Sensitivity of museum and fresh strains to antimycotics has been determined. 5-Fluorocytosine (86.2%) and amphotericine B (93.2%) were highly effective as to results on test-systems, considerable part of strains was resistant to fluconasole (93.2%) and itraconasole (62.1%). Due to disk-diffusion method it was determined that nystatine was an effective inhibitor of growth of 100% of all species cultures, amphotericine B--93.3%, resistance to clotrimasole was 56.6%. During the last three years the part of polyresistant strains of yeastlike fungi exceeds considerably the critical level. A comparison of antibiotic sensitivity of C. albicans representatives and strains of non-albicans species did not manifest cardinal differences.
Triazole resistance in Aspergillus fumigatus has been increasing. We explored the A. fumigatus azole resistance profiles in bronchoalveolar lavage (BAL) fluid samples from Danish patients examined for aspergillosis.
A total of 94 BAL samples from 87 patients were evaluated by galactomannan (GM) test and A. fumigatus CYP51A profiling by PCR.
Aspergillus spp. were isolated from 27/48 (56.3%) cultured samples, including 23 A. fumigatus with one resistant strain (4.3%). Samples were classified into GM-positive (=3.0), GM-intermediate (0.5 to
Azole-resistant Aspergillus fumigatus originating from the environment as well as induced during therapy are continuously emerging in Danish clinical settings. We performed a laboratory-based retrospective study (2010-2014) of azole resistance and genetic relationship of A. fumigatus at the national mycology reference laboratory of Denmark. A total of 1162 clinical and 133 environmental A. fumigatus isolates were identified by morphology, thermotolerance and/or ß-tubulin sequencing. Screening for azole resistance was carried out using azole agar, and resistant isolates were susceptibility tested by the EUCAST (European Committee on Antimicrobial Susceptibility Testing) E.Def 9.2 reference method and CYP51A sequenced. Genotyping was performed for outbreak investigation and, when appropriate, short tandem repeat Aspergillus fumigatus microsatellite assay. All 133 environmental A. fumigatus isolates were azole susceptible. However, from 2010 to 2014, there was an increasing prevalence of azole resistance (from 1.4 to 6% isolates (p 50% of the azole resistance mechanisms. Among 184 Danish A. fumigatus isolates, 120 unique genotypes were identified and compared to a collection of 1822 international genotypes. Seven (5.8%) Danish genotypes were shared between isolates within Denmark but with different origin, 19 (15.8%) were shared with foreign genotypes, and two (11.8%) of 17 genotypes of isolates carrying the TR34/L98H resistance mechanisms were identical to two Dutch TR34/L98H isolates. Our findings underlines the demand for correct identification and susceptibility testing of clinical mould isolates. Furthermore, although complex, genotyping supported the hypotheses regarding clonal expansion and the potential of a single origin for the TR34/L98H clone.
A prospective observational nationwide investigation was performed from September 2005 to August 2006 to study the epidemiology of candidaemia in Sweden. From 385 patients, 403 isolates were recovered, yielding an incidence of 4.2 cases per 100 000 inhabitants. Candida albicans was the most common species (61%), followed by Candida glabrata (20%) and Candida parapsilosis (9%). The rates of resistance to fluconazole were = 1% in C. albicans and 6-29% in non-albicans species other than C. glabrata and Candida krusei. Resistance to voriconazole was rare, except for C. glabrata and C. krusei. Only three isolates had reduced susceptibility to amphotericin B, and one had reduced susceptibility to caspofungin.
During recent years a rise in the occurrence of candidaemia has been reported in the USA as well as in Europe, and especially in intensive care units (ICUs). The aim of this study was to describe the frequency of candidaemia and related Candida infections in the hospitals of Aarhus County, Denmark, from 1993 to 2002, and to assess possible causal factors, among these the consumption of antimicrobial agents.
The material included blood cultures carried out at the Department of Clinical Microbiology, Aarhus University Hospital (AUH), during the study period, plus Candida-positive cultures from other normally sterile sites from patients with candidaemia. Microbiological findings were compiled from our laboratory information system, MADS. Information regarding the use of antimicrobial agents in the hospitals of Aarhus County was obtained from the University Hospital pharmacy and the Danish Medicines Agency Web site.
During the study period the fraction of positive blood cultures was constant, while the fraction of positive cultures yielding Candida species increased from 1.8% to 3.4%, with an especially marked increase among patients in AUH. An increase in the proportion of Candida non-albicans species compared to C. albicans was noted, and it was also noted that the consumption of antimicrobial agents had risen markedly during the period.
The present study adds to the assumption of a causal relationship between candidaemia and the use of antimicrobials and foreign bodies.
