Candida glabrata fungaemia in intensive care units.

Candidaemia is increasingly important in intensive care units (ICUs). Compared with Candida albicans fungaemia, the impact of C. glabrata fungaemia on ICU patients is not well-known. The aim of this study was to investigate the clinical features, the antifungal susceptibility and the treatment outcomes of C. glabrata fungaemia in ICU patients. The medical records of ICU patients with candidaemia between 2000 and 2005 were reviewed retrospectively, and antifungal susceptibility testing was performed for isolates of C. glabrata. Among 147 episodes of candidaemia occurring in adult ICUs, C. glabrata was the second most common species and accounted for 45 (30%) episodes of candidaemia. The incidence of C. glabrata fungaemia was 1.3/1000 ICU admissions. Fluconazole resistance was found in 11% of C. glabrata isolates. The 30-day all-cause mortality rate was 58%. Therapeutic regimens containing amphotericin B were associated with better outcome. Despite higher fluconazole resistance, C. glabrata candidaemia was not associated with greater mortality than non-glabrata candidaemia in the ICU setting.     

Aetiology, antifungal susceptibility, risk factors and outcome in 201 fungaemic children: data from a 12-year prospective national study from Slovakia

A total of 201 cases of fungaemia in children in a 12-year national survey from seven University Paediatric Clinics in Slovakia in 1990-2001 was assessed to determine risk factors, therapy and outcome, and to compare those cases with fungaemia in 130 adult cancer patients studied in a similar survey. Four univariate analyses were performed to assess differences in aetiology, antifungal susceptibility and outcome between fungaemia in neonates and paediatric intensive care unit (ICU) patients as well as between paediatric and adult cancer patients with fungaemia. There was a significant difference in aetiology and antifungal susceptibility between the subgroups of children with fungaemia: 83.3% of neonates versus 40.2% in children with cancer were due to Candida albicans. None of the non-albicans Candida spp. (NAC) in neonates but 23.5% of NAC isolates from children with cancer were resistant to fluconazole. C. albicans caused 144 (71.1%) episodes and NAC 48 (23.7%) episodes. Trichosporon beigelii, Blastoschizomyces (Trichosporon) capitatus, Rhodotorula rubra and Cryptococcus laurentii were found less frequently in neonates than in children with cancer (18.8%). There were not many differences in risk factors between paediatric fungaemia and adult cancer fungaemia except C. albicans aetiology, corticosteroid use in therapy, breakthrough fungaemia after ketoconazole prophylaxis and meningitis as a complication, which were observed significantly more frequently among children than in adults, both with cancer and fungaemia. Thirty-three of the paediatric fungaemias were breakthrough cases and appeared frequently in children with cancer. Fifty-one (25.1%) children died with fungaemia (attributable mortality) and 25 (12.7%) due to underlying disease with fungaemia; overall mortality was 37.8% and there was no significant difference in death rates between the subgroups of paediatric patients (neonates, children in ICUs and children with cancer).     

Anticandidal activity and interleukin-1 beta and interleukin-6 production by polymorphonuclear leukocytes are preserved in subjects with AIDS.

Polymorphonuclear granulocytes (PMN; or neutrophils) from uninfected or human immunodeficiency virus-infected subjects were tested for their ability to inhibit growth of Candida albicans and produce interleukin-1 beta (IL-1 beta) and IL-6 in vitro. It was seen that PMN from AIDS (Centers for Disease Control stage IV) patients expressed equal if not greater anticandidal activity compared with the activity expressed by neutrophils from all other subjects examined. On exposure to granulocyte macrophage-colony-stimulating factor or to a mannoprotein constituent (MP-F2) from C. albicans itself, PMN from AIDS patients showed enhanced antifungal activity and production of remarkable quantities of IL-1 beta and IL-6. These findings suggest that the functional abilities of PMN to inhibit Candida growth and secrete relevant proinflammatory and immunomodulatory cytokines are intrinsically preserved in AIDS patients.     

Combined effect of fluconazole and thymosin alpha 1 on systemic candidiasis in mice immunosuppressed by morphine treatments.

