Antibiotics | Study on Treatment Strategies for Metallo-β-Lactamase (MBL)-Producing Gram-Negative Bacterial Infections

This article systematically reviews multiple antibiotic treatment strategies for MBL-producing Gram-negative bacterial infections, covering clinical data on newer agents such as cefiderocol and aztreonam-avibactam, as well as established drugs like colistin and fosfomycin, providing critical references for clinical management.

 

Literature Overview
This paper, 'Antibiotics for the Treatment of Patients with Metallo-β-Lactamase (MBL)-Producing Gram-Negative Bacterial Infections' published in the journal *Antibiotics*, reviews and summarizes antibiotic treatment strategies targeting MBL-producing Gram-negative bacterial infections. It analyzes clinical efficacy, drug resistance patterns, and combination therapies of various new and legacy antibiotics, offering guidance for managing multidrug-resistant bacterial infections.

Background Knowledge
Metallo-β-lactamase (MBL) represents a key resistance mechanism in Gram-negative pathogens, including *Klebsiella pneumoniae*, *Escherichia coli*, *Pseudomonas aeruginosa*, and *Acinetobacter baumannii*. Infections caused by these organisms exhibit high morbidity and mortality with limited therapeutic options. Current antibiotics like carbapenems are ineffective against MBL-producing strains, necessitating alternative treatment approaches. Novel agents such as cefiderocol and aztreonam-avibactam demonstrate MBL activity but face challenges due to high costs and limited accessibility. Legacy antibiotics including colistin and fosfomycin show partial efficacy in combination regimens, yet nephrotoxicity and insufficient clinical evidence remain critical concerns. This study aims to synthesize existing clinical evidence to provide evidence-based treatment recommendations while highlighting the need for future research.

 

 

Research Methods and Experiments
The article systematically reviewed multiple clinical studies, including randomized controlled trials, multicenter retrospective analyses, prospective observational studies, and case series, to evaluate efficacy and safety profiles of various antibiotics against MBL-producing pathogens. Investigated agents included cefiderocol, aztreonam-avibactam, colistin, fosfomycin, tigecycline, and aminoglycosides. Study endpoints encompassed clinical cure rates, microbiological eradication rates, 30-day mortality, and adverse event incidence.

Key Conclusions and Perspectives

• New antibiotic cefiderocol demonstrated high clinical cure rates (65.8%–75%) and microbiological eradication rates (62.5%) in clinical trials and retrospective studies, though resistance development during therapy was observed in some patients.
• Aztreonam-avibactam showed a clinical cure rate of 41.7% (vs. 0% in best available therapy groups) in a Phase 3 trial, with low 28-day mortality (8.3%).
• Ceftazidime-avibactam combined with aztreonam serves as an alternative when aztreonam-avibactam is unavailable, with observational studies reporting mortality rates of 19.2%–23.8% and clinical cure rates of 58.3%–71.4%.
• Legacy antibiotics colistin and fosfomycin, when used in combination regimens across multiple studies, exhibited high 30-day mortality (50%–59.3%) and frequent nephrotoxicity.
• Tigecycline and aminoglycosides showed limited clinical evidence, with some studies indicating partial efficacy in combination therapy but lacking validation from large-scale randomized controlled trials.
• The study emphasizes the necessity of personalized treatment based on in vitro antimicrobial susceptibility testing and highlights the potential for resistance development during therapy, requiring close monitoring.

Research Significance and Prospects
This study provides a comprehensive systematic review of current antibiotic strategies for MBL-producing bacterial infections, underscoring the clinical potential of novel agents and the practical utility of legacy antibiotics in resource-limited settings. Given the predominance of observational studies and case series in existing literature, future research should prioritize randomized controlled trials to validate efficacy and safety profiles, while exploring novel antimicrobial agents and combination therapies.

 

 

Conclusion
Current clinical evidence supports the use of novel antibiotics like cefiderocol and aztreonam-avibactam for treating MBL-producing Gram-negative infections. However, their high cost and limited availability hinder widespread application. In settings where novel agents are inaccessible, legacy antibiotics such as colistin and fosfomycin demonstrate partial efficacy in combination regimens but require careful monitoring due to toxicity and variable outcomes. The article stresses the importance of in vitro susceptibility testing and advocates for future research focusing on large-scale randomized controlled trials to optimize treatment protocols. Additionally, development of novel antimicrobial agents and combination strategies remains critical for combating MBL-mediated resistance.

 

Matthew E Falagas, Dimitrios S Kontogiannis, Dimitrios Ragias, and Stylianos A Kakoullis. Antibiotics for the Treatment of Patients with Metallo-β-Lactamase (MBL)-Producing Gram-Negative Bacterial Infections. Antibiotics.