Are topical antibiotics an alternative to oral antibiotics for children with acute otitis media and ear discharge?
BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i308 (Published 04 February 2016) Cite this as: BMJ 2016;352:i308All rapid responses
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We thank Dr Zedan for the insightful comments on our manuscript. We agree that AOM with and without ear discharge (due to a spontaneous perforation of the eardrum) are two clinical entities of the disease spectrum. This distinction has been highlighted in the introduction section of our paper.
In contrast to common beliefs that the ear discharging means that symptoms of ear pain and fever are on the wane, it is to these children in particular that AOM poses a real burden: individual patient data meta-analysis data showed that (i) 80% of children with AOM and ear discharge have ear pain at presentation, and (ii) 60% of children with AOM and ear discharge managed without oral antibiotics still suffer from ear pain and/or fever at 3-7 days as opposed to 40% of those with AOM who do no present with ear discharge.[1] Furthermore, observational data from UK primary care indicated that children with AOM and ear discharge have a worse prognosis with higher rates of ear pain at 1 week, and more AOM recurrences and hearing problems at 3 months despite being similar with regards to age, gender and socio-economic status to children with AOM who do not present with ear discharge.[2] Ear pain as primary outcome variable was also based on our public and patient involvement (PPI) group, consisting of parents of children with AOM, who indicated a clear preference for pain over fever, ear discharge and other symptoms.
We respectfully disagree that topical antibiotics cannot penetrate through the lumen of a middle ear ventilation tube (grommet). Evidence from randomised controlled trials in children with grommets and ear discharge convincingly demonstrates that topical antibiotics (with corticosteroids) are superior to oral antibiotics, saline rinsing and watchful waiting.[3-5] This indirectly suggests that topical antibiotics may be as effective as oral antibiotics for children with AOM presenting with ear discharge caused by spontaneous perforation of the eardrum since the perforation provides an opportunity to instil topical antibiotics directly into the middle ear. We, however, acknowledge that the perforation may be too small or may close too early (within days) to allow eardrops to express their mode of action. As such, the evidence on the benefits of topical antibiotics in children with grommets and ear discharge cannot easily be applied to those with AOM and ear discharge due to a spontaneous perforation of the eardrum. We therefore feel that our proposed trial comparing the clinical and cost-effectiveness of topical versus oral antibiotics in children with AOM and ear discharge is not only justified but also highly warranted.
1. Rovers MM, Glasziou P, Appelman CL, et al. Antibiotics for acute otitis media: a meta-analysis with individual patient data. Lancet 2006;368:1429-35.
2. Smith L, Ewings P, Smith C, et al. Ear discharge in children presenting with acute otitis media: observational study from UK general practice. Br J Gen Pract 2010;60:101-5.
3. Dohar J, Giles W, Roland P, et al. Topical ciprofloxacin/dexamethasone superior to oral amoxicillin/clavulanic acid in acute otitis media with otorrhea through tympanostomy tubes. Pediatrics 2006;118:561-9.
4. Heslop A, Lildholdt T, Gammelgaard N, et al. Topical ciprofloxocin is superior to topical saline and systemic antibiotics in the treatment of tympanostomy tube otorrhea in children: The results of randomized clinical trial. Laryngoscope 2010; 120:2516-20.
5. Van Dongen TM, van der Heijden GJ, Venekamp RP, et al. A trial of treatment for acute otorrhea in children with tympanostomy tubes. N Engl J Med 2014;370:723-33.
Competing interests: No competing interests
Are antibiotics (topical or oral) effective in acute otitis media and ear discharge? What are the effective alternatives?
Sarrel et al.(2003) (and many others) described otitis media as one of the most frequent diseases of early infancy and childhood. They wrote, “Over the past 2 decades, there has been a substantial increase in the diagnosis of otitis media worldwide”.
This increase resulted in the increasing development and use of many new antibiotics, after penicillin became ineffective due to the world wide development of bacterial resistance to it. Amoxicillin became the antibiotic of choice. The question of its effectiveness (or otherwise) in otitis media with effusion became the subject of controversy (Rennie 1991).
In the meantime, without much fanfare, a number of naturopathic treatments continued to be used and researched.
Sarrell et al.(2003) studied 171 children (5 to18 years old) with otalgia and clinical findings associated with middle-ear infection, who were randomly assigned to receive Naturopathic Herbal Extract Ear Drops (NHED) or anaesthetic ear drops, with or without amoxicillin in a double-blind trial in an outpatient community clinic, to determine the efficacy and tolerability of naturopathic versus traditional treatment for the management of otalgia commonly associated with acute otitis media (AOM).
