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Madura Foot
1. A chronic infection involving the feet and characterised by
the formation of localised lesions with tumefactions and multiple draining
sinuses. The exudate contains granules that may be yellow, white, red, brown, or
black, depending upon the causative agent. Mycetoma is caused by two principal
groups of microorganisms:
A. Actinomycotic mycetoma is caused by actinomycetes,
including species of Streptomyces, Actinomadurae, and Nocardia.
B. Eumycotic mycetoma is caused by true fungi, including
species of Madurella, Exophiala, Pseudallescheria, Curvularia, Neotestudina,
Pyrenochaeta, Aspergillus, Leptosphaeria, Plemodomus, Polycytella, Fusarium,
Phialophora, Corynespora, Cylindrocarpon, Pseudochaetosphaeronema, Bipolaris,
and Acremonium.
Synonym: fungous foot, Madura boil, Madura foot, maduromycosis.
2. Any tumour with draining sinuses produced by filamentous
fungi.
The term mycetoma was created by Carter (1861)1 to
distinguish this condition from other tumors. There existed quite a variety of
names for this condition:2 Madura foot, from its prevalence in the
district of Madura (India); morbus tuberculosis pedis from a fancied resemblance
to tuberculosis; fungus disease of India; Godfrey and Eyre's disease; endemic
degeneration of the bones of the foot; fungus foot; morbus pedis entophyticus-affection
singuliere; perforating ulcer of the foot, and so on.
Today the only surviving names are mycetoma and Madura foot.
Mahgoub and Murray (1973)2 described mycetoma as a chronic
progressive fungal tumor of the subcutaneous tissue that ultimately attacks
bone. Development is slow, pain is not a marked feature and the disease is
exogenous. An organism is implanted into the host tissue through a break in the
skin caused by a sharp object (most commonly a horn). According to the same
authors, the radiological manifestations vary from soft tissue to the bones.
However, bone involvement in mycetoma is an ultimate feature
that again may be localized or lead to extensive destruction. The tendons and
nerves are usually not involved in the disease. The radiological features of
this disease have also been reported by several authors: Davies (1957), Gumaa et
al. (1975, 1986), Sutton (1980, 1987), Bendl et al. (1987),
Sharif et al. (1991) and Fahal and Hassan (1992).
Mycetoma describes a chronic granulomatous disorder due to
fungal or actinomycetes infection. The actinomycotic mycetoma is caused by
aerobic actinomycetes such as Nocardia brasilensis and Streptomycetes madurae
while the mycotic group are caused by true fungi such as Madurella mycetomii.
The infection is often introduced by foreign body innoculation such as a thorn
or from minor injury. It is common where patients walk bare-footed. It was first
described by Gill in Madura, India and hence the expression “Madura Foot”.
This lesion is however prevalent throughout tropical Africa, Saudi Arabia,
India, Central and South America(1,2).
The foot is the most commonly infected region, followed by the hand and
retroperitoneum(3).
There is usually a long asymptomatic incubation period, followed by the
formation of a subcutaneous granuloma. This spreads by contiguity into deeper
soft tissues such as the plantar aponeurosis and muscles. Lymphatic spread to
regional lymph nodes is common. Skin sinus formation is common with pus
discharge which characteristically contains fungal granules. Subcutaneous
nodules and abscesses may also be seen.
Bone involvement is common(3).
There is contiguous spread from the infected soft tissues, with development of
cortical erosions and periosteal reaction (Fig
1). The development of marked sclerosis is common, particularly in those
patients infected with actinomycetes, Streptomyces pelletieri and madurae(2)
(Fig 2). In
some patients, there is diffuse osteopaenia with marked bony and cartilage
destruction which may be mistaken for neurogenic arthropathy(4)
(Fig 3).
Treatment depends on the causative organism. Actinomycotic soft tissue
infections are usually treatable with antibiotics while mycotic infections are
more resistant to antifungal agents(3).
Once bone is infected, surgical excision is necessary(5).
Therefore the early radiological detection of bone infection is important for
correct patient management.
