Invitro Apramycin Activity against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa.
The in vitro activity of apramycin was compared to that of amikacin, gentamicin, and tobramycin against multidrug-resistant, extensively drug-resistant, and pandrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Apramycin demonstrated an MIC50/MIC90of 8/32μg/ml for A. baumannii and 16/32μg/ml for P. aeruginosa. Only 2% of A. baumannii and P. aeruginosa had an MIC greater than an epidemiological cutoff value of 64μg/ml. In contrast, the MIC50/MIC90for amikacin, gentamicin, and tobramycin were ≥64/>256μg/ml for A. baumannii with 57%, 95%, and 74% of isolates demonstrating resistance, respectively, and the MIC50/MIC90were ≥8/256μg/ml for P. aeruginosa with 27%, 50%, and 57% of strains demonstrating resistance, respectively. Apramycin appears to offer promising in vitro activity against highly resistant pathogens. It therefore may warrant further pre-clinical study to assess potential for repurposing as a human therapeutic and relevance as a scaffold for further medicinal chemistry exploration.
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; U.S. Army Medical Department Center and School, Fort Sam Houston, TX.
Anthony D
AD
Kang
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Kenneth P
KP
Smith
Division of Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
George M
GM
Eliopoulos
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Anders H
AH
Berg
Department of Pharmacy, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Christopher
C
McCoy
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA. Electronic address: jekirby@bidmc.harvard.edu.
James E
JE
Kirby
D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000583:Amikacin / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D005839:Gentamicins / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009328:Nebramycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D014031:Tobramycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009328:Nebramycin; C011666:apramycin; D000583:Amikacin; D014031:Tobramycin
Acinetobacter; Activity spectrum; Aminoglycoside; Apramycin; Pseudomonas aeruginosa; Repurposing