In Vitro Activity of Rifabutin and Rifampin against Antibiotic-Resistant Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae

Abstract

Rifabutin has been recently described as a potential adjunctive therapy for antibiotic-resistant A. baumannii infections due to hypersensitivity in iron-depleted media, which may more closely mimic an in vivo environment. Here, we report that this hyperactivity is specific for A. baumannii , rather than being a general effect for other pathogens.

Siderophore conjugation with cleavable linkers boosts the potency of RNA polymerase inhibitors against multidrug-resistantE. coli

“…34 Prior medicinal chemistry efforts at the 3 ′ /4 ′ position retained or increased the molecule's antibiotic activity and even yielded potent, clinically used antibiotics like rifampicin, or rifabutin (Table S1 †). [35][36][37][38] As the binding site of rifamycin is located within a shallow concave pocket formed by the RNAP b subunit, linkers at least 6 atoms long were employed to reduce negative steric effects perturbing target binding. 39 We initially aimed to introduce a conjugation handle of the naphthyl core of 1 based on existing protocols using mono TBS protected 2-amino-resorcinol 72 to give 73 (Fig.…”

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

“…It was not previously known how broadly active AZM was against carbapenem-resistant A. baumannii isolates, as no single study has tested more than 6 unique clinical isolates ( 2 , 12 , 13 ). Therefore, we determined the AZM MICs against a larger panel of 77 carbapenem-resistant A. baumannii clinical isolates, using the broth microdilution method per the Clinical and Laboratory Standards Institute (CLSI) in either MHII or RPMI 1640 as the culture medium ( 7 – 9 , 14 ).…”

“…Our group previously characterized rifabutin’s iron-dependent efficacy against A. baumannii using more physiologically relevant RPMI 1640 mammalian culture medium, which does contain a physiologically normal concentration of bicarbonate, to perform antimicrobial susceptibility testing (AST) ( 8 , 9 ). AZM’s mechanism of entry into bacterial cells depends on transmembrane proton motive force, powered by bicarbonate, which is present in the host environment and RPMI 1640 but absent from Mueller-Hinton II (MHII) medium ( 10 , 11 ).…”

How to treat severe Acinetobacter baumannii infections

“…The rifamycins (Rifampicin, Rifabutin, Rifapentine) have in vitro activity against AB, but this activity is not uniform among them and it is superior in the case of Rifabutin [76,143,144]. ''In vitro'' synergy has been demonstrated for Rifabutin, polymyxins and other agents against AB [145][146][147].…”