Table 2. Treatment regimens used
Research ID Class of drugs used (Topical unless specified) Treatment (Detailed) Duration of treatment Ear toileting
Cimolai N, 2020
Hydroxyquinoline
1% - 3% Clioquinol
Unspecified
Unspecified
Jimenez-Garcia L et al, 2020
Azole versus thiocarbamate
Group 1 - Clotrimazole cream was applied to ears and left for 7 days Group 2 - Patients were instructed to apply Tolnaftate solution 2 drops every 12 h for 7 days
1 week
Group 1 - Cream residue removed from EAC after 7 days Group 2 - EAC cleaned and dried after 7 days
Mohammed W et al, 2020
Azoles (topical & oral) and polyene
Clotrimazole, fluconazole, nystatin or miconazole. If no response, patient treated with systemic antifungal (fluconazole and voriconazole)
Unspecified
Clearance of fungal mass
Moslem M & Mahmoudabadi AZ, 2020
Azoles versus echinocandin versus polyene
Luliconazole, voriconazole, caspofungin and amphotericin B
Not applicable
Not applicable
Abastabar M, 2019
Cephalosporin (oral), aminoglycosides, polyene and allylamine
Oral Cefixime 400 mg/d and topical gentamicin Topical nystatin 100 000 U/g TDS and terbinafine 250 mg TDS
Unspecified
Unspecified
Al-Hashimi et al, 2019
Azole versus thiocarbamate versus combination of azole and steroids
1st group - Clotrimazole solution / clotrimazole cream 2nd group - Tolnaftate solution 3rd group for severe candida infection- Clotrimazole mixed with steroid for 2 days, then extraction of mass, then clotrimazole with steroid for a further 5 days, then steroid cessation and continuation of clotrimazole for 2 weeks For severe Aspergillus niger infection - Tolnaftate mixed with steroid for 2 days, then extraction of mass, then tolnaftate with steroid for a further 5 days, then steroid cessation and continuation of tolnaftate for 2 weeks
2 weeks
Suction of ear canal and cleaning by dry method For severe infection, extraction of mass, after washing, complete cleaning and drying of ear
Teharia RK & Narvey VP, 2019
Antiseptic versus azole
Group A - Betadine (povidone iodine 10%) 10 ml solution ear wash using syringes at each visit Group B - 4 drops of clotrimazole 1% QID
20 days
Ear washing with 10% betadine 10 ml solution using syringes at each visit
Sumbria D et al, 2019
Azole versus azole versus thiocarbamate versus combination of azole, antibiotic and steroids
Group 1 - 1% Luliconazole lotion Group 2 - 2% Sertaconazole cream Group 3 - 1% Terbinafine hydrochloride cream Group 4 - 0.5% Fluconazole gel Group 5 - 1% Clotrimazole lotion Group 6 - Combination of 1% clotrimazole, chloramphenicol and beclomethasone eardrops
4 weeks
Dry aural toileting with swab stick
Kiakojori K et al, 2019
Azole
Clotrimazole 2 drops 3 times per week
4 weeks
Cleaning and drying of ear canal
Dundar R & Iynen I, 2019
Azole
The ear canal was filled with 1% clotrimazole cream
7-15 days
Cleaning of ear canal by microsuction
Hivary S et al, 2019
Azoles versus polyene versus echinocandin
Luliconazole, amphotericin B, posaconazole and caspofungin
Not applicable
Not applicable
Kanade SM, 2018
Azole versus Azole
Group A - 1% Clotrimazole eardrops, 3-5 drops TDS instilled by the patient Group B - 0.3% Fluconazole eardrops, 3-5 drops TDS instilled by the patient For proper administration of eardrops, instructions were given by a trained nurse assistant
3 weeks
Patients were advised to keep the ear dry
Ahmed MR et al, 2018
Azoles versus polyene macrolide antibiotic
Ketoconazole 2% cream, Miconazole 2% cream Nystatin 100 000 U/g cream was used for Candida spp.
