Choosing the Best Practice: Evidence to Support Fluoroquinolone Drops for Acute Otitis Media Through Tympanostomy Tubes (2007)

To the Editor.—In his commentary, “Why Don't Those Ear Drops Work for My Patients?”1 Isaacson presented his argument against the use of ototopical fluoroquinolones alone or in combination with a steroid as the first line of defense for the treatment of acute tube otorrhea in infants. He made several points to discount the use of these agents in pediatric patients with acute otitis media with tympanostomy tubes. However, rooted in the first sentence of the commentary was the fact that seems to lie at the epicenter of his concerns: “‘Topical Ciprofloxacin/Dexamethasone Is Superior to Oral Amoxicillin/Clavulanic Acid in Acute Otitis Media With Otorrhea Through Tympanostomy Tubes,’ [is] the latest in a series of pharmaceutical industry–funded articles… .”Isaacson's first critique of this article2 pertains to the study population. He stated that “[i]f one were trying to design a study to demonstrate the superiority of ototopical drops over oral antibiotics, the ideal population would be older children.” This statement directly contradicted his other criticism that “more than half of their subjects were >22 months of age.” In fact, 58% of the subjects in the study were <23 months of age, and the remaining patients were 2 to 11 years of age. These age distributions reflect that seen in daily pediatric practice, as supported in Isaacson's statement “… infants with acute tube otorrhea, who make up much of the population seen in daily practice.” Furthermore, experts agree that otitis media studies with a preponderance of infants are more compelling, because these are the patients who are most difficult to treat.Isaacson continued by stating that patients with ear drainage for more than 1 week or who had been treated with antibiotics should have also been the focus of the study.The goal of this study was to look at a cohort of patients with untreated acute otorrhea and compare topical antibiotic therapy to systemic therapy with the antibiotic that most guidelines consider the “best” for treating otitis media. Evaluating a different strategy of treatment supports the new directive3 of the Centers for Disease Control and Prevention to reduce antimicrobial resistance through the promotion of more appropriate antibiotic use. Contrary to this goal, this commentary both directly and indirectly supported systemic paradigms, although topical antibiotics have been shown to be safe and effective and less likely to lead to increased antibiotic resistance.4 Isaacson referred to a “protocol for controlling acute tube otorrhea … devised by clinicians at the Otitis Media Research Center in Pittsburgh, Pennsylvania.” However, the reference cited to support the protocol5 is not one directly published by the Otitis Media Research Center in Pittsburgh but was written by Isaacson and Richard Rosenfeld. It was extracted from a book with a copyright suggesting that the article was written before the availability of most of the supporting evidence for ototopical quinolone drops.Isaacson credited our exclusion of children from whom pure cultures of Pseudomonas aeruginosa were isolated. However, we disagree with his criticism that the “organisms they recovered from culture do not reflect the usual pathogens of acute otitis media, with only 15 of 154 cultures growing S[treptococcus] pneumoniae.” Having participated in numerous studies with a collective experience of >1000 patients, we have found that this same microbiological profile has almost always been the case. Furthermore, the data on the recovery rates of S pneumoniae must be evaluated against the rates after pneumococcal vaccination. Before this time, Roland et al6 reported a rate of S pneumoniae recovery of 17% during 2000–2001. On the basis of an approximate 30% reduction in any S pneumoniae isolate in acute otitis media as reported by the Finnish Otitis Media Study Group,7 the 10% recovery rate for S pneumoniae in our study was expected.We also disagree that drops instilled into the ear canal do not enter the middle ear. In addition to pharmacokinetic studies,8 which challenge this statement, one would not expect cure rates over double expected with spontaneous resolution (41%) after 1 week of treatment.9 In addition, no studies to our knowledge have ever suggested that drops should be “dribbled on top of a collection of pus” as suggested in this commentary. Aural toilet is recommended by most published authorities on this subject, including the World Health Organization. Dry mopping has been shown to be an effective means of aural toilet, and this clearly is practical in any physician's office.Finally, Isaacson made a statement that we enthusiastically embrace: “We should think twice about our approach to infectious disease in children and choose best practices on the basis of strong evidence.” We believe that strong evidence exists, and more is being generated to support both the safety and efficacy of ototopical quinolones and quinolone/steroid combinations such as ciprofloxacin/dexamethasone as first-line treatment for tympanostomy tube otorrhea. Without question, several of the studies have been funded by corporate sponsors with no attempt to hide or conceal this fact. We should appreciate such funding support, because it is extremely unlikely that noncorporate sponsors such as the National Institutes of Health would fund such work, especially in light of federal budget cuts. We do, however; recognize the importance of constructive and ethical partnerships between medicine and industry to advance the care of our patients. Although improprieties regarding the conduct of certain industry-funded studies have been a reality, it is unwarranted and erroneous to presume guilt by association for all such studies. When one reviews the type of evidence that Isaacson expects, such as Cochrane reviews, meta-analyses, and evidence-based, best-practice guidelines, one finds no such exclusion of evidence on the basis of the funding source. In many ways, industry-funded studies undergo more careful oversight and scrutiny. They must withstand preapproval by the US Food and Drug Administration and must be approved by several investigators and subinvestigators, as well as countless institutional review boards. They are subject to internal reviews, external audits, and, in select cases, scientific advisory boards convened by the Food and Drug Administration. And, like all studies, they can only be published after thorough peer review. We should be no more willing to condemn all such industry-sponsored trials than we are willing to condemn all physicians for the documented malfeasances of a few.