MYCETOMA INTERNATIONAL MYCETOMA INTERNATIONAL CONFERENCECONFERENCE

Monterrey, MexicoMonterrey, Mexico2424thth-26-26thth. May 2007. May 2007Elsheikh MahgoubElsheikh Mahgoub

Faculty of Medicine ,University of Khartoum,Sudan.

THERAPY OF MYCETOMATHERAPY OF MYCETOMA

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

It is characterised by It is characterised by tumefaction, destructive tumefaction, destructive granuloma, deformity and granuloma, deformity and discharging sinuses with discharging sinuses with intercommunicating intercommunicating channels which exude pus channels which exude pus with granules of varying with granules of varying colour and sizecolour 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 Later on in 1976 we published on the published on the treatment of 144 cases treatment of 144 cases ofof actinomycetoma actinomycetoma using using COMBINATION THERAPY COMBINATION THERAPY of of Streptomycin and Streptomycin and cotrimoxazolecotrimoxazole or or streptomycin and DDS.streptomycin and DDS.

In 1984, together, with In 1984, together, with Professor Samia Gumaa, Professor Samia Gumaa, we reported on the first we reported on the first successful treatment of successful treatment of Eumycetoma due to Eumycetoma due to MadurellaMadurella mycetomatismycetomatis by by ketoconazoleketoconazole

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

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

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

Preliminary results are Preliminary results are impressiveimpressive

TOPICAL APPROACHTOPICAL 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.

Photo 19

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.

Antifungal Concn.

0

2

4

6

8

10

12

14

16

1/1000 500 250 125 62.5 31.2 15.6 7.8 3.9 1.9 0.97 0.48 0.24

No o

f Str

ains

Flucanarale Itraconozole Ketocurazde

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

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

S.Somaliensis Mycetoma pedis Before Treatment with Streptomycin cotrimoxazole.

After Treatment

Trt.Amikacin /Cotrimoxazole

Before treatment

After Treatment

TreatmentTreatment

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

Treatment

If no response, start Amoxycillin/clavulanic acid.

Trt. EUMYCETOMA

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

ReferencesReferences

1.Gonzalez-Ochoa A ,1955.Effectiveness ofDDS in 1.Gonzalez-Ochoa A ,1955.Effectiveness ofDDS in

the treatment of Chromoblastomycosis and of the treatment of Chromoblastomycosis and of Mycetoma caused by Mycetoma caused by Nocardia brasiliensis,pp Nocardia brasiliensis,pp 321-3270In SternbergTH and Newcomer VD 321-3270In SternbergTH and Newcomer VD EdsTherapy of Fungus Diseases.Little,Brown & EdsTherapy of Fungus Diseases.Little,Brown & Co.,Boston.Co.,Boston.

2.2.Lavalle P,1966.Clinica Terapeutica de los Lavalle P,1966.Clinica Terapeutica de los micetomas.Dermatology International,5,117-120.micetomas.Dermatology International,5,117-120.

3.Mahgoub ES, 1972.Treatment of 3.Mahgoub ES, 1972.Treatment of Actinomycetoma with Sulphamethoxazole plus Actinomycetoma with Sulphamethoxazole plus Trimethoprim.Journal of Tropical medicine and Trimethoprim.Journal of Tropical medicine and Hygiene 332-335.Hygiene 332-335.

4.Mahgoub ES,1976.Medical Management of 4.Mahgoub ES,1976.Medical Management of Mycetoma.Bulletin of the World Health Mycetoma.Bulletin of the World Health Organization,54,303-311Organization,54,303-311..

ReferencesReferences

5.Mahgoub ES & Gumaa 5.Mahgoub ES & Gumaa SA,1984.Ketoconazole in the SA,1984.Ketoconazole in the treatment of eumycetoma due to treatment of eumycetoma due to Madurella mycetomatis.Madurella mycetomatis.Transactions Transactions of the Royal Society of Tropical of the Royal Society of Tropical medicine and Hygiene 78,376-369.medicine and Hygiene 78,376-369.

6.Welch O,Sauceda E,Gonzalez 6.Welch O,Sauceda E,Gonzalez J,Ocampo J,1987.Amikacin alone and J,Ocampo J,1987.Amikacin alone and in combination with trimethoprim-in combination with trimethoprim-sulphamethoxazole in the treatment sulphamethoxazole in the treatment of actinomycotic mycetoma.Journal of actinomycotic mycetoma.Journal of the American Academy of of the American Academy of Dermatology,17,443-448.Dermatology,17,443-448.

ReferencesReferences

7.Fahal AH.Unpublished data.7.Fahal AH.Unpublished data.

8.ElFadil AB.Treatment of Eumycetoma 8.ElFadil AB.Treatment of Eumycetoma with a topical herbwith a topical herb( Sativa ( Sativa lipdium).lipdium).Thesis submitted for Thesis submitted for MD,University of Khartoum.MD,University of Khartoum.

9.Bonifaz A,2007.Treatment of 9.Bonifaz A,2007.Treatment of actinomycetoma due to actinomycetoma due to Nocardia sppNocardia spp

With amoxycillin-clavulanate.British With amoxycillin-clavulanate.British Journal of Dermatology,156,308 -311.Journal of Dermatology,156,308 -311.

ReferencesReferences

10.BasillioJ,2007.Mycetoma.www.em10.BasillioJ,2007.Mycetoma.www.emedicine.com/med/topic30.hto,1-15.edicine.com/med/topic30.hto,1-15.

11.Welch O,Salinas_Carmona 11.Welch O,Salinas_Carmona MC,2007.Mycetoma.www.emedicine.MC,2007.Mycetoma.www.emedicine.com/derm/topic280.htm1-13.com/derm/topic280.htm1-13.