TABLE 2.
In vitro activities of ceftazidime-avibactam and comparator antimicrobial agents tested against β-lactamase-positive Enterobacteriaceae and P. aeruginosa isolatesa
| Organism or genotype (no. of isolates)a | Antimicrobial agent | MIC (μg/ml)b |
% Susceptiblec | ||
|---|---|---|---|---|---|
| MIC50 | MIC90 | Range | |||
| Enterobacteriaceae (2,321) | |||||
| OSBL positive (55) | Ceftazidime-avibactam | 0.25 | 0.5 | ≤0.03 to 2 | 100 |
| Ceftazidime | 4 | 32 | ≤0.015 to >128 | 58.2 | |
| Cefepime | 1 | 16 | ≤0.12 to >16 | 80.0 | |
| Aztreonam | 1 | 64 | ≤0.015 to 128 | 72.7 | |
| Piperacillin-tazobactam | 128 | >128 | ≤0.25 to >128 | 43.6 | |
| Doripenem | 0.06 | 0.5 | 0.03 to 2 | 96.4 | |
| Imipenem | 0.25 | 4 | 0.06 to 8 | 80.0 | |
| Meropenem | 0.06 | 0.12 | 0.03 to 2 | 96.4 | |
| Amikacin | 2 | 16 | ≤0.25 to >32 | 90.9 | |
| Colistin (n = 24)d | 1 | >4 | 0.25 to >4 | 83.3 | |
| Tigecycline | 0.5 | 2 | 0.25 to 4 | 92.7 | |
| Levofloxacin | 0.5 | >4 | ≤0.03 to >4 | 63.6 | |
| Spectrum undefined (2)e | Ceftazidime-avibactam | —b | — | 0.12 to 1 | 100 |
| Ceftazidime | — | — | 16 to 32 | 0 | |
| Cefepime | — | — | ≤0.12 to 16 | 50.0 | |
| Aztreonam | — | — | 4 to 32 | 50.0 | |
| Piperacillin-tazobactam | — | — | 4 to 64 | 50.0 | |
| Doripenem | — | — | 0.03 to 0.06 | 100 | |
| Imipenem | — | — | 0.25 to 0.25 | 100 | |
| Meropenem | — | — | 0.03 to 0.06 | 100 | |
| Amikacin | — | — | 0.5 to 1 | 100 | |
| Colistin (n = 0)d | — | — | NDd | ND | |
| Tigecycline | — | — | 0.5 to 2 | 100 | |
| Levofloxacin | — | — | 0.5 to >4 | 50.0 | |
| ESBL positive (1,701)f | Ceftazidime-avibactam | 0.25 | 1 | ≤0.015 to 128 | 99.9 |
| Ceftazidime | 32 | >128 | 0.25 to >128 | 14.8 | |
| Cefepime | >16 | >16 | ≤0.12 to >16 | 5.9 | |
| Aztreonam | 64 | >128 | ≤0.25 to >128 | 5.9 | |
| Piperacillin-tazobactam | 16 | >128 | ≤0.25 to >128 | 62.4 | |
| Doripenem | 0.06 | 0.25 | ≤0.008 to >4 | 96.4 | |
| Imipenem | 0.25 | 0.5 | 0.06 to >8 | 96.8 | |
| Meropenem | 0.06 | 0.12 | ≤0.004 to >8 | 94.2 | |
| Amikacin | 4 | 32 | ≤0.25 to >32 | 89.8 | |
| Colistin (n = 988)d | 0.5 | 1 | 0.12 to >4 | 94.5 | |
| Tigecycline | 0.5 | 2 | ≤0.015 to >8 | 95.4 | |
| Levofloxacin | >4 | >4 | ≤0.03 to >4 | 27.9 | |
| AmpC positive (199)g | Ceftazidime-avibactam | 0.25 | 1 | 0.03 to 32 | 99.0 |
| Ceftazidime | 16 | >128 | 0.03 to >128 | 45.7 | |
| Cefepime | 0.25 | 8 | ≤0.12 to >16 | 81.4 | |
| Aztreonam | 4 | 64 | ≤0.015 to >128 | 52.3 | |
| Piperacillin-tazobactam | 4 | >128 | ≤0.25 to >128 | 70.4 | |
| Doripenem | 0.12 | 0.5 | ≤0.008 to >4 | 96.5 | |
| Imipenem | 2 | 4 | 0.12 to >8 | 45.7 | |
| Meropenem | 0.06 | 0.25 | 0.015 to >8 | 95.5 | |
| Amikacin | 2 | 8 | ≤0.25 to >32 | 96.5 | |
| Colistin (n = 94)d | 1 | >4 | 0.25 to >4 | 86.2 | |
| Tigecycline | 0.5 | 2 | 0.06 to 4 | 95.5 | |
| Levofloxacin | 0.12 | >4 | ≤0.03 to >4 | 72.4 | |
