TABLE 1.
In vitro activity of cefepime-taniborbactam and comparator agents against isolates of Enterobacterales with antimicrobial-resistant phenotypes
| Phenotype (no. of isolates; % of total) | Antimicrobial agent | MIC (μg/mL) |
MIC interpretation |
||||
|---|---|---|---|---|---|---|---|
| MIC50 | MIC90 | MIC range | Susceptible (%) | Intermediate (%) | Resistant (%) | ||
| All isolates (13,731; 100) | Cefepime-taniborbactama | 0.06 | 0.25 | ≤0.008 to >16 | 99.7 | NAb | 0.3 |
| Ceftazidime-avibactam | ≤0.12 | 0.5 | ≤0.12 to >16 | 97.8 | NA | 2.2 | |
| Ceftolozane-tazobactam | 0.5 | 8 | ≤0.25 to >8 | 87.1 | 2.4 | 10.5 | |
| Meropenem-vaborbactam | ≤0.06 | 0.12 | ≤0.06 to >16 | 97.4 | 0.3 | 2.2 | |
| Piperacillin-tazobactam | ≤4 | 128 | ≤4 to >128 | 84.2 | 4.9 | 10.9 | |
| ESBL phenotype (4,335; 31.6)c | Cefepime-taniborbactam | 0.12 | 1 | ≤0.008 to >16 | 99.1 | NA | 0.9 |
| Ceftazidime-avibactam | 0.25 | 2 | ≤0.12 to >16 | 93.1 | NA | 6.9 | |
| Ceftolozane-tazobactam | 2 | >8 | ≤0.25 to >8 | 59.6 | 7.1 | 33.3 | |
| Meropenem-vaborbactam | ≤0.06 | 2 | ≤0.06 to >16 | 91.9 | 1.0 | 7.0 | |
| Piperacillin-tazobactam | 16 | >128 | ≤4 to >128 | 55.5 | 13.5 | 31.0 | |
| Cefepime resistant (2,390; 17.4) | Cefepime-taniborbactam | 0.25 | 4 | ≤0.008 to >16 | 98.3 | NA | 1.7 |
| Ceftazidime-avibactam | 0.5 | >16 | ≤0.12 to >16 | 88.3 | NA | 11.7 | |
| Ceftolozane-tazobactam | 2 | >8 | ≤0.25 to >8 | 52.1 | 5.2 | 42.7 | |
| Meropenem-vaborbactam | ≤0.06 | 16 | ≤0.06 to >16 | 85.6 | 1.8 | 12.6 | |
| Piperacillin-tazobactam | 32 | >128 | ≤4 to >128 | 48.7 | 12.0 | 39.3 | |
| MDR phenotype (1,781; 13.0)d | Cefepime-taniborbactam | 0.25 | 4 | 0.016 to >16 | 97.9 | NA | 2.1 |
| Ceftazidime-avibactam | 0.5 | >16 | 0.12 to >16 | 83.9 | NA | 16.1 | |
| Ceftolozane-tazobactam | >8 | >8 | 0.25 to >8 | 32.8 | 5.1 | 62.2 | |
| Meropenem-vaborbactam | ≤0.06 | >16 | 0.06 to >16 | 80.3 | 2.6 | 17.1 | |
| Piperacillin-tazobactam | 128 | >128 | 4 to >128 | 30.7 | 12.3 | 57.0 | |
| Piperacillin-tazobactam resistant (1,498; 10.9) | Cefepime-taniborbactam | 0.5 | 4 | 0.016 to >16 | 97.5 | NA | 2.5 |
| Ceftazidime-avibactam | 1 | >16 | ≤0.12 to >16 | 81.7 | NA | 18.3 | |
| Ceftolozane-tazobactam | >8 | >8 | ≤0.25 to >8 | 20.5 | 5.1 | 74.9 | |
| Meropenem-vaborbactam | ≤0.06 | >16 | ≤0.06 to >16 | 77.0 | 2.9 | 20.2 | |
| Piperacillin-tazobactam | >128 | >128 | 128 to >128 | 0 | 0 | 100 | |
| Ceftolozane-tazobactam resistant (1,444; 10.5) | Cefepime-taniborbactam | 0.5 | 4 | 0.016 to >16 | 97.4 | NA | 2.6 |
| Ceftazidime-avibactam | 1 | >16 | ≤0.12 to >16 | 79.5 | NA | 20.5 | |
| Ceftolozane-tazobactam | >8 | >8 | 8 to >8 | 0 | 0 | 100 | |
| Meropenem-vaborbactam | 0.12 | >16 | ≤0.06 to >16 | 75.9 | 3.1 | 21.0 | |
