#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:

#9 Delayed Antibiotics

We want to reduce the use of antibiotics but at the same time we also want to keep our patients satisfied. Otherwise, they’ll just go and find another doctor.  This week we look into a really great study that compared refusing to give that antibiotic script, to giving them the script straight away, to a delayed prescription – which is where you tell them to only use the script if symptoms don’t get better in a few days. Which method is the best for reducing antibiotic use? and which method is best for keeping patients satisfied? Let’s take a look.

Introduction

There is a lot of antibiotic prescribing in primary care. A new report on the Australian BEACH data found that around 80 to 90% of all antibiotics prescribed by GP’s for respiratory tract infections were completely unnecessary. And this is likely to be an overestimate because the doctors volunteering to  participate in the BEACH study are probably different to the average GP.

The whole issue of antibiotic resistance has been getting constant attention and is considered a massive public health threat. So simple methods to reduce antibiotic prescribing should be welcomed with open arms.

One such method is called “delayed prescribing”  where the doctor writes out a prescription for the patient but in one way or another gets them to only use it if their symptoms don’t improve in a few days.

I’m pulling out this particular trial published in the BMJ in 2014 out of the large body of evidence on delayed prescribing – mainly because I think it was one of the more excellent trials.  But there has been heaps of trials like this, and amazingly they all show similar results. They will be discussed later.

Methods

So this trial was published in the BMJ in 2014 and it randomised patients who didn’t need immediate antibiotics into 5 groups.

They recruited 53 GPs in 25 different practices and they gave them each a bunch of envelopes. Anytime a patient would come in with a respiratory tract infection the GP would decide if the patient needed immediate antibiotics. If they didn’t need immediate antibiotics, they picked an envelope at random and in that envelope it would tell the doctor which group the patient should be assigned to. It also had an advice sheet to give to the patient based on which intervention they were getting.

The five group were:

  1. No prescription – so here the doctor would read the envelope and use their own approach to not give them a prescription, but they had to offer advise to come back if things got worse. So they said things like: “this is viral, you don’t need antibiotics, this will get better on its own, etc.“
  2. The other 4 groups used different approaches to delayed prescription. The second group was given the script and asked not to use it unless they didn’t get better in the next few days.
  3. The third group was given the script for antibiotics like the other group, but the script was dated in the future, so they couldn’t fill it until that date had come some days later
  4. In the fourth group, the doctor left the script with reception and told the patient they could come at any time without booking an appointment to collect the script if their symptoms don’t pick up over the next few days.
  5. And finally, the fifth group had to actually call the clinic and leave a message for the doctor that things weren’t getting better and they wanted the script – then the doctor would leave it at reception for the patient to pick up.
  6. They also analysed the data together with the participants who got an immediate script. So really there were 6 groups: 1 immediate antibiotic group, 1 no antibiotic group and 4 delayed antibiotic groups.

The advice on how long they should delay taking the antibiotics was different depending on the type of respiratory tract infection. So if it was an ear infection they would say: “if things don’t get better in 3 days then use the antibiotics”, or “come pick it up from reception” or “call the clinic” (depending on which group they were assigned to). If it was a sore throat the delay was for 5 days, and if it was for an acute bronchitis, the delay was for 10 days.

They managed to recruit 889 respiratory tract infection suffering patients but 333 were given immediate antibiotics because the doctor thought they needed them. So only 556 were randomised into the five delayed prescribing groups.

The outcomes they assessed were symptom severity –  to see if those with delayed prescriptions had worse symptoms, they also looked at how much antibiotic was actually being used in each group, and patient satisfaction. Anyone over the age of 3 with any respiratory tract infection was included in the study. Including: cold, flu, sore throat, middle ear infection, bronchitis or sinusitis.

Results

Severity of Illness

In terms of severity of illness, there was no difference between the groups. There was also no difference in the duration of the respiratory tract infection nor in the amount of analgesia used. Even those who were given the antibiotics to take immediately had no difference in their illness compared to the others. So telling your patient: “no, you can’t have these antibiotics” or offering them one of the four different delayed prescription strategies did not effect their actual illness compared to giving them the antibiotics straight away.

Antibiotic Use

There was a massive reduction in the amount antibiotics used with the delayed prescriptions:

Of those who were given the immediate antibiotic script, 97% ended up taking the antibiotics. This is remarkable because in general, if a doctor gives a patient a script for almost anything else, study after study has shown that only about 70% ever go and fill that script. So there is something special about antibiotics. Or maybe there is something special about respiratory tract infections and the desperation to get rid of them as quickly as possible.

If the patient was denied a script for antibiotics 26% of them used antibiotics. And this is very interesting. Many just went to a different doctor and got their script. Makes you think hey?

