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Susceptibility of Cutibacterium acnes to topical minocycline foam.
Anaerobe ( IF 2.3 ) Pub Date : 2020-01-28 , DOI: 10.1016/j.anaerobe.2020.102169
Joyce Sutcliffe 1 , Robert McLaughlin 1 , Guy Webster 2 , Andrew F Read 3 , Karl Drlica 4 , Russell Elliott 5 , Iain Stuart 5
Affiliation  

FMX101 4% minocycline foam (FMX101 4%) is a novel, topical minocycline formulation for treatment of acne vulgaris. We report that FMX101 4% had an MIC90 of 0.25 μg/ml and was ≥4-fold more active than comparator antimicrobials against a panel of 98 clinical Cutibacterium acnes isolates. The panel was diverse by clonal complex and sequence type, having 20 novel multi-locus sequence types including clonal complexes and sequence types associated with acne (CC1, CC3, and CC4; ST1 and ST3). Some isolates were phenotypically resistant to clindamycin (6.1%), erythromycin (14.3%), and tetracycline (2.0% intermediate resistance). Six isolates (6.4%) carried a mutation in the quinolone resistance-determining region of gyrA. With C. acnes, spontaneous resistance to FMX101 4% occurred at frequencies ranging from ≤5 × 10−9 to <1 × 10−8; mutations were identified in rpsJ, a gene encoding 30S ribosomal protein S10. No mutant exhibited a minocycline MIC above 0.5 μg/ml. No second-step mutation in previously isolated mutants or strains containing rpsJ ± 16S rRNA mutations was detected following minocycline challenge. Minocycline retained antibacterial activity against C. acnes over 15 multiple passages; thus, no selective growth advantage for minocycline-resistant mutants occurred under the experimental conditions. FMX101 4% has the potential to retain the favorable resistance profile of minocycline in diverse C. acnes isolates while providing the benefits of a topical formulation for treatment of acne vulgaris.



中文翻译:

痤疮皮肤炎杆菌对局部米诺环素泡沫的敏感性。

FMX101 4%米诺环素泡沫(FMX101 4%)是用于治疗寻常性痤疮的新型局部米诺环素配方。我们报告说FMX101 4%的MIC 90为0.25μg/ ml,并且对98种临床痤疮痤疮杆菌分离物的活性比对照抗菌剂高≥4倍。该小组的克隆复合物和序列类型各不相同,具有20种新颖的多基因座序列类型,包括克隆复合物和与痤疮相关的序列类型(CC1,CC3和CC4; ST1和ST3)。一些分离株对克林霉素(6.1%),红霉素(14.3%)和四环素(2.0%中等耐药)在表型上具有抗性。六个分离株(6.4%)在gyrA的喹诺酮抗性决定区域中携带一个突变。与痤疮丙酸杆菌,在≤5×10 -9到<1×10 -8的频率范围内发生对FMX101 4%的自发抵抗;在编码30S核糖体蛋白S10的基因rpsJ中鉴定出突变。没有突变体表现出高于0.5μg/ ml的米诺环素MIC。在米诺环素攻击后,在先前分离的包含rpsJ ±16S rRNA突变的突变体或菌株中检测到第二步突变。米诺环素在15次传代过程中保留了针对痤疮丙酸杆菌的抗菌活性;因此,在实验条件下没有发生对米诺环素抗性突变体的选择性生长优势。FMX101 4%可能保留各种痤疮丙酸杆菌中美满霉素的良好耐药性 分离,同时提供外用制剂治疗寻常痤疮的好处。

更新日期:2020-01-28
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