Decreased susceptibility of Candida albicans to azole antifungals: a complication of long-term treatment in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS1) is an autosomal recessive disease exceptionally common in Finland. Most patients have chronic oral candidiasis from early childhood and this infection has been shown to be carcinogenic. Hence, patients receive repeated treatment and prophylactic courses of antifungals throughout life. In Finland, 92 patients have been diagnosed with APECED and 66 of them are currently alive. Our aim was to study the effect of long-term azole treatment on the candidal colonization of APECED patients and the influence on antifungal susceptibilities.
We evaluated the culture reports from 1994 to 2004 of 56 APECED patients followed in Helsinki University Central Hospital. Candida albicans strains of all 11 patients initially reported resistant (n = 27) and 12 patients reported susceptible (n = 16) to fluconazole were re-analysed for their susceptibility to fluconazole. Antifungal usage was analysed up to 30 years back.
A total of 162 fungal cultures had been performed. Of these, 75% had been reported positive for Candida and 63% for C. albicans. Eleven patients (31.4%) had been reported to harbour at least once a C. albicans strain resistant to fluconazole. Re-analysis of the stored C. albicans strains originally reported to be resistant to fluconazole revealed a mean MIC of 19.5 mg/L.
Multiple courses (>6) of fluconazole annually and low dose prophylaxis are major risk factors for persistent colonization with C. albicans with decreased susceptibility in APECED patients.
The aim of the present study was to investigate whether HIV-infected patients, a group that is supposedly at risk for infection with antibiotic-resistant microbes, really does so, and to assess possible risk factors for acquiring these organisms. During the period from January 1998 to July 1999, samples of normal flora were obtained from 107 HIV-infected patients attending an outpatient clinic in Oslo, Norway. The samples were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, coagulase-negative staphylococci and Candida spp., and the resulting isolates were tested for antimicrobial susceptibility. The patients studied represented all stages of HIV infection, from recently infected to severely immunocompromised. Samples were taken at one, two or three time-points to determine whether antimicrobial resistance in colonising microorganisms increases over time. Antimicrobial resistance was linked primarily to antimicrobial prophylaxis, but it did not increase during the observation period. The level of a patient's immunodeficiency and the consequently intensified medical care was also of some importance. Even though about 50% of the patients were receiving antimicrobial agents at the time of sampling, the level of resistance found in these patients was very similar to that found in other patient groups in Norway; except for Candida albicans isolates, which were less susceptible to fluconazole. Overall, antimicrobial resistance was uncommon in the HIV-seropositive patients studied, a finding that is probably related to the overall low prevalence of antimicrobial resistance in the general population in Norway.
BACKGROUND: The incidence of invasive fungal infections is increasing in parallel with an increase of patients with immunodeficiencies. Resistance to these drugs is becoming a problem in spite of increased and improved treatment options. MATERIAL AND METHODS: Literature retrieved from Medline and personal findings and experience form the basis for this article. RESULTS: Candida albicans is still the most common species causing invasive fungal infections, but Candida non-albicans species are increasing in number. Invasive Aspergillus infections and infection with other moulds than Aspergillus spp. do occur, but do not constitute a large proportion of these infections. As of today we have four classes of antifungal agents and seven drugs with different mechanisms of action are registered in Norway. Primary resistance to several of these drugs has been observed in a number of Candida and Aspergillus species and this is the dominating form of resistance we observe today. Secondary resistance due to treatment is still an uncommon finding. Clinical resistance, which, in spite of in vitro susceptibility does not lead to eradication of the fungus, is also commonly observed. INTERPRETATION: The incidence of natural resistant fungi is increasing. Our main current challenge is therefore to rapidly and precisely identify the fungi so the proper drug is used to quickly initiate treatment on the correct indication.
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
To identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates to identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates in Sweden.
The study was a retrospective, observational nationwide laboratory-based surveillance for fungaemia and fungal meningitis and was conducted from September 2015 to August 2016.
In total, 488 Candida blood culture isolates were obtained from 471 patients (58% males). Compared to our previous study, the incidence of candidaemia has increased from 4.2/100 000 (2005-2006) to 4.7/100 000 population/year (2015-2016). The three most common Candida spp. isolated from blood cultures were Candida albicans (54.7%), Candida glabrata (19.7%) and species in the Candida parapsilosis complex (9.4%). Candida resistance to fluconazole was 2% in C. albicans and between 0% and 100%, in non-albicans species other than C. glabrata and C. krusei. Resistance to voriconazole was rare, except for C. glabrata, C. krusei and C. tropicalis. Resistance to anidulafungin was 3.8% while no Candida isolate was resistant to amphotericin B.
We report an overall increase in candidaemia but a minor decrease of C. albicans while C. glabrata and C. parapsilosis remain constant over this 10-year period.