Persistent fungemia--risk factors and outcome in 40 episodes.

The aim of this multicenter survey was to assess risk factors and mortality in patients with persistent fungemia (PF). Cases of persistent fungemia, defined as positive blood culture for at least 3 causative days of antifungal therapy were selected. Forty cases of persistent fungemia (lasting more than 3 days) were compared with 270 non-persistent fungemias appearing within the same period, and analyzed by univariate and multivariate analysis for risk factors and outcome. The median number of days of positive culture was 4.4 (3 - 20): 22 episodes were due to Candida albicans, 1 due to non-albicans Candida spp., 6 episodes due to non-Candida spp. Yeasts: 15 were catheter related, 16 patients had yeast-infected surgical wounds, 12 were neutropenic, 4 cases were caused by species resistant in vitro, 2 to amphotericin B (Trichosporon spp.) and 2 to fluconazole (C. laurentii, C. glabrata). Fifteen patients (37.5%) died, 7 of whom due to fungemia. Nineteen cases had one known risk factor (10 had infected wound, 4 infected vascular catheter, 3 were neutropenic and 2 had inappropriate therapy). Fourteen cases had two known risk factors (4 had wound and infected catheter, 4 neutropenia and infected catheter, 2 neutropenia and resistant organism, 4 other combinations. Two cases had 3 known risk factors and one had 4 risk factors for persistent fungemia. Artificial ventilation, C. glabrata etiology, non-Candida spp. yeasts such as Trichosporon spp. and Cryptococcus spp. and prior surgery were significantly associated with persistent fungemia in univariate, whereas only C. glabrata etiology in multivariate analysis. Breakthrough fungemia during empiric therapy with fluconazole was also observed more frequently in patients with persistent fungemia. However, there was no difference in both attributable and overall mortality between both groups.

Nosocomial fungemia due to amphotericin B-resistant Candida spp. in three pediatric patients after previous neurosurgery for brain tumors.

Amphotericin B (AmB) resistance in Candida spp. is very rare. Three cases of fungemia, due to amphotericin B-resistant Candida spp. in pediatric patients after previous neurosurgery for brain tumors, are reported. The Candida strains - one C. guillermondii, one C. lusitaniae, and one C. parapsilosis - showed minimum inhibitory concentrations (MICs) to AmB of 2-4 microg/ml. Two of the three patients had been pretreated with AmB for 5-11 days. All three patients were successfully treated with intravenous fluconazole (6-10 mg/kg per day) for 16-28 days, and all survived. Despite AmB resistance in Candida spp. being very rare, C. lusitaniae, C. guillermondii, and C. parapsilosis isolates in documented infections should be tested for AmB resistance, mainly in patients not responding to therapy with AmB.

National and local antibiotic policies in Central and Eastern Europe.

To assess the antibiotic policies of Central European countries, we performed an overview of antibiotic stewardship, prescription habits and antibiotic prescription regulatory procedures. Since most Central European countries have had centralized health care and drug policies, the situation 10 years after decentralization is surprising. Only 3 of 10 Central European countries have some regulation of prescription of antibiotics, only 4 restrict some antibiotics, only 5 have hospital and only 3 national antibiotic policies. In all but 3 countries physicians can prescribe quinolones and/or 3rd generation oral cephalosporins as first-line antibiotics. Information on local and national antibiotic policies in Central and Eastern European countries is given including prescription guidelines for antibiotic use in community and hospital.

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.