Mycetoma
|
|
| Synonyms and
related keywords: maduromycosis, Madura foot, actinomycetes,
fungi, fungus, fungal infection, bacterial infection, bacteria,
bacterium, actinomycetoma, eumycetoma, disfigurement, deformity, Pseudallescheria
boydii, P boydii, Actinomadura madurae, A madurae, Actinomadura
pelletieri, A pelletieri, Streptomyces somaliensis, S somaliensis,
Nocardia |
| |
AUTHOR
INFORMATION |
Section
1 of 11 
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| Author: Basilio
J Anía, MD, PhD, Associate Professor, Department of
Internal Medicine, Division of Infectious Diseases, Universidad De
Las Palmas De Gran Canaria, Spain
Coauthor(s): Margarita
Asenjo, MD, Associate Professor, Department of
Radiology, Medical School of the University of Las Palmas De Gran
Canaria, Spain; Raphael J Kiel, MD, Associate
Program Director, Head of Infectious Disease Section, Associate
Professor of Internal Medicine, Department of Internal Medicine,
Oakwood Hospital, Wayne State University School of Medicine
|
|
|
| Editor(s): Larry I Lutwick, MD,
Director, Division of Infectious Diseases, Veterans Affairs New
York Harbor Health Care System, Professor, Department of Internal
Medicine, State University of New York at Downstate; Francisco
Talavera, PharmD, PhD, Senior Pharmacy Editor, Pharmacy,
eMedicine; Michael Stuart Bronze, MD, Chairman,
Professor, Department of Medicine, University of Oklahoma Health
Science Center; Eleftherios Mylonakis, MD, PhD,
Graduate Assistant in Medicine, Instructor in Medicine, Division
of Infectious Disease, Massachusetts General Hospital, Harvard
University; and Burke A Cunha, MD, Professor of
Medicine, State University of New York School of Medicine; Chief,
Infectious Disease Division, Vice-Chair, Department of Internal
Medicine, Winthrop-University Hospital |
| |
INTRODUCTION |
Section
2 of 11 
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Background: Mycetoma is a chronic subcutaneous infection
caused by actinomycetes or fungi. This infection results in a
granulomatous inflammatory response in the deep dermis and subcutaneous
tissue, which can extend to the underlying bone. Mycetoma is characterized
by the formation of grains containing aggregates of the causative
organisms that may be discharged onto the skin surface through multiple
sinuses. This disease was described first in the mid 1800s and initially
named Madura foot, after the region of Madura in India where it first was
identified.
Actinomycetomas are mycetomas caused by microaerophilic
actinomycetes, and mycetomas caused by true fungi are called eumycetomas.
These conditions are to be differentiated from actinomycosis.
Actinomycosis is an endogenous suppurative infection caused by Actinomyces
israelii or other species of Actinomyces or related
bacteria, affecting the cervical-facial, thoracic, and pelvic sites (the
latter usually is associated with the use of intrauterine devices). The
branching bacteria causing actinomycosis are non–acid-fast anaerobic or
microaerophilic bacteria. These bacteria are less than 1 micrometer in
diameter and are small compared to the larger diameter of eumycotic
agents. On the other hand, the agents of actinomycetoma always are aerobic
and sometimes are weakly acid-fast.
More than 20 species of fungi and bacteria can cause
mycetoma. Approximately 60% of mycetomas are caused by bacteria (actinomycetoma),
and 40% are caused by true fungi (eumycetoma).
Pathophysiology: The body parts
affected most commonly are the foot or lower leg, with infection of the
dorsal aspect of the forefoot being typical. The hand is the next most
common location; however, lesions can occur anywhere on the body. Lesions
on the chest and back frequently are caused by Nocardia species,
whereas lesions on the head and neck usually are caused by Streptomyces
somaliensis.
The causative organism enters through sites of local
trauma (eg, cut on the hand, foot splinter, local trauma related to
carrying soil-contaminated material). A neutrophilic response initially
occurs, which may be followed by a granulomatous reaction. Spread occurs
through skin facial planes and can involve the bone. Hematogenous or
lymphatic spread is uncommon.
