#20 Evidence Based Pearls for Respiratory Tract Infections

Dr. Daniel Aronov

This episode is a live broadcast from a lecture given at the Royal Australian College of General Practitioners conference. It is a collection of my favourite evidence-based clinical pearls for the most common presentation in primary care: respiratory tract infections. We’ll cover antibiotics for otitis media, sore throat and bronchitis, steroids for sore throat, Tamiflu, treatments for cough and a few other random things in between.
To watch this talk with the slides head on over to my YouTube channel (and subscribe while you’re there ;-p): www.youtube.com/drdanMD

References:

  • Ebell, M., et al., How Long Does a Cough Last? Comparing Patients’ Expectations With Data From a Systematic Review of the Literature. Annals of Family Medicine  Feb 2013
  • Thompson M, Vodicka TA, Blair PS, et al, for the TARGET Programme Team. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ 2013;347:f2027
  • Smith SM,, Fahey T,, Smucny J,, Becker LA.. Antibiotics for acute bronchitis.. Cochrane Database of Systematic Reviews 2014,, Issue 3.. Art.. No..:: CD000245.. DOI:: 10.1002//114651858..
  • Paul;, et al., Effect of honey, dextromethorphan (robitussin), and no treatment on nocturnal cough and sleep quality for coughing children and their parents., Arch Pediiatric Adolescent Medicine 2007
  • Shadkam, et al., A Comparison of the Effect of Honey, Dextromethorphan, and Diphenhydramine on Nightly Cough and Sleep Quality in Children and Their Parents. Journal of Alternative Complementary Medicine, 2010.
  • Cohen., et al. Effect of honey on nocturnal cough and sleep quality: a double blind, randomized, placebo-controlled study. Pediatrics 2012
  • Paul, et al. Vapor Rub, Petrolatum, and No Treatment for children with nocturnal cough and cold symptoms. Pediatrics Nov 2010
  • Centor, et al. The diagnosis of strep throat in adults in the emergency room. Medical Decision Making., 1981
  • Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD000023. DOI: 10.1002/14651858.CD000023.pub4.
  • Hayward G, Thompson MJ, Perera R, Glasziou PP, Del Mar CB, Heneghan CJ. Corticosteroids as standalone or add-on treatment for sore throat. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No.: CD008268. DOI: 10.1002/14651858.CD008268.pub2.
  • https://www.theguardian.com/business/2014/apr/10/tamiflu-saga-drug-trials-big-pharma
  • Vergison, et al., Otitis media and its consequences: beyond the earache. Lancet 2010
  • Venekamp RP, Sanders SL, Glasziou PP, Del Mar CB, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database of Systematic Reviews 2015, Issue 6. Art. No.: CD000219. DOI: 10.1002/14651858.CD000219.pub4.

#11 Antibiotics for Otitis Media with Paul Glasziou

Otitis media, or middle ear infection, is a very common issue. It is the second most common reason for a child to see a GP and is the most common reason antibiotics are prescribed to children. According to a large Australian database called the BEACH data, 80% of kids with otitis media are prescribed an antibiotic.

The dilemma

A study was published in the NEJM in December of 2016 by Hoberman, et al.,  that compared 10 days of amoxycillin/clavulanate to 5 days for treating kids with acute otitis media. They randomised 520 kids between the ages of 6 and 23 months and this was a very well designed trial. They found that 10 days was far superior to 5 days – Clinical failure occurred in 34% of those getting 5 days of antibiotics versus 16% in those getting 10 days. This makes a number needed to treat of 6 – so one in every six kids will avoid clinical failure if they are treated with 10 days of antibiotics versus 5 days. This paper got a lot of press – “should we be treating otitis media with antibiotics again?”, “Did we get it wrong with the recommendation that we shouldn’t treat?, “Should we change the guidelines to recommend 10 days of antibiotic use?”

But this is weird! because when you compare antibiotics to placebo, the benefit is nowhere near as good.  So comparing antibiotics to less antibiotics was way better than comparing antibiotics to no antibiotics! How does this make sense. To put it more starkly, the exact same research team that did this study, did a different study in 2011, also published in the NEJM, where they compared 10 days of amoxycillin/clavulanate to placebo. And here there was no difference. So the same team of researchers with almost identical study design on the one hand showed that 10 days of antibiotics doesn’t work, yet on the other hand showed that 10 days of antibiotics is better than 5 days! Whats going on here?

