TABLE 2.
Kinetic parameters of carbapenemases for S-649266 and other antibacterial agents
| β-Lactamase | Molecular classa | Antibacterial agent | kcat (s−1)b | Km or Ki (μM)b | kcat/Km (μM−1 s−1) |
|---|---|---|---|---|---|
| IMP-1 | B | S-649266c | 0.92 ± 0.0089 | 190 ± 19 | 0.0048 |
| Meropenem | 6.5 ± 0.23 | 3.3 ± 1.2 | 2.0 | ||
| Ceftazidime | 7.2 ± 0.24 | 55 ± 2.6 | 0.13 | ||
| Cefepime | 10 ± 0.50 | 29 ± 2.6 | 0.34 | ||
| Nitrocefin | 220 ± 33 | 2.6 ± 1.3 | 85 | ||
| VIM-2 | B | S-649266c | 1.0 ± 0.019 | 200 ± 12 | 0.0050 |
| Meropenem | 4.4 ± 0.27 | 2.4 ± 0.63 | 1.8 | ||
| Ceftazidime | 3.3 ± 0.13 | 64 ± 1.1 | 0.052 | ||
| Cefepimec | 49 ± 0.74 | 100 ± 9.3 | 0.49 | ||
| Nitrocefin | 890 ± 6.3 | 4.9 ± 0.29 | 182 | ||
| L1 | B | S-649266 | 12 ± 0.57 | 510 ± 64 | 0.024 |
| Meropenem | 45 ± 1.6 | 7.1 ± 0.94 | 6.3 | ||
| Ceftazidime | 71 ± 2.8 | 470 ± 33 | 0.15 | ||
| Cefepimec | NDd | >500 | NCf | ||
| Imipenem | 250 ± 8.5 | 60 ± 1.9 | 4.2 | ||
| KPC-3 | A | S-649266 | NDe | >1,600 | NC |
| Meropenem | 1.3 ± 0.035 | 6.5 ± 0.37 | 0.20 | ||
| Ceftazidimec | NDd | 3,100 ± 520 | NC | ||
| Cefepimec | 19 ± 0.058 | 350 ± 19 | 0.054 | ||
| Nitrocefin | 47 ± 19 | 15 ± 7.6 | 3.1 | ||
| OXA-23 | D | S-649266c | NH | 4,800 ± 1,100 | NC |
| Meropenemc | NDe | 0.028 ± 0.0023 | NC | ||
| Ceftazidimec | NH | 9,800 ± 270 | NC | ||
| Cefepimec | NDd | 1,500 ± 170 | NC | ||
| Nitrocefin | 350 ± 7.7 | 34 ± 4.9 | 10 |
a
Classification as described by Ambler (14).
b
Each kcat, Km, and Ki value is the mean ± standard deviation (SD) of three different measurements. ND, not determined; NH, no hydrolysis detected.
c
Ki values were obtained using 100 μM nitrocefin for IMP-1, VIM-2, KPC-3, and OXA-23 or 100 μM imipenem for L1 as a reporter substrate.
d
Hydrolysis was observed, but the Km or Ki value was too high to determine the kcat value.
e
Hydrolysis was too weak to determine the kcat value.
f
NC, not calculated.