Abstract
Introduction
Chronic suppurative otitis media (CSOM) is a common cause of hearing impairment and disability. Occasionally it can lead to fatal intracranial infections and acute mastoiditis, especially in developing countries.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for chronic suppurative otitis media in adults and in children? What are the effects of treatments for cholesteatoma in adults and in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 51 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: topical ear cleansing, surgery for cholesteatoma, systemic antibiotics, topical antibiotics, topical antibiotics plus topical corticosteroids, topical antiseptics, topical corticosteroids, tympanoplasty (with or without mastoidectomy).
Key Points
Chronic suppurative otitis media (CSOM) causes recurrent or persistent discharge (otorrhoea) through a perforation in the tympanic membrane, and can lead to thickening of the middle-ear mucosa and mucosal polyps. It usually occurs as a complication of persistent acute otitis media with perforation in childhood.
CSOM is a common cause of hearing impairment, disability, and poor scholastic performance. Occasionally it can lead to fatal intracranial infections and acute mastoiditis, especially in developing countries.
In children with CSOM, topical antibiotics may improve symptoms compared with antiseptics. The benefits of ear cleansing are unknown, although this treatment is usually recommended for children with ear discharge.
We don't know whether topical antiseptics, topical or systemic antibiotics, or topical corticosteroids, alone or in combination with antibiotics, improve symptoms in children with CSOM compared with placebo or other treatments.
In adults with CSOM, topical antibiotics either alone or in combination with topical corticosteroids may improve symptoms compared with placebo or either treatment alone, although we found few adequate studies. There is consensus that topical antibiotics should be combined with ear cleansing so that the antibiotics are able to reach the middle ear space.
We don't know whether topical antiseptics, topical corticosteroids, or systemic antibiotics are beneficial in reducing symptoms.
It is possible that antibiotics against gram-negative bacteria may reduce ear discharge more than other classes of antibiotics or placebo.
We don't know whether tympanoplasty with or without mastoidectomy improves symptoms compared with no surgery or other treatments in adults or children with CSOM.
Cholesteatoma is an abnormal accumulation of squamous epithelium usually found in the middle ear cavity and mastoid process of the temporal bone. Granulation tissue and ear discharge are often associated with secondary infection of the desquamating epithelium.
Cholesteatoma can be either congenital (behind an intact tympanic membrane) or acquired. If untreated, it may progressively enlarge and erode the surrounding structures.
Clinical context
About this condition
Definition
Chronic suppurative otitis media (CSOM) is persistent inflammation of the middle ear or mastoid cavity. Synonyms include "chronic otitis media", chronic mastoiditis, and chronic tympanomastoiditis. CSOM is characterised by recurrent or persistent ear discharge (otorrhoea) over 2 to 6 weeks through a perforation of the tympanic membrane. CSOM usually begins as a complication of persistent acute otitis media (AOM) with perforation in childhood. Typical findings may also include thickened granular middle-ear mucosa and mucosal polyps. Occasionally, CSOM will be associated with a cholesteatoma within the middle ear. CSOM is differentiated from chronic otitis media with effusion, in which there is an intact tympanic membrane with fluid in the middle ear but no active infection. CSOM does not include chronic perforations of the eardrum that are dry, or only occasionally discharge, and have no signs of active infection. Cholesteatoma is an abnormal accumulation of squamous epithelium usually found in the middle ear cavity and mastoid process of the temporal bone. Granulation tissue and ear discharge are often associated with secondary infection of the desquamating epithelium. Cholesteatoma is most often detected by careful otoscopic examination in children or adults with persistent discharge that does not respond to treatment.
