In vitro antimicrobial activity of daptomycin alone and in adjunction with either amoxicillin, cefotaxime or rifampicin against the main pathogens responsible for bacterial meningitis in adults

Objectives: As daptomycin adjunction is currently under clinical evaluation in the multicentre phase II AddaMAP study to improve the prognosis of pneumococcal meningitis, the present work aimed at evaluating the in vitro antimicrobial activity of daptomycin-based combinations against some of the most frequent species responsible for bacterial meningitis. Methods: Clinically relevant strains of Streptococcus pneumoniae, Listeria monocytogenes, Haemophilus influenzae and Neisseria meningitidis were obtained from National Reference Centers. The antimicrobial activity of amoxicillin, cefotaxime and rifampicin, either alone or in association with daptomycin, was explored through the determination of minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) as well as time-kill assay (TKA) using the broth microdilution method. Results: All species taken together, the adjunction of daptomycin had no deleterious impact on the antimicrobial activity of amoxicillin, cefotaxime or rifampicin in vitro. Regarding Gram-positive bacteria, FICI and TKA analysis confirmed a global improvement of growth inhibition and bactericidal activity due to the adjunction of daptomycin. The synergistic effect prevailed for L monocytogenes as demonstrated by FICI mainly <0.5 and a dynamic TKA-based synergy rate >50%. In addition, daptomycin based associations did not modify the activity of beta lactam antibiotics or rifampicin against Gram negative bacteria, notably N. meningitidis. Conclusion: These results bring comforting evidence towards the clinical potential of daptomycin adjunc- tion in the treatment of bacterial meningitis, which supports the ongoing AddaMAP clinical trial. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

Automated summary

The study aimed to evaluate the in vitro antimicrobial activity of daptomycin-based combinations against bacterial meningitis pathogens and found that the adjunctive use of daptomycin did not impact the antimicrobial activity of amoxicillin, cefotaxime, or rifampicin. For Gram-positive bacteria, the addition of daptomycin enhanced growth inhibition and bactericidal activity, particularly demonstrating a synergistic effect against Listeria monocytogenes.