Current and future treatment options for infections caused by multidrug-resistant Gram-negative pathogens

Area of Science:

• Infectious Diseases
• Pharmacology
• Microbiology

Background:

• The increasing prevalence of multidrug-resistant, extensively drug-resistant, and pan-drug-resistant pathogens presents a significant global public health crisis.
• Limited therapeutic options necessitate the re-evaluation and optimized use of existing antibiotics.

Purpose of the Study:

• To review the current understanding of colistin and fosfomycin pharmacokinetics in critically ill patients.
• To discuss the appropriate use of tigecycline for non-approved indications.
• To emphasize the importance of combination antibiotic regimens and the potential of novel antibacterials.

Main Methods:

• Literature review of pharmacokinetic studies for colistin and fosfomycin.
• Analysis of clinical practice guidelines and in vitro data for tigecycline.
• Evaluation of emerging antibacterial agents and resistance mechanisms.

Main Results:

• Pharmacokinetic data for colistin and fosfomycin in specific patient populations and body compartments require further elucidation.
• Tigecycline use for non-approved indications warrants caution, potentially requiring higher dosages based on in vitro activity.
• Combination therapies are crucial for preventing resistance and improving outcomes with current agents.

Conclusions:

• Optimizing the use of colistin, fosfomycin, and tigecycline, particularly in combination regimens, is essential for managing infections caused by resistant pathogens.
• New antibacterials like avibactam, ceftolozane/tazobactam, and plazomicin show promise but will not entirely overcome existing resistance mechanisms.