G. Kovacicova

Longitudinal 10-year prospective survey of fungaemia in Slovak Republic: trends in etiology in 310 episodes☆

A 10-year prospective survey of fungaemia in the Slovak Republic, involving 31 microbiology laboratories and 71 hospitals, was conducted from 1989-1998 (10 years): 310 fungaemias were analyzed for etiology, clinical characteristics, therapy, and outcome. C. albicans was responsible for 191 (61.6%) fungaemias, non-albicans Candida spp. (NAC) for 97 (31.3%), non-Candida yeasts for 18 (5.8%) and moulds (Fulsarium spp.) for four fungaemias. The most frequent NAC isolated from blood cultures were C. parapsilosis--30 (9.7%), C. krusei--18 (5.8%), C. tropicalis--14 (4.5%), and C. glabrata--10 (3.2%). Secular trends in etiology showed a sustaining decrease of C. albicans (from 100% in 1989 to 50.7% in 1998) and increase of NAC (from 0% in 1989-1990 to 46.3% in 1998). Non-Candida yeasts and moulds showed a stable proportion during the investigated period. There were statistically significant differences in etiology of fungaemia various subgroups of patients: non-albicans Candida spp. was significantly more frequent observed among subgroups of patients with pancreatitis and coma (53.3% vs. 31.3%, p < or = 0.02) and less frequently in the subgroup of neonates (15.0% vs. 31.3%, p < or = 0.006). Vice versa, C. albicans appeared more frequently in neonates (85%).

Prospective Study of Fungaemia in a Single Cancer Institution over a 10-y Period: Aetiology, Risk Factors, Consumption of Antifungals and Outcome in 140 Patients

Over a 10-y period (1989-99) we prospectively evaluated all patients with fungaemia among 16,555 admissions (21,004 blood cultures) at a national cancer referral institution in the Slovak Republic. A prospective protocol was completed on 140 patients with fungaemia, which was then analysed in terms of aetiology, clinical characteristics, potential risk factors and outcome. The most frequently isolated organism was C. albicans, in 75 patients (52.9%), followed by non-albicans Candida spp. in 45 patients (32.1%). Non-Candida spp. yeasts represented 16 episodes in 16 patients (11.4%). Moulds caused 4 episodes in 4 patients (3.6% of all fungaemias) and all were caused by Fusarium spp. Mucositis (p = 0.025), > or = 3 positive blood cultures (p = 0.02), acute leukaemia (p = 0.00001), neutropenia (p = 0.0015), quinolone prophylaxis (p < 0.000005) and breakthrough fungaemia (p = 0.004) during prophylaxis with fluconazole (p = 0.03) and itraconazole (p = 0.005) were significantly more associated with non-Candida than C. albicans spp. Furthermore, attributable mortality was higher in the subgroup of non-Candida than C. albicans spp. (50.0 vs. 18.7%, p < 0.02). The only independent risk factor for inferior outcome was antifungal therapy of < 10 d duration (odds ratio 2.1, 95% confidence interval, p < 0.001). Aetiology, neutropenia and mucositis were not independent risk factors for higher mortality in multivariate analysis; however, they were risk factors for inferior outcome in univariate analysis (p < 0.05-0.005).Over a 10-y period (1989-99) we prospectively evaluated all patients with fungaemia among 16,555 admissions (21,004 blood cultures) at a national cancer referral institution in the Slovak Republic. A prospective protocol was completed on 140 patients with fungaemia, which was then analysed in terms of aetiology, clinical characteristics, potential risk factors and outcome. The most frequently isolated organism was C. albicans, in 75 patients (52.9%), followed by non-albicans Candida spp. in 45 patients (32.1%). Non-Candida spp. yeasts represented 16 episodes in 16 patients (11.4%). Moulds caused 4 episodes in 4 patients (3.6% of all fungaemias) and all were caused by Fusarium spp. Mucositis (p

National and local antibiotic policies in Central and Eastern Europe.

Abstract 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.

Breakthrough candidaemias during empirical therapy with fluconazole in non-cancer and non-HIV adults caused by in vitro-susceptible Candida spp.: report of 33 cases.

