Columns , Dermatology , Journal Club

Journal Club: Focus on Otitis

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Over the past year, more than 20 journal articles addressing otitis in dogs and cats have been published worldwide. The following four abstracted articles provide useful preliminary data for practitioners on treatment of ear disease.

Multidrug resistance can present a challenge when treating otic infections, particularly those caused by methicillin-resistant staphylococci and Pseudomonas species. There is a need to identify both:

  1. Therapeutic alternatives
  2. Whether there is risk of iatrogenic bacterial transfer during treatment at home.
    • Boyen and colleagues showed that miconazole and polymyxin B have promising in vitro efficacy against methicillin-resistant staphylococci. This data suggest that Surolan (elanco.com) may be an effective topical treatment for methicillin-resistant staphylococci, as well as gram-negative bacteria and yeast.
    • The study by Bateman and colleagues demonstrated excellent in vitro efficacy and shelf stability of a novel solution (ticarcillin-clavulanic acid; Timentin, gsk.com) that may be compounded in-clinic for treatment of Pseudomonas otitis.
    • Steen and Paterson’s study revealed good in vitro efficacy of commercial ear cleansers against Pseudomonas species and provided evidence that ear cleansers may have valuable adjunctive activity against drug-resistant pathogens.
    • Bartlett and colleagues found that bacterial contamination of ear cleansers used in the pet owner’s home is rare. These findings may be used to develop recommendations for minimizing bacterial contamination.

Therefore, recent veterinary literature has provided several exciting articles regarding management of ear disease, particularly antimicrobial-resistant infections. Hopefully, future in vivo studies will build upon preliminary in vitro data.—Christine L. Cain, DVM, Diplomate ACVD, University of Pennsylvania

Article abstracts submitted by Heather Akridge, DVM, Resident in Dermatology, and Darcie Kunder, VMD, Resident in Dermatology; University of Pennsylvania School of Veterinary Medicine

TICARCILLIN-CLAVULANIC ACID FOR PSEUDOMONAS OTITIS

Pseudomonas aeruginosa is a common cause of otitis externa and often challenging to treat due to its resistance to multiple antimicrobials. Ticarcillin-clavulanic acid (Timentin) has been used off-label topically for the treatment of Pseudomonas otitis, with few published studies on its stability and efficacy once reconstituted.

  • This study investigated the efficacy and stability of Timentin stock concentrate solution and Timentin diluted in Methopt against 4 P aeruginosa isolates over various time periods and temperatures.
  • Methopt (hypromellose, 5 mg/mL; benzalkonium chloride, 0.2 mg/mL; disodium edetate, 0.5 mg/mL) has been previously used clinically in place of sterile water to decrease maceration of the ear canal lining. Tears Renewed (akorn.com) and Isopto Plain (alcon.com) are similar ophthalmic solutions.
  • Timentin powder (3.1-g vial; ticarcillin sodium, 3000 mg; potassium clavulanate, 100 mg) was diluted in 12.9 mL sterile water; then stored at 4°C (refrigerated) and -20°C (frozen) for the stock concentrate.
  • A Timentin/Methopt solution was created with 12 mL of stock concentrate diluted 1:4 with sterile Methopt; then stored at 4°C (refrigerated) or 24°C (room temperature).

Efficacy of the stock concentrate and Timentin/Metopt solution following storage was tested by evaluating minimum inhibitory concentration (MIC) levels for all 4 Pseudomonas strains using the broth microdilution method. The stock concentrate remained stable when refrigerated for 4 to 6 months or frozen for 12 months. The Timentin/Methopt solution remained stable for 28 days when refrigerated or stored at room temperature.

This in vitro study suggests that a Timentin/Methopt solution is likely efficacious clinically for topical treatment of Pseudomonas otitis; anecdotal clinical evidence supports this conclusion although in vivo testing should be pursued. Repeated freezing and thawing effects are unknown for these solutions.

Bateman FL, Moss, SM, Trott, DJ, et al. Biological efficacy and stability of diluted ticarcillin-clavulanic acid in the topical treatment of Pseudomonas aeruginosa infections. Vet Dermatol 2012; 23:97-102.

MICONAZOLE & POLYMYXIN B FOR METHICILLIN-RESISTANT STAPHYLOCOCCI

Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) infections are increasingly reported causes of canine otitis.

