PEDIATRICS Vol. 118 No. 3 September 2006, pp. e561-e569 (doi:10.1542/peds.2005-2033)
ARTICLE |
Topical Ciprofloxacin/Dexamethasone Superior to Oral Amoxicillin/Clavulanic Acid in Acute Otitis Media With Otorrhea Through Tympanostomy Tubes
a Department of Otolaryngology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania;
b CENTA Medical Group, Columbia, South Carolina
c Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas, Texas
d Ogden Clinic, Ogden, Utah
e ENT Specialists of NW Pennsylvania, Erie, Pennsylvania
f Pediatric ENT Institute of South Texas, San Antonio, Texas
g Florida Otolaryngology Group, Orlando, Florida
h Alcon Research, Ltd, Fort Worth, Texas
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVE. This study was a comparison of topical ciprofloxacin/dexamethasone otic suspension to oral amoxicillin/clavulanic acid suspension in children with acute otitis media with otorrhea through tympanostomy tubes.
METHODS. This was a randomized, observer-masked, parallel-group, multicenter trial of topical ciprofloxacin/dexamethasone otic suspension versus amoxicillin/clavulanic acid suspension in 80 children aged 6 months to 12 years with acute otitis media with otorrhea through tympanostomy tubes of 
3 weeks' duration and visible otorrhea. Patients were randomly assigned to receive either 4 drops of topical ciprofloxacin 0.3%/dexamethasone 0.1% (Ciprodex Sterile Otic Suspension) into the affected ear(s) twice daily for 7 days or 600 mg of amoxicillin/42.9 mg of clavulanic acid oral suspension (Augmentin ES-600 Oral Suspension) every 12 hours for 10 days. Clinical signs and symptoms of acute otitis media with otorrhea through tympanostomy tubes were evaluated on days 1 (baseline), 3, 11 (end-of-therapy), and 18 (test-of-cure), and twice-daily assessments of otorrhea were recorded in patient diaries.
RESULTS. The median time to cessation of otorrhea was significantly shorter with ciprofloxacin/dexamethasone otic suspension than with amoxicillin/clavulanic acid suspension (4.0 vs 7.0 days; n = 79). This resulted in significantly more clinical cures at the test-of-cure visit (85% vs 59%, respectively). Frequent adverse events (>3%) related to ciprofloxacin/dexamethasone otic suspension included ear pain (5.1%) and related to amoxicillin/clavulanic acid suspension included diarrhea (19.5%), dermatitis (7.3%), and gastroenteritis (4.9%).
CONCLUSIONS. Topical otic treatment with ciprofloxacin/dexamethasone otic suspension is superior to treatment with oral amoxicillin/clavulanic acid suspension and results in more clinical cures and earlier cessation of otorrhea with fewer adverse effects in children with acute otitis media with otorrhea through tympanostomy tubes.
Key Words: otitis media • tympanostomy tubes • ciprofloxacin • dexamethasone • oral antibiotics
Abbreviations: CDC—Centers for Disease Control and Prevention • AOM—acute otitis media • AOMT—acute otitis media with otorrhea through tympanostomy tubes • TT—tympanostomy tube • FDA—US Food and Drug Administration • CIP/DEX—ciprofloxacin/dexamethasone otic suspension • AMOX/CLAV—amoxicillin/clavulanic acid suspension • TOC—test-of-cure • ITT—intent-to-treat • MITT—modified intent-to-treat
Since 1995, the Centers for Disease Control and Prevention (CDC) have launched a national campaign to reduce antimicrobial resistance through promotion of more appropriate antibiotic use.1 With the CDC having laid this foundation, major medical academies throughout the United States and abroad have applied their position to specific and common infections managed by their constituencies. Otitis media has been one such infection. Guidelines have been published for the management of otitis media with effusion2 and for the management of acute otitis media (AOM).3 Unfortunately, these guidelines have considered "more appropriate antibiotic use" to mean "no antibiotic use" in certain scenarios. A strategy not specifically addressed in these guidelines but very consistent with the spirit in which they were developed is one that substitutes topical for systemic antibiotics. Topical antibiotics are far less likely to lead to increased antibiotic resistance.4,5