Incidence/ Prevalence
The worldwide prevalence of CSOM is 65 to 330 million people, and 39 to 200 million (60%) have clinically significant hearing impairment.[1] Cholesteatoma can be either congenital (behind an intact tympanic membrane) or acquired. The overall incidence is estimated to be around 9 per 100,000 people. At least 95% of cholesteatomas are acquired. The incidence is similar in children and adults.[2]
Aetiology/ Risk factors
CSOM is usually a complication of persistent AOM, but the risk factors for CSOM vary in different settings. Frequent upper respiratory tract infections and poor socioeconomic conditions (overcrowded housing[3] [4] and poor hygiene and nutrition[4]) are often associated with the development of CSOM.[5] [6] In developed countries and advantaged populations, previous insertion of tympanostomy tubes is now probably the single most important aetiological factor.[7] Of those children with tympanostomy tubes in place, a history of recurrent AOM, older siblings, and attendance at child care centres all increase the risk of developing CSOM.[7] In developing countries and disadvantaged populations, poverty, overcrowding, family history, exposure to smoke, and being Indigenous are important.[4] [8] [9]Improvement in housing, hygiene, and nutrition in Maori children was associated with a halving of the prevalence of CSOM between 1978 and 1987[10](see also review on acute otitis media). The most commonly isolated microorganisms are Pseudomonas aeruginosa and Staphylococcus aureus;[11] P aeruginosa has been particularly implicated in the causation of bony necrosis and mucosal disease. One systematic review found a lack of studies assessing the role of prophylactic antibiotics in preventing the progression of disease to CSOM.[12]Most cholesteatomas are thought to occur as a complication of a retraction pocket in the tympanic membrane. They are associated with recurrent or persistent middle ear disease, family history, and craniofacial abnormalities. If untreated, a cholesteatoma may progressively enlarge and erode the surrounding structures.[2]
Prognosis
The natural history of CSOM is poorly understood. The perforation may close spontaneously in an unknown portion of cases, but it persists in others leading to mild to moderate hearing impairment (about 26–60 dB increase in hearing thresholds), based on surveys among children in Africa, Brazil,[13] India,[14] and Sierra Leone,[15] and among the general population in Thailand.[16] In many developing countries, CSOM represents the most frequent cause of moderate hearing loss (40–60 dB).[17] Persistent hearing loss during the first 2 years of life may increase learning disabilities and poor scholastic performance.[18] Progressive hearing loss may occur among those in whom infection persists and discharge recurs. Less frequently, spread of infection may lead to life-threatening complications such as intracranial infections and acute mastoiditis.[19] The frequency of serious complications fell from 20% in 1938 to 2.5% in 1948 worldwide and is currently estimated to be about 0.7% to 3.2% worldwide.[11] This is believed to be associated with increased use of antibiotic treatment, tympanoplasty, and mastoidectomy.[20] [21] [22] Otitis media was estimated to have caused 3599 deaths and a loss of almost 1.5 disability-adjusted life years in 2002, 90% of which were in developing countries.[23] Most of these deaths were probably owing to CSOM, because AOM is a self-limiting infection (see review on acute otitis media).
Aims of intervention
To improve symptoms of otorrhoea; heal perforations; improve hearing; and reduce complications, with minimum adverse effects of treatment.
Outcomes
Death; reduction in otorrhoea: proportion of people with otorrhoea measured subjectively or by otoscopy; with tympanic perforation; hearing loss; intra- and extracranial complications; duration of otorrhoea-free periods. The correlation between subjective cessation of otorrhoea and otoscopic findings was poor in one RCT.[24] Many RCTs used compound outcomes denoting otoscopic activity (i.e., otorrhoea or inflammation in the middle ear). Hearing: severity of hearing loss; intra- and extracranial complications; adverse effects of treatment.
