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Multidrug-resistant Gram-negative bacterial infections: Key Updates and Practical Strategies

25 Jan, 2025 | 22:53h | UTC

Introduction: This summary highlights essential points from a recent review in The Lancet addressing multidrug-resistant Gram-negative bacterial (MDR-GNB) infections. It discusses the global epidemiology, diagnostic advances, and therapeutic approaches, aiming to guide clinicians in managing these difficult-to-treat pathogens, which include resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

Key Recommendations:

  1. Use Rapid Diagnostics to Guide Therapy
    • Employ molecular tests (e.g., multiplex PCR) to detect resistance genes quickly and facilitate targeted treatment.
    • Consider phenotypic assays (e.g., CarbaNP, carbapenemase inactivation method) and MALDI-TOF for rapid organism identification and mechanism-specific information.
  2. Optimize Antibiotic Selection Based on Resistance Mechanisms
    • AmpC-Producing Enterobacterales (e.g., Enterobacter spp.): Use cefepime if in vitro susceptibility is confirmed.
    • ESBL-Producing Enterobacterales: Carbapenems (e.g., meropenem) remain the mainstay for serious infections.
    • Carbapenem-Resistant Enterobacterales (CRE): Use novel β-lactam/β-lactamase inhibitor agents (e.g., ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam) based on specific carbapenemase mechanisms. For metallo-β-lactamase producers, consider aztreonam plus ceftazidime–avibactam or future co-formulations (e.g., aztreonam–avibactam).
    • DTR-Pseudomonas aeruginosa: Ceftolozane–tazobactam is preferred if active in vitro. Ceftazidime–avibactam or imipenem–relebactam may also be options depending on local susceptibility data.
    • Carbapenem-Resistant Acinetobacter baumannii (CRAB): High-dose sulbactam combinations (e.g., sulbactam–durlobactam) were studied in combination with imipenem–cilastatin during trials; further data are needed to clarify optimal clinical use.
  3. Consider Non-Antibiotic Modalities for Refractory Cases
    • Investigational therapies—such as bacteriophages and antivirulence agents—are under clinical evaluation.
    • Fecal microbiota transplantation has shown variable decolonization efficacy in small studies, and randomized trials have yielded limited or inconclusive results.
  4. Emphasize Antimicrobial Stewardship and Infection Control
    • Restrict newer agents to cases where standard treatments have failed or resistance patterns require them.
    • Maintain rigorous infection control practices (e.g., contact precautions, hand hygiene, isolation measures) to reduce nosocomial spread of MDR-GNB.
    • Observational data suggest shorter antibiotic courses (7–10 days) might be adequate in select cases, but robust clinical trial evidence is still pending.

Conclusion:
By combining rapid diagnostics, judicious use of existing and novel antibiotics, and robust infection prevention measures, clinicians can significantly improve outcomes for patients with MDR-GNB infections. However, access to advanced diagnostics and new therapies remains limited in many regions, and further clinical trials are needed to determine optimal treatment and duration strategies. Early mechanism-focused detection and targeted therapy enhance clinical success, reduce toxicity, and help preserve the efficacy of newly approved agents.

Reference:
Macesic N, Uhlemann A-C, Peleg AY. Multidrug-resistant Gram-negative bacterial infections. The Lancet. 2025;405(10474):257-272. DOI: https://doi.org/10.1016/S0140-6736(24)02081-6

 


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