyevaluations, conduct risk assessments, implement national antimicrobial resistancemonitoring systems, develop responsible use guidelines for key animal species, conductresearch into non-antibiotic alternatives and other related topics. Together, thesestrategies will minimize and contain antibiotic resistant food borne bacteria that maycome from food animal production.

Emerging Antimicrobial Resistance Trends in Human Medicine: A Global Review of Selected Surveillance ProgramsR. JonesJMI LaboratoriesNorth Liberty, IA

The national, as well as, global problem of antimicrobial resistance in humanmedicine can only be understood via the knowledge of the infections requiring therapyand the burden of resistant pathogens causing each type of infection. Approximately80% of all antimicrobials are prescribed for community-acquired respiratory tract(RTIs; pneumonia, bronchitis, sinusitis, pharyngitis), uncomplicated cutaneous andurinary tract (UTI) infections. An additional small volume of antimicrobial treatmentsaddress diarrheal illnesses (most untreated) and STD’s. Among the RTIs, S.pneumoniae, H. influenzae, M. catarrhalis and b-haemolytic streptococci predominatewith resistances of concern being to penicillin and macrolide in pneumococci and b-lactamase-mediated resistances in the Gram-negative species; most follow humanantimicrobial utilization patterns. Fluoroquinolone resistance has emerged in severalspecies found in ambulatory medicine including: E. coli (UTIs), S. pneumoniae (RTIs),N. gonorrhoeae (STDs), Salmonella spp. and Campylobacter spp. (diarrheal disease);most at lower levels in the USA compared to other nations. Community-acquired MRSArecently presents a serious challenge to oral treatment of skin and soft tissue infections.

Hospital-based infections have greater pathogen range dominated by S. aureus(approximately 50% MRSA), coagulase-negative staphylococci (CoNS), Enterococcusspp., P. aeruginosa, Acinetobacter spp. and numerous species of Enterobacteriaceaeincluding E. coli, Klebsiella spp. and Enterobacter spp. The most troublesomeresistance mechanisms have been: 1) increasing MRSA rates to over 50% (higher inEurope, Latin America and Asia); 2) multidrug-resistant (MDR) CoNS in bloodstreaminfections (BSI); 3) vancomycin-resistant enterococci (VRE) and more recently VISAand VRSA; 4) extended-spectrum b-lactamases (ESBLs) in Enterobacteriaceae especiallyE. coli and Klebsiella spp.; 5) persisting AmpC-mediated resistances in enteric bacilli

like Enterobacters; 6) MDR-P. aeruginosa and Acinetobacter spp. mediated bynumerous mechanisms including carbapenemases; and 7) epidemic MDR clonesdisseminating within and between medical centers (compromised infection control).Animal sources of these resistance patterns have been remote, but rarely noted amongso-called “cross-over pathogens” such as enterococci and diarrheal pathogens. Thenumber of these cases remains small and resistance burden more limited whenconsidering the total volume of resistant pathogens documented by comprehensivenational and international surveillance programs (Alexander Project, MYSTICProgramme, PROTEKT, SENTRY Antimicrobial Surveillance Program, EARSS, etc.).Continued longitudinal surveillance of resistance patterns will be critical to theunderstanding of the contribution of animal use of antimicrobials on documentedresistant human cases. Such programs must be sustained including those directed atmonitoring animal isolates and contaminated food products (NARMS, FIS, etc.).Information from these sources can be used to determine the type and scope ofintervention strategies based to risk assessments and accurate impact statements forall stakeholders.

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Animal Antibiotic Overuse: Public Health Concerns and Policy OptionsD. WallingaInstitute for Agriculture and Trade PolicyMinneapolis, MN

Recent estimates agree that antimicrobial use in U.S. animals exceeds 20 millionpounds annually. In 2003, the National Academy of Sciences’ Institute of Medicinearticulated what has become the consensus scientific opinion with respect to globalproblems of antibiotic resistance: "Clearly, a decrease in the inappropriate use ofantimicrobials in human medicine alone is not enough. Substantial efforts must bemade to decrease inappropriate overuse of antimicrobials in animals and agriculture as well." But disagreement remains as to how best and how rapidly to meet this goal.This presentation compares policies and actions already taken by European countries tolimit routine and non-prescription use of antibiotics in food animals, with those beingconsidered in the United States. European government and other published data on theresulting changes in antibiotic use, and on economic and public health impacts, will besummarized. The presentation will also contrast bacterial resistance as an ecologicalphenomenon with the risk assessment approaches to the problem used by U.S.regulatory agencies. The latter approaches typically consider only food ingestionamong the multiple potential routes of exposure to resistant bacteria from agriculturalenvironments, and they assess single "drug-bug" combinations rather than alsoconsidering co-selection which may occur when exposure to one antibiotic increasesresistance to other antibiotics.

Measuring Attributable Costs of Antibiotic ResistanceA. HarrisUniversity of MarylandBaltimore, MD

In this symposium, the impact of antimicrobial resistance on outcomes will bediscussed. A particular emphasis will be placed on the methodological challenges ofantimicrobial resistance outcomes studies. Three main topics will be dealt with: 1) What outcomes are being measured in studies and what additional outcomes shouldbe measured? 2) What confounding variables should be adjusted for and when shouldthey be measured? 3) What study design should be used? In the outcome measuretopic, length of stay, mortality, costs and charges will be discussed. In theconfounding variables topic, severity of illness, comorbidity and time at risk will bediscussed as important confounding variables. In the study design section, thedistinction between cohort and case control studies will be discussed as will the debateabout whether to choose random patients or patients with the susceptible-form of theorganism as the appropriate comparator group. Examples from the literature will beused to illustrate important points.

Cost Drivers of Infection Management: Why are Infections with ResistantOrganisms More Costly and When Do Expensive Antimicrobials SaveYou Money?R. OwensMaine Medical CenterPortland, ME

Antimicrobial resistance continues to evolve, become more prevalent, and to burdenexisting resources to new thresholds. To make matters worse, several leadingpharmaceutical companies have greatly reduced or eliminated their antimicrobial researchefforts. This is, in part, due to the fact that chronic medical conditions (eg, hypertension,baldness, erectile dysfunction) have a greater return on investment.

Costs related to infection depend on the differing perspectives (hospitals, third-partypayers, patients, society). Studies have demonstrated that patients who develop infection(vs. those who do not) incur greater costs. In a like manner, it is often found that infectionsdue to antimicrobial resistant organisms inflict greater costs than those caused by theirsusceptible counterparts. Rarely have all three scenarios been compared (no infection,susceptible infection, resistant infection). Thus, although the findings from these studiesseem intuitive, few studies have been adequately conducted to provide substantiation, andfew have taken into account all of the necessary perspectives. For the purposes of thispresentation, I will focus on the hospital perspective and a distillation of some of the currentliterature.

When do more expensive therapies make a difference in reducing overall costs?Therapeutic failures associated with inadequate treatment (often due to antimicrobialresistance or suboptimal drug exposure) are costly for several reasons, including the needfor retreatment with additional antimicrobials, costs associated with isolation (if resistantorganism), diagnostic modalities, adverse events, and the incremental length ofhospitalization. Thus, antimicrobials regardless of their purchase cost that are associatedwith greater efficacy rates clearly provide an opportunity for a reduction in overall costs (not to mention morbidity and mortality). The utility of a more expensive antimicrobialagent that may reduce length of stay may indeed reduce excess overall costs (e.g., oralformulation with activity against resistant organisms, convenient once-daily intravenousregimens that may facilitate therapy to the outpatient venue). The most costly antimicrobialagents are not necessarily the ones that are the most expensive to purchase, but rather arethe ones that do not work.

Cost Impact of Strategies to Reduce Resistance: Implications for theReal World – Things You Can Do, What They Cost, and Do They Work?D. GoldmannChildren’s HospitalBoston, MA

Disseminated On-site

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The Role of Antiviral Resistance in the Treatment of InfluenzaJ. TreanorUniversity of RochesterRochester, NY

Two classes of antiviral agents are available for the treatment and prevention ofinfluenza: M2 inhibitors, which are active only against influenza A viruses, andneuraminidase inhibitors (NAIs) which are active against both influenza A and B.Resistant viruses can be detected in individuals treated with either class of agent but aresignificantly more common in those treated with M2 inhibitors. In individuals with anintact immune system, shedding of resistant virus is not associated with treatmentfailure. However, transmission of M2 inhibitor resistant viruses from treatedindividuals to close contacts is well documented and associated with failure of antiviralprophylaxis in both family and institutional settings. This has not been documented intreatment with NAIs, possibly because resistance is less common and because somemutations associated with resistance also appear to result in decreased viral fitness.There is a critical need for continued surveillance of resistant viruses, particularly asthe use of antiviral agents increases. The role of combinations of antiviral agents toreduce generation of resistant viruses, particularly in immunocompromised hosts,remains to be explored. In addition, increasing use of influenza vaccine would likelyreduce the impact of antiviral resistance by preventing cases. Both vaccination andantiviral strategies play important roles in pandemic planning.

Resistance in the Management of Hepatitis B InfectionD. LauUniversity of Texas Medical BranchGalveston, TX


Antiretroviral Therapy: Resistance and the Role of Resistance Testing in Clinical ManagementR. GulickWeill Medical College and Cornell UniversityNew York, NY

HIV/AIDS-related mortality decreased 80% since 1995, due in large part to thedevelopment of effective antiretroviral therapy. Today there are 20 unique antiretroviraldrugs approved for the treatment of HIV infection in 3 distinct mechanistic classes:reverse transcriptase inhibitors, protease inhibitors and entry inhibitors. The goal ofantiretroviral treatment is to reduce the HIV RNA level as low as possible for as long as possible – this will lead to immune system enhancement and delay of clinicalprogression and concurrently, to the avoidance of the emergence of drug resistance. In an untreated HIV-infected individual, 10 billion virions are produced daily, leading toextensive viral diversity. With antiretroviral drug pressure, resistant viral variants areselected that lead to drug resistance and ultimately, drug failure. HIV drug resistance isassessed clinically and in the laboratory with a viral genotype, virtual phenotype, and/orphenotype. Clinical studies demonstrate benefits to conducting drug resistance testingand current HIV treatment guidelines recommend their use for patient management inspecific clinical situations. Investigational antiretroviral agents are in development thatdemonstrate activity against drug-resistant viruses. Additional basic and clinicalinvestigation will further refine HIV drug resistance, resistance testing and its role inclinical management.

15. Epidemiology of Antimicrobial Resistant Gram Negative InfectionsA. SrinivasanCenters for Disease Control and PreventionAtlanta, GA

Surveillance data indicate that both the incidence and resistance patterns of gramnegative infections in healthcare settings are continuing to change. While somestudies show these infections may be becoming less common, there is other data thatsuggests these infections might be a re-emerging problem in some settings. Manystudies also indicate that gram negative pathogens are becoming increasingly resistantto antimicrobial agents, a problem that is compounded by the lack of new agents indevelopment to treat these infections. This talk will briefly review some of thesestudies to give the attendee a sense of these merging issues.

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Mechanisms of Resistance in ESBL-Producing OrganismsJ. QuinnCook County HospitalChicago, IL

ESBLs occur amongst gram negative pathogens worldwide and pose challenges fordetection, reporting, infection control and therapy. In this presentation we will reviewrecent developments in this area. Surveys indicate that these enzymes appear to bemuch more common in Asia/Pacific and Latin American countries. The genetic diversityof these enzymes is impressive, with more than 200 variants described to date.

