Combination therapy for carbapenem-resistant Gram-negative bacteria

Area of Science:

• Infectious Diseases
• Microbiology
• Pharmacology

Background:

• Emergence of carbapenem-resistant Gram-negative bacteria (CR GNB) poses a significant threat to antimicrobial therapy.
• Polymyxins are often the last resort, but monotherapy has drawbacks, necessitating alternative strategies.
• Pre-clinical data support antimicrobial combinations against CR GNB.

Purpose of the Study:

• To review the clinical evidence for combination therapy against CR GNB.
• To discuss the optimization of pharmacokinetic/pharmacodynamic (PK/PD) targets for cornerstone and adjuvant drugs.
• To guide the clinical prescription of combination therapies based on PK/PD characteristics.

Main Methods:

• Review of clinical evidence for major drugs used in combination schemes against CR GNB.
• Analysis of pharmacokinetic/pharmacodynamic principles relevant to combination therapy.
• Discussion on optimizing drug dosing and combinations for improved outcomes.

Main Results:

• Combination therapy is a viable strategy to overcome limitations of single-agent therapy for CR GNB.
• Polymyxins, tigecycline, and carbapenems are key components in combination regimens.
• Achieving PK/PD targets for both cornerstone and adjuvant drugs is critical for success.

Conclusions:

• Combination therapy offers a promising approach to manage infections caused by CR GNB.
• Careful consideration of PK/PD properties is essential for effective drug selection and dosing.
• Further clinical research is needed to refine optimal combination strategies.