Frequency:
 | In the US: Mycetoma is rare. Pseudallescheria
boydii is the most common cause of this condition. |
| Internationally: This condition is
endemic in Africa, from Sudan and Somalia through Mauritania and
Senegal. Other endemic countries are Mexico and India; however, the
disease also can be found in natives of areas of Central and South
America and the Middle or Far East between latitudes 15°S and 30°N.
In Sudan, at least 300-400 patients are diagnosed in hospitals every
year. |
Mortality/Morbidity: The disease causes
disfigurement but rarely is fatal; however, when the skull is involved, a
risk to life exists. The lesions are painless and slowly progressive;
however, pain may occur when secondary bacterial infection or bone
expansion occurs. In advanced cases, deformities or ankylosis and their
corresponding disabilities can appear.
Race: No particular risk based on race
has been described.
Sex: The male-to-female ratio is 5:1.
Age: This condition most frequently
occurs in patients aged 20-40 years.
History:
| The earliest sign is a painless subcutaneous
swelling. Some patients have a history of a penetrating injury at that
site. |
| Several years later, a painless subcutaneous nodule
is observed. After some years, massive swelling of the area occurs,
with induration, skin rupture, and sinus tract formation. |
| As the infection spreads to contiguous body parts,
old sinuses close and new ones open. |
| Pain occurs in nearly 20% of patients and usually is
due to secondary bacterial infection or, less commonly, bone invasion. |
| Constitutional symptoms and signs are rare. |
| Patients may complain of a deep itching sensation. |
Physical:
| Irrespective of the causal agent, the appearance of
the lesion is similar and consists of the following: |
 | Initially, subcutaneous swelling is present. |
| In a later phase, a subcutaneous nodule develops. |
| Eventually, massive swelling with induration,
rupture of the skin, and formation of sinus tracts occur. |
| In general, eumycetomas are more circumscribed and
progress slower than actinomycetomas. |
| Regional lymphadenopathy is unusual, but when it does
occur, it is due to one of the following: |
| Lymphatic spread of mycetoma to regional nodes
occurs in only 1-3% of patients. |
| Secondary bacterial infection or local
immunological reaction can cause enlargement of regional lymph
nodes. |
| Lymphatic obstruction and fibrosis can cause
lymphedema and erythema. |
Causes:
| This condition most often occurs in farmers,
shepherds, Bedouins, nomads, or people living in rural areas. |
| Frequent exposure to penetrating wounds by thorns or
splinters is a risk factor. |
| Actinomycetoma can be caused by the following: |
| Actinomadura madurae |
| Actinomadura pelletieri |
| S somaliensis |
| Nocardia species |
| Eumycetoma is caused primarily by P boydii. |
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DIFFERENTIALS |
Section
4 of 11
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Actinomycosis
Cellulitis
Kaposi Sarcoma
Malignant Melanoma
Other Problems to be Considered:
Botryomycosis
Thorn granuloma
Fibrolipoma
Neurofibroma
Necrotizing fasciitis
Cold abscess
|
Lab Studies:
| Staining |
| Hematoxylin-eosin staining of a biopsy sample
allows for detection of grains. |
| Process hematoxylin-eosin and May-Grünwald-Giemsa
staining of a cytologic smear of a sample obtained by fine-needle
aspiration. Mycetoma grains can be distinguished from artifacts and
other organisms by the intimate relationship between the grain and
neutrophils. The appearance of the grains is determined as follows:
 | Actinomycetoma - Homogenously eosinophilic with
hematoxylin-eosin stain; blue in the center with pink filaments
in the periphery with May-Grünwald-Giemsa stain
| Eumycetoma - Brownish color with hematoxylin-eosin
stain; black with a green tinge with May-Grünwald-Giemsa stain |
|
|
| The causal agent of each type of mycetoma can be
visualized better with the following:
| Tissue Gram stain to detect fine,
gram-positive, branching filaments within the actinomycetoma
grain
| Gomori methenamine silver or periodic acid-Schiff
stain to demonstrate the larger hyphae of eumycetoma |
|
|
| Evaluation of the characteristics of the associated
granules suggests an initial differential diagnosis, as follows: |
| White-to-yellow grains are indicative of P
boydii, Nocardia species, or A madurae infection. |
| Yellow-to-brown grains are indicative of S
somaliensis infection. |
| Black grains are indicative of Streptomyces
paraguayensis, Madurella species, or Leptosphaeria
species infection. |
| Red-to-pink grains are indicative of A
pelletieri infection. |
| Culture the grains obtained from a deep-seated wedge
biopsy or a sample obtained by puncture and fine-needle aspiration.
