Associations between blood cultures after surgery for colorectal cancer and long-term oncological outcomes.

BACKGROUND: Systemic inflammation following curative surgery for colorectal cancer may be associated with increased risk of recurrence. [Correction added on 29 November 2019, after first online publication: text amended for accuracy.] This study investigated whether a clinically suspected infection, for which blood cultures were sent within 30 days after surgery for colorectal cancer, was associated with long-term oncological outcomes. METHODS: This register-based national cohort study included all Danish residents undergoing surgery with curative intent for colorectal cancer between January 2003 and December 2013. Patients who developed recurrence or died within 180 days after surgery were not included. Associations between blood cultures taken within 30 days after primary surgery and overall survival, disease-free survival and recurrence-free survival were analysed using Cox regression models adjusted for relevant clinical confounders, including demographic data, cancer stage, co-morbidity, blood transfusion, postoperative complications and adjuvant chemotherapy. RESULTS: The study included 21 349 patients, of whom 3390 (15·9 per cent) had blood cultures taken within 30 days after surgery. Median follow-up was 5·6 years. Patients who had blood cultures taken had an increased risk of all-cause mortality (hazard ratio (HR) 1·27, 95 per cent c.i. 1·20 to 1·35; P < 0·001), poorer disease-free survival (HR 1·22, 1·16 to 1·29; P < 0·001) and higher risk of recurrence (HR 1·15, 1·07 to 1·23; P < 0·001) than patients who did not have blood cultures taken. CONCLUSION: A clinically suspected infection requiring blood cultures within 30 days of surgery for colorectal cancer was associated with poorer oncological outcomes.

ANTECEDENTES: La inflamación sistémica en el cáncer colorrectal puede asociarse con un aumento del riesgo de recidiva. En este estudio se investigó si la sospecha clínica de infección, en la que se obtuvieron cultivos de sangre periférica durante los primeros 30 días de la cirugía por cáncer colorrectal, se asociaba con los resultados oncológicos a largo plazo. MÉTODOS: Se trata de un estudio de cohortes de un registro de una base de datos nacional, que incluyía todos los sujetos residentes en Dinamarca sometidos a cirugía por cáncer colorrectal con intención curativa desde enero de 2003 a diciembre de 2013. Los pacientes con recidiva o que fallecieron durante los primeros 180 días después de la cirugía fueron excluidos. Se estimaron las asociaciones entre los cultivos de sangre periférica efectuados en los primeros 30 días tras la cirugía primaria y la supervivencia global, supervivencia libre de enfermedad y supervivencia libre de recidiva mediante modelos de regresión de Cox, ajustados por variables clínicas confusoras relevantes (incluyendo datos demográficos, estadio del cáncer, comorbilidad, transfusión de sangre, complicaciones postoperatorias y quimioterapia adyuvante). RESULTADOS: El estudio incluyó 21.349 pacientes, de los cuales en 3.390 (16%) se habían obtenido cultivos de sangre periférica durante los primeros 30 días tras la cirugía. La mediana de seguimiento fue de 5,6 años. Los pacientes en los que se había obtenido cultivos de sangre periférica presentaron un riesgo aumentado de mortalidad por cualquier causa (cociente de riesgos instantáneos, hazard ratio, HR 1,27, i.c. del 95% 1,20-1,35; P < 0.0001), peor supervivencia libre de enfermedad (HR 1,22, i.c. del 95% 1,16-1,29; P < 0,0001) y mayor riesgo de recidiva (HR 1,15, i.c. del 95% 1,07-1,23; P < 0,0001) que los pacientes en los que no se habían obtenido cultivos. CONCLUSIÓN: La presencia de una infección sospechada clínicamente para la cual se requiere obtener cultivos de sangre periférica en los primeros 30 días tras cirugía por cancer colorrectal se asoció con peores resultados oncológicos.

Update from a 12-Year Nationwide Fungemia Surveillance: Increasing Intrinsic and Acquired Resistance Causes Concern.

New data from the years 2012 to 2015 from the Danish National Fungemia Surveillance are reported, and epidemiological trends are investigated in a 12-year perspective (2004 to 2015). During 2012 to 2015, 1,900 of 1,939 (98%) fungal bloodstream isolates were included. The average incidence was 8.4/100,000 inhabitants, and this appears to represent a stabilizing trend after the increase to 10.1/100,000 in 2011. The incidence was higher in males than females (10.0 versus 6.8) and in patients above 50 years, and those changes were mainly driven by an increasing incidence among 80-to-89-year-old males (65.3/100,000 in 2014 to 2015). The proportion of Candida albicans isolates decreased from 2004 to 2015 (64.4% to 42.4%) in parallel with a doubling of the proportion of Candida glabrata isolates (16.5% to 34.6%, P < 0.0001). C. glabrata was more common among females (34.0% versus 30.4% in males). Following an increase in 2004 to 2011, the annual drug use stabilized during the last 2 to 3 years of that time period but remained higher than in other Nordic countries. This was particularly true for the fluconazole and itraconazole use in the primary health care sector, which exceeded the combined national levels of use of these compounds in each of the other Nordic countries. Fluconazole susceptibility decreased (68.5%, 65.2%, and 60.6% in 2004 to 2007, 2008 to 2011, and 2012 to 2015, respectively, P < 0.0001), and echinocandin resistance emerged in Candida (0%, 0.6%, and 1.7%, respectively, P < 0.001). Amphotericin B susceptibility remained high (98.7%). Among 16 (2.7%) echinocandin-resistant C. glabrata isolates (2012 to 2015), 13 harbored FKS mutations and 5 (31%) were multidrug resistant. The epidemiological changes and the increased incidence of intrinsic and acquired resistance emphasize the importance of continued surveillance and of strengthened focus on antifungal stewardship.

Clinical consequences of using PNA-FISH in Staphylococcal bacteraemia.

To optimize patient treatment and rational use of antimicrobials, it is important to provide fast information on findings in blood-cultures (BCs). The purpose of this study was to evaluate the impact of using peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) on positive BCs containing Gram-positive cocci in clusters to differentiate between Staphylococcus aureus (SA) and coagulase negative staphylococci (CoNS) on the prescribed antimicrobial therapy and on the number of contacts between microbiologist and clinician. All cases of positive BCs in our laboratory with SA or CoNS in the year 2011 were identified and the charts were reviewed retrospectively. The group of patients with BCs tested with PNA-FISH was compared to the group of patients with untested BCs. A total of 200 patients with SA and 725 patients with CoNS were included. The mean number of contacts was 0.82 when PNA-FISH showed CoNS and 1.39 when PNA-FISH was not done (p < 0.0001). More patients were recommended appropriate antimicrobial therapy for SA bacteraemia in the PNA-FISH group (98.0%) than in the non-PNA-FISH group (89.4 %) (p = 0.025). The percentage treated with dicloxacillin was 29.6 in the PNA-FISH group, and 8.2 in the non-PNA-FISH group (p = 0.0003). The use of PNA-FISH on BCs in this study was associated with more appropriate and narrow spectrum antimicrobial therapy for patients with SA in an area with low prevalence of methicillin-resistant SA, and a lower number of contacts between clinical microbiologist and clinician about BCs with CoNS as contaminants.

A single-source nosocomial outbreak of Aspergillus flavus uncovered by genotyping.