2 weeks
Removal ear canal debris
Kiakojori K et al, 2018
Azole
2% Miconazole ointment
Unspecified
Suction clearance and removal of colonies ± 2% oxygenated solution / distilled water / normal saline followed by drying of the ear
Mofatteh MR et al, 2018 Antiseptic alone versus azole, thiocarbamate & antiseptic Group 1 - washed by physician using 10 ml betadine 10% with syringe Group 2 - 8 drops of clotrimazole 8 hourly For resistant cases, tolnaftate and Gentian Violet were used
20 days
Ear washing with 10 ml betadine 10% with syringe
Mahdavi OS et al, 2018
Combination of cephalosporin and azole versus azole alone
1% Clotrimazole cream injected into ear canal under the microscope for both groups Intervention group received ceftizoxime 1 g powder sprayed in ear canal using insufflation
Unspecified
Suction clearance
Ali K et al, 2018
Polyenes versus azoles versus allylamine
Amphotericin B 100 units and nystatin 100 units fluconazole 25 ug, ketoconazole 10 ug, clotrimazole 10 ug, voriconazole 1 ug and itraconazole 10 ug Terbinafine 25 ug
Not applicable
Not applicable
Nagl M et al, 2018
Chloramine, steroids and azole
Cotton strip soaked with 1% N-chlorotaurine (NCT) plus 0.1% dexamethasone. The strip was changed daily 1% clotrimazole strip was used in case of relapse Treatment was changed again to 1% NCT plus 0.1% dexamethasone
8 days
Unspecified
Chappe M et al, 2018
Polyene & azole
Nystatin (Auricularum®, Grimberg) BD for 1 month Econazole cream was started 7 months later due to relapse, but was difficult to apply. Finally, 1% voriconazole solution was used TDS / QID for 14 days
14 days after relapse
Ear canal suction
Baumgardner DJ, 2017
Mixture of acidifying agent and alcohol or azole
2% acetic acid in propylene glycol or 1% clotrimazole solution
Unspecified
Unspecified
Agarwal P & Devi LS, 2017
Azole
Clotrimazole drops, 4-5 times daily
10-14 days
Thorough aural toilet
Mishra D et al, 2017
Azole versus azole
Group A - Patients were instructed to instil 1% clotrimazole 3 drops TDS Group B - 1% clotrimazole cream was squirted into 2 ml syringe and ear canal was filled with this cream under endoscopic guidance
1 week
Unspecified
Arndal E et al, 2016
Azoles versus polyene versus steroids versus antiseptics versus allylamine
Clotrimazole, miconazole Nystatin Hydrocortisone Methylrosanilin (Gentian Violet) Terbinafine
Unspecified
Unspecified
Arifullah et al, 2016
Acidifying agent & azole
1% clotrimazole lotion or cream (impregnated gauze)
1-3 weeks
Local debridement, ear cleaning with dilute aluminium acetate solution combined with acetic acid
Nandyal CB & Choudhari AS, 2015
Azole versus Azole
1% Clotrimazole eardrops TDS were used in 70 cases 1% miconazole eardrops TDS were used in 65 cases
2 months
Cleaning of fungal mass and debris in infected ear canal either by dry mopping (98%), microsuction (4.4%) or syringing (0.74%)
Vadisha SB et al, 2015
Azoles
Topical clotrimazole was widely used For patients who did not respond to clotrimazole, fluconazole was an alternative
3 weeks
Suction clearance of fungal debris
Zarei Mahmoudabadi A et al, 2015
Azoles versus polyene versus allylamine
Clotrimazole 50 ug/disk Miconazole 10 ug/disk Nystatin 100 ug/disk 10% terbinafine (Lamisil) stock was prepared with dimethyl sulfoxide 12 ug/disk
