Saturday, March 31, 2012

Sinusitis - FDA vs. Physicians

The Infectious Diseases Society of America just released updated guidelines for the treatment of acute bacterial sinusitis in adults and children.  The IDSA recommends antibiotic treatment for patients where bacterial infections are more likely -

1. The following clinical presentations (any of 3) are recommended for identifying patients with acute bacterial vs viral rhinosinusitis:
            i. Onset with persistent symptoms or signs compatible with acute rhinosinusitis, lasting for ≥10 days without any evidence of clinical improvement (strong, low-moderate);
            ii. Onset with severe symptoms or signs of high fever (≥39°C [102°F]) and purulent nasal discharge or facial pain lasting for at least 3–4 consecutive days at the beginning of illness (strong, low-moderate); or
                        iii. Onset with worsening symptoms or signs characterized by the new onset of fever, headache, or increase in nasal discharge following a typical viral upper respiratory infection (URI) that lasted 5–6 days and were initially improving (“double-sickening”) (strong, low-moderate).

This is because only bacterial infections will respond to antibiotic therapy – viral infections will not.

The FDA, in 2003, decided that this was a self-limited disease for which there was no evidence of a benefit for antibiotic treatment. So – who do you trust – the FDA or infectious diseases specialists?

Two recent studies examined this question.  Both enrolled patients with signs and symptoms of sinusitis.  Half the patients received placebo (sugar pill) and half received antibiotics. One was carried out in children and the antibiotic was amoxicillin-clavulanate (active against certain resistant strains of bacteria).  The other studied adults and the antibiotic was amoxicillin – not active against certain resistant strains. The study in children found that the cure rate among antibiotic treated patients was 50% compared to 14% among those receiving placebo.  At the same time, only 14% of those receiving antibiotics failed therapy while 68% of placebo recipients failed.  The study of adults using amoxicillin showed no difference between amoxicillin and placebo.  How could two similar studies come up with opposite results? Well – the most likely answer is that the study of adults was seriously flawed.  First, the study only enrolled patients with severe symptoms early in the course of disease.  But the guidelines have always suggested that patients with prolonged symptoms – 10 days or more and those that have had relapsing symptoms where they first started to get better then got worse again were good candidates for acute bacterial sinusitis that might benefit from antibiotics. The second flaw is that the study used amoxicillin that is not active against many resistant strains of bacteria that commonly cause sinusitis.  In fact the new IDSA guidelines call for using amoxicillin-clavulanate as was used in the pediatric study where a clear benefit was identified.

But, in fact, the FDA and the EMA now both require placebo-controlled trials for the approval of any new antibiotic for the treatment of acute bacterial sinusitis (see our Lancet ID article from 2008).  Imagine the scenario.  You have fever, you have been sick for 10 days already, you have facial pain and you finally drag yourself to the emergency room.  The doctor, when they finally get around to actually seeing you, offers you the possibility of participating in this exciting new clinical trial where you have a 50% chance of getting either a new antibiotic active against resistant bacterial pathogens or an equal chance of getting an identical sugar pill.  What would your choice be?  So, as it stands now, because of this requirement, trust me, no new antibiotics will ever be approved for sinusitis.  Is that a good thing?  I’ll leave that up to you. 
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  1. The hospital is becoming a dangerous place to spend time and gives real headache to physicians. Wish to get to know more about these and share it to my medical student friends.

  2. Is the best thank ya for your information...