The TEM and SHV families were described first but the most common familyworldwide appear to be the CTX-M enzymes. They preferentially hydrolyze cefotaxime,sometimes without conferring resistance to ceftazidime, and usually mediate resistanceto cefepime as well. The structural basis for this has been facilitated by Xraycrystallography. Organisms producing CTX enzymes are particularly likely to beresistant to quinolones. They have been reported among community acquired infectionsin the United Kingdom, Spain and Canada. Several studies have reported isolation ofCTX producing enterics from animals intended for human consumption.

A large international study of bloodstream infections due to ESBL producersconfirmed earlier data that the carbapenems are the drugs of choice for seriousinfection, conferring a survival advantage over comparators.

Susceptibility Testing and Treatment of Gram Negative Infections inCystic FibrosisL. SaimanCollege of Physicians and Surgeons of Columbia UniversityNew York, NY

CF lung disease is characterized by a relentless cycles of infection andinflammation associated with predictable pathogens including Staphylococcus aureus,Haemophilus influenzae, and most importantly, Pseudomonas aeruginosa. Inaddition, some patients may harbor other multidrug-resistant (MDR) gram negativepathogens including Burkholderias spp., Stenotrophomonas maltophilia, andAchromobacter xylosoxidans. Treatment strategies for CF address different aspects of the natural history of lung disease. Pulmonary exacerbations are usually treatedwith two intravenous antibiotics with different mechanisms of action. Aerosolizedantibiotics (e.g., TOBI or colistin) and oral azithromycin are used for chronicsuppressive therapy and assorted strategies are used to eradicate initial P. aeruginosa.With time due to numerous, prolonged courses of oral, aerosolized, and intravenousantibiotics, CF pathogens become progressively MDR. Agar-based diffusion assays are the optimal methods for susceptibility testing for mucoid and non-mucoid P. aeruginosa as commercial microbroth dilution assays have unacceptably high ratesof very major and major errors for MDR strains.

However, traditional methods of antimicrobial susceptibility testing may notalways be applicable to CF. CF lung disease consists of an endobrochial biofilm whereinin vitro antimicrobial activity may not predict in vivo efficacy of antibiotics. Sputumglycoproteins bind aminoglycosides and decrease their activity. Breakpoints areunknown for aerosolized antibiotics as high concentrations of drug can be deliveredwith minimal toxicity. Synergy studies are used to guide treatment of MDR isolates.Furthermore, resistance patterns in non-CF isolates may not predict those noted in CFisolates. In summary, management of CF lung disease is complex, but may serve as amodel for other chronic infections, biofilm disease, and/ or hospital acquired MDRpathogens.

Control of Multi-drug Resistant Gram Negative Infections in theHealthcare SettingH. BlumbergEmory UniversityAtlanta, GA


Clinicians View of the Use of BreakpointsG. EliopoulosBeth Israel Deaconess Medical CenterBoston, MA

Clinicians use susceptibility test data provided by the microbiology laboratory toselect the most appropriate antibiotics for treating infections. The laboratory providessuch data in two forms: (1) as cumulative summary data for bacterial speciescommonly isolated in that laboratory, showing the percent susceptible to relevantantibiotics during a recent time period; and (2) as specific susceptibility data for anisolate obtained from an individual patient.

When prompt initiation of appropriate antimicrobial therapy is important,antibiotics are often chosen empirically based on likely pathogens for the type and site of infection, general susceptibility traits of suspected pathogens, and the localresistance patterns reported in institution-specific cumulative antibiograms. Definitivetherapy is then designed based on response to empirical therapy, and with knowledgeof the identity of the microorganism and of susceptibility test results.

Antibiotic susceptibility test interpretive criteria are developed by the Clinical andLaboratory Standards Institute (formerly NCCLS) to reflect the likelihood that aninfection may be appropriately treated, or not, with an antimicrobial agent dosed asrecommended for that type of infection.

As with any laboratory test result, susceptibility test information must beconsidered in the broader context of the patient and the infection. For a variety ofreasons, an antimicrobial with the lowest minimum inhibitory concentration in vitromay not always be the best agent for a particular infection.

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Data Used in Selecting Breakpoints: A View from NCCLSM. FerraroMassachusetts General HospitalBoston, MA

Throughout the world, different governmental agencies and professionalorganizations have responsibility for the initial establishment of antibiotic susceptibilitybreakpoints. In the United States, both the US FDA and the Clinical and LaboratoryStandards Institute (CLSI), formerly called NCCLS, have procedures in place toestablish breakpoints initially. In addition, CLSI is able to review, change when needed,and publish breakpoint updates on an annual basis. The breakpoints used to interpretantimicrobial susceptibility tests should be carefully determined initially, usingmicrobiological, pharmacokinetic/pharmacodynamic (PK/PD), and clinical data, andthen reevaluated periodically as changes in bacterial resistance, susceptibility testmethods, or antibiotic formulations occur. Microbiological data include frequencydistributions of MICs of microorganisms for which the drug is likely to be used, andcorrelation of MIC for organisms with specific, known resistance mechanisms. PK/PDdata may include standard PK information such as Cmax, AUC, and Time above MIC,etc. Information from animal models to select the most predictive PK/PD parameter foran antimicrobial class, and Monte Carlo analysis to predict the likelihood of success of agiven breakpoint among a large group of patients and microorganism MICs may also bereviewed. Lastly, correlations of MICs with clinical outcome and microbiologicaleradication data are reviewed.

Putting Breakpoints into Practice: A View from the Clinical LaboratoryJ. HindlerUniversity of California, Los Angeles Medical CenterLos Angeles, CA

Clinical microbiologists are faced with continuing challenges in detectingemerging resistance. Documents provided by the Clinical and Laboratory StandardsInstitute (CLSI, formerly NCCLS) are the primary resources for developing proceduresfor detecting antimicrobial resistance and these include interpretive standards orbreakpoints for interpreting disk diffusion and MIC results as susceptible, intermediateor resistant. There are increasing numbers of drug/organism combinations for whichspecial breakpoint rules must be considered. This presentation will provide insightinto a variety of breakpoint issues and strategies for dealing with them in the clinicallaboratory. For example, some non-epidermidis coagulase-negative staphylococci withoxacillin MICs just above the resistant breakpoint may require supplemental testing toavoid reporting false oxacillin resistance. Salmonella spp. from bacteremic patientswith ciprofloxacin MICs in the susceptible range must be tested with nalidixic acid todetect subtle decreases in fluoroquinolone susceptibility that may translate intoclinical resistance. Reporting cefotaxime or ceftriaxone MICs on blood isolates ofStreptococcus pneumoniae requires application of both meningitis and non-meningitis breakpoints. In addition to these and other breakpoint rules, application of CLSI breakpoints to commercial testing and reporting systems can be challengingand requires support from information technology.

Impact of Breakpoints on the Medical System: A View from a Regulatory AgencyJ. PowersFood and Drug AdministrationRockville, MD


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22 Molecular Methods to Detect Drug Resistance in ParasitesR. PrichardMcGill UniversityQuebec, Canada

Parasitic diseases are increasingly being targeted for regional and global control andelimination programs. This is particularly true for the filarial parasitic diseases, such aslymphatic filariasis and onchocerciasis, as well as for other helminth diseases such asschistosomiasis. For reasons of effectiveness and cost, these control and eliminationprograms rely almost entirely on the use of a very small number of antiparasitic drugs.Currently, for onchocerciasis the only drug available is ivermectin (Mectizan‰) and forlymphatic filariasis, albendazole is being used in combination with ivermectin ordiethylcarbamazine. Resistance to albendazole and ivermectin has developed rapidly innematode parasites of veterinary importance. In Onchocerca volvulus and Wuchereriabancrofti there is evidence that resistance to ivermectin and albendazole, respectively, maybe developing. These parasites cannot be maintained in laboratory animals nor readilytested in vitro for susceptibility to antiparasitic drugs and DNA based methods for thedetection of genetic changes associated with drug selection are needed to monitor for drugresistance.

In the case of albendazole, the mechanism of resistance is relatively well understood asPhe200Tyr or Phe167Tyr single nucleotide polymorphisms (SNPs) in b-tubulin and wehave routinely assayed for these SNPs using Real Time PCR or Pyrosequencing. Ivermectinresistance is not so well understood. However, genetic changes in ABC transporter genes,such as P-glycoprotein, and in also in b-tubulin have been found in ivermectin resistantveterinary nematode parasites and in O. volvulus that have been under ivermectinselection. These genes, and possibly other genes that can contribute to ivermectinresistance, can be monitored for changes in genetic polymorphism using a variety ofmethods, such as single strand conformational polymorphism (SSCP), restrictionfragment length polymorphism (RFLP) and amplicon length gel electrophoresis. However,further research is needed to identify SNPs that are highly correlated with ivermectinresistance. These DNA based methods are being used on individual parasites, includinglarval stages, to monitor for anthelmintic drug selection in parasitic nematodes.

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African TrypanosomiasisA. MooreCenters for Disease Control and PreventionAtlanta, GA

A resurgence of human African trypanosomiasis (HAT) caused by Trypanosomabrucei gambiense occurred during the past two decades in central Africa. Humansconstitute the infection reservoir and, therefore, effective treatment is a critical elementof disease control. Melarsoprol is the most important therapeutic agent, and theemergence and potential spread of drug resistance is a serious threat, in view of thelimited number of alternative drugs and the fatal outcome of untreated disease.HATSENTINEL is a hospital-based sentinel surveillance system for HAT treatmentfailure, sponsored by the World Health Organization and CDC, with Ministries of Health and other partners. There are currently more than 2500 patients enrolled from nine facilities in five central and East African countries. The surveillance hasdocumented high rates of melarsoprol-refractory infection at sites within Angola andthe Democratic Republic of Congo. These results have led to changes in first linetherapy in the affected provinces. Current efforts to establish the cause of treatmentfailure and improve therapy for this challenging disease will be discussed.

Drug Resistance in Visceral LeishmaniasisS. SundarBanaras Hindu UniversityVaranasi, India

Antimonial compounds (Sbv) are used worldwide for the treatment of visceralleishmaniasis (VL) for over six decades with little variation in sensitivity. In theseventies, its low dose would be curative for most patients with Indian VL.Unresponsiveness in a significant proportion of patients in the early eighties led tosuccessive upward revisions in doses, leading to six to ten times more drugs beingrecommended. However, this did not stem the increasing unresponsiveness and nowonly 35% patient respond to Sbv in North Bihar, India. Sbv resistance appears to bespreading to Nepal. Important reasons for drug failure have been rampant use of Sbvin subtherapeutic doses, incomplete duration of treatment, substandard drugs etc, and majority of patients may not receive the drug according to the prevailingrecommendations. Being anthroponotic transmission in the Indian Subcontinent,once established, there is an exponential rise in Sbv refractoriness. In vitroexperiments have established emergence of Sbv resistant strains of L donovani.Efficacy of pentamidine, a toxic second line drug, has also declined from a 99% to 69-78% patients. Fortunately, inventory of clinically useful antileishmanial drug hasexpanded in recent years, and combination therapy with improved compliance appearsto the way forward.

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Veterinary HelminthesR. KaplanUniversity of GeorgiaAthens, GA


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Molecular Characterization and Kinetic Mechanism of StreptomycinAdenylyltransferase from a Recombinant Escherichia coliS. Jana, J. DebDepartment of Biochemical Engineering and Biotechnology, Indian Institute of Technology-Delhi, New Delhi, INDIA.

Background: Streptomycin is inactivated via ATP-dependent O-adenylation bystreptomycin adenylyltransferases (SMATase), leading to chemically modifiedstreptomycin which binds poorly to ribosomes and results in high level resistance [1]. Tounderstand the biochemical interactions between the streptomycin adenylyltransferase(SMATase) and the associated substrates, it is necessary to know its three-dimentionalstructure. There is also no information available on three-dimentional structure,biochemical properties and secondary structure of SMATase. It is an ideal candidate for amore thorough investigation of the biochemical mechanism and secondary structure ofSMATase.

