How do you compound ear powder out of chloramphenicol, amphotericin B, and sulfamethoxazole? What studies are available on utilizing these treatments in the ear for ear infections as a powder form? Include drug combinations that have one or more of the active ingredients listed? I am interested in seeing data regarding product efficacy (include clinical data from other countries as well).

Comment by InpharmD Researcher

Published evidence evaluating compounded otic powders containing chloramphenicol, amphotericin B, and sulfonamides is very limited. Available literature consists primarily of one published compounding formula, review articles, observational studies with limitations, and isolated case reports, with no randomized studies evaluating the specific combination of chloramphenicol, amphotericin B, and sulfamethoxazole (or sulfanilamide) as a compounded ear powder. The published compounding instructions describe formulation, preparation, packaging, and recommended quality-control measures, but provide no clinical validation, stability, or microbiologic data. Indirect evidence from studies evaluating other otic powder formulations and topical combination products containing one or more of the requested ingredients suggests that these therapies can be effective for otitis externa or otomycosis (Tables 1-7). Therefore, the available evidence provides only indirect support for compounded chloramphenicol/amphotericin B/sulfonamide otic powders, and high-quality studies evaluating their efficacy, safety, and stability are lacking.

Background

A 2009 publication in the International Journal of Pharmaceutical Compounding (IJPC) elaborated on the formulation of a multi-component otic powder containing Amphotericin B, Chloramphenicol Palmitate, Hydrocortisone, and Sulfanilamide. The formulation yields 10 g of otic powder containing amphotericin B 470 mg, chloramphenicol palmitate 4.7 g, hydrocortisone 75 mg, sulfanilamide 4.7 g, and silica gel 55 mg. Silica gel is included as a desiccant and viscosity-enhancing excipient to help maintain a free-flowing powder. Compounding instructions consist of calculating the required quantities, accurately weighing each ingredient, triturating the powders together until a uniform mixture is obtained, and packaging the finished product in a tight, light-resistant container, with the authors noting that an accordion-style "puffer" device is suitable for administration. The instruction recommends a beyond-use date of up to 6 months, although storage conditions for the finished preparation are not otherwise specified. Recommended quality-control assessments include evaluation of overall and individual weight variation, uniformity of fill, physical appearance, color, uniformity, closure integrity, active drug assay, and physical stability (e.g., discoloration or other physical changes). The article also provides brief descriptions of the individual ingredients, including their physicochemical properties and pharmaceutical characteristics. Amphotericin B is described as a polyene antifungal antibiotic that binds ergosterol and should be protected from light during storage. Chloramphenicol palmitate, hydrocortisone, and sulfanilamide are described primarily in terms of their physical properties and topical uses. No clinical efficacy, safety, microbiologic, stability, or validation studies specific to this compounded otic powder were presented. [1]

A 2011 review on the management of chronic otitis externa advocates the use of topical therapies, including chloromycetin (chloramphenicol)-sulfanilamide-fungizone (amphotericin B)-hydrocortisone (CSF-HC) powder. The article only describes the powder as a mixture consisting of chloramphenicol 50 mg, sulfanilamide 50 mg, amphotericin B 50 mg, and hydrocortisone 1 mg. No information regarding efficacy, safety, stability, or compounding was mentioned. [2]

One of the few studies on the use of a combination otic powder for acute external otitis compared Auricularum powder (dexamethasone 10 mg, oxytetracycline HCl 90,000 U, polymyxin B Sulfate 100,000 U, nystatin 1,000,000 U) with ciprofloxacin drops and tobramycin drops in a randomized prospective trial of 120 adults (Table 1). After 3-4 days, 86% of the patients taking the Auricularum powder were cured compared to 77% of ciprofloxacin patients and 56% of tobramycin patients (p<0.05), although all patients achieved complete clinical resolution by day 14. The study evaluated a commercially manufactured powder supplied in a prepackaged multidose squeeze bottle and did not describe any compounding methods, preparation techniques, formulation procedures, stability, storage, or beyond-use dating. The authors also note that antibiotic powders such as chloramphenicol have historically been advocated because they deliver high local antibiotic concentrations without contributing moisture to the ear canal; however, there are no studies evaluating chloramphenicol powder alone or in combination with other products at the time of the publication of this review. [3]

Amphotericin deoxycholate 5 mg (typically co-formulated with chloramphenicol, sulfamethoxazole, sulfanilamide, ciprofloxacin, and/or hydrocortisone) otic capsules, administered via insufflator bulb, have been described for treatment of otitis externa or otomycosis. However, guidelines from the American Academy of Otolaryngology—Head and Neck Surgery Foundation recommend only using FDA-approved formulations for acute otitis externa; these preparations do not contain antifungals. [4], [5]

