MYCETOMA INTERNATIONAL CONFERENCE Monterrey, Mexico 24 th -26 th. May 2007 Elsheikh Mahgoub Faculty of Medicine,University of Khartoum,Sudan.

THERAPY OF MYCETOMA

Mycetoma is a chronic, localised slowly progressive disease, involving cutaneous, subcutaneous tissue and ultimately bone.

It is characterised by tumefaction, destructive granuloma, deformity and discharging sinuses with intercommunicating channels which exude pus with granules of varying colour and size It is characterised by tumefaction, destructive granuloma, deformity and discharging sinuses with intercommunicating channels which exude pus with granules of varying colour and size

It is 52 years since Professor Gonzalez – Ochoa from your country published his work on the treatment of mycetoma due to Nocardia brasiliensis with Diamino-diphenyl sulphone(DDS)and 41 years since the publication of Professor Pedro Lavalle.

We published on successful treatment of mycetoma caused by Actinomadura madurae, A.pelletierii, Streptomyces somaliensis and Nocardia brasiliensis with Sulphamethoxazole plus Trimethoprim 35 years ago.

Later on in 1976 we published on the treatment of 144 cases of actinomycetoma using COMBINATION THERAPY of Streptomycin and cotrimoxazole or streptomycin and DDS. Later on in 1976 we published on the treatment of 144 cases of actinomycetoma using COMBINATION THERAPY of Streptomycin and cotrimoxazole or streptomycin and DDS.

In 1984, together, with Professor Samia Gumaa, we reported on the first successful treatment of Eumycetoma due to Madurella mycetomatis by ketoconazole In 1984, together, with Professor Samia Gumaa, we reported on the first successful treatment of Eumycetoma due to Madurella mycetomatis by ketoconazole

Oliverio Welch and his colleagues 20 years ago, in 1987, reported on the use of Amikacin alone and in combination with Trimethoprim- sulphamethoxazole in the treatment of actinomycetoma caused by N.brasiliensis. Oliverio Welch and his colleagues 20 years ago, in 1987, reported on the use of Amikacin alone and in combination with Trimethoprim- sulphamethoxazole in the treatment of actinomycetoma caused by N.brasiliensis.

Ahmed Fahal had a trial Itraconazole to treat patients with eumycetoma caused by Ahmed Fahal had a trial with Itraconazole to treat patients with eumycetoma caused by Madurella mycetomatis (Data not yet published).

At present a trial is going on at the Mycetoma Centre in Khartoum where patients with mycetomata due to A.madurae,Apelletierii and S.somaliensis are being treated with amikacin. At present a trial is going on at the Mycetoma Centre in Khartoum where patients with mycetomata due to A.madurae,Apelletierii and S.somaliensis are being treated with amikacin. Preliminary results are impressive Preliminary results are impressive

TOPICAL APPROACH Elfadil got his MD in 2004 by working on the seeds of a Sudanese herb (Lipdium sativum) growing along the White Nile.The seeds of this plant are ground and emulsified in yogurt and applied daily as a dressing to the mycetoma even if the lesion is closed.

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The latest report is that of Bonifaz et al February 2007 who reported on successful treatment of Actinomycetoma due to Nocardia spp. with Amoxyclav 875/125

In a recent electronic article on Mycetoma in eMedicine, January 2007,Basillio et al have narrated all drugs used in medical treatment of mycetoma,their dosage,mode of action and side effects.

Oliverio Welch and Salinas-Carmona in February 2007 in the same web site published a comprehensive article updating treatment of both actinomycetoma and eumycetoma.

We are conducting an experiment to test in vitro Sensitivity of 15 strains of M. mycetomatis against Fluconazole, Itraconazole, Ketoconazole and Voriconazole.

Ketoconazole

Itraconazole

M.Mycetomatis against Voriconazole

Our results show that Ketoconazole is still the most potent followed by voriconazole, Itraconazole and least by Flucconazole.

With this array of drugs what approach or strategy should we advise for Therapy or treatment of MYCETMA?? With this array of drugs what approach or strategy should we advise for Therapy or treatment of MYCETMA??

