Abstract
Background
Tebipenem, an orally bioavailable carbapenem administered as a pro-drug, completed a phase 3 clinical trial for evaluating its safety and efficacy for the treatment of complicated urinary tract infection and acute pyelonephritis. The purpose of this study was to investigate the in vitro activity of tebipenem and comparator agents, including ertapenem and meropenem, against a recent collection of Gram-positive isolates associated with clinical infections.
Methods
The susceptibility of 580 Gram-positive organisms were tested, including: methicillin-susceptible Staphylococcus aureus (MSSA, 489 isolates), methicillin-susceptible Staphylococcus epidermidis (MSSE, 31), other methicillin-susceptible coagulase-negative staphylococci (MSCoNS, 29), and vancomycin-susceptible Enterococcus faecalis (31). The isolates were collected primarily from pneumonia in hospitalized patients (498 isolates; 85.9%), urinary tract infections (42 isolates; 7.2%), and bloodstream infections (38 isolates; 6.6%). Organisms were tested using reference broth microdilution methods in a central laboratory.
Results
Tebipenem had an MIC90 value of 0.03 mg/L against MSSA and 0.015 mg/L against MSSE isolates. Ertapenem MIC90 values were 8-fold higher against MSSA (MIC90, 0.25 mg/L) and 32-fold higher against MSSE (MIC90, 0.5 mg/L). Tebipenem displayed an MIC90 value of 0.03 mg/L against MSCoNS species other than S. epidermidis. This result was 8- and 32-fold lower than those of meropenem (MIC90, 0.25 mg/L) and ertapenem (MIC90, 1 mg/L), respectively. Tebipenem inhibited all E. faecalis isolates at ≤1 mg/L (MIC90, 1 mg/L), with an MIC90 value at least 2-fold lower than meropenem (MIC90, >1 mg/L) and 16-fold lower than ertapenem (MIC90, >8 mg/L).
Conclusion
Tebipenem displayed potent activity against methicillin susceptible staphylococci, including MSSA, MSSE, and other MSCoNS. Tebipenem in vitro activity was greater than meropenem and ertapenem when tested against E. faecalis. These data indicate that tebipenem may be an option for treating urinary tract infections caused by these organisms or as an empiric option to provide broader coverage against Gram-negative and -positive organisms.
Disclosures
S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Abby L. Klauer, n/a, Cidara Therapeutics, Inc. (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Ian A. Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)
1038. In Vitro Activity of Tebipenem, an Orally Available Carbapenem Agent, Against a Collection of Surveillance Gram-Positive Clinical Isolates