| ESBL positive + AmpC positive (64)h | Ceftazidime-avibactam | 0.5 | 2 | 0.03 to 2 | 100 |
| Ceftazidime | 128 | >128 | 0.12 to >128 | 6.3 | |
| Cefepime | >16 | >16 | ≤0.12 to >16 | 12.5 | |
| Aztreonam | 128 | >128 | 0.25 to >128 | 4.7 | |
| Piperacillin-tazobactam | 128 | >128 | 2 to >128 | 31.3 | |
| Doripenem | 0.12 | 1 | 0.03 to >4 | 90.6 | |
| Imipenem | 0.5 | 4 | 0.06 to >8 | 78.1 | |
| Meropenem | 0.06 | 1 | 0.03 to >8 | 90.6 | |
| Amikacin | 4 | 32 | 0.5 to >32 | 76.6 | |
| Colistin (n = 26)d | 0.5 | 4 | 0.25 to >4 | 88.5 | |
| Tigecycline | 1 | 2 | 0.12 to 4 | 90.6 | |
| Levofloxacin | >4 | >4 | 0.06 to >4 | 17.2 | |
| KPC positive (269)i | Ceftazidime-avibactam | 0.5 | 2 | 0.03 to 16 | 99.6 |
| Ceftazidime | 64 | >128 | 0.5 to >128 | 8.2 | |
| Cefepime | >16 | >16 | ≤0.12 to >16 | 10.8 | |
| Aztreonam | >128 | >128 | 4 to >128 | 1.5 | |
| Piperacillin-tazobactam | >128 | >128 | 8 to >128 | 0.7 | |
| Doripenem | >4 | >4 | 0.06 to >4 | 10.4 | |
| Imipenem | >8 | >8 | 0.12 to >8 | 1.5 | |
| Meropenem | >8 | >8 | 0.03 to >8 | 5.9 | |
| Amikacin | 8 | >32 | 0.5 to >32 | 68.4 | |
| Colistin (n = 181)d | 1 | >4 | 0.25 to >4 | 79.0 | |
| Tigecycline | 1 | 2 | 0.12 to 8 | 94.8 | |
| Levofloxacin | >4 | >4 | ≤0.03 to >4 | 25.3 | |
| OXA-48-like positive (14)j | Ceftazidime-avibactam | 1 | 2 | 0.06 to 8 | 100 |
| Ceftazidime | 128 | >128 | 16 to >128 | 0 | |
| Cefepime | >16 | >16 | 2 to >16 | 7.1 | |
| Aztreonam | 64 | 128 | 1 to >128 | 7.1 | |
| Piperacillin-tazobactam | >128 | >128 | 4 to >128 | 7.1 | |
| Doripenem | 0.12 | >4 | 0.03 to >4 | 85.7 | |
| Imipenem | 0.5 | 2 | 0.12 to 2 | 85.7 | |
| Meropenem | 0.12 | >8 | 0.015 to >8 | 85.7 | |
| Amikacin | 8 | 32 | 1 to >32 | 78.6 | |
| Colistin (n = 10)d | 1 | 1 | 0.5 to 1 | 100 | |
| Tigecycline | 0.5 | 2 | 0.12 to 2 | 100 | |
| Levofloxacin | >4 | >4 | 0.06 to >4 | 21.4 | |
| MBL positive (17)k | Ceftazidime-avibactam | 64 | >128 | 0.12 to >128 | 5.9 |
| Ceftazidime | >128 | >128 | 0.25 to >128 | 5.9 | |
| Cefepime | >16 | >16 | 1 to >16 | 5.9 | |
| Aztreonam | 16 | 128 | 0.03 to >128 | 47.1 | |
| Piperacillin-tazobactam | >128 | >128 | 1 to >128 | 5.9 | |
| Doripenem | >4 | >4 | 2 to >4 | 0 | |
| Imipenem | 8 | >8 | 4 to >8 | 0 | |
| Meropenem | 8 | >8 | 1 to >8 | 5.9 | |
| Amikacin | 16 | >32 | 2 to >32 | 64.7 | |
| Colistin (n = 93)d | 1 | >4 | 0.25 to >4 | 68.8 | |
| Tigecycline | 1 | 4 | 0.5 to 4 | 82.4 | |
| Levofloxacin | 1 | >4 | 0.25 to >4 | 58.8 | |
| P. aeruginosa (750) | |||||
| OSBL positive (4)l | Ceftazidime-avibactam | —b | — | 4 to 16 | 75.0 |
| Ceftazidime | — | — | 4 to 64 | 50.0 | |
| Cefepime | — | — | 8 to >16 | 25.0 | |
| Aztreonam | — | — | 16 to 64 | 0 | |
| Piperacillin-tazobactam | — | — | 64 to >128 | 0 | |
| Doripenem | — | — | 1 to >4 | 50.0 | |
| Imipenem | — | — | 2 to >8 | 25.0 | |
| Meropenem | — | — | 2 to >8 | 25.0 | |
| Amikacin | — | — | >32 to >32 | 0 | |