The primary isolation media used should be Löwenstein-Jensen for
actinomycetoma or blood agar for eumycetoma. |
| Serologic diagnosis is available in a few centers and
can be helpful with some patients for diagnosis or follow-up care
during medical treatment. Antibodies can be determined by means of (1)
immunodiffusion, (2) counterimmunoelectrophoresis, (3) enzyme-linked
immunosorbent assay, or (4) Western blot. |
| Caution: Superficial samples of the draining sinuses
are inadequate for culture due to frequent contamination with
bacteria. |
Imaging Studies:
| Bone radiograph: Once mycetoma has invaded the bone,
several changes can be observed, as follows: |
| Cortical thinning is due to compression from the
outside by the mycetoma. |
| Cortical hypertrophy or periosteal proliferation
may present as a sunray appearance and a Codman triangle. |
| Multiple lytic lesions or cavities may be large,
few in number, and with well-defined margins in eumycetoma or small,
numerous, and with ill-defined margins in actinomycetoma. |
| Disuse osteoporosis may occur in late mycetoma. |
| Performing a CT scan allows better definition of the
changes observed on bone x-ray films. |
| MRI helps with the differential diagnosis of the
swelling and can provide a better assessment of the degree of bone
involvement. |
| Ultrasonography: Single or multiple thick-walled
cavities with hyperreflective echoes and no acoustic enhancement
always are observed with mycetoma, whereas these features are not
demonstrated in nonmycetoma swellings. |
| In eumycetoma, the hyperreflective echoes are
sharp, corresponding to the grains in the lesion. |
| In actinomycetoma, the hyperreflective echoes are
fine, closely aggregated, and commonly settle at the bottom of the
cavities. |
Procedures:
| Perform a deep-seated wedge biopsy or puncture and
fine-needle aspiration to obtain a grain sample. |
Histologic Findings: Grains are surrounded
closely and sometimes infiltrated by neutrophils. The causal agent can be
stained better in biopsy samples with Gram stain for actinomycetoma and
with Gomori methenamine silver or periodic acid-Schiff stains for
eumycetoma.
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TREATMENT |
Section
6 of 11
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Medical Care: Antibiotic or antifungal treatment should
be attempted first and may need to be combined with limited surgery.
Surgical Care: Surgery is recommended
for localized lesions that can be excised completely without residual
disability. Surgical reduction of large lesions can improve the patient's
response to medical treatment; however, partial surgical resection without
subsequent use of appropriate antimicrobial or antifungal agents is prone
to failure.
Consultations: Consultation with
specialists in infectious disease or tropical medicine is advised in areas
of the world in which these conditions are unfamiliar.
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MEDICATION |
Section
7 of 11
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Actinomycetoma is a bacterial infection that can respond to antibiotics if
treatment is administered early in the course of the disease. A
combination of 2 drugs in 5-week cycles is used. If needed, the cycles can
be repeated once or twice. The following agents have been used in
combination: trimethoprim-sulfamethoxazole (TMP-SMZ), dapsone (diaminodiphenylsulfone),
and streptomycin sulfate. Amikacin can be substituted for streptomycin but
usually is kept as a second-line drug because of its cost. Rifampin has
been used as a second-line drug in resistant cases. In one case report, a
patient required salvage therapy with amikacin and imipenem for 6 months.
Eumycetoma may respond partially to antifungal agents,
although surgical therapy is preferred if the disease is localized. Madurella
mycetomatis may respond to ketoconazole (200 mg bid). P boydii
may respond to itraconazole. Other agents of eumycetoma may respond
intermittently to itraconazole (200 mg bid) or amphotericin B. The minimum
treatment duration is 10 months.
