Meta-analysis and discussion on challenges to translate Leishmania drug resistance phenotyping into the clinic

Area of Science:

• * Infectious Diseases and Microbiology
• * Parasitology and Tropical Medicine

Background:

• * Antimicrobial resistance (AMR) poses a significant threat to treating infections, including those caused by Leishmania parasites.
• * Increasing treatment failures due to drug-resistant Leishmania highlight the urgent need for reliable diagnostic methods.
• * Current molecular methods for tracking drug resistance and antimicrobial susceptibility testing (AST) are not clinically applicable.

Purpose of the Study:

• * To explore and propose methodologies for diagnosing Leishmania drug resistance by translating basic research into practical applications.
• * To evaluate the reliability of promastigote-based AST in predicting the susceptibility of intracellular amastigotes.
• * To establish a framework for diagnosing Leishmania drug resistance, aligning with guidelines for bacterial resistance diagnosis.

Main Methods:

• * A meta-analysis of existing literature was conducted to assess the predictive value of promastigote AST for amastigote susceptibility.
• * The study proposes using standardized AST performed on promastigote cultures.
• * Discussion includes challenges in defining clinical breakpoints and epidemiological cutoff values (ECOFF) for tracking resistant isolates.

Main Results:

• * Meta-analysis confirmed the reliability of promastigote AST in predicting intracellular amastigote susceptibility.
• * Promastigote cultures are identified as a feasible, cost-effective, and standardizable candidate for resistance diagnosis.
• * The proposed approach aims to improve the diagnosis of Leishmania drug resistance.

Conclusions:

• * Standardized promastigote AST offers a viable method for diagnosing Leishmania drug resistance.
• * This approach can guide clinical decisions, characterize resistant isolates, and aid in the search for new molecular markers.
• * Further work is needed to define clinical breakpoints and ECOFFs for effective implementation.