Multidrug-resistant gram-negative infections. Bringing back the old

Area of Science:

• Infectious Diseases
• Microbiology
• Pharmacology

Background:

• Multidrug-resistant (MDR) gram-negative infections present a significant global health challenge.
• Increasing resistance in key pathogens like Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species limits treatment efficacy.
• Carbapenems, once a primary treatment for ESBL-producing E. coli and Klebsiella, are becoming less effective due to carbapenemase-producing strains.

Purpose of the Study:

• To highlight the challenges in treating MDR gram-negative infections.
• To review current limited treatment options for MDR gram-negative pathogens.
• To emphasize the need for novel antimicrobial development.

Main Methods:

• Literature review of current antimicrobial armamentarium.
• Analysis of resistance patterns in gram-negative pathogens.
• Discussion of treatment limitations and emerging therapeutic strategies.

Main Results:

• Limited commercially available anti-infectives are effective against MDR gram-negative infections.
• Current options include tigecycline, polymyxin B, and colistin, each with potential toxicities (nephrotoxicity, neurotoxicity).
• The rise of carbapenemase-producing K. pneumoniae necessitates alternative treatment approaches.

Conclusions:

• Treatment of MDR gram-negative infections is increasingly difficult due to resistance.
• Vigilance is required to manage adverse effects of polymyxins.
• Support for initiatives like the Infectious Diseases Society of America's 10 × '20 Initiative is vital for future antimicrobial development.