美国FDA调整青霉素对肺炎链球菌折点

木瓜

size=3]Penicillin’s Back: FDA Raises Breakpoints for S. pneumoniae Pneumonia
青霉素又回来了！美国FDA提高了青霉素对肺炎链球菌的折点，CLSI于去年6月接受了这个调整，新的CLSI文件于2008年1月发布，不知何时能到手噢！
Penicillin, one of the safest and most effective drugs for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae, is back in the armamentarium following action by the Food and Drug Administration (FDA) and pressure from IDSA and several key members.
FDA has raised the concentration at which S. pneumoniae is considered susceptible to penicillin, according to an amended package insert for Baxter Healthcare Corporation’s penicillin G approved by FDA and obtained by IDSA. The breakpoint changes are:

	Minimum Inhibitory Concentration (MIC) (mcg/mL)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Updated	≤2	4	≥8
Previous	≤0.06	0.12-1.0	≥2

The susceptible breakpoint for meningitis caused by S. pneumoniae remains unchanged (0.06 mcg/mL). The package insert is available online from FDA’s website.
Evidence has been mounting for years that penicillin is effective against pneumococcal pneumonia at concentrations that would fail for meningitis or otitis media. Victor L. Yu, MD, FIDSA, co-authored one significant study in Clinical Infectious Diseases in 2003 looking at patients with pneumococcal bacteremia who were initially treated with penicillin before laboratory tests came back resistant. “It turned out they uniformly did fine,” Dr. Yu said. The study won IDSA’s Emmanuel Wolinsky Award in 2003. Since then, several other studies have been published showing penicillin is effective against pneumococcal pneumonia at concentrations that would fail for other diseases.
IDSA strongly supported legislation passed last fall that requires FDA to update antimicrobial breakpoints. The Clinical and Laboratory Standards Institute (CLSI) adopted the revised breakpoints in June 2007 and published them in January 2008.  CLSI also supported a citizens’ petition written by Dr. Yu and others urging FDA to raise the penicillin breakpoints by submitting two “citizens petitions” of its own. Dr. Yu learned this month that FDA had signed an approval letter for Baxter’s amended package insert on March 1. “This was a case where FDA acted expeditiously,” Dr. Yu said.
Although a formal response from the FDA to Dr. Yu’s group and CLSI has not yet been received and the package inserts of other generic penicillins have not yet been changed, “the implication of the FDA’s action is that all of the package inserts for generic penicillins should be changed and that microbiology laboratories and clinicians should feel comfortable using the revised breakpoints to guide therapy for pneumococcal infections,” said Melvin P. Weinstein, MD, FIDSA, IDSA’s liaison to CLSI.
This is good news, Dr. Yu said, because now that quinolones have become the standard therapy for community-acquired pneumonia, reports of quinolone failures are on the rise. “You use it and you lose it,” he said.
“People laughed at me when I said I would bring back penicillin,” Dr. Yu said. But, he added, it will take some time and some effort for penicillin to really make a comeback. As empiric therapy has taken over, he said, clinicians and laboratories have lost the skills and the tools to diagnose the causes of CAP. “If anyone should be delighted, it should be infectious diseases specialists, because the skill of making a diagnosis returns. But because the practice of giving empiric therapy without thinking has become so inculcated in the last seven years, I think it’s going to take publicity to go back to what we were so good at.”

hxwsw

霉素又回来了！美国FDA提高了青霉素对肺炎链球菌的折点，CLSI于去年6月接受了这个调整，新的CLSI文件于2008年1月发布，不知何时能
微生物之家论坛已有老师提供2008版的CLSI，欢迎去下载！

巴斯德之徒

该标准分成了三部分：非脑膜炎来源标本、脑膜炎标本、以及口服青霉素分别有不同解释标准。

野渡无人

中文版估计5月底将会面世。到时第一时间上传！:lol

薇荷

原帖由 野渡无人 于 2008-5-3 23:02 发表

                               
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中文版估计5月底将会面世。到时第一时间上传！:lol

往年都是孙长贵老师翻译,不知今年他还有没有时间.他太忙了.

野渡无人

估计五月底吧！:lol

fyk8595

期待着！先谢过！:ketou :ketou

gjs661

青霉素对肺炎链球菌的折点调整以后，青霉素、阿莫西林等对于肺炎链球菌肺炎的疗效如何？
我指的是原来判断为中介现在判断敏感，原来判断耐药现在判断中介的菌株。
:favav 急切想知道！谢谢！

[ 本帖最后由 gjs661 于 2009-2-6 22:47 编辑 ]

巴斯德之徒

与细菌对药物的敏感性无关，只是说我们对于自然科学的认识又进步一点而已。更新后，我们发出错误报告的几率就降低了。
    需要清楚的是，即是现在最权威的CLSI也不能保证所有规则都是完全科学和可靠的，所以才会每年更新。每更新一次，我们就越接近临床真实情况一步。
    更应该清楚的是，我们的报告几乎随时都存在错误，有些通过现有的质量控制措施是可以避免的，而有些是随着研究的深入和认识的加深慢慢减少的。

gjs661

巴版的回复看了好几遍没大理解——“发出错误报告的几率降低”。
这种错误与正确如果不是与治疗效果判断，是以什么判断？

巴斯德之徒

肺炎球菌对青霉素的敏感性分布在一定地域范围内，一定时期内是相对恒定的，呈典型的正态分布。大多数菌株的MIC均分布在中位值附近，与采用什么标准去判断它在人体的敏感性无关。但随着时间的迁移中位值会发生变迁，此时就需要调节判断折点了。否则很容易出现错误结果，把耐药的判断为敏感。所以CLSI将折点调高了。
由于引起肺部感染和脑膜炎的情况并不相同，口服和静滴液不相同，存在PK-PD上的不同，所以要区别对待。这样修改是基于大量的实验室与临床的研究而逐步完善的。在标准没有完善前采用有瑕疵的标准出的报告肯定比现在的错误率要高——所以说，标准修改后发出与临床不符合报告的可能性就自然降低了。