Complications
Management of Complications in Patients with Cryptococcosis
Persistence
ÎÎCheck that adequate measures have been taken to improve immune
status (eg, decrease immunosuppressants and introduce HAART) and
optimize management of increased intracranial pressure (B-III).
ÎÎReinstitute induction phase of primary therapy for longer course
(4-10 weeks) (B-III).
ÎÎIf the initial dosage of induction therapy was ≤ 0.7 mg/kg IV of AmBd per
day or ≤ 3 mg/kg of LFAmB per day, consider increasing the dose up to
1 mg/kg IV of AmBd per day or 6 mg/kg of liposomal AmB per day. In
general, combination therapy is recommended (B-III).
ÎIf the patient is polyene intolerant, consider fluconazole (≥ 800 mg per day
Î
orally) plus flucytosine (100 mg/kg per day orally in 4 divided doses) (B-III).
ÎÎIf patient is flucytosine intolerant, consider AmBd (0.7 mg/kg per day IV)
plus fluconazole (800 mg [12 mg/kg] per day orally) (B-III).
ÎÎUse of intrathecal or intraventricular AmBd is generally discouraged and
is rarely necessary (C-III).
ÎÎIdeally, persistent and relapse isolates should be checked for changes in
the Minimum Inhibitory Concentration (MIC) from the original isolate; a
≥ 3-dilution difference suggests development of direct drug resistance.
Otherwise, an MIC of the persistent or relapse isolate ≥ 16 mg/mL for
fluconazole or ≥ 32 mg/mL for flucytosine may be considered resistant,
and alternative agents should be considered (B-III).
ÎÎIn azole-exposed patients, increasing the dose of the azole alone is
unlikely to be successful and is not recommended (C-III).
ÎÎAdjunctive immunological therapy with recombinant interferon (IFN)-γ
at a dosage of 100 mcg/m2 for adults who weigh ≥ 50 kg (for those who
weigh < 50 kg, consider 50 mcg/m2) 3 times per week for 10 weeks can
be considered for refractory infection, with the concomitant use of a
specific antifungal drug (B-III).
Relapse
ÎÎRestart induction phase therapy (see Persistence) (B-III).
ÎÎDetermine susceptibility of the relapse isolate (see Persistence) (B-III).
ÎÎAfter induction therapy and in vitro susceptibility testing, consider
salvage consolidation therapy with either fluconazole (800-1200 mg
per day orally), voriconazole (200-400 mg twice per day orally), or
posaconazole (200 mg orally 4 times per day or 400 mg twice per day
orally) for 10-12 weeks (B-III); if there are compliance issues and a
susceptible isolate, prior suppressive doses of fluconazole may be
reinstituted (B-III).
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