Impact of fluconazole prophylaxis on fungal colonization and infection rates in neutropenic patients

Fungal colonization profiles from four different anatomical sites were eval uated in 266 neutropenic cancer patients receiving intensive cytotoxic ther apy for acute leukaemia or for autologous marrow transplantation. At the be ginning of chemotherapy patients were allocated randomly to receive oral fl uconazole 400 mg daily or an identical placebo until prophylaxis failure or marrow recovery. Candida albicans colonization was reduced from 30 to 10% in the fluconazole recipients while it increased from 32 to 57% in the plac ebo patients (P < 0.001). By the end of prophylaxis, colonization with non- albicans Candida species increased from 7 to 21% and 8 to 18% in the flucon azole and placebo patients, respectively (P = 0.396). Although Candida glab rata was isolated more frequently at the end of the prophylactic period in the fluconazole patients than in the placebo patients (16 versus 7%), only one definite invasive C. glabrata infection was noted. Overall, definite in vasive fungal infections were documented in 26 patients [four fluconazole v ersus 22 placebo patients (P <less than or equal to> 0.001)]. In 23 (92%) p atients the infections were caused by persistently colonizing or newly acqu ired organisms. While probable invasive fungal infections were noted in fiv e fluconazole patients, 10 placebo patients were also affected (P = 0.19). An end-of-prophylaxis colonization index >0.25 was 76% sensitive but only 6 9% specific for invasive fungal infection. However, a colonization index le ss than or equal to 0.25 at baseline had a negative predictive value of 88% for development of invasive fungal infection. Fluconazole prophylaxis decr eased colonization by fungi and subsequent invasive fungal infections in ne utropenic cancer patients.