Drug Category: Antibiotics -- Empiric
antimicrobial therapy must be comprehensive and should cover all likely
pathogens in the context of a clinical setting suggestive of
actinomycetoma.
Drug Name
|
Trimethoprim-sulfamethoxazole
(Bactrim DS, Septra) -- DOC; inhibits bacterial growth by
inhibiting synthesis of dihydrofolic acid. Should be used
continuously in combination with another antimicrobial for 5 wk.
Cycle may be repeated prn.
| Adult Dose |
160
mg TMP/800 mg SMZ PO q6h
| Pediatric Dose |
<2
months: Not recommended
>2 months: 8 mg/kg TMP 40 mg/kg SMZ PO bid
| Contraindications |
Documented
hypersensitivity; megaloblastic anemia due to folate deficiency;
do not use during pregnancy (at term) or breastfeeding
| Interactions |
May
increase PT when used with warfarin (perform coagulation tests,
and adjust dose accordingly); coadministration with dapsone may
increase blood levels of both drugs; coadministration of diuretics
increases incidence of thrombocytopenia purpura in elderly
patients; phenytoin levels may increase with coadministration; may
potentiate effects of methotrexate in bone marrow depression;
hypoglycemic response to sulfonylureas may increase with
coadministration; may increase levels of zidovudine
| Pregnancy |
C -
Safety for use during pregnancy has not been established.
| Precautions |
Discontinue
at first appearance of skin rash or sign of adverse reaction;
obtain CBCs frequently; discontinue therapy if significant
hematologic changes occur; higher risk of hematologic toxicity in
renal allograft recipients; goiter, diuresis, and hypoglycemia may
occur; prolonged IV infusions or high doses may cause bone marrow
depression (if signs occur, give 5-15 mg/d leucovorin); caution in
folate deficiency (eg, patients with chronic alcoholism, elderly
patients, patients receiving anticonvulsant therapy, patients with
malabsorption syndrome); hemolysis may occur in patients deficient
of G-6-PD; patients with AIDS may not tolerate or respond to
TMP-SMZ; caution in renal or hepatic impairment (perform
urinalyses and renal function tests during therapy); give fluids
to prevent crystalluria and stone formation
|
| | | | | |
Drug Name
|
Amikacin
(Amikin) -- Irreversibly binds to 30S subunit of bacterial
ribosomes, blocks recognition step in protein synthesis, and
causes growth inhibition.
Should be given continuously for 3 wk. Although somewhat
expensive, it usually is active against the bacteria causing
actinomycetoma. Use the patient's IBW for dosage calculation.
| Adult Dose |
15
mg/kg/d IV/IM qd or divided bid; not to exceed 1.5 g/d regardless
of higher BW
| Pediatric Dose |
Administer
as in adults
| Contraindications |
Documented
hypersensitivity
| Interactions |
Coadministration
with other aminoglycosides, penicillins, cephalosporins, and
amphotericin B increases nephrotoxicity; enhances effects of
neuromuscular blocking agents; causes respiratory depression;
irreversible hearing loss may occur with coadministration of loop
diuretics
| Pregnancy |
C -
Safety for use during pregnancy has not been established.
| Precautions |
Not
intended for long-term therapy; caution in patients with renal
failure (not on dialysis), hypocalcemia, myasthenia gravis, and
conditions that depress neuromuscular transmission; risk of
nephrotoxicity and ototoxicity
|
| | | | | |
Drug Name
|
Dapsone
(Avlosulfon) -- Bactericidal and bacteriostatic against
mycobacteria. Mechanism of action is similar to sulfonamides where
competitive antagonists of PABA prevent formation of folic acid,
inhibiting bacterial growth. Lowest-cost regimen. Change to
TMP-SMZ if no response occurs after 1 mo.
| Adult Dose |
100
mg PO bid
| Pediatric Dose |
Not
established
| Contraindications |
Documented
hypersensitivity; G-6-PD deficiency
| Interactions |
May
inhibit anti-inflammatory effects of clofazimine; hematologic
reactions may increase with folic acid antagonists, eg,
pyrimethamine (monitor for agranulocytosis during the second and
third mo of therapy); probenecid increases toxicity; TMP may
increase toxicity of both drugs; due to increase in renal
clearance, levels may decrease significantly when administered
concurrently with rifampin
| Pregnancy |
C -
Safety for use during pregnancy has not been established.
