Abstract
BackgroundThe Infectious Diseases Society of America published in 2000 practical guidelines for the management of cryptococcosis. However, treatment strategies have not been fully validated in the various clinical settings due to exclusion criteria during therapeutic trials. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals.Methodology/Principal FindingsPatients were enrolled if at least one culture grew positive with Cryptococcus neoformans. Control of sterilization was warranted 2 weeks (Wk2) and 3 months (Mo3) after antifungal therapy onset. 208 HIV-positive or -negative adult patients were analyzed. Treatment failure (death or mycological failure) at Wk2 and Mo3 was the main outcome measured. Combination of amphotericin B+flucytosine (AMB+5FC) was the best regimen for induction therapy in patients with meningoencephalitis and in all patients with high fungal burden and abnormal neurology. In those patients, treatment failure at Wk2 was 26% in the AMB+5FC group vs. 56% with any other treatments (p<0.001). In patients treated with AMB+5FC, factors independently associated with Wk2 mycological failure were high serum antigen titer (OR [95%CI] = 4.43[1.21–16.23], p = 0.025) and abnormal brain imaging (OR = 3.89[1.23–12.31], p = 0.021) at baseline. Haematological malignancy (OR = 4.02[1.32–12.25], p = 0.015), abnormal neurology at baseline (OR = 2.71[1.10–6.69], p = 0.030) and prescription of 5FC for less than 14 days (OR = 3.30[1.12–9.70], p = 0.030) were independently associated with treatment failure at Mo3.Conclusion/SignificanceOur results support the conclusion that induction therapy with AMB+5FC for at least 14 days should be prescribed rather than any other induction treatments in all patients with high fungal burden at baseline regardless of their HIV serostatus and of the presence of proven meningoencephalitis.
Highlights
Major information on the best therapeutic strategies for cryptococcal meningoencephalitis derives from therapeutic trials involving HIV-positive [1,2,3] or HIV-negative patients [4]
Induction therapy using a combination of amphotericin B (AMB, 0.7–1 mg/kg/d) and flucytosine (5FC, 100 mg/kg/d) for 2 weeks followed by a consolidation phase of 10 weeks by fluconazole (FCZ, 400 mg/d) should be prescribed for central nervous system infection (CNS) in both HIV-positive and -negative patients, based mostly on data extrapolated from trials in HIV-infected patients [5] and retrospective studies on HIV-negative patients [6,7]
Since they are excluded from therapeutic trials, data are missing on the optimal antifungal treatment for non CNS infections and for the most severe cases of meningoencephalitis
Summary
Major information on the best therapeutic strategies for cryptococcal meningoencephalitis derives from therapeutic trials involving HIV-positive [1,2,3] or HIV-negative patients [4]. According to the current Infectious Diseases Society of America (IDSA) guidelines, the treatment should depend on anatomic site and host’s immunological status. Alternative options to the AMB+5FC combination are advocated and the place of 5FC is still questioned by numerous clinicians especially in HIV-negative patients or in case of mild-to-moderate symptoms, even if AMB+5FC combination therapy is the most fungicidal regimen for CNS infections [8]. Since they are excluded from therapeutic trials, data are missing on the optimal antifungal treatment for non CNS infections and for the most severe cases of meningoencephalitis. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
