Pfaller Michael A, Jones Ronald N
CAST Laboratories, University of Iowa College of Medicine, Iowa City, Iowa, USA.
Diagn Microbiol Infect Dis. 2002 Sep;44(1):77-84. doi: 10.1016/s0732-8893(02)00446-7.
Recently FDA-approved fluoroquinolones like gatifloxacin possess enhanced activity against Gram-positive pathogens such as Streptococcus pneumoniae. However, experience with adverse events among previously used fluoroquinolones has led to expanded post-marketing investigations of clinical efficacy and safety. An open-label gatifloxacin trial was initiated in early 2000, using 2795 (>15000 enrolled cases) primary care providers for treatment of community-acquired respiratory tract infections (CARTI) such as community-acquired pneumonia (CAP), acute bacterial exacerbation of chronic bronchitis (ABECB), acute sinusitis. Microbiology specimens and sputum slides were referred to a reference laboratory, pathogens identified and reference antimicrobial susceptibility tests performed. Results were classified by infection site, geographic census region and patient profile/demographics. The most frequent pathogens were: for CAP (n = 384)-S. pneumoniae (37%) > Hemophilus influenzae (31%) > Moraxella catarrhalis (13%); for ABECB (528)-H. influenzae (37%) > M. catarrhalis (26%) > S. pneumoniae (17%); and for sinusitis (2691)-M. catarrhalis (29%) > H. influenzae (24%) > S. pneumoniae (17%). H. parainfluenzae (ABECB) and S. aureus (sinusitis) were also commonly isolated. CAP S. pneumoniae isolates had significantly less high-level resistance (5% at > or =2 micro g/ml) than those isolates from ABECB or sinusitis (13-15%). United States census zone differences in S. pneumoniae resistance were identified (greatest in West or East South Central, South Atlantic). S. pneumoniae macrolide resistance was high (23-33%) and H. influenzae clarithromycin susceptibility was only 56-62%. beta-lactamase rates in H. influenzae and M. catarrhalis were 21-29% and 88-92%, respectively. Only one S. pneumoniae was not susceptible to gatifloxacin, and this new fluoroquinolone was fourfold more potent than levofloxacin (MIC(50,) 0.25 vs. 1 micro g/ml). This Phase IV surveillance trial (TeqCES) confirmed the clinical importance of S. pneumoniae, H. influenzae and M. catarrhalis in CARTI, and high fluoroquinolone potency/spectrum (>97% susceptible). beta-lactams and macrolides continue to be compromised by increasing resistances in pathogens isolated in these monitored primary care settings.
最近美国食品药品监督管理局（FDA）批准的氟喹诺酮类药物，如加替沙星，对革兰氏阳性病原体（如肺炎链球菌）具有更强的活性。然而，以往使用氟喹诺酮类药物时出现的不良事件经历，促使对其临床疗效和安全性展开了更广泛的上市后调查。2000年初启动了一项加替沙星开放标签试验，利用2795名（超过15000名登记病例）初级保健提供者治疗社区获得性呼吸道感染（CARTI），如社区获得性肺炎（CAP）、慢性支气管炎急性细菌性加重（ABECB）、急性鼻窦炎。微生物标本和痰涂片被送往一家参考实验室，鉴定病原体并进行参考抗菌药敏试验。结果按感染部位、地理普查区域和患者概况/人口统计学进行分类。最常见的病原体为：对于CAP（n = 384）——肺炎链球菌（37%）>流感嗜血杆菌（31%）>卡他莫拉菌（13%）；对于ABECB（528）——流感嗜血杆菌（37%）>卡他莫拉菌（26%）>肺炎链球菌（17%）；对于鼻窦炎（2691）——卡他莫拉菌（29%）>流感嗜血杆菌（24%）>肺炎链球菌（17%）。副流感嗜血杆菌（ABECB）和金黄色葡萄球菌（鼻窦炎）也经常被分离出来。CAP中肺炎链球菌分离株的高水平耐药性（≥2μg/ml时为5%）明显低于ABECB或鼻窦炎分离株（13 - 15%）。发现美国人口普查区域在肺炎链球菌耐药性方面存在差异（西部或东中南部、南大西洋地区最高）。肺炎链球菌对肺炎链球菌对大环内酯类药物的耐药性较高（23 - 33%），流感嗜血杆菌对克拉霉素的敏感性仅为56 - 62%。流感嗜血杆菌和卡他莫拉菌的β-内酰胺酶发生率分别为21 - 29%和88 - 92%。只有一株肺炎链球菌对加替沙星不敏感，这种新型氟喹诺酮类药物的效力是左氧氟沙星的四倍（MIC50，0.25对1μg/ml）。这项IV期监测试验（TeqCES）证实了肺炎链球菌、流感嗜血杆菌和卡他莫拉菌在CARTI中的临床重要性，以及氟喹诺酮类药物的高效力/广谱性（>97%敏感）。在这些受监测的初级保健机构中分离出的病原体耐药性不断增加，继续对β-内酰胺类药物和大环内酯类药物造成影响。
