Abstract
Antibiotic-resistant microorganisms, particularly carbapenem-resistant Acinetobacter baumannii (CRAB), are a significant threat to global public health due to limited treatment options. This study evaluated the antimicrobial potential and biofilm inhibition activities of 560 compounds from the Medicines for Malaria Venture (MMV) Pandemic Response Box and COVID Box against a multidrug-resistant CRAB strain. Compounds with a bacterial inhibition rate of ≥ 80% were further analyzed. The analyses included determining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Additionally, their effects on biofilm inhibition, protein leakage, and synergy with meropenem were assessed. Among the tested compounds, 10 demonstrated notable antimicrobial activity, including doxycycline, atazanavir, alexidine, eravacycline, erythromycin, gepotidacin, trimetrexate, MMV1634402 (brilacidin), MMV1580854 and MMV1578564. Drugs such as doxycycline, gepotidacin, and eravacycline effectively inhibited biofilm formation at low concentrations, with inhibition rates of 33.05%, 40.99%, and 59.37%, respectively. Synergy testing revealed a strong synergistic effect (FICI = 0.37) between brilacidin and meropenem, enhancing antibacterial efficacy. The present study highlights the antimicrobial activity of MMV1634402 (brilacidin) and gepotidacin, providing preliminary evidence of their potential as therapeutic candidates against CRAB. However, further studies involving a broader range of isolates and clinical validation are essential to confirm their efficacy and safety.