Their trial established that each group had a statistically significant improvement in ear pain over the course of 3 days. Those who were given eardrops alone had a better response than those who were given eardrops together with amoxicillin. Results were better in the NHED group than in controls. “Concomitant antibiotic treatment is apparently not contributory.”
According to Sarrell and al (2003) “The American Academy of Otolaryngology-Head and Neck Surgery quidelines recommended topical medications as the first line of treatment for ear pain in the absence of systemic infection or serious underlying disease.”
And,
“The alternative naturopathic herbal extract medications may offer many new possibilities in the management of ear pain associated with AOM. As it was widely reported in medical literature, these herb, these herbal extracts have the potential to meet all of the requirements of appropriate medication that could be routinely used in the pediatric patient, namely in vitro bacteriostatic and bactericidal activity against common pathogens, immunostimulation ability, antioxidant activity, and anti-inflammatory effects. They are also well-absorbed with good penetration into the tissue surrounding the tympanic membrane. They have been found to enhance local immunologic activity. Finally, herbal extracts are well-tolerated (owing their long elimination time), easy to administer, and less expensive than the new antibiotics. There are no documented side effects.”
Kristinsson et al. (2005) described effective treatment of experimental acute otitis media by application of volatile fluids in to the ear canal of rats. They reasoned that “Antimicrobial resistance has become wide-spread in many areas…This has led to problems in the treatment for diseases caused by these pathogens [Streptococcus pneumoniae and Haemophilus influenzae] and treatment failures have become more frequent. National campaigns to reduce unnecessary antimicrobial use stress that antimicrobials are often not needed for the treatment of uncomplicated acute otitis media. An alternative treatment that does not require the systemic administration of antimicrobials would offer a significant advantage over existing treatment options”
And
“Numerous essential oils, including oil of basil (Ocimum basilicum) can have antimicrobial activity, and a recent study clearly demonstrates the rapid bactericidal effect that the vapours from these oils have. Because the tympanic membrane is not considered to be permeable to antimicrobial agents in liquid form, treatment of acute otitis media through the external ear canal is not advised. However, the vapours of essential oils may potentially diffuse from the external ear canal into the middle ear in quantities that are sufficient to produce an antimicrobial effect on acute otitis media.
“
The less than desirable effectiveness of oral administration of amoxicillin in otitis media with effusion has unwittingly been demonstrated by Mandel et al.(1987).
They wrote, “Among the 474 subjects who were evaluated at the four week endpoint, the rate of resolution of middle ear effusion was twice as high in those treated with amoxicillin, either with or without decongestant-antihistamine, as in those who received placebo. (P less than 0.001), but 69.8 percent of the amoxicillin treated subjects still had effusion. Among both the amoxicillin-treated subjects and the placebo treated subjects, resolution was more likely in those with initially unilateral effusion, in those who had had effusion for eight weeks or less, and in those without an upper respiratory tract infection at the four week end point. Side effects were reported more often in subjects who received decongestant-antihistamine than in those who did not. Among the subjects without effusion at the four-week end point, recurrent effusion developed in approximately half [of] those in both the amoxicillin and placebo groups during the subsequent three months. We conclude that in infants and children with otitis media with effusion amoxicillin treatment increases to some extent the likelihood of resolution.
Cantekin et al. (1991) re-examined the Mandel’s et al.’s data and wrote,
“Six weeks after the termination of amoxicillin therapy, the recurrence of effusion was two to six times higher in the amoxicillin-treated children than in those treated with placebo (P=.001), and resolution of effusion was not significantly different among antibiotic and placebo groups (13.6% and 11.3%, respectively; P=.477)“. They concluded that “Amoxicillin with and without decongestant-antihistamine combination is not effective for the treatment of persistent asymptomatic middle ear effusions in infants and children.”
Considering the dire warnings by all and sundry about the ‘apocalyptic’ threat of the world-wide antimicrobial resistance, the use of safe and more effective, and well-known topical naturopathic remedies in otitis media (with or without effusion) , is indicated.
References
Sarell et al.2003. Naturopathic treatment for ear pain in children. Pediatrics; May: 111(5 pt 1): e574-9.
Rennie 1991. The Cantekin Affair. JAMA; December 18; 266(23): 3333-3337.
Kristinsson et al. 2005. Effective treatment of experimnental acute otitis media by application of volatile fluids into the ear canal. J Infect Dis; 191 (1June): 1876-1880.
