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Published on: April 5, 2017
In vitro activity of apramycin against 16S-RMTase-producing Gram-negative isolates
François Caméléna1, Mathilde Liberge1, Inès Rezzoug2
1Department of Bacteriology, Saint-Louis-Lariboisière Hospital Group, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris Cité, INSERM 1137, IAME, Paris, France.
Objectives:
Apramycin is an aminoglycoside (AG) with a unique structure that is little affected by plasmid-mediated mechanisms of AG resistance, including most AG-modifying enzymes and 16S rRNA methyltransferases (16S-RMTases). We evaluate the activity of apramycin against a collection of 16S-RMTase-producing isolates, including Enterobacterales, non-fermenting bacteria, and carbapenemase producers.
Methods:
In total, 164 non-duplicate 16S-RMTase-producing isolates, including 84 Enterobacterales, 53 Acinetobacter baumannii and 27 Pseudomonas aeruginosa isolates, were included in the study. Whole-genome sequencing (WGS) was performed on all isolates with Illumina technology. The minimum inhibitory concentration (MIC) of apramycin was determined by broth microdilution with customized Sensititre plates (Thermo Fisher Scientific, Dardilly, France).
Results:
We found that 95% (156/164) of the 16S-RMTase-producing isolates were susceptible to apramycin, with a MIC50 of 4 mg/L and a MIC90 of 16 mg/L, respectively. Resistance rates were higher in P. aeruginosa (11%) than in A. baumannii (4%) or Enterobacterales (4%) (P < 0.0001 for each comparison). Eight isolates were resistant to apramycin, including one isolate with an MIC >64 mg/L due to the acquisition of the aac(3)-IV gene. The genetic environment of the aac(3)-IV gene was similar to that in the pAH01-4 plasmid of an Escherichia coli isolate from chicken in China.
Conclusion:
Resistance to apramycin remains rare in 16S-RMTase-producing isolates. Apramycin may, therefore, be an interesting alternative treatment for infections caused by 16S-RMTase and carbapenemase producers.
Insights
Apramycin shows high susceptibility (95%) against resistant bacteria, including those producing 16S rRNA methyltransferases. This makes apramycin a promising alternative for treating challenging infections caused by these resistant pathogens.
Area of Science:
- Microbiology
- Antimicrobial Resistance
- Drug Discovery
Background:
- Aminoglycoside (AG) resistance is a growing global health concern.
- Plasmid-mediated resistance mechanisms, such as 16S rRNA methyltransferases (16S-RMTases), significantly reduce the efficacy of existing AGs.
- Apramycin possesses a unique structure less susceptible to common AG resistance mechanisms.
Purpose of the Study:
- To evaluate the in vitro activity of apramycin against a diverse collection of clinically relevant bacterial isolates.
- To determine the susceptibility of 16S-RMTase-producing bacteria, including Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa, to apramycin.
- To assess the potential of apramycin as an alternative treatment for infections caused by multidrug-resistant organisms.
Main Methods:
- A collection of 164 non-duplicate 16S-RMTase-producing bacterial isolates was studied.
- Whole-genome sequencing (WGS) was performed on all isolates.
- Apramycin's minimum inhibitory concentration (MIC) was determined using broth microdilution.
Main Results:
- 95% of the 16S-RMTase-producing isolates were susceptible to apramycin.
- The MIC50 and MIC90 values for apramycin were 4 mg/L and 16 mg/L, respectively.
- Resistance was rare, observed in 8 isolates, with P. aeruginosa showing higher rates (11%) compared to A. baumannii (4%) and Enterobacterales (4%).
Conclusions:
- Apramycin demonstrates significant activity against a broad range of 16S-RMTase-producing bacteria.
- Resistance to apramycin in these challenging isolates is currently rare.
- Apramycin represents a potential therapeutic option for infections caused by 16S-RMTase and carbapenemase-producing pathogens.
