Davies Todd A, Yee Y Cheung, Goldschmidt Raul, Sahm Daniel F, Evangelista Alan T
Johnson and Johnson Pharmaceutical Research and Development LLC, Raritan, NJ 08869, USA.
Postgrad Med. 2008 Sep;120(3 Suppl 1):39-45. doi: 10.3810/pgm.2008.09.suppl52.283.
Fluoroquinolone-resistant variants of pandemic clones Spain(23F)-1, Spain(6B)-2, Spain(9V)-3, and Spain(14)-5 have been seen in various regions of the United States and the world, leading to the speculation that fluoroquinolone resistance among US Streptococcus pneumoniae may increase because of clonal spread. Using levofloxacin as a representative of the fluoroquinolone class, all 196 levofloxacin-resistant pneumococci from a total of 22 794 isolates in the Tracking Resistance in the United States Today (TRUST) 5-8 studies (2001-2004) were subjected to pulsed-field gel electrophoresis (PFGE), serotyping, and sequencing of parC/E and gyrA/B quinolone resistance-determining regions (QRDR) to measure the extent of clonality. In addition, susceptibility testing of these isolates to ciprofloxacin, gatifloxacin, levofloxacin, and moxifloxacin was performed. ATCC type strains of Spain(23F)-1, Spain(6B)-2, Spain(9V)-3, and Spain(14)-5 clones were included as comparators. Levofloxacin-resistant isolates with Spain(23F)-1-related PFGE patterns decreased from 28% of the resistant isolates in 2001 to 6% in 2004. These isolates, with serotypes 23F (n = 17), 19F (n = 17), or 19A (n = 1), had 15 different QRDR profiles and were all ciprofloxacin- and gatifloxacin-resistant. Levofloxacin-resistant isolates with Spain(9V)-3-related PFGE patterns decreased from 13% of the resistant isolates in 2001 to 2% in 2004. The Spain(9V)-3-related isolates were serotype 9V (n = 9), 9A (n = 2), and 9N (n = 1) and exhibited 6 different QRDR profiles. All were resistant to all fluoroquinolones tested. None of the levofloxacin-resistant isolates had PFGE patterns related to Spain(6B)-2 or Spain(14)-5. Resistance to respiratory fluoroquinolones among pneumococci has remained constant at about 1% (0.8%-1.1%) since 2001, and there has been a decrease in the prevalence of levofloxacin-resistant isolates similar to Spain(23F)-1 or Spain(9V)-3. Considerable QRDR variability among these strains appears to be the result of sporadic independent mutational events as opposed to clonal expansion.
在美国和世界的不同地区已发现大流行克隆株西班牙(23F)-1、西班牙(6B)-2、西班牙(9V)-3和西班牙(14)-5的耐氟喹诺酮变异株,这引发了一种推测,即美国肺炎链球菌中的氟喹诺酮耐药性可能因克隆传播而增加。以左氧氟沙星作为氟喹诺酮类的代表,对来自“今日美国耐药性追踪”(TRUST)5 - 8项研究(2001 - 2004年)中总共22794株分离菌的196株耐左氧氟沙星肺炎球菌进行了脉冲场凝胶电泳(PFGE)、血清分型以及parC/E和gyrA/B喹诺酮耐药决定区(QRDR)的测序,以测定克隆性程度。此外,还对这些分离菌进行了对环丙沙星、加替沙星、左氧氟沙星和莫西沙星的药敏试验。将西班牙(23F)-1、西班牙(6B)-2、西班牙(9V)-3和西班牙(14)-5克隆株的美国典型培养物保藏中心(ATCC)标准菌株作为对照。具有西班牙(23F)-1相关PFGE图谱的耐左氧氟沙星分离株从2001年耐药分离株的28%降至2004年的6%。这些分离菌,血清型为23F(n = 17)、19F(n = 17)或19A(n = 1),有15种不同的QRDR图谱,并且对环丙沙星和加替沙星均耐药。具有西班牙(9V)-3相关PFGE图谱的耐左氧氟沙星分离株从2001年耐药分离株的13%降至2004年的2%。与西班牙(9V)-3相关的分离菌血清型为9V(n = 9)、9A(n = 2)和9N(n = 1),并呈现出6种不同的QRDR图谱。所有这些分离菌对所有测试的氟喹诺酮类药物均耐药。没有耐左氧氟沙星分离株具有与西班牙(6B)-2或西班牙(14)-5相关的PFGE图谱。自2001年以来,肺炎球菌对呼吸喹诺酮类药物的耐药率一直保持在约1%(0.8% - 1.1%),并且与西班牙(23F)-1或西班牙(9V)-3相似的耐左氧氟沙星分离株的流行率有所下降。这些菌株中相当大的QRDR变异性似乎是零星独立突变事件的结果,而非克隆扩增。