Powderly WG, Tuazon C, Cloud GA, Saag MS, Van Der Horst C; Washington U, St. Louis, MO.
We examined the usefulness of measurement of serum and cerebrospinal fluid (CSF) cryptococcal antigen (CRAG) titers in monitoring antifungal therapy in patients with AIDS-associated cryptococcal meningitis (CM). Serum and CSF CRAG was measured at baseline, during (2 weeks, 4 weeks) and at the conclusion of therapy (10 weeks) in patients who participated in the MSG-ACTG randomized trial of amphotericin B followed by fluconazole or itraconazole for CM. We examined the correlation of baseline titers and changes in titers with clinical and mycologic outcome at 2 weeks (conclusion of the AmB phase) and at 10 weeks (conclusion of azole phase). We found no correlation between baseline serum CRAG titers or changes in serum titers with outcome at any point. Patients with mycologic failure (persistence of positive cultures) at 2 weeks had significantly higher CSF CRAG titers at baseline compared with responders (P=0.0002); however, baseline CSF cryptococcal antigen titers were not correlated with clinical or mycologic outcome at 10 weeks. Changes in CSF antigen titer were strongly associated with outcome. 88% of patients with a successful mycologic outcome to therapy at 10 weeks (negative CSF cultures) had a reduction from baseline of at least 0.5 log in the geometric mean of the CRAG titer compared to only 56% of patients who failed therapy (P=0.008); a similar difference was noted for clinical response (88% of responders versus 64% of failures, p=0.006). We conclude that measurement of serum CRAG has no value in the management of AIDS associated CM. CSF CRAG may provide some limited information and may serve as a surrogate for culture in some settings.
Keywords: AEGIS, Meningitis, Cryptococcal, Acquired Immunodeficiency Syndrome, Fluconazole, Amphotericin B, Colony-Stimulating Factors, Antibiotics, Antifungal, Itraconazole, Plasma, Human, cerebrospinal fluid, AIDS