| Piperacillin-tazobactam | >128 | >128 | ≤4 to >128 | 6.3 | 16.0 | 77.7 | |
| Meropenem resistant (637; 4.6) | Cefepime-taniborbactam | 1 | 8 | 0.016 to >16 | 94.5 | NA | 5.5 |
| Ceftazidime-avibactam | 4 | >16 | ≤0.12 to >16 | 59.0 | NA | 41.0 | |
| Ceftolozane-tazobactam | >8 | >8 | 1 to >8 | 1.1 | 1.6 | 97.3 | |
| Meropenem-vaborbactam | 8 | >16 | ≤0.06 to >16 | 44.9 | 7.2 | 47.9 | |
| Piperacillin-tazobactam | >128 | >128 | ≤4 to >128 | 0.2 | 1.9 | 98.0 | |
| DTR phenotype (623; 4.5)e | Cefepime-taniborbactam | 1 | 16 | 0.016 to >16 | 94.4 | NA | 5.6 |
| Ceftazidime-avibactam | 4 | >16 | ≤0.12 to >16 | 61.2 | NA | 38.8 | |
| Ceftolozane-tazobactam | >8 | >8 | 2 to >8 | 0 | 0 | 100 | |
| Meropenem-vaborbactam | 8 | >16 | ≤0.06 to >16 | 47.8 | 6.3 | 45.9 | |
| Piperacillin-tazobactam | >128 | >128 | 32 to >128 | 0 | 1.4 | 98.6 | |
| Meropenem-vaborbactam resistant (305; 2.2) | Cefepime-taniborbactam | 2 | 16 | 0.12 to >16 | 90.2 | NA | 9.8 |
| Ceftazidime-avibactam | >16 | >16 | ≤0.12 to >16 | 32.8 | NA | 67.2 | |
| Ceftolozane-tazobactam | >8 | >8 | 2 to >8 | 0.3 | 0.3 | 99.3 | |
| Meropenem-vaborbactam | >16 | >16 | 16 to >16 | 0 | 0 | 100 | |
| Piperacillin-tazobactam | >128 | >128 | 32 to >128 | 0 | 1.0 | 99.0 | |
| Ceftazidime-avibactam resistant (299; 2.2) | Cefepime-taniborbactam | 1 | >16 | 0.03 to >16 | 89.6 | NA | 10.4 |
| Ceftazidime-avibactam | >16 | >16 | 16 to >16 | 0 | NA | 100 | |
| Ceftolozane-tazobactam | >8 | >8 | ≤0.25 to >8 | 0.3 | 0.7 | 99.7 | |
| Meropenem-vaborbactam | >16 | >16 | ≤0.06 to >16 | 24.8 | 6.7 | 68.6 | |
| Piperacillin-tazobactam | >128 | >128 | ≤4 to >128 | 4.4 | 4.0 | 91.6 | |
For comparative purposes only, percent susceptible and percent resistant for cefepime-taniborbactam correspond to the percentage of isolates inhibited at ≤16 μg/mL and ≥32 μg/mL, respectively.
NA, not applicable.
ESBL phenotype screening criteria were modified from those published by CLSI (31) for the purpose of this study, with an ESBL-positive phenotype assigned to isolates of Enterobacterales with ceftazidime and/or cefepime MICs of ≥2 μg/mL.
An MDR phenotype was assigned to isolates resistant to at least one agent from ≥3 of the following antimicrobial agent classes: aminoglycosides (gentamicin), β-lactam combination agents (piperacillin-tazobactam, ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam), carbapenems (meropenem or imipenem), cephems (ceftazidime, cefepime), and fluoroquinolones (levofloxacin or ciprofloxacin).
DTR isolates were identified using the definition of Kadri et al. (42) as isolates intermediate or resistant to fluoroquinolones (levofloxacin) and all β-lactams, including carbapenems and piperacillin-tazobactams but excluding ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam.