Antifungal susceptibility of 262 bloodstream yeast isolates from a mixed cancer and non-cancer patient population: is there a correlation between in-vitro resistance to fluconazole and the outcome of fungemia?

The aim of this study was to test the antifungal susceptibility of 262 bloodstream yeast isolates (164 Candida albicans strain, 88 non-albicans Candida spp. and 10 non-Candida yeasts) recovered from 169 surgical, neonatal, critically ill intensive care unit patients (ICU), and cancer patients (mixed patient population) to amphotericin B (AmB), fluconazole (FLU), 5-flucytosine (5-FC), itraconazole (ITRA), ketoconazole (KETO), miconazole (MICO), and nystatin (NYS), in order to correlate in-vitro resistance to fluconazole with the outcome of fungemia. The agar disk diffusion test was used to assess the susceptibility of the 262 bloodstream yeasts isolates. In addition, 78 strains isolated from cancer patients were also tested with the E-test. There were no differences in the susceptibility of the various C. albicans strains tested, except in 40 isolates from surgery patients, which showed a somewhat lower susceptibility to KETO and MICO to (3.7-5.5% resistance). There were no C. albicans strains resistant to AmB, NYS, or FLU. There were slight differences in the susceptibility patterns of the 88 non-albicans Candida spp. (NAC) isolates. Resistance to AmB and NYS appeared in 1 strain of C. guillermondii (minimum inhibitory concentration; MIC to AmB; 4 microg/ml) and in 1 strain of C. parapsilosis (MIC to NYS, 8 microg/ml and MIC to AmB, 2 microg/ml). All other NACs were susceptible to both polyenes (AmB and NYS). Nine of the 11 strains of C. krusei were resistant to FLU (MIC >or= 64 microg/ml), the 2 exceptions showed, respectively, MICs for FLU of 6 and 32 microg/ml ("dose-dependent" susceptibility). However, only 2 of 29 C. glabrata strains were fully FLU-resistant (MIC >or= 64 microg/ml), 27 being susceptible with MIC values of 0.5-8 microg/ml. Apart from 9 C. krusei and 2 C. glabrata strains, 2 C. parapsilosis strains and 1 strain of C. tropicalis were also FLU-resistant. Among the 88 NACs, 17.04% were FLU-resistant and 3.7% were KETO- and ITRA-resistant. Resistance to 5-FC and AmB was minimal. We compared the outcomes of patients infected with FLU-resistant vs FLU-susceptible yeasts in 161 evaluable patients treated with FLU. Attributable mortality was significantly higher (19.0% vs 8.6%; P < 0.01) in patients infected with the FLU-resistant yeasts

Cytokine gene polymorphisms and the outcome of invasive candidiasis: a prospective cohort study.

Item does not contain fulltextBACKGROUND: Candida bloodstream infections cause significant morbidity and mortality among hospitalized patients. Although clinical and microbiological factors affecting prognosis have been identified, the impact of genetic variation in the innate immune responses mediated by cytokines on outcomes of infection remains to be studied. METHODS: A cohort of 338 candidemia patients and 351 noninfected controls were genotyped for single-nucleotide polymorphisms (SNPs) in 6 cytokine genes (IFNG, IL10, IL12B, IL18, IL1beta, IL8) and 1 cytokine receptor gene (IL12RB1). The association of SNPs with both candidemia susceptibility and outcome were assessed. Concentrations of pro- and antiinflammatory cytokines were measured in in vitro peripheral blood mononuclear cell stimulation assays and in serum from infected patients. RESULTS: None of the cytokine SNPs studied were associated with susceptibility to candidemia. Persistent fungemia occurred in 13% of cases. In the multivariable model, persistent candidemia was significantly associated with (odds ratio [95% confidence interval]): total parenteral nutrition (2.79 [1.26-6.17]), dialysis dependence (3.76 [1.46-8.64]), and the SNPs IL10 rs1800896 (3.45 [1.33-8.93]) and IL12B rs41292470 (5.36 [1.51-19.0]). In vitro production capacity of interleukin-10 and interferon-gamma was influenced by these polymorphisms, and significantly lower proinflammatory cytokine concentrations were measured in serum from patients with persistent fungemia. CONCLUSIONS: Polymorphisms in IL10 and IL12B that result in low production of proinflammatory cytokines are associated with persistent fungemia in candidemia patients. This provides insights for future targeted management strategies for patients with Candida bloodstream infections

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis.

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