An infection that lends itself perfectly to such an algorithm switch is AOM with tympanostomy tubes (AOMT). None of the guidelines referenced above consider AOMT. This is a very common disease given that AOM is the most common diagnosis for which children are treated with antibiotics and that tympanostomy tube (TT) placement is the most common surgery performed on children. With a TT in place, the middle ear is accessible to topical medications applied to the external auditory canal. Despite that, AOMT continues to be managed in a large percentage of cases with oral antibiotics often to the exclusion of a topical agent. Ciprodex Sterile Otic Suspension (Ciprodex is a registered trademark of Bayer AG, licensed to Alcon Inc, by Bayer AG) is an ototopical formulation containing 0.3% ciprofloxacin and 0.1% dexamethasone. It has been approved recently by the US Food and Drug Administration (FDA) to treat AOMT. Although shown to be superior to the only other topical antibiotic approved by the FDA for AOMT, namely, topical ofloxacin,6 no studies to date, have evaluated its superiority or noninferiority to an oral FDA-approved antibiotic for AOM. For the reasons stated above, such a comparison would be meaningful, because it would pave the way to yet another strategy of achieving more appropriate antibiotic use. This study compared ciprofloxacin (0.3%)/dexamethasone (0.1%) otic suspension (CIP/DEX) with (600 mg) amoxicillin/(42.9 mg) clavulanic acid oral suspension (AMOX/CLAV) in children with AOMT.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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This study was conducted as a randomized, prospective, observer-masked, parallel-group clinical trial comparing CIP/DEX with AMOX/CLAV in children with AOMT. Six otolaryngologists located in the United States participated as investigators. The primary objective was to evaluate the safety and efficacy of CIP/DEX relative to AMOX/CLAV for the treatment of AOMT in pediatric patients based on time to cessation of otorrhea and proportion of patients rated as cured at the test-of-cure (TOC). With
30 patients per arm, this study was powered adequately to describe the proportion of cures at TOC within each treatment group with an accuracy of 15.2%, based on the expected width of a 95% confidence interval with 90% cures in both treatment groups. The study protocol was approved by an independent institutional review board for each investigative site and conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from the parents or legal guardians of all of the patients before enrollment.
Patients and Medication
A total of 80 children, aged 6 months to 12 years, with patent TTs and a clinical diagnosis of uncomplicated AOM with otorrhea (drainage visible to the parent or guardian) of 3 weeks' duration in 1 or both ears were enrolled into the study. Patients were randomly assigned to receive either topical CIP/DEX (Ciprodex Sterile Otic Suspension, manufactured by Alcon Laboratories Inc, Fort Worth, TX) dosed 4 drops twice daily for 7 days or AMOX/CLAV (Augmentin ES-600 Oral Suspension, manufactured by GlaxoSmithKline, Research Triangle Park, NC) dosed 90 mg/kg per day divided every 12 hours for 10 days.
Patients were sequentially assigned to treatment according to a randomization code provided by the Alcon Biostatistics Department. The randomization was blocked within center to ensure balanced treatment groups within each center. Because of the differences between a topically and an orally administered medication, as well as the difference in the dosing regimens, this study was considered observer masked. That is, the investigator conducting the clinical evaluations had no knowledge of the patient's treatment assignment. Dosing assignments were provided to the study coordinator who was responsible for dispensing and providing dosing instructions to the patient (parent/guardian).
Patients who were not eligible for enrollment included those with otorrhea present for 3 weeks and those with acute or malignant otitis externa. Additional enrollment exclusions included known or suspected fungal or mycobacterial ear infections, a history of or active viral infections of the tympanic membrane, mastoiditis, or infections requiring systemic antibiotic therapy. Patients were also excluded for otologic surgery (except that confined to the tympanic membrane) in the previous year or if they presented with or had a history of diabetes, immunosuppressive disorders, acute or chronic renal disease, active hepatitis, chronic nasal obstruction and/or persistent rhinorrhea, complicating structural abnormalities, known or suspected quinolone hypersensitivity, and, in girls, menarche. Patients were not permitted to receive topical (otic or ophthalmic) corticosteroids or antibiotics concurrently or within the preceding 3 days, systemic corticosteroids within the preceding 7 days, inhaled corticosteroids at doses 800 µg/day, topical antibiotics for skin infections within the preceding 7 days, topical otic analgesics/anesthetics or antiseptic washes, or nonsteroidal anti-inflammatory drugs, with the exception of oral acetaminophen for relief of pain. Additional exclusions associated with amoxicillin/clavulanic acid included previous history of chronic diarrhea or pseudomembranous colitis, current diagnosis of mononucleosis, current or previous history of cholestatic jaundice or hepatic dysfunction, or concurrent administration of allopurinol or probenecid.
