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MANAGEMENT
OF OPPORTUNISTIC INFECTIONS
IN
HIV-POSITIV PATIENTS
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FACT
SHEETS
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Cryptococcosis
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A fungal
infection
Causative organisms
Cryptococcus neoformans. There are 2 pathogenic varieties,
C. neoformans var. neoformans and
C. neoformans var. gattii, which can be distinguished
on the basis of capsular subtypes.
Symptoms of active infection
Meningitis
This is most common. Mild headache and intermittent fevers.
Progressive malaise, nausea, fatigue, loss of appetite.
Altered mental status, seizures (rare). Intracranial hypertension
is a common complication and may cause blindness or death.
Pneumonia
May also cause a form of pneumonia mimicking Pneumocystis
carinii pneumonia (PCP), sometimes occurring at the same
time as PCP.
Disseminated infection
Cryptococcosis in HIV-positive patients is typically disseminated,
with infections of the skin, joints, eye, adrenal glands,
GI tract, liver, pancreas, peritoneum, heart, prostate
and urinary tract having been described. Cutaneous cryptococcosis
is usually a sign of dissemination. The lesions vary greatly
and mimic many other dermatologic entities.
Diagnostic procedures |
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Cryptococcal smear India ink preparation brings out
the prominenttranslucent capsule of the organisms.
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India ink stain on CSF; testing for cryptococcal antigen
(CRAG) in serum, cerebrospinal fluid (CSF). Chest x-ray
for pneumonia. With altered mental status, seizures
or other neurological problems CT scan or MRI scan should
be done to rule out other factors, followed by lumbar
puncture (spinal tap).
Treatment
Induction treatment
A regimen of amphotericin B, 0.7 mg/kg I.V. daily +
flucytosine 25 mg/kg q.i.d. for 2 weeks, followed by
fluconazole 400 mg orally for 8 weeks. Itraconazole
200-400 mg orally b.i.d. can be used for patients who
cannot tolerate fluconazole.
Addition of 5-flucytosine 25 mg/kg orally q.i.d. achieves
a more rapid sterilization of the CSF. Newer liposomal
preparations of amphotericin B may have better tolerability.
Maintenance therapy
The risk for recurrence after induction therapy is nearly
100% after 1 year if suppressive therapy is not provided.
Fluconazole 200 mg/day orally is 98% effective for prevention
of recurrence and is well-tolerated (Powderly et al
N Engl J Med 1992; 326: 793). Amphotericin B 1 mg/kg
i.v. weekly is less effective and poorly tolerated.
Prevention
In a prospective trial, fluconazole 200 mg/day orally
reduced the occurrence of cryptococcal meningitis from
7.1% to 0.9% (Powderly et al N Engl J Med 1995; 332:
700). Prophylaxis with fluconazole, but not itraconazole,
also markedly reduces the incidence of oropharyngeal
and oesophageal candidiasis.
However, routine prophylaxis is not recommended because:
1. May lead to emergence of drug-resistant fungi
2. Does not reduce mortality
3. Expensive
4. Complicated drug interactions, particularly
with rifampicin
Drug Interactions
Fluconazole
Avoid astemizole, terfenadine, warfarin, rifampin, oral
contraceptives, cimetidine, phenytoin, hydrochlorothiazide
and sulfonylureas.
Amphotericin B
Avoid steroids, some antineoplastics. May be synergistic
with flucytosine. Requires frequent monitoring of blood
levels.
Flucytosine
Requires close monitoring of blood, kidney and liver
functions.
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