| Precautions |
Perform
weekly blood counts for the first mo; then, perform WBC counts
monthly for 6 mo and semiannually thereafter; discontinue if
significant reduction in platelets, leukocytes, or hematopoiesis
is observed; caution in methemoglobin reductase deficiency, G-6-PD
deficiency (patients receiving >200 mg/d), or hemoglobin M due
to high risk for hemolysis and Heinz body formation; caution in
patients exposed to other agents or conditions (eg, infection,
diabetic ketosis) capable of producing hemolysis; peripheral
neuropathy can occur (rare); phototoxicity may occur when exposed
to UV light
|
| | | | | |
Drug Name
|
Rifampin
(Rimactane, Rifadin) -- For use in combination with at least 1
other agent. Inhibits DNA-dependent bacterial but not mammalian
RNA polymerase. Cross-resistance may occur.
| Adult Dose |
10
mg/kg/d PO qd
| Pediatric Dose |
10
mg/kg/d PO; not to exceed 600 mg/d
| Contraindications |
Documented
hypersensitivity
| Interactions |
Induces
microsomal enzymes, which may decrease effects of acetaminophen,
oral anticoagulants, barbiturates, benzodiazepines, beta-blockers,
chloramphenicol, oral contraceptives, corticosteroids, dapsone,
mexiletine, cyclosporine, digitoxin, disopyramide, estrogens,
hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam,
sulfonylureas, theophyllines, tocainide, and digoxin; blood
pressure may increase with coadministration of enalapril;
coadministration with isoniazid may result in higher rate of
hepatotoxicity than with either agent alone (discontinue 1 or both
agents if alterations in LFTs occur)
| Pregnancy |
C -
Safety for use during pregnancy has not been established.
| Precautions |
May
cause abnormal liver function, drug fever, flu syndrome, or
hematological cytopenias; obtain CBCs and baseline clinical
chemistries prior to and throughout therapy; in liver disease,
weigh benefits against risk of further liver damage; interruption
of therapy and high-dose intermittent therapy are associated with
thrombocytopenia that is reversible if therapy is discontinued as
soon as purpura occurs; if treatment is continued or resumed after
appearance of purpura, cerebral hemorrhage or death may occur
|
| | | | | |
Drug Name
|
Imipenem
and cilastatin (Primaxin) -- For treatment of multiple-organism
infections in which other agents do not have wide spectrum
coverage or are contraindicated due to potential for toxicity.
| Adult Dose |
Base
initial dose on severity of infection and administer in equally
divided doses; 0.5-1 g IV q6h; not to exceed 3-4 g/d
Alternate dose: 500-750 mg IM q12h
| Pediatric Dose |
<12
years: Not established; 15-25 mg/kg/dose IV q6h suggested for
>3 mo
Fully susceptible organisms: Not to exceed 2 g/d
Infections with moderately susceptible organisms: Not to exceed 4
g/d
| Contraindications |
Documented
hypersensitivity
| Interactions |
Coadministration
with cyclosporine may increase adverse CNS effects of both agents;
coadministration with ganciclovir may result in generalized
seizures
| Pregnancy |
C -
Safety for use during pregnancy has not been established.
| Precautions |
Adjust
dose in renal insufficiency; avoid use in children <12 y
|
| | | | | |
Drug Category: Antifungal agents -- In combination
with surgical therapy, antifungal agents may help to attain partial
response in cases of eumycetoma.