Eligible patients were evaluated at 4 scheduled visits: baseline (day 1), on-therapy (3 + 2 days), end-of-therapy (11 + 2 days), and TOC (18 + 3 days). At the baseline visit, a complete clinical assessment was performed. The ear canal was cleaned of all fluid and debris via suction, and then an otorrhea specimen was obtained from the lumen of the tube using the Juhn Tym-Tap aspirator/collection device and direct microscope, paying particular attention to avoid contamination by contact with the surface of the external auditory canal. Aural toilet by the physician is an important aspect of treating all cases of AOMT. To subtract any therapeutic effect, we performed aural toilet in both treatment arms of the study to remove debris so a more accurate culture of the otorrhea could be obtained. Otorrhea specimens were collected in all of the patients at baseline and were repeated in patients who the investigator declared a "clinical failure," regardless of the visit day. If no drainage was present at TOC, the patient was considered a microbiologic success. Any patient with pretherapy cultures of pure yeast, group A streptococci, or Pseudomonas aeruginosa were discontinued from the study and started on alternative therapy. The parent or guardians were instructed in the use of patient diaries and the need for avoiding significant water contamination of their ears. At subsequent visits, clinical assessments were repeated to assess the presence or absence of otorrhea, patient diaries were reviewed, and adverse events were recorded. To minimize the likelihood of having the topical drops interfere with the assessment of otorrhea, patients were instructed not to administer their drops within 2 hours before their study visit. A complete audiologic evaluation, including pure tone threshold testing at varying frequencies with masking and speech reception threshold, was conducted by certified audiologists in children aged 4 to 12 years at the baseline and TOC (or exit) visits.
Microbiology Methods
The aspirated otorrhea was split on 2 swabs, 1 for the recovery of bacteria and 1 for the detection of bacteria. The swab for recovery of bacteria was transferred in transport media overnight to North Coast Clinical Laboratory (Sandusky, OH). Standard bacteria culture media (both broth and agar-based) were used for the recovery of aerobic and anaerobic bacteria present in the otorrhea specimen.
The swab for detection of bacteria was kept frozen until the DNA extraction. Total DNA was extracted using QIAamp DNA minikit (Diagen Inc, Dusseldorf, Germany). From these extracts, 500 bp of 16S rRNA gene fragments were amplified using the MicroseQ 500 16S rDNA PCR kit (Applied Biosystems). Because this amplification was on DNA extracts of the otorrhea, generally there were several unique amplicons present. The mixed amplicons were purified over the WAVE HPLC System (Transgenomics Inc, Omaha, Nebraska) before determining the DNA sequence of the amplicon (16S rRNA gene fragment). Phylogenetic analysis of all of the sequences was performed using MicroSeq software.
Efficacy Assessment
Two primary efficacy variables were selected for evaluation at the TOC visit: (1) time to cessation of otorrhea as recorded twice daily in the patient's diary (0: absent; 1: present); and (2) clinical cure (cured versus not cured). Clinical response to therapy was assessed by the investigator based on a 4-point scale (0: cured/resolved; 1: improved; 2: not changed; 3: worsened; compared with the baseline visit). An overall clinical response of cured/resolved was defined as the absence of otorrhea at the TOC visit. "Improved" was defined as a significant improvement in clinical signs or symptoms compared with the baseline visit. Secondary variables included microbiologic response (success or failure) in patients with bacteria present at the pretherapy visit. There were several possible microbiologic outcomes: (1) "microbiologic failure" as a result of the persistence of pretherapy pathogen(s), (2) "microbiologic failure" as a result of superinfection (if a new pathogen was recovered during therapy), and (3) "microbiologic failure" as a result of reinfection (if a new pathogen was recovered after the end of therapy).
