Meropenem plus Ceftaroline Is Active against Enterococcus faecalis in an In Vitro Pharmacodynamic Model Using...

Area of Science:

• Infectious Diseases
• Pharmacology
• Microbiology

Background:

• Standard treatment for severe Enterococcus faecalis infections involves ampicillin plus ceftriaxone.
• Limitations of current therapy include ampicillin's dosing and stability issues, and ceftriaxone's association with Clostridioides difficile infection and vancomycin-resistant enterococci (VRE) promotion.
• Exploring alternative antibiotic combinations is crucial for managing serious enterococcal infections.

Purpose of the Study:

• To investigate the efficacy of carbapenems in combination with cephalosporins against Enterococcus faecalis.
• To evaluate meropenem and ceftaroline as potential alternatives to the current standard of care.

Main Methods:

• Utilized an in vitro pharmacodynamic model (IVPD) simulating human therapeutic dosing over 48 hours.
• Tested ampicillin, ertapenem, meropenem, ceftriaxone, and ceftaroline against two ampicillin- and penicillin-susceptible E. faecalis strains.
• Assessed bacterial kill, regrowth, and minimum inhibitory concentration (MIC) changes.

Main Results:

• Ampicillin plus ceftriaxone demonstrated enhanced activity without increasing MICs.
• Meropenem and ceftaroline monotherapy showed significant bacterial kill with no regrowth or MIC increases.
• Meropenem plus ceftaroline exhibited activity comparable to the standard of care, with meropenem plus ceftriaxone showing significant kill but minor regrowth.

Conclusions:

• Meropenem-based combination therapy, particularly meropenem plus ceftaroline, is a viable alternative for treating severe E. faecalis infections.
• This combination demonstrated comparable efficacy to ampicillin plus ceftriaxone in vitro.
• Further clinical studies are necessary to confirm the efficacy of meropenem-based regimens.