PMID- 26716103 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20151230 LR - 20230717 IS - 2328-8957 (Print) IS - 2328-8957 (Electronic) IS - 2328-8957 (Linking) VI - 2 IP - 4 DP - 2015 Dec TI - Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis. PG - ofv157 LID - 10.1093/ofid/ofv157 [doi] LID - ofv157 AB - Background. Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%-50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods. Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7-1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by "enhanced consolidation" therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1-2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results. Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6-2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions. Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes. FAU - Rolfes, Melissa A AU - Rolfes MA AD - Department of Medicine , Medical School, University of Minnesota. FAU - Rhein, Joshua AU - Rhein J AD - Department of Medicine , Medical School, University of Minnesota ; Infectious Diseases Institute, Makerere University , Kampala , Uganda. FAU - Schutz, Charlotte AU - Schutz C AD - Institute of Infectious Disease and Molecular Medicine and Department of Medicine , University of Cape Town , South Africa. FAU - Taseera, Kabanda AU - Taseera K AD - Internal Medicine, Faculty of Medicine , Mbarara University of Science and Technology, Mbarara , Uganda. FAU - Nabeta, Henry W AU - Nabeta HW AD - Infectious Diseases Institute, Makerere University , Kampala , Uganda. FAU - Huppler Hullsiek, Kathy AU - Huppler Hullsiek K AD - Division of Biostatistics , School of Public Health, University of Minnesota , Minneapolis. FAU - Akampuira, Andrew AU - Akampuira A AD - Infectious Diseases Institute, Makerere University , Kampala , Uganda ; Department of Microbiology , College of Health Sciences, Makerere University , Kampala , Uganda. FAU - Rajasingham, Radha AU - Rajasingham R AD - Department of Medicine , Medical School, University of Minnesota ; Infectious Diseases Institute, Makerere University , Kampala , Uganda. FAU - Musubire, Abdu AU - Musubire A AD - Infectious Diseases Institute, Makerere University , Kampala , Uganda. FAU - Williams, Darlisha A AU - Williams DA AD - Department of Medicine , Medical School, University of Minnesota ; Infectious Diseases Institute, Makerere University , Kampala , Uganda. FAU - Thienemann, Friedrich AU - Thienemann F AD - Institute of Infectious Disease and Molecular Medicine and Department of Medicine , University of Cape Town , South Africa. FAU - Bohjanen, Paul R AU - Bohjanen PR AD - Department of Medicine , Medical School, University of Minnesota ; Infectious Diseases Institute, Makerere University , Kampala , Uganda. FAU - Muzoora, Conrad AU - Muzoora C AD - Internal Medicine, Faculty of Medicine , Mbarara University of Science and Technology, Mbarara , Uganda. FAU - Meintjes, Graeme AU - Meintjes G AD - Institute of Infectious Disease and Molecular Medicine and Department of Medicine , University of Cape Town , South Africa ; Department of Medicine , Imperial College London , United Kingdom. FAU - Meya, David B AU - Meya DB AD - Department of Medicine , Medical School, University of Minnesota ; Infectious Diseases Institute, Makerere University , Kampala , Uganda ; School of Medicine, College of Health Sciences, Makerere University , Kampala , Uganda. FAU - Boulware, David R AU - Boulware DR AD - Department of Medicine , Medical School, University of Minnesota. LA - eng GR - U01 AI089244/AI/NIAID NIH HHS/United States GR - K24 AI096925/AI/NIAID NIH HHS/United States GR - T32 AI055433/AI/NIAID NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - K23 AI073192/AI/NIAID NIH HHS/United States PT - Journal Article DEP - 20151228 PL - United States TA - Open Forum Infect Dis JT - Open forum infectious diseases JID - 101637045 PMC - PMC4692307 OTO - NOTNLM OT - HIV OT - amphotericin OT - clinical outcome OT - cryptococcal meningitis EDAT- 2015/12/31 06:00 MHDA- 2015/12/31 06:01 PMCR- 2015/12/28 CRDT- 2015/12/31 06:00 PHST- 2015/06/16 00:00 [received] PHST- 2015/10/19 00:00 [accepted] PHST- 2015/12/31 06:00 [entrez] PHST- 2015/12/31 06:00 [pubmed] PHST- 2015/12/31 06:01 [medline] PHST- 2015/12/28 00:00 [pmc-release] AID - ofv157 [pii] AID - 10.1093/ofid/ofv157 [doi] PST - epublish SO - Open Forum Infect Dis. 2015 Dec 28;2(4):ofv157. doi: 10.1093/ofid/ofv157. eCollection 2015 Dec.