[MEDSCAPE感染性疾病]：美國FDA建議氟喹諾酮不應作為一線用藥

Medscape Infectious Diseases>Auwaerter on Infectious DiseasesCOMMENTARYFluoroquinolones Not First Line: FDA Advisory Reinforces Standard Practice in Ambulatory CarePaul G. Auwaerter, MDJune02,2016

Hello. This is Paul Auwaerter, with Medscape Infectious Diseases and the Johns Hopkins University School of Medicine. The US Food and Drug Administration (FDA) recently announced^[1]that it will upgrade its package warnings on fluoroquinolones to include instructions that they should not be used for routine respiratory tract infections or uncomplicated urinary tract infections unless there is no suitable alternative agent.

你好，我是Medscape感染性疾病專欄以及Johns Hopkins大學醫學院的Paul Auwaerter。美國食品藥品監督管理局(FDA)近期宣布將更新氟喹諾酮類藥物的包裝警示，說明中包括氟喹諾酮類藥物不應用於常規呼吸道感染或非複雜性泌尿系感染的治療，除非沒有其他合適的替代藥物。

Why these warnings are being reinforced at this point rests on several foundational issues. When I was a medical student the late 1980s, fluoroquinolones were embraced as "wonder drugs." We had ciprofloxacin, which offered oral treatment forPseudomonas aeruginosaand was thought to be effective forStaphylococcus aureus, even in deep bone infections. Over time, these drugs have been widely embraced with new additions, such as levofloxacin and moxifloxacin. But a number of other drugs (eg, trovafloxacin, lomefloxacin, and others) have fallen to the wayside, deservedly, because of serious toxicities.

此時強調上述警示其實源於幾個重要問題。上個世紀80年代，當我還是一名醫學生時，氟喹諾酮被稱為神奇的藥物。當時我們有環丙沙星可供口服治療銅綠假單胞菌，同時對金黃色葡萄球菌感染有效，即使對於深部骨髓感染而言。隨著時間推移，這些藥物又不斷有新的成員加入，如左旋氧氟沙星和莫西沙星等。但是，很多其他藥物（如trovafloxacin，lomefloxacin及其他）因嚴重的毒性反應宣告失敗。

It seems to be true, however, that the fluoroquinolones remain broadly prescribed both by primary care practitioners and in hospital settings and skilled nursing facilities. Studies looking at the use of fluoroquinolones in ambulatory settings for uncomplicated urinary tract and respiratory infections show that over the past few years there has been little diminishment in the use of fluoroquinolones.^[2]Because of their wide use and adoption, we are experiencing problems such as pathogen resistance. The fluoroquinolones are no longer recommended for gonorrhea because of widespread resistance. They are no longer recommended for routine first-line treatment of uncomplicated cystitis because of increased resistance ofEscherichia colito this class of drugs.^[3]

然而，現實情況卻是家庭醫生以及醫院內和安養院處方氟喹諾酮的情況非常普遍。對於門診適用氟喹諾酮治療非複雜性泌尿系感染及呼吸道感染的研究發現，在過去數年間，氟喹諾酮的使用僅有輕度減少。由於氟喹諾酮的廣泛使用，我們目前面臨很多難題如抗生素耐葯。因為廣泛耐葯的緣故，不再推薦氟喹諾酮用於淋病的治療。由於大腸桿菌對氟喹諾酮的耐葯日益嚴重，因此也不再推薦氟喹諾酮作為非複雜性膀胱炎的常規一線治療藥物。

Another issue is that, over the years, the remaining fluoroquinolones have been associated with adverse effects, including increased risk forClostridium difficileinfection (compared with many other antibiotics), tendinopathy, arthropathy, QT prolongation, retinal issues, and central and peripheral nervous system toxicities.^[4]These adverse effects have been reported, although perhaps not thoroughly vetted through careful analysis. However, the FDA now feels that owing to potential irreversible or permanent side effects, these drugs should not be used for first-line treatment.

另一個問題是，過去數年發現，其他的氟喹諾酮類藥物伴隨很多不良反應，包括難辨梭狀芽孢桿菌感染（與很多其他抗生素相比）、肌腱病、關節病、QT間期延長、視網膜疾病以及中樞和周圍神經系統毒性的風險增加。儘管沒有經過系統的分析，但是這些不良反應時有報告。但是，FDA目前認為，由於上述不良反應可能無法逆轉或永久存在，這些藥物不應作為一線治療的選擇。

Many infectious diseases practitioners, out of concern about antibiotic resistance, have been broadly beating the drum for many years that these drugs should not be used in office settings and practices for mundane and pedestrian upper respiratory tract infections such as bronchitis or sinusitis, or for urinary tract infections.

除有關抗生素耐葯的顧慮外，多年來很多感染科醫生敲響了警鐘，認為這些藥物不應在門診使用，也不應用於普通的上呼吸道感染（如支氣管炎或鼻竇炎）或泌尿系感染。

So why are these drugs still so widely used? There is a perception (and perhaps a reality) that the fluoroquinolones are still quite safe. I have never seen a case of peripheral neuropathy although I have certainly seenC difficileinfection, tendinopathy, and arthropathy. Obviously as drugs are getting more attention and being looked at in terms of adverse effects, it does not make sense to prescribe these drugs, which have quite broad-spectrum activity, to treat conditions that could be treated with a narrower-spectrum and more targeted drug.

那麼，為什麼這些藥物仍然在廣泛使用呢？人們感覺到（可能也是事實）氟喹諾酮仍然非常安全。我從未看到周圍神經病變的病例，儘管我遇到過難辨梭狀芽孢桿菌感染、肌腱病和關節病。很顯然，隨著藥物的到更多關注，尤其在不良反應方面，我們不應將這些廣譜藥物用於治療那些本應使用窄譜藥物進行針對性治療的疾病。

The FDA is upgrading its warnings about these drugs in spite of what practitioners are seeing. The diminished use of these broad-spectrum antibiotics for certain conditions is a worthy goal and probably will benefit patient care, either by avoiding the use of antibiotics altogether if appropriate, or targeting antibiotics, as recommended in guidance on sinusitis, bronchitis, exacerbations of bronchitis, and urinary tract infections. Thanks very much for listening.

儘管臨床醫生可能有不同觀點，但是FDA更新了這些藥物的警示。對於某些疾病減少上述廣譜抗生素的使用可能是值得的，可能使得患者獲益，如避免使用抗生素，或使用針對性的抗生素治療，正如鼻竇炎、支氣管炎、支氣管炎加重及泌尿系感染的指南所推薦。

References

1. US Food and Drug Administration. Fluoroquinolone antibacterial drugs. Drug Safety Communication - FDA advises restricting use for certain uncomplicated infections. Posted May 12, 2016.http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm500665.htmAccessed May 15, 2016.

2. Lee GC, Reveles KR, Attridge RT, et al. Outpatient antibiotic prescribing in the United States: 2000 to 2010. BMC Med. 2014;12:96.

3. Kim M, Lloyd A, Condren M, Miller MJ. Beyond antibiotic selection: concordance with the IDSA guidelines for uncomplicated urinary tract infections. Infection. 2015;43:89-94.Abstract

4. Douros A, Grabowski K, Stahlmann R. Safety issues and drug-drug interactions with commonly used quinolones. Expert Opin Drug Metab Toxicol. 2015;11:25-39.Abstract

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