Safety Assessment
A safety evaluation was conducted on all of the patients who were randomly assigned into the trial and received 1 dose of study drug. The safety analysis was based on the extent of exposure to the study drug, adverse events, and audiometric examination. The occurrence of adverse events was assessed at each study visit and via questioning of parents or guardians during daily telephone contacts related to completion of the patient diaries. Patients who experienced adverse events that, in the opinion of the investigator, presented a significant risk to their safety or well-being were withdrawn from the study. Data from the exit audiometric examinations were evaluated to determine whether any clinically significant decrease in hearing had occurred.
Statistical Analysis
Statistical analyses were performed using validated programs prepared in SAS 8.0 for Windows (SAS Institute Inc, Cary, NC). Kaplan-Meier survival curves were constructed to compare median time to cessation of otorrhea between the 2 treatments. The log-rank test (Kaplan-Meier survival analysis) was then conducted to evaluate between-group differences. The number and proportion of patients per treatment group were presented and differences were assessed using the 
2 test of independence (Fisher's exact test when N < 5).
The hypothesis being tested for the primary variable of time to cessation of otorrhea was as follows:
 | (1) |
 | (2) |
 | (3) |
 | (4) |
C denotes the probability of clinical cure (or microbiologic eradication) for CIP/DEX patients and A denotes the probability of clinical cure (or microbiologic eradication) for AMOX/CLAV patients. |
RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Patients were enrolled during a 13-month period from May 2003 through May 2004.
Demographics
Study demographics for all 80 patients enrolled are summarized in Table 1. The mean age of all of the patients in the intent-to-treat (ITT) data set was 1.88 years (SD: 1.72 years), with a range from 6 months to 8 years. No statistically significant differences were identified between the 2 groups with respect to age, gender, ethnicity, or affected ear(s). The majority of the patients enrolled in this study (64 patients [80%]) had only 1 ear enrolled. The right ear was the enrolled ear for 27 patients (33.75%), the left ear was the enrolled ear for 37 patients (46.25%), and both ears were enrolled for 16 patients (20%). The right ear was declared the worst ear for 43 patients (53.75%). The majority of the patients enrolled had no granulation tissue. No statistically significant differences between treatment groups were detected for otorrhea, patency, or granulation tissue.
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Data Sets Analyzed
A total of 80 patients were randomly assigned (39 in the CIP/DEX group and 41 in the AMOX/CLAV group), received treatment, and were assessable for the ITT analysis. Of these, 60 patients (31 in the CIP/DEX group and 29 in the AMOX/CLAV group) were included in the modified ITT ([MITT] ie, microbiologically evaluable) analysis in that they had received treatment, had met inclusion/exclusion criteria at baseline, and had a positive culture for bacteria at baseline. All of the data presented are based on detected and recovered microbiologic analysis.
Clinical Efficacy
CIP/DEX was superior to AMOX/CLAV for time to cessation of otorrhea in all of the data sets analyzed. The median time to absent otorrhea for CIP/DEX was 4.0 days (ITT and MITT) compared with 7.0 days (ITT) and 9.5 days (MITT) for AMOX/CLAV (Table 2 and Fig 1). In addition, CIP/DEX was superior to AMOX/CLAV for clinical cures in the ITT and MITT data sets (Table 2 and Fig 2). Kaplan-Meier survival curves for time to cessation of otorrhea also show an advantage for CIP/DEX treatment compared with AMOX/CLAV (Fig 3).
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Microbiologic Efficacy
The bacteria present at baseline (visit 1 before the initiation of therapy) are listed in Table 3. The distribution of each species between the 2 treatment groups is also presented.
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The overall microbiologic response of bacteria-positive patients in the per-protocol data set is presented in Table 4. This data set includes only the therapeutic successes and failures. The per-protocol analysis did not include 13 patients in the CIP/DEX group and 7 patients in the AMOX/CLAV group who were included in the MITT data set (see Table 2). The difference in the microbiologic response between the 2 treatment groups in this modified per-protocol data set was not statistically significant (83% vs 63%) because of the reduced numbers of patients in this data set compared with the MITT data set. However, the percentage of successfully treated patients with CIP/DEX (83% vs 74%) and AMOX/CLAV (59% vs 55%) is approximately the same in both data sets.
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The CIP/DEX treatment group had 3 treatment failure patients (Table 5). Each patient had 2 pathogens at the pretherapy visit, and 2 of the patients had 1 pathogen each at time of failure. One patient had otorrhea at time of failure, but no organisms were present at time of failure. The AMOX/CLAV treatment group had 9 treatment failure patients (Table 6). Four of the 9 failure patients had polymicrobic cultures at time of failure. These polymicrobic cultures all contained new pathogens at time of failure. Three of the 4 patients had superinfectors, a new pathogen recovered or detected during therapy. One patient had multiple reinfecting pathogen, which were recovered or detected at TOC.