Methods
Clinical Evidence search and appraisal May 2010. Studies that included both adults (aged 16 years or older) and children (aged 10 years or younger) or which failed to specify the age of participants were excluded from the benefits section. However, we have included harms data from systematic reviews that included both adults and children. The RCTs varied in their definitions of CSOM and measurements of severity. Most RCTs were brief (7 days to 4 weeks). Most had inadequate methods from which to draw reliable conclusions (see main text for descriptions). Participants with cholesteatoma were excluded from most, but not all, trials of treatments for CSOM. All trials excluded people with impending serious complications. The following databases were used to identify studies for this systematic review: Medline 1966 to May 2010; Embase 1980 to May 2010; and The Cochrane Database of Systematic Reviews 2010, Issue 2 (1966 to April 2010). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, and containing >20 individuals. There was no minimum length of follow-up required to include studies. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition we did an observational harms search for ototoxicity of topical antibiotics and topical antiseptics as highlighted by the contributor. We searched for prospective and retrospective cohort and case series studies of at least 20 individuals. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Chronic suppurative otitis media.
| Important outcomes | Death, Hearing, Intra- and extracranial complications, Reduction in otorrhoea | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatments for chronic suppurative otitis media in adults? | |||||||||
| 2 (154) | Reduction in otorrhoea | Topical antibiotics plus topical corticosteroids versus placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for uncertainty about benefit |
| 1 (64) | Reduction in otorrhoea | Topical antibiotics plus topical corticosteroids versus topical corticosteroids alone | 4 | –3 | 0 | 0 | +1 | Low | Quality points deducted for sparse data, no intention-to-treat analysis, and uncertainty about blinding. Effect-size point added for RR <0.5 |
| 2 (402) | Reduction in otorrhoea | Topical antibiotics plus topical corticosteroids versus topical antibiotics alone | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for uncertainty about definition of outcome |
| 5 (247) | Reduction in otorrhoea | Systemic antibiotics versus topical antibiotics | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for wide range of comparators |
| 1 (51) | Reduction in otorrhoea | Systemic antibiotics versus topical antiseptics | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 3 (286) | Reduction in otorrhoea | Systemic antibiotics versus each other | 4 | 0 | –1 | 0 | 0 | Moderate | Consistency point deducted for conflicting results |
| 1 (26) | Reduction in otorrhoea | Systemic antibiotics added to mastoidectomy or tympanoplasty | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for baseline differences in disease severity |
| 3 (150) | Reduction in otorrhoea | Topical plus systemic antibiotics versus topical antibiotics alone | 4 | –1 | –1 | –1 | 0 | Very low | Quality point deducted for sparse data. Consistency point deducted for conflicting results. Directness point deducted for wide range of comparators |
| 2 (308) | Reduction in otorrhoea | Topical antibiotics plus systemic antibiotics versus systemic antibiotics alone | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| 1 (35) | Reduction in otorrhoea | Topical antibiotics versus placebo | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data and methodological issues (poor follow-up, and uncertainty about randomisation and blinding) |
| at least 4 (at least 402) | Reduction in otorrhoea | Topical antibiotics versus each other | 4 | 0 | –1 | 0 | 0 | Moderate | Consistency point deducted for conflicting results |
| 2 (89) | Reduction in otorrhoea | Topical antibiotics versus topical antiseptics | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for conflicting results |
| 1 (101) | Reduction in otorrhoea | Topical antibiotics added to tympanoplasty | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (68) | Reduction in otorrhoea | Tympanoplasty plus mastoidectomy versus tympanoplasty alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (68) | Hearing | Tympanoplasty plus mastoidectomy versus tympanoplasty alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| What are the effects of treatments for chronic suppurative otitis media in children? | |||||||||
| 1 (33) | Reduction in otorrhoea | Systemic antibiotics versus placebo or no treatment in children having ear cleansing and debridement | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 2 (63) | Reduction in otorrhoea | Systemic antibiotics versus each other | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (96) | Reduction in otorrhoea | Topical antibiotics versus each other | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data and methodological issues (uncertainty about methodology and short follow-up) |
| 1 (97) | Reduction in otorrhoea | Topical antibiotics versus topical antibiotics plus topical corticosteroids | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (73) | Hearing | Topical antibiotics versus topical antibiotics plus topical corticosteroids | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 2 (103) | Reduction in otorrhoea | Topical antiseptics versus placebo or no treatment | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and for 1 study being underpowered |
| 3 (666) | Reduction in otorrhoea | Topical antiseptics versus topical antibiotics | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for uncertainty about methodology in 1 study |
| 1 (427) | Hearing | Topical antiseptics versus topical antibiotics | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for uncertainty about clinical significance of difference in hearing outcome |
| 2 (658) | Reduction in otorrhoea | Ear cleansing versus no treatment | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for allocation and blinding flaws. Consistency point deducted for conflicting results |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Cholesteatoma
An accumulation of epithelial debris in the middle ear cavity, which can arise congenitally or can be acquired. The tissue is probably derived from skin. It grows slowly but can erode and destroy adjacent structures (ossicles, the mastoid, the inner ear, or the bone leading to the intracranial cavity), potentially leading to persistent pain and otorrhoea, hearing loss, dizziness, facial nerve paralysis, and intracranial infection.