Treatment of systemic infection with Candida albicans with a combination of an antifungal agent (i.e. fluconazole) and a thymus-derived immunostimulant (i.e. thymosin alpha 1 (T alpha 1)) in mice immunosuppressed by morphine treatments was investigated. In normal mice, fluconazole given after infection with 10(6) C. albicans cells was more effective than in mice treated with morphine. Combination treatment with fluconazole and T alpha 1 prolonged survival and reduced the fungal burden in the kidneys of immunosuppressed mice. We also investigated the influence of this combined treatment on killing properties of polymorphonuclear leucocytes (PMN) and natural killer (NK) cell activity, inhibited by morphine administrations. Treatment with T alpha 1 or fluconazole as single agents promoted a recovery of normal NK cell activity and intracellular killing of C. albicans by PMN, while the combination significantly increased both of these responses, probably through the modulation of lymphokine production. Our data suggest that the additive effect of T alpha 1 and fluconazole is due to a direct antifungal action and activation of the immunocompetence.     

Critically ill anergic patients demonstrate polymorphonuclear neutrophil activation in the intravascular compartment with decreased cell delivery to inflammatory focci.

Skin test anergy, the failure to produce a delayed type hypersensitivity (DTH) response, is associated with an increase in infection-related complications and death usually due to multiple organ failure (MOF). Refractory intravascular activation of polymorphonuclear neutrophils (PMNs) has been implicated in the development of MOF. We studied 20 critically ill surgical patients with life threatening infections to determine if PMN intravascular activation was present and how this affected essential PMN functions such as exudation. The 11 anergic patients had a more intense inflammatory response to their infection. Plasma lactoferrin was 6.1 +/- 0.3 microgram/ml in anergic patients compared to 3.9 +/- 1.5 in reactive P less than 0.05, accompanied by reduced total primary (3.3 +/- 1.9 vs 4.7 +/- 2.1 micrograms/10(6) PMN P less than 0.01) and secondary (2.8 +/- 0.4 vs 5.0 +/- 0.9 microgram/10(6) PMN P less than 0.01) granule content, respectively. In vitro superoxide production following 100 ng/ml PMA stimulation was 0.44 +/- 0.1 in anergics vs 0.36 +/- 0.1 nmol/microgram PMN protein in reactivities, P less than 0.05. PMN chemotaxis was 8.2 +/- 0.6 PMNs/HPF in anergics compared to 10.2 +/- 1.6 PMNs/HPF in reactives P less than 0.05, accompanied by decreased PMN delivery to skin blister windows (3.2 +/- 1.4 vs 4.5 +/- 1.9 x 10(7) PMN/ml, respectively, P less than 0.05). We conclude that critically ill anergic surgical patients have increased intravascular PMN activation, which may contribute to oxygen-derived tissue damage in the vascular space, as well as a deficient delivery of effector cells in areas of bacterial invasion. This may lead to inability to clear the inflammatory signals which set up the vicious circle of MOF leading to death.     

Lactoferrin release and interleukin-1, interleukin-6, and tumor necrosis factor production by human polymorphonuclear cells stimulated by various lipopolysaccharides: relationship to growth inhibition of Candida albicans.

Lipopolysaccharides (LPSs) from Escherichia coli, Serratia marcescens, and Salmonella typhimurium, at doses from 1 to 100 ng/ml, strongly enhanced growth inhibition of Candida albicans by human polymorphonuclear leukocytes (PMN) in vitro. Flow cytometry analysis demonstrated that LPS markedly augmented phagocytosis of Candida cells by increasing the number of yeasts ingested per neutrophil as well as the number of neutrophils capable of ingesting fungal cells. LPS activation caused augmented release of lactoferrin, an iron-binding protein which itself could inhibit the growth of C. albicans in vitro. Antibodies against lactoferrin effectively and specifically reduced the anti-C. albicans activity of both LPS-stimulated and unstimulated PMN. Northern (RNA blot) analysis showed enhanced production of mRNAs for interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 and in neutrophils within 1 h of stimulation with LPS. The cytokines were also detected in the supernatant of the activated PMN, and their synthesis was prevented by pretreatment of LPS-stimulated PMN with protein synthesis inhibitors, such as emetine and cycloheximide. These inhibitors, however, did not block either lactoferrin release or the anti-Candida activity of LPS-stimulated PMN. These results demonstrate the ability of various bacterial LPSs to augment neutrophil function against C. albicans and suggest that the release of a candidastatic, iron-binding protein, lactoferrin, may contribute to the antifungal effect of PMN. Moreover, the ability to produce cytokines upon stimulation by ubiquitous microbial products such as the endotoxins points to an extraphagocytic, immunomodulatory role of PMN during infection.     