During construction work (2017-2019), an increase in Aspergillus flavus infections was noted among pediatric patients, the majority of whom were receiving amphotericin B prophylaxis. Microsatellite genotyping was used to characterize the outbreak. A total of 153 A. flavus isolates of clinical and environmental origin were included. Clinical isolates included 140 from 119 patients. Eight patients were outbreak-related patients, whereas 111 were outbreak-unrelated patients from Danish hospitals (1994-2023). We further included four control strains. Nine A. flavus isolates were from subsequent air sampling in the outbreak ward (2022-2023). Typing followed Rudramurthy et al.(S. M. Rudramurthy, H. A. de Valk, A. Chakrabarti, J. Meis, and C. H. W. Klaassen, PLoS One 6:e16086, 2011, https://doi.org/10.1371/journal.pone.0016086). Minimum spanning tree (MST) and discriminant analysis of principal components (DAPC) were used for cluster analysis. DAPC analysis placed all 153 isolates in five clusters. Microsatellite marker pattern was clearly distinct for one cluster compared to the others. The same cluster was observed in an MST. This cluster included all outbreak isolates, air-sample isolates, and additional patient isolates from the outbreak hospital, previously undisclosed as outbreak related. The highest air prevalence of A. flavus was found in two technical risers of the outbreak ward, which were then sealed. Follow-up air samples were negative for A. flavus. Microsatellite typing defined the outbreak as nosocomial and facilitated the identification of an in-hospital source. Six months of follow-up air sampling was without A. flavus. Outbreak-related/non-related isolates were easily distinguished with DAPC and MST, as the outbreak clone's distinct marker pattern was delineated in both statistical analyses. Thus, it could be a variant of A. flavus, with a niche ability to thrive in the outbreak-hospital environment. IMPORTANCE: Aspergillus flavus can cause severe infections and hospital outbreaks in immunocompromised individuals. Although lack of isogeneity does not preclude an outbreak, our study underlines the value of microsatellite genotyping in the setting of potential A. flavus outbreaks. Microsatellite genotyping documented an isogenic hospital outbreak with an internal source. This provided the "smoking gun" that prompted the rapid allocation of resources for thorough environmental sampling, the results of which guided immediate and relevant cleaning and source control measures. Consequently, we advise that vulnerable patients should be protected from exposure and that genotyping be included early in potential A. flavus outbreak investigations. Inspection and sampling are recommended at any site where airborne spores might disperse from. This includes rarely accessed areas where air communication to the hospital ward cannot be disregarded.

Differentiation of Candida glabrata, C. nivariensis and C. bracarensis based on fragment length polymorphism of ITS1 and ITS2 and restriction fragment length polymorphism of ITS and D1/D2 regions in rDNA.

Different molecular methods for the discrimination of Candida glabrata, C. bracarensis and C. nivariensis were evaluated and the prevalence of these species among Danish blood isolates investigated. Control strains were used to determine fragment length polymorphism in the ITS1, ITS2, ITS1-5.8S-ITS2 regions and in the D1/D2 domain of 26S rDNA using primers designed for this study. A total of 133 blood isolates previously identified as C. glabrata were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the peptide nucleic acid-fluorescent in situ hybridization (PNA-FISH) method. The size of ITS1 allowed differentiation between C. glabrata (483), C. nivariensis (361) and C. bracarensis (385), whereas the ITS2 region was of similar size in C. nivariensis (417) and C. glabrata (418). Sequence analysis of the ITS region suggested that many restriction enzymes were suitable for RFLP differentiation of the species. Enzymatic digestion of the D1/D2 domain with TatI produced unique band sizes for each of the three species. PCR-RFLP and PNA-FISH were in agreement for all of the isolates tested. None of the 133 Danish blood isolates were C. nivariensis or C. bracarensis. Fragment size polymorphism of ITS1 and RFLP of the D1/D2 domain or the ITS region are useful methods for the differentiation of the species within the C. glabrata group. C. bracarensis and C. nivariensis are rare among Danish C. glabrata blood isolates.

A prospective survey of Aspergillus spp. in respiratory tract samples: prevalence, clinical impact and antifungal susceptibility.