Methods: The streptomycin adenylyltransferase activity was determined by radioactiveassay method of Hass and Dowding (1975) [2]. The initial velocities were determined as afunction of the concentration of one substrate (_-32P-ATP) at a fixed saturating second-substrate (streptomycin) concentration and vice versa. Far-UV CD spectrum of SMATasewas recorded in a Jasco J-810 spectro polarimeter

Results: We have developed an expression system pETSm6 for recombinant thioredoxin-his6-tagged-SMATase. Kinetic results surmised that streptomycin adenylyltransferasefollowed an ordered, sequential kinetic mechanism in which the nucleotide substrate(ATP) binds prior to the antibiotic and pyrophosphate is released prior to the AMP-streptomycin. The results of secondary structure analysis showed that the SMATase hadthe secondary structural content with 44% _-sheet, 23% _-helix, 13 % _-turn, and 20%random coil.

Conclusion: The kinetic results confirm that SMATase follows an ordered sequentialmechanism. The analysis of the CD features for the determination of secondarystructural class reveals that it is an _ + _-type protein.

References:1. Davies J, Wright GD. Bacterial resistance to aminoglycoside antibiotics. Trends

Microbiol 1997; 5:234-240.

2. Hass JH, Dowding JE. Aminoglycoside modifying enzymes. Methods Enzymol 1975;43: 611-640.

S1 Antibiotic Resistance in Chlamydia spp.: Fitness Cost Associated with Spectinomycin Resistance due to Spontaneous Mutations in the 16S rRNA in C. psittaci 6BC.R. Binet, A. T. MaurelliMicrobiology, USUHS, Bethesda, MD.

Analysis of the genome sequence of several members of the Chlamydiaceae revealedthat these obligate intracellular bacteria harbor only one or two sets of rRNA genes. Astetracyclines and macrolides are the ribosomal drugs currently used to treat chlamydialinfections, we studied the contribution of rRNA mutations to the emergence ofantibiotic resistance in Chlamydia species, using the sensitivity of C. trachomatis L2(two rrn operons) and C. psittaci 6BC (one rrn operon) to spectinomycin as a model.Confluent cell monolayers were infected in the plaque assay with 108 wild-typeinfectious particles then treated with the antibiotic. After a two-week incubation time,plaques formed by spontaneous spectinomycin resistant (SpcR) mutants appeared witha frequency of 5 x 10-5 for C. psittaci 6BC. No SpcR mutants were isolated for C.trachomatis L2 although the frequencies of rifampicin resistance were in the samerange for both strains (i.e. 10-7). Sequencing of the 16S rRNA from 59 independentSpcR isolates identified mutations at position 1192, 1191 and 1193 (according to theEscherichia coli numbering system), previously described in other SpcR bacteria orchloroplasts. We found that C. psittaci 6BC isolates carrying A1191 to G or G1193 to Cmutations displayed a longer doubling time and were severely out-competed by theparent strain in co-infection assays. By contrast, mutations at 1192 had minor effectson the bacterial life cycle. This study provides a new strategy to predict, monitor andperhaps prevent emergence of antibiotic resistance in chlamydiae.

Reference:1. Wang SA, Papp JR, Stamm WE, Peeling RW, Martin DH, Holmes KK. Evaluation of

antimicrobial resistance and treatment failures for Chlamydia trachomatis: ameeting report. J Infect Dis 2005; 191:917-923.

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Mechanisms of Acquired Microbial Resistance to Chlorine DioxideS. Powis1, M. Riley2, J. Hoying1, S. K. Williams1

1Biomedical Engineering, University of Arizona, Tucson, AZ, 2Agricultural andBiosystems Engineering, University of Arizona, Tucson, AZ.

Background: Chlorine dioxide (ClO2) is a biocide utilized for the disinfection of food andwater. We are developing ClO2-generating biomaterials for the in situ prevention ofinfection. While testing the bactericidal activity of a ClO2-generating material, aspontaneous mutant of Staphylococcus epidermidis (S. epidermidis) with a reducedsusceptibility to ClO2 was isolated (SP030724). A review of works by other investigatorson acquired microbial resistance to biocides yielded no prior demonstration of microbesdeveloping resistance to ClO2. The mechanisms behind the development of biocideresistance are not well established, and there is a growing concern about the clinicalsignificance of biocide resistance [1]. Investigating this new resistant microbe willadvance our understanding of the mechanisms responsible for biocidal resistance.

Methods: The supernatant produced by SP030724 was analyzed to determine if themechanism of resistance was intracellular or extracellular. The results established thatresistance was due to an extracellular factor. The unknown molecule was assessed for:temperature stability, degree of hydrophobicity, and molecular weight.

Results: Experimental results indicated the molecule: is inactivated by temperatures ≥60°C, but stable at 4°C, is hydrophilic, and has a MW ≥ 100kDa. Preliminary gelelectrophoresis experiments suggest the presence of a protein in SP030724 supernatant,not present in wildtype S. epidermidis supernatant.

Conclusions: SP030724 produces a molecule that reduces the susceptibility of themicroorganism to ClO2.

References:1. Russell AD. Introduction of biocides into clinical practice and the impact on

antibiotic-resistant bacteria. J Appl Microbiol 2002; 92(Suppl):121S-135S.

2. Poole K. Mechanisms of bacterial biocide and antibiotic resistance. J Appl Microbiol2002; 92(Suppl):55S-64S.

S3 Antibiotic Use and Beliefs in the Hispanic CommunityE. L. Larson1, M. Garcia2, J. Dilone1, J. Smolowitz1

1School of Nursing, Columbia University, New York, NY, 2Hispanic Researchand Recruitment Center, Columbia University, New York, NY.

Background: Antibiotic use is generally measured from prescription information and istherefore likely to be underreported. This paper presents results from severalhousehold-level surveys among Hispanics in northern Manhattan.

Methods: Two prevalence surveys (n=2,840) and eight focus groups of recentlyimmigrated Hispanics to determine use and beliefs regarding antibiotics, plus a surveyof small businesses in NYC regarding selling antibiotics over-the-counter.

Results: More than one-third of respondents reported antibiotic use in previous 3months. All (n=34) small bodegas and pharmacies in the Hispanic neighborhood soldantibiotics without prescription. Knowledge regarding antibiotics and resistance waspoor.

Conclusions: To be effective among recent Hispanic immigrants, interventions toimprove antibiotic use must involve small businesses and community organizations aswell as conventional health care providers.

References:1. Larson E, Grullon-Figueroa L. Availability of antibiotics without prescription in

New York City. J Urban Health 2004; 81:498-504.

2. Aiello A, Cimiotti J, Della-Latta P, Larson E. A comparison of bacteria found onhands of homemakers and neonatal intensive care unit nurses. J Hosp Infect 2003;54:310-315.

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Vancomycin-resistant Enterococci (VRE) from Human Stools in theCommunityA. May, K. Gay, K. Lewis, T. Barrett, T. Chiller, &. NARMS EnterococciWorking Group; CDC, Atlanta, GA.

Background: Vancomycin-resistant enterococci (VRE) infections are an importantcause of morbidity and mortality. VRE transmission has been documented in thehospital setting. There is little evidence, however, for VRE transmission in thecommunity in the United States.

Methods: From 2000-2002, 10-20 stool specimens per month were obtained fromhealthy volunteers or outpatients with diarrhea, who reported no hospital contact in atleast 6 months, in five states (Georgia, Maryland, Michigan, Minnesota, and Oregon).One enterococcal isolate per specimen was sent to CDC. Following incubation inEnterococcosel media, enterococci were speciated by biochemical assays and tested forantimicrobial susceptibility by broth microdilution.

Results: VRE was isolated from 29 (1.4%) of 2061 stool specimens; 28 were E. faeciumand 1 was E. faecalis. VRE were isolated from participants in three states. Of VREisolates tested 87% (20/23) were additionally resistant to ciprofloxacin, 83% (20/24) to bacitracin, 54% (13/25) to tetracycline, 50% (12/24) to gentamicin, 12% (3/25)quinupristin-dalfopristin (Q/D), and none to linezolid. Two VRE isolates were resistantto both Q/D and tetracycline

Conclusion: VRE was isolated from outpatient stool samples, including persons with no apparent contact with hospitals, suggesting that VRE may have been acquired in the community. More than 10% of VRE isolated were also resistant to quinupristin-dalfopristin, one of the few available options for the treatment of VRE. It will beimportant to further characterize the epidemiology of acquisition of VRE and themolecular mechanism of vancomycin resistance among these isolates.

Reference:Bonten MJ, Willems R, Weinstein RA. Vancomycin-resistant enterococci: why are theyhere, and where do they come from? Lancet Infect Dis 2001; 1:314-325.

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Priorities for Controlling Antimicrobial Use: Linked Databases Can Show the WayD. M. Patrick, F. Marra, M. Chong, L. Lin, D. Roscoe, W. R. BowieUniversity of British Columbia, Vancouver, BC, CANADA.

Background: We linked several comprehensive, population databases to elucidate trendsand indications for antimicrobial consumption and their correlates with resistance.

Methods: BC Pharmanet records all ambulatory prescriptions in British Columbia (BC).Pharmanet records were classified by the Anatomical Therapeutic Chemical system anddefined daily dose (DDD) conversions performed. Overall and class-specific consumptionwas described by year. Consumption and resistance trends were correlated using theSpearman rank correlation coefficient. Indications for prescription were determined bylinkage of Pharmanet data with the physician billing and diagnostic database from theMedical Services Plan (MSP), a single payer system for BC.

Results: Between 1996 and 2002, consumption of antibiotics (ATC code J01) declined from18.5 to 15.1 DDD per 1000 inhabitant days but rebounded to 15.9 in 2003. The rebound isdriven largely by a longer-term increase (1999-2003) in prescription of macrolides (2.7-3.4DDD/1000 inhabitant-days), especially azithromycin and clarithromycin (0.7-2.3 DDD/1000inhabitant-days). Consumption of new (longer half-life) macrolides correlates withincreasing resistance to erythromycin among pneumococci in BC (r=0.77; p=0.036).Linkage with MSP indicates that 37.6% of macrolide prescriptions were for bronchitis(other than chronic), 12.6% for upper respiratory infections commonly caused by virusesand <6% for pneumonia.

Conclusion: A recent increase in new macrolide consumption is reversing historictrends to reduced antimicrobial consumption and is associated with increasingresistance in pneumococci in BC. This implies a need to launch and evaluate a campaignto reduce overuse of these agents for bronchitis and other upper respiratory infections.

References:1. Patrick DM, Marra F, Hutchinson J, Monnet DL, Ng H, Bowie WR. Antibiotic

consumption in populations: How doe s a North American jurisdiction compare withEurope? Clin Infect Dis 2004; 39:11-17.

2. Marra F, Patrick DM, White R, Ng H, Bowie WR, Hutchinson JM. Effect of formularypolicy decisions on antimicrobial drug utilization in British Columbia. J AntimicrobChemother 2005; 55:95-101.

S5 Characterization of Glycopeptide-Resistant Enterococcus faecium Isolatedfrom a Semi-closed Vertically Integrated Population of Humans and Swinein the United StatesT. L. Poole1, M. E. Hume1, L. D. Campbell2, H. M. Scott2, W. Q. Alali2, R. B. Harvey1

1USDA, ARS, SPARC, College Station, TX, 2Veterinary IntegratedBiosciences, Texas A&M University, College Station, TX.

Background: Vancomycin-resistant Enterococcus faecium (VRE) have emerged asimportant nosocomial pathogens, but have rarely been isolated outside of a hospitalsetting in the United States (2). A longitudinal epidemiological study of sewageeffluents from a semi-closed vertically integrated population of humans and swine inTexas resulted in the isolation of VRE from the human community.