Not applicable
Not applicable
Abed AR & Hussein IM, 2015
H2O2 versus antiseptic versus acidifying agent
3% H2O2, 1% Iodine, 2% Acetic acid
Not applicable
Not applicable
Navaneethan N & YaadhavaKrishnan RP, 2015
Azole versus azole
Group A - 1% Clotrimazole eardrops, 3-5 drops TDS Group B - Two application of miconazole cream, once during initial visit and second application during first week review for persistent disease Group C - Fluconazole drops, 3-5 drops TDS
2 weeks
Aural toileting
Naqi S et al, 2014
Azole
Clotrimazole lotion BD
2 weeks
Unspecified
Anwar K & Gohar MS, 2014
Azole / acidifying agents in alcohol / polyene (oral)
Clotrimazole 1% lotion or cream / 2% salicylic acid in alcohol / ototopical drops with propylene glycol / antimicrobial / fluconazole / nystatin (Nilstat)
1 week
Aural cleaning
Adoga AS & Iduh AA, 2014
Combination of azole, antibiotic, local anaesthetics, steroid, alcohol, hydroxyquinoline / steroid
Discontinuation of antibiotics Combination of clotrimazole, Chloramphenicol, lignocaine hydrochloride, Beclomethasone, glycerine (Candibiotic®) in 98.0%, Clioquinol / Flumethasone (Locacorten Vioform®) in 2.0%
2 weeks
Aural toileting
Nemati S et al, 2014
Azoles & polyene
Clotrimazole, fluconazole, ketoconazole and nystatin
Not applicable
Not applicable
Prasad SC et al, 2014
Azole
Clotrimazole 4-5 drops TDS
7-14 days
Aural toilet by suctioning and removal of fungal debris
Philip A et al, 2013
Antiseptic versus combination of azole with local anaesthetic
Group 1 - 3 drops of 1% clotrimazole & 2% lignocaine in propyl glycerol were instilled in the affected ear OD Group 2 - 3 drops of 7.5% povidone-iodine were instilled in the affected ear OD
2 weeks
Thorough toileting of the ear canal
Khan F et al, 2013
Azole
Clotrimazole lotion 5 drops TDS
2 weeks
Unspecified
Neji S et al, 2013
Azole
Ecorex ® (econazole nitrate) 5 drops BD
10 weeks
Intense cleaning
Dorasala SP & Dorasala S, 2013
Antifungal & antibiotic
Pressed and cut medicated Gelfoam pieces soaked in topical antifungal and antibiotic ear drops Patients advised to instil eardrops over Gelfoam for 3 days
3 days
Cleaning of all fungal debris
Shraga S et al, 2013
Antifungal
Shraga Cream: 0.1% Betamethasone, 10% Griseofulvin, 35% Lanolin, 20% Petroleum jelly (Vaseline®) , 15% Tea tree oil and 20% Distilled water Shraga Ear drops: 0.1% Betamethasone, 10% Griseofulvin, 15% Tea Tree oil, 25% Petroleum jelly (Vaseline®) and 50% Distilled water OD
1 week
Unspecified
Kolling WM et al, 2013
Combination of azole and anaesthetic vs azole alone vs analgesic (oral)
1% clotrimazole 4 drops TDS Oral ibuprofen 2 drops of 1% topical tetracaine in propylene glycol 5 minutes followed by 4 drops of 1% clotrimazole
2 weeks
Cleaning of ear canal
Block TK & Munson E, 2012
Azole
1% Clotrimazole eardrops
Improvement noted following 2 days of therapy
Unspecified
Schaefer P & Baugh RF, 2012
Acidifying agent, half acidifying agent/ half alcohol or antifungals
Acetic acid 2% (Vosol) otic solution 2 drops BD
7 to 10 days
Meticulous cleaning of ear canal
Viswanatha B et al, 2012
Azole versus Azole
Discontinuation of topical antibiotics Initial treatment regimen - clotrimazole eardrops. Patients who did not respond to clotrimazole were switched to fluconazole eardrops.
