Τετάρτη 11 Δεκεμβρίου 2019

Clioquinol for Otomycosis: A Lesser Understood Antimicrobial

Clioquinol for Otomycosis: A Lesser Understood Antimicrobial:






To the Editor: Peled et al. (1) provide a detailed analysis of their experience with otitis externa. Treatment of this disease should be augmented with knowledge of the following antimicrobial which is less well understood in comparison to more traditional topical antibacterial and antimycotic agents. Clioquinol is a halogenated 8-hydroxyquinoline (also known as iodochlorohydroxyquin) and is primarily used for its antimicrobial activity (2). It has been marketed under many different proprietary names worldwide in both otic solutions and skin creams. Since clioquinol is not a member of commonly-used and broadly active antimicrobial families, little specific knowledge of it is had by the vast majority of medical practitioners. Yet, there are many physicians that are more likely to use clioquinol anecdotally than many other antimicrobials that are formally explored in their medical training, even though the drug's indications are very limited.



Introduced in the 1930s as a medicinally useful quinoline derivative for its antiseptic potential, clioquinol was intended to be a topical treatment for skin wounds and superficial infections. Clinical application became common well before rigorous clinical trials were ever completed. It then became a component of various dermatological preparations, often combined with one or more other pharmaceuticals. Clioquinol was formerly administered orally as a prophylactic agent for traveller's diarrhea and as an anti-amoebic agent. Although limited for oral absorption, blood levels have been found, and skin absorption, once thought incapable, is now acknowledged (3,4).



The drug has broad antimicrobial activity including many bacteria, yeast, and molds that would be obtained from most external ear or superficial skin infections (5–7). The antibacterial spectrum is broad and includes common Gram-positive cocci, many Gram-negative bacilli, and mycobacteria. The antifungal effects are also broad spectrum (including both Candida spp. and Aspergillus spp.), although as an individual antimycotic, clioquinol is weaker than both clotrimazole and tolnaftate. The specific mechanisms of antimicrobial activity are not well understood, and the drug provides more of a microbistatic than microbicidal action (8). Nevertheless, the concentration of clioquinol in topical preparations is usually 1% to 3% which should exceed required local concentrations many-fold. As a single agent, therefore, clioquinol can be considered a broad spectrum antimicrobial with both antibacterial and antifungal properties.



Although most physicians have likely never heard of clioquinol by name, it was the subject of considerable controversy by the 1970s. Given its initial promise as a traveller's diarrhea and anti-amoebic agent, prophylactic use in large populations became commonplace in some regions of the world. When used orally, however, studies found a dose- and time-related toxicity of the central nervous system including subacute myelo-optic neuropathy and amnesia (9–11). Cumulative data in regards to neurotoxicity then led to a ban on oral clioquinol use in many countries (12). Elsewhere, oral use continues to attract clinical controversy (13).



Skin toxicity from local exposure, or a worsening of eczema has occurred (14,15). Some 0.7 to 2.2% of patients will develop a primary dermatitis with topical clinical applications (16,17). Fixed drug eruptions after topical or other use were also reported (18,19). Patch test sensitivity varied over 0.73 to 12% (20,21). Cross-sensitization to other halogenated compounds has been reported (22). By 1965, flumethasone became available for clinical use as a topical steroid and was thought to be an improvement over hydrocortisone. Some otic solutions contain 1% clioquinol and 0.02% flumethasone pivalate for clinical use. The latter combination with flumethasone has been successfully exploited for the treatment of otitis externa generally and specifically for mycotic otitis externa (23–26). Simultaneous efficacy against both bacterial and mycotic pathogens has attracted such therapeutic interest.



Several precautions with otic use should be observed. Significant absorption of clioquinol systemically with topical ear use is unlikely, but past concerns of neurotoxicity should lead physicians to refrain use in the context of tympanic perforation. Although clioquinol has quite broad antimicrobial activity, resistance among some Gram-negative bacteria has been found. A microbial culture should be obtained when there is seemingly drug failure after 5 to 7 days of application. Given clioquinol's potential to cause a local hypersensitivity reaction, despite being compounded with flumethasone, contact dermatitis due to clioquinol should also be considered in addition to resistant infection when the outer ear pathology continues during extended application.



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REFERENCES

1. Peled C, El-Seid S, Bahat-Dinur A, Tzvi-Ran LR, Kraus M, Kaplan D. Necrotizing otitis externa – analysis of 83 cases: clinical findings and course of disease. Otol Neurotol 2019; 40:56–62.

Cited Here... |

View Full Text | PubMed | CrossRef

2. Neldner KH. The halogenated 8-hydroxyquinolines. Int J Dermatol 1977; 16:267–273.

Cited Here... |

PubMed | CrossRef

3. Degen PH, Moppert J, Schmid K, et al. Percutaneous absorption of clioquinol (Vioform®). Dermatologica 1979; 159:295–301.