The objective of this study was to assess risk factors and the outcome of breakthrough fungaemias (BFs) occurring during fluconazole (FLU) therapy in non-cancer and non-HIV individuals. Thirty-three fungaemias occurring during therapy with FLU among a total of 310 fungaemias observed within a 10-y national survey were analysed. The agar disk diffusion method was used for antifungal susceptibility testing and the Vitek system for species identification. Univariate and multivariate analysis was performed to determine risk factors for BF. All BFs were due to species known to be susceptible to FLU: Candida albicans (25/33), C. parapsilosis (6/33) and C. guillermondii (2/33). The mean number of positive blood cultures per episode was 2.4. The MIC of Candida spp. to FLU was 0.5-8 mg/ml (all strains were susceptible in vitro). Neonatal age (< 4 weeks), very low birth weight, prior surgery, central venous catheter placement, artificial ventilation, total parenteral nutrition and C. parapsilosis were significantly related to BF in univariate analysis, but only central venous catheter placement was significantly related in multivariate analysis. However, the outcome of BFs and non-BFs was similar. All BFs occurred in non-HIV patients who were not previously treated with azoles, and were caused by in vitro FLU-susceptible species (C. albicans and C. tropicalis). Thus factors other than in vitro susceptibility play a role in BFs.

Persistent Fungemia - Risk Factors and Outcome in 40 Episodes

Abstract 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 neu-tropenia 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 Meningitis Due to Pseudomonas aeruginosa in Children

Although Pseudomonas aeruginosa is a common hospital pathogen, nosocomial meningitis after ventriculoperitoneal shunt insertion (VPS) due to P. aeruginosa is relatively rare and represents about 5% of all foreign-body related nosocomial meningitis cases 1. Here we present 6 cases of nosocomial paediatric meningitis, 3 of them related to VPS insertion and exchange. Table 1 summarizes 6 children from 1 month to 13 years of age who developed nosocomial meningitis during a period of the last 8 years in 3 major pediatric neurosurgery departments in Kosice, Bratislava, and Banska Bystrica teaching hospitals in the Slovak Republic. Two children had hydrocephalus and infected ventriculoperitoneal shunt which was extracted and antibiotics (chloramphenicol plus gentamicin or meropenem) were given; both children survived. Two children had congenital B-cell mediated immunodeficiency and despite antibiotic therapy, both died. Another patient had acute lymphatic leukemia and probably developed meningitis after numerous intrathecal administrations of cytotoxic drugs; this patient was cured. Another patient had perinatal trauma, and after VPS insertion, the foreign device was infected. The VPS was extracted and ceftazidime plus gentamicin were administered for 12 days. This child survived, but neurologic sequellae developed (hydrocephalus)–probably because the treatment was too short. After Journal of Chemotherapy Vol. 12 n. 6 (538-539) 2000

Susceptibility of 57 Bloodstream and Urinary Isolates of Candida Species from a Single Children’s University Hospital to 6 Antifungals

Accessible online at: www.karger.com/journals/che Increasing resistance to azole antifungals in isolates from cancer and HIV-positive patients has been reported within the last 5 years [1–3]. These reports were limited to an adult patient population pre-exposed to azoles used for maintenance therapy (HIV) or prophylaxis (bone marrow transplantant recipients and other haemopoietic individuals). Overall resistance to antifungals in children is estimated to be lower because fluconazole (FLU) was introduced in children after 1992 (4 years later than in adults), and the consumption of azoles in adults is much higher than in children [4]. However, data on antifungal susceptibility in paediatric HIV-negative and non-cancer patients are missing. Therefore, we report the results of antifungal susceptibility testing of Candida spp. from a non-HIV and non-cancer patient population from a single university hospital in Slovakia. Bloodstream and urinary isolates detected in a 1-year period (1999), from paediatric surgery, ICU and neonatology departments were tested for their susceptibility to FLU by the agar disc diffusion method according to Bille and Glauser [5]. The results are summarised in table 1 and show that 57 Candida spp. (77% C. albicans and 23% non-albicans Candida spp.) from 57 children 0–11 years old hospitalised in 3 departments (surgery, general ICU, neonatal ICU) were isolated. C. albicans was isolated in 44 patients, C. tropicalis in 6, C. glabrata in 4 and C. krusei, C. parapsilosis and C. kefyr in 1 patient each. Resistance of Candida spp. to FLU was 21.1%, and surprisingly, 6 of 44 C. albicans (13.3%) had an MIC 132 Ìg/ml to FLU (resistant). All C. glabrata were also FLU resistant (MIC 164 Ìg/ml), as well as 1 of the C. tropicalis isolates. This decrease in susceptibility to FLU in Candida spp., especially in C. albicans, in a paediatric population which has not been exposed as much as adults to FLU, is surprising. Reports on the antifungal susceptibility of Candida spp. from cancer patients [1–3] showed 5–10% resistance (mainly due to primarily resistant C. krusei and partially also C. glabrata). Resistance of C. albicans to FLU in cancer patients was found to be minimal (!5%), but in patients with HIV it is common (10–25%) [4–6]. There are some reports on FLU-resistant C. albicans in surgical and ICU patients not exposed to azole prophylaxis or therapy; however, these were only from adults [6, 7]. From our surprising results, we assume that FLU resistance is not related only to consumption or prior exposure to antifungals. Consumption of FLU in our children’s hospital is 5.5 times lower than in a similarly sized adult hospital [7, 8]. Since antifungal resistance is not transferable [5], other factors should be studied, and antifungal susceptibility testing should be performed in all bloodstream isolates of Candida spp. to understand the epidemiology of antifungal resistance in the HIV-negative and non-cancer paediatric population.