In the delayed groups, there was no difference in antibiotic use no matter which method of delayed prescribing you used. Around 37% took antibiotics in the delayed groups: whether they were given a script and told to only fill it if they didn’t get better in a few days, whether they had to come to reception to collect their script, whether they had to call the doctor a few days later if they wanted their script or whether they got a script which was dated in the future, it didn’t matter. 37% of them used antibiotics.

So offering a delayed antibiotic script reduced antibiotic use by doctors 60%. And denying them a script only reduced antibiotic use by 10% over what a delayed script did. (Note: this difference in antibiotic use between delayed prescriptions and no prescriptions was not statistically significant)

Patient Satisfaction

With regards to patient satisfaction: 80% of patients were very satisfied with the consult if they didn’t get a script at all. So the fear that patients always want antibiotics and will not be satisfied if they don’t get them is not indicated in this study. Or perhaps the doctors where very good at explaining why they didn’t need antibiotics. The highest level of patient satisfaction was 89% and this was in the patient led delayed script  group- where they were given a script and told only to fill it if things didn’t get better.

Other Evidence on Delayed Antibiotic Prescribing

A Cochrane Systematic Review was done in 2013 (before this study was published), and it found 10 trials making a total of 3157 patients comparing delayed prescribing for respiratory tract infections.

Just like in the BMJ study, if given an immediate script for antibiotics 93.3% will use antibiotics.

Again, just like our study, when given a delayed script only 32% will use antibiotics. Looking at the forrest plot, all the studies in this Cochrane review showed this same result with regards to this massive reduction in antibiotic use with delayed prescriptions.

Of those who were denied antibiotics, 14% still used antibiotics according to this Cochrane review. This is a little bit lower than the 27% in the BMJ who used antibiotics even though they were refused them initially.

Again, this review found no difference in the clinical outcomes whether you got immediate antibiotics, delayed antibiotics or no antibiotics.

 

So the results are very consistent. Offering a script and asking the patient to only use it if things don’t get better in a few days, will reduce antibiotic use by 60% and that’s the absolute reduction. Thats huge.

 

Bottom Line

Offering a delayed antibiotic prescription for a respiratory tract infection –  where you give the patient a script and tell them only to use if things don’t get better in a few days – will reduce antibiotic use by 60%. Completely refusing to give a script for antibiotics will only marginally decrease antibiotic use compared to a delayed prescription.  There is no difference in clinical outcomes when giving an immediate script, a delayed script or no script.

Discussion

Firstly,  no other tool that has been studied is as effective at reducing antibiotic use as this. Delayed prescribing achieves a 60% absolute reduction in antibiotic use.  The trials that look at patient education and doctor education do not come anywhere near this in terms of reducing antibiotic use.

Secondly, the qualitative evidence on why doctor prescribe antibiotics for respiratory tract infections seem to indicate four main reasons:

  1. The first is the fear that patient will develop a bad complication from their illness – and you can understand this  because if you’re a GP who has been working for several decades, it’s almost inevitable that you’ll send someone home with a mild infection that will then end up getting really sick. And that might scare the bageebes out of you and change the way you deal with these respiratory tract infections.
  2. The second reason is that we think the patient wanted the antibiotic – and it turns out that we’re usually off target with this one, patients often don’t want them at all. They just want an explanation. In my own experience, I’ve had patients who I could have sworn were just coming because they wanted antibiotics and after I explained why I didn’t think it was necessary, to my shock they’re like: “oh few….I was so scared you were going to tell me to take antibiotics…I really hate taking them”.
  3. The third reason antibiotics are prescribed when they probably shouldn’t be is because of diagnostic uncertainty. So here the doctor is not sure whether its viral or bacterial, so to er on the side of caution they give antibiotics.
  4. Finally, the fourth reason is to do with time. Doctors fear that spending the time to explain why a patient doesn’t need antibiotics will take much more time than just printing a script and giving it to the patient. And will make them run late for the rest of the day.

Delayed prescriptions are brilliant because they tackle all four of these reasons. If a doctor fears the patient will develop a nasty complication from not getting antibiotics, they still have a script should things get worse.  If the doctor fears the they will lose the patient by not giving them a script because they think the patient really wants one – well in delayed prescribing the patient still gets a script. And if the doctor is worried about time, it’s just as quick and easy to give a script and say use these in a couple of days if things don’t get better.

Lastly, all four methods of delayed prescribing led to the same amount of antibiotic use, so it makes sense to use the method that’s easiest for the patient – which is to give them the script and let them drive their decision take it or not, rather than make them call me or leave it with reception.