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CDC’s Role in Tracking Trends in Resistance

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NARMS Surveillance and Laboratory Testing

CDC, through NARMS, tracks antibiotic resistance and studies patterns of emerging resistance in select bacteria transmitted commonly through food. Surveillance helps identify patterns of emerging resistance that can guide public health prevention and policy efforts to protect people from resistant infections. This information is used by a variety of stakeholders, including federal regulatory agencies, policymakers, consumer advocacy groups, industry, and the public.

National surveillance for NARMS is in all 50 states with several large metropolitan areas participating independently (New York City, Los Angeles, Houston, and Washington, D.C.)

Laboratory Testing and Isolate Submissions

The CDC NARMS laboratory conducts antibiotic susceptibility testing on isolates from sporadic cases and outbreaks of illness. The lab also confirms and studies bacteria that have new antibiotic resistance patterns and performs research to understand the genetic mechanisms of resistance and how they are spread.

Routine Surveillance

Public health laboratories submit every 20th non-typhoidal Salmonella, Shigella, and Escherichia coli O157 isolate received at their laboratories to CDC NARMS for antibiotic susceptibility testing. They also submit every Salmonella serotype Typhi, serotype Paratyphi A, serotype Paratyphi C, and Vibrio (other than V. cholerae) isolate received at their laboratories.

Public health laboratories of the 10 state health departments that participate in CDC’s Foodborne Diseases Active Surveillance Network (FoodNet) also forward a sample of Campylobacter isolates to CDC for susceptibility testing. The FoodNet sites are Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, Tennessee, and selected counties in California, Colorado, and New York.

Pathogen tested Year testing began Current sampling scheme
Salmonella, non-Typhi1 1996 1 in 20
E. coli O157 1996 1 in 20
Shigella 1999 1 in 20
Campylobacter 1997 varies
Salmonella Typhi 1999 all
Salmonella Paratyphi A and C1 2008 all
Vibrio species other than V. cholerae 2009 all

1 From 1996–2007, Salmonella Paratyphi A, B, and C were included in the 1:20 sampling scheme for non-Typhi Salmonella. Since January 2008, sites were asked to submit all Paratyphi A and C isolates to NARMS. Salmonella Paratyphi B isolates continue to be included in the 1 in 20 sampling scheme for non-Typhi Salmonella.

Outbreak Investigations

CDC NARMS tests bacteria from outbreaks for antibiotic resistance. Resistance patterns and mechanisms can help investigators identify the source of an outbreak or provide clues about the source of the outbreak. Outbreaks in 2011, 2011-2012, and 2013 of multi-resistant Salmonella traced to ground beef and poultry show how animal and human health are linked.

Antibiotics Tested by NARMS

NARMS tests isolates to determine their antibiotic susceptibility. This task is accomplished by finding the lowest concentration of a particular antibiotic that will inhibit the growth of the bacteria, which is called the minimum inhibitory concentration (MIC). CDC NARMS tests for susceptibility to 22 antibiotic agents that are in 13 classes of drugs. The names and classes of drugs and the testing methods used for susceptibility testing depend on the type of bacteria being tested:

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Salmonella, Shigella, and Escherichia coli O157