Methods: E. faecium isolates were identified and speciated by standard microbiologicalmethods and PCR, respectively (1). Heterogeneity of the isolates was determined byPCR, Pulsed-field gel electrophoresis and PCR fragment length polymorphism analysis.

Results: Fifty VRE were obtained from human sewage effluent at multiple locations,including swine workers’ dormitories, from 2002 to present. To date no VRE have beenisolated from swine fecal samples. Forty-nine of the VREs carried the vanA glycopeptideresistance gene cluster and one carried the vanB gene cluster. There were 21 pulsed-field gel electrophoresis types. PCR fragment length polymorphism analysis revealedthe presence of an insertion sequence (IS1251) in 38 isolates.

Conclusions: In the study population over a two year period clonal and non-clonalstrains of VRE were identified from swine workers’ sewage effluent. IS1251 has onlybeen described in human VRE isolates in the U.S. There was no apparent disseminationof VRE from humans to swine. This is the first known community isolation of VRE inthe U.S.

References:1. Jackson CR, Fedorka-Cray PJ, Barrett JB. Use of a genus-and species-specific

multiplex PCR for identification of enterococci. J Clin Microbiol 2004; 42:3558-3565.

2. Simjee S, White DB, McDermott PF, et al. Characterization of Tn1546 invancomycin-resistant Enterococcus faecium isolated from canine urinaryinfections: evidence of gene exchange between human and animal enterococci. JClin Microbiol 2002; 40:4659-4665.

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Nalidixic Acid Resistance in Salmonella Serotype Enteritidis, NARMS,1996-2003F. Medalla, K. Gay, T. J. Barrett, T. M. Chiller, and the NARMS WorkingGroup Centers for Disease Control and Prevention (CDC), Atlanta, GA.

Background: Salmonella serotype enteritidis (SE) is a leading cause of salmonellosis.Egg, chicken, and egg-containing foods are important sources of SE. For seriousillness, quinolones (i.e. ciprofloxacin) are considered primary treatment in adults.Nalidixic acid (NA) resistance in Salmonella is correlated with decreased susceptibilityto ciprofloxacin and treatment failure.

Methods: Since 1996, participating state health departments submitted non-typhiSalmonella isolates to the National Antimicrobial Resistance Monitoring System(NARMS) for Enteric Bacteria at CDC for antimicrobial susceptibility testing usingbroth microdilution to determine minimum inhibitory concentration (MIC). NAresistance was defined as MIC > 32 µg/ml.

Results: From 1996 to 2003, 2370 SE isolates were tested, of which 67 (3%) were NA-resistant. The age, gender, and specimen source for patients with NA-resistant andNA-susceptible SE were similar. The percentage of SE resistant to > 1 antimicrobialagent decreased from 31% (110/357) in 1996 to 9% (24/257) in 2003 (p<0.0001).However, the percentage of SE resistant to NA increased from 1% (3/357) in 1996 to 6%(15/257) in 2003 (p<0.01). 88% of NA-resistant SE had decreased susceptibility tociprofloxacin (MIC > 0.12 µg/ml).

Conclusions: The prevalence of NA-resistant SE has increased in NARMS since 1996.Whether these infections were acquired domestically needs to be determined. However,as SE infections are primarily associated with egg and chicken consumption, it isimportant to understand how the use of quinolones in poultry may have contributed toemerging resistance. Continued monitoring of this trend is important given its clinicaland public health implications.

References:1. Hakanen A, Kotilainen P, Jalava J, Siitonen A, and Huovinen P. Detection of

decreased fluoroquinolone susceptibility in Salmonellas and validation of nalidixicacid screening test. J Clin Microbiol 1999; 37:3572-3577.

2. Schroeder CM, Naugle AL, Schlosser WD, et al. Estimate of illnesses from Salmonellaenteritidis in eggs, United States, 2000. Emerg Infect Dis 2005; 11:113-115.

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Epidemiology of Methicillin-resistant Staphylococcus aureus Infectionsat a Non-teaching Community HospitalA. Ramani1, M. Eckl2, M. Sweet2

1Medicine, Columbia Memorial Hospital, Hudson, NY, 2InfectionControl, Columbia Memorial Hospital, Hudson, NY.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as amajor cause of morbidity and mortality in the United States. Originally confined tohospitals especially tertiary care centers, it has now spread beyond the confines ofhealth care facilities, emerging anew in the community, where it is rapidly becoming adominant pathogen. In order to understand the epidemiology of MRSA and to monitorits pattern in a community hospital, we conducted a prospective study at the ColumbiaMemorial Hospital (CMH) in Hudson, NY.

Methods: We prospectively evaluated all MRSA infections from January to December2004 in patients admitted to CMH. MRSA was considered community acquired (CA) ifrecovered within the first 48 hours of hospitalization. Medical records for each newlyidentified inpatient with MRSA infection were reviewed. We studied the age, sexdistribution, source and antibiogram patterns.

Results: During the study, 78 cases of MRSA infections were identified. Age: 72.1 ± 13,median age: 75, female 43.59% male 56.41%. Of the 78 patients 74.36% infections werecommunity acquired and 25.64% were nosocomially acquired. Source (%): pulmonary(48.87), blood (15.38), Urine (12.82), and soft tissue (26.92). Antibiotic susceptibilityprofile of MRSA isolates (%): clindamycin, erythromycin, linezolid, oxacillin,tetracycline, and TMP/SMX (11, 5, 100, 0, 96, 98).

Conclusions: This study demonstrates that even in smaller non-teaching communityhospitals prevalence of community acquired MRSA infections is high and beta-lactamantibiotics may no longer be a reliable empirical antibiotic choice.

References:1. Saiman L, O’Keefe M, Graham PL 3rd, et al. Hospital transmission of community-

acquired methicillin-resistant Staphylococcus aureus among postpartum women.Clin Infect Dis 2003; 37:1313-1319.

2. O’Brien FG, Pearman M, Gracey T, et al. Community strain of methicillin-resistantStaphylococcus aureus involved in a hospital outbreak. J Clin Microbiol 1999;37:2858-2862.

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Developing Video Education on Methicillin-resistant Staphylococcusaureus for Correctional Facility Inmates: A Collaboration of PublicHealth and Correctional Health Resources, New Jersey, 2004C. TanNJ Department of Health and Senior Services, Trenton, NJ.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasinglyrecognized among correctional facility populations nationwide. However, littleliterature exists about educational materials on MRSA for correctional facilities. NewJersey public health and correctional health officials collaborated on identifying,developing and implementing educational efforts targeting inmates. We conductedfocus groups with selected inmates at two state correctional facilities to characterizetheir knowledge of MRSA and preferred educational tools. We interviewed 26 inmatesfrom a women’s and a male youth correctional facility. Eighteen (69%) inmates hadnever heard of MRSA prior to the focus groups, and nearly all inmates demonstratedlack of knowledge about MRSA preventive measures such as handwashing. All inmatespreferred video as an educational tool. We developed a 20-minute video that providedMRSA information and personal protective recommendations. We distributed 35 videosto all state and county correctional facilities which showed videos to inmates on intakeand during activity hours. We promoted the video in national correctional healthvenues; subsequently we also distributed the video to 30 other states that requested itand granted permission to one state that will reproduce the video for all its facilities.Collaboration between public health and correctional health officials facilitateddevelopment of an educational video tailored to identified inmate needs. Further post-video evaluations of inmates to assess the video’s impact on inmates’ MRSA knowledgeare in progress.

Reference:1. Methicillin-resistant Staphylococcus aureus infections in correctional facilities—

Georgia, California, and Texas, 2001-2003. MMWR 2003; 52:992-996.

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Effectiveness of Carbapenem in Infections Due to Extended Spectrum BetaLactamase (ESBL) Producing OrganismsJ. L. Murillo, R. Elysee, M. HamraEpidemiology, Newark Beth Israel Medical Center, Newark, NJ.

Background: Patients infected with ESBL-producing organisms are frequently treatedwith carbapenems.

Methods: A retrospective chart review of 91 patients with infections due to ESBLproducing organisms was performed from January 1, 2002 to June 30, 2004 andanalyzed using Student t test and chi-square analysis.

Results: The mean age was 66.2 years (range 13-99 years). 45 patients were males and46 were females. Escherichia coli caused 45 infections, Klebsiella pneumoniae 40 andKlebsiella oxytoca 6. The overall mortality rate was 20.8% (19/91). The mortality ratefor E coli was 20% (9/45), Klebsiella pneumoniae 22.5% (9/40) and Klebsiella oxytoca16.6% (1/6). The average length of stay (LOS) was 54.1 days (range 1 to 429 days). Theaverage LOS for E coli (35.4 days) was significantly different from Klebsiellapneumoniae (75.3 days), p value <0.01. The common sites of infection were urine48.4%, blood 23.1%, respiratory 7.7% and wound 5.5%. Most patients had at least 3 co-morbid conditions. Excluding patients who were already infected on admission, theaverage time to infection was 39.1 days (range 3-201 days). Of 31 patients who receiveda carbapenem, 8 died (25.8%) while 11 of 42 patients (26.1%) who did not receive acarbapenem died. The APACHE II score at the time of positive culture was significantlyworse among patients who died (p<0.001).

Conclusions: No difference in mortality rates between patients whether they received acarbapenem or not. Patients infected with ESBL-producing Klebsiella pneumoniaestayed longer in the hospital.

References:1. Kang CI, Kim SH, Park WB, et al. Bloodstream infections due to extended-

spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae:risk factors for mortality and treatment outcome. Antimicrob Agents Chemother2004; 48:4574-4581.

2. Du B, Long Y, Liu H, Chen D, et al. Extended spectrum beta-lactamase-producingEscherichia coli and Klebsiella pneumoniae bloodstream infection. Intensive CareMed 2002; 28:1718-1723.

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ABSTRACTS OFSUBMITTED POSTER

PRESENTATIONS



Complicated Skin and Skin Structure Infections (cSSSI) Treated withDaptomycin (DAP) in the Cubicin® Outcomes Registry and Experience(CORE)W. J. Martone, K. C. Lamp Medical Affairs, Cubist Pharmaceuticals, Lexington, MA.

Background: DAP (Cubicin®) was approved in September 2003 for treatment of cSSSIdue to certain susceptible Gram-positive pathogens, including methicillin-susceptibleStaphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Little isknown about post-approval clinical experience with DAP.

Methods: CORE is a retrospective observational chart review to quantitatecharacteristics and clinical outcome of patients (PTS) receiving DAP. 165 records ofPTS with cSSSI due to culture confirmed MSSA or MRSA were analyzed.

Results: 143 PTS had MRSA, 20 had MSSA, and 2 had MRSA and MSSA (classified asMRSA) infections. 61% of PTS were > 50 yrs; diabetes (20%) and hypertension (10%)were the most common underlying diseases. 74% of MRSA and 70% of MSSA PTSreceived other antibiotics before starting DAP and 30% reported concomitantantibiotics (cephalosporins 9.1% and fluoroquinolones 9.7%). Most common DAPdosages were 4mg/kg/d (52%), 6 mg/kg/d (15%) and 4mg/kg qod (5%). Clinical successwas reported in 89% PTS (52% cure and 37% improved), failure in 2%, andnonevaluable/other in 8%. Outcomes were similar in MRSA (90% success) and MSSA(85% success). Average days to clinical response: MRSA 5.2 d, MSSA 4.9 d. Conclusion:DAP therapy of cSSSI was predominately second line, frequently with concomitantantibiotics. PTS with MRSA and MSSA cSSSIs had similar outcomes and days toclinical response, however MSSA numbers were small.

Reference:1. Arbeit RD et al. The safety and efficacy of daptomycin for the treatment of

complicated skin and skin structure infections. Clin Infect Dis 2004;38:1673-81.

