Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 74, Issue 5, Pages 1311-1316Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkz012
Keywords
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Funding
- Beth Israel Deaconess Medical Center
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R21 AI142040-01, F32 AI124590, R33AI119114, R01 AI099122, R21 AI130434]
- United States Army
- Harvard Catalyst Pilot Grant
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [F32AI124590, R33AI119114, R21AI130434, R21AI142040] Funding Source: NIH RePORTER
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Background: The emergence of Neisseria gonorrhoeae resistant to all currently available antimicrobial therapies poses a dire public health threat. New antimicrobial agents with activity against N. gonorrhoeae are urgently needed. Apramycin is an aminocyclitol aminoglycoside with broad-spectrumin vitro activity against MDR Gram-negative pathogens and Staphylococcus aureus. However, its activity against N. gonorrhoeae has not been described. Objectives: The activity spectrum of apramycin against a collection of MDR N. gonorrhoeae was assessed. Isolates tested included those susceptible and resistant to the structurally distinct aminocyclitol, spectinomycin. Results: The modal MICs for apramycin and spectinomycin were 16 mg/L and 32mg/L, respectively. The epidemiological cut-off (ECOFF) for apramycin was 64 mg/L. No strains among 77 tested had an MIC above this ECOFF, suggesting very low levels of acquired apramycin resistance. In time-kill analysis, apramycin demonstrated rapid bactericidal activity comparable to that of spectinomycin. Conclusions: Apramycin has broad-spectrum, rapidly bactericidal activity against N. gonorrhoeae. Future pharmacokinetic and pharmacodynamic studies will be needed to determine whether apramycin and/or apramycin derivatives hold promise as new therapeutics for N. gonorrhoeae infection.
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