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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). Currently CDC NARMS routinely tests for susceptibility to 18 antibiotic agents that are in 12 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:

Salmonella

Antimicrobial agents used for susceptibility testing for Salmonella isolates
CLSI Class Antimicrobial Agent Years
Tested
Antimicrobial Agent
Concentration Range
(μg/mL)
MIC Interpretive Standard (μg/mL)
Susceptible Intermediate* or S-DD Resistant
Aminoglycosides Amikacin 1997–2010 0.5–64 ≤16 32 ≥64
Gentamicin 1996–present 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 combination agents Amoxicillin-clavulanic acid 1996–present 1/0.5–32/16 ≤8/4 16/8 ≥32/16
Piperacillin-tazobactam§ 2011–2015 0.5–128 ≤16/4 32/4–64/4 ≥128/4
Cephems Cefepime†,§ 2011–2015 0.06–32 ≤2 4-8 ≥16
Cefotaxime§ 2011–2015 0.06–128 ≤1 2 ≥4
Cefoxitin 2000–present 0.5–32 ≤8 16 ≥32
Ceftazidime§ 2011–2015 0.06–128 ≤4 8 ≥16
Ceftiofur 1996–2015 0.12–8 ≤2 4 ≥8
Ceftriaxone 1996–present 0.25–64 ≤1 2 ≥4
Cephalothin 1996–2003 2–32 ≤8 16 ≥32
Folate pathway antagonists Sulfamethoxazole 1996–2003 16–512 ≤256 N/A* ≥512
Sulfisoxazole 2004–present 16–256 ≤256 N/A* ≥512
Trimethoprim-
sulfamethoxazole
1996–present 0.12/2.38–4/76 ≤2/38 N/A* ≥4/76
Macrolides Azithromycin** 2011–present 0.25–32
0.12–16††
≤16 N/A* ≥32
Monobactams Aztreonam§ 2011–2015 0.06–32 ≤4 8 ≥16
Penems Imipenem§ 2011–2015 0.06–16 ≤1 2 ≥4
Meropenem 2016–present 0.06–4 ≤1 2 ≥4
Penicillins Ampicillin 1996–present 1–32 ≤8 16 ≥32
Phenicols Chloramphenicol 1996–present 2–32 ≤8 16 ≥32
Quinolones Ciprofloxacin†† 1996–present 0.015–4 ≤0.06 0.12–0.5 ≥1
Nalidixic acid 1996–present 0.5–32 ≤16 N/A* ≥32
Tetracyclines Tetracycline 1996–present 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;  interpretive standards used 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. Interpretive criteria for Salmonella ser. Typhi are based on MIC distribution data and limited clinical data. The azithromycin interpretive standards used for Salmonella serotypes other than ser. Typhi are NARMS-established breakpoints for resistance monitoring and should not be used to predict clinical efficacy.
††Concentration range used for azithromycin during 2011–2015

‡‡CLSI updated the ciprofloxacin interpretive standards for Salmonella in January, 2012. NARMS Human Isolate Reports for 1996 through 2010 used susceptible ≤1 µg/mL, intermediate 2 µg/mL, and resistant ≥4 µg/mL.

Shigella

Antimicrobial agents used for susceptibility testing for Shigella isolates
CLSI Class Antimicrobial Agent Years
Tested
Antimicrobial Agent
Concentration Range
(μg/mL)
MIC Interpretive Standard (μg/mL)
Susceptible Intermediate* Resistant
Aminoglycosides Amikacin 1999–2010 0.5–64 ≤16 32 ≥64
Gentamicin 1999–present 0.25–16 ≤4 8 ≥16
Kanamycin 1999–2013 8–64 ≤16 32 ≥64
Streptomycin 1999–2013 32–64 ≤32 N/A* ≥64
2014–present 2–64 ≤16 N/A* ≥32
β–lactam combination agents Amoxicillin-clavulanic acid 1999–present 1/0.5–32/16 ≤8/4 16/8 ≥32/16
Cephems Cefoxitin 2000–present 0.5–32 ≤8 16 ≥32
Ceftiofur 1999–2015 0.12–8 ≤2 4 ≥8
Ceftriaxone 1999–present 0.25–64 ≤1 2 ≥4
Cephalothin 1999–2003 2–32 ≤8 16 ≥32
Folate pathway antagonists Sulfamethoxazole 1999–2003 16–512 ≤256 N/A* ≥512
Sulfisoxazole 2004–present 16–256 ≤256 N/A* ≥512
Trimethoprim-
sulfamethoxazole
1999–present 0.12/2.38–4/76 ≤2/38 N/A* ≥4/76
Macrolides Azithromycin§
(Shigella species other than S. flexneri)
2011–present 0.25–32
0.12–16
≤16 N/A* ≥32
Azithromycin§
(Shigella flexneri)
2011–present 0.25–32
0.12–16
≤8 N/A* ≥16
Penems Meropenem 2016–present 0.06–4 ≤1 2 ≥4
Penicillins Ampicillin 1999–present 1–32 ≤8 16 ≥32
Phenicols Chloramphenicol 1999–present 2–32 ≤8 16 ≥32
Quinolones Ciprofloxacin 1999–present 0.015–4 ≤1 2 ≥4
Nalidixic acid 1999–present 0.5–32 ≤16 N/A* ≥32
Tetracyclines Tetracycline 1999–present 4–32 ≤4 8 ≥16

* N/A indicates that no MIC range of intermediate susceptibility exists
CLSI breakpoints are not established for streptomycin;  interpretive standards used are NARMS-established breakpoints for resistance monitoring and should not be used to predict clinical efficacy. During 1999–2013 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.
CLSI updated the ceftriaxone interpretive standards in January, 2010. NARMS Human Isolate reports for 1999 through 2008 used susceptible ≤8 μg/mL, intermediate 16-32 μg/mL, and resistant ≥64 μg/mL.
§ CLSI  interpretive standards for azithromycin are only established for Shigella sonnei and Shigella flexneri. 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  interpretive standards used for other Shigella species are NARMS-established breakpoints for resistance monitoring and should not be used to predict clinical efficacy.
Concentration range used for azithromycin during 2011–2015.

