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

Abstract

OBJECTIVES\nAs daptomycin adjunction is currently under clinical evaluation in the multicenter phase II AddaMAP study to improve the prognosis of pneumococcal meningitis, the present work aims at evaluating the in vitro antimicrobial activity of daptomycin-based associations towards some of the most frequent species responsible for bacterial meningitis.\n\n\nMETHODS\nClinical 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 rifampin - either alone or in association with daptomycin - was explored through the determination of minimal inhibitory concentration (MIC), fractional inhibitory concentration index (FICI) and Time-Kill Kinetics Assay (TKA) using broth microdilution method.\n\n\nRESULTS\nAll species taken together, the adjunction of daptomycin had no deleterious impact on the antimicrobial activity of amoxicillin, cefotaxime and rifampin 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 Listeria monocytogenes as demonstrated by FICI largely below 0.5 and a dynamic TKA-based synergy rate above 50%. In addition, daptomycin-based associations did not modify the activity of beta-lactam antibiotics or rifampin against Gram-negative bacteria, notably Neisseria meningitidis.\n\n\nCONCLUSIONS\nThese results bring comforting evidence towards the clinical potential of daptomycin adjunction in the treatment of bacterial meningitis which support the ongoing AddaMAP clinical trial.