J. Hanzen

Comparative activity of carbapenem testing: the COMPACT study

OBJECTIVES Doripenem is a new carbapenem recently introduced into Europe. The COMParative Activity of Carbapenem Testing (COMPACT) study compared the susceptibility of common Gram-negative bacilli causing serious infections in hospitalized patients with doripenem, imipenem and meropenem. METHODS Gram-negative isolates (4498 total: 2171 Pseudomonas species; 1910 Enterobacteriaceae; and 417 other Gram-negative bacilli) were collected from 80 centres in 16 countries in Europe, the Middle East and Africa during 2008-09. The MICs of doripenem, imipenem and meropenem were determined using Etest methodology and broth microdilution. Susceptibility was interpreted according to CLSI, EUCAST and FDA breakpoints. RESULTS The MIC(90)s of doripenem, imipenem and meropenem for all isolates were 8, ≥64 and 32 mg/L, respectively. Doripenem had the lowest MIC(90) for Pseudomonas species at 16 mg/L, with imipenem and meropenem values of ≥64 mg/L. Enterobacteriaceae were highly susceptible to all three carbapenems, with MIC(90)s of doripenem, imipenem and meropenem of 0.06, 0.5 and 0.12 mg/L, respectively. Other Gram-negative isolates, predominantly Acinetobacter baumannii, were resistant to all three carbapenems (MIC(90) ≥64 mg/L). Susceptibility to doripenem was observed in 14.9% of isolates resistant to imipenem and/or meropenem. CONCLUSIONS Doripenem showed excellent activity against Gram-negative isolates; generally it was more active than imipenem and at least as good as meropenem. Against Pseudomonas species, doripenem was more active than both imipenem and meropenem, with doripenem susceptibility observed for some imipenem- and/or meropenem-resistant isolates.

Prospective study of antibacterial susceptibility, risk factors and outcome of 157 episodes of Acinetobacter baumannii bacteremia in 1999 in Slovakia.

This study prospectively investigated all 157 cases of Acinetobacter baumannii bacteremia occurring in major university hospitals or tertiary care institutions in Slovakia during 1999 in order to determine the antimicrobial susceptibility, risk factors and outcome. Resistance to meropenem was 7.4, gentamicin 35.6, amikacin 26.5, cefepime 20.4 and ciprofloxacin 32.7%, but was only 17.3% to cefoperazone/sulbactam or ampicillin/sulbactam. Antimicrobial susceptibility of A. baumanii was lowest among isolates from cancer patients (ceftazidime 58%, piperacillin/tazobactam 52% and azthreonam 48%; p < or = 0.01-0.001). In univariate analysis, several risk factors, such as wound infection (p < or = 0.01) and ventilatory support (p < or = 0.0001), were significantly related to A. baumannii bacteremia in surgical patients. Neutropenia (p < or = 0.0001), antineoplastic chemotherapy (p < or = 0.0001) and prior antibiotic therapy (p < or = 0.0006) were significant risk factors for A. baumannii bacteremia in cancer patients. In addition, ventilatory support and surgery (p < or = 0.0001) and prior antibiotic therapy (p < or = 0.01) were significantly related to A. baumannii bacteremia in children. Colonization at other body sites (p < or = 0.05), diabetes mellitus (p < or = 0.04) and decubital ulcers/burns (p < or = 0.002) as underlying disease were significantly related to death due to A. baumannii bacteremia. In a multiple logistic regression model, decubital ulcers/burns as underlying disease (p < or = 0.0006; relative risk 5.08) and nosocomial pneumonia (p < or = 0.045; relative risk 5.08) were independent predictors of mortality. Mortality was similar between cancer and surgical patients but significantly lower in children vs. adults (p < or = 0.009).

Fungemia in neonates: report of 80 cases from seven university hospitals.

To the Editor. Candidemia is an emerging infection in neonatology, due to multiple risk factors for fungal infections in neonates, eg, central venous catheter (CVC) insertion, total parenteral nutrition (TPN), corticosteroid and antibiotic therapy, very low birth weight (VLBW) and arteriovenous support (AV).1–3 Within 10 years, from 1989 to 1998, a prospective nation-wide survey of fungemia in 7 university childrens clinics in Slovakia was performed. A total of 310 fungemias developed; 145 appeared in children (48.5%) and 80 (55.3% of all children and 23.3% of all cases) appeared in neonates. The most common risk factors (Table 1) for fungemia in neonates were prior antibiotic therapy, CVC insertion, and TPN, which appeared in …

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.

Bacteremia Due to Pseudomonas aeruginosa: Results from a 3-Year National Study in the Slovak Republic

Abstract Risk factors, mortality and antimicrobial susceptibility of Pseudomonas aeruginosa bacteremias isolated from 148 patients from all University Hospitals in Slovakia were analyzed. Only 1.2% of 169 strains of P. aeruginosa were resistant to meropenem, 4.1% to piperacillin/tazobactam, 7.7% to ceftazidime as well as cefepime and 12% to amikacin. More than 30% of P. aeruginosa were resistant to ciprofloxacin. Our analysis of risk factors for antimicrobial resistance to the particular antimicrobials, indicated no difference in risk factors and outcome in cases infected with P. aeruginosa bacteremias resistant to amikacin, piperacillin/tazobactam or ceftazidime in comparison to episodes caused by P. aeruginosa due to susceptible isolates. When comparing risk factors for P. aeruginosa bacteremia in children vs. adults, cancer vs. non-cancer patients, several differences in risk factors were observed. Neither antimicrobial resistance to amikacin, ceftazidime or piperacillin/tazobactam, nor appropriateness of therapy according to two separate analyses were associated with better outcome.

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.