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Adverse Events
Adverse events related to CIP/DEX and AMOX/CLAV are presented in Table 7. Treatment-related adverse events were reported in 12.8% of patients receiving CIP/DEX compared with 29.3% of patients receiving AMOX/CLAV. These adverse events were nonserious, mild to moderate, and generally resolved with or without treatment. One patient in each treatment group discontinued the study because of related adverse event(s). A 1-year-old male receiving CIP/DEX discontinued the study because of tube obstruction in the study ear, and a 1-year-old male receiving AMOX/CLAV discontinued the study because of dermatitis and diarrhea. Treatment with AMOX/CLAV was associated with greater gastrointestinal adverse effects, including gastroenteritis and diarrhea. Reports of oral thrush and worsening in diaper rash likely secondary to yeast infections were also observed more frequently with AMOX/CLAV. Neither treatment group had any negative effect on patient audiometry.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The results of this study are consistent with other multicenter AOMT trials.7 Eighty percent of the patients in this study presented with unilateral AOMT, like other AOMT studies published to date where unilateral presentation predominates.6,7 The median time to cessation of otorrhea was 4.0 days in both the ITT and the MITT groups for the combination drop. This compares favorably with larger trials that demonstrated a 4.0-day cessation of otorrhea for Ciprodex Sterile Otic Suspension.6,7
This is the second clinical trial comparing an ototopical strategy to a systemic strategy for the treatment of AOMT. The first, by Goldblatt et al,8 involved purulent otorrhea from AOM in the presence of a TT. Patients were treated for 10 days with either 40 mg/kg per day of oral amoxicillin-clavulanic acid 3 times per day or 5 ofloxacin drops applied twice per day directly to the ear canal. Patients who had P aeruginosa as a sole pathogen were also omitted from the study, because amoxicillin-clavulanic acid would not be expected to adequately cover this organism. Although the cure rates were statistically no different (76.3% for ofloxacin and 68.3% for amoxicillin-clavulanic acid), had the 34 patients from whom P aeruginosa was isolated as the sole pathogen been included, the difference in favor of ototopical ofloxacin would probably have been greater. Not surprisingly, the present study demonstrates superior cure rates for the ototopically treated group, because Ciprodex Sterile Otic Suspension resulted in superior cure rates when compared with topical ofloxacin in a previous trial. That notwithstanding, even noninferiority of the ototopical against the systemic antibiotics favors the topical risk/benefit ratio over the systemic strategy.
The advantages of a topical rather than a systemic antibiotic are multiple. First, topical medications are delivered directly to the target organ, thereby bypassing pharmacokinetic factors, such as intestinal absorption and hepatic first-pass effects, which can significantly influence tissue concentrations. Therefore, 1000-fold higher tissue concentrations may be realized with topical administration compared with the oral route.9 This is a tremendous pharmacokinetic and pharmacodynamic asset, because the potential for systemic adverse effects is substantially reduced with topical otic versus oral administration, principally because of the lower systemic exposure associated with the topical route. In addition, Roland et al5 have demonstrated that AOMT is often caused by micro-organisms that are not susceptible to oral antibiotics that are approved for pediatric patients but are sensitive to topical otic drops.
Perhaps more important is the advantage that topical antibiotics are less likely to lead to the development of resistance. A previous study conducted in Pittsburgh10 demonstrated a 99.6% sensitivity of aural isolates of P aeruginosa to polymyxin B, one of the antibiotics in Cortisporin (Monarch Pharmaceuticals Inc, Bristol, TN), despite its topical use for >30 years. Of course, polymyxin B is a poor empiric choice for the treatment of either otitis externa or AOMT, because it fails to cover Gram-positive organisms, such as Staphylococcus and Streptococcus species, and can also cause ototoxicity. A consensus otolaryngological panel concluded that resistant formulations of ototopicals are remote.5,11 This failure to provoke resistance has also been observed for topical skin antibiotics and topical eye drops. One reason for this is that the concentrations of topical antibiotics exceed the minimal inhibitory concentrations at the site of infection to such a degree that eradication is more rapid and complete. Resistant clonal selection is less likely, because the area under the curve over minimum inhibitory concentration for the concentration-dependent quinolones favors a rapid and complete bactericidal outcome. Also, topical therapy is generally used in relatively short treatment courses. It is important to note that all 5 of the significant pathogens most commonly isolated from draining ears, P aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis, are of major concern because of their propensity to develop resistance. This fact, coupled with the relatively high prevalence of otitis media and substantial public health concern over bacterial resistance, strongly supports the development of strategies to minimize the emergence of resistant strains in the future.
