New Antibiotics for Treating Multidrug-Resistant Bacterial Infections

This literature systematically reviews the 16 new antibiotics and their combinations approved by the FDA since 2017, focusing on recent advances in treating multidrug-resistant (MDR) Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA), providing guidance for clinical rational drug use.

 

Literature Overview
The article 'New Antibiotics for Treating Multidrug-Resistant Bacterial Infections,' published in the journal Antibiotics, reviews and summarizes recent developments in new antibiotics targeting multidrug-resistant bacteria. It details the antimicrobial spectra, mechanisms of action, clinical indications, and limitations of these antibiotics, highlighting the importance of rational drug use and resistance monitoring.

Background Knowledge
Multidrug-resistant bacteria (MDR) have become a significant global public health challenge, particularly in hospital-acquired infections, chronic disease patients, and post-surgical recovery. Resistant strains such as carbapenem-resistant Enterobacterales (CR-E), carbapenem-resistant Pseudomonas aeruginosa (CR-PA), Acinetobacter baumannii (CR-AB), and multidrug-resistant Mycobacterium tuberculosis (pre-XDR M. tuberculosis) have developed extensive resistance to traditional antibiotics. In recent years, the pharmaceutical industry has developed multiple new antibiotics to combat the spread of these pathogens, including β-lactam/β-lactamase inhibitor combinations, siderophore antibiotics, and novel protein synthesis inhibitors. However, most of these new drugs are optimized versions of existing antibiotics and have not fully broken through traditional mechanisms, so their long-term efficacy and resistance risks still require close monitoring.

 

 

Research Methods and Experiments
This literature is primarily based on clinical trials and pharmacological studies to systematically review new antibiotics and their combinations approved by the FDA since 2017. The authors analyzed each antibiotic's chemical structure, mechanism of action, antimicrobial spectrum, indications, administration routes, and adverse reactions, and compared their efficacy across various drug-resistant mechanisms, such as stability against different β-lactamases or carbapenemases.

Key Conclusions and Perspectives

• Since 2017, 16 new antibiotics or antibiotic combinations have been approved for treating MDR infections, such as carbapenem-resistant Enterobacterales (CR-E), MRSA, and drug-resistant Mycobacterium tuberculosis.
• Most new antibiotics still belong to existing classes, such as fluoroquinolones, tetracyclines, and β-lactams, but their antimicrobial activity has been enhanced through structural modifications or combination therapies.
• Siderophore antibiotics like Cefiderocol exploit bacterial iron uptake mechanisms to enter cells, bypassing traditional porin channels, and show effectiveness against CR-E, CR-PA, and CR-AB.
• β-lactamase inhibitors such as Avibactam, Vaborbactam, and Enmetazobactam, when combined with β-lactam antibiotics, significantly enhance antimicrobial activity against ESBL- or carbapenemase-producing Enterobacterales.
• Plazomicin, a next-generation aminoglycoside, exhibits high stability against CR-E but is not effective for CR-PA or CR-AB infections.
• For MRSA, new drugs such as Omadacycline and Contezolid provide effective alternatives, with the former offering good oral bioavailability, facilitating continuation of therapy outside the hospital.
• For pre-XDR tuberculosis, Pretomanid in combination with Bedaquiline and Linezolid forms a novel six-month treatment regimen that significantly shortens the treatment duration.
• Despite offering promising treatment options, the clinical application of new antibiotics is still limited by insufficient efficacy data, limited experience in special populations, and high costs.

Research Significance and Prospects
The article emphasizes the importance of rational new antibiotic use, including precise pathogen identification, antimicrobial susceptibility testing, and empirical treatment based on epidemiological data. Future development still requires antibiotics with entirely novel mechanisms of action or alternative non-antibiotic strategies, such as phage therapy, antivirulence drugs, and microbiome modulation techniques.

 

 

Conclusion
The rapid spread of multidrug-resistant bacteria poses a serious threat to global health. While progress has been made in new antibiotic development, most remain based on traditional classes and have not yet achieved a true breakthrough. Rational prescribing, accurate diagnosis, and continuous resistance monitoring are essential to ensure long-term effectiveness of these drugs. Additionally, non-antibiotic treatment strategies (e.g., phage lysins, antivirulence antibodies) are emerging and offer potential solutions for the post-antibiotic era. In the future, combining precision medicine with novel antimicrobial technologies will be critical to effectively delay the spread of drug-resistant bacteria and preserve the efficacy of antibiotic therapies.

 

Elisabete Machado and João Carlos Sousa. New Antibiotics for Treating Infections Caused by Multidrug-Resistant Bacteria. Antibiotics.