Meropenem: activity against resistant gram-negative bacteria and interactions with beta-lactamases

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Carbapenem antibiotics are crucial for treating severe Gram-negative bacterial infections.
• Understanding antibiotic resistance mechanisms is vital for effective treatment strategies.

Purpose of the Study:

• To evaluate the in vitro activity of meropenem against a panel of Gram-negative bacteria.
• To investigate the influence of beta-lactamase production and other resistance mechanisms on meropenem susceptibility.
• To compare meropenem's activity and induction of beta-lactamases with imipenem.

Main Methods:

• Agar dilution tests were performed on 82 Gram-negative bacterial isolates.
• Bacterial isolates with characterized resistance mechanisms were utilized.
• Susceptibility testing included meropenem, imipenem, ceftazidime, and piperacillin.

Main Results:

• Meropenem demonstrated excellent activity against most Gram-negative bacteria, including those producing various beta-lactamases.
• Aeromonas hydrophila and Pseudomonas maltophilia isolates producing metalloenzymes showed resistance to both meropenem and imipenem.
• Clinical isolates of Pseudomonas aeruginosa resistant to imipenem exhibited reduced susceptibility to meropenem, associated with outer membrane protein alterations.
• Meropenem was a less potent inducer of Class I beta-lactamases compared to imipenem.

Conclusions:

• Meropenem possesses broad-spectrum activity against Gram-negative bacteria.
• Enzymatic and non-enzymatic mechanisms can lead to cross-resistance between meropenem and imipenem.
• Meropenem's efficacy may be limited in specific resistant strains, necessitating careful consideration of resistance mechanisms.