Mycetoma Infectious Disease

1. MYCETOMA
PRESENTED BY:
DR.P.NIKITHA CHAUHAN
PHARMD INTERN
NOVA COLLEGE OF PHARMACEUTICAL
EDUCATION AND RESEARCH
TO
DR.RAVI KIRAN BARIGALA
SENIOR CONSULTANT, INFECTIOUS DISEASE

2. OUTLINE
I. INTRODUCTION VIII. MYCETOMA SPREAD
II. HISTORY AND INCIDENCE IX. DIAGNOSIS
III.TYPES & HISTOLOGICAL DIFFERENCE X. TREATMENT
IV. SYMPTOMS XI. SUMMARY
V.EPIDEMIOLOGY
VI.PROGNOSIS
VII.ETIOLOGY

3. I. INTRODUCTION
Mycetoma is a chronic granulomatus disease usually of the foot but any
part of the body can be affected. Infection is most probably acquired by
traumatic inoculation of fungi or bacteria into the subcutaneous tissue.
• These bacteria or fungi may enter the body through a break in the
skin, often on a person’s foot.
• From soil - Trauma to Skin eg: Thorn prick
• Initial - micro abscess - Slow progressive- Chronic Granulomatous

4. • Affects skin and subcutaneous tissue.
• The resulting infection causes firm, usually painless but
debilitating masses under the skin that can eventually affect the
underlying bone.
• This is chronic, suppurative, granulomatous inflammation which
can involve subcutaneous tissue,fascia, and bone.
• It is characterized by the tumefaction, draining sinuses, and the
presence of granules.

5. II. HISTORY AND INCIDENCE:
• Mycetoma was described in the modern literature in 1694 but was first reported in the mid 19th
century in the indian town of Madura, and hence was intially called Madura foot.
• In 1913, Pinoy observed that the disease was caused by two etiologic agents and divided the
disease into two categories: actinomycetoma (bacterial agents) and eumycetoma (fungal agents).
• The first attempt to map the distribution of mycetoma throughout the world was made by Abott in
1956.
• He studied 1321 cases of mycetoma in Sudan during a period of two and half years.
• New studies were then carried out by other researchers in regions such as Congo, Somalia,
Argentina and Mexico.
• Mycetoma commonly affects young adults particularly males aged between 20 and 40 years,
mostly in developed countries.

6. III.TYPES:
There are three types of mycetoma.They are
a) Eumycetoma - due to fungus
b) Actinomycetoma - due to bacteria (actinomycetes)
c) Botryomycosis - staph aureus
EUMYCETOMA ACTINOMYCETOMA
Caused due to Fungi Bacteria - Actinomycetes
Grains Black/White White/Red
Granules Black granules if caused by
Madurella mycetomatus
White granules if caused by
Pseudallescheria boydii
White to yellow granules if caused due to
Actinomadura madurae, Nocardia species,
Streptomyces som-alien-sis
Pink to Red granules if caused due to
Actinomadura pelletieri
Tumor Single, well defined margins Multiple tumor masses with ill defined
margins
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7. EUMYCETOMA ACTINOMYCETOMA
Sinues Appear late, few in number Appear early, numerous with raised
inflamed opening
Discharge Serous Purulent
Bone OsteoSclerotic Lesions OsteoLytic Lesions
Grains contain Fungushyphea Filamentous Bacteria
The only way I could think
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8. IV. SYMPTOMS:
v Mycetoma is characterized by a triad of
a) Painless subcutaneous mass.
b) Multiple sinuses.
c) Discharge containing grains.
v It usually spreads to involve the skin, deep structures and bone resulting in destruction , deformity
and loss of function, which may be fatal
v Mycetoma commonly involves the extremities, back and gluteal region.
v Secondary bacterial infection is common, and lesions may cause increased pain and disability and
fatal septicaemia (severe infections involving the entire human system ) if untreated.

