Yamaguchi Keizo, Ohno Akira, Ishii Yoshikazu, Tateda Kazuhiro, Iwata Morihiro
Department of Advanced and Integrated Analysis of Infectious Diseases, Toho University School of Medicine.
Jpn J Antibiot. 2012 Jun;65(3):181-206.
Postmarketing surveillance of levofloxacin (LVFX) has been conducted continuously since 1992. The present survey was performed to investigate in vitro susceptibility of recent clinical isolates in Japan to 30 selected antibacterial agents, focusing on fluoroquinolones (FQs). The common respiratory pathogens Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae continue to show a high susceptibility to FQs. In contrast, widely-prevailing resistance to macrolides was markedly noted among S pneumoniae and S. pyogenes. Regarding H. influenzae, the prevalence of beta-lactamase-negative ampicillin-resistant isolates has been increasing year by year (25.8% in 2002, 40.0% in 2004, 50.1% in 2007, and 57.9% in 2010). Enterobacteriaceae showed high susceptibility to FQs, however, prevalence of LVFX-resistant Escherichia coli, including intermediate resistance, was 29.3%, showing an increase over time. Nevertheless, the increase in the prevalence of LVFX-resistant E. coli isolates has slowed since 2007 (8.2% in 2000, 11.8% in 2002, 18.8% in 2004, 26.2% in 2007, and 29.3% in 2010), suggesting the influence of LVFX 500 mg tablets since its approval in 2009. Another Enterobacteriaceae member, Klebsiella pneumoniae, showed low resistance to FQs, in contrast with E. coli. In methicillin-resistant Staphylococcus aureus (MRSA), the percentage of FQ-susceptible isolates was low, at 51.6% for susceptibility to sitafloxacin, and at only around 10% for susceptibility to other FQs. However, methicillin-susceptible S. aureus (MSSA) isolates were highly susceptible to FQs, with the percentage ranging from 88.5% to 99.1%. The prevalence of FQs-resistant isolates in methicillin-resistant coagulase-negative staphylococci was higher than that in methicillin-susceptible coagulase-negative staphylococci, although it was lower than the prevalence of FQ-resistance in MRSA. The prevalence of FQs-resistant Pseudomonas aeruginosa isolates derived from urinary tract infections (UTIs) was 15.4-21.3%, higher than the prevalence of 6.1-12.3% in P. aeruginosa isolates from respiratory tract infections (RTIs). While this trend was consistent with the results of previous surveillance, gradual decreases were noted in the prevalence of FQ-resistant P. aeruginosa isolates derived from UTIs. The prevalence of multidrug-resistant P. aeruginosa was 2.3% among isolates derived from UTIs and 0.3% among isolates from RTIs, a decrease from the results of 2007. Acinetobacter spp. showed high susceptibility to FQs. Imipenem-resistant Acinetobacter baumannii, which is currently an emerging issue, was detected at a prevalence of 2.4% (13 isolates). Neisseria gonorrhoeae showed a high resistance of 81.3-82.5%, to FQs. Ceftriaxone (CTRX) continued to show 100% susceptibility until 2007, but the present survey revealed the advent of resistance to CTRX in some clinical isolates. The result of the present survey indicated that although methicillin-resistant staphylococci, Enterococcus faecium, P. aeruginosa from UTIs, N. gonorrhoeae, and E. coli showed resistance of about 20% or more (19.5-89.2%) against the FQs which have been used clinically for over 17 years, the trends observed were similar to the results of previous surveillance. While FQ resistance has been prevailing in E. coli, E. coli still shows more than 70% susceptibility to FQs. The other bacterial species maintained high susceptibility rates of greater than 80%, against FQs.
自1992年以来，一直在持续开展左氧氟沙星（LVFX）的上市后监测。本次调查旨在研究日本近期临床分离株对30种选定抗菌药物的体外敏感性，重点关注氟喹诺酮类（FQs）。常见呼吸道病原体化脓性链球菌、肺炎链球菌、卡他莫拉菌和流感嗜血杆菌对FQs仍表现出高敏感性。相比之下，在肺炎链球菌和化脓性链球菌中，对大环内酯类药物的广泛耐药性明显可见。关于流感嗜血杆菌，β-内酰胺酶阴性氨苄西林耐药菌株的流行率逐年上升（2002年为25.8%，2004年为40.0%，2007年为50.1%，2010年为57.9%）。肠杆菌科对FQs表现出高敏感性，然而，包括中介耐药在内的耐LVFX大肠埃希菌的流行率为29.3%，呈随时间上升趋势。尽管如此，自2007年以来，耐LVFX大肠埃希菌分离株流行率的上升已放缓（2000年为8.2%，2002年为11.8%，2004年为18.8%，2007年为26.2%，2010年为29.3%），这表明自2009年LVFX 500mg片剂获批以来的影响。肠杆菌科的另一个成员肺炎克雷伯菌与大肠埃希菌相比，对FQs的耐药性较低。在耐甲氧西林金黄色葡萄球菌（MRSA）中，对FQs敏感的分离株比例较低，对司帕沙星的敏感性为51.6%，对其他FQs的敏感性仅约为10%。然而，甲氧西林敏感金黄色葡萄球菌（MSSA）分离株对FQs高度敏感，比例范围为88.5%至99.1%。耐甲氧西林凝固酶阴性葡萄球菌中FQs耐药分离株的流行率高于甲氧西林敏感凝固酶阴性葡萄球菌，尽管低于MRSA中FQs耐药的流行率。源自尿路感染（UTIs）的铜绿假单胞菌FQs耐药分离株的流行率为15.4 - 21.3%，高于呼吸道感染（RTIs）来源的铜绿假单胞菌分离株6.1 - 12.3%的流行率。虽然这一趋势与以往监测结果一致，但源自UTIs的FQs耐药铜绿假单胞菌分离株的流行率逐渐下降。UTIs来源的分离株中多重耐药铜绿假单胞菌的流行率为2.3%，RTIs来源的分离株中为0.3%，较2007年的结果有所下降。不动杆菌属对FQs表现出高敏感性。目前一个新出现问题的耐亚胺培南鲍曼不动杆菌的检出率为2.4%（13株）。淋病奈瑟菌对FQs表现出81.3 - 82.5%的高耐药率。头孢曲松（CTRX）直到2007年仍保持100%的敏感性，但本次调查显示在一些临床分离株中出现了对CTRX的耐药性。本次调查结果表明，尽管耐甲氧西林葡萄球菌、粪肠球菌、UTIs来源的铜绿假单胞菌、淋病奈瑟菌和大肠埃希菌对已临床使用超过17年的FQs表现出约20%或更高（19.5 - 89.2%）的耐药性，但观察到的趋势与以往监测结果相似。虽然大肠埃希菌中FQs耐药情况普遍，但大肠埃希菌对FQs仍表现出超过70%的敏感性。其他细菌物种对FQs保持大于80%的高敏感率。