Cited Here... |

PubMed

4. EditorialClioquinol and other halogenated hydroxyquinolines. Lancet 1968; 1:679.

Cited Here...

5. Regös J, Zak O, Solf R, et al. Antimicrobial spectrum of triclosan, a broad-spectrum antimicrobial agent for topical application. II. Comparison with some other antimicrobial agents. Dermatologica 1979; 158:72–79.

Cited Here... |

PubMed

6. Maher A, Bassiouny A, Moawad K, et al. Otomycosis: an experimental evaluation of six antimycotic agents. J Laryngol Otol 1982; 96:205–213.

Cited Here... |

PubMed | CrossRef

7. You Z, Ran X, Dai Y, Ran Y. Clioquinol, an alternative antimicrobial agent against common pathogenic microbe. J Mycol Med 2018; 28:492–501.

Cited Here... |

PubMed | CrossRef

8. Pippi B, Lopes W, Reginatto P, et al. New insights into the mechanism of antifungal action of 8-hydroxyquinolines. Saudi Pharm J 2019; 271:41–48.

Cited Here... |

PubMed | CrossRef

9. Mao X, Schimmer AD. The toxicology of clioquinol. Toxicol Lett 2008; 182:1–6.

Cited Here... |

PubMed | CrossRef

10. Tateishi J. Subacute myelo-optico-neuropathy: clioquinol intoxication in humans and animals. Neuropathology 2000; 20:S20–S24.

Cited Here... |

PubMed

11. Konagaya M. SMON: toxicity of clioquinol and the status quo. Brain Nerve 2015; 67:49–62.

Cited Here...

12. Wolfe MS, Mishtowt GL. Entero-Vioform in traveler's diarrhea. JAMA 1972; 220:275–276.

Cited Here... |

PubMed | CrossRef

13. van Hunsel F, van Nieuwkoop C, Stricker BHC. Clioquinol use for Dientamoeba fragilis infections is questionable. Ned Tijdschr Geneeskd 2017; 161:D1477.

Cited Here... |

PubMed

14. Saunders TS. The use of Vioform in local dermatologic therapy. Arch Derm Syphilol 1946; 54:456–460.

Cited Here... |

PubMed

15. Maibach HI. Iodochlorohydroxyquin-hydrocortisone treatment of fungal infections. Arch Dermatol 1978; 114:1773–1775.

Cited Here... |

PubMed | CrossRef

16. Bandmann H-J, Calnan CD, Cronin E, et al. Dermatitis from applied medicaments. Arch Dermatol 1972; 106:335–337.

Cited Here... |

PubMed | CrossRef

17. Kero M, Hannuksela M, Sothman A. Primary irritant dermatitis from topical clioquinol. Contact Dermatitis 1979; 5:115–117.

Cited Here... |

PubMed | CrossRef

18. Mussani F, Poon D, Skotnicki-Grant S. Systemic contact dermatitis to topical clioquinol/hydrocortisone combination cream. Dermatitis 2013; 24:196–197.

Cited Here... |

View Full Text | PubMed | CrossRef

19. Janier M, Vignon MD. Recurrent fixed drug eruption due to clioquinol. Br J Dermatol 1995; 133:1013–1014.

Cited Here... |

PubMed | CrossRef

20. Holmes RC, Johns AN, Wilkinson JD, et al. Medicament contact dermatitis in patients with chronic inflammatory ear disease. J Soc Med 1982; 75:27–30.

Cited Here...

21. Meneghini CL, Rantuccio F, Lomuto M. Additives, vehicles and active drugs of topical medicaments as causes of delayed-type allergic dermatitis. Dermatologica 1971; 143:137–147.

Cited Here... |

PubMed

22. Soesman-van Waadenoijen Kernekamp A, van Ketel WG. Persistence of patch test reactions to clioquinol (Vioform®) and cross-sensitization. Contact Dermatitis 1980; 6:455–460.

Cited Here... |

PubMed | CrossRef

23. Bear VD. Otitis externa: immediate and long-term results with flumethasone pivalate/iodochlorhydroxyquinoline ear drops. Med J Aust 1969; 1:273–276.

Cited Here... |

PubMed | CrossRef

24. Khambata AS. Ear dressings in the treatment of otitis externa. Practitioner 1969; 202:269–272.

Cited Here... |

PubMed

25. Sen Gupta RP, Kacker SK. Otomycosis. Ind J Med Sci 1978; 32:5–7.

Cited Here...

26. Herasym K, Bonaparte JP, Kilty S. A comparison of Locacorten-Vioform and clotrimazole in otomycosis: a systematic review and one-way meta-analysis. Laryngoscope 2016; 126:1411–1419.

Cited Here... |

PubMed | CrossRef

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