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Assessment of drug resistance in Streptococcus thermophilusL. Morelli, L. Tosi, G. Berruti Istituto di Microbiologia, Facoltà di Agraria UCSC, Piacenza, ITALY.

Background: Fermented foods are part of our diet and it is estimated that one-quarterof fermented food production involves lactic acid bacteria. An assessment of bacteriaused in food for their profile of antibiotics resistances is thus relevant. Unfortunatelythere is noconsensus on how to measure microbiological breakpoints in LAB and a lackof information exists about the presence in these bacteria of transferable drug resistantgenes.

Methods: The bacterial species of choice is Streptococcus thermophilus; 70 strainsbelonging to the Istituto di Microbiologia Culture Collection (CUP) were analysed byusing different culture media, in order to assess the influence of media components. Acomparison between the disc diffusion, the microdilution broth method and Etest wascarried out. Antibiotic used were erythromycin, tetracycline and streptomycin.

Results: All 70 S. thermophilus strains were subjected to MIC testing with brothmicrodilution, E-test and Disk diffusion methods. Iso-sensitest medium supplementedwith lactose 1%w/v was found as an optimal medium for susceptibility testing.. TheMIC range for S. thermophilus population was from 0.02 to 0.1 µg/ml forerythromycin, from 0.2 to 0.5 µg/ml for tetracycline, and from 2 to 8 µg/ml forstreptomycin. Six strains isolated from raw milk in 2004, displayed MIC values for Em>100 µg/ml. This erythromycin resistance phenotype was shown to be due to thepresence of the ermB gene. Conclusion: Level of intrinsic resistance for antibioticsincluded in the study were established for S. thermophilus and it was found, for thefirst time, an ermB gene in this food related bacterial species

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Animal Arm of NARMS Recovery of Salmonella Heidelberg from1998–2003J. D. Tankson1, P. J. Fedorka-Cray1, M. Headrick2

1Bacterial Epidemiology and Antimicrobial Resistance Unit, USDA-ARS, Athens, GA, 2FDA-CVM, Rockville, MD.

Over 2500 different serotypes of Salmonella have been identified. Results from theanimal arm of the National Antimicrobial Resistance Monitoring System - EntericBacteria (NARMS) located in Athens, GA, indicate that Salmonella Heidelberg hasappeared among the top 5 most prevalent serotypes recovered from various animalsources from 1998–2003. In this study, we evaluated 160 Salmonella Heidelbergisolates recovered between 1998 and 2003 exhibiting an MIC ≥ 2 µg/ml for ceftiofur andceftriaxone which is indicative of reduced susceptibility since resistance breakpointsare ≥ 8 µg/ml and 64 µg/ml, respectively. Total numbers of isolates by species werechicken (n = 116; 73%), turkey (n = 16; 10%), cattle (n = 23; 14%), swine (n = 3; 2%),and eggs (n = 2; 1%). Collectively, isolates were geographically diverse in that theywere recovered from all five designated NARMS regions of the US; 49 (30%) isolatesfrom the Northeast, 44 (28%) isolates from the Southeast, 13 (8%) isolates from theNorth Central, 43 (27%) isolates from the South Central, and 6 (4%) isolates from theWest. Antimicrobial susceptibility testing indicated that 159 (99%) isolates exhibitedmultiple drug resistance (MDR; defined as resistance to 2 or more antimicrobials)patterns while one (1%) isolate was resistant to only one antimicrobial. The mostprevalent MDR profile (n = 39; 24%) was to amoxicillin/clavulanic acid, ampicillin,cefoxitin, ceftiofur, and cephalothin. Pulse-field gel electrophoresis results to dateindicate that approximately 33% of the isolates have unique pulseotypes.

Reference:1. http://www.ars.usda.gov/saa/athens/rbrrc/bear

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Perspective on Multi-Drug Resistant Salmonella enterica serotypeTyphimuriumDefinitive Phage Type 104 from the Animal Arm of NARMSP. J. Fedorka-Cray1, N. Anandaraman2, D. A. Dargatz3, M. Headrick4

1BEAR, USDA-ARS-RRC, Athens, GA, 2OPHS, USDA-FSIS, Washington,DC, 3CEAH, USDA-APHIS-VS, Fort Collins, CO, 4OR, FDA-CVM, Laurel,MD.

Salmonellae are ubiquitous in nature and over 2500 different serotypes have beenidentified. The top 25 serotypes identified from 1997 through 2004 as part of the AnimalArm of the National Antimicrobial Resistance Monitoring System (NARMS) accountedfor 83.5% of the total number of isolates tested (n=44,182). Of these, S. Typhimurium isfrequently associated with human illness. Recently, multi-drug resistance (MDR;resistance to > two antimicrobials) has emerged among salmonellae, and illnessassociated with MDR Typhimurium Definitive Type 104 (DT104) has been observed inthe United States, particularly following consumption of raw or undercooked groundbeef. Data collected as part of the NARMS program were analyzed to determine if theprevalence of DT104 isolates from various animals had increased over time. From 1997through 2004, 44,182 isolates were tested. The total number of isolates identified asserotype Typhimurium including var. copenhagen ranged from 13.7% in 1997 to 18.4%in 1999. The total percent of isolates which were confirmed as DT104 was 2.5, 3.4, 3.6,3.6, 3.2, 2.2, 2.2, and 2.9 for the years 1997 through 2004, respectively. A majority of theDT104 isolates (n=1329) originated from swine (45%) followed by cattle (beef and dairy;37%) and chicken (8%). These data indicate that the percent of DT104 tested throughNARMS among animal sources has not increased over time and that the majority ofthese did not originate from a cattle source.

References:1. White DG, Zhao S, Sudler R, et al. The isolation of antibiotic-resistant salmonella

from retail ground meats. NEJM 2001;345:1147-54

2. http://www.ars.usda.gov/Main/docs.htm?docid=6750

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Effects of Enrofloxacin treatment in intestinal bacteria of ChickenJ. M. Miranda, C. M. Franco, C. A. Fente, B. I. Vazquez, A. CepedaQuÃmica AnalÃtica, NutriciÃ_n y BromatologÃa, Universidad deSantiago de Compostela, Lugo, SPAIN.

Background: In this work we studied the evolution of several microbial groups infaeces of chicken treated with enrofloxacin as well as the rates of resistance to thisantimicrobial agent during the treatment and after withdrawn period.

Methods: Chickens were orally treated (in drinking water). Faecal samples were takenduring treatment and during the withdrawn period. Enterobacteriaceae, E. coli, LacticAcid Bacteria, Enterococcus and Campylobacter populations were estimated. A total of540 strains were isolated before starting treatment, at the end of treatment and at theend of the withdrawn period. These strains were characterized and Minimal InhibitoryConcentrations (MIC) to enrofloxacin were determined using the broth microdilutionmethod. Results were analyzed using ANOVA with treatment and day as models. Thechi-square test was used to compare differences in susceptibility of strains.

Results: Significant differences in populations during the treatment and the withdrawnperiod were found between treated and controls for Enterobacteriaceae, (p=0,003) E.coli (p=0,0116) and Enterococcus (p=0,0469). Resitance rates in bacteria from poultryafter the withdrawn period were significatively higher than controls forEnterobacteriaceae spp (p=0,001), E. coli (p=0,0136) and Campylobacter spp(p=0,0207).

Conclusions: More microbial studies are neccessary to establish a withdrawn periodprior to permit an antimicrobial usage for veterinary use.

References:1. National Committee for Clinical Laboratory Standards, 2001. Methods for Dilution

Antimicrobial Susceptibility Test for bacteria that grow aerobically. ApprovedStandard M7-A4. National Committee for Laboratory Standards, Villanova, PA.

2. Peters, J., Mac, K., Wichman-Schauer, H., Klein, G., Ellerbroek, L. 2003. Speciesdistribution and antibiotic resistance patters of enterococci isolated from food ofanimal origin in Germany. International Journal of Food Microbiology. 88, 311-314.

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A USDA Multi-Agency Project: Collaboration In Animal Health, FoodSafety & Epidemiology (CAHFSE): On-Farm UpdateJ. S. Bailey1, P. J. Fedorka-Cray1, N. E. Wineland2, D. A. Dargatz2, S. R. Ladely1, J. F. Robens3, R. R. Kraeling1

1Bacteriological Epidemiology and Antimicrobial Resistance, USDA, ARS,Athens, GA, 2USDA, APHIS, Fort Collins, CO, 3USDA, ARS, Beltsville,MD.

The emergence of antimicrobial resistant zoonotic bacteria continues to be a globalconcern. In response to growing surveillance needs, USDA-ARS, APHIS and FSIScollectively developed CAHFSE. CAHFSE will enhance our overall understanding ofpathogens that pose a food-safety risk by tracking these organisms from farm to plant.The first commodity of CAHFSE is pork. Blood and fecal samples have been collected onfarms in four states through four quarters. Herd health and management data are alsobeing collected from these farms. To date, fecal samples from 100 site visits have beencollected and cultured for Salmonella, Campylobacter and E. coli. In the fourth quarter,24 sites were visited and Salmonella was recovered from 7.5% (63/223) of the submittedsamples. Eight serotypes were identified, of which the top three serotypes accounted for86% of the isolates and included S. Derby, S. Bovis-morbificans, and S. Give. Across allserotypes, resistance was most commonly observed for tetracycline (91.0%),sulfamethoxazole (41.8%) and streptomycin (32.8%). Additionally, E. coli ,Campylobacter and Enterococcus were recovered from 89.6% (303/338), 77.8%(263/338) and 65.7% (222/338) of samples, respectively. Over time, the epidemiology,phenotypic and genotypic characterization, and determination of risk factors related toprevalence and antimicrobial resistance of these organisms will lead to practicalmethods of mitigating food borne illness.

Reference:1. Fedorka-Cra, PJ, Dargatc, DA, Wells, SJ, Wineland, NE, Miller, MA, Tollefson, L,

petersen, KE. Impact of antimicrobic use in veterinary medicine. J Amer Vet MedAssoc 1998; 213:1739-1741.

P5 Cephalosporin susceptibility of amoxi-R Salmonella Typhimuriumisolated from cattle in the UK.V. Thomas1, M. Rose2, C. Wilhelm1, R. Davis3

1Profiling, Intervet Innovation GmbH, Schwabenheim, GERMANY,2Product Development, Intervet Innovation GmbH, Schwabenheim,GERMANY, 3Food and Environmental Safety Department, VeterinaryLaboratories Agency, Weybridge, UNITED KINGDOM.

Background: Amoxicillin-resistant Salmonella Typhimurium isolated from cattle inthe UK over a period of nine years were analysed for susceptibility to cephalosporins.

Methods: A total of 232 amoxicillin-resistant Salmonella Typhimurium obtained fromthe culture collection of the Veterinary Laboratory Agency in the UK were tested forsusceptibility to cephalosporins. The isolates were collected between 1993 and 2001.Resistance rates were calculated based on breakpoints (1, 2) and minimum inhibitoryconcentrations (MIC) determined according to NCCLS standards.

Results: Antibiotic Resistance Rate 1993 1994 1995 1996 1997 1998 1999 2000 2001(%) (n=23) (n=26) (n=26) (n=26) (n=29) (n=30) (n=29) (n=23) (n=20)Cephapirin 30.4 3.8 07.7 0 3.4 3.3 3.4 0 0 Cephalothin 30.4 0 3.8 0 3.4 0 0 0 0Cefoxitin 0 0 3.8 0 3.4 0 0 0 0Ceftiofur 0 0 3.8 0 0 0 0 0 0 Ceftazidime 0 0 0 0 0 0 0 0 0Cefquinome 0 0 0 0 0 0 0 0 0Cefepime 0 0 0 0 0 0 0 0 0

Conclusions: High and sustained susceptibility to 3rd and 4th generationcephalosporins was observed in the amoxicillin-resistant Salmonella Typhimuriumisolates. Between 1993 and 1999 some isolates showed resistance to oldercephalosporins, however this was not observed between 2000 and 2001.

