Research on gonococcal resistance to antibiotics including new quinolone

耐抗生素淋球菌的流行：我们于2001年测定了福冈市208株淋病奈瑟菌的最低抑菌浓度。耐喹诺酮类(CPFX MIC≧1μg/m l)、青霉素耐药(PCG MIC≧2μg/m l)和四环素耐药(TC MIC≧2μg/m l)分别为64.4%、13.4%和13.9%。产青霉素酶淋球菌(PPNG)的感染率仅为1.4%。未发现对壮观霉素耐药(SPCM MIC≧128μg/ml)或对头孢克辛中等耐药(CFIX MIC≧0.5μg/ml)的菌株。然而，2001年MIC值为0.125~0.25MICg/ml的耐甲氧西林金黄色葡萄球菌的敏感度降低的患病率(23.6%)高于1995年至1996年的1.6%(P<0.05)。结果表明，2001年分离株对氟喹诺酮类药物的耐药率较高，对…的敏感性有所降低。II.头孢菌素类药物的耐药机制更接近：我们研究了染色体介导的对CFIX耐药的遗传机制。染色体介导的青霉素(一种β-内酰胺类抗生素)耐药淋球菌的部分原因是青霉素结合蛋白(PBPs)的改变和外膜通透性的降低。转化为高水平青霉素耐药性的第一步是由Pena基因介导的，Pena基因编码PBP2的改变形式。因此，我们分析了6株对CFIX中度耐药(CFIXMIC=0.5μg/ml)和3株敏感株(CFIXMIC；≦为0.001~0.004μg/ml)的Pena基因突变，用聚合酶链式反应和直接测序的方法检测了Pena基因转肽酶结构域的突变。所有6个对CFIX中等抗性的菌株都有相同的33个氨基酸替换，位于PBP2转肽酶结构域的323到480位。然而，3株敏感菌株的PBP2基因的同一区域没有发现单一的突变。我们的数据表明，PBP2的多重改变在头孢克新对淋病奈瑟菌的耐药性中起着重要作用。较少

I. Prevalence of antibiotic-resistant Neisseria gonorrhoeae : We determined the MIC for 208 N. gonorrhoeae isolates in 2001 in Fukuoka city. The prevalence rates of quinolone resistance (CPFX MIC≧1 μg/ml), penicillin resistance (PCG MIC≧2 μg/ml), and tetracycline resistance (TC MIC≧2 μg/ml) in those isolates were 64.4%, 13.4%, and 13.9%, respectively. The prevalence rate of penicillinase-producing N. gonorrhoeae (PPNG) was only 1.4% in those isolates. There were no isolates resistant to spectinomycin (SPCM MIC≧128 μg/ml) or intermediately resistant to cefixime (CFIX MIC≧0.5 μg/ml) in those isolates. However, the prevalence rate of reduced susceptibility to CFIX with MIC of 0.125 to 0.25 μg/ml was relatively higher (23.6%) in 2001 as compared with that (1.6%) in 1995-96. These results indicate that the prevalence rate of quinolone resistance in the isolates in 2001 was remarkably high and that the isolates in 2001 showed reduced susceptibility to CFIX.II. Mechanism of resistance to cefi … More xime : We examined the genetic mechanisms of chromosomally mediated resistance to CFIX. Chromosomally mediated penicillin (a variety of β-lactam antibiotics) resistance in N. gonorrhoeae occurs in part through alterations in penicillin-binding proteins (PBPs) and a decrease in outer membrane permeability. The first step in transformation to high-level penicillin resistance is mediated by the penA gene, which encodes altered forms of PBP2. Therefore, we analyzed mutations in the penA gene of the 6 gonococcal isolates intermediately resistant (CFIX MIC=0.5 μg/ml) and 3 susceptible (CFIX MIC; ≦0.001 to 0.004 μg/ml) to CFIX, PCR and direct DNA sequencing were performed to identify mutations in a region including the transpeptidase domain of the penA gene. All 6 isolates intermediately resistant to CFIX had same 33 amino acid substitutions through position 323 to 480 within the region of the transpeptidase domain of PBP2. However, no single alteration was identified in the same region of the PBP2 of the 3 susceptible isolates. Our data suggest that multiple alterations in PBP2 play an essential role in conferring cefixime resistance to N. gonorrhoeae. Less