Drug Name
|
Ketoconazole
(Nizoral) -- Fungistatic activity. Imidazole broad-spectrum
antifungal agent; inhibits synthesis of ergosterol, causing
cellular components to leak, resulting in fungal cell death.
| Adult Dose |
200
mg PO bid
| Pediatric Dose |
<2
years: Not established
>2 years: 3.3-6.6 mg/kg/d PO single dose
| Contraindications |
Documented
hypersensitivity; fungal meningitis
| Interactions |
Isoniazid
may decrease bioavailability; coadministration decreases effects
of either rifampin or ketoconazole; may increase effect of
anticoagulants; may increase toxicity of corticosteroids and
cyclosporine (cyclosporine dosage can be adjusted); may decrease
theophylline levels
| Pregnancy |
C -
Safety for use during pregnancy has not been established.
| Precautions |
Hepatotoxicity
may occur; may reversibly decrease corticosteroid serum levels
(adverse effects avoided with dose of 200-400 mg/d); administer
antacids, anticholinergics, or H2 blockers at least 2 h after
taking ketoconazole
|
| | | | | |
Drug Name
|
Itraconazole
(Sporanox) -- Fungistatic activity. Synthetic triazole antifungal
agent that slows fungal cell growth by inhibiting cytochrome
P-450–dependent synthesis of ergosterol, a vital component of
fungal cell membranes.
| Adult Dose |
200
mg/d PO; not to exceed 400 mg/d; increase in 100-mg increments if
no improvement (administer >200 mg/d in divided doses)
200 mg IV bid for 4 doses, followed by 200 mg/d
| Pediatric Dose |
Not
established; suggested dose of 100 mg/d
| Contraindications |
Documented
hypersensitivity; coadministration with cisapride may cause
adverse cardiovascular effects (possibly death)
| Interactions |
Antacids
may reduce absorption of itraconazole; edema may occur with
coadministration of calcium channel blockers (eg, amlodipine,
nifedipine); hypoglycemia may occur with sulfonylureas; may
increase tacrolimus and cyclosporine plasma concentrations when
high doses are used; rhabdomyolysis may occur with
coadministration of HMG-CoA reductase inhibitors (ie, lovastatin,
simvastatin); coadministration with cisapride can cause cardiac
rhythm abnormalities and death; may increase digoxin levels;
coadministration may increase plasma levels of midazolam or
triazolam; phenytoin and rifampin may reduce levels (phenytoin
metabolism may be altered)
| Pregnancy |
C -
Safety for use during pregnancy has not been established.
| Precautions |
Caution
in hepatic insufficiencies
|
| | | | | |
Drug Name
|
Amphotericin
B (Fungizone) -- Polyene antibiotic produced by a strain of Streptomyces
nodosus; can be fungistatic or fungicidal. Binds to sterols,
such as ergosterol, in the fungal cell membrane, causing
intracellular components to leak with subsequent fungal cell
death.
Conventional formulation (complexed with deoxycholate) has a poor
tolerability profile. Liposomal amphotericin B incorporates the
drug into small unilamellar liposomes; this formulation retains
the antifungal activity with less hypokalemia, anemia and infusion
reactions, and far less nephrotoxicity than the conventional
formulation.
Although the acquisition cost of liposomal amphotericin B is
considerably higher than that of the conventional formulation,
when adverse effects are considered, the calculated total costs of
treatment for fungal infections are not clearly different.
| Adult Dose |
3-5
mg/kg/d IV of liposomal amphotericin B over approximately 120 min
| Pediatric Dose |
Administer
as in adults
| Contraindications |
Documented
hypersensitivity
| Interactions |
Antineoplastic
agents may enhance the potential of amphotericin B for renal
toxicity, bronchospasm, and hypotension; corticosteroids,
digitalis, and thiazides may potentiate hypokalemia; the risk of
renal toxicity is increased with cyclosporine.
| Pregnancy |
B -
Usually safe but benefits must outweigh the risks.