| Colistin (n = 1)d | — | — | 1 | 100 | |
| Levofloxacin | — | — | >4 to >4 | 0 | |
| ESBL positive (29)l,m | Ceftazidime-avibactam | 16 | 64 | 4 to >128 | 31.0 |
| Ceftazidime | >128 | >128 | 8 to >128 | 3.4 | |
| Cefepime | >16 | >16 | 0.25 to >16 | 3.4 | |
| Aztreonam | >128 | >128 | 8 to >128 | 3.4 | |
| Piperacillin-tazobactam | 64 | >128 | 8 to >128 | 20.7 | |
| Doripenem | >4 | >4 | 2 to >4 | 13.8 | |
| Imipenem | >8 | >8 | >8 to >8 | 0 | |
| Meropenem | >8 | >8 | 4 to >8 | 0 | |
| Amikacin | >32 | >32 | 8 to >32 | 27.6 | |
| Colistin (n = 19)d | 1 | 4 | 0.5 to >4 | 89.5 | |
| Levofloxacin | >4 | >4 | 1 to >4 | 24.1 | |
| KPC positive (48)l | Ceftazidime-avibactam | 8 | 32 | 1 to 128 | 77.1 |
| Ceftazidime | 64 | 128 | 8 to >128 | 2.1 | |
| Cefepime | >16 | >16 | 0.5 to >16 | 2.1 | |
| Aztreonam | >128 | >128 | 64 to >128 | 0 | |
| Piperacillin-tazobactam | >128 | >128 | 32 to >128 | 0 | |
| Doripenem | >4 | >4 | >4 to >4 | 0 | |
| Imipenem | >8 | >8 | >8 to >8 | 0 | |
| Meropenem | >8 | >8 | >8 to >8 | 0 | |
| Amikacin | 8 | >32 | 1 to >32 | 77.1 | |
| Colistin (n = 31)d | 2 | 2 | 0.5 to 4 | 93.5 | |
| Levofloxacin | >4 | >4 | 0.25 to >4 | 8.3 | |
| GES carbapenemase positive (33)l,n | Ceftazidime-avibactam | 32 | 128 | 0.12 to >128 | 27.3 |
| Ceftazidime | >128 | >128 | 0.25 to >128 | 0 | |
| Cefepime | >16 | >16 | 1 to >16 | 0 | |
| Aztreonam | 128 | >128 | 0.03 to >128 | 9.1 | |
| Piperacillin-tazobactam | >128 | >128 | 1 to >128 | 0 | |
| Doripenem | >4 | >4 | 2 to >4 | 0 | |
| Imipenem | >8 | >8 | 4 to >8 | 15.2 | |
| Meropenem | >8 | >8 | 1 to >8 | 0 | |
| Amikacin | >32 | >32 | 2 to >32 | 15.2 | |
| Colistin (n = 27)d | 2 | 2 | 0.25 to >4 | 92.6 | |
| Levofloxacin | >4 | >4 | 0.25 to >4 | 0 | |
| GES, spectrum-undefined positive (1)l | Ceftazidime-avibactam | —b | — | >128 | 0 |
| Ceftazidime | — | — | >128 | 0 | |
| Cefepime | — | — | >16 | 0 | |
| Aztreonam | — | — | >128 | 0 | |
| Piperacillin-tazobactam | — | — | >128 | 0 | |
| Doripenem | — | — | >4 | 0 | |
| Imipenem | — | — | >8 | 0 | |
| Meropenem | — | — | >8 | 0 | |
| Amikacin | — | — | >32 | 0 | |
| Colistin (n = 1)d | — | — | 1 | 100 | |
| Levofloxacin | — | — | >4 | 0 | |
| MBL-positive (110)l,o | Ceftazidime-avibactam | 32 | >128 | 2 to >128 | 5.5 |
| Ceftazidime | 32 | >128 | 4 to >128 | 2.7 | |
| Cefepime | 16 | >16 | 4 to >16 | 10.0 | |
| Aztreonam | 16 | 64 | 2 to >128 | 21.8 | |
| Piperacillin-tazobactam | 64 | >128 | 4 to >128 | 7.3 | |
| Doripenem | >4 | >4 | 1 to >4 | 2.7 | |
| Imipenem | >8 | >8 | 4 to >8 | 0 | |
| Meropenem | >8 | >8 | 1 to >8 | 3.6 | |
| Amikacin | >32 | >32 | 2 to >32 | 13.6 | |
| Colistin (n = 88)d | 2 | 2 | 0.5 to 4 | 95.5 | |
| Levofloxacin | >4 | >4 | 0.25 to >4 | 13.6 | |
| No acquired β-lactamase detected (525)l | Ceftazidime-avibactam | 4 | 16 | 0.5 to >128 | 89.5 |
| Ceftazidime | 8 | 64 | 1 to >128 | 61.1 | |