Epidemiology of candidaemia and antifungal susceptibility patterns in an Italian tertiary-care hospital

The epidemiological and antifungal susceptibility data for 94 episodes of candidaemia in an Italian tertiary-care hospital between January 2000 and August 2003 were evaluated by prospective laboratory-based surveillance. The incidence of fungaemia was 0.90 episodes/10 000 patient-days, and the most common species isolated were Candida albicans (40.4%), Candida parapsilosis (22.3%), Candida tropicalis (16.0%) and Candida glabrata (12.8%). Among 24 patients who received antifungal prophylaxis, non-albicans Candida spp. were more prevalent than C. albicans (p 0.012). The 30-day mortality rate was high (38.2%), particularly for haematological (71.4%) and solid-organ transplant patients (50.0%), and in individuals with C. tropicalis and C. glabrata bloodstream infections (60.0% and 50.0%, respectively). In-vitro susceptibility tests demonstrated that 95% of the isolates were susceptible to amphotericin B (MIC < 2 mg/L), 98.1% to posaconazole (MIC < 1 mg/L), 95.8% to flucytosine (MIC < 32 mg/L) and fluconazole (MIC < 64 mg/L), and 94.7% to itraconazole (MIC < 1 mg/L). Posaconazole was active (MIC 0.5 mg/L) against all three isolates of Candida krusei, which had reduced susceptibility to both fluconazole and itraconazole. Overall, non-albicans Candida spp. accounted for 60% of the episodes of candidaemia, which could be related to the use of antifungal prophylaxis. Resistance is still uncommon in Candida spp. recovered from blood cultures. The in-vitro activity of posaconazole is encouraging, and this agent could play an important role in the management of invasive candidiasis, including episodes caused by inherently less susceptible species such as C. krusei.     

Semi-national surveillance of fungaemia in Denmark 2004-2006: increasing incidence of fungaemia and numbers of isolates with reduced azole susceptibility.

A semi-national laboratory-based surveillance programme for fungaemia was initiated in 2003 that now covers c. 3.5 million inhabitants (64%) of the Danish population. In total, 1089 episodes of fungaemia were recorded during 2004-2006, corresponding to an annual incidence of 10.4/100 000 inhabitants. The annual number of episodes increased by 17% during the study period. Candida spp. accounted for 98% of the fungal pathogens. Although Candida albicans remained predominant, the proportion of C. albicans decreased from 66.1% in 2004 to 53.8% in 2006 (p <0.01), and varied considerably among participating departments, e.g., from 51.1% at a university hospital in Copenhagen to 67.6% in North Jutland County. Candida glabrata ranked second, and increased in proportion from 16.7% to 22.7% (p 0.04). Candida krusei was isolated rarely (4.1%), but the proportion doubled during the study period from 3.2% to 6.4% (p 0.06). MIC distributions of amphotericin B and caspofungin were in close agreement with the patterns predicted by species identification; however, decreased susceptibility to voriconazole, defined as an MIC of >1 mg/L, was detected in one (2.5%) C. glabrata isolate in 2004 and in 12 (14.0%) isolates in 2006 (p 0.03). Overall, the proportion of isolates with decreased susceptibility to fluconazole exceeded 30% in 2006. The incidence of fungaemia in Denmark was three-fold higher than that reported from other Nordic countries and is increasing. Decreased susceptibility to fluconazole is frequent, and a new trend towards C. glabrata isolates with elevated voriconazole MICs was observed.     