Antimicrobial agents used for susceptibility testing for Salmonella, Shigella, and Escherichia coli O157 isolates
CLSI Class Antimicrobial Agent Years
Tested
Antimicrobial Agent
Concentration Range
(μg/mL)
MIC Interpretive Standard (μg/mL)
Susceptible Intermediate*/
S-DD
Resistant
Aminoglycosides Amikacin 1997–2010 0.5–64 ≤16 32 ≥64
Gentamicin all 0.25–16 ≤4 8 ≥16
Kanamycin 1996–2013 8–64 ≤16 32 ≥64
Streptomycin 1996–2013 32–64 ≤32 N/A* ≥64
2014–present 2–64 ≤16 N/A* ≥32
β–lactam /
β–lactamase
inhibitor combinations
Amoxicillin-clavulanic acid all 1/0.5–32/16 ≤8/4 16/8 ≥32/16
Piperacillin-tazobactam§ 2011–present 0.5–128 ≤16/4 32/4–64/4 ≥128/4
Cephems Cefepime†,§ 2011–present 0.06–32 ≤2 4-8 ≥16
Cefotaxime§ 2011–present 0.06–128 ≤1 2 ≥4
Cefoxitin 2000–present 0.5–32 ≤8 16 ≥32
Ceftazidime§ 2011–present 0.06–128 ≤4 8 ≥16
Ceftiofur all 0.12–8 ≤2 4 ≥8
Ceftriaxone all 0.25–64 ≤1 2 ≥4
Cephalothin 1996–2003 2–32 ≤8 16 ≥32
Folate pathway inhibitors Sulfamethoxazole 1996–2003 16–512 ≤256 N/A* ≥512
Sulfisoxazole 2004–present 16–256 ≤256 N/A* ≥512
Trimethoprim-
sulfamethoxazole
all 0.12/2.38–4/76 ≤2/38 N/A* ≥4/76
Macrolides Azithromycin**
(Salmonella serotypes, Shigella species other than S. flexneri, and E. coli O157)
2011–present 0.12–16 ≤16 N/A* ≥32
Azithromycin**
(Shigella flexneri)
2011–present 0.12–16 ≤8 N/A* ≥16
Monobactams Aztreonam§ 2011–present 0.06–32 ≤4 8 ≥16
Penems Imipenem§ 2011–present 0.06–16 ≤1 2 ≥4
Penicillins Ampicillin all 1–32 ≤8 16 ≥32
Phenicols Chloramphenicol all 2–32 ≤8 16 ≥32
Quinolones Ciprofloxacin
(Shigella and E. coli O157)
all 0.015–4 ≤1 2 ≥4
Ciprofloxacin††
(Salmonella serotypes)
all 0.015–4 ≤0.06 0.12–0.5 ≥1
Nalidixic acid all 0.5–32 ≤16 N/A* ≥32
Tetracyclines Tetracycline all 4–32 ≤4 8 ≥16

* N/A indicates that no MIC range of intermediate susceptibility exists
Cefepime MICs above the susceptible range, but below the resistant range are designated by CLSI to be susceptible-dose dependent (S-DD)
CLSI breakpoints are not established for streptomycin; breakpoints used in this report are NARMS-established breakpoints for resistance monitoring and should not be used to predict clinical efficacy. During 1996–2013 resistance was defined as ≥64 µg/mL; the breakpoint was updated to ≥32 µg/mL in 2014. The 2014 breakpoint could not be applied to previous years due to limited concentrations tested.
§ Broad-spectrum β-lactam antimicrobial agent only tested for 2011 non-typhoidal Salmonella isolates displaying ceftriaxone and/or ceftiofur resistance
CLSI updated the ceftriaxone interpretive standards in January, 2010. NARMS Human Isolate reports for 1996 through 2008 used susceptible ≤8 μg/mL, intermediate 16-32 μg/mL, and resistant ≥64 μg/mL.
**CLSI breakpoints for azithromycin are only established for Salmonella ser. Typhi, Shigella sonnei, and Shigella flexneri. Interpretive criteria for Salmonella ser. Typhi are based on MIC distribution data. In December 2015, CLSI established epidemiological cutoff values (ECVs) for Shigella species sonnei and flexneri. The ECVs should not be used as clinical breakpoints and CLSI uses the terms “wild-type” and “non-wild-type” instead of susceptible and resistant, respectively, to reflect the nature of the populations of bacteria in each group and to highlight that these categories are not to be used to predict clinical efficacy. The azithromycin breakpoints used elsewhere in this report for other Shigella species, non-Typhi Salmonella, and E.coli O157 isolates are NARMS-established breakpoints for resistance monitoring and should not be used to predict clinical efficacy.
†† CLSI updated the ciprofloxacin interpretive standards for Salmonella in January, 2012. The previous breakpoints were susceptible ≤1 µg/mL, intermediate 2 µg/mL, and resistant ≥4 µg/mL.