3 weeks
Microscopic suction clearance of fungal mass
Edward et al, 2012
Antiseptics, polyene, azoles
Boric acid, Gentian Violet 1%, Castellani’s paint, Cresylate Otic drops, Mercurochrome, Nystatin cream / ointment / powder, Clotrimazole, ketoconazole, fluconazole, miconazole cream 2%, Bifonazole 1% solution, Itraconazole Case report - Gentian Violet
5 days
Mechanical debridement
Vyas DH & Shah PD, 2011
Polyene (IV)
IV Amphotericin B
Unspecified
Suction clearance & debridement
Viswanatha B & Nasseruddin K, 2011
Azoles
Clotrimazole eardrops / fluconazole eardrops
3-4 weeks
Microscopic suction clearance of fungal mass
Hsu CL et al, 2011
Azoles (oral & IV), aminoglycoside (oral), polyene (oral), beta-lactams (oral)
Initially, oral ketoconazole 400 mg QID for 2 weeks IV fluconazole 200 mg QID, gentamicin 160 mg QID, gentamicin replaced after 3 days by amphotericin B 30 mg QID and piperacillin and tazobactam 2.25 g 8 hourly for 4 days After obtaining culture result, IV voriconazole (loading dose 300 mg every 12 h for 1 day; maintenance dose 200 mg every 12 h for 5 days) Oral voriconazole 200 mg BD was administered for 5 further days
4 weeks
Daily clearing of ear discharge
Lee A et al, 2011
Azole
1% clotrimazole
14 days
Suction clearance and dry mopping of debris
Yaganeh Moghadam A et al, 2010
Mixture of alcohol & acidifying agent
Mixture of 90 ml of 70% isopropyl alcohol + 10 ml of 2% acetic acid every 8 h
3 weeks
Unspecified
Mgbe R et al, 2010
Hydroxyquinoline / steroids / azole / local anaesthetics / antiseptic
Ears packed with wick impregnated with either clioquinone / flumethasone (Locacorten Vioform eardrops/cream) or beclomethasone dipropionate / clotrimazole / lidocaine hydrochloride (Candibiotic ear drops) or Gentian Violet changed thrice daily
2 weeks
Aural syringing
Chalabi EY & Ahmed TS, 2010
Azole drops
1% clotrimazole 2 drops BD
3 weeks
Group A - Suction cleaning (dry ear cleaning) Group B - Gentle (wet ear cleaning) syringing by using clean water at body temperature or normal saline
Parize P et al, 2009
Azoles (oral), polyene (oral), echinocandin (oral)
1st case: Oral voriconazole 200 mg BD 2nd case: Oral voriconazole first at 200 mg BD, then at 300 mg BD to obtain a trough concentration of more than 1 mg/L Review: 17 patients received 2 g amphotericin B, 9 of the 17 patients received amphotericin B and itraconazole. 1 patient first received itraconazole and was switched to amphotericin B because of a relapse In 3 cases, itraconazole was used as the only antifungal 1 patient received both voriconazole and caspofungin 3 months for the 1st case 12 months for the 2nd case
Unspecified
Malik MF et al, 2009
Antiseptic versus azoles
Tincture Merthiolate or clotrimazole or miconazole 4 drops BD
14 days
Cleaning by dry mopping
Ibiam FA, 2009
Hydroxyquinoline
Locorten-Vioform® 2-3 drops QID
3 weeks
Aural dry mopping
Kiakojori K et al, 2007
Azole versus combination of azole and acidifying agent
First step - 2% miconazole Second step - Combination of 2% miconazole and acidic acid drops (acetic acid 3% in ethanol 97%)
21 days
Suction clearance
Ong YK & Chee G, 2005
Acidifying / drying agent and azole
Acetic acid 2% and topical clotrimazole eardrops
Unspecified
Aural toilet
Özcan KM et al, 2005
Antiseptic in distilled water versus antiseptic in alcohol
Boric acid solution in 70% distilled water, boric acid solution in 70% ethanol
Not applicable
Not applicable
Panizza BJ, 2002
Combination of antibiotic, corticosteroids and antifungal
Combination of ciprofloxacin, hydrocortisone and antifungal ear drops
1 week
Suction clearance, dry mopping of canal with probe
Sander R, 2001
Acidifying drops / azoles (topical / oral)
2% acetic acid TDS / QID If symptoms persist, 1% clotrimazole (Lotrimin) Aspergillus infection resistant to clotrimazole required oral itraconazole (Sporanox)
1 week
Cleansing of ear canal by suctioning
BD - Twice daily OD - Once daily QID - Four times a day TDS - Three times daily NCT - N-Chlorotaurine EAC - External auditory canal BD - Twice daily OD - Once daily QID - Four times a day TDS - Three times daily NCT - N-Chlorotaurine EAC - External auditory canal BD - Twice daily OD - Once daily QID - Four times a day TDS - Three times daily NCT - N-Chlorotaurine EAC - External auditory canal BD - Twice daily OD - Once daily QID - Four times a day TDS - Three times daily NCT - N-Chlorotaurine EAC - External auditory canal BD - Twice daily OD - Once daily QID - Four times a day TDS - Three times daily NCT - N-Chlorotaurine EAC - External auditory canal