TABLE 2.
MICs of irrational BL-BLI combinations and ceftazidime-avibactam against contemporary Indian ESBL- and/or class C β-lactamase-producing Enterobacterales isolatesa
| β-Lactam or BL-BLI (dose or ratio) | MIC50 (mg/liter) | MIC90 (mg/liter) |
|---|---|---|
| Ceftriaxone | >128 | >128 |
| Ceftriaxone + tazobactam (4 mg/liter) | 2 | 128 |
| Ceftriaxone + sulbactam (2:1)b | 32 | 64 |
| Ceftazidime | 128 | >128 |
| Ceftazidime + tazobactam (4 mg/liter) | 4 | 128 |
| Cefepime | 32 | >128 |
| Cefepime + tazobactam (4 mg/liter) | 0.5 | 8 |
| Cefepime + sulbactam (4 mg/liter) | 4 | 32 |
| Cefoperazone | >128 | >128 |
| Cefoperazone + tazobactam (4 mg/liter) | 8 | 128 |
| Cefotaxime | >128 | >128 |
| Cefotaxime + sulbactam (4 mg/liter) | 32 | >128 |
| Meropenem | 0.06 | 0.25 |
| Meropenem + sulbactam (4 mg/liter) | 0.06 | 0.12 |
| Ceftazidime + avibactam (4 mg/liter)c | 0.5 | 2 |
Total isolates (n = 103), E. coli (n = 50), Klebsiella spp. (n = 36), Enterobacter spp. (n = 10), Citrobacter spp. (n = 5), Serratia spp. (n = 2). These isolates were collected from various Indian tertiary care hospitals from 2015 to 2018. All the MICs were determined by the agar dilution method as per CLSI guideline M07-A12 (2018) (44). MICs of BLs in the presence of a fixed concentration (8 mg/liter) of a BLI showed similarly high MIC values, except the MIC50 and MIC90 of cefepime-tazobactam, which were 0.5 and 8 mg/liter, respectively.
The MIC50 and MIC90 of ceftriaxone-sulbactam combinations in the presence of EDTA (25 mg/liter) were 16 and 32 mg/liter, respectively. The EDTA concentration of 25 mg/liter represents the Cmax attained after administration of CSE 1034 (ceftriaxone at 2 g plus sulbactam at 1 g plus EDTA at 74 mg) (43).
One hundred percent of isolates were susceptible to ceftazidime-avibactam based on 2019 CLSI breakpoints.