A recently published meta-analysis included 15 randomized controlled trials involving 2,309 adult patients and aimed to evaluate the efficacy and safety of commonly used topical therapies for otomycosis given the lack of standardized treatment recommendations. The meta-analysis demonstrated an overall pooled eradication rate of 73.6% across topical agents, with subgroup analyses showing wide variability in complete eradication rates ranging from 29.0% to 98.3%, largely reflecting heterogeneity in study design and treatment protocols. Adverse effects were generally mild and included otalgia, pruritus, and burning sensations. The authors concluded that topical antifungal therapy, particularly clotrimazole, remains the most commonly used and consistently effective option, although higher-quality standardized trials are still needed. Unfortunately, this analysis did not address compounded otic powder formulations or multi-drug regimens such as chloramphenicol, amphotericin B, and sulfamethoxazole. [6]

Background References: [1] Allen LV Jr. Amphotericin B, chloramphenicol palmitate, hydrocortisone, and sulfanilamide otic powder. IJPC. 2009;13(1):65.
[2] Kesser BW. Assessment and management of chronic otitis externa. Curr Opin Otolaryngol Head Neck Surg. 2011;19(5):341-7.
[3] Goldenberg D, Golz A, Netzer A, Joachims HZ. The use of otic powder in the treatment of acute external otitis. Am J Otolaryngol. 2002;23(3):142-147. doi:10.1053/ajot.2002.123461
[4] Rosenfeld RM, Schwartz SR, Cannon CR, et al. Clinical practice guideline: acute otitis externa. Otolaryngol Head Neck Surg. 2014;150(1 Suppl):S1-S24. doi:10.1177/0194599813517083
[5] Drew RH, Perfect JR. Conventional Antifungals for Invasive Infections Delivered by Unconventional Methods; Aerosols, Irrigants, Directed Injections and Impregnated Cement. J Fungi (Basel). 2022;8(2):212. Published 2022 Feb 21. doi:10.3390/jof8020212
[6] Hussain S, Philteos J, Kim H, Spiegel JL, Lin V. Management of Otomycosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Otol Neurotol. 2026;47(1):17-25. doi:10.1097/MAO.0000000000004684
Literature Review

A search of the published medical literature revealed 7 studies investigating the researchable question:

How do you compound ear powder out of chloramphenicol, amphotericin B, and sulfamethoxazole? What studies are available on utilizing these treatments in the ear for ear infections as a powder form? Include drug combinations that have one or more of the active ingredients listed? I am interested in seeing data regarding product efficacy (include clinical data from other countries as well).

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-7 for your response.


The use of otic powder in the treatment of acute external otitis

Design

Randomized controlled trial

N= 120

Objective

To compare the efficacy of Auricularum powder with ciprofloxacin drops and tobramycin drops in treating acute external otitis (AEO)

Study Groups

Auricularum powder (dexamethasone 10 mg, oxytetracycline Hcl 90,000 units, ploymyxin B sulfate 100,000 units, nystatin 1,000,000 units) (n= 40)

Tobramycin drops (n= 40)

Ciprofloxacin drops (n= 40) 

Methods

Inclusion criteria: diagnosis of AEO, at least 18 years old, no perforation of the tympanic membrane

Exclusion criteria: under 18 years old, previous treatment with other drops or systemic antibiotics 

Duration

14 days

Outcome Measures

Clinical resolution of AEO at days 3-4 and day 14

Baseline Characteristics

 

Auriculum powder

Ciprofloxacin drops

Tobramycin drops

Age, years

23.3 24.1 23.8

Female

17 19 12

# drops/day

2 3 3

Results

Endpoint

Auriculum powder

Ciprofloxacin drops

Tobramycin drops

Clinical resolution (day 3-4)

86% 77% 56%

Clinical resolution (day 14)

100%

100%

100%

Adverse Events

Common Adverse Events: cutaneous sensitivity 

Study Author Conclusions

The authors conclude that Auricularum powder is effective in the treatment of acute otitis externa. They acknowledge that cipromycin drops and tobramycin drops are also effective, however they may take longer to relieve symptoms. 

