Metallo-β-lactamases: a last frontier for β-lactams?

Area of Science:

• Microbiology and Infectious Diseases
• Molecular Biology
• Antimicrobial Resistance

Background:

• Metallo-β-lactamases (MBLs) are enzymes that confer resistance to a broad spectrum of β-lactam antibiotics, including carbapenems.
• MBLs are increasingly detected in Gram-negative pathogens like Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii.
• The emergence and international spread of MBL-producing bacteria, such as carbapenem-resistant Klebsiella pneumoniae, represent a growing global health crisis.

Purpose of the Study:

• To review the current knowledge on metallo-β-lactamases, focusing on their clinical relevance and impact.
• To highlight the challenges in managing infections caused by MBL-producing Gram-negative bacteria.
• To underscore the need for improved infection control strategies and public health preparedness.

Main Methods:

• Review of existing literature on metallo-β-lactamase molecular biology, genetics, and epidemiology.
• Analysis of clinical data and case reports related to MBL-producing bacterial infections.
• Assessment of current treatment guidelines and infection control policies.

Main Results:

• Metallo-β-lactamases exhibit broad-spectrum carbapenemase activity and are resistant to available β-lactamase inhibitors.
• Mobile genetic elements facilitate the rapid dissemination of MBL genes among Gram-negative pathogens.
• Despite extensive molecular data, epidemiological surveillance and clinical experience remain limited, leading to diagnostic and therapeutic challenges.

Conclusions:

• Metallo-β-lactamase-producing bacteria pose a significant threat due to their resistance profiles and widespread dissemination.
• Inconsistent epidemiological data and limited clinical experience hinder effective management and infection control.
• Urgent improvements in public health infrastructure and global collaboration are necessary to combat the rising emergency of MBL-mediated resistance.