 

Campylobacter

Antimicrobial agents used for susceptibility testing of Campylobacter isolates
CLSI Class Antimicrobial Agent Years Tested Antimicrobial Agent
Concentration Range (μg/mL)
MIC Interpretive Standard (μg/mL)
C. jejuni C. coli
Susceptible Resistant Susceptible Resistant
Aminoglycosides Gentamicin 1998–present 0.12–32
0.016–256*
≤2 ≥4 ≤2 ≥4
Ketolides Telithromycin 2005–present 0.015–8 ≤4 ≥8 ≤4 ≥8
Lincosamides Clindamycin all 0.03–16
0.016–256*
≤0.5 ≥1 ≤1 ≥2
Macrolides Azithromycin 1998–present 0.015–64
0.016–256*
≤0.25 ≥0.5 ≤0.5 ≥1
Erythromycin all 0.03–64
0.016–256*
≤4 ≥8 ≤8 ≥16
Phenicols Chloramphenicol 1997–2004 0.016–256* ≤16 ≥32 ≤16 ≥32
Florfenicol 2005–present 0.03–64 ≤4 ≥8 ≤4 ≥8
Quinolones Ciprofloxacin all 0.015–64
0.002–32*
≤0.5 ≥1 ≤0.5 ≥1
Nalidixic acid all 4–64
0.016–256*
≤16 ≥32 ≤16 ≥32
Tetracyclines Tetracycline all 0.06–64
0.016–256*
≤1 ≥2 ≤2 ≥4

* Etest dilution range used from 1997–2004
MIC interpretative standard is based on epidemiological cutoff values established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST – last accessed on 8/4/2016). This approach was adopted in 2012 and applied to all years. EUCAST uses the terms “wild-type” and “non-wild-type” instead of susceptible and resistant, respectively, to reflect the nature of the populations of bacteria in each group and to highlight that these categories are not to be used to predict clinical efficacy.
‡ A telithromycin ECV for Campylobacter coli is not currently published by EUCAST. We apply the previously published [PDF – 3 pages] ECV of 4 µg/mL to all C. coli isolates, designating “wild-type” isolates (MIC ≤4 µg/mL) as sensitive and “non-wild-type” isolates (MIC ≥8 µg/mL) as resistant.

Vibrio species other than V. cholerae

Antimicrobial agents used for susceptibility testing of Vibrio species other than V. cholerae isolates
CLSI Class Antimicrobial Agent Years Tested Antimicrobial Agent
Concentration Range (μg/mL)
MIC Interpretive Standard (μg/mL)
Susceptible Intermediate* Resistant
Aminoglycosides Gentamicin 2013–present 0.064–1024 ≤4 8 ≥16
Kanamycin 2009–2012 0.016–256 No CLSI or NARMS breakpoints
Streptomycin 2009–2012 0.064–1024 No CLSI or NARMS breakpoints
Cephems Cefotaxime 2013–present 0.016–256 ≤1 2 ≥4
Ceftazidime 2013–present 0.016–256 ≤4 8 ≥16
Cephalothin 2009–2012 0.016–256 No CLSI or NARMS breakpoints
Folate pathway inhibitors Trimethoprim-sulfamethoxazole all 0.002–32 ≤2/38 N/A* ≥4/76
Penems Imipenem 2013–present 0.002–32 ≤1 2 ≥4
Penicillins Ampicillin all 0.016–256 ≤8 16 ≥32
Phenicols Chloramphenicol all 0.016–256 No CLSI or NARMS breakpoints
Quinolones Ciprofloxacin all 0.002–32 ≤1 2 ≥4
Nalidixic acid all 0.016–256 No CLSI or NARMS breakpoints
Tetracyclines Tetracycline all 0.016–256 ≤4 8 ≥16

*N/A indicates that no MIC range of either intermediate or resistant susceptibility exists
CLSI updated the imipenem interpretive standards in October, 2015. The previous breakpoints were susceptible ≤4 µg/mL, intermediate 8 µg/mL, and resistant ≥16 µg/mL.

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