InpharmD Researcher Critique

It is important to note that adherence to otic solutions and powders is typically low. Therefore, the data should be interpreted with caution 

Table 1 References:
[7] Goldenberg D, Golz A, Netzer A, Joachims HZ. The use of otic powder in the treatment of acute external otitis. Am J Otolaryngol. 2002;23(3):142-147. doi:10.1053/ajot.2002.123461

Efficacy and safety of topical combination therapy in patients with acute otitis externa

Design

Retrospective study

N= 963

Objective

To characterize the microbial landscape of acute otitis externa and evaluate the efficacy and safety of the combination product chloramphenicol/clotrimazole/beclomethasone/lidocaine (Candibiotic) as empiric therapy for the condition.

Study Groups

All patients (n= 963)

Inclusion Criteria

Not available in study abstract

Exclusion Criteria

Not available in study abstract

Methods

The outpatient records of 963 patients with otitis externa were retrospectively reviewed in this real-world study. A subgroup analysis of patients who received Candibiotic (chloramphenicol/clotrimazole/beclomethasone/lidocaine) was performed to evaluate its clinical and microbiological effectiveness as well as its safety profile.

Duration

2017 to 2022

Outcome Measures

Resolution of clinical symptoms of otitis externa within 7 days, complete eradication of microorganisms, and adverse events

Baseline Characteristics

 

All patients (n= 963) 

Microbiology

          Bacterial

          Fungal

          No growth

 

60.6% 

26.0%

11.6% 

Microorganisms isolated

          Pseudomonas spp.

          Staphylococcus spp.

          Candida spp.

          Aspergillus spp.

 

29.2%

21.4%

19.4%

13.3% 

Received Candibiotic

71.0%

Results

Endpoint

All patients (n= 963)

Clinical symptoms resolved with 7 days

69.7% 

Complete eradication of microorganisms

87.0%   

Adverse events 

0.04% 

Adverse Events

See results

Study Author Conclusions

The study demonstrated an extremely high level of clinical efficacy and safety of therapy in patients with acute external infectious otitis who received the Candibiotic, which can be used as an initial empirical therapy in patients with otitis externa.

Critique

This retrospective, single-center observational study lacked a comparator group, limiting the conclusions regarding the efficacy and safety of Candibiotic. Additionally, only the English-language abstract was available, as the full article was published in Russian, preventing a detailed assessment of the study methods and results.

Table 2 References:
[8] Gurov AV, Kriukov AI, Shadrin GB, Izotova GN, Zotova PK. Ter Arkh. 2023;95(11):937-942. Published 2023 Dec 22. doi:10.26442/00403660.2023.11.202455
Chloramphenicol-Boric Acid Powder in the Treatment of Otitic Infections: A Clinical Report
Design

Clinical report with bacteriological studies

N= 69 patients with 95 infected ears

Objective To present clinical experiences with chloramphenicol and boric acid in the treatment of otitic infections and to explain the beneficial results through bacteriological studies
Study Groups

All patients (n= 69)

Inclusion Criteria Patients with diffuse otitis externa, chronic suppurative otitis media, or infected radical mastoidectomy cavities
Exclusion Criteria Not specified
Methods The external auditory canal was thoroughly cleansed and dried before applying chloramphenicol-boric acid powder (1:4) using a DeVilbiss powder-blower. The powder was insufflated to cover the entire canal wall and drum head. Patients were instructed to avoid water in the ear and return for follow-up every four to five days. Pain was managed with narcotics or roentgen therapy. In cases of granulation tissue, curettage or cauterization was performed before powder application
Duration Not specified
Outcome Measures

Primary: Dryness of the ear

Secondary: Improvement in symptoms, bacteriological studies

Baseline Characteristics   All patients (n= 69)*

Diffuse Otitis Externa 

          Acute

          Chronic

 

19 (20.0%)

59 (62.1%)

Chronic Suppurative Otitis Media 

          Central Perforation

          Marginal Perforation

 

12 (12.6%)

1 (1.1%)

Infected Radical Mastoidectomy Cavities 4 (4.2%)
* Percentages were calculated with 95 infected ears as the denominator 
Results   Number of Ears Ears Became Dry Percentage Dry

Diffuse Otitis Externa

          Acute

          Chronic

 

19

59

 

17

57

 

89%

96%

Chronic Suppurative Otitis Media 

          Central Perforation

          Marginal Perforation

 

12

1

 

12

0

 

