TABLE 4.
In vitro activities of antimicrobial agents tested against carbapenem-nonsusceptible KPC-producing isolates collected in 2012 to 2014
| Organism subset (n) and agenta | MIC (μg/ml) |
% susceptibleb | ||
|---|---|---|---|---|
| Range | 50% | 90% | ||
| All Enterobacteriaceae (38,266) | ||||
| Ceftazidime | ≤0.015 to >128 | 0.25 | 64 | 76.9 |
| Ceftazidime-avibactamc | ≤0.015 to >128 | 0.12 | 0.5 | 99.5 |
| Aztreonam | ≤0.015 to >128 | 0.12 | 64 | 75.7 |
| Aztreonam-avibactamc | ≤0.015 to >128 | 0.03 | 0.12 | NA |
| Cefepime | ≤0.12 to >16 | ≤0.12 | >16 | 78.8 |
| Meropenem | ≤0.004 to >8 | 0.03 | 0.12 | 97.3 |
| Imipenem | ≤0.03 to >8 | 0.25 | 2 | 85.3 |
| Piperacillin-tazobactam | ≤0.25 to >128 | 2 | 64 | 84.7 |
| Amikacin | ≤0.25 to >32 | 2 | 8 | 96.6 |
| Tigecycline | ≤0.015 to >8 | 0.5 | 2 | 92.9 |
| Colistind | ≤0.12 to >4 | ≤0.12 | >4 | 83.2 |
| KPC-positive Enterobacteriaceae | ||||
| All (557) | ||||
| Ceftazidime | 0.12 to >128 | >128 | >128 | 3.9 |
| Ceftazidime-avibactam | ≤0.015 to >128 | 1 | 4 | 97.5 |
| Aztreonam | 0.06 to >128 | >128 | >128 | 1.3 |
| Aztreonam-avibactam | ≤0.015 to 8 | 0.25 | 0.5 | NA |
| Cefepime | ≤0.12 to >16 | >16 | >16 | 4.8 |
| Meropenem | 0.06 to >8 | >8 | >8 | 3.1 |
| Imipenem | 0.5 to >8 | >8 | >8 | 0.5 |
| Piperacillin-tazobactam | 0.5 to >128 | >128 | >128 | 0.9 |
| Amikacin | ≤0.25 to >32 | 32 | >32 | 48.3 |
| Tigecycline | 0.06 to 8 | 1 | 2 | 91.6 |
| Colistin | ≤0.12 to >4 | 0.03 | >4 | 83.3 |
| KPC ± OSBL (291) | ||||
| Ceftazidime | 1 to >128 | 128 | >128 | 3.8 |
| Ceftazidime-avibactam | ≤0.015 to 128 | 1 | 4 | 98.6 |
| Aztreonam | 4 to >128 | >128 | >128 | 1.0 |
| Aztreonam-avibactam | ≤0.015 to 8 | 0.12 | 0.5 | NA |
| Cefepime | ≤0.12 to >16 | >16 | >16 | 5.5 |
| Meropenem | 0.25 to >8 | >8 | >8 | 3.1 |
| Imipenem | 2 to >8 | >8 | >8 | 0.0 |
| Piperacillin-tazobactam | 2 to >128 | >128 | >128 | 0.7 |
| Amikacin | 0.5 to >32 | 32 | 32 | 49.1 |
| Tigecycline | 0.06 to 8 | 1 | 2 | 91.8 |
| Colistin | ≤0.12 to >4 | 0.03 | >4 | 89.0 |
| KPC + ESBL ± OSBLe (219) | ||||
| Ceftazidime | 1 to >128 | >128 | >128 | 1.4 |
| Ceftazidime-avibactam | ≤0.015 to 16 | 1 | 4 | 99.1 |
| Aztreonam | 2 to >128 | >128 | >128 | 1.4 |
| Aztreonam-avibactam | ≤0.015 to 4 | 0.25 | 0.5 | NA |
| Cefepime | ≤0.12 to >16 | >16 | >16 | 2.3 |
| Meropenem | 0.5 to >8 | >8 | >8 | 1.4 |
| Imipenem | 0.5 to >8 | >8 | >8 | 0.9 |
| Piperacillin-tazobactam | 8 to >128 | >128 | >128 | 0.9 |
| Amikacin | ≤0.25 to >32 | 32 | >32 | 42.5 |