- Disability-adjusted life year (DALY)
A measure of the impact of a condition, designed to include the loss attributable to premature death and the loss caused by a disability of known duration and severity. One DALY is equivalent to the loss of 1 year of healthy life.
- Ear cleansing
Also known as aural toilet, this consists of mechanical removal of ear discharge and other debris from the ear canal and middle ear by mopping with cotton pledgets, wicking with gauze, flushing with sterile solution, or suctioning. This can be done with an otomicroscope or under direct vision with adequate illumination of the middle ear.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Mastoidectomy
A general term used to describe various surgical procedures that are usually used to remove abnormal parts of the mastoid bone and surrounding structures, or to allow access to the middle ear.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Tympanoplasty
A general term used to describe various surgical repairs of the eardrum or ossicles of the middle ear to improve hearing in people with conductive deafness.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Acute otitis media
Otitis media with effusion
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
References
- 1.World Health Organization. Chronic suppurative otitis media. Burden of illness and management options. 2004. http://www.who.int/entity/pbd/deafness/activities/hearing_care/otitis_media.pdf (last accessed 3 May 2012). [Google Scholar]
- 2.Isaacson GC. Cholesteatoma in children. In: Friedman EM, ed. UpToDate online 18.3. Waltham, MA: UpToDate, 2010. [Google Scholar]
- 3.Homoe P. Otitis media in Greenland. Studies on historical, epidemiological, microbiological, and immunological aspects. Int J Circumpolar Health 2001;60(suppl 2):1–54. [PubMed] [Google Scholar]
- 4.Lasisi AO, Olaniyan FA, Muibi SA, et al. Clinical and demographic risk factors associated with chronic suppurative otitis media. Int J Pediatr Otorhinolaryngol 2007;71:1549–1554. [DOI] [PubMed] [Google Scholar]
- 5.Tos M. Sequelae of secretory otitis media and the relationship to chronic suppurative otitis media. Ann Otol Rhinol Laryngol 1990;99:18–19. 2294830 [Google Scholar]
- 6.Daly KA, Hunter LL, Levine SC, et al. Relationships between otitis media sequelae and age. Laryngoscope 1998;108:1306–1310. [DOI] [PubMed] [Google Scholar]
- 7.van der Veen EL, Schilder AG, van Heerbeek N, et al. Predictors of chronic suppurative otitis media in children. Arch Otolaryngol Head Neck Surg 2012;132:1115–1118. [DOI] [PubMed] [Google Scholar]
- 8.Koch A, Homøe P, Pipper C, et al. Chronic suppurative otitis media in a birth cohort of children in Greenland: population-based study of incidence and risk factors. Pediatr Infect Dis J 2011;30:25–29. [DOI] [PubMed] [Google Scholar]
- 9.Fliss DM, Shoham I, Leiberman A, et al. Chronic suppurative otitis media without cholesteatoma in children in southern Israel: incidence and risk factors. Pediatr Infect Dis J 1991;10:895–899. [DOI] [PubMed] [Google Scholar]