Mortality of Enterococcal Bacteremia: Are Inappropriately Treated Cases Associated with Higher Mortality?

2test was used to determine risk factors for death and comparisons of appropriate therapy versus inappropriate therapy. A multivariate logistic regression model (EPI INFO and STAT ADV computerized package of CDC and Postgraduate Medical School) was also used. Of 101 patients with enterococcal bacteremias, 40 died (39.9%). Predictors for inferior outcome identie ed in univariate analysis were 2 or more positive blood cultures ( pB0.0061), burns or decubital ulcer as underlying diseases ( pB0.004). The latter was the only predictor of death also in multivariate analysis ( pB 0.0006, OR 5.07 Cl (1.4‐ 18 5)). Surprisingly neutropenia and vascular catheters seemed to be protective in univariate analysis (pB0.0475 and pB0.0417, respectively). In multivariate analysis neutropenia was found to be signie cantly ( pB0.007) corrected to a lower mortality probably because of the use of early empirical therapy in neutropenia patients. In this subgroup of patients, death was 3.48 times less likely than in enterococcal bacteremia in non-neutropenic patients. We performed another univariate analysis comparing those who were appropriately treated ( nae81) versus inappropriately treated ( nae20, 19.9%) for enterococcal bacteremia. Both groups were comparable except in 6 of 36 risk factors. Only endocarditis ( pB0.0026) and 2 positive blood cultures (pB0.0267) were more frequently observed in inappropriately treated patients. Appropriate treatment was signie cantly more common in patients with cancer ( pB0.0165) and cytotoxic chemotherapy ( pB0.0147). In summary both analyses showed, that inappropriate therapy (either late therapy of drugs ineffective against enterococci) were associated with higher mortality, in patients with febrile neutropenia, fungaemia and endocarditis (1‐ 3). Vancomycin or other antibiotic resistance in enterococci was however, not associated with higher mortality.

Nosocomial Candidemia in Geriatric Patients

There are few published articles about candidemia in geriatric patients, although elderly patients are known to have a different clinical course and worse prognosis of various infections 1,2. We present our experience regarding the etiology, clinical characteristics, risk factors and outcome of candidemia in 20 patients who were 70+ years old selected from a 10-year survey (1.1.1990 to 31.12.1999) on fungemia in Slovakia. Risk factors such as diabetes, surgical intervention, central venous catheter insertion (CVC), total parenteral nutrition (TPN), artificial ventilation (AV), prior antibiotic therapy, etiology, therapy and outcome were prospectively recorded. Species were identified by API – 32 Rapid (Bio Mérieux) or the Vitek Jr. (Bio Mérieux) identification systems during the routine blood culturing, where two sets of blood culture bottles were obtained when patients had fever >38°C and incubated with Bactec Signal Blood Culturing System (Becton Dickinson, BBL). Strains were tested for antifungal susceptibility using the E-test (Biodisk, Solna, Sweden). Breakpoints for fluconazole were >64 mg/mL for resistant and ≥ 34 mg/mL for intermediate resistance. Univariate analysis was performed to assess differences in risk factors, etiology and mortaliJournal of Chemotherapy Vol. 13 n. 3 (340-343) 2001