Another 10th Year Anniversary:A NARMS Update

Tom Chiller MD MPHEnteric Diseases Epidemiology Branch

Division of Foodborne, Bacterial and Mycotic DiseasesCenters for Disease Control and Prevention

Atlanta GA

National Antimicrobial Resistance Monitoring System (NARMS)

• Established in 1996 (10 years old)• Three components

– CDC: Human surveillance (1996)– USDA: Animal surveillance (1996)– FDA-CVM: Retail meat surveillance (2002)

• Microbiologists and Epidemiologists• Human, Veterinary, and Food Disciplines

1944

Antibiotic Resistance• Global problem

– Emergence – Dissemination

• Antibiotics are widely used in humans and animals– Overuse and misuse in humans and animals

• Empirical therapy • Non-therapeutic uses

• Complex: interaction of antimicrobials, resistance mechanisms, and pathogenicity of bacteria

There are > 100 antibacterial agents currently approved for

use in clinical medicine.

However, resistance has followed the development of

each new antibiotic.

Antimicrobial Resistance and the role of the Food Supply

• Antibiotics are commonly used in food animals– Selects for antimicrobial resistant bacteria

• Food animals constitute an important reservoir of– Resistant bacteria– Resistance genes - transferable

• Resistant bacteria can be transmitted to humans through the food supply– Most evident with pathogens (Salmonella and

Campylobacter)– Also occurs with commensal bacteria (Enterococci)

0

5

10

15

20

25

30

Human use Animal use(AHI)

Animal use(UCS)

Use inmillions ofpounds

Estimates of Antibiotic Use

Dissemination of StreptothricinResistance in E. coli

Origin 1982 1983 1984 1985 1986 1987

Pigs - + + + + +Farm Personnel - - + + + +Farm Families - - + + + +Community - - - + + +Community UTI’s - - - + + +S. sonnei - - - - - +

From: Witte, W. 1997. Antibiotic resistance, Ciba Foundation SymFrom: Witte, W. 1997. Antibiotic resistance, Ciba Foundation Symposium 207posium 207

Nourseothricin introduced in animal feed in 1983 in former East Germany

Bacteria Tested in NARMSHuman, Food, Animal• Non-Typhi Salmonella• Campylobacter• Enterococci

Food, Animal• Generic E. coli

Human & Animal• E. coli 0157:H7• Listeria

Human only• S. Typhi• Shigella• Listeria - sometimes

1996: 14 sites 1999: 17 sitesHuman NARMS 1996-2006

2002: 28 sites 2003: 54 sites

NARMS Sites

Human Isolate Sampling • Bacteria are isolated and identified at the

state health departments• Passive Surveillance

– Isolates Submitted to CDC/NARMS• Nationwide

– Every 20th non-Typhi Salmonella, Shigella, and E. coli O157

– All Salmonella Typhi, Listeria, and Vibrio– Representative sample of Campylobacter from 10

states sites

Unique Characteristics

• Only surveillance system where all 50 states send bacteria routinely to CDC

• High level of ivolvement– Quarterly conference calls with over 45

states joining– Nationwide IRB for special studies

Accomplishments and Goals

• 2005 PulseNet Goals– Pulse all NARMS isolates– Common state ID for NARMS/PulseNet

• Provide summary data and integrate• Link data • Increase outbreak isolate testing• Web access to data

Percentage of Campylobacter isolates resistant to ciprofloxacin (MIC≥4), by year,1997-2004*

12.9 13.918.3

14.819.5 20.1

17.7 18.3

0

10

20

30

40

1997(N=217)

1998(N=310)

1999(N=317)

2000(N=324)

2001(N=384)

2002(N=354)

2003(N=328)

2004(N=415)

Year

Perc

ent

Preliminary 2004

*

2002 vs 1997: OR=1.7 (95% CI 1.1, 2.7)

Fluoroquinolone use and percent resistance in Campylobacter, 1987-2004

13 14

1815

19 2018 18

86 90 94 97 02 05Year

Approved for use in humans

Approved for use in poultry

2004 Preliminary Data

FDA withdrewapproval

County surveys

0

Regulatory Action: Flouroquinolones and Poultry

• FDA proposes withdrawal of flouroquinolones use for poultry in 2003

• Industry appeals decision • NARMS data used at hearings to

support FDA’s withdrawal• Judge rules to withdraw FQ• FDA commissioner officially withdraws

FQ in 2005

Avian Influenza and Antiviral Use in Poultry

• Evidence for use of anti-virals (amantadine) in poultry in China and SE Asia

• Joint FAO/OIE/WHO statement: ‘‘Use of Antiviral Drugs in Poultry, a Threat to Their Effectiveness for The Treatment of Human AvianInfluenza,’’ November 11, 2005

March 2006• The Food and Drug Administration (FDA) is issuing an order

prohibiting the extralabel use of anti-influenza adamantane and neuraminidase inhibitor drugs in chickens, turkeys, and ducks. We are issuing this order based on evidence that extralabel use of these antiinfluenza drugs in chickens, 21 CFR Part 530 [Docket No. 2006N–0106]

Order of Prohibition: New Animal DrugsEffective date June 1 2006

0

20

40

60

80

100

1980 1983 1986 1989 1992 1995 1998 2001 2004

Perc

ent

Percent of Salmonella Typhimurium isolates with multidrug ACSSuT

resistance pattern (1980 – 2004)