- 10.New Zealand Health Technology Assessment Clearing House. Screening programmes for the detection of otitis media with effusion and conductive hearing loss in pre-school and new entrant school children. A critical appraisal of the literature (NZHTA report 3). Christchurch, New Zealand, June 1998. Available at http://nzhta.chmeds.ac.nz/publications/nzhta3.pdf (last accessed 3 May 2012). Search date 1998. [Google Scholar]
- 11.Verhoeff M, Van der Veen EL, Rovers MM, et al. Chronic suppurative otitis media: a review. Int J Pediatr Otorhinolaryngol 2006;70:1–12. [DOI] [PubMed] [Google Scholar]
- 12.Leach AJ, Morris PS. Antibiotics for the prevention of acute and chronic suppurative otitis media in children. In: The Cochrane Library, Issue 4, 2006. Chichester, UK: John Wiley & Sons, Ltd. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Bastos I. Otitis media and hearing loss among children in developing countries. Malmo: University of Malmo, 1994. [Google Scholar]
- 14.Jacob A, Rupa V, Job A, et al. Hearing impairment and otitis media in a rural primary school in south India. Int J Pediatr Otorhinolaryngol 1997;39:133–138. [DOI] [PubMed] [Google Scholar]
- 15.Seely DR, Gloyd SS, Wright AD, et al. Hearing loss prevalence and risk factors among Sierra Leonean children. Arch Otolaryngol Head Neck Surg 1995;121:853–858. [DOI] [PubMed] [Google Scholar]
- 16.Antarasena S, Antarasena N, Lekagul S, et al. The epidemiology of deafness in Thailand. Otolaryngol Head Neck Surg 1988;3:9–13. [Google Scholar]
- 17.Muya EW, Owino O. Special education in Africa: research abstracts. Nairobi: UNESCO, 1986. [Google Scholar]
- 18.Teele DW, Klein JO, Chase C, et al. Otitis media in infancy and intellectual ability, school achievement, speech, and language at age 7 years. Greater Boston Otitis Media Study Group. J Infect Dis 1990;162:685–694. [DOI] [PubMed] [Google Scholar]
- 19.Osma U, Cureoglu S, Hosoglu S. The complications of chronic otitis media: report of 93 cases. J Laryngol Otol 2000;114:97–100. [DOI] [PubMed] [Google Scholar]
- 20.Kenna M. Incidence and prevalence of complications of otitis media. Ann Otol Rhinol Laryngol 1990;99(suppl 149):38–39. [Google Scholar]
- 21.Berman S. Otitis media in developing countries. Pediatrics 1995;96:126–131. [PubMed] [Google Scholar]
- 22.Sorensen H. Antibiotics in suppurative otitis media. Otolaryngol Clin North Am 1977;10:45–50. [PubMed] [Google Scholar]
- 23.World Health Organization. Revised global burden of disease (GBD) 2002 estimates. Available at http://www.who.int/healthinfo/global_burden_disease/estimates_regional_2002_revised/en/ (last accessed 3 May 2012). [Google Scholar]
- 24.Browning GG, Gatehouse S, Calder IT. Medical management of active chronic otitis media: a controlled study. J Laryngol Otol 1988;102:491–495. [DOI] [PubMed] [Google Scholar]
- 25.Picozzi G, Browning G, Calder I. Controlled trial of gentamicin and hydrocortisone ear drops in the treatment of active chronic otitis media. Clin Otolaryngol 1983;8:367–368. [Google Scholar]
- 26.Crowther JA, Simpson D. Medical treatment of chronic otitis media: steroid or antibiotic with steroid ear-drops? Clin Otolaryngol 1991;6:142–144. [DOI] [PubMed] [Google Scholar]
- 27.Podoshin L, Fradis M, Ben David J, et al. Ototoxicity of ear drops in patients suffering from chronic otitis media. J Laryngol Otol 1989;103:46–50. [DOI] [PubMed] [Google Scholar]