Semi-national surveillance of fungaemia in Denmark 2004–2006: increasing incidence of fungaemia and numbers of isolates with reduced azole susceptibility

A semi-national laboratory-based surveillance programme for fungaemia was initiated in 2003 that now covers c.  3.5 million inhabitants (64%) of the Danish population. In total, 1089 episodes of fungaemia were recorded during 2004–2006, corresponding to an annual incidence of 10.4/100 000 inhabitants. The annual number of episodes increased by 17% during the study period. Candida spp. accounted for 98% of the fungal pathogens. Although Candida albicans remained predominant, the proportion of C. albicans decreased from 66.1% in 2004 to 53.8% in 2006 (p <0.01), and varied considerably among participating departments, e.g., from 51.1% at a university hospital in Copenhagen to 67.6% in North Jutland County. Candida glabrata ranked second, and increased in proportion from 16.7% to 22.7% (p 0.04). Candida krusei was isolated rarely (4.1%), but the proportion doubled during the study period from 3.2% to 6.4% (p 0.06). MIC distributions of amphotericin B and caspofungin were in close agreement with the patterns predicted by species identification; however, decreased susceptibility to voriconazole, defined as an MIC of >1 mg/L, was detected in one (2.5%) C. glabrata isolate in 2004 and in 12 (14.0%) isolates in 2006 (p 0.03). Overall, the proportion of isolates with decreased susceptibility to fluconazole exceeded 30% in 2006. The incidence of fungaemia in Denmark was three-fold higher than that reported from other Nordic countries and is increasing. Decreased susceptibility to fluconazole is frequent, and a new trend towards C. glabrata isolates with elevated voriconazole MICs was observed.     

Risk factors for candidemia-related mortality at a medical center in central Taiwan.

BACKGROUND AND PURPOSE: Bloodstream infections due to Candida spp. are associated with significant mortality and morbidity. This study analysed the epidemiology and outcome of candidemia cases in a teaching hospital in central Taiwan. METHODS: We retrospectively studied the clinical characteristics and antifungal susceptibility of isolates and risk factors for mortality in 91 cases of candidemia treated from January 1, 2001 to June 30, 2003. RESULTS: The mean age of the patients was 67 years (range, 30-90 years). Three episodes (3%) were community acquired. Adequate antifungal therapy was given to 78 patients (78%). Cancer (38.5%) and diabetes mellitus (36.3%) were the 2 most common underlying diseases. The most frequent risk factors identified for candidemia were prior broad-spectrum antibiotic use (84.6%), central venous catheterization (83.5%) and Candida colonization (79.5%). The most frequent isolates were Candida albicans (64.8%) and Candida tropicalis (19.8%). All of the C. albicans and C. tropicalis isolates were sensitive to fluconazole (minimal inhibitory concentration 相似文献   

In vitro investigation of antifungal activities of phenotypic variation Candida albicans strains against fluconazole, itraconazole and voriconazole.

The aim of this study was to investigate the susceptibility of the different phenotypes of Candida albicans strains isolated from clinical specimens to three antifungal agents, fluconazole, itraconazole and voriconazole. Totally 215 specimens were collected from oropharyngeal, gastrointestinal and urogenital tracts of non-neutropenic patients who had received no previous prophylactic treatment. Each of the 215 C. albicans strains recovered was found to express one of the six phenotypes: smooth 73%, fuzzy 10.7%, irregular 2.3%, star 2.8%, ring 6% or stipple 5.1%. The mean MICs for the six phenotypes of C. albicans strains ranged between 0.25 microg/ml and 64 microg/ml for fluconazole, 0.03 microg/ml and 1 microg/ml for itraconazole and 0.03 microg/ml and 0.5 microg/ml for voriconazole. The mean minimum inhibitory concentration (MIC) of fluconazole was consistently higher for C. albicans strains expressing the stipple phenotype. The antifungal susceptibility of the phenotypic switching requires attention, especially in patients who are clinically unresponsive to fluconazole chemotherapy or in cases of serious C. albicans infections of immunocompromised hosts.     

Hyperthermia-induced priming effect in neutrophil granulocytes]

