Fuzi Miklos, Rodriguez Baño Jesus, Toth Akos
Institute of Medical Microbiology, Semmelweis University, Budapest, Hungary.
Unit of Infectious Diseases, Clinical Microbiology and Preventive Medicine, Department of Medicine, Hospital Universitario Virgen Macarena, University of Seville - Biomedicine Institute of Seville (IBiS), Seville, Spain.
Front Microbiol. 2020 Feb 25;11:271. doi: 10.3389/fmicb.2020.00271. eCollection 2020.
It is well-established that the spread of many multidrug-resistant (MDR) bacteria is predominantly clonal. Interestingly the international clones/sequence types (STs) of most pathogens emerged and disseminated during the last three decades. Strong experimental evidence from multiple laboratories indicate that diverse fitness cost associated with high-level resistance to fluoroquinolones contributed to the selection and promotion of the international clones/STs of hospital-associated methicillin-resistant (HA-MRSA), extended-spectrum β-lactamase-(ESBL)-producing , ESBL-producing and . The overwhelming part of the literature investigating the epidemiology of the pathogens as a function of fluoroquinolone use remain in concordence with these findings. Moreover, recent data clearly show the potential of fluoroquinolone exposure to shape the clonal evolution of Enteritidis. The success of the international clones/STs in all these species was linked to the strains' unique ability to evolve multiple energetically beneficial gyrase and topoisomerase IV mutations conferring high-level resistance to fluorquinolones and concomittantly permitting the acquisition of an extra resistance gene load without evoking appreciable fitness cost. Furthermore, by analyzing the clonality of multiple species, the review highlights, that in environments under high antibiotic exposure virulence factors play only a subsidiary role in the clonal dynamics of bacteria relative to multidrug-resistance coupled with favorable fitness (greater speed of replication). Though other groups of antibiotics should also be involved in selecting clones of bacterial pathogens the role of fluoroquinolones due to their peculiar fitness effect remains unique. It is suggested that probably no bacteria remain immune to the influence of fluoroquinolones in shaping their evolutionary dynamics. Consequently a more judicious use of fluoroquinolones, attuned to the proportion of international clone/ST isolates among local pathogens, would not only decrease resistance rates against this group of antibiotics but should also ameliorate the overall antibiotic resistance landscape.
众所周知，许多耐多药（MDR）细菌的传播主要是克隆性的。有趣的是，大多数病原体的国际克隆/序列类型（STs）在过去三十年中出现并传播开来。多个实验室的有力实验证据表明，与对氟喹诺酮类药物的高水平耐药性相关的多种适应性代价，促成了医院相关耐甲氧西林金黄色葡萄球菌（HA-MRSA）、产超广谱β-内酰胺酶（ESBL）、产ESBL以及[此处原文缺失部分内容]的国际克隆/STs的选择和传播。大量研究病原体流行病学与氟喹诺酮类药物使用关系的文献，绝大多数与这些发现一致。此外，最近的数据清楚地表明，接触氟喹诺酮类药物有可能影响肠炎沙门氏菌的克隆进化。所有这些物种中国际克隆/STs的成功，与菌株独特的能力有关，即能够进化出多个在能量上有益的gyrase和拓扑异构酶IV突变，从而赋予对氟喹诺酮类药物的高水平耐药性，同时允许获得额外的耐药基因负荷而不会引发明显的适应性代价。此外，通过分析多个物种的克隆性，该综述强调，在高抗生素暴露的环境中，相对于耐多药以及良好适应性（更快的复制速度），毒力因子在细菌克隆动态中仅起次要作用。尽管其他抗生素组也应参与选择细菌病原体的克隆，但由于氟喹诺酮类药物独特的适应性效应，其作用仍然是独特的。有人认为，可能没有细菌能免受氟喹诺酮类药物对其进化动态的影响。因此，根据当地病原体中国际克隆/ST分离株的比例，更明智地使用氟喹诺酮类药物，不仅会降低对这类抗生素的耐药率，还应改善整体抗生素耐药情况。
