Managing multidrug resistant Gram-negative bacteraemia in immunocompromised hosts

Area of Science:

• Infectious Diseases
• Hematology
• Transplantation Medicine

Background:

• Multidrug-resistant Gram-negative bloodstream infections (MDR-GNBSI) pose a significant threat to immunocompromised individuals, including solid organ transplant (SOT) recipients and patients with hematological malignancy (HM).
• These infections are increasingly prevalent in these vulnerable populations undergoing intensive treatments like chemotherapy and cellular therapies.

Purpose of the Study:

• To review current evidence and practical approaches for managing MDR-GNBSI in immunocompromised hosts.
• To discuss empirical, quasi-targeted, and targeted therapeutic strategies.

Main Methods:

• Review of contemporary cohort data on MDR-GNBSI rates in SOT and HM patients.
• Analysis of diagnostic and therapeutic management strategies, including risk stratification, rapid diagnostics, and novel antimicrobial agents.
• Evaluation of emerging tools like machine-learning models and antimicrobial stewardship bundles.

Main Results:

• Rising rates of MDR-GNBSI observed in both SOT and HM patient cohorts.
• Risk-adapted empirical therapy should consider colonization, local epidemiology, and individual risk factors; screening is crucial.
• Rapid diagnostics aid timely therapy but interpretation of genotypic resistance in Gram-negatives can be challenging; novel agents and PK/PD optimization are key for targeted therapy.
• Evidence supports oral step-down and shorter treatment courses, but routine follow-up cultures are debated.

Conclusions:

• Management of MDR-GNBSI in immunocompromised patients necessitates individualized, data-driven strategies.
• Integration of risk stratification, rapid microbiology, and pharmacokinetics/pharmacodynamics (PK/PD) optimization is essential.
• Adherence to antimicrobial stewardship principles is a priority in managing these complex infections.