Mandel et al.1987. Efficacy of amoxicillin with and without decongestant-antihistamine for otitis media with effusion in children : results of a double-blind, randomised trial. NEJM; 316: 432-437.
Cantekin et al. 1991. Antimicrobial therapy for otitis media with effusion (‘secretory otitis media’), JAMA; 266:3309-3317.
Competing interests: No competing interests
A fundamental oversight in this article is the lack of distinction between acute suppurative otitis media, i.e. ASOM, without tympanic membrane, i.e. TM, perforation or ear discharge, on one hand, and acute suppurative otitis media (ASOM) with tympanic membrane (TM) perforation and ear discharge, on the other hand.
Although the two processes could be consecutive stages in ASOM, their symptoms and signs are different. Additionally, ASOM could resolve without TM perforation and ear discharge and lasting a shorter course than if ear discharge had developed.
A mainstay in the management of ASOM is oral antibiotics, in an attempt to reach the infected middle ear mucosa through the blood stream. Topical antibiotic ear drops would not get into the middle ear cavity unless the TM perforation is large. In most cases of ASOM with ear discharge, the TM perforation is small or of pin-head size which will not allow topical ear drops, or spray, through. Most of these small perforations heal spontaneously after an episode of ASOM. Similarly, a drop or droplet of topical antibiotics can’t penetrate through the lumen of a middle ear ventilation tube (grommet).
Infected middle ear mucosa and collection of muco-pus in the confined space of the middle ear cavity is associated with marked earache. Pressure necrosis in a weakened part of the tympanic membrane and release of muco-pus from the middle ear to the external auditory canal relieve most of this earache. So, while pain is a predominant feature in ASOM without tympanic membrane perforation or discharge, ASOM with ear discharge is mostly painless or much less painful. Ear discharge is also a late stage in the course of ASOM. Ear pain, as a primary outcome measure, is not therefore a convincing indicator for comparing the effect of interventions on ASOM, with TM perforation and ear discharge.
Competing interests: No competing interests
I would like to underline and remind colleagues about the extremely powerful broad spectrum fungicidal and bactericidal activity, of carvacrol rich essential oil of oregano that has proved to be active, even against antibiotic and antimycotic resistant strains, without any side effects. [1][2]
Concomitant topical administration of carvacrol rich emulsions of essential oil of oregano, or other herbal monoterpenes, with current systemic pharmacologic therapies must be investigated and pursued, in order to achieve synergistic effects.
Carvacrol has also antinociceptive[5] and potent anti-inflammatory activity[3][4].
No bacterial resistance has ever been observed.
References
[1] http://www.bmj.com/content/317/7159/609/rr/634773
[2] http://www.bmj.com/content/337/bmj.39357.558183.94/rr/630538
[3] http://www.ncbi.nlm.nih.gov/pubmed/22363615
[4] http://www.ncbi.nlm.nih.gov/pubmed/22892022
[5] http://www.ncbi.nlm.nih.gov/pubmed/23146035
Competing interests: No competing interests
With regards to the above article it is stated with quinlones with steroid ear drops are available in Britain. I do not see any in the current BNF 70. We commonly use ciprofloxacin eye drops off licence for otitis externa etc. It can be difficult to get pharmacists to dispense gentisone or sofradex due to supply issues. We are left with otomize usually as an alternative. We would be grateful to know what other drops/ sprays can be used off or on licence for topical administration to the external auditory meatus.
Competing interests: No competing interests
Re: Are topical antibiotics an alternative to oral antibiotics for children with acute otitis media and ear discharge?
We thank Dr Simpson for his interest in our article and agree that the range of topical antibiotic products available for the treatment of AOMd will be dictated by: (i) the evidence for their use and (ii) their availability. Regarding the first, any doctor choosing to prescribe off-license needs to be prepared to justify the choice of product (using best available evidence) and advise the patient they are prescribing off-license. In our article we conclude that there is currently insufficient evidence to justify the use of topical antibiotics for children with AOM and ear discharge due to a spontaneous perforation of the eardrum (AOMd) but that doctors may choose to use indirect evidence from children with grommets to justify the use of topical (non-aminoglycoside) antibiotics. In our experience, the availability of topical antibiotic drops varies both geographically and month to month so we acknowledge doctors will need to take local supply issues into account when deciding to prescribe topical antibiotics. This is an area where further research is required to fill the gap in evidence.
Competing interests: No competing interests