BACKGROUND AND OBJECTIVE: Whole-body infrared-A irradiation (WBIAI) according to Ardenne is a newly developed version of hyperthermia. In clinical use benefits for patients with chronic infections have been reported. In order to find out more about the immunological background of the method we studied the question whether hyperthermia leads to priming effects in human polymorphonuclear leukocytes (PMN). MATERIAL AND METHODS: We therefore investigated the production of reactive oxygen radical species (ROS) measured by lucigenin-dependent chemiluminescence after stimulation with N-formylpeptide (FMLP, 10(-6) and 10(-7) M), C5a complement (10(-7) and 10(-8) M) or phorbolester (PMA, 10(-7) and 10(-8) M) in isolated PMN of 8 volunteers undergoding a 60-min hyperthermia treatment with the WBIAI. Blood was drawn 0/60/240/510 min after the start of hyperthermia treatment. In addition, we measured blood pressure, pulse, and temperature. RESULTS: In 5 cases a significant increase in ROS (p < 0.05) could be measured beginning 240 min after start of hyperthermia and further increasing until the 510-min time point. These results suggest a priming effect in PMN lasting far beyond the actual treatment period. The increase of ROS production following stimulation with FMLP, C5a or PMA was 60.4 +/- 21.6, 86.0 +/- 23.3, and 63.3 +/- 15.9% (SEM), respectively. Moreover, in all probands the maximal ROS production in PMN was observed 510 min after the beginning of WBIAI treatment. In 3 cases no difference in ROS could be observed. There was no difference in temperature, blood pressure, and pulse between responders and nonresponders. CONCLUSIONS: Our results show a hyperthermia-dependent priming effect of ROS production in PMN, suggesting an increase in immune reaction within the observation period of 510 min. Further investigations are necessary in order to specify responders and nonresponders and to characterize the results in specific diseases and the constitutions of the patients.     

Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme

Significant changes in the management of fungaemia have occurred over the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. These changes may impact the epidemiology of fungaemia. We present nationwide data for Denmark from 2010 to 2011. A total of 1081 isolates from 1047 episodes were recorded in 995 patients. The numbers of patients, episodes and recovered isolates increased by 13.1%, 14.5% and 14.1%, respectively, from 2010 to 2011. The incidence rate was significantly higher in 2011 (10.05/100 000) than in 2010 (8.82/100 000), but remained constant in the age groups 0–79 years. The incidence rate was highest at the extremes of age and in males. Candida albicans accounted for 52.1% but declined during 2004–11 (p 0.0155). Candida glabrata accounted for 28% and increased during 2004–2011 (p <0.0001). Candida krusei, Candida tropicalis and Candida parapsilosis remained rare (3.3–4.2%). The species distribution changed with increasing age (fewer C. parapsilosis and more C. glabrata) and by study centre. Overall, the susceptibility rates were: amphotericin B 97.3%, anidulafungin 93.8%, fluconazole 66.7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002–2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were azoles. The incidence of fungaemia continues to increase in Denmark and is associated with a decreasing proportion being susceptible to fluconazole. Changes in demography, higher incidence in the elderly and higher antifungal consumption can at least in part explain the changes.     

Stimulation of human polymorphonuclear leukocyte oxidative metabolism by type 1 pili from Escherichia coli.

We compared the degree to which Escherichia coli phase variants which do (T1P+ E. coli) or do not (T1P- E. coli) express type 1 pili (T1P) stimulate human polymorphonuclear leukocyte (PMN) oxidative activity. Unopsonized T1P+ E. coli stimulated the release of 0.20 to 0.24 nmol of H2O2 per 10(6) PMN per min and the consumption of 1.4 to 4.0 nmol of O2 per 10(6) PMN per min; no measurable PMN oxidative activity was stimulated by unopsonized T1P- E. coli. In the presence of serum opsonins, T1P+ E. coli stimulated the release of 1.12 to 1.16 nmol of H2O2 per 10(6) PMN per min and the consumption of 5.0 to 6.0 nmol of O2 per 10(6) PMN per min, whereas T1P- E. coli stimulated the release of 0.42 to 0.43 nmol of H2O2 per 10(6) PMN per min and the consumption of 0.6 to 2.0 nmol of O2 per 10(6) PMN per min. Although unaggregated T1P did not stimulate PMN, latex beads coated with T1P (T1P-latex) stimulated alpha-methylmannoside-inhibitable, opsonin-independent PMN oxidative activity. The activity stimulated by either T1P+ E. coli or T1P-latex was susceptible to inhibition by cytochalasin B. Latex particles coated with bovine serum albumin or mannose-resistant pili did not stimulate PMN. These data indicate that T1P+ E. coli stimulate PMN oxidative metabolism more effectively than do T1P- E. coli and that a similar PMN oxidative response follows cellular stimulation by either unopsonized T1P+ or opsonized T1P- E. coli. Furthermore, T1P-latex faithfully mimics the ability of T1P+ E. coli to stimulate PMN oxidative metabolism. Such particles may be useful in further analyses of cellular responses to T1P+ E. coli.     

