New-variant Creutzfeldt-Jakob disease and treatment of haemophilia
New-variant Creutzfeldt-Jakob disease and treatment of haemophilia
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新变种克雅氏病与血友病的治疗
DOI：
10.1016/s0140-6736(05)79357-0
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
C. Ludlam
中科院分区：
文献类型：
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作者：
C. Ludlam
先生-我们和默多克及其同事一样担心耐喹诺酮类伤寒沙门氏菌在亚洲的传播。伤寒多年来一直在越南流行，是进入胡志明市热带疾病中心(CTD)的常见原因，CTD是该国南部的传染病转诊中心。2本中心80%的S伤寒分离株对氯霉素、氨苄西林、甲氧嘧啶(复方新诺明)具有质粒介导的耐药性。在过去的5年里，我们观察到耐喹诺酮类伤寒的发病率稳步上升。这些菌株对氧氟沙星的MIC90为0.5 mg/L(90%的菌株生长抑制浓度)，而敏感菌株的MIC90为0.06 mg/L。尽管纸片敏感性试验显示它们对氟喹诺酮类药物仍然敏感(尽管区带尺寸缩小)，但它们在临床上是耐药的。退烧时间延长，治愈率仅为50%，而敏感菌株的治愈率超过97%。3耐喹诺酮类S斑疹伤寒杆菌对奈立地酸耐药(MIC90128 mg/L)。CTD对喹诺酮类药物耐药的S伤寒杆菌比例从1993年的4%(10/246)缓慢上升至1997年前9个月的12%(27/228)。在过去的4个月里，76%(161/213)的S伤寒血液培养分离株对奈立地酸(即喹诺酮类)耐药。新分离株对氧氟沙星(MIC90.1 mg/L)和环丙沙星(MIC90.05 mg/L)的MIC值均显著高于过去4年的耐奈立克酸的菌株。这些耐药菌株对头孢曲松、头孢克新和阿奇霉素敏感，但临床对这些药物的反应缓慢(退烧需要7天或更长时间)，失败率可能超过20%。4、5越南和塔吉克斯坦的这些耐喹诺酮类伤寒疫情突显了伤寒抗生素治疗面临的迫在眉睫的危机，因为耐药感染需要昂贵的治疗，而这些治疗效果较差，且与较高的粪便携带率相关，因此比对喹诺酮敏感的感染具有更大的传播潜力。大剂量的长疗程氟喹诺酮类药物可能在临床上有效，但这会增加治疗成本，并重申对儿童使用氟喹诺酮类药物的担忧。在持续的选择压力下，可能很快就会出现完全的氟喹诺酮耐药。在越南，氟喹诺酮治疗奈立克酸敏感型伤寒的费用为6-10美元。治疗耐氟喹诺酮菌株的费用为28-42美元，阿奇霉素35-50美元，口服头孢菌素80-90美元，非肠道头孢菌素150-200美元。伤寒流行地区的患者可能负担不起治疗费用，因此迫切需要对新的负担得起的耐药菌株方案进行临床评估。
SIR—We share the worries of DA Murdoch and colleagues (Jan 31, p 339) 1 about the spread of quinoloneresistant Salmonella typhi in Asia. Typhoid fever has been endemic in Vietnam for many years and is a common cause of admission to the Centre for Tropical Diseases (CTD) in Ho Chi Minh City, an infectious disease referral centre for the south of the country. 2 80% of blood culture isolates of S typhi at this centre carry plasmidmediated resistance to chloramphenicol, ampicillin, and trimethoprimsulphamethoxazole (co-trimoxazole). Over the past 5 years we have observed a steady increase in the incidence of quinolone-resistant typhoid fever. These isolates have an ofloxacin MIC90 of 0· 5 mg/L (the concentration inhibiting growth in 90% of isolates) compared with 0· 06 mg/L in sensitive isolates. Although they still appear sensitive to fluoroquinolones by disc sensitivity testing (albeit with reduced zone sizes) they are clinically resistant. Time to fever clearance is prolonged and cure rates are only 50% compared with over 97% for sensitive strains. 3 These quinolone-resistant S typhi are characterised by resistance to nalidixic acid (MIC90 128 mg/L). The proportion of quinolone-resistant S typhi at CTD increased slowly from 4%(10/246) in 1993 to 12%(27/228) in the first 9 months of 1997. Since then there has been an alarming increase; over the past 4 months 76%(161/213) of blood culture isolates of S typhi were nalidixic acid (ie, quinolone) resistant. The MICs of these recent isolates to ofloxacin (MIC90 1· 0 mg/L) and ciprofloxacin (MIC900· 5 mg/L) were significantly higher than that for the nalidixic-acid-resistant isolates seen in the previous 4 years. These resistant strains are sensitive to ceftriaxone, cefixime, and azithromycin, but clinical response to these drugs is slow (fever clearance takes 7 days or more) and failure rates can be over 20%. 4, 5 These epidemics of quinoloneresistant typhoid fever in Vietnam and Tajikistan1 highlight an approaching crisis in the antibiotic therapy of typhoid fever since resistant infections require expensive treatments which are less effective and associated with higher stool carriage rates, and thus greater transmission potential than quinolonesensitive infections. Long courses of fluoroquinolones at a high dose may be clinically effective, but this would increase the cost of treatment and reassert worries about fluoroquinolone use in children. Full fluoroquinolone resistance is likely to appear soon, under continued selection pressure.Fluoroquinolone treatment of nalidixic-acid-sensitive typhoid fever in Vietnam costs $ US6–10. To treat quinolone-resistant strains a prolonged course of fluoroquinolone would cost $28–42, azithromycin $35–50, oral cephalosporins $80–90, and parenteral cephalosporins $150–200. Treatment may become unaffordable for patients in typhoid endemic areas and the clinical evaluation of new affordable regimens for resistant strains is pressing.