Antimicrobial Susceptibility Testing Performed in RPMI 1640 Reveals Azithromycin Efficacy against Carbapenem-Resistant Acinetobacter baumannii and Predicts In Vivo Outcomes in Galleria mellonella

Abstract

Antimicrobial susceptibility testing (AST) in RPMI 1640, a more physiologically relevant culture medium, revealed that a substantial proportion of carbapenem-resistant Acinetobacter baumannii isolates were susceptible to azithromycin, a macrolide antibiotic not currently considered effective against A. baumannii . Experiments using Galleria mellonella validated these in vitro data.

Repurposing Anthracycline Drugs as Potential Antibiotic Candidates and Potentiators to Tackle Multidrug-Resistant Pathogens

“…29,30 For instance, the therapeutic potential of AZM against MDR-Gram-negative pathogens was revealed through RPMI screening. 10,31 Despite the fact that many efforts have been employed in developing novel antibacterial compounds, few antibiotics have been approved by the FDA in the past decades. Repurposing previously approved drugs as novel antibacterial agents or antibiotic adjuvants provides a distinct and feasible approach to overcoming drug-resistant pathogens.…”

“…To circumvent this challenge, host-simulated medium RPMI, which is specifically formulated with a blend of inorganic salts to promote the growth of mammalian cells, was employed to mimic the physiological conditions in vivo. , For instance, the therapeutic potential of AZM against MDR-Gram-negative pathogens was revealed through RPMI screening. , Despite the fact that many efforts have been employed in developing novel antibacterial compounds, few antibiotics have been approved by the FDA in the past decades. Repurposing previously approved drugs as novel antibacterial agents or antibiotic adjuvants provides a distinct and feasible approach to overcoming drug-resistant pathogens. , In our study, we uncovered that the antitumor agent MX exhibited broad-spectrum antibacterial activity against MDR bacteria in the RPMI medium and was capable of combining with colistin to fight against MCR-positive pathogens.…”

Defining the minimum inhibitory concentration of 22 rifamycins in iron limited, physiologic medium against Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae clinical isolates

“…Unless otherwise indicated, the standard broth microdilution method following CLSI methodology was used to determine MICs [ 5 ]. The media used for the minimum inhibitory concentration (MIC) assays performed in this study were MHII or RPMI-1640 as previously described [ 1 – 3 , 6 , 11 , 12 ].…”

“…We determined rifamycin MICs (n = 185) against a larger panel of 21 rifamycin compounds against A. baumannii (n = 5), K. pneumoniae (n = 3), and E. coli (n = 1) clinical isolates using the broth microdilution method per the Clinical & Laboratory Standards Institute (CLSI), but modified to use the iron-limited medium RPMI-1640 as previously described [1][2][3]5,6]. A summary of the compounds tested is listed in Table 1.…”