- 28.Kaygusuz I, Karlidag T, Gok U, et al. Efficacy of topical ciprofloxacin and tobramycin in combination with dexamethasone in the treatment of chronic suppurative otitis media. Kulak Burun Bogaz Ihtisas Dergisi 2002;9:106–111. [In Turkish] [PubMed] [Google Scholar]
- 29.Miro N, Perello E, Casamitjana F, et al. Controlled multicenter study on chronic suppurative otitis media treated with topical applications of ciprofloxacin 0.2% solution in single-dose containers or combination of polymyxin B, neomycin, and hydrocortisone suspension. Otolaryngol Head Neck Surg 2000;23:617–623. [DOI] [PubMed] [Google Scholar]
- 30.Macfadyen CA, Acuin JM, Gamble C. Systemic antibiotics versus topical treatments for chronically discharging ears with underlying eardrum perforations. In: The Cochrane Library, Issue 1, 2006. Chichester, UK: John Wiley & Sons, Ltd. [DOI] [PubMed] [Google Scholar]
- 31.Browning G, Picozzi G, Calder I, et al. Controlled trial of medical treatment of active chronic otitis media. BMJ 1983;287:1024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Esposito S, D'Errico G, Montanaro C. Topical and oral treatment of chronic otitis media with ciprofloxacin. Arch Otolaryngol Head Neck Surg 1990;116:557–559. [DOI] [PubMed] [Google Scholar]
- 33.Esposito S, D'Errico G, Mantanaro C. Topical ciprofloxacin vs. intramuscular gentamicin for chronic otitis media. Arch Otolaryngol Head Neck Surg 1992;118:842–844. [DOI] [PubMed] [Google Scholar]
- 34.Povedano Rodriguez V, Seco Pinero M, Jurado Ramos A, et al. Efficacy of topical ciprofloxacin in the treatment of chronic otorrhea. Acta Otorrinolaringol Esp 1995;46:15–18. [In Spanish] [PubMed] [Google Scholar]
- 35.Yuen P, Lau S, Chau P, et al. Ofloxacin eardrop treatment for active chronic suppurative otitis media: prospective randomized study. Am J Otol 1994;15:670–673. [PubMed] [Google Scholar]
- 36.Legent F, Bordure P, Beauvillain C, et al. Controlled prospective study of oral ciprofloxacin versus amoxicillin/clavulanic acid in chronic suppurative otitis media in adults. Chemotherapy 1994;40(suppl 1):16–23. [DOI] [PubMed] [Google Scholar]
- 37.Cannoni M, Bonfils P, Sednaoui P, et al. Cefotiam hexetil versus amoxicillin/clavulanic acid for the treatment of chronic otitis media in adults. Med Mal Infect 1997;27:915–921. [Google Scholar]
- 38.Gonzalez A, Galindo T. Estudio abierto comparativo del tratamiento de otitis media cronica con levofloxacino vs amoxicillina/clavulanato. Invest Med Int 2001;28:33–36. [In Spanish] [Google Scholar]
- 39.Lildholdt T, Felding J, Juul A, et al. Efficacy of perioperative ceftazidime in the surgical treatment of chronic otitis media due to Pseudomonas aeruginosa. Arch Otorhinolaryngol 1986;243:167–169. [DOI] [PubMed] [Google Scholar]
- 40.Picozzi G, Browning G, Calder I. Controlled trial of gentamicin and hydrocortisone ear drops with and without systemic metronidazole in the treatment of active chronic otitis media. Clin Otolaryngol 1984;9:305. [Google Scholar]
- 41.Supiyaphun P, Kerekhanjanarong V, Koranasophonepun J, et al. Comparison of ofloxacin otic solution with oral amoxycillin plus chloramphenicol ear drop in treatment of chronic suppurative otitis media with acute exacerbation. J Med Assoc Thai 2000;83:61–68. [PubMed] [Google Scholar]
