Johnson James R, Porter Stephen, Thuras Paul, Castanheira Mariana
Minneapolis VA Medical Center, Minneapolis, Minnesota, USA
University of Minnesota, Minneapolis, Minnesota, USA.
Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.00732-17. Print 2017 Aug.
The 30 subclone of sequence type 131 (ST131-30) has become the leading antimicrobial resistance lineage in the United States and often exhibits resistance to one or both of the two key antimicrobial classes for treating Gram-negative infections, extended-spectrum cephalosporins (ESCs) and fluoroquinolones (FQs). However, the timing of and reasons for its recent emergence are inadequately defined. Accordingly, from clinical isolates collected systematically across the United States by the SENTRY Antimicrobial Surveillance Program in 2000, 2003, 2006, and 2009, 234 isolates were selected randomly, stratified by year, within three resistance categories: (i) ESC-reduced susceptibility, regardless of FQ phenotype (ESC-RS); (ii) FQ resistance, ESC susceptible (FQ-R); and (iii) FQ susceptible, ESC susceptible (FQ-S). Susceptibility profiles, phylogroup, ST, ST131 subclone, and virulence genotypes were determined, and temporal trends and between-variable associations were assessed statistically. From 2000 to 2006, concurrently with the emergence of ESC-RS and FQ-R strains, the prevalence of (virulence-associated) phylogroup B2 among such strains also rose dramatically, due entirely to rapid emergence of ST131, especially 30. By 2009, 30 was the dominant lineage overall (22%), accounting for a median of 43% of all single-agent and multidrug resistance (68% for ciprofloxacin). 30's emergence increased the net virulence gene content of resistant (especially FQ-R) isolates, giving stable overall virulence gene scores despite an approximately 4-fold expansion of the historically less virulent resistant population. These findings define more precisely the timing and tempo of 30's emergence in the United States, identify possible reasons for it, and suggest potential consequences, including more frequent and/or aggressive antimicrobial-resistant infections.
序列类型131(ST131-30)的30亚克隆已成为美国主要的抗菌药物耐药谱系,并且常常对治疗革兰氏阴性菌感染的两类关键抗菌药物中的一种或两种表现出耐药性,即超广谱头孢菌素(ESCs)和氟喹诺酮类药物(FQs)。然而,其近期出现的时间和原因尚未明确界定。因此,从哨兵抗菌监测计划于2000年、2003年、2006年和2009年在美国系统收集的临床分离株中,随机选择了234株分离株,按年份分层,分为三个耐药类别:(i)对ESCs敏感性降低,无论FQ表型如何(ESCs-RS);(ii)对FQ耐药,对ESCs敏感(FQ-R);(iii)对FQ敏感,对ESCs敏感(FQ-S)。测定了药敏谱、系统发育群、ST、ST131亚克隆和毒力基因型,并对时间趋势和变量间关联进行了统计学评估。从2000年到2006年,随着ESCs-RS和FQ-R菌株的出现,此类菌株中(与毒力相关的)B2系统发育群的流行率也急剧上升,这完全是由于ST131尤其是30的迅速出现。到2009年,30总体上成为主导谱系(22%),占所有单药和多药耐药的中位数为43%(环丙沙星为68%)。30的出现增加了耐药(尤其是FQ-R)分离株的净毒力基因含量,尽管历史上毒力较低的耐药群体扩大了约4倍,但总体毒力基因评分仍保持稳定。这些发现更精确地界定了30在美国出现的时间和速度,确定了其可能的原因,并暗示了潜在后果,包括更频繁和/或更具侵袭性的抗菌药物耐药感染。