Management of chronic suppurative otitis media

To the Editor: Although the study by Couzos et al1 is important, I have serious concerns about (i) the lack of “intention-to-treat” analysis and (ii) the implication that the use of ototopical aminoglycosides is unethical and could lead to litigation.

The CONSORT statement indicates that analysis by intention-to-treat (ITT) is a key measure of methodological quality in reporting of randomised trials.2,3 Of 147 children randomly allocated to the two treatments in this trial, the primary outcome (resolution of otorrhoea) is only reported for 111 children (75.5%), and the secondary outcomes of healed tympanic membrane perforation in 64 (43.5%), and of improved hearing in 49 (33.3%). In addition, although the difference in cure rates is indeed 24.6% if drop-outs are ignored, the authors report incorrect 95% confidence intervals (15.8%–33.4%, instead of 7.3%–41.8%).

Analysis by intention-to-treat means that the 36 children lost to follow-up are assumed to still have ear discharge, so 33 of 75 in the ciprofloxacin group and 43 of 72 in the combined framycetin, gramicidin and dexamethasone group would not have “clinical cure”. This reduces the absolute difference to 15.7% (95% CI, 0–32%; P = 0.07), which is no longer a significant difference.

It is also unlikely that the clinical cure rates of 50%–70% in the study can be replicated in the real world of remote Top End Aboriginal communities with a high prevalence of chronic suppurative otitis media (CSOM). Cleaning ears twice a day with gentle syringing with 0.5% povidone-iodine, followed by ototopical ciprofloxacin for 10–14 days is not a feasible intervention among the competing priorities in most Aboriginal communities in the Northern Territory. The really important clinical outcomes for CSOM are the two secondary outcomes of healed perforations and improved hearing, but these outcomes were not significantly improved by ciprofloxacin compared with combined framycetin, gramicidin and dexamethasone.

Couzos and colleagues conclude that the use of aminoglycosides in CSOM is unethical and could lead to litigation on the basis of potential ototoxicity. Were this true, it would make this trial unethical. This misuse of ethics and law in the medical literature must be denounced. Nearly all drugs have potential side effects which have to be measured against their potential benefits. The potential ototoxicity of ototopical aminoglycosides (and other antibiotics) is not an absolute contraindication to their use, and has not been documented in any of the randomised controlled trials that have measured hearing before and after use of topical aminoglycosides.4

Couzos and colleagues misinterpret the strength of evidence for changing to ototopical ciprofloxacin. Although it is probably true that ciprofloxacin is superior to combined framycetin, gramicidin and dexamethasone in eradicating Pseudomonas aeruginosa, and for the short-term resolution of ear discharge, it is still unclear whether this transient benefit will be maintained in the long term, or whether resistant organisms will emerge in the middle ear, mitigating any benefit from the new drug. Haphazard use of ototopical ciprofloxacin in Top End Aboriginal communities is likely to result in resistance (indeed there is already anecdotal and unpublished evidence of this), so I believe that its use should currently be restricted to studies and programs whose outcomes are healed perforations and improved hearing (rather than only transient resolution of ear discharge).