A three-month laboratory-based prospective survey was conducted at four major university hospitals covering one-third of the Danish population in order to determine the prevalence, significance, and susceptibility pattern of aspergilli in airway samples. Samples received in January-March 2007 for routine microbiologic investigation were examined for Aspergillus following routine procedures and with extended incubation (5 days). Identification was done by morphologic criteria and susceptibility testing using EUCAST method for azoles and amphotericin B E-test. Invasive aspergillosis (IA) was evaluated using modified EORTC/MSG criteria. A total of 11,368 airway samples were received. Growth of Aspergillus spp. was found in 129 and 151 patients using routine and extended incubation, respectively. Three patients had proven IA (2%), 11 probable (7%), four had allergic bronchopulmonary aspergillosis (ABPA) (3%), but the majority was colonised (88%). Underlying conditions were cystic fibrosis in 82 patients (55%), chronic obstructive pulmonary disease in 19 (13%) and haematological disorder in 11 (7%). Twenty-six patients (18%) were at intensive care unit and 69 (47%) received steroid treatment. Azole MICs were elevated for five isolates as follows (itraconazole, posaconazole, voriconazole MICs [mg/L]): two A. fumigatus isolates (>4; >4; 2 and >4; 0.125; 1), one A. lentulus isolate (2; 2; 0.5) and two A. terreus isolates (2; 2; 2 and 2; 0.125; 1). For four isolates the amphotericin B MIC was >1 µg/ml (3/112 A. fumigatus, 1/2 A. terreus). In conclusion, Aspergillus appears to be an important pathogen in Denmark. Elevated itraconazole MICs were detected in 4% of the isolates including a multi-azole resistant isolate.

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.

Antibiotic treatment and mortality in patients with Listeria monocytogenes meningitis or bacteraemia.

Invasive Listeria monocytogenes infections carry a high mortality despite antibiotic treatment. The rareness of the infection makes it difficult to improve antibiotic treatment through randomized clinical trials. This observational study investigated clinical features and outcome of invasive L. monocytogenes infections including the efficacy of empiric and definitive antibiotic therapies. Demographic, clinical and biochemical findings, antibiotic treatment and 30-day mortality for all episodes of L. monocytogenes bacteraemia and/or meningitis were collected by retrospective medical record review in the North Denmark Region and the Capital Region of Denmark (17 hospitals) from 1997 to 2012. Risk factors for 30-day all-cause mortality were assessed by logistic regression. The study comprised 229 patients (median age: 71 years), 172 patients had bacteraemia, 24 patients had meningitis and 33 patients had both. Significant risk factors for 30-day mortality were septic shock (OR 3.0, 95% CI 1.4-6.4), altered mental state (OR 3.6, 95% CI 1.7-7.6) and inadequate empiric antibiotic therapy (OR 3.8, 95% CI 1.8-8.1). Cephalosporins accounted for 90% of inadequately treated cases. Adequate definitive antibiotic treatment was administered to 195 patients who survived the early period (benzylpenicillin 72, aminopenicillin 84, meropenem 28, sulfamethoxazole/trimethoprim 6, and piperacillin/tazobactam 5). Definitive antibiotic treatment with benzylpenicillin or aminopenicillin resulted in a lower 30-day mortality in an adjusted analysis compared with meropenem (OR 0.3; 95% CI 0.1-0.8). In conclusion, inadequate empiric antibiotic therapy and definitive therapy with meropenem were both associated with significantly higher 30-day mortality.

Demonstration of toxin A and B by polymerase chain reaction and McCoy cell assay in clinical isolates of Clostridium difficile from Denmark.