10. Intramuscular mycetoma

11. V. EPIDEMIOLOGY:
• Although mycetoma is found worldwide, it is endemic in tropical and subtropical countries.The countries
with the highest incidence of the disease are Sudan, Venezuela, Mexico, and India, but Sudan and Mexico
have the highest number of cases reported.
• Cases have also been reported in other African countries such as Egypt, Senegal, Mauritania, Kenia, Niger,
Nigeria, Ethiopia, Chad, Cameroon, Djibouti, and Somalia.
• In sudanese hospitals, at least 300 - 400 patients are diagnosed with mycetoma every year.
• Mycetoma is rare in the United states. Some cases are acquired during International travel, but cases
acquired on US soil have also been reported.
• In Mexico and Brasil, actinomycetomas are more prevalent and Nocardia brasiliensis is the
main etiologic agent.

12. • Mycetomas are considered occupational diseases of individuals who work in rural areas, such as
farmers and shepherds, or that engage in activities related to the environment.
• Mycetomas can affect all age groups, but it occurs more commonly in young men aged between 20
and 40 years. Men are more likely to be affected than women, with the male to female ratio ranging
from 3:1 to 5:1.
• In India, Nocardia species and Madurella grisea are the most common causes of mycetoma.
• Around 75% of mycetomas are actinomycotic in certain parts of India.However, eumycotic mycetoma
accounts for the majority of cases reported from the Northern region.
• Maximum cases are seen in Rajasthan and Tamil Nadu.

13. VI. PROGNOSIS:
• Mycetoma carries a good prognosis if the disease is promptly diagnosed and treated.
• Although mycetoma carries a low risk of mortality, amputations or ankylosis can lessen the quality
of life.
• In late stages of mycetoma, the treatment response is limited.
• The lesions are painless and slowly progressive; however, secondary bacterial infection or bone
expansion may cause pain.
• When secondary infection occurs, staphylococcus aureus is the most common etiologic agent.
• Complications of mycetoma result mainly from toxicity due to prolonged administration of
antimicrobial or antifungal drugs.
• Disfigurementr of the affected body parts may be a consequence of delayed treatment.
• Secondary bacterial infections can progress to full- blown bacteremia or septicemia, resulting in
death.

14. VII. ETIOLOGY:
1) Mycetoma is caused by two types of microorganisms:
2) Bacteria are aerobic actinomycetes which are the cause of Mycetoma called Actinomycetoma, in
more than 50% of the cases.
Ø The organism in this group are:
a) Nocardia brasiliensis.
b) Actinomadura pelletieri.
c) Actinomadura madurae.
d) Streptomyces somaliensis.
e) Actinomyces are:
Actinomyces israelli.
Actinomyces bovis.

15. 3) Fungal infection causes in the other 50% of the cases.This is called Eumycetoma, and also
known as maduromycosis, and caused by true fungus.
Ø There are at least 23 types of filamentous fungi that cause Mycetoma. An important one is:
a) Pseudallescheria boydii (There are yellow granules).
b) Madurella mycetomatis (There are big black granules).
c) Medurella grisea.
• These etiological agents gain entry into the body through the foot from the soil which may be due
to trauma.
• When there is the involvement of the foot, where it is swollen and discolored and numerous
draining sinuses.

16. • This disease is characterized by tumor formation and draining the abscess.
• There is the presence of granules or grains. in the pus.
• These granules have different colors, white, black, yellow, and brown depending upon the causative
agents.
• When fungi are implanted in the subcutaneous tissue following the trauma.
a) There is a destructive granulomatous lesion that drains through multiple sites.
b) There is local spread but no dissemination.

18. VIII. MYCETOMA SPREAD:
• May spread along the fascial planes involving - skin, subcutaneous tissue & underlying structures.
• Spread is rapid and extensive in case of involvement of trunk and buttocks.
• Bone involvement early in mycetoma of scalp.
• 1 - 3 % lymphatic spread to the regional lymph nodes - may suppurate & discharge
1) More common with actinomycetes.
2) Incidence augmented - repeated incomplete surgical excision attempts.
• Blood borne spread - reported only in case of infection by, Norcardia and Streptomyces.

