Department of Bacteriology, Saint-Louis-Lariboisière Hospital Group, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris Cité, INSERM 1137, IAME, Paris, France.
Department of Bacteriology, Saint-Louis-Lariboisière Hospital Group, Assistance Publique-Hôpitaux de Paris, Paris, France.
J Glob Antimicrob Resist. 2023 Jun;33:21-25. doi: 10.1016/j.jgar.2023.02.005. Epub 2023 Feb 22.
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.
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).
We found that 95% (156/164) of the 16S-RMTase-producing isolates were susceptible to apramycin, with a MIC of 4 mg/L and a MIC 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.
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.
安普霉素是一种结构独特的氨基糖苷（AG），很少受到质粒介导的 AG 耐药机制的影响，包括大多数 AG 修饰酶和 16S rRNA 甲基转移酶（16S-RMTases）。我们评估了安普霉素对包括肠杆菌科、非发酵菌和碳青霉烯酶生产者在内的 16S-RMTase 产生分离株的活性。
总共有 164 个非重复的 16S-RMTase 产生分离株，包括 84 个肠杆菌科、53 个鲍曼不动杆菌和 27 个铜绿假单胞菌分离株，被纳入本研究。所有分离株均采用 Illumina 技术进行全基因组测序（WGS）。采用定制 Sensititre 平板（Thermo Fisher Scientific，Dardilly，法国）进行肉汤微量稀释来确定安普霉素的最小抑菌浓度（MIC）。
我们发现，95%（156/164）的 16S-RMTase 产生分离株对安普霉素敏感，MIC 分别为 4 mg/L 和 16 mg/L。铜绿假单胞菌（11%）的耐药率高于鲍曼不动杆菌（4%）或肠杆菌科（4%）（每个比较均 P<0.0001）。有 8 个分离株对安普霉素耐药，其中一个分离株的 MIC>64 mg/L，原因是获得了 aac(3)-IV 基因。aac(3)-IV 基因的遗传环境与来自中国鸡源大肠杆菌分离株的 pAH01-4 质粒相似。
在 16S-RMTase 产生分离株中，对安普霉素的耐药性仍然罕见。因此，安普霉素可能是治疗 16S-RMTase 和碳青霉烯酶生产者引起的感染的一种有趣的替代治疗方法。
