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Invitro Apramycin Activity against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa
Anthony D Kang1, Kenneth P Smith2, George M Eliopoulos3
1Department 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.
Abstract:
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/MIC90 of 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/MIC90 for amikacin, gentamicin, and tobramycin were ≥64/>256μg/ml for A. baumannii with 57%, 95%, and 74% of isolates demonstrating resistance, respectively, and the MIC50/MIC90 were ≥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.
Insights
Apramycin shows strong in vitro antibacterial activity against drug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Further research is recommended for its potential as a human therapeutic agent.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa pose significant clinical challenges.
- Limited treatment options are available for infections caused by these highly resistant Gram-negative pathogens.
Purpose of the Study:
- To evaluate the in vitro antibacterial activity of apramycin against MDR, XDR, and PDR A. baumannii and P. aeruginosa.
- To compare apramycin's efficacy with established aminoglycosides: amikacin, gentamicin, and tobramycin.
Main Methods:
- Minimum Inhibitory Concentrations (MICs) were determined for apramycin, amikacin, gentamicin, and tobramycin.
- Activity was assessed against a panel of clinical isolates of A. baumannii and P. aeruginosa.
- Results were compared against epidemiological cutoff values (ECOFFs).
Main Results:
- Apramycin exhibited potent in vitro activity with MIC50/MIC90 values of 8/32 μg/ml for A. baumannii and 16/32 μg/ml for P. aeruginosa.
- A low percentage (2%) of isolates exceeded the ECOFF of 64 μg/ml for apramycin.
- In contrast, amikacin, gentamicin, and tobramycin showed significantly higher resistance rates and MIC values against both pathogens.
Conclusions:
- Apramycin demonstrates promising in vitro activity against highly resistant A. baumannii and P. aeruginosa.
- Apramycin warrants further preclinical investigation for potential repurposing as a human therapeutic.
- Its structure may serve as a valuable scaffold for developing novel antimicrobial agents.
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