| Precautions |
Monitor
renal function, serum electrolytes (eg, magnesium, potassium),
liver function, CBC, and hemoglobin concentrations; resume therapy
at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for
more than 7 d; hypoxemia, acute dyspnea, and interstitial
infiltrates may occur in patients with neutropenia who are
receiving leukocyte transfusions (separate time of amphotericin
infusion from time of leukocyte transfusion); fever and chills are
not uncommon after first few administrations; rare acute reactions
may include hypotension, bronchospasm, arrhythmias, and shock
|
| | | | | |
| |
FOLLOW-UP |
Section
8 of 11
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Further Outpatient Care:
| Maintain medical treatment and follow-up care for at
least 10 months. |
Deterrence/Prevention:
| Educate patients to avoid activities that expose them
to agents of mycetoma. Instruct patients to avoid carrying sticks and
thorny branches that have had contact with the soil. |
Complications:
| Complications result mainly from toxicity due to
prolonged administration of antimicrobial or antifungal drugs. |
| Amputation may result from neglected chronic
infections. |
Prognosis:
| Prognosis is good with prompt diagnosis and
treatment. Although prognosis for survival is good, amputations or
ankylosis can lessen the quality of life. |
| In late stages, response to treatment is limited. |
| |
MISCELLANEOUS |
Section
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Medical/Legal Pitfalls:
| Mistaking actinomycosis for actinomycetoma is
possible. |
| Performing incomplete surgery as the sole therapy for
this disease can lead to recurrence and a poor cosmetic outcome. |
| |
PICTURES |
Section
10 of 11
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| Caption:
Picture 3. Mycetoma. MRI coronal section of actinomycetoma in a
47-year-old shepherd from Mauritania who had a painless
progressive swelling of the face for more than 20 years. On this
T1-potentiated image, a large heterogenous mass surrounds the
cranium. Bone invasion can be observed only in the area of the
zygomatic fossa. |
 |
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| Picture
Type: MRI |
| Caption:
Picture 4. Mycetoma. MRI with coronal view of actinomycetoma in a
47-year-old shepherd from Mauritania who had a painless
progressive swelling of the face for more than 20 years. The
actinomycetoma mass invades the left parapharyngeal space and
almost reaches the lumen of the pharynx. |
 |
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| Picture
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| |
BIBLIOGRAPHY |
Section
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| Akhtar MA, Latief PA: Actinomycetoma pedis. Postgrad
Med J 1999 Nov; 75(889): 671[Medline].
| Bapat KC, Pandit AA: Actinomycotic mycetoma. Report
of a case with diagnosis by fine needle aspiration. Acta Cytol 1991
Nov-Dec; 35(6): 770-2[Medline].
| Baril L, Boiron P, Manceron V: Refractory
craniofacial actinomycetoma due to Streptomyces somaliensis that
required salvage therapy with amikacin and imipenem. Clin Infect Dis
1999 Aug; 29(2): 460-1[Medline].
| Coukell AJ, Brogden RN: Liposomal amphotericin B.
Therapeutic use in the management of fungal infections and visceral
leishmaniasis. Drugs 1998 Apr; 55(4): 585-612[Medline].
| EL Hag IA, Fahal AH, Gasim ET: Fine needle aspiration
cytology of mycetoma. Acta Cytol 1996 May-Jun; 40(3): 461-4[Medline].
| Fahal AH, Sheik HE, Homeida MM: Ultrasonographic
imaging of mycetoma. Br J Surg 1997 Aug; 84(8): 1120-2[Medline].
| Fahal AH, Hassan MA: Mycetoma. Br J Surg 1992 Nov;
79(11): 1138-41[Medline].
| Hay RJ, Moore M: Mycology. In: Champion RH, Wilkinson
DS, Ebling FJG, Breathnach SM, eds. Rook/Wilkinson/Ebling Textbook of
Dermatology. Vol 2. 6th ed. Oxford, UK: Blackwell Science; 1998:
1277-376.
| Hay RJ: Fungal infections. In: Cook GC, ed. Manson's
Tropical Diseases. 20th ed. London, UK: WB Saunders; 1996: 1047-74.
| Mahgoub ES: Medical management of mycetoma. Bull
World Health Organ 1976; 54(3): 303-10[Medline].
| Mahgoub ES: Agents of mycetoma. In: Mandell GL,
Bennett JE, Dolin R, eds. Principles and Practice of Infectious
Diseases. Vol 2. 5th ed. Philadelphia, Pa: Churchill Livingstone;
2000: 2702-6.
| Saag MS: Mycetoma. In: Goldman L, Bennett JC, eds.
Cecil Textbook of Medicine. 21st ed. Philadelphia, Pa: WB Saunders;
2000: 1885-7. |
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