Evaluation of apramycin against spectinomycin-resistant and -susceptible strains of Neisseria gonorrhoeae

J Antimicrob Chemother. 2019 May 1;74(5):1311-1316. doi: 10.1093/jac/dkz012.

Abstract

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-spectrum in 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 32 mg/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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Drug Resistance, Bacterial*
  • Gonorrhea / microbiology
  • Humans
  • Microbial Sensitivity Tests
  • Nebramycin / analogs & derivatives*
  • Nebramycin / pharmacology
  • Neisseria gonorrhoeae / drug effects*
  • Spectinomycin / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Nebramycin
  • apramycin
  • Spectinomycin