References:1. NCCLS. MIC Testing: Supplemental Tables; M100-S13 (M7). For use with: Methods

for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically;Approved Standard – Fifth Edition, M7-A6, NCCLS, Wayne, PA, 2003

2. Luhofer, G., Böttner, A., Hafez, H.M., Kaske, M., Kehrenberg, C., Kietzmann, M.,Klarmann, D., Klein, G., Krabisch, P., Kühn, T., Richter, A., Sigge, C., Traeder, W.,Waldmann, K-H., Wallmann, J., Werckenthin, C., and Schwarz, S. (2004).

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In-vitro susceptibility of E. coli isolated from feces of US feedlot cattle tocephalosporins.M. Rose1, C. Wilhelm2, G. Martin3

1Product Development, Intervet Innovation GmbH, Schwabenheim,GERMANY, 2Product Profiling, Intervet Innovation GmbH, Schwabenheim,GERMANY, 3Product Development, Intervet Inc., Millsboro, DE.

Background: The aim of this study was to obtain a baseline of cephalosporinsusceptibility of E. coli as representative commensal of the gut flora in cattle.

Methods: Fecal samples were collected from newly arrived feedlot cattle (n = 190) in fourgeographic locations (Nebraska, Idaho, Texas, California) in 2002. The fecal samples wereshipped to a central laboratory for isolation of E. coli. A total of 189 E. coli isolates wereanalysed for determination of the minimum inhibitory concentration (MIC) of the 4-GCcefquinome and cefepime, and the 3-GC ceftriaxone and ceftazidime according to NCCLSstandards (1). Cefquinome is licensed for therapeutic use in cattle and swine in Europe;the other cephalosporins tested are licensed for therapeutic use in human medicine.

Results: MIC of E. coli Cefquinome Cefepime Ceftriaxone Ceftazidime(n = 189) (µg/ml) (µg/ml) (µg/ml) (µg/ml)

MIC50 0.063 0.031 0.125 0.125MIC90 0.125 0.063 0.125 0.25Minimum 0.031 0.016 0.031 0.031Maximum 0.5 2.0 4.0 4.0

Conclusions: The MIC90 of cefquinome indicates high susceptibility of commensal fecalE. coli isolates from cattle. Similar MIC90 were observed for cefepime, ceftriaxone andceftazidime. According to NCCLS resistance breakpoints for cefepime (> 32 µg/ml),ceftriaxone (> 64 µg/ml), and ceftazidime (> 32 µg/ml), none of the isolates wereresistant to these cephalosporins used for antimicrobial therapy in human medicine (2).

References:1. NCCLS. Performance Standards for Antimicrobial Disk and Dilution Susceptibility

Tests for Bacteria Isolated from Animals; Approved Standard – Second Edition, M31-A2, NCCLS, Wayne, PA, 2002.

2. NCCLS. MIC Testing: Supplemental Tables; M100-S13 (M7). For use with: Methodsfor Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically;Approved Standard – Fifth Edition, M7-A6, NCCLS, Wayne, PA, 2003

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A cationic steroid antibiotic active against highly tobramycin-resistantPseudomonas aeruginosaP. B. Savage1, T. Orsak1, J. L. Burns2

1Chemistry and Biochemistry, Brigham Young University, Provo, UT,2Pediatrics, University of Washington, Seatle, WA.

Background: Cationic steroid antibiotics (CSAs) are small molecule mimics ofendogenous peptide antibiotics and are not expected to engender bacterial resistance.Because both aminoglycosides and CSAs contain multiple amine groups, the possibilityexists of similar mechanisms deactivating both types of antibiotics. Considering theprevalence of drug-resistant Pseudomonas aeruginosa in cystic fibrosis patients, thereis a need for novel antibiotics in treating chronic infections. To determine iftobramycin resistance translates to CSA resistance and if CSAs are active againstclinical isolates of Pseudomonas aeruginosa, we tested the susceptibility of tobramycin-resistant isolates to a bactericidal CSA.

Methods: Minimum inhibition concentrations (MICs) were determined using NCCLSapproved methods.

Results: Isolates were categorized as moderately tobramycin resistant (MIC 8-50ug/mL) and highly resistant (MIC >100 ug/mL). An MIC of 2 ug/mL was measured forCSA-13 against a standard strain of P. aeruginosa (ATCC 27853), and MICs of 1-3 ug/mLwere measured with tobramycin resistant strains.

Conclusions: Mechanisms of tobramycin resistance do not affect the antibacterialeffects of CSAs even though both types of antibiotics are polyamine based. BecauseCSAs selectively disrupt bacterial membranes, they may not be exposed to theacetyltransferases that provide one mechanism of tobramycin resistance. Theantibacterial activity of CSAs against drug-resistant bacteria makes them an attractivealternative to aminoglycoside antibiotics.

References:1. Savage PB, Li C, Taotafa U, Ding B, Guan Q. Antibacterial properties of cationic

steroid antibiotics. FEMS Lett. 2002;217: 1-7.

2. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonaryinfections in cystic fibrosis. Am. J. Resp. Crit. Care Med. 2003;168:918-51.

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Effects of Sulfonamides treatment in intestinal bacteria of chickenJ. M. Miranda, C. M. Franco, C. A. Fente, B. I. Vazquez, A. CepedaQuÃmica AnalÃtica, NutriciÃ_n y BromatologÃa, Universidad deSantiago de Compostela, Lugo, SPAIN.

Background: The purpose of this work was to evaluate the effects of Sulfonamidestreatments along a therapeutic treatment in poultry intestinal bacteria populations andits resistance rates.

Methods: Chickens were orally treated by medicated water. Faecal samples were takenduring treatment and as well as the withdrawn period. Enterobacteriaceae, E. coli,Lactic Acid Bacteria, Enterococcus and Campylobacter were estimated. A total of 540strains were isolated before starting treatment, at the end of treatment and at the endof the withdrawn period. These strains were characterized and Minimal InhibitoryConcentrations (MIC) were determined using the broth microdilution method as it isestablished. Results were analyzed using ANOVA with treatment and day as models. Thechi-square test was used to compare differences in susceptibility of strains.

Results: Significative differences in populations during the treatment and thewithdrawn period were found between treated and control batches for Enterococcus,(p=0,0311) and Lactic Acid Bacteria (p=0,0282). Resitance rates in bacteria islated fromtreated poultry along treatment were significatively higher than control batches for E.coli (p=0,0017); Enterobacteriaceae (p<0,0001); Enterococcus (p=0,001) andCampylobacter (0,0025).

Conclusions: Resistance promoting in the intestinal bacterial populations is animportant parameter to consider in veterinary usage of this antimicrobial.

Reference:1. National Committee for Clinical Laboratory Standards, 2001. Methods for Dilution


P9 Effects of Doxicyclyne treatment in intestinal bacteria of chickenJ. M. Miranda, C. M. Franco, C. A. Fente, B. I. Vazquez, A. Cepeda QuÃmica AnalÃtica, NutriciÃ_n y BromatologÃa, Universidad deSantiago de Compostela, Lugo, SPAIN.

Background: The purpose of this work was to evaluate the effects of Doxicyclynetreatments in poultry intestinal bacteria population and its resistance rates.

Methods: Chickens were orally treated. Faecal samples were taken during treatmentand as well as the withdrawn period. Enterobacteriaceae, E. coli, Lactic Acid Bacteria,Enterococcus and Campylobacter were estimated. A total of 540 strains were isolatedbefore starting treatment, at the end of treatment and at the end of the withdrawnperiod. These strains were characterized and Minimal Inhibitory Concentrations (MIC)to Doxicyclyne were determined using the broth microdilution method as it isestablished for tetracyclyne. Results were analyzed using ANOVA with treatment andday as models. The chi-square test was used to compare differences in susceptibility ofstrains.

Results: Significative differences in populations during the treatment and thewithdrawn period were found between treated and control batches for Enterococcus,(p=0,0261) Lactic Acid Bacteria (p=0,0459) and Campylobacter (p=0,0259). Resitancerates in bacteria from poultry after the withdrawn period were significatively higherthan before starting treatment for Enterobacteriaceae spp (p=0,0314) andCampylobacter spp (0,0057).

Conclusions: Resistance promoting in the intestinal bacterial populations is aparameter to consider in veterinary usage of this antimicrobial.

Reference:1. National Committee for Clinical Laboratory Standards, 2001. Methods for Dilution


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A cationic steroid antibiotic active against vancomycin-resistantstaphylococci and enterococciP. B. Savage1, T. Bogdanovich2, P. C. Appelbaum2

1Chemistry and Biochemistry, Brigham Young University, Provo, UT,2Pathology, Milton S. Hershey Medical Center, Hershey, PA.

Background: Emergence of vancomycin-resistant Enterococcus faecium and laterStaphylococcus aureus strains partially (VISA) and fully (VRSA) resistant to vancomycinas well as coagulase-negative staphylococci with reduced vancomycin susceptibility(VIConS) shows that Gram-positive cocci can develop resistance even to drugs that are“held in reserve.” The fact that vancomycin-resistant Gram-positive cocci are generallyresistant to other antibiotics highlights the need for development of antibiotics that areunlikely to engender stable resistance in pathogenic bacteria. Cationic steroid antibiotics(CSAs) are small molecule mimics of endogenous peptide antibiotics and as such offerthe possibility of not engendering mutational resistance.

Methods: Minimum inhibition concentrations (MICs) were determined using NCCLSapproved methods.

Results: Antibacterial properties of CSA-13 were tested against four strains of VISA,three strains of VRSA, four strains of VIConS, and 10 strains of VRE (five faecalis and fivefaecium). The drug was very potent against all strains tested with MICs of 0.06-0.25ug/ml against VISA, VRSA and VIConS, 1-4 ug/ml against VRE (faecalis), and 0.25 ug/mlagainst VRE (faecium). Conclusions: Because CSAs have a mechanism distinct frommost antibiotics they retain potent antibacterial activity against antibiotic-resistantclinical isolates. CSAs are broad-spectrum antibiotics, relatively easy to prepare, andamenable to long-term storage; consequently, they appear well suited for broad usage.

References:

1. Savage PB, Li C, Taotafa U, Ding B, Guan Q. Antibacterial properties ofcationic steroid antibiotics. FEMS Lett. 2002;217: 1-7.

2. Tenover FC, Weigel LM, Appelbaum PC, et al. Vancomycin-resistantStaphylococcus aureus from a patient in Pennsylvania. Antimicrob. AgentsChemother. 2004;48:275-80.

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Effectiveness of Carbapenem in Infections Due to Extended SpectrumBeta Lactamase (ESBL) Producing OrganismsJ. L. Murillo, R. Elysee, M. HamraEpidemiology, Newark Beth Israel Medical Center, Newark, NJ.

Background: Patients infected with ESBL-producing organisms are frequently treatedwith carbapenems.

Methods: A retrospective chart review of 91 patients with infections due to ESBLproducing organisms was performed from January 1, 2002 to June 30, 2004 andanalyzed using Student t test and chi-square analysis.