E. coli

Antimicrobial agents used for susceptibility testing for E. coli O157 isolates
CLSI Class Antimicrobial Agent Years
Tested
Antimicrobial Agent
Concentration Range
(μg/mL)
MIC Interpretive Standard (μg/mL)
Susceptible Intermediate* Resistant
Aminoglycosides Amikacin 1997–2010 0.5–64 ≤16 32 ≥64
Gentamicin 1996–present 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 combination agents Amoxicillin-clavulanic acid 1996–present 1/0.5–32/16 ≤8/4 16/8 ≥32/16
Cephems Cefoxitin 2000–present 0.5–32 ≤8 16 ≥32
Ceftiofur 1996–2015 0.12–8 ≤2 4 ≥8
Ceftriaxone 1996–present 0.25–64 ≤1 2 ≥4
Cephalothin 1996–2003 2–32 ≤8 16 ≥32
Folate pathway antagonists Sulfamethoxazole 1996–2003 16–512 ≤256 N/A* ≥512
Sulfisoxazole 2004–present 16–256 ≤256 N/A* ≥512
Trimethoprim-
sulfamethoxazole
1996–present 0.12/2.38–4/76 ≤2/38 N/A* ≥4/76
Macrolides Azithromycin§ 2011–present 0.25–32
0.12–16
≤16 N/A* ≥32
Penems Meropenem 2016–present 0.06–4 ≤1 2 ≥4
Penicillins Ampicillin 1996–present 1–32 ≤8 16 ≥32
Phenicols Chloramphenicol 1996–present 2–32 ≤8 16 ≥32
Quinolones Ciprofloxacin 1996–present 0.015–4 ≤1 2 ≥4
Nalidixic acid 1996–present 0.5–32 ≤16 N/A* ≥32
Tetracyclines Tetracycline 1996–present 4–32 ≤4 8 ≥16

* N/A indicates that no MIC range of intermediate susceptibility exists
CLSI breakpoints are not established for streptomycin; interpretive standards used 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.
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 are not established for azithromycin and E. coli O157; interpretive standards used are NARMS-established breakpoints for resistance monitoring and should not be used to predict clinical efficacy.
Concentration range used for azithromycin during 2011–2015

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 1997–present 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 1997–present 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 1997–present 0.015–64
0.002–32*
≤0.5 ≥1 ≤0.5 ≥1
Nalidixic acid 1997–present 4–64
0.016–256*
≤16 ≥32 ≤16 ≥32
Tetracyclines Tetracycline 1997–present 0.06–64
0.016–256*
≤1 ≥2 ≤2 ≥4

* Etest dilution range used before 2005
MIC interpretative standard is based on epidemiological cutoff values established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST – last accessed on 7/21/2017). 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 0.25–16
0.064–1024
≤4 8 ≥16
Kanamycin 2009–2012 0.016–256 No CLSI or NARMS breakpoints
Streptomycin 2009–2012;
2015–present
2–64
0.064–1024
No CLSI or NARMS breakpoints
 β–lactam combination agents  Amoxicillin-clavulanic acid  2015–present  1/0.5–32/16  ≤8/4  16/8  ≥32/16
Cephems Cefotaxime 2013–2014 0.016–256 ≤1 2 ≥4
Cefoxitin 2015–present 0.5–32 ≤8 16 ≥32
Ceftazidime 2013–2014 0.016–256 ≤4 8 ≥16
Ceftiofur 2015 0.12–8 No CLSI or NARMS breakpoints
Ceftriaxone 2015–present 0.25–64 No CLSI or NARMS breakpoints
Cephalothin 2009–2012 0.016–256 No CLSI or NARMS breakpoints
Folate pathway antagonists Sulfisoxazole 2015–present 16–256 No CLSI or NARMS breakpoints
Trimethoprim-sulfamethoxazole 2009–present 0.12/2.38–4/76
0.002–32
≤2/38 N/A* ≥4/76
Macrolides Azithromycin 2015–present 0.25–32
0.12–16
See footnote§
Penems Imipenem 2013–2014 0.002–32 ≤1 2 ≥4
Meropenem 2016–present 0.06–4 ≤1 2 ≥4
Penicillins Ampicillin 2009–present 1–32
0.016–256
≤8 16 ≥32
Phenicols Chloramphenicol 2009–present 2–32
0.016–256
No CLSI or NARMS breakpoints
Quinolones Ciprofloxacin 2009–present 0.015–4
0.002–32
≤1 2 ≥4
Nalidixic acid 2009–present 0.5–32
0.016–256
No CLSI or NARMS breakpoints
Tetracyclines Tetracycline 2009–present 4–32
0.016–256
≤4 8 ≥16

*N/A indicates that no MIC range of either intermediate or resistant susceptibility exists
Etest dilution range used before 2015
Concentration range used for azithromycin in 2015
§CLSI has only established a susceptible breakpoint (≤2 µg/mL) for azithromycin and cautions that the utility of this interpretation for Vibrio species other than V. cholerae is uncertain due to limited clinical or in vitro MIC data. Because of this, NARMS will not apply any interpretive criteria to azithromycin MICs for non-cholerae Vibrio until further data are available.
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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