A polymerase chain reaction (PCR) for demonstration of gene fragments of Clostridium difficile was established. One hundred and sixty-eight clinical isolates of C. difficile from three population groups were tested for production of cytotoxins by McCoy cell line assay (MCA) and for fragments of toxin A and B genes by PCR. The fragments for PCR amplification were at the 5' end of the toxin genes, which was found to be specific for C. difficile. Full agreement between the PCR and MCA results was found with respect to toxicity. Fifty-eight of the 168 strains were cytotoxin positive. Isolates from 41 normal healthy children did not differ regarding cytotoxicity compared to isolates from hospitalized children. In adult hospitalized patients a much higher frequency of toxin-producing isolates was found. In two strains from two children, not of the same family, only the toxin A gene fragment was demonstrated, indicating that some strains of C. difficile only harbour the gene for enterotoxin. When two isolates from different periods of time were tested from 36 of the healthy children, a variation in cytotoxicity was found: in seven children strains changed from non-toxic to toxic and in four vice versa. This may be explained by a fluctuating colonization of toxic and non-toxic C. difficile strains, or it may indicate the need for examination of more than one strain from a positive faecal sample to demonstrate cytotoxicity.

Treatment of shunt-related cerebral ventriculitis due to Corynebacterium jeikeium with vancomycin administered intraventricularly. Case report.

A 52-year-old female with subarachnoid haemorrhage and hydrocephalus was treated with external and later internal drainage. She developed ventriculoperitoneal shunt-related ventriculitis caused by Corynebacterium jeikeium. The infection was unsuccessfully treated with intravenous vancomycin. It was controlled only after shunt removal and administration of intraventricular vancomycin as well as systemic vancomycin, rifampicin and fusidic acid. A review of the literature confirmed our experience that vancomycin given intraventricularly is well tolerated and doses can be individualized by measuring vancomycin levels in cerebrospinal fluid.

Detection of penicillin resistance in Streptococcus pneumoniae by diffusion tests.

Four different diffusion tests used to detect penicillin resistance in Streptococcus pneumoniae were evaluated for 34 penicillin-susceptible pneumococci (MIC < 0.1 microgram/ml), 35 intermediate pencillin-resistant (MIC 0.1-1.0 microgram/ml) and 23 penicillin-resistant strains (MIC > 2 micrograms/ml). The 1 microgram oxacillin disk from AB Biodisk, the 1 microgram oxacillin Neo-Sensitabs from Rosco, the 5 micrograms penicillin Low Neo-Sensitabs and the penicillin E test were tested on Mueller-Hinton blood agar, PDM Antibiotic Sensitivity Medium II supplemented with blood, and Danish Blood Agar. MICs obtained by the agar dilution method were used as reference. The 1 microgram oxacillin AB Biodisk was able to separate all the penicillin-susceptible pneumococci correctly from those with reduced penicillin susceptibility (MIC > or = 0.1 microgram/ml), whereas use of the 1 microgram oxacillin Neo-Sensitabs resulted in high frequencies (14-29%) of intermediate penicillin-resistant strains interpreted as penicillin susceptible. The 5 micrograms penicillin Low Neo-Sensitabs proved completely useless for detecting penicillin resistance in pneumococci. High rates of agreement (82-93%) were found between the penicillin E test and the reference MIC determination method on all the tested media.

In vitro activity of six macrolides, clindamycin and tetracycline on Streptococcus pneumoniae with different penicillin susceptibilities.

A collection of 99 clinical isolates of Streptococcus pneumoniae, chosen due to their different susceptibilities to penicillin, were investigated with respect to their susceptibility to the macrolides azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, spiramycin, and to clindamycin and tetracycline by the agar dilution method. We found complete cross resistance among the macrolides. The pneumococci were either susceptible, MIC < or = 0.5 micrograms/ml, or resistant, MIC > or = 16 micrograms/ml, to the tested macrolides, giving a bimodal distribution. In addition, complete cross resistance was observed between clindamycin and macrolides. Pneumococci resistant to macrolides were also resistant to tetracycline, and 26% of the macrolide-susceptible strains were tetracycline resistant.

[Gonorrheal ophthalmia neonatorum in a premature infant delivered by cesarean section]. / Gonoroisk ophthalmia neonatorum hos praetermt barn født ved sectio.