A prospective study on fungal infection in children with cancer

A prospective study was conducted in 1999 at the National Cancer Institute, Cairo University, to estimate the incidence, morbidity and mortality of fungal infections along with the evaluation of risk factors influencing outcome of infections among paediatric cancer patients. Of 1917 infectious episodes, the fungal infection rate as documented both clinically and microbiologically was 3.7% (70 cases). Fungal pathogens isolated were yeasts in 55 patients (78.6%) and moulds in 15 patients (21.11%). Among yeasts, Candida parapsilosis was the commonest, followed by C. tropicalis. Pneumonia was the most common fungal infection (n = 25, 35.7%), followed by fungaemia (n = 18, 25.7%). The overall mortality rate was 40% (n = 28), with an infection-related mortality of 28.5% (n = 20). Risk factors that accompanied mortality were relapsing or recurrent disease, profound neutropenia, ADE (Ara-C, daunorubocin and etoposide) protocol of chemotherapy, C. tropicalis isolated and fungaemia as a site of infection. Early use of empirical antifungal therapy (day 4) was not associated with a better outcome. In the light of the poor outcome of patients with fungaemia and fungal pneumonia, every effort should be made to prevent these infections in paediatric cancer patients.     

A first Portuguese epidemiological survey of fungaemia in a university hospital

A prospective, observational study was conducted at the biggest Portuguese hospital, aiming to evaluate the epidemiology of bloodstream fungal infection. During a period of 12 months (2004), all yeasts isolated from the blood cultures of patients with fungaemia admitted at a university hospital of Porto were collected. Demographic and clinical data, as well as haematological and biochemical profiles, were registered. Antifungal susceptibility was evaluated. The incidence of fungaemia and nosocomial fungaemia were 2.7 and 2 per 1,000 hospital admissions, respectively. Blood strains from 117 patients were identified. Thirty-five percent of yeast isolates were Candida albicans, followed by C. parapsilosis (25.6%). The mortality rate associated with fungaemia was 39.3%; the highest values were found in patients with C. glabrata and C. tropicalis infection. Seventy-five percent of the fungaemia episodes were nosocomial, with 48% mortality; the main predisposing factors were parenteral nutrition, gastric protection with omeprazole, surgical drainage and the presence of central venous catheters (CVCs). Thrombocytopaenia, urinary catheter, gastrointestinal pathology and nosocomial fungaemia were independently associated with a poor outcome. Antifungal susceptibility testing showed high fluconazole resistance (15%), mostly in C. tropicalis. We observed a high incidence of nosocomial fungaemia with high mortality rates. Important predisposing factors were identified, deserving further investigation. Local surveillance is warranted to monitor the incidence of in vitro antifungal resistance.     

Antibodies against antigens of Candida albicans in patients with fungaemia and bacteraemia, studied by ELISA, precipitation, passive haemagglutination and immunofluorescence techniques

Antibodies against commercially available antigens of Candida albicans were assayed in 54 sera from 24 patients with fungaemia and in 66 sera from 33 patients with bacteraemia. In patients with persistent fungaemia, antibody was found during the week after the fungus was first cultured from the blood, but peak titres did not usually occur until the end of the second week. A significant rise in titre in C. albicans infection was observed in 50% of paired sera tested by passive haemagglutination (PHA), indirect immunofluorescence (IF) and Ouchterlony immunodiffusion (ID). The same percentage was obtained by counterimmunoelectrophoresis (CIE) against candida metabolic antigens, whereas it was increased to 88% when somatic antigens were used. Enzyme-linked immunosorbent assay (ELISA) demonstrated a rise of titre in 25, 75 and 50% of sera in IgM, IgG and IgA assays, respectively. Sera from patients with transient fungaemia demonstrated persistent antibody titres. In paired sera from patients with bacteraemia, ID and CIE titres were low (greater than or equal to 4). There was an increase of candida antibodies in 0-9% of patients by ELISA, ID or CIE and in 18-21% by PHA or IF. Clinically significant fungaemia was most reliably differentiated serologically from bacteraemia by CIE S-antigen and ELISA IgG assays.     