The microbiologic data produced by this clinical trial further support the theme of less resistance resulting from topical antibiotic strategies. Most striking was the fact that none of the CIP/DEX treatment failures rendered new pathogens at the end of treatment, whereas nearly half of those who failed on AMOX/CLAV (4 of 9) had polymicrobic cultures containing new pathogens, either superinfectors or reinfectors, at the time of failure. Concern has been voiced about the potential for topical quinolones in children to adversely affect ecology and, thus, resistance. To date, no support for this speculation exists in the published literature. Similarly, our study not only fails to support this speculation but supports the opposite conclusion.
Another advantage of topical antibiotics compared with systemic antibiotics is the lower incidence of adverse events compared with oral antibiotics. Common adverse effects of oral therapy, such as diarrhea, nausea, rash, vomiting, abdominal pain, and headache, and more severe adverse effects, such as Stevens-Johnson syndrome, aplastic anemia, seizure, and anaphylaxis, are not seen with topical administration. A trial comparing the efficacy and safety of a nonototoxic quinolone to amoxicillin-clavulanic acid found an incidence of 6% for treatment-related adverse effects associated with the ototopical agent compared with 31% for the systemic agent.8 Our trial revealed similar results. The improved safety profile of topical over systemic antimicrobials is unequivocal.
Not only do the 2 trials that report head-to-head comparisons of topical and systemic antibiotic treatments for AOMT support the ototopical as first-line treatment for uncomplicated infections, but 2 consensus reports arrived at the same conclusion.12,13 The biggest question that these trials leave unanswered is whether or not an ototopical antibiotic in combination with a systemic antibiotic would provide significant advantage over the ototopical CIP/DEX alone. Although, to date, no such trial has been conducted to definitively answer this question, there are several reasons to speculate that such an approach seems unwise. First, the cure rates in this and other trials are in the vicinity of 90%, which would be difficult to improve on. In a disease with a relatively low risk of suppurative complications and a medical environment trying to decrease systemic antibiotic use, the overall risk/benefit ratio of adding a systemic antibiotic to a topical antibiotic as first-line therapy in otherwise uncomplicated cases of AOMT is ill advised. It remains, nonetheless, important to treat AOMT to prevent progression to chronic suppurative otitis media with its attendant complications, which are quite significant.
There is strong support for treating AOMT with a combination product that adds a potent anti-inflammatory agent, such as dexamethasone, to a quinolone antibiotic. Alper et al14 showed in a cynomolgus monkey draining ear model an advantage to adding a topical steroid to an antibiotic. Human trials by Roland et al6,7 confirmed an overall cure rate advantage, a microbiologic eradication advantage, and a time-to-cessation of otorrhea advantage to the steroid/quinolone combination.
Our report clearly demonstrates that there are viable strategies that answer the call by the CDC for more appropriate antibiotic use other than simply not using them at all. We are not implying that elimination of antibiotic treatment when inappropriate (as in viral upper respiratory infections) is imprudent. Recent otitis media guidelines, however, call for withholding them even when a bacterial middle ear infection is diagnosed, a recommendation with which many experts take issue.15 We are unaware of published natural history studies that would support a "watchful waiting" treatment algorithm. Nonetheless, this article clearly provides a treatment strategy that is "the best of both worlds." It is hoped that the data to date will help to affect an algorithm switch to topical management of uncomplicated AOMT.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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This study demonstrates that topical otic treatment with the combination of ciprofloxacin 0.3% and dexamethasone 0.1% dosed for 7 days is superior to treatment with the oral antibiotic combination of amoxicillin (600 mg) and clavulanic acid (42.9 mg) dosed for 10 days. The topical otic drop resolved otorrhea 3.0 to 5.5 days faster and resulted in more clinical cures than did the oral antibiotic suspension. Topical treatment is associated with fewer gastrointestinal adverse effects and complications from yeast infections. The lower incidence of these adverse effects may result in greater tolerability in pediatric patients resulting in improved acceptance and compliance over oral administration.