| Tigecycline | 0.06 to 8 | 1 | 2 | 92.2 |
| Colistin | ≤0.12 to >4 | 0.03 | >4 | 75.8 |
| KPC + AmpC ± OSBLf (25) | ||||
| Ceftazidime | 0.12 to >128 | 32 | >128 | 24.0 |
| Ceftazidime-avibactam | 0.03 to 2 | 0.5 | 2 | 100 |
| Aztreonam | 0.06 to >128 | >128 | >128 | 4.0 |
| Aztreonam-avibactam | ≤0.015 to 4 | 0.12 | 1 | NA |
| Cefepime | ≤0.12 to >16 | 16 | >16 | 16.0 |
| Meropenem | 0.06 to >8 | 8 | >8 | 16.0 |
| Imipenem | 2 to >8 | 8 | >8 | 0.0 |
| Piperacillin-tazobactam | 0.5 to >128 | >128 | >128 | 4.0 |
| Amikacin | 0.5 to >32 | 4 | >32 | 76.0 |
| Tigecycline | 0.06 to 4 | 1 | 2 | 92.0 |
| Colistin | ≤0.12 to >4 | ≤0.12 | >4 | 80.0 |
| KPC + ESBL + AmpC ± OSBLf (14) | ||||
| Ceftazidime | 2 to >128 | 64 | >128 | 14.3 |
| Ceftazidime-avibactam | 0.25 to 4 | 1 | 2 | 100 |
| Aztreonam | 16 to >128 | >128 | >128 | 0.0 |
| Aztreonam-avibactam | 0.03 to 1 | 0.25 | 0.5 | NA |
| Cefepime | ≤0.12 to >16 | >16 | >16 | 14.3 |
| Meropenem | 0.5 to >8 | 4 | >8 | 7.1 |
| Imipenem | 1 to >8 | 8 | >8 | 7.1 |
| Piperacillin-tazobactam | 64 to >128 | >128 | >128 | 0.0 |
| Amikacin | ≤0.25 to >32 | 4 | 32 | 78.6 |
| Tigecycline | 0.25 to 8 | 1 | 4 | 71.4 |
| Colistin | ≤0.12 to 0.06 | ≤0.12 | 0.06 | 100 |
| KPC + OXA-48-like + OSBL ± ESBL (2) | ||||
| Ceftazidime | 128 to >128 | 0.0 | ||
| Ceftazidime-avibactam | 1 to 2 | 100 | ||
| Aztreonam | 64 to >128 | 0.0 | ||
| Aztreonam-avibactam | 0.25 to 0.5 | NA | ||
| Cefepime | >16 to >16 | 0.0 | ||
| Meropenem | 2 to >8 | 0.0 | ||
| Imipenem | 4 to 8 | 0.0 | ||
| Piperacillin-tazobactam | >128 to >128 | 0.0 | ||
| Amikacin | 16 to >32 | 50.0 | ||
| Tigecycline | 2 −2 | 100 | ||
| Colistin | ≤0.12 to ≤0.12 | 100 | ||
| KPC + MBL ± ESBL ± AmpC ± OSBL (6) | ||||
| Ceftazidime | >128 to >128 | 0.0 | ||
| Ceftazidime-avibactam | >128 to >128 | 0.0 | ||
| Aztreonam | >128 to >128 | 0.0 | ||
| Aztreonam-avibactam | 0.5 to 1 | NA | ||
| Cefepime | >16 to >16 | 0.0 | ||
| Meropenem | >8 to >8 | 0.0 | ||
| Imipenem | >8 to >8 | 0.0 | ||
| Piperacillin-tazobactam | >128 to >128 | 0.0 | ||
| Amikacin | 16 to >32 | 16.7 | ||
| Tigecycline | 0.5 to 2 | 100 | ||
| Colistin | ≤0.12 to >4 | 50.0 | ||
| All P. aeruginosa (8,010) | ||||
| Ceftazidime | 0.06 to >128 | 2 | 64 | 77.4 |
| Ceftazidime-avibactam | 0.06 to >128 | 2 | 8 | 92.4 |
| Aztreonam | ≤0.015 to >128 | 8 | 32 | 61.4 |
| Aztreonam-avibactam | ≤0.015 to >128 | 8 | 32 | NA |
| Cefepime | ≤0.12 to >16 | 4 | 16 | 78.6 |
| Meropenem | ≤0.06 to >8 | 0.5 | >8 | 73.3 |