A case of gonococcal ophthalmia neonatorum in a preterm boy (gestational age 29 weeks) delivered by caesarean section 22 hours after rupture of the membranes is described. The neonate made an uneventful recovery after treatment with ampicillin, gentamicin and methicillin for concomitant cutaneous infection.

Incidence, clinical characteristics and 30-day mortality of enterococcal bacteraemia in Denmark 2006-2009: a population-based cohort study.

Enterococci currently account for approximately 10% of all bacteraemias, reflecting remarkable changes in their epidemiology. However, population-based data of enterococcal bacteraemia are scarce. A population-based cohort study comprised all patients with a first episode of Enterococcus faecalis or Enterococcus faecium bacteraemia in two Danish regions during 2006-2009. We used data collected prospectively during clinical microbiological counselling and hospital registry data. We determined the incidence of mono- and polymicrobial bacteraemia and assessed clinical and microbiological characteristics as predictors of 30-day mortality in monomicrobial bacteraemia by logistic regression analysis. We identified 1145 bacteraemic patients, 700 (61%) of whom had monomicrobial bacteraemia. The incidence was 19.6/100 000 person-years (13.0/100 000 person-years for E. faecalis and 6.6/100 000 person-years for E. faecium). The majority of bacteraemias were hospital-acquired (E. faecalis, 45.7%; E. faecium, 85.2%). Urinary tract and intra-abdominal infections were the predominant foci for the two species, respectively. Infective endocarditis (IE) accounted for 25% of patients with community-acquired E. faecalis bacteraemia. Thirty-day mortality was 21.4% in patients with E. faecalis and 34.6% in patients with E. faecium. Predictors of 30-day mortality included age, co-morbidity and hospital-acquired bacteraemia. In addition, intra-abdominal infection, unknown focus and high-level gentamicin resistance were predictors of mortality in E. faecalis patients. E. faecium was associated with increased risk of mortality compared with E. faecalis. The study emphasizes the importance of enterococci both in terms of incidence and prognosis. The frequency of IE in patients with E. faecalis bacteraemia emphasizes the importance of echocardiography, especially in community-acquired cases.

Case fatality ratio and mortality rate trends of community-onset Staphylococcus aureus bacteraemia.

Lethal outcomes can be expressed as a case fatality ratio (CFR) or as a mortality rate per 100 000 population per year (MR). Population surveillance for community-onset methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus bacteraemia was conducted in Canada, Australia, Sweden and Denmark to evaluate 30-day CFR and MR trends between 2000 and 2008. The CFR was 20.3% (MSSA 20.2%, MRSA 22.3%) and MR was 3.4 (MSSA 3.1, MRSA 0.3) per 100 000 per year. Although MSSA CFR was stable the MSSA MR increased; MRSA CFR decreased while its MR remained low during the study. Community-onset S. aureus bacteraemia, particularly MSSA, is associated with major disease burden. This study highlights complementary information provided by evaluating both CFR and MR.

The changing epidemiology of Staphylococcus aureus bloodstream infection: a multinational population-based surveillance study.

Although the epidemiology of Staphylococcus aureus bloodstream infection (BSI) has been changing, international comparisons are lacking. We sought to determine the incidence of S. aureus BSI and assess trends over time and by region. Population-based surveillance was conducted nationally in Finland and regionally in Canberra, Australia, western Sweden, and three areas in each of Canada and Denmark during 2000-2008. Incidence rates were age-standardized and gender-standardized to the EU 27-country 2007 population. During 83 million person-years of surveillance, 18,430 episodes of S. aureus BSI were identified. The overall annual incidence rate for S. aureus BSI was 26.1 per 100,000 population, and those for methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) were 24.2 and 1.9 per 100,000, respectively. Although the overall incidence of community-onset MSSA BSI (15.0 per 100,000) was relatively similar across regions, the incidence rates of hospital-onset MSSA (9.2 per 100,000), community-onset MRSA (1.0 per 100,000) and hospital-onset MRSA (0.8 per 100,000) BSI varied substantially. Whereas the overall incidence of S. aureus BSI did not increase over the study period, there was an increase in the incidence of MRSA BSI. Major changes in the occurrence of community-onset and hospital-onset MSSA and MRSA BSI occurred, but these varied significantly among regions, even within the same country. Although major changes in the epidemiology of community-onset and hospital-onset MSSA and MRSA BSIs are occurring, this multinational population-based study did not find that the overall incidence of S. aureus BSI is increasing.