- 42.Mira E, Benazzo M. Uso topico delle cefalosporine nel trattamento delle otiti medie purulente: valutazione della ceftizoxima (Eposerin�). Riv Ital Otorinolaringol Audiol Foniat 1992;12:219–225. [Google Scholar]
- 43.Macfadyen CA, Acuin JM, Gamble C. Topical antibiotics without steroids for chronically discharging ears with underlying eardrum perforations. In: The Cochrane Library, Issue 4, 2005. Chichester, UK: John Wiley & Sons, Ltd. Search date 2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Gyde MC, Randall RF. Comparative double-blind study of trimethoprim–sulfacetamide–polymyxin B and of gentamicin in the treatment of otorrhoea. Ann Otolaryngol Chir Cervicofac 1978;95:43–55. [PubMed] [Google Scholar]
- 45.Gyde M. A double-blind comparative study of trimethoprim–polymyxin B versus trimethoprim–sulfacetamide–polymyxin B otic solutions in the treatment of otorrhea. J Laryngol Otol 1981;95:251–259. [DOI] [PubMed] [Google Scholar]
- 46.Fradis M, Brodsky A, Ben David J, et al. Chronic otitis media treated topically with ciprofloxacin or tobramycin. Arch Otolaryngol Head Neck Surg 1997;123:1057–1060. [DOI] [PubMed] [Google Scholar]
- 47.Tong MC, Yue V, Ku PK, et al. Preoperative topical ofloxacin solution for tympanoplasty: a randomized, controlled study. Otol Neurotol 2002;23:18–20. [DOI] [PubMed] [Google Scholar]
- 48.Lazo Sáenz GJ, Alonzo Rojo SE, Pérez Blanco A. Topical treatment in chronic otitis media. An Otorrinolaringol Mex 1999;45:17–19. [In Spanish] [Google Scholar]
- 49.Marias J, Rutka JA. Ototoxicity and topical eardrops. Clin Otolaryngol 1998;23:360–367. [DOI] [PubMed] [Google Scholar]
- 50.Leliever WC. Topical gentamicin-induced positional vertigo. Otolaryngol Head Neck Surg 1985;93:553–555. [DOI] [PubMed] [Google Scholar]
- 51.Longridge NS. Topical gentamicin vestibular toxicity. J Otolaryngol 1994;23:444–446. [PubMed] [Google Scholar]
- 52.Matz G, Rybak L, Roland PS, et al. Ototoxicity of ototopical antibiotic drops in humans. Otolaryngol Head Neck Surg 2004;130:S79–S82. [DOI] [PubMed] [Google Scholar]
- 53.Bhat KV, Naseeruddin K, Nagalotimath US, et al. Cortical mastoidectomy in quiescent, tubotympanic, chronic otitis media: is it routinely necessary? J Laryngol Otol 2009;123:383–390. [DOI] [PubMed] [Google Scholar]
- 54.Colletti V, Fiorino FG, Indelicato T. Surgery vs natural course of chronic otitis media. Long term hearing evaluation. Acta Otolaryngol 1991;111:762–768. [DOI] [PubMed] [Google Scholar]
- 55.Soldati D, Mudry A. Cholesteatoma in children: techniques and results. Int J Pediatr Otorhinolaryngol 2000;52:269–276. [DOI] [PubMed] [Google Scholar]
- 56.Chang CC, Chen MK. Canal-wall-down tympanoplasty with mastoidectomy for advanced cholesteatoma. J Otolaryngol 2000;29:270–273. [PubMed] [Google Scholar]
- 57.Vartiainen E, Kansanen M. Tympanomastoidectomy for chronic otitis media without cholesteatoma. Otolaryngol Head Neck Surg 1992;106:230–234. [DOI] [PubMed] [Google Scholar]
- 58.Mishiro Y, Sakagami M, Takahashi Y, et al. Tympanoplasty with and without mastoidectomy for non-cholesteatomatous chronic otitis media. Eur Arch Otorhinolaryngol 2001;258:13–15. [DOI] [PubMed] [Google Scholar]