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ACKNOWLEDGMENTS |
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This study was supported by a grant from Alcon Research Ltd (Fort Worth, TX).
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FOOTNOTES |
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Accepted Mar 2, 2006.
Address correspondence to Sheryl Dupre, MS, Alcon Research Ltd, 6201 S Fwy, Ft Worth, TX 76135. E-mail: sheryl.dupre{at}alconlabs.com
Financial Disclosure: Drs Dohar, Giles, Bikhazi, Carroll, Moe, and Reese are independent physicians who received compensation from the sponsor for the study expenses but received no other financial incentives. Dr Roland is an independent physician who is paid by the sponsor for services as a medical monitor and consultant.
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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- Centers for Disease Control and Prevention. Get smart: know when antibiotics work. Available at: www.cdc.gov/drugresistance/community. Accessed February 1, 2006
- The Otitis Media Guideline Panel. Managing otitis media with effusion in young children.
Pediatrics. 1994;94
:766
–773
[Abstract/Free Full Text] - Subcommittee on Management of Acute Otitis Media. American Academy of Pediatrics and American Academy of Family Physicians. Clinical practice guideline: diagnosis and management of acute otitis media.
Pediatrics. 2004;113
:1451
–1465
[Abstract/Free Full Text] - Dohar JE, Kenna MA, Wadowsky RM. In vitro susceptibility of aural isolates of P. aeruginosa to commonly used ototopicals antibiotics. Am J Otol. 1996;17 :207 –209[CrossRef][Web of Science][Medline]
- Roland PS, Perry D, Stroman D. Microbiology of acute otitis media with a tympanostomy tube. Otolaryngol Head Neck Surg. 2005;133 :585 –595[CrossRef][Web of Science][Medline]
- Roland PS, Kreisler LS, Reese B, et al. Topical Ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes. Pediatrics. 2004;113(1) . Available at: www.pediatrics.org/cgi/content/full/113/1/e40
- Roland PS, Anon JB, Moe RD, et al. Topical ciprofloxacin/dexamethasone is superior to ciprofloxacin alone in pediatric patients with acute otitis media and otorrhea through tympanostomy tubes. Laryngoscope. 2003;113 :2116 –2122[CrossRef][Medline]
- Goldblatt EL, Dohar JE, Nozza RJ, et al. Topical ofloxacin versus systemic amoxicillin/clavulanate in purulent otorrhea in children with tympanostomy tubes. Int J Pediatr Otorhinolaryngol. 1998;46 :91 –101[CrossRef][Web of Science][Medline]
- Campoli-Richards DM, Monk JP, Price A, Benfield P, Todd PA, Ward A. Ciprofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1988;35 :373 –447[Web of Science][Medline]
- Dohar JE, Kenna MA, Wadowsky RM. Therapeutic implications in the treatment of aural pseudomonal infections based on in vitro susceptibility patterns over a five-year period.
Arch Otolaryngol Head Neck Surg. 1995;121
:1022
–1025
[Abstract/Free Full Text] - Weber PC, Roland PS, Hannley M, et al. The development of antibiotic resistant organisms with the use of ototopical medications. 2004;130(suppl) :S89 –S94
- Hannley M, Denneny J, Holzer S, et al. Use of ototopical antibiotics in treating three common ear disease. Otolaryngol Head Neck Surg. 2000;122 :934 –940[CrossRef][Web of Science][Medline]
- Roland PS, Stuart MG, Hannley M, et al. Consensus panel on role of potentially ototoxic antibiotics for topical middle ear use: introduction, methodology, and recommendations. Otolaryngol Head Neck Surg. 2004;130(suppl 3) :S51 –S56[CrossRef]
- Alper CM, Dohar JE, Gulhan M, et al. Treatment of chronic suppurative otitis media with topical tobramycin and dexamethasone.
Arch Otolaryngol Head Neck Surg. 2000;126
:165
–173
[Abstract/Free Full Text] - Wald ER. Otitis media.
N Engl J Med. 2003;348
:363
[Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
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