Characterisation of yeasts implicated in vulvovaginal candidosis in Irish women

High-vaginal swabs were taken from 98 women attending a genitourinary clinic in Dublin city who presented with symptoms of vaginitis. Twenty-eight (28.6%) proved culture-positive for yeasts. Candida albicans was isolated from 26 of the yeast-positive patients and Candida glabrata and Candida tropicalis were isolated from a further two patients. Two patients were colonized by two yeasts simultaneously (C. albicans and Candida lucitaniae, and C. albicans and Candida krusei). Yeasts were characterised on the basis of their adherence ability, extracellular enzyme production and resistance to antifungal agents. All C. albicans isolates demonstrated high adherence abilities to buccal epithelial cells, but produced relatively low levels of phospholipase and acid proteinase. The non-C. albicans isolates demonstrated low levels of adherence, but no extracellular enzyme production was detected. Isolates were most sensitive to the polyenes amphotericin B and nystatin but a large proportion (50%) of C. albicans isolates were resistant to clotrimazole, which is an important agent in the treatment of vulvovaginal candidosis.     

Comparative study of two systems for the determination of the sensitivity of yeasts to antifungal agents]

One hundred yeast strains (including 60 Candida albicans) were tested in two laboratories using two different antifungal susceptibility test kits, ATB Fungus and Mycostandard. Tests were carried out under everyday work conditions. Four antifungal agents were compared: amphotericin B, flucytosine, miconazole, and ketoconazole. Results were discrepant in 19.2% (77/400) of cases. Following retesting of discordant cases with both kits, the agreement rate for strain characterization was 95.5%. Few discrepancies were seen with flucytosine. Conflicting results obtained with amphotericin B were due to poor reproducibility of Mycostandard results, especially for species other than C. albicans. In contrast, reproducibility of the ATB Fungus kit was inadequate for miconazole. The rate of discrepant results was greatest for ketoconazole. Intermediate susceptibility was seen more often with ATB Fungus for C. albicans and with Mycostandard for C. glabrata and C. krusei. The lack of reproducibility under routine working conditions should lead gallery manufacturers to strive to achieve clearer readings.     

International surveillance of Candida spp. and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2003)

During 2003, a total of 1,397 Candida isolates, 73 Aspergillus isolates, 53 Cryptococcus neoformans isolates, and 25 other fungal isolates from infected, normally sterile, body sites in patients hospitalized in North America, Europe, and Latin America were studied as a component of the longitudinal SENTRY Antimicrobial Surveillance Program. The MICs for seven antifungal agents were determined in a central laboratory (JMI Laboratories, North Liberty, IA) using testing methods promulgated by the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards). The rank order of Candida spp. occurrence was as follows: C. albicans (48.7%), C. parapsilosis (17.3%), C. glabrata (17.2%), C. tropicalis (10.9%), C. krusei (1.9%), and other Candida spp. (4.0%). C. albicans accounted for 51.5, 47.8, and 36.5% of candidal infections in North America, Europe, and Latin America, respectively. Ravuconazole, voriconazole, and fluconazole were highly active against C. albicans, C. parapsilosis, and C. tropicalis, with both former agents being more potent (MIC at which 90% of the isolates tested are inhibited [MIC90] of < or =0.008 to 0.12 microg/ml) than fluconazole (MIC90 of 0.5 to 2 microg/ml). C. glabrata isolates were less susceptible to these agents, with MIC90s of 1, 1, and 64 microg/ml, respectively. Ravuconazole and voriconazole were the most active agents tested against C. krusei (MIC90 of 0.5 microg/ml). Among Aspergillus spp., A. fumigatus was the most commonly (71.2% of isolates) recovered species; 96.2, 96.2, 84.6, and 11.5% of strains were inhibited by < or =1 microg/ml of ravuconazole, voriconazole, itraconazole, and amphotericin B, respectively. Of the antifungal agents tested, ravuconazole and voriconazole displayed the greatest spectrum of activity against pathogenic Candida and Aspergillus spp., regardless of geographic origin. These results extend upon previous findings from SENTRY Program reports (1997 to 2000), further characterizing species composition as seen in local clinical practice and demonstrating the potent activity of selected, newer triazole antifungal agents.