Questions to be answered first:   Site of mycetoma? (Is Surgery Possible)   Actinomycetoma or Eumycetoma ?(Drugs Different)   Any Previous mycetoma treatment? (Try Different Drug)   Any previous surgery? (Recurrence)   What drug cost can he/she afford? (For Sustaining Trt)

Actinomycetoma All agents of actinomycetoma start with Streptomycin 1 gram per day intramuscular. plus 2 tablets cotrimoxazole twice daily for one month.Do not disturb successful treatment. If treatment fails shift to Amikacin. All agents of actinomycetoma start with Streptomycin 1 gram per day intramuscular. plus 2 tablets cotrimoxazole twice daily for one month.Do not disturb successful treatment. If treatment fails shift to Amikacin.

S.Somaliensis Mycetoma pedis Before Treatment with Streptomycin cotrimoxazole. After Treatment

Trt.Amikacin /Cotrimoxazole Before treatment After Treatment

Treatment If No Response, shift to Streptomycin Dapsone [Beware toxic effects to Bone marrow Anaemia Leucopenia. Supplement trt with Fe and Folic acid.]

Treatment If no response, start Amoxycillin/clavulanic acid.

Trt. EUMYCETOMA Ketoconazole 200 mg b.d. for 3 weeks. If response is minimal try Voriconazole 6mg/kg iv infused over 2 hrs and then Itraconazole. [ Check Liver Function Tests before and monthly during trt.] Ketoconazole 200 mg b.d. for 3 weeks. If response is minimal try Voriconazole 6mg/kg iv infused over 2 hrs and then Itraconazole. [ Check Liver Function Tests before and monthly during trt.]

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References 1.Gonzalez-Ochoa A,1955.Effectiveness ofDDS in the treatment of Chromoblastomycosis and of Mycetoma caused by Nocardia brasiliensis,pp In SternbergTH and Newcomer VD EdsTherapy of Fungus Diseases.Little,Brown & Co.,Boston. 1.Gonzalez-Ochoa A,1955.Effectiveness ofDDS in the treatment of Chromoblastomycosis and of Mycetoma caused by Nocardia brasiliensis,pp In SternbergTH and Newcomer VD EdsTherapy of Fungus Diseases.Little,Brown & Co.,Boston. 2.Lavalle P,1966.Clinica Terapeutica de los micetomas.Dermatology International,5, Lavalle P,1966.Clinica Terapeutica de los micetomas.Dermatology International,5, Mahgoub ES, 1972.Treatment of Actinomycetoma with Sulphamethoxazole plus Trimethoprim.Journal of Tropical medicine and Hygiene Mahgoub ES, 1972.Treatment of Actinomycetoma with Sulphamethoxazole plus Trimethoprim.Journal of Tropical medicine and Hygiene Mahgoub ES,1976.Medical Management of Mycetoma.Bulletin of the World Health Organization,54, Mahgoub ES,1976.Medical Management of Mycetoma.Bulletin of the World Health Organization,54,

References 5.Mahgoub ES & Gumaa SA,1984.Ketoconazole in the treatment of eumycetoma due to Madurella mycetomatis.Transactions of the Royal Society of Tropical medicine and Hygiene 78, Mahgoub ES & Gumaa SA,1984.Ketoconazole in the treatment of eumycetoma due to Madurella mycetomatis.Transactions of the Royal Society of Tropical medicine and Hygiene 78, Welch O,Sauceda E,Gonzalez J,Ocampo J,1987.Amikacin alone and in combination with trimethoprim- sulphamethoxazole in the treatment of actinomycotic mycetoma.Journal of the American Academy of Dermatology,17, Welch O,Sauceda E,Gonzalez J,Ocampo J,1987.Amikacin alone and in combination with trimethoprim- sulphamethoxazole in the treatment of actinomycotic mycetoma.Journal of the American Academy of Dermatology,17,

References 7.Fahal AH.Unpublished data. 8.ElFadil AB.Treatment of Eumycetoma with a topical herb( Sativa lipdium).Thesis submitted for MD,University of Khartoum. 9.Bonifaz A,2007.Treatment of actinomycetoma due to Nocardia spp With amoxycillin-clavulanate.British Journal of Dermatology,156,

References 10.BasillioJ,2007.Mycetoma. edicine.com/med/topic30.hto, BasillioJ,2007.Mycetoma. edicine.com/med/topic30.hto, Welch O,Salinas_Carmona MC,2007.Mycetoma. com/derm/topic280.htm Welch O,Salinas_Carmona MC,2007.Mycetoma. com/derm/topic280.htm1-13.