100%

0%

Infected Radical Mastoidectomy Cavities 4 3 75%
Adverse Events No adverse events or new infections due to non-susceptible organisms such as candida were noted
Study Author Conclusions Chloramphenicol-boric acid powder mixture (1:4) is effective in treating otitic infections, maintaining desirable acidity, and is free from undesirable side effects. It is a useful addition to otitic infection therapy.
Critique The study provides valuable insights into the use of chloramphenicol-boric acid powder for otitic infections, demonstrating effectiveness and safety. However, the lack of a control group and detailed follow-up duration limits the ability to generalize the findings. The study's observational nature and reliance on clinical outcomes without a randomized design may introduce bias.
Table 3 References:
[9] Hearn PP. Chloramphenicol-boric acid powder in the treatment of otitic infections; a clinical report. Ann Otol Rhinol Laryngol. 1954;63(2):310-323. doi:10.1177/000348945406300205
In vitro susceptibilities of Aspergillus spp. causing otomycosis to amphotericin B, voriconazole and itraconazole
Design

Laboratory study

N= 120

Objective To investigate the in vitro activities of amphotericin B, voriconazole and itraconazole against Aspergillus isolates causing otomycosis
Study Groups

A. niger (n= 57)

A. fumigatus (n= 42)

A. flavus (n= 9)

A. nidulans (n= 6)

A. terreus (n= 6)

Inclusion Criteria Patients clinically diagnosed with otomycosis, with samples taken from the ear canals
Exclusion Criteria Not specified
Methods Mycological analysis of ear canal samples was performed by culturing onto Sabouraud Dextrose Agar. Aspergillus species were identified with colony morphology and microscopic appearance. Susceptibilities to amphotericin B, itraconazole, and voriconazole were tested using the CLSI reference broth microdilution method (M38-A document)
Duration Not specified
Outcome Measures Primary: In vitro susceptibility of Aspergillus isolates to amphotericin B, voriconazole, and itraconazole
Baseline Characteristics   All patients (n= 120)
A. niger 57 (47.5%)
A. fumigatus 42 (35%)
A. flavus 9 (7.5%)
A. nidulans 6 (5%)
A. terreus 6 (5%)
Results Organism  Amphotericin B MIC (µg ml⁻¹) Itraconazole MIC (µg ml⁻¹) Voriconazole MIC (µg ml⁻¹)
A. niger  0.12–1 0.25–16 0.12–0.5
A. fumigatus 0.12–1 0.12–16 0.12–0.25
A. flavus  0.12–0.5 0.5–1 0.12–0.5
A. nidulans 0.12–0.5 0.25–0.5 0.12–0.25
A. terreus 0.25–0.5 1–2 0.12–0.5
Adverse Events Not applicable
Study Author Conclusions In vitro data suggest that Aspergillus spp. can be resistant to itraconazole, while voriconazole and amphotericin B show no resistance. Voriconazole seems to be an alternative in the treatment of infections related to Aspergillus spp.
Critique The study provides valuable insights into the susceptibility of Aspergillus spp. to common antifungal agents. However, the study is limited by its in vitro nature and does not account for clinical outcomes or resistance mechanisms in vivo. Further studies with larger sample sizes and clinical correlations are needed to validate these findings.
Table 4 References:
[10] Kaya AD, Kiraz N. In vitro susceptibilities of Aspergillus spp. causing otomycosis to amphotericin B, voriconazole and itraconazole. Mycoses. 2007;50(6):447-450. doi:10.1111/j.1439-0507.2007.01409.x

Mycological and histological investigations in humans with middle ear infections

Design

Case report

Case presentation

A 52-year-old man presented with a 4-month history of otitis externa complicated by tympanic membrane perforation, persistent right-sided hearing loss, and otorrhea. Computed tomography findings were interpreted as chronic otitis media and mastoiditis. He underwent surgical removal of a meatal stenosis with extensive debridement of the tympanum and mastoid followed by tympanoplasty. Intraoperative examination demonstrated chronically inflamed polypoid mucosa without cholesteatoma, while mycological culture and histopathology identified Aspergillus fumigatus with Aspergillus hyphae present within inflamed tympanic tissue and severe chronic mastoiditis with granulation tissue. Following surgery, the patient received topical amphotericin B for 4 weeks; however, he returned 3 months later with recurrent otorrhea and enlargement of the tympanic membrane perforation. Magnetic resonance imaging demonstrated opacification of the middle ear and mastoid, and repeat mastoidectomy again yielded A. fumigatus on mycological examination. He was subsequently treated with intensive topical Castellani solution for 6 weeks, resulting in complete remission, and the tympanic membrane perforation closed spontaneously after 10 weeks.

Study Author Conclusions

The interconnection of fungi and chronic inflammation of the ear seems evident. The clinical signs of inflammation abated after topical antimycotic therapy in all examined patients. The exact mechanism by which chronic inflammation and fungal infection promote each other remains unclear.
Table 5 References:
[11] Vennewald I, Schnlebe J, Klemm E. Mycological and histological investigations in humans with middle ear infections. Mycoses. 2003;46(1-2):12-18. doi:10.1046/j.1439-0507.2003.00835.x

A double-blind comparative study of Trimethoprim-Polymyxin B versus Trimethoprim-Sulfacetamide-Polymyxin B otic solutions in the treatment of otorrhea
Design

Double-blind randomized study

N= 68

Objective To compare the safety and efficacy of trimethoprim-polymyxin B (TP) and trimethoprim-sulfacetamide-polymyxin B (TSP) drops in the treatment of otorrhea
Study Groups

TP group (n= 33)

TSP group (n= 35)

Inclusion Criteria Patients with otorrhea associated with external otitis, recurrent otitis media with tympanic membrane perforation, infected mastoid cavities, or post-operative tympanoplasties. Presence of gram-negative or gram-positive organisms such as Staphylococcus aureus, Pseudomonas aeruginosa, Proteus species, E. coli, Klebsiella oxytoca, Mima species, Enterobacter, H. influenzae, D. pneumoniae
Exclusion Criteria History of sensitivity to trial drugs, pregnant or lactating women, recent ototopical corticosteroid use, tuberculosis, fungal or viral diseases, previous ototoxic drug therapy, acute otitis media, recent antibiotic use, unsafe ears, inability to complete treatment or follow-up
Methods Patients received either TSP or TP otic drops for a maximum of 14 days. Initial and follow-up examinations were conducted, including audiometry and culture tests. Treatment involved cleaning the ear canal and applying the otic solution. Patients were assessed for clinical criteria and adverse reactions.
Duration October 1978 to March 1979
Outcome Measures Cure rate of otorrhea 
Baseline Characteristics   TP (n= 33) TSP (n= 35)
Pediatric cases 13 (total)
Geriatric cases 12 (total)
Females 16 10
Results   TP Success TP Failure TSP Success TSP Failure
External otitis 13 0 18 0
Chronic S.O. media 6 8 9 1
Sub-acute otitis media 1 1 2 0
Post-operative otorrhea + mastoid cavity infection 0 4 2 0
Adverse Events No signs of ototoxicity, fungal infection overgrowth, or local sensitivity to either of the solutions.
Study Author Conclusions The addition of sulfacetamide to trimethoprim and polymyxin B significantly improves the cure rate of chronic ear infections and otorrhea associated with otitis media, making TSP more effective than TP.
Critique The study's double-blind design and randomization are strengths, ensuring unbiased results. However, the sample size is relatively small, and the study does not account for potential variations in patient adherence to treatment protocols. Additionally, the study does not explore long-term outcomes beyond three months post-treatment.
Table 6 References:
[12] Gyd MC. 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(3):251-259. doi:10.1017/s002221510009068x

 

Otic administration of amphotericin B 0.25% in sterile water

Design

Case report

Case presentation

A 44-year-old man with HIV infection (CD4 250 cells/µL) presented with persistent bilateral ear pain due to refractory otitis externa in the setting of polymicrobial infection, including Aspergillus fumigatus and coagulase-negative Staphylococcus. Initial management with ciprofloxacin, amoxicillin/clavulanate, and systemic itraconazole 400 mg/day failed to produce clinical improvement, with ongoing purulent drainage and canal inflammation.

Given refractory disease and limited formulary options, amphotericin B otic drops were prepared through extemporaneous compounding by reconstituting a 50-mg vial of parenteral amphotericin B in sterile water to a 0.25% solution, which was transferred to an amber dropper bottle, assigned a one-week refrigerated beyond-use date, and administered as 1–2 drops per ear three times daily. The patient tolerated the compounded preparation without local irritation or adverse effects and experienced gradual resolution of symptoms over a six-week course. Although multiple pathogens and prior antimicrobial exposure limit causal attribution, this case supports the feasibility, tolerability, and clinical utility of compounded amphotericin B otic drops for refractory fungal otitis externa in an immunocompromised patient.

Study Author Conclusions

This patient tolerated topical otic administration of amphotericin B 0.25% in sterile water when administered three times daily.
Table 7 References:
[13] Kintzel PE, Trausch DE, Copfer AL. Otic administration of amphotericin B 0.25% in sterile water. Ann Pharmacother. 1994;28(3):333-335. doi:10.1177/106002809402800308