The answer lies in a wonderfully written opinion article published in the BMJ by Paul Glasziou entitled: “How to hide trial results in plain sight”

But before going into that, let’s first cover the previous evidence on treating otitis media with antibiotics

Cochrane Review

A Cochrane review on antibiotics for otitis media was done in 2015 which found 13 randomised controlled trials that were of a low risk of bias making a total of 3,400 children with otitis media. These studies compared antibiotics versus placebo.

They looked at a heap of outcomes but the main ones are:

  • There was a reduction in symptoms at 2-3 days in those who took antibiotics. 84% of children had improved by 2-3 days in the placebo group versus 89% in those who took antibiotics. So antibiotics increase the chance of recovery by 5% making a number needed to treat of 20.
  • There was no difference in hearing loss, no difference in suppurative complications like meningitis or mastoiditis.
  • There was a reduction in ear drum perforations – this went from 5% in the placebo group to 2% in the antibiotic group.
  • And in terms of adverse events, the number needed to harm for vomiting, diarrhoea or rash was 14 in those taking the antibiotic.

The Answer

Almost every other study had used the child’s symptoms as their primary outcome, including the Cochrane review and even including the 2011 Hoberman study that compared 10 days of amoxycillin/clavulanate to placebo. This is the AOM-SOS score or the Acute Otitis Media Severity Of Symptoms Scale. This scale assesses things that parents and children really care about: Ear pain, ear tugging, irritability, decreased play, eating less and fever.  The 2016 Hoberman study that compared 10 days to 5 days of amoxycillin/clavulanate used a different primary outcome. Their primary outcome was any of these three things:

  • If they still had otoscopic signs of infection
  • If they did not have a complete or nearly complete resolution of signs and symptoms by the end of treatment
  • Worsening infection

There are three problems with this outcome:

  1. Who cares about how the ear looks otoscopically? This is a disease oriented outcome rather than a patient oriented outcome. As a parent I care if my child is eating, if they’re not in pain and if they’re not miserable. I really couldn’t care less if their ear drum was still red or not.
  2. This outcome is very subjective “if they did not have complete or nearly complete resolution of signs and symptoms”.
  3. All the other trials have used the AOM-SOS scale as their primary outcome which is a patient oriented outcome, why did they change it?

The authors did also use the AOM-SOS scale but used it as a secondary outcome, and it was very difficult to find the results for this – you had to look at different rows from two different tables to find this result. Paul Glasziou has done that for us in his article and has even draws us a nice graph comparing the severity of symptoms over time. And when you compare this change in symptoms, there was really no difference between the 10 days or the 5 days.

Harms

  • 1 in 3 kids in this trial had diaper dermatitis (nappy rash). Now as a parent of 2 kids who are still in nappies – this is a nightmare. They’re in pain when you wipe them, you’re forever putting creams on and getting peed on all the time as you try to maximise nappy-free time.
  • 1 in 3 had diarrhoea. 

Other Issues

This study was done out of hospital setting, so these kids were going to the emergency department. And they had very strict criteria for which kids were allowed into the study. They had to have obvious bulging of the tympanic membrane and the presence of middle ear effusions. A lot of the children had a fever as well. So if we struggle to show a benefit for antibiotics in these patients, how much more so will they be useless in those with a slightly red drums, a bit grizzly, coming to their GP and not hospital.

The lead author, Hoeberman, apparently has a patent on an amoxycillin clavulate combination. And this doesn’t make the data wrong, but given that there is potential gain by him proving more amoxycillin/clavunate is better, it definitely warrants a more skeptical eye when looking at the methods and results.

Bottom Line:

The evidence suggests that antibiotics will increase the chance of recovery by 5% over placebo, it will decrease the risk of ear drum perforation by 3%, but has no impact on long term hearing or other complications like mastoiditis or meningitis. Using amoxycillin/clavulanate for 10 days will improve otoscopic signs compared to 5 days of use but will not impact patient symptoms. 1 in 3 children will develop diarrhoea and 1 in 3 will develop nappy dermatitis with the use of amoxycillin/clavulanate (whether for 5 days or 10 days).

References: