TABLE 1.
Evaluation of in vitro activities of CAZ-AVI plus ATM, by both disk diffusion and agar MIC testinga
| Isolate | Known bla gene(s) | Disk diffusion assay inhibition zone diam (mm) |
MIC (μg/ml) by agar MIC test |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 30 μg CAZ (CLSI S ≥ 21, I = 18–20, R ≤ 17 mm) | 30 μg ATM (CLSI S ≥ 21, I = 18–20, R ≤ 17 mm) | 30 μg CAZ–20 μg AVI (FDA S ≥ 21, R ≤20 mm) | CAZ-AVI with ATMb | CAZ (CLSI S ≤ 4, I = 8, R ≥ 16 μg/ml) | ATM (CLSI S ≤ 4, I = 8, R ≥ 16 μg/ml) | CAZ with ATM at 16 μg/ml | CAZ-AVI (FDA S ≤ 8/4, R ≥ 16/4 μg/ml) | CAZ-AVI with ATM at constant concn of: |
|||||
| 8 μg/ml | 16 μg/ml | 32 μg/ml | 64 μg/ml | ||||||||||
| E. coli DH10B | None | 33 | 35 | 35 | 40 (5) | 0.125 | 0.25 | <0.0625 | 0.25 | <0.0625 | <0.0625 | ||
| E. cloacae 6.31 | NDM-1, CTX-M-15, ACT/MIR, OXA-48 | 6 | 6 | 14 | 26 (12) | >512 | >>512 | >512 | 64 | 0.5 | 0.5 | ||
| E. cloacae 6.43 | NDM-1, CTX-M-15, ACT/MIR | 6 | 6 | 17 | 25 (8) | >512 | >512 | >512 | 128 | 0.5 | 0.25 | ||
| E. cloacae joint infection | NDM-1, CTX-M, TEM-1, AmpCc | 6 | 6 | 18 | 28 (10) | >512 | 256 | >512 | 128 | 0.5 | 0.25 | ||
| E. coli 8.68 | NDM-1, CTX-M-15, CMY-2, TEM | 6 | 6 | 19 | 21 (2) | >512 | >512 | >512 | 64 | 16 | 16 | 8 | 1 |
| E. coli 8.69 | NDM-1, CTX-M-15, CMY-2, SHV-5 | 6 | 6 | 17 | 24 (7) | >512 | >512 | >512 | 64 | 8 | 4 | ||
| E. coli 8.70 | NDM-1, CTX-M-15, CMY-2, TEM, SHV-5 | 6 | 6 | 20 | 22 (2) | >512 | 512 | >512 | 64 | 16 | 4 | 0.5 | 0.25 |
| E. coli 8.71 | NDM-1, CTX-M-15, CMY-2, TEM | 6 | 6 | 17 | 20 (3) | >512 | >512 | >512 | 64 | 32 | 8 | 1 | 0.25 |
| E. coli 8.72 | NDM-1, CTX-M-15, CMY-2, TEM | 6 | 6 | 18 | 23 (5) | >512 | >512 | >512 | 64 | 8 | 2 | ||
| E. coli 8.73 | NDM-1, CTX-M-15, CMY-2, TEM | 6 | 6 | 17 | 20 (3) | >512 | >512 | >512 | 32 | 8 | 2 | ||
| E. coli 8.74 | NDM-1, TEM | 6 | 6 | 20 | 27 (7) | >512 | 2 | <0.0625 | 64 | 0.0625 | <0.0625 | ||
| E. coli 6728 | NDM-1 | 6 | 15 | 18 | 18 (0) | >512 | 32 | >512 | 64 | 16 | 4 | 0.125 | 0.06 |
| K. pneumoniae 1.41 | NDM-1, CTX-M-15, DHA, SHV, TEM | 6 | 6 | 17 | 32 (15) | >512 | 128 | >512 | 64 | 1 | 0.5 | ||
| K. pneumoniae 1.42 | NDM-1, CTX-M-15, SHV-12 | 6 | 6 | 17 | 27 (10) | >512 | >512 | >512 | 64 | 1 | 0.5 | ||
| K. pneumoniae 1.44 | NDM-1, CTX-M-15, CMY-2, DHA, SHV, TEM | 6 | 6 | 15 | 25 (10) | >512 | >512 | >512 | 128 | 16 | 8 | 8 | 4 |
| K. pneumoniae 1.50 | NDM-1, CTX-M-15, SHV | 6 | 6 | 20 | 30 (10) | >512 | >512 | >512 | 128 | 0.25 | 0.25 | ||
| K. pneumoniae 1.63 | NDM-1, CTX-M-15, CMY-2, SHV, TEM | 6 | 6 | 15 | 30 (15) | >512 | 512 | >512 | 256 | 1 | 0.125 | ||
| K. pneumoniae 6913 | IMP, SHV | 6 | 28 | 17 | 28 (0) | 256 | 0.5 | 0.0625 | 128 | <0.0625 | <0.0625 | ||
| K. pneumoniae 11-01-13 | NDM-1, CTX-M-15, SHV | 6 | 6 | 17 | 30 (13) | >512 | 512 | >512 | 128 | 1 | 0.5 | ||
| Providencia rettgeri 6384 | NDM-1, SHV | 6 | 37 | 6 | 34 (−3) | 512 | 0.0625 | <0.0625 | 256 | <0.0625 | <0.0625 | ||
| P. rettgeri 1.27 | NDM-1, CMY-2, DHA | 6 | 14 | 10 | 20 (6) | >512 | 64 | >512 | >512 | 32 | 16 | ||
| Morganella morganii 1.39 | NDM-1, CTX-M-15, DHA | 6 | 12 | 10 | 25 (13) | >512 | 256 | >512 | 512 | 0.125 | <0.0625 | ||
Shown are the genetic background of isolates and inhibition zone diameters of disks with CAZ, ATM, or CAZ-AVI and CAZ-AVI disks to which ATM was added. Isolates in this table were available from the laboratories of the authors and characterized previously (8). Interpretative criteria for CAZ and ATM MICs were according to the Clinical and Laboratory Standards Institute (CLSI) guidelines (9). For CAZ-AVI, MICs were interpreted according to FDA guidelines from the package insert. For CAZ, suceptible (S), intermediate (I), and resistant (R) are ≤4, 8, and ≥16 μg/ml, respectively. For ATM, S, I, and R are ≤4, 8, and ≥16 μg/ml, respectively. For CAZ-AVI, S and R are ≤8/4 and ≥16/4 μg/ml, respectively. The values reported for CAZ-AVI reflect the concentration of the CAZ in the 4:1 ratio formulation.
The data presented represent the zone diameter of the CAZ-AVI disk to which ATM was added. In parentheses is the difference between this zone size and the zone of inhibition of either CAZ-AVI or ATM alone—whichever of the two was greater.
Presumed AmpC.