Objective:

To provide updated guidance on treating antimicrobial-resistant gram-negative infections, incorporating newer therapies and evolving evidence.

Approach:

• Guidance Development: The guidance was developed by a panel of infectious diseases specialists based on literature review, clinical expertise, and expert consensus, without using GRADE methodology.
• Target Pathogen Groups: It addresses six groups of resistant gram-negative pathogens: ESBL-E, AmpC-E, CRE, DTR P. aeruginosa, CRAB, and S. maltophilia.
• Treatment Recommendations: Recommendations emphasize susceptibility testing, appropriate empiric treatment, and reassessment based on susceptibility profiles.

Key Findings:

• Carbapenems are preferred for invasive ESBL-E infections outside the urinary tract.
• Cefepime is preferred for AmpC-E infections when susceptible.
• For CRE infections, treatment varies by resistance mechanism, with ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam preferred for KPC-producing infections.
• Aztreonam-avibactam and cefiderocol are preferred for New Delhi metallo-beta-lactamase-producing infections.
• Newer beta-lactam agents like cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam may be effective against DTR P. aeruginosa.
• Sulbactam-durlobactam combined with imipenem or meropenem is preferred for invasive CRAB infections.
• Cefiderocol monotherapy is preferred for invasive S. maltophilia infections.

Interpretation:

The guidance aims to assist clinicians in making informed treatment decisions amidst evolving antimicrobial resistance.

Limitations:

• Specific dosing guidance is provided only for adults.
• The recommendations are based on expert consensus and literature review, not GRADE methodology.

Conclusion:

The guidance is intended to help clinicians navigate treatment decisions for serious infections caused by drug-resistant pathogens.

Sources:

• Clinical Infectious Diseases