  • This study aimed to determine the in vitro susceptibility of canine MRSA and MRSP isolates to various antimicrobial agents, including miconazole and polymyxin B, as single agents and in combination, and Surolan (polymyxin B/miconazole/prednisolone).
  • Fifty MRSP isolates and 24 MRSA isolates were collected from North America and Europe. MICs were determined, using a broth microdilution assay, for 12 antimicrobial agents, polymyxin B, miconazole, polymyxin B/miconazole combination (1:43.5 ratio), and Surolan (polymyxin B, 0.53 mg/mL; miconazole, 23 mg/mL; 1:43.5 ratio).
  • Results confirmed acquired resistance to all tested agents (macrolides, aminoglycosides, and fluoroquinolones, among others) except linezolid, polymyxin B, and miconazole.
  • Two MRSP strains were exposed to the polymyxin and miconazole combination at concentrations below the MIC for 7 days, with no evidence of rapid development of resistance.

Miconazole had higher in vitro antimicrobial activity compare to polymyxin. There was no evidence of enhanced in vitro activity when combining polymyxin B and miconazole versus using them as single agents. These factors suggest that the antistaphylococcal activity of Surolan is mainly due to miconazole. Further studies in vivo are needed to confirm the effectiveness of Surolan in MRSA and MRSP otitis cases.

Boyen F, Verstappen K, De Bock M, et al. In vitro antimicrobial activity of miconazole and polymyxin B against canine meticillin-resistant Staphylococcus aureus and meticillin-resistant Staphylococcus pseudintermedius isolates. Vet Dermatol 2012; 23:381-385.

EAR CLEANSERS EFFICACIOUS AGAINST PSEUDOMONAS SPECIES

Approximately 10% to 20% of dogs presented to veterinary practices have otitis externa and/or otitis media. As otitis becomes more chronic, Pseudomonas species are often grown from canine ears and can display a wide spectrum of innate resistance to several classes of antimicrobials.

  • Otic swabs were collected from client-owned dogs with clinical evidence of otitis and submitted for bacterial culture and susceptibility testing.
  • All culture plates with confirmed Pseudomonas species had 8 sterile wells cut into the agar; each well was filled with 200 mcgL of a commercial ear cleanser. The diameter of the zone of inhibition around each well was measured after 15 to 18 hours of incubation.
  • Three cleansers consistently inhibited growth of the test organism in 50/50 (100%) of cases:
    • Sancerum (lactic acid 2.5%, salicylic acid 0.1%; msd-uk.com)
    • MalAcetic Otic (acetic acid 2%, boric acid 2%; dechra.com)
    • Otodine (propylene glycol, chlorhexidine gluconate 0.15%, Tris EDTA; vetruus.com).
  • Three cleansers consistently failed to inhibit the growth of Pseudomonas in 50/50 (100%) of cases:
    • CerumAural (squalene in isopropyl myristate, liquid petroleum; dechra.com)
    • Cleanaural (propylene glycol, isopropyl alcohol, citric acid, L-menthol, chlorothymol, thomethamine; dechra.com)
    • Surosolve® (salicylic acid, tris EDTA, chlorxylenol, sodium docusate, propylene glycol; fidavet.com).

This study demonstrates variability among ear cleansers regarding their antimicrobial activity against different Pseudomonas isolates. It also demonstrates that Pseudomonas does not appear to be a pH-dependent bacterium. Ototoxicity needs to be taken into account with certain active ingredients; some ingredients may work better in vivo.

Steen SI, Paterson S. The susceptibility of Pseudomonas spp. isolated from dogs with otitis to topical ear cleaners. J Small Animal Pract 2012; 53:599-603.

BACTERIAL CONTAMINATION OF EAR CLEANSERS

Commercial ear cleansers contain a wide variety of antimicrobial ingredients. These ingredients not only help prevent recurrent otitis but also prevent contamination of the solution. Studies in human medicine have shown that topical drops and cleansers can be iatrogenically contaminated, which can lead to continued or resistant infections in patients.

  • A total of 140 ear cleanser bottles were examined for cleanliness, purchase date, expiration date, amount of solution remaining, and bottle size. The applicator tip and remaining solution in each bottle was aseptically cultured.
  • Bacteria were cultured from 17 bottles (12.1%); 14 (10%) bottles had bacterial growth from the applicator tip, while 3 (2.1%) had solution contamination.
  • There were no significant differences in contamination rates regarding time since purchase or last use, frequency of use, whether the bottle touched the ear canal or was cleaned after use, visual dirtiness of bottle at time of culture, or recurrence of ear infections and bottle use.
  • Factors that contributed significantly to contamination were:
    • Expiration status of the solution
    • Size of bottle
    • Tris EDTA as active ingredient.

Pathogenic bacterial contamination of routine home ear cleansers is relatively low. However, risk may be increased if ear cleansers are used past their expiration date, if a large bottle is selected, or if Tris EDTA is an active ingredient. Clients should be encouraged to dispose of expired cleansers, use smaller bottles, and practice strict hand hygiene.

Bartlett SJ, Rosenkrantz WS, Sanchez S. Bacterial contamination of commercial ear cleaners following routine home use. Vet Dermatol 2011; 22:546-553.

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