Complications
Management of Complications in Patients with Cryptococcosis Persistence
ÎCheck 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).
ÎReinstitute induction phase of primary therapy for longer course (4-10 weeks) (B-III).
ÎIf 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 orally) plus flucytosine (100 mg/kg per day orally in 4 divided doses) (B-III).
ÎIf 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).
ÎUse of intrathecal or intraventricular AmBd is generally discouraged and is rarely necessary (C-III).
ÎIdeally, 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).
ÎIn azole-exposed patients, increasing the dose of the azole alone is unlikely to be successful and is not recommended (C-III).
ÎAdjunctive immunological therapy with recombinant interferon (IFN)-γ at a dosage of 100 mcg/m2
weigh < 50 kg, consider 50 mcg/m2 Relapse
ÎRestart induction phase therapy (see Persistence) (B-III). ÎDetermine susceptibility of the relapse isolate (see Persistence) (B-III). ÎAfter induction therapy and
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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be considered for refractory infection, with the concomitant use of a specific antifungal drug (B-III).
for adults who weigh ≥ 50 kg (for those who ) 3 times per week for 10 weeks can
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