TABLE 1

In vitro activities of ceftazidime-avibactam and comparative antimicrobial agents tested against Enterobacteriaceae collected by the INFORM global surveillance program from 2012 to 2014

Organism group (n)Antimicrobial agentMIC values (μg/ml)MIC interpretation (%)a
MIC50MIC90MIC rangeSusceptibleIntermediateResistant
All Enterobacteriaceae (34,062)bCeftazidime-avibactam0.120.5≤0.015 to >12899.50.5
Ceftazidime0.2564≤0.015 to >12875.61.922.5
Cefepimec≤0.12>16≤0.12 to >1677.34.917.8
Aztreonam0.1264≤0.015 to >12874.31.923.8
Piperacillin-tazobactam2128≤0.25 to >12884.05.910.1
Doripenem0.060.25≤0.008 to >497.30.52.2
Ertapenem (n = 20,885)d0.0150.25≤0.002 to >194.51.63.9
Imipenem0.252≤0.03 to >885.17.67.3
Meropenem0.030.12≤0.004 to >897.20.42.4
Amikacin28≤0.25 to >3296.31.52.2
Colistine≤0.12>4≤0.015 to >483.116.9
Tigecycline0.52≤0.015 to >892.95.71.4
Levofloxacin0.06>4≤0.03 to >475.02.522.5
Meropenem nonsusceptible (961)Ceftazidime-avibactam1>128≤0.015 to >12883.516.5
Ceftazidime>128>1280.06 to >1285.32.392.4
Cefepime>16>16≤0.12 to >165.49.085.6
Aztreonam>128>128≤0.015 to >1288.90.890.3
Piperacillin-tazobactam>128>1280.5 to >1283.23.793.1
Doripenem>4>40.03 to >49.613.277.2
Ertapenem (n = 534)>1>10.015 to >12.80.896.4
Imipenem>8>80.06 to >812.25.282.6
Meropenem>8>82 to >80.016.283.8
Amikacin16>32≤0.25 to >3258.122.019.9
Colistin≤0.12>4≤0.015 to >481.418.6
Tigecycline120.06 to >891.07.51.5
Levofloxacin>4>4≤0.03 to >418.64.377.1
Meropenem nonsusceptible, MBL negative (816)Ceftazidime-avibactam14≤0.015 to >12897.72.3f
Ceftazidime128>1280.06 to >1285.92.791.4
Cefepime>16>16≤0.12 to >165.69.485.0
Aztreonam>128>128≤0.015 to >1284.70.694.7
Piperacillin-tazobactam>128>1280.5 to >1282.63.893.6
Doripenem>4>40.03 to >411.215.073.8
Ertapenem (n = 452)>1>10.015 to >12.40.497.2
Imipenem>8>80.06 to >814.15.580.4
Meropenem>8>82 to >80.017.482.6
Amikacin16>32≤0.25 to >3257.925.216.9
Colistin≤0.12>4≤0.015 to >481.518.5
Tigecycline120.06 to 891.47.41.2
Levofloxacin>4>4≤0.03 to >416.53.779.8
Meropenem nonsusceptible, carbapenemase positive, MBL negative (609)Ceftazidime-avibactam14≤0.015 to >12898.71.3
Ceftazidime128>1280.06 to >1285.62.991.5
Cefepime>16>16≤0.12 to >165.19.485.5
Aztreonam>128>128≤0.015 to >1283.60.396.1
Piperacillin-tazobactam>128>1282 to >1280.52.097.5
Doripenem>4>40.5 to >44.810.285.0
Ertapenem (n = 329)>1>10.25 to >10.90.398.8
Imipenem>8>80.5 to >80.83.595.7
Meropenem>8>82 to >80.08.491.6
Amikacin16>32≤0.25 to >3252.132.015.9
Colistin≤0.12>4≤0.015 to >481.019.0
Tigecycline120.06 to 891.57.70.8
Levofloxacin>4>4≤0.03 to >414.83.981.3
KPC positive, MBL negative (476)gCeftazidime-avibactam14≤0.015 to 12898.71.3
Ceftazidime>128>1281 to >1282.13.494.5
Cefepime>16>16≤0.12 to >162.910.786.4
Aztreonam>128>1282 to >1280.40.299.4
Piperacillin-tazobactam>128>1282 to >1280.62.197.3
Doripenem>4>40.5 to >42.18.489.5
Ertapenem (n = 269)>1>10.25 to >11.10.498.5
Imipenem>8>80.5 to >80.41.198.5
Meropenem>8>82 to >80.03.696.4
Amikacin32>32≤0.25 to >3244.640.115.3
Colistin≤0.12>4≤0.015 to >482.617.4
Tigecycline120.06 to 891.67.41.0
Levofloxacin>4>4≤0.03 to >412.83.284.0
OXA-48-like positive, MBL negative (134)hCeftazidime-avibactam0.520.03 to 6498.51.5
Ceftazidime64>1280.06 to >12817.91.580.6
Cefepime>16>16≤0.12 to >1612.74.582.8
Aztreonam128>128≤0.015 to >12814.90.884.3
Piperacillin-tazobactam>128>12832 to >1280.01.598.5
Doripenem>4>40.5 to >414.916.468.7
Ertapenem (n = 62)>1>1>10.00.0100
Imipenem8>81 to >82.212.085.8
Meropenem>8>82 to >80.026.173.9
Amikacin8>320.5 to >3278.43.018.6
Colistin≤0.12>4≤0.015 to >475.424.6
Tigecycline120.12 to 491.09.00.0
Levofloxacin>4>4≤0.03 to >420.96.772.4
Meropenem nonsusceptible, MBL negative, carbapenemase negative (207)Ceftazidime-avibactam240.06 to >12894.75.3
Ceftazidime128>1280.12 to >1286.81.991.3
Cefepime>16>16≤0.12 to >167.29.783.1
Aztreonam128>1280.03 to >1287.71.590.8
Piperacillin-tazobactam>128>1280.5 to >1288.79.282.1
Doripenem2>40.03 to >430.429.040.6
Ertapenem (n = 123)>1>10.015 to >16.50.892.7
Imipenem1>80.06 to >853.111.635.3
Meropenem4>82 to >80.044.056.0
Amikacin8>32≤0.25 to >3274.95.319.8
Colistin≤0.12>4≤0.015 to >483.116.9
Tigecycline120.06 to 891.36.32.4
Levofloxacin>4>4≤0.03 to >421.72.975.4
MBL positive (145)iCeftazidime-avibactam>128>1280.5 to >1283.496.6
Ceftazidime>128>1280.5 to >1282.10.097.9
Cefepime>16>16≤0.12 to >164.16.289.7
Aztreonam64>128≤0.015 to >12832.42.165.5
Piperacillin-tazobactam>128>1280.5 to >1286.92.890.3
Doripenem>4>42 to >40.03.496.6
Ertapenem (n = 82)>1>10.12 to >14.92.492.7
Imipenem>8>80.5 to >81.43.495.2
Meropenem>8>82 to >80.09.790.3
Amikacin16>321 to >3259.34.136.6
Colistin≤0.12>4≤0.015 to >480.719.3
Tigecycline140.06 to >888.38.33.4
Levofloxacin>4>40.06 to >430.37.662.1
  • a MICs were interpreted according to CLSI breakpoints (16), with the exception of the following: ceftazidime-avibactam, for which MICs were interpreted using the MIC interpretative criteria according to the FDA (18); tigecycline, for which MICs were interpreted using the MIC interpretative criteria according to the FDA (19); and colistin, for which EUCAST breakpoints were applied (20).

