Chemical engineers at Boston’s Laboratory for Biomaterials have created a single-application bioengineered gel that could deliver a full course of antibiotic therapy for paediatric middle ear infections. While current Australian guidelines state that the vast majority of children do not need antibiotics for otitis media, the gel is claimed to offer hard-to-treat cases a “safer and easier solution”.

Whilst topical treatments may have the advantage of reduced systemic exposure and limiting the effects on the patient’s microbial flora, the equation is not so simple when it comes to broader otitis media treatment issues in children which we try to unpack in this posting.

The paper by Yang et al. describes a pentablock copolymer poloxamer 407 gel that hardens once placed into the ear and stays in place, gradually dispensing antibiotics across the eardrum into the middle ear. This might have several potential benefits, including increased therapy adherence, reduced need for systemic antibiotics and less potential for toxicity/adverse reactions.   An aspect of concern about the study is the choice of antibiotic being delivered by the gel: ciprofloxacin, a recommended agent for topical use in chronic suppurative otitis media (CSOM) in Australia (see below).

Whilst topical treatments do have the advantage of reduced systemic exposure and limiting the effects on the patient’s microbial flora, the equation is not so simple when it comes to broader otitis media treatment issues in children. For instance:

• Diagnostic uncertainty with acute otitis media (AOM) is a significant issue –  visualisation of the tympanic membrane is difficult in infancy. Overdiagnosis may occur.  Furthermore most viral upper respiratory tract infections cause tympanic membrane redness and some viruses, particularly RSV, are thought to cause otitis media per se with redness and dullness of the tympanic membrane indicating middle ear inflammation.
• The role of antibiotics in AOM remains debatable –  regardless of microbial cause, an extensive range of studies show that 60% of children treated with placebo become pain-free in 24 hours, and spontaneous resolution of AOM occurs in approximately 80% of children.
• The occurrence of suppurative sequelae of AOM (mastoiditis, chronic suppurative otitis media (CSOM)) is rare in the Australian non-Indigenous populations, again weakening the rationale for routine antibiotic treatment.
• Parental expectations and preconceptions of prescribers may drive antibiotic prescription despite presence of guidelines that promote a more conservative approach

Also notable is the vastly different epidemiology of middle ear disease in Australian and Torres Strait Indigenous children who are commonly affected by aggressive forms  of AOM and CSOM with marked impact on childhood hearing and learning.  There is certainly a need for novel therapies and perhaps this new topical antimicrobial gel might play a role if supported by future research.  Newcastle recently hosted the 2016 OMOZ conference and future postings will highlight some of the learnings from that event.

Clearly topical use of antimicrobials does not avoid the risk of resistance – significant emergence of resistance has been documented with use of topical mupirocin use (nose and skin), moxifloxacin (conjunctiva after intravitreal injection) and erythromycin gel (skin use).  Prolonged topical use of ciprofloxacin (as used currently in CSOM in Australia) or in the form of the new gel may well lead to bacterial resistance and continued vigilance is required.

Picture:  Severe acute otitis media-erythema, bulging, effusion, opacification (from https://www.utmb.edu/pedi_ed/aom-otitis/grading.htm )

References

1. Coker TR, Chan LS, Newberry SJ, Limbos MA, Suttorp MJ, Shekelle PG, et al. Diagnosis, microbial epidemiology, and antibiotic treatment of acute otitis media in children: a systematic review. JAMA 2010;304(19):2161–9.
2. Mills O, Jr., Thornsberry C, Cardin CW, et al. Bacterial resistance and therapeutic outcome following three months of topical acne therapy with 2% erythromycin gel versus its vehicle. Acta Derm Venereol. 2002;82(4):260-5.
3. Rovers MM, Schilder AG, Zielhuis GA, Rosenfeld RM. Otitis media. Lancet 2004;363:465-73.
4. Venekamp RP, Sanders S, Glasziou PP, Del Mar CB, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev 2013;(1):CD000219.
5. Yin VT, Weisbrod DJ, Eng KT, Schwartz C, Kohly R, Mandelcorn E, Lam WC, Daneman N, Simor A, Kertes PJ. Antibiotic resistance of ocular surface flora with repeated use of a topical antibiotic after intravitreal injection. JAMA ophthalmology. 2013 Apr 1;131(4):456-61.