Deep Fungal Infections
Saturday, January 01, 2011
Sporotrichosis is acquired from decaying vegetation or sphagnum
moss or from infected felines. Disease follows accidental
inoculation of the organism by thorns or splinters or scratches.
The guidelines provided are for the treatment of the chronic
lymphocutaneous form of the disease. Joint or pulmonary involvement
requires treatments of longer duration and higher dosage.
Itraconazole 200 mg daily until all lesions have resolved, then
an additional 4 weeks of treatment. (Total duration of treatment is
usually 3-6 months.)
- Terbinafine 250 mg daily until complete resolution, then 4 more
- Saturated solution of potassium iodide (SSKI). Begin with 5-10
drops 3 times daily and increase over several weeks to 15 drops 3
times daily until the disease is cleared and then 4 more
- In refractory cases, the dose of itraconazole may be increased
to 200 mg twice daily. The duration of therapy may be quite
prolonged in refractory cases.
- The lymphangitic lesions of sporotrichosis must be
differentiated from some types of atypical mycobacterial and
nocardial infection. Tularemia and staphylococcal lymphangitis can
present with clinically similar lesions, but patients are usually
- As with all systemic mycoses, erythema nodosum may occur.
- Iodism is a universal, dose-related concomitant condition of
SSKI therapy. Symptoms include coryza, rhinorrhea, nausea, salivary
gland swelling, metallic taste, and a toxic iododerma. Therapy
should be adjusted according to drug tolerance.
- Amphotericin B may be used in cases refractory to the above
treatments. Once the disease is improving, change the patient to
- For AIDS patients with sporotrichosis, lifelong prophylaxis
with itraconazole 200 mg once daily is recommended.
For practical purposes, coccidioidomycosis occurs only in
residents or visitors to the Southwestern United States. Black
(14-fold increase) and Filipino populations (75-fold increase) have
a much higher rate of dissemination than white populations. Primary
pulmonary infection may be asymptomatic or mildly symptomatic and
does not require treatment. Erythema nodosum may appear during this
period. Extrapulmonary disease is serious and should be treated
aggressively. Specific cutaneous lesions containing the spherules
on biopsy may be the presenting sign of dissemination.
Dissemination is far more likely to occur in Filipino and black
populations and in the immunosuppressed. The therapeutic strategy
is to eliminate the causative microorganism.
Itraconazole or fluconazole at a dose of at least 400 mg daily.
Fluconazole is preferred if there is evidence of coccidioidal
meningitis. Azole therapy may not be effective in eradicating CNS
Intravenous amphotericin B is used in cases failing azole
therapy. The daily dose ranges from 0.4 to 1.0 mg/kg. Cumulative
doses range is from 0.5 g to 3.0 g. Liposomal amphotericin may be
used in patients intolerant of amphotericin side effects. Note: For
patients with meningeal involvement, amphotericin must be given
intrathecally as well.
Surgical drainage and/or debridement may be required for
encapsulated abscesses or avascular necrotic lesions.
- Coccidioidomycosis may become a chronic disease, and patients
may require lifelong maintenance therapy.
- Relapses may occur after cessation of azole or amphotericin B
- Pregnancy is a risk factor for dissemination.
- Disseminated coccidioidomycosis results from hematogenous
spread of the fungus. Subcutaneous abscesses, cellulitis, and
draining sinuses are the cutaneous hallmarks, although bone and
meninges are frequently involved. A negative skin test to
coccidioidin with rising antibody titers suggests impending
- Amphotericin B can produce toxicity especially if infused too
rapidly. Reactions, including chills, fever, nausea, malaise, and
anorexia, although reversible, can be severe. These symptoms can be
aborted by premedication regimens. Kidney function must be
monitored closely (e.g., twice-weekly BUN and creatinine). Other
side effects include hypokalemia, hypomagnesemia, and anemia.
Mycetoma, a disease primarily of tropical climatic zones, is a
chronic, slowly progressive infection of the subcutaneous tissue
and deeper structures including bone. It is characterized by
scarring, tumefaction, and sinus tracts exuding "grains." The
therapeutic strategy is to identify the infectious agent and
attempt to eradicate it. Mycetoma is divided into two groups for
therapeutic purposes: Actinomycetoma, caused by filamentous aerobic
actinomycetes; and eumycetoma, caused by true fungi.
The expected response rate should be about 90%, and surgery is
rarely a primary treatment modality.
The treatment is directed at the infectious agent, and its
documented susceptibilities: Trimethoprim sulfamethoxazole 1 to 2
double-strength tablets twice daily with or without rifampin 600 mg
- If there is an initial response after 1 month, continue
treatment for 9-12 months, or 2 months beyond any evidence of
grains and drainage.
- Surgery is of limited benefit in most cases, but may help
manage some small refractory areas once antibiotics have been used
for 6-9 months.
- In unresponsive cases, streptomycin up to 2 g daily plus
dapsone 100-200 mg daily.
- Refractory Norcardia infections may respond to daily amikacin
Response rates are poor (about 50%), and amputation more often
occurs. It should be reserved for advanced and refractory
Ketoconazole 200 mg twice daily for 9-12 months.
- Itraconazole 200 mg twice daily or terbinafine up to 500 mg
twice daily for 9-12 months may be attempted.
Amphotericin may be used as rescue therapy, but many of the
fungi causing eumycetoma are amphotericin resistant.
Chromoblastomycosis (chromomycosis) is a chronic infection of
the dermis and epidermis caused by dematiaceous fungi from the soil
and decaying plant matter. Lesions present as vegetative, verrucous
plaques. The treatment strategy is to eradicate the infectious
- Itraconazole 200 mg twice daily until the lesion is resolved
(often up to 6 months), then for an additional 1 month.
- Voriconazole 200 mg twice daily as above.
Limited lesions may be approached surgically, if antibiotic
therapy is given appropriately before, during, and after the
In refractory cases, terbinafine 500 mg twice daily may be
All patients with cutaneous lesions of blastomycosis are
considered to have disseminated infection and require
- Itraconazole 200-400 mg daily for at least 6 months.
- Fluconazole up to 200-400 mg twice daily is an
Amphotericin B up to 1 mg/ kg to a total of 1-2 g. After
clinical improvement, patient may be switched back to Itraconazole
Cutaneous lesions of histoplasmosis often indicate
immunosuppression, and appropriate evaluation of the immune system
is indicated. All patients with symptomatic disseminated infection
or skin lesions should receive systemic antifungal treatment.
Itraconazole 200 mg twice daily for 12 months.
- Continue treatment until all signs and symptoms have resolved,
which may be longer than 12 months.
- Chronic suppressive therapy of itraconazole 200 mg once daily
is required for immunosuppressed patients and may be started after
the patient has received 3 months of twice daily itraconazole
- In severe disseminated histoplasmosis, give amphotericin B
0.7-1.0 mg/kg daily to a total dosage of 35 mg/kg. Lipid
formulations are appropriate for patients with renal