Background. We describe an immune reconstitution syndrome (IRS)–like entity in the course of evolution ofCryptococcus neoformans infection in organ transplant recipients.

Methods. The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study.

Results. In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative forC. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy.

Conclusions. This study demonstrated that an IRS-like entity occurs in organ transplant recipients withC. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.