  • b The 34,062 Enterobacteriaceae isolates were composed of the following: Citrobacter amalonaticus (n = 21), Citrobacter braakii (n = 109), Citrobacter diversus (n = 1), Citrobacter farmeri (n = 4), Citrobacter freundii (n = 1,033), Citrobacter gillenii (n = 1), Citrobacter koseri (n = 707), Citrobacter murliniae (n = 5), Citrobacter sedlakii (n = 3), Citrobacter youngae (n = 1), Citrobacter, species not determined (n = 4), Enterobacter aerogenes (n = 1,350), Enterobacter amnigenus (n = 1), Enterobacter asburiae (n = 250), Enterobacter cancerogenus (n = 1), Enterobacter cloacae (n = 2,207), Enterobacter gergoviae (n = 4), Enterobacter hormaechei (n = 1), Enterobacter kobei (n = 93), Enterobacter ludwigii (n = 24), Escherichia coli (n = 11,770), Escherichia fergusonii (n = 1), Escherichia hermannii (n = 2), Escherichia vulneris (n = 1), Hafnia alvei (n = 4), Klebsiella oxytoca (n = 1,900), Klebsiella ozaenae (n = 1), Klebsiella pneumoniae (n = 9,098), Klebsiella variicola (n = 7), Kluyvera ascorbata (n = 2), Morganella morganii (n = 979), Pantoea agglomerans (n = 2), Proteus hauseri (n = 3), Proteus mirabilis (n = 2,235), Proteus penneri (n = 42), Proteus rettgeri (n = 2), Proteus vulgaris (n = 995), Providencia alcalifaciens (n = 14), Providencia rettgeri (n = 141), Providencia stuartii (n = 161), Raoultella ornithinolytica (n = 57), Raoultella planticola (n = 13), Raoultella terrigena (n = 2), Serratia liquefaciens (n = 16), Serratia marcescens (n = 785), Serratia odorifera (n = 1), Serratia rubidaea (n = 1), and Serratia ureilytica (n = 7).

  • c For cefepime, the susceptible-dose-dependent (SDD) interpretive category replaced the intermediate category in 2014.

  • d Ertapenem was not tested against isolates collected in 2014.

  • e Colistin was tested with a final concentration of 0.002% polysorbate-80 in each panel well.

  • f The 19 MBL-negative isolates that were resistant to ceftazidime-avibactam (MIC, >8 μg/ml) were composed of the following: C. braakii (n = 1), E. aerogenes (n = 1), E. coli (n = 2), K. oxytoca (n = 2), K. pneumoniae (n = 11), P. vulgaris (n = 1), and S. marcescens (n = 1).

  • g Includes two isolates carrying KPC-2 and OXA-163 and one isolate carrying KPC-2 and GES-6; does not include 6 isolates carrying KPC and MBL.

  • h Includes isolates carrying OXA-48 (n = 116), OXA-244 (n = 9), OXA-181 (n = 4), and OXA-163 (n = 5); two of these carry both OXA-163 and KPC-2. Does not include 7 isolates carrying OXA-48-like and MBL.

  • i The 145 isolates that were MBL positive were composed of the following: C. freundii (n = 8), E. asburiae (n = 4), E. cloacae (n = 31), E. coli (n = 5), K. oxytoca (n = 7), K. pneumoniae (n = 73), P. mirabilis (n = 8), P. rettgeri (n = 1), P. stuartii (n = 3), and S. marcescens (n = 5). Also included are 13 isolates carrying MBLs and serine carbapenemases: VIM-1 and KPC-2 (n = 4), IMP-4 and KPC-2 (n = 2), VIM-4 and OXA-48 (n = 2), VIM-31 and OXA-48 (n = 1), NDM-1 and OXA-48 (n = 3), and NDM-1 and OXA-232 (n = 1).