Results: The mean age was 66.2 years (range 13-99 years). 45 patients were males and46 were females. Escherichia coli caused 45 infections, Klebsiella pneumoniae 40 andKlebsiella oxytoca 6. The overall mortality rate was 20.8% (19/91). The mortality ratefor E coli was 20% (9/45), Klebsiella pneumoniae 22.5% (9/40) and Klebsiella oxytoca16.6% (1/6). The average length of stay (LOS) was 54.1 days (range 1 to 429 days). Theaverage LOS for E coli (35.4 days) was significantly different from Klebsiellapneumoniae (75.3 days), p value <0.01. The common sites of infection were urine48.4%, blood 23.1%, respiratory 7.7% and wound 5.5%. Most patients had at least 3 co-morbid conditions. Excluding patients who were already infected on admission, theaverage time to infection was 39.1 days (range 3-201 days). Of 31 patients who receiveda carbapenem, 8 died (25.8%) while 11 of 42 patients (26.1%) who did not receive acarbapenem died. The APACHE II score at the time of positive culture was significantlyworse among patients who died (p<0.001).

Conclusions: No difference in mortality rates between patients whether they received acarbapenem or not. Patients infected with ESBL-producing Klebsiella pneumoniaestayed longer in the hospital.

References:1. Kang CI, Kim SH, Park WB, Lee KD et al. Bloodstream infections due to extended-

spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae:risk factors for mortality and treatment outcome. Antimicrob Agents Chemother2004; 48:4574

2. Du B, Long Y, Liu H, Chen D et al. Extended spectrum beta-lactamase-producingEscherichia coli and Klebsiella pneumoniae bloodstream infection. Intensive CareMed 2002; 28:1718-23.

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The use of fluoroquinolones as second-line agents in the treatment ofMulti-drug resistant tuberculosisD. SeyoumThe United States Pharmacopeial Convention, Inc., Rockville, MD.

Background: The anti-TB activities of the fluoroquinolones have been underinvestigation since the 1980s. Many fluoroquinolones are active in vitro against M.tuberculosis. Incorporation of fluoroquinolones in second-line regimens for themanagement of MDR-TB has been recommended, including by the WHO. However,only a few have been clinically tested.

Methods: The USP DQI analyzed published articles on the anti-TB activities ofciprofloxacin, levofloxacin, and ofloxacin. Analysis was also focused on safety,effectiveness, and the problem of fluoroquinolone drug resistance. USP DQI presentedthe analysis in the form of evidence tables to the USP Drug Information ExpertCommittees for further review.

Results: MIC50 and MIC90 values for ciprofloxacin against M. tuberculosis rangedfrom 0.5 – 2 and 0.5 – 4 µg/mL while MIC50 and MIC90 values for ofloxacin ranged from0.5 - 1 and 1 - 2 µg/mL, respectively. The in vitro activity of levofloxacin against 18susceptible isolates of M. tuberculosis were evaluated and MIC50 and MIC90 values forlevofloxacin were 0.5 and 1 µg/mL. Selection of fluoroquinolone-resistant isolatesoccurred when a fluoroquinolone is given alone and/or in a combination of a poorlyactive drug.

Conclusions: The USP Drug Information Expert Committees recommended that theuse of ciprofloxacin, levofloxacin, and ofloxacin, as part of a second-line regimen in thetreatment of MDR-TB, should be considered only in consultation with an expert in thetreatment of TB so that monitoring the regimen for drug resistance and changing theregimen, if needed, can be achieved.

P13 Antibiotic Resistance in Chlamydia spp.: Fitness Cost Associated withSpectinomycin Resistance due to Spontaneous Mutations in the 16SrRNA in C. psittaci 6BC.R. Binet, A. T. MaurelliMicrobiology, USUHS, Bethesda, MD.

Analysis of the genome sequence of several members of the Chlamydiaceae revealedthat these obligate intracellular bacteria harbor only one or two sets of rRNA genes. Astetracyclines and macrolides are the ribosomal drugs currently used to treat chlamydialinfections, we studied the contribution of rRNA mutations to the emergence ofantibiotic resistance in Chlamydia species, using the sensitivity of C. trachomatis L2(two rrn operons) and C. psittaci 6BC (one rrn operon) to spectinomycin as a model.Confluent cell monolayers were infected in the plaque assay with 108 wild-typeinfectious particles then treated with the antibiotic. After a two-week incubation time,plaques formed by spontaneous spectinomycin resistant (SpcR) mutants appeared witha frequency of 5 x 10-5 for C. psittaci 6BC. No SpcR mutants were isolated for C.trachomatis L2 although the frequencies of rifampicin resistance were in the samerange for both strains (i.e. 10-7). Sequencing of the 16S rRNA from 59 independent SpcR

isolates identified mutations at position 1192, 1191 and 1193 (according to theEscherichia coli numbering system), previously described in other SpcR bacteria orchloroplasts. We found that C. psittaci 6BC isolates carrying A1191 to G or G1193 to Cmutations displayed a longer doubling time and were severely out-competed by theparent strain in co-infection assays. By contrast, mutations at 1192 had minor effectson the bacterial life cycle. This study provides a new strategy to predict, monitor andperhaps prevent emergence of antibiotic resistance in chlamydiae.

Reference:1. Wang SA, Papp JR, Stamm WE, Peeling RW, Martin DH, Holmes KK. Evaluation of

Antimicrobial Resistance and Treatment Failures for Chlamydia trachomatis: AMeeting Report. J Infect Dis 2005;191:917-23.

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Availability of Antibiotics Without Prescription in New York CityE. LarsonSchool of Nursing, Columbia University, New York, NY

NOT AVAILABLE

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Mechanisms of Acquired Microbial Resistance to Chlorine DioxideS. Powis1, M. Riley2, J. Hoying1, S. K. Williams1

1Biomedical Engineering, University of Arizona, Tucson, AZ, 2Agriculturaland Biosystems Engineering, University of Arizona, Tucson, AZ.

Background: Chlorine dioxide (ClO2) is a biocide utilized for the disinfection of food

and water. We are developing ClO2-generating biomaterials for the in situ prevention ofinfection. While testing the bactericidal activity of a ClO2-generating material, aspontaneous mutant of Staphylococcus epidermidis (S. epidermidis) with a reducedsusceptibility to ClO2 was isolated (SP030724). A review of works by other investigatorson acquired microbial resistance to biocides yielded no prior demonstration ofmicrobes developing resistance to ClO2. The mechanisms behind the development ofbiocide resistance are not well established, and there is a growing concern about theclinical significance of biocide resistance [1]. Investigating this new resistant microbewill advance our understanding of the mechanisms responsible for biocidal resistance.

Methods: The supernatant produced by SP030724 was analyzed to determine if themechanism of resistance was intracellular or extracellular. The results established thatresistance was due to an extracellular factor. The unknown molecule was assessed for:temperature stability, degree of hydrophobicity, and molecular weight. Results:Experimental results indicated the molecule: is inactivated by temperatures ≥ 60°C, butstable at 4°C, is hydrophilic, and has a MW ≥ 100kDa. Preliminary gel electrophoresisexperiments suggest the presence of a protein in SP030724 supernatant, not present inwildtype S. epidermidis supernatant. Conclusions: SP030724 produces a molecule thatreduces the susceptibility of the microorganism to ClO2.

References:1. Russell, A.D., Introduction of biocides into clinical practice and the impact on

antibiotic-resistant bacteria. J Appl Microbiol, 2002. 92 Suppl: p. 121S-35S.

2. Poole, K., Mechanisms of bacterial biocide and antibiotic resistance. J ApplMicrobiol, 2002. 92 Suppl: p. 55S-64S.

P17 Vancomycin-resistant Enterococci (VRE) from Human Stools in theCommunityA. May, K. Gay, K. Lewis, T. Barrett, T. Chiller, &. NARMS EnterococciWorking Group CDC, Atlanta, GA.

Background: Vancomycin-resistant enterococci (VRE) infections are an importantcause of morbidity and mortality. VRE transmission has been documented in thehospital setting. There is little evidence, however, for VRE transmission in thecommunity in the United States.

Methods: From 2000-2002, 10-20 stool specimens per month were obtained fromhealthy volunteers or outpatients with diarrhea, who reported no hospital contact in atleast 6 months, in five states (Georgia, Maryland, Michigan, Minnesota, and Oregon).One enterococci isolate per specimen was sent to CDC. Following incubation inEnterococcosel media, enterococci were speciated by biochemical assays and tested forantimicrobial susceptibility by broth microdilution.

Results: VRE was isolated from 29 (1.4%) of 2061 stool specimens; 28 were E. faeciumand 1 was E. faecalis. VRE were isolated from participants in three states. Of VREisolates tested 87% (20/23) were additionally resistant to ciprofloxacin, 83% (20/24) tobacitracin, 54% (13/25) to tetracycline, 50% (12/24) to gentamicin, 12% (3/25)quinupristin-dalfoprostin (Q/D), and none to linezolid. Two VRE isolates were resistantto both Q/D and tetracycline

Conclusion: VRE was isolated from outpatient stool samples, including persons with noapparent contact with hospitals, suggesting that VRE may have been acquired in thecommunity. More than 10% of VRE isolated were also resistant to quinupristin-dalfoprostin, one of few available options for the treatment of VRE. It will be importantto further characterize the epidemiology of acquisition of VRE and the molecularmechanism of vancomycin resistance among these isolates.

Reference:1. Bonten MJ, Willems R, Weinstein RA. Vancomycin-resistant enterococci: why are

they here, and where do they come from? Lancet Infect Dis. 2001 Dec;1(5):314-25

P18

Nalidixic Acid Resistance in Salmonella Enteritidis, NARMS, 1996-2003F. Medalla, K. Gay, T. J. Barrett, T. M. Chiller, and the NARMS Working Group Centers for Disease Control and Prevention (CDC), Atlanta, GA.

Background: Salmonella serotype Enteritidis (SE) is a leading cause of salmonellosis.Egg, chicken, and egg-containing foods are important sources of SE. For serious illness,quinolones (i.e. ciprofloxacin) are considered primary treatment in adults. Nalidixic acid(NA) resistance in Salmonella is correlated with decreased susceptibility to ciprofloxacinand treatment failure.

Methods: Since 1996, participating state health departments submitted non-TyphiSalmonella isolates to the National Antimicrobial Resistance Monitoring System(NARMS) for Enteric Bacteria at CDC for antimicrobial susceptibility testing using brothmicrodilution to determine minimum inhibitory concentration (MIC). NA resistance wasdefined as MIC>=32 µg/ml.

Results: From 1996 to 2003, 2370 SE isolates were tested, of which 67 (3%) were NA-resistant. The age, gender, and specimen source for patients with NA-resistant and NA-susceptible SE were similar. The percentage of SE resistant to >=1 antimicrobial agentdecreased from 31% (110/357) in 1996 to 9% (24/257) in 2003 (p<0.0001). However, thepercentage of SE resistant to NA increased from 1% (3/357) in 1996 to 6% (15/257) in2003 (p<0.01). 88% of NA-resistant SE had decreased susceptibility to ciprofloxacin(MIC>=0.12 µg/ml).

Conclusions: The prevalence of NA-resistant SE has increased in NARMS since 1996.Whether these infections were acquired domestically needs to be determined. However,as SE infections are primarily associated with egg and chicken consumption, it isimportant to understand how the use of quinolones in poultry may have contributed toemerging resistance. Continued monitoring of this trend is important given its clinicaland public health implications.

References:1. Hakanen A, Kotilainen P, Jalava J, Siitonen A, and Huovinen P. Detection of

decreased fluoroquinolone susceptibility in Salmonellas and validation of nalidixicacid screening test. Journal of Clinical Microbiology 1999; 37: 3572-77.

2. Schroeder CM, Naugle AL, Schlosser WD, Hogue AT, Angulo FJ, Rose JS, Ebel ED,Disney WT, Holt KG, and Goldman DP. Estimate of illnesses from Salmonella Enteritidisin eggs, United States, 2000. Emerging Infectious Diseases 2005; 11: 113-115.