- 59.Berenholz LP, Rizer FM, Burkey JM, et al. Ossiculoplasty in canal wall down mastoidectomy. Otolaryngol Head Neck Surg 2000;123:30–33. [DOI] [PubMed] [Google Scholar]
- 60.Fliss D, Dagan R, Houri Z, et al. Medical management of chronic suppurative otitis media without cholesteatoma in children. J Pediatr 1990;116:991–996. [DOI] [PubMed] [Google Scholar]
- 61.Somekh E, Cordova Z. Ceftazidime versus aztreonam in the treatment of pseudomonal chronic suppurative otitis media in children. Scand J Infect Dis 2000;32:197–199. [DOI] [PubMed] [Google Scholar]
- 62.Van Hasselt P. Treatment of chronic suppurative otitis media with suction cleaning and antiseptic versus antibiotic ear drops. Internal Report of Christian Blind Mission International: Bensheim, Germany, 1997. [Google Scholar]
- 63.Abes G, Espallardo N, Tong M, et al. A systematic review of the effectiveness of ofloxacin otic solution for the treatment of suppurative otitis media. ORL J Otorhinolaryngol Relat Spec 2003;65:106–116. Search date 2000. [DOI] [PubMed] [Google Scholar]
- 64.Leach A, Wood Y, Gadil E, et al. Topical ciprofloxin versus topical framycetin-gramicidin-dexamethasone in Australian aboriginal children with recently treated chronic suppurative otitis media: a randomized controlled trial. Pediatr Infect Dis J 2008;27:692–698. [DOI] [PubMed] [Google Scholar]
- 65.van Hasselt P, van Kregten E. Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi. Int J Pediatr Otorhinolaryngol 2002;63:49–56. [DOI] [PubMed] [Google Scholar]
- 66.Thorp MA, Gardiner IB, Prescott CA. Burow's solution in the treatment of active mucosal chronic suppurative otitis media: determining an effective dilution. J Laryngol Otol 2000;114:432–436. [DOI] [PubMed] [Google Scholar]
- 67.Eason R, Harding F, Nicholson R, et al. Chronic suppurative otitis media in the Solomon Islands: a prospective microbiological, audiometric and therapeutic survey. N Z Med J 1986;99:812–815. [PubMed] [Google Scholar]
- 68.Macfadyen C, Gamble C, Garner P, et al. Topical quinolone vs. antiseptic for treating chronic suppurative otitis media: a randomized controlled trial. Trop Med Int Health 2005;10:190–197. [DOI] [PubMed] [Google Scholar]
- 69.Smith A, Hatcher J, Mackenzie I, et al. Randomised controlled trial of treatment of chronic suppurative otitis media in Kenyan schoolchildren. Lancet 1996;348:1128–1133. [DOI] [PubMed] [Google Scholar]
- 70.Darrouzet V, Duclos JY, Portmann D, et al. Preference for the closed technique in the management of cholesteatoma of the middle ear in children: a retrospective study of 215 consecutive patients treated over 10 years. Am J Otol 2000;21:474–481. [PubMed] [Google Scholar]
- 71.Tos M, Stangerup SE, Orntoft S. Reasons for reperforation after tympanoplasty in children. Acta Otolaryngol Suppl 2000;543:143–146. [DOI] [PubMed] [Google Scholar]
- 72.Mak DB, MacKendrick A, Bulsara MK, et al. Long-term outcomes of middle-ear surgery in Aboriginal children. Med J Aust 2003;179:324–325. [DOI] [PubMed] [Google Scholar]
- 73.Hamilton JW. Efficacy of the KTP laser in the treatment of middle ear cholesteatoma. Otol Neurotol 2005;26:135–139. [DOI] [PubMed] [Google Scholar]