title: Correlation of susceptibility of Cryptococcus neoformans to amphotericin B with clinical outcome.
abstract: Testing of Cryptococcus neoformans for susceptibility to antifungal drugs by standard microtiter methods has not been shown to correlate with clinical outcomes. This report describes a modified quantitative broth macrodilution susceptibility method showing a correlation with both the patient's quantitative biological response in the cerebrospinal fluid (CSF) and the survival of 85 patients treated with amphotericin B (AMB). The Spearman rank correlation between the quantitative in vitro measure of susceptibility and the quantitative measure of the number of organisms in the patient's CSF was 0.37 (P < 0.01; 95% confidence interval [95% CI], 0.20, 0.60) for the first susceptibility test replicate and 0.46 (P < 0.001; 95% CI, 0.21, 0.62) for the second susceptibility test replicate. The median in vitro estimated response (defined as the fungal burden after AMB treatment) at 1.5 mg/liter AMB for patients alive at day 14 was 5 CFU (95% CI, 3, 8), compared to 57 CFU (95% CI, 4, 832) for those who died before day 14. These exploratory results suggest that patients whose isolates show a quantitative in vitro susceptibility response below 10 CFU/ml were more likely to survive beyond day 14.
authors.affiliation: Department of Medicine, Infectious Diseases, University of Southern California, Los Angeles, California, USA. rlarsen@usc.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Larsen
authors.forename: M
authors.initials: M
authors.lastname: Bauer
authors.forename: P
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: A
authors.initials: A
authors.lastname: Sanchez
authors.forename: S
authors.initials: S
authors.lastname: Tansuphaswadikul
authors.forename: V
authors.initials: V
authors.lastname: Wuthiekanun
authors.forename: S J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: A J H
authors.initials: AJ
authors.lastname: Simpson
authors.forename: A W
authors.initials: AW
authors.lastname: Fothergill
authors.forename: M G
authors.initials: MG
authors.lastname: Rinaldi
authors.forename: B
authors.initials: B
authors.lastname: Bustamante
authors.forename: A M
authors.initials: AM
authors.lastname: Thomas
authors.forename: R
authors.initials: R
authors.lastname: Altomstone
authors.forename: N P J
authors.initials: NP
authors.lastname: Day
authors.forename: N J
authors.initials: NJ
authors.lastname: White
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002555:Cerebrospinal Fluid / Q000382:microbiology; D015169:Colony Count, Microbial; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D008826:Microbial Sensitivity Tests / Q000379:methods; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B