P19


AUTHOR INDEX


AUTHOR INDEX

Author Abstract Number

A

Alali, W. . . . . . . . . . . . . . . . . . . . .S6

Anandaraman, N. . . . . . . . . . . . . .P3

Appelbaum, P. . . . . . . . . . . . . . . .P11

B

Bailey, J. . . . . . . . . . . . . . . . . . . . .P5

Barrett, T. . . . . . . . . . . . . . . . .S7, S8

Baltz, R. . . . . . . . . . . . . . . . . . . . . .3

Barrett, T. . . . . . . . . . . . . . . . . . . .S8

Berruti, G. . . . . . . . . . . . . . . . . . .P4

Binet, R. . . . . . . . . . . . . . . . .S2, P14

Blumberg, H. . . . . . . . . . . . . . . . .18

Bogdanovich, T. . . . . . . . . . . . . .P11

Bowie, W. . . . . . . . . . . . . . . . . . . .S5

Burns, J. L. . . . . . . . . . . . . . . . . .P12

C

Campbell, L. . . . . . . . . . . . . . . . . .S6

Cepeda, A. . . . . . . . . . . .P10, P6, P9

Chiller, T. . . . . . . . . . . . . . . . . .S7, Si

Chong, M. . . . . . . . . . . . . . . . . . . .S5


D

Dargatz, D. . . . . . . . . . . . . . . .P3, P5

Davis, R. . . . . . . . . . . . . . . . . . . . .P8

Deb, J. . . . . . . . . . . . . . . . . . . . . . .S1

Dilone, J. . . . . . . . . . . . . . . . . . . .S4

E

Eckl, M. . . . . . . . . . . . . . . . . . . .S10

Eliopoulos, G. . . . . . . . . . . . . . . . .19

Elysee, R. . . . . . . . . . . . . . . .S9, P16

F

Fedorka-Cray, P. . . . . . . . .P2, P3, P5

Fente, C. . . . . . . . . . . . . .P10, P6, P9

Ferraro, M. . . . . . . . . . . . . . . . . . .20

Franco, C. . . . . . . . . . . .P10, P6, P9

G

Garcia, M. . . . . . . . . . . . . . . . . . . .S4

Gay, K. . . . . . . . . . . . . . . . . . .S7, S8

Goldmann, D. . . . . . . . . . . . . . . . .11

Grundmann, H. . . . . . . . . . . . . . . .1

Gulick, R. . . . . . . . . . . . . . . . . . . .14


H

Hamra, M. . . . . . . . . . . . . . .S9, P16

Harris, A. . . . . . . . . . . . . . . . . . . . .9

Harvey, R. . . . . . . . . . . . . . . . . . . .S6

Headrick, M. . . . . . . . . . . . . . .P2, P3

Hindler, J. . . . . . . . . . . . . . . . . . . .21

Hoying, J. . . . . . . . . . . . . . . . . . . .S3

Hume, M. . . . . . . . . . . . . . . . . . . .S6

J

Jana, S. . . . . . . . . . . . . . . . . . . . . .S1

Jones, R. . . . . . . . . . . . . . . . . . . . . .7

Judice, J. . . . . . . . . . . . . . . . . . . . . .4

K

Kaplan, R. . . . . . . . . . . . . . . . . . . .26

Kraeling, R. . . . . . . . . . . . . . . . . .P5

L

Ladely, S. . . . . . . . . . . . . . . . . . . .P5

Lamp, K. . . . . . . . . . . . . . . . . . . . .P1

Larson, E. . . . . . . . . . . . . . . .S4, P15

Lau, D. . . . . . . . . . . . . . . . . . . . . .13

Lewis, K. . . . . . . . . . . . . . . . . . . . .S7

Lin, L. . . . . . . . . . . . . . . . . . . . . . .S5

Numbers beginning with “P” are for abstracts of poster presentations. Numbers beginning with “S” are for the abstracts of submitted presentations.

AUTHOR INDEX



Lynch, A. . . . . . . . . . . . . . . . . . . . . .5

M

Marra, F. . . . . . . . . . . . . . . . . . . . .S5

Martin, G. . . . . . . . . . . . . . . . . . . .P7

Martone, W. . . . . . . . . . . . . . . . . .P1

Maurelli, A. . . . . . . . . . . . . . .S2, P14

May, A. . . . . . . . . . . . . . . . . . . . . .S7

Medalla, F. . . . . . . . . . . . . . . . . . .S8

Miranda, J. . . . . . . . . . . .P10, P6, P9

Moore, A. . . . . . . . . . . . . . . . . . . .24

Morelli, L. . . . . . . . . . . . . . . . . . . .P4

Murillo, J. . . . . . . . . . . . . . . .S9, P16

N

NARMS . . . . . . . . . . . . . . . . . .S7, S8

O

Orsak, T. . . . . . . . . . . . . . . . . . . .P12

Owens, R. . . . . . . . . . . . . . . . . . . .10

P

Patrick, D. . . . . . . . . . . . . . . . . . .S5

Patti, J. . . . . . . . . . . . . . . . . . . . . . .2

Poole, T. . . . . . . . . . . . . . . . . . . . .S6

Powers, J. . . . . . . . . . . . . . . . . . . .22


Powis, S. . . . . . . . . . . . . . . . . . . . .S3

Prichard, R. . . . . . . . . . . . . . . . . .23

Q

Quinn, J. . . . . . . . . . . . . . . . . . . . .16

R

Ramani, A. . . . . . . . . . . . . . . . . .S10

Riley, M. . . . . . . . . . . . . . . . . . . . .S3

Robens, J. . . . . . . . . . . . . . . . . . . .P5

Roscoe, D. . . . . . . . . . . . . . . . . . . .S5

Rose, M. . . . . . . . . . . . . . . . . .P7, P8

S

Saiman, L. . . . . . . . . . . . . . . . . . .17

Savage, P. . . . . . . . . . . . . . .P11, P12

Scott, H. . . . . . . . . . . . . . . . . . . . .S6

Seyoum, D. . . . . . . . . . . . . . . . . .P13

Shyrock, T. . . . . . . . . . . . . . . . . . . .6

Smolowitz, J. . . . . . . . . . . . . . . . .S4

Srinivasan, A. . . . . . . . . . . . . . . . .15

Sundar, S. . . . . . . . . . . . . . . . . . . .25

Sweet, M. . . . . . . . . . . . . . . . . . .S10

T

Tan, C. . . . . . . . . . . . . . . . . . . . .S11


Tankson, J. . . . . . . . . . . . . . . . . . .P2

Thomas, V. . . . . . . . . . . . . . . . . . .P8

Tosi, L. . . . . . . . . . . . . . . . . . . . . .P4

Treanor, J. . . . . . . . . . . . . . . . . . . .12

Vazquez, B. . . . . . . . . . . .P10, P6, P9

W

Wallinga, D. . . . . . . . . . . . . . . . . . .8

Wilhelm, C. . . . . . . . . . . . . . .P7, P8

Williams, S. . . . . . . . . . . . . . . . . .S3

Wineland, N. . . . . . . . . . . . . . . . . .P5

AUTHOR INDEXAUTHOR INDEX


Continuing Medical Education DisclosuresAs a sponsor accredited by the Accreditation Council for Continuing Medical Education (ACCME) the NationalFoundation for Infectious Diseases must insure balance, independence, objectivity, and scientific rigor in all itsindividually sponsored or jointly sponsored educational activities. All faculty participating in a sponsoredactivity and all Scientific Program Committee Members are expected to disclose to the activity audience: (1) anysignificant financial interest or other relationship (a) with the manufacturer(s) of any commercial product(s)and/or provider(s) of commercial services discussed in an educational presentation and and/or (b) with anycommercial supporters of the activity. (Significant financial interest or other relationship can include suchthings as grants or research support, employee, consultant, major stock holder, member of speakers bureau,etc.); and (2) any intention to discuss off-label uses of regulated substances or devices.

The intent of this disclosure is not to prevent a speaker, nor a Scientific Program Committee member, with asignificant financial or other relationship from making a presentation, or assisting in conference organization,but rather to provide listeners with information on which they can make their own judgments. It remains for theaudience to determine whether the speaker's interests or relationships may influence the presentation withregard to exposition or conclusion.

The following Program Committee members have no relationships to disclose:

M. Cohen D. Dixon S. Jennings E. Larson M. Miller J. Powers

J. Robens D. Ross K. Shea P. Sundberg T. Weber

The following Program Committee members have disclosed the following relationship(s):

Member Company Relationship*

S. Cohen Bristol-Myers Squibb, Cubist, Merck E

Ortho-McNeil, Pfizer, Schering-Plough

Sanofi aventis

Genzyme B

B. Eisenstein Cubist Pharmaceuticals C

F. Hayden sanofi aventis, Loder Croklaan,

MedImmune, Perlan, Roche, Nexbio

Protein Sciences B

Arrow Therapeutics, sanofi pasteur

Biota Holdings, MedImmune, Perlan

Roche, Merck, Corixa,

Schering-Plough E

M. Kunkel Pfizer, Inc A, C

J. Rex AstraZeneca C

S. Rehm Cubist B,E

GlaxoSmithKline, Pfizer, Roche E

sanofi aventis, Wyeth


The following presenters have disclosed the following relationship(s):

Presenter Company Relationship*

R. Baltz Cubist Pharmaceuticals A, C, E, G

G. Eliopoulos Cubist Pharmaceuticals, E

Pfizer, Sanofi aventis, Wyeth

D. Goldmann Merck A

R. Gulick Abbott, Boehringer-Ingelhelm B, E

GlaxoSmithKline, Gilead

Merck, Pfizer, Roche, Schering

Tibotec, Virco, Viraogic E

A. Harris Ortho-McNeil B

J. Hindler Becton Dickinson Biomerieux Vitek E

Dave Behring Microscan

Ortho McNeil

R. Jones AstraZeneca, Bristol-Myers Squibb B, E

Cubist, Schering-Plough

Merck & Co., Pfizer, Theravance, B

Vicuron

J. Judice Achaogen, Inc C

R. Kaplan Divergence, Inc, Merial, Ltd B, E

Pfizer B

S. Lynch Cumbre, Inc. A, C

W. Martone Cubist Pharmaceuticals A, C

J. Patti Inhibitex A, C, F

R. Prichard GlaxoSmithKline B

Wyeth (Ft Dodge Animal Health) B

The following presenters reported no relationship to disclose:

J. Bailey

H. Blumberg

R. Binet

P. Fedorka-Cray

M. Ferraro

C. Franco

H. Grundmann

S. Jana

E. Larson

A. May

F. Medalla

A. Moore

L. Morelli

J. Murillo

T. Poole

J. Powers

S. Powis

A. Ramani

C. Robertson

L. Saiman

D. Seyoum

A. Srinivasan

S. Sundar

J. Tankson


*Please refer to the following relationship table

Label Relationship

A I have stocks, stock options, and/or bond holdings in this company

B I have a research grant, stipend, and/or fellowship from this company

C I am employed by this company, or it employs a member of my immediate family

D I or a member of my immediate family own or is a partner in this company

E I or a member of my immediate family receive consulting fees, honoraria, paid meetingregistration fees, paid travel, speaking fees, or other financial compensation from this company

F I or a member of my immediate family hold a nonrenumerative position of influence with thiscompany such as officer, board member, trustee, or public spokesperson.

G I or a member of my immediate hold a patent for and/or receive royalties from this company’sproduct

M. Rose Intervet Innovation GmBh C

P. Savage Osmostics Pharma E

T. Shryock Eli Lilly C

V. Thomas Intervet Innovation GmBh C

J. Treanor Corixa Corp, Wyeth E

Protein Sciences, Vaxgen B

D. Wallinga Keep Antibiotics Working Steering Committee

FINAL PROGRAM


NOTES