| Cefepime | 8 | >16 | 0.25 to >16 | 61.5 | |
| Aztreonam | 16 | 64 | 0.25 to >128 | 33.9 | |
| Piperacillin-tazobactam | 32 | >128 | ≤0.25 to >128 | 45.7 | |
| Doripenem | 4 | >4 | 0.12 to >4 | 25.5 | |
| Imipenem | >8 | >8 | 1 to >8 | 6.9 | |
| Meropenem | 8 | >8 | ≤0.06 to >8 | 19.4 | |
| Amikacin | 8 | >32 | 0.5 to >32 | 74.9 | |
| Colistin (n = 369)d | 2 | 2 | 0.25 to 8 | 95.1 | |
| Levofloxacin | 4 | >4 | ≤0.03 to >4 | 45.9 | |
Isolates (n = 3,071) of β-lactamase-positive Enterobacteriaceae and P. aeruginosa were collected in the Latin American region as part of the INFORM global surveillance program in 2012 to 2015. OSBL, original-spectrum β-lactamase (e.g., TEM-1, SHV-1, SHV-11); ESBL, extended-spectrum β-lactamase; MBL, metallo-β-lactamase.
—, MIC50 and MIC90 were not calculated for n <10 isolates.
Percent susceptibility was determined according to CLSI 2016 breakpoints, with the exception of those for ceftazidime-avibactam and tigecycline, where U.S. FDA breakpoints were applied, and for colistin, where EUCAST breakpoints were applied.
Values are for colistin tested without 0.002% polysorbate-80; isolates collected in 2014 to 2015 only. ND, not determined; MIC range and % susceptible were not determined for n = 0 isolates.
“Spectrum undefined” refers to SHV-type and/or TEM-type β-lactamases with undefined spectrum of activity.
Included isolates carrying the chromosomal ESBL common to K. oxytoca, SHV-type and/or TEM-type β-lactamases with undefined spectrum of activity, and/or OSBLs.
Included isolates carrying the chromosomal AmpCs common to Citrobacter spp., Enterobacter spp., M. morganii, and Serratia spp.; plasmid-mediated AmpCs; and isolates cocarrying OSBLs.
Included isolates carrying the chromosomal β-lactamases common to Citrobacter spp., Enterobacter spp., Providencia spp., Serratia spp., and K. oxytoca, and isolates cocarrying OSBLs.
Included isolates carrying ESBLs, plasmidic and chromosomal AmpC β-lactamases, β-lactamases with unknown spectrum of activity, OSBLs, and OXA-48-like β-lactamases (KPC-2 and OXA-163, 1 isolate; KPC-2 and OXA-370, 1 isolate).
Included isolates carrying OXA-163 (10 isolates), OXA-48 (1 isolate), OXA-232 (1 isolate), OXA-370 (1 isolate), OXA-439 (1 isolate), and ESBLs, AmpC, and/or OSBLs. OXA-163 possesses weak carbapenemase activity that impacts the activity of carbapenems when combined with additional mechanisms of resistance, such as porin deficiencies. OXA-439 has not been confirmed to possess carbapenemase activity.
Included isolates cocarrying ESBLs, chromosomal AmpC β-lactamases, and/or OSBLs.
Assumed to carry the chromosomal AmpC common to P. aeruginosa.
Included one isolate carrying a GES β-lactamase with an undefined spectrum of activity.
Included isolates carrying GES β-lactamases with ESBL activity (GES-19 and GES-1).
Included 1 isolate cocarrying an OSBL and 5 isolates cocarrying VIM-2 and KPC-2.