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Negatu, D. A.

Publications and source records attributed to Negatu, D. A..

2 recordsLinked to original sources

Strongly bactericidal all-oral β-lactam combinations for the treatment of Mycobacterium abscessus lung disease

Bioactive forms of oral {beta}-lactams were screened in vitro against Mycobacterium abscessus with and without the bioactive form of the oral {beta}-lactamase inhibitor avibactam-ARX1796. Sulopenem was equally active without avibactam, while tebipenem, cefuroxime and amoxicillin required avibactam for optimal activity. Systematic pairwise combination of the four {beta}-lactams revealed strong bactericidal synergy for each of sulopenem, tebipenem and cefuroxime combined with amoxicillin in the presence of avibactam. These all-oral {beta}-lactam combinations warrant clinical evaluation.

microbiology↗

Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus

Tricyclic pyrrolopyrimidines (TPPs) are a new class of antibacterials inhibiting the ATPase of DNA gyrase. TPP8, a representative of this class, is active against Mycobacterium abscessus in vitro. Spontaneous TPP8 resistance mutations mapped to the ATPase domain of M. abscessus DNA gyrase and the compound inhibited DNA supercoiling activity of recombinant M. abscessus enzyme. Further profiling of TPP8 in macrophage and mouse infection studies demonstrated proof-of-concept activity against M. abscessus ex vivo and in vivo.

microbiology↗