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.

Decreasing candidaemia rate in abdominal surgery patients after introduction of fluconazole prophylaxis*.

Although abdominal surgery is an established risk factor for invasive candidiasis, the precise role of antifungal prophylaxis in these patients is not agreed upon. In 2007, fluconazole was added to the prophylactic antibiotic treatment for patients with gastrointestinal tract perforations or reoperation after colorectal surgery in two university hospitals in Copenhagen. Changes in candidaemia rates associated with this intervention were examined and potential interfering factors evaluated. Rates and clinical characteristics of candidaemias and other blood stream infections (BSIs) in abdominal surgery patients were compared before (1 January 2006 to 30 June 2007) and after the intervention (1 January 2008 to 30 June 2009). The departments' activity was assessed by number of bed-days, admissions and surgical procedures, and the consumption of antifungals was analysed. The candidaemia rate decreased from 1.5/1000 admissions in the pre-intervention to 0.3/1000 admissions in the post-intervention period (p 0.002). Numbers of BSIs and bed-days remained stable, and numbers of admissions and surgical procedures performed increased during the study period. Fluconazole consumption in the two abdominal surgery departments increased from 4.6 to 12.2 defined daily doses per 100 bed-days (p <0.001), and 3.2 to 5.0 (p 0.01), respectively, but remained unchanged in the intensive care units. We could not detect any increase in fluconazole-resistant strains (14/29 pre- and 2/7 post-intervention, p 0.43). The introduction of fluconazole prophylaxis was followed by a significantly decreased candidaemia rate. However, the observational study design does not allow conclusions regarding causality. No increase in resistance was detected, but follow-up was short and continuing surveillance is needed.

Risk factors for recurrence and death after bacteraemia: a population-based study.

Although most bacteraemic outcome studies have focused on mortality, a repeated episode(s) is another important outcome of bacteraemia. We sought to characterize patient factors and microbial species associated with recurrence and death from bacteraemia. Population-based surveillance for bacteraemia was conducted in a Canadian health region during 2000-2008. Episodes of bacteraemia were extracted and characterized. Transition intensities of both recurrence and death were estimated by separate multivariate Cox proportional hazards models. We identified 9713 patients with incident episodes of bacteraemia. Within 1 year: 892 (9.2%) had recurrent bacteraemia, 2401 (24.7%) had died without a recurrent episode and 330 (3.4%) had died after a recurrent episode. Independent risk factors for recurrence within 1 year (hazard ratio; 95% confidence interval) were: increasing Charlson comorbidity scores (score 1-2: 2.2; 1.8-2.7 and score 3+: 3.4; 2.8-4.2), origin of infection (nosocomial: 2.1; 1.8-2.6 and healthcare-associated: 2.4; 2.0-2.8), microorganism (polymicrobial: 1.5; 1.2-2.0 and fungal: 2.8; 1.9-4.2) and focus of infection (verified urogenital: 0.4; 0.3-0.6). Independent risk factors for death within 1 year included: a recurrent bacteraemic episode 3.6 (3.1-4.0), increasing age and different foci of infection. This study identifies patient groups at risk of having a recurrent episode and dying from these infections. It adds recurrent bacteraemia as an independent risk factor of death within 1 year and may help to target patients for prevention or changes in management.