19. IX. DIAGNOSIS:
• Clinical diagnosis:
a) Biopsy tissue
b) Pus
c) Blood (for serology only)
• Imaging techniques including X-rays, ultrasound, magnetic resonance and computer tomography
( these techniques can be used to assess the extent of lesions and planning the clinical management).
• Microscopic examination:
a) Grains (Observing the size of the filaments, the color of the grain)
eg: White to Yellow grains indicate P.boydii , Nocardia species and A. madurae infection.
Black grains indicate, Madurella species infection.
b) Cultures : Fungi are identified based on the macroscopic and microscopic features.
For Actinomycetes biochemical and other tests are used for identification.
• Identification by Polymerase chain reaction (PCR) is the most reliable method but has high cost and
lacks standardized techniques.

20. STAGING: bone involvement has been radiographically classified , as follows:
Stage 0 - Soft tissue swelling without bone involvement.
Stage 1 - Extrinsic pressure effects on the intact bones in the vicinity of an expanding granuloma.
Stage 2 - Irritation of the bone surface without intraosseous invasion.
Stage 3 - Cortical erosion and central cavitation.
Stage 4 - Longitudinal spreading along a single ray.
Stage 5 - Horizontal spread along a single row
Stage 6 - Multidirectional spread due to uncontrolled infection.

21. X.TREATMENT:
• Therapies that work against mycetoma are limited, may have to be taken for a long time, and can
be expensive. The treatment for mycetoma depends on whether it is caused by bacteria
(actinomycetoma) or fungi (eumycetoma).
• Actinomycetoma is usually treatable with antibiotics, and surgery is usually not needed.
• Eumycetoma is usually treated with long-term antifungal medicine, but treatment may not be
completely effective. In this case, surgery or amputation are sometimes needed to cut away the
infected tissue.
• Actinomycetoma drugs: Antibiotics like Doxycycline, TMA (trimethoprim+sulphamethoxazole)
Cotrimazole.
• Eumycetoma drugs : Anti-fungal drugs like Itraconazole, ketoconazole , Voricanozole and
posaconzole.

22. Dosage forms & Strengths: 6mg/kg IV q12hr for first 24hours, then 4mg/kg IV q12hr
200mg/5mL [ Oral Suspension]
Mechanism of Action: It acts by inhibition of fungal cytochrome P-450 and sterol C-14
alphademethylation;decreases ergosterol synthesis and inhibits fungal cell membrane formation.
Pharmacokinetics: Half life - Variable, dose-dependent due to non-linear kinetics
Peak plasma time: 1 - 2hr
Vd : 4.6L/kg
Metabolism: Hepatic
Bioavailability: 96%
Excretion: Urine (80%)
Adverse Effects: Rash, Pruritus, Diarrhea, Hypotension and Photosensitizing skin reactions.
Contraindication: Hypersensitivity

23. ITRACONAZOLE:
Dosage Forms & Strengths : 400mg/day in 2 divided doses
Mechanism of Action: It inhibits cytochrome P450 - dependent synthesis of ergosterol, which in turn
inhibits cell membrane formation.
Pharmacokinetics:
Half life : 32 - 42hr
Distribution: Protein bound - 99.8% ; 0.2% (free drug)
Metabolism: Extensively metabolized by the liver into a large no of metabolites.
Excretion: Urine (35%); feces (54%)
Contraindication: Congestive Heart Failure ( when itraconazole IV was administered to healthy human
volunteers and dogs, negative inotropic effects are seen.