NARMS launchedCounty surveys

Percentage of S. Typhimurium resistant to at least ACSSuT, by year, 1996-2004*

34 35 32 28 28 3021 26 23

0

10

20

30

40

50

1996 1997 1998 1999 2000 2001 2002 2003 2004

Year

Perc

ent

* 2004 preliminary data

34% in 1996 to 23% in 2004 OR=0.6 [95% CI 0.4, 0.8]

PositiveCulture

PulseNet

Case ReportForms

PHLIS/FoodNet

eFORS

NARMS

Routine NARMSIsolates(34,816)

PulseNet Isolates(170,927)

Salmonellaisolates(17,617)

SalmonellaSchwarzengrund

isolates(71)

Linked isolates with PFGE and susceptibility results

(40)

Salmonellaisolates(118,179)

SalmonellaSchwarzengrund

isolates(582)

US SalmonellaSchwarzengrund

Isolates

19 18

2723

10

4

7

4

1

0

5

10

15

20

25

30

35

40

2002 2003 2004 2005

Num

ber o

f Uni

que

XbaI

Pat

tern

s BothACSSuTACSSuT Susceptible

Number of Unique XbaI Patterns Among Linked SalmonellaTyphimurium with ACSSuT Resistance

Number of Isolates N=36 N=34 N=68 N=53

JPXX01.0003

Clinical Relevance of Nalidixic Acid Resistance in Non-Typhi Salmonella

• Nalidixic acid is the prototype quinolone• Nalidixic acid resistance correlates with

decreased susceptibility to ciprofloxacin (MIC ≥ 0.12 µg/mL)

• Fluoroquinolone-susceptible strains of Salmonella that test resistant to nalidixic acid may be associated with clinical failure/delayed response in fluoroquinolone-treated patients with salmonellosis

Percentage of S. Enteritidis resistant to nalidixic acid, by year, 1996-2004*

0

5

10

15

20

Perc

ent

1996 1997 1998 1999 2000 2001 2002 2003 2004

Year

Resistant to nalidixic acid

* 2004 preliminary data

1% in 1996 to 6% in 2004 OR=8.9 [95% CI 2.3, 50.3]

117 9

12

2

12

21

1

1

1

0

5

10

15

20

25

30

35

40

2002 2003 2004 2005

Num

ber o

f Uni

que

XbaI

Pat

tern

s Both

Resistant to Nalidixic Acid

Nalidixic Acid Susceptible

Number of Unique XbaI Patterns Among Linked Salmonella Enteritidis with Nalidixic Acid Resistance

Number of Isolates N=38 N=43 N=66 N=99

JEGX01.0002

JEGX01.0002

JEGX01.0002JEGX01.0002

S. Paratyphi A:Emergence of Quinolone Resistance

• Ciprofloxacin, a fluoroquinolone, is the first line agent• Increasing resistance to nalidixic acid (18 - 100%) • Correlates with decreased susceptibility to

ciprofloxacin (DSC)• DSC causes poor clinical response or treatment failure• Full ciprofloxacin resistance also reported • Resistance to other drugs has already occurred, and

so could become impossible to treat in endemic areas

Salmonella Paratyphi A and TyphiUnited States, 1968-2003

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

1968 1973 1978 1983 1988 1993 1998 2003Year

Rat

e pe

r 100

,000

per

sons

National Salmonella Surveillance System, CDC

S. Typhi

S. Paratyphi A

Methods

• One year study beginning April 1, 2005

• For all paratyphoid fever patients, all state health departments agreed to:

– Perform standard interview, asking about clinical and travel history

– Send clinical isolates to CDC for antimicrobial susceptibility testing

• Interview and laboratory data compared at CDC

ResultsApril 1, 2005 to January 31, 2006

• 93 S. Paratyphi A cases identified– 62 interviews completed– 59 isolates tested– 40 with both interview and test results

• 224 S. Typhi cases in 2003

Results are preliminary

Foreign travel

• 95% (58/61) traveled outside United States within 30 days before illness onset

• 85% (45/53) travelers visited friends or family

• 70% (40/57) born outside the United States

Countries visited (N=58)• South Asia 53 91%

– India 40 69%

– Bangladesh 9 16%

– Pakistan 5 9%

• Southeast Asia 5 9%– Indonesia 2 3%

– Cambodia 2 3%

• Latin America 1 2%– Brazil 1 2%

Antimicrobial susceptibility (N=59)

• Nalidixic acid resistant 47 80%

– DSC * 46 78%

– Ciprofloxacin sensitive 1 2%

* MIC between 0.12 and 1 mcg/ml

0

10

20

30

40

Nalidixic AcidResistant

Nalidixic AcidSensitive

Trav

el to

Sou

th A

sia

p < 0.01, Fisher’s exact test

94%

44%

n=31

n=9

Quinolone resistance and travel to South Asia

International ActivitiesWHO Global Salm-Surv

Argentina

Mexico

Poland

ThailandTrinidad

Cameroon

Egypt

Russia, St. Petersburg

China

Regional CentreTraining SiteProposed Training Site

Kazakhstan

Kenya

Brazil

Western/Southern Europe

South Africa

Russia, Moscow

India

International Network of Integrated Antimicrobial Resistance Surveillance in

Enteric Bacteria(INISAR)

• Emerging bacteria – C. diff

• Testing methods– Support– Harmonize

• Reporting– Res vs Non-Sus– Define MDR (class or drug)– Statistical issues

CDC’s Programs To Reduce the Spread of

Antimicrobial Resistance

Environment

HospitalCommunity

Cycle of Foodborne Disease Control and Prevention

Surveillance

EpidemiologicInvestigation

AppliedResearch

PreventionMeasures

LINKING

Thank You