Abstract
Background
Sulopenem is a thiopenem antibacterial with oral and parenteral formulations being developed for the treatment of urinary tract infection (UTI) or complicated intra-abdominal infection (cIAI). The activity of sulopenem aligns with the most urgent drug-resistant antimicrobial threats defined by the Centers for Disease Control (CDC), including ESBL-producing strains of Escherichia coli and Klebsiella species. We evaluated the in vitro antibacterial activity of sulopenem against clinical Enterobacteriaceae isolates from patients in North America with UTI or cIAI collected during 2016–2017.
Methods
Sulopenem and other antimicrobial agents were tested for in vitro activity against 1,008 recent (2016–2017) consecutive Enterobacteriaceae isolates collected through the SENTRY Antimicrobial Surveillance Program from patients in North America with UTI (906 isolates) or cIAI (102 isolates). Reference broth microdilution susceptibility testing was conducted using frozen-form panels produced by JMI Laboratories according to CLSI (M07, 2018) guidelines using cation-adjusted Mueller–Hinton broth. Quality control (QC) and interpretation of results were performed in accordance with CLSI M100 (2018) guidelines.
Results
Table 1. Activity of sulopenem and comparator antimicrobial agents against 1,008 Enterobacteriaceae North American isolates
| CLSI | |||||
|---|---|---|---|---|---|
| Antibiotic | MIC50 | MIC90 | %S | %I | %R |
| Sulopenem | – | – | – | 0.03 | 0.25 |
| Meropenem | 99.6 | 0.1 | 0.3 | 0.03 | 0.06 |
| Ertapenem | 99.3 | 0.3 | 0.4 | ≤0.008 | 0.03 |
| Ceftriaxone | 87.3 | 0.6 | 12.1 | ≤0.06 | >8 |
| Piperacillin–tazobactam | 96.3 | 2.2 | 1.5 | 2 | 8 |
| Amoxicillin–clavulanate (2:1) | 75.8 | 7.7 | 16.5 | 4 | 64 |
| Levofloxacin | 82.8 | 1.8 | 15.4 | 0.06 | 16 |
| Nitrofurantoin | 63.8 | 22.2 | 14.0 | 32 | 128 |
The sulopenem MIC50/90 values for Enterobacteriaceae were 0.03/0.25 µg/mL. For Escherichia coli, Klebsiella species and Proteus mirabilis, the MIC50/90 results were 0.03/0.03 µg/mL, 0.03/0.06 µg/mL, and 0.12/0.25 µg/mL, respectively.
Conclusion
Sulopenem demonstrated potent in vitro activity against organisms commonly implicated in UTI and cIAI. These data support the further clinical development of sulopenem for Gram-negative infections.
Disclosures
S. Puttagunta, Iterum Therapeutics: Employee and Shareholder, Salary. S. Aronin, Iterum Therapeutics: Employee and Shareholder, Salary. M. Huband, JMI Labs: Research Contractor, Grant recipient. R. K. Flamm, Allergan: Research Contractor, Research support. M. Dunne, Iterum Therapeutics: Employee and Shareholder, Salary.
Session: 144. Novel Agents
Friday, October 5, 2018: 12:30 PM