| Imipenem | ≤0.03 to >8 | 2 | >8 | 61.7 |
| Piperacillin-tazobactam | ≤0.25 to >128 | 8 | >128 | 69.1 |
| Amikacin | ≤0.25 to >32 | 4 | 16 | 90.2 |
| Colistin | ≤0.12 to >8 | 0.5 | 1 | 99.5 |
| KPC-positive P. aeruginosa | ||||
| All (29) | ||||
| Ceftazidime | 64 to >128 | 64 | >128 | 0.0 |
| Ceftazidime-avibactam | 4 to 64 | 8 | 32 | 75.9 |
| Aztreonam | >128 to >128 | >128 | >128 | 0.0 |
| Aztreonam-avibactam | 8 to >128 | 32 | 64 | NA |
| Cefepime | 0.5 to >16 | >16 | >16 | 3.4 |
| Meropenem | >8 to >8 | >8 | >8 | 0.0 |
| Imipenem | >8 to >8 | >8 | >8 | 0.0 |
| Piperacillin-tazobactam | >128 to >128 | >128 | >128 | 0.0 |
| Amikacin | 1 to >32 | 8 | >32 | 75.9 |
| Colistin | ≤0.06 to >8 | 0.5 | 2 | 96.6 |
| KPC + AmpCf (28) | ||||
| Ceftazidime | 64 to >128 | 64 | >128 | 0.0 |
| Ceftazidime-avibactam | 4 to 64 | 8 | 32 | 78.6 |
| Aztreonam | >128 to >128 | >128 | >128 | 0.0 |
| Aztreonam-avibactam | 8 to >128 | 32 | 64 | NA |
| Cefepime | 0.5 to >16 | >16 | >16 | 3.6 |
| Meropenem | >8 to >8 | >8 | >8 | 0.0 |
| Imipenem | >8 to >8 | >8 | >8 | 0.0 |
| Piperacillin-tazobactam | >128 to >128 | >128 | >128 | 0.0 |
| Amikacin | 1 to >32 | 8 | >32 | 78.6 |
| Colistin | ≤0.06 to >8 | 0.5 | 2 | 96.4 |
| KPC + AmpC + MBLf (1) | ||||
| Ceftazidime | 64 | 0.0 | ||
| Ceftazidime-avibactam | 64 | 0.0 | ||
| Aztreonam | >128 | 0.0 | ||
| Aztreonam-avibactam | 16 | NA | ||
| Cefepime | >16 | 0.0 | ||
| Meropenem | >8 | 0.0 | ||
| Imipenem | >8 | 0.0 | ||
| Piperacillin-tazobactam | >128 | 0.0 | ||
| Amikacin | >32 | 0.0 | ||
| Colistin | 2 | 100 | ||
a
MBL, metallo-β-lactamase; ESBL, extended-spectrum β-lactamase; OSBL, original-spectrum β-lactamase (includes TEM-1, TEM-2, SHV-1, and SHV-11).
b
Susceptibility percentages were determined using CLSI interpretive criteria. FDA breakpoints were applied for ceftazidime-avibactam (≤8 μg/ml, susceptible; ≥16 μg/ml, resistant) and tigecycline (≤2 μg/ml, susceptible; 4 μg/ml, intermediate; ≥8 μg/ml, resistant). EUCAST breakpoints were applied for colistin tested against Enterobacteriaceae (≤2 μg/ml, susceptible; ≥4 μg/ml, resistant).
c
Aztreonam-avibactam and ceftazidime-avibactam were tested at a fixed concentration of 4 μg/ml avibactam.
d
Colistin was tested with 0.002% polysorbate 80.
e
Includes the presumed chromosomally encoded ESBL common to K. oxytoca.
f
Includes plasmid-encoded and presumed chromosomally encoded AmpC β-lactamases common to Enterobacter spp., Citrobacter spp., M. morganii, S. marcescens, and P. aeruginosa.