24. Dosage forms & Strengths: 200 - 400 mg/day PO.
Mechanism of Action: Inhibits cytochrome P450- dependent synthesis of ergosterol, which in turn
inhibits cell-membrane formation.
Pharmacokinetics:
Absorption: Rapid
Bioavailability: Decrease as gastric pH increases
Peak Plasma time: 1 - 2hr
Metabolism: Partially metabolized in liver via CYP3A4 to inactive compounds.
Half life: Biphasic; intitial, 2 hr; terminal. 8hr.
Excretion: Feces (57%), Urine (13%).
Adverse effects: Nausea and vomiting, Pruritus , Abdominal pain.
Contraindication: Hypersensitivity.

25. Dosage form & Indications: 40mg/mL (oral suspension)
100mg (tablet)
18mg/mL (injectable solution)
Mechanism of Action: Inhibits fungal cell membrane sterol biosynthesis.
Pharmacokinetics: Absorption: Increased by food
Peak plasma time: 3-5hr (oral suspension); 3-4hr (tablet); 1.5hr (IV)
Distribution: protein bound - >98%
Vd: 287L (oral); 261L (IV)
Metabolism: Metabolized primarily by glucuronide conjugates; Strong CYP3A4
inhibitor.
Elimination: Half life - 35hr (oral susp); 26-31hr tablet); 24.6hr (IV)
Excretion: 71% feces; 13% urine.
Contraindication: Hypersensitivity to posaconazole or other azoles.
Adverse effects: Diarrhea, pyrexia, nausea, hypokalemia, rash, epistaxis, peripheral edema,
hypomagnesemia, decreased appetite.

26. Dosage forms & Indications: 50mg , 75mg, 100mg. 150mg (capsule)
100mg (solution, reconstituted powder for IV)
50mg/5mL(syrup)
25mg/5mL (oral suspension)
20mg, 50mg,100mg,150mg (tablet)
Mechanism of Action: Inhibits protein synthesis and, thus bacterial growth by binding to 30s and
possibly 50s ribosomal subunits of susceptible bacteria; may block dissociation of peptidyl t-RNA
from ribosomes, causing RNA dependent protein synthesis to arrest.
Pharmacokinetics:
Absorption: Bioavaliability- reduced at high pH; peak serum time: 1.5 - 4hr
Distribution: protein bound - 90%
Metabolism: Liver
Elimination: Half life - 15 to 25hr
Excretion: Urine (23%); feces (30%).
Contraindications: Documentated Hypersensitivity.
Adverse effects: Anorexia, Dental discoloration, Dysphagia, Enterocolitis, Erythema multiform, Esophagitis.

27. Dosage forms & strengths: 1-2 DS tablets PO q12hr to 24 hours. (single strength (tmp+sulf) = 400+80
double strength= 800+160mg)
Mechanism of Action: Inhibits dihydrofolate reductase, which in turn inhibits folic acid reduction to
tetrahydrofolate, causing inhibition of microorganism growth.
Pharmacokinetics: Absorption: Time to peak - 1 to 4hrs
Half life: 8-14hr; prolonged in renal impairment
Metabolism: Partially Hepatic
Excretion: Urine
Renal Impairment:
CrCl 15 - 30ml/min- 50mg q12hr
CrCl < 15ml/min- 100mg every 24hr/ avoid use
Contraindications: Known hypersensitivity.
Adverse Effects: Pruritis, Hyponatremia, Hyperkalemia

28. XI. SUMMARY:
• Mycetoma is a chronic, progressively destructive infectious disease of the subcutaneous tissues
that spreads to affect the skin, deep tissues and bone.
• Mycetoma can be caused by different species of bacteria or fungi.
• Mycetoma occurs in tropical and subtropical environments characterized by short rainy seasons
and prolonged dry seasons that favour the growth of thorny bushes.
• Global burden is unknown, but the disease is endemic in Africa, Asia, Europe and Latin America.
• Mycetoma has numerous adverse medical, health and socioeconomic consequences for patients,
communities and health services in affected areas.
• People living in or travelling to endemic areas should be advised not to walk barefoot, as footwear
and clothing in general can protect against puncture wounds.