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.

One-year incidence of prosthetic joint infection in total hip arthroplasty: a cohort study with linkage of the Danish Hip Arthroplasty Register and Danish Microbiology Databases.

OBJECTIVE: To examine the trend of Prosthetic Joint Infections (PJI) following primary total hip arthroplasty (THA) and the antimicrobial resistance of the bacteria causing these infections. MATERIALS AND METHODS: We identified a population-based cohort of patients in the Danish Hip Arthroplasty Register (DHR) who had primary THA and received their surgery in Jutland or Funen between 2005 and 2014. We followed the patients until revision, emigration, death, or up to 1-year of follow-up. Data from the DHR were combined with those from microbiology databases, the National Register of Patients, and the Civil Registration System. We estimated the cumulative 1-year incidence of PJI for two 5-year periods; 2005-2009 and 2010-2014. The hazard ratio of PJI as a measure of relative risk after adjusting for multiple risk factors was calculated. RESULTS: Of 48,867 primary THAs identified, 1120 underwent revision within 1 year. Of these, 271 were due to PJI. The incidence of PJI was 0.53% (95% confidence interval (CI): 0.44; 0.63) during 2005-2009 and 0.57% (95% CI: 0.49; 0.67) during 2010-2014. The adjusted relative risk was 1.05 (95% CI: 0.82; 1.34) for the 2010-2014 period vs the 2005-2009 period. The most common micro-organisms identified in the 271 PJI were Staphylococcus aureus (36%) and coagulase-negative staphylococci (CoNS) (33%); others commonly identified included Enterobacteriaceae, enterococci, and streptococci. Antimicrobial resistance to beta-lactams and gentamicin did not change during the study period. CONCLUSION: The risk of PJI within 1-year after primary THA and the antimicrobial resistance of the most prevalent bacteria remained unchanged during the 2005-2014 study period.

Description and validation of a new automated surveillance system for Clostridium difficile in Denmark.

The surveillance of Clostridium difficile (CD) in Denmark consists of laboratory based data from Departments of Clinical Microbiology (DCMs) sent to the National Registry of Enteric Pathogens (NREP). We validated a new surveillance system for CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects microbiological test results from all Danish DCMs. We built an algorithm to identify positive test results for CD recorded in MiBa. A CD case was defined as a person with a positive culture for CD or PCR detection of toxin A and/or B and/or binary toxin. We compared CD cases identified through the MiBa-based surveillance with those reported to NREP and locally in five DCMs representing different Danish regions. During 2010-2014, NREP reported 13 896 CD cases, and the MiBa-based surveillance 21 252 CD cases. There was a 99·9% concordance between the local datasets and the MiBa-based surveillance. Surveillance based on MiBa was superior to the current surveillance system, and the findings show that the number of CD cases in Denmark hitherto has been under-reported. There were only minor differences between local data and the MiBa-based surveillance, showing the completeness and validity of CD data in MiBa. This nationwide electronic system can greatly strengthen surveillance and research in various applications.

Mortality in cancer patients previously diagnosed with herpes zoster in the hospital setting: a nationwide cohort study.

BACKGROUND: Herpes zoster (HZ) is associated with underlying immunodeficiency and may thereby predict mortality of subsequent cancer. METHODS: By using Danish nationwide medical databases, we identified all cancer patients with a prior hospital-based HZ diagnosis during 1982-2011 (n=2754) and a matched cancer cohort without prior HZ (n=26 243). We computed adjusted mortality rate ratios (aMRRs) associating prior HZ with mortality following cancer. RESULTS: Prior HZ was associated with decreased mortality within the year after cancer diagnosis (aMRR 0.87; 95% confidence interval (CI): 0.81-0.93), but not thereafter (aMRR 1.07; 95% CI: 0.99-1.15). However, prior HZ predicted increased mortality throughout the entire follow-up among patients aged <60 years (aMRR 1.39; 95% CI: 1.15-1.68) and those with disseminated HZ (aMRR 1.18; 95% CI: 1.01-1.37). The increased mortality rates were observed primarily for haematological and immune-related cancers. CONCLUSIONS: Overall, HZ was not a predictor of increased mortality following subsequent cancer.

Increased risk of venous thromboembolism within the first year after Staphylococcus aureus bacteraemia: a nationwide observational matched cohort study.

OBJECTIVES: Recent evidence suggests that there is an association between infection and venous thromboembolism (VTE). Here, we examined the risk of VTE after Staphylococcus aureus bacteraemia (SAB) compared to the risk in control subjects. DESIGN AND SETTING: Register-based nationwide observational cohort study of hospitalized patients and matched control subjects from the general population in Denmark between 1995 and 2008. RESULTS: Amongst 15 669 SAB cases and 156 690 controls, 182 and 511, respectively, experienced VTE within 1 year. The overall incidence rate (IR) of VTE amongst cases was highest within the first 30 days [IR of deep vein thrombosis (DVT), 39.3 (95% confidence interval (CI) 28.9-53.4)/1000 person-years (PYs); IR of pulmonary embolism (PE), 16.3 (95% CI 10.1-26.2)/1000 PYs]. IRs of DVT were particularly increased amongst cases with a previous diagnosis of VTE, community-acquired infection, a history of injection drug use and in younger age groups. The overall hazard ratio of VTE for cases compared to controls declined from 15.6 (95% CI 10.3-23.5) in the first 30 days after SAB to 4.5 (95% CI 3.2-6.2) from 181 to 365 days after infection. The increased risk of VTE amongst SAB patients persisted after excluding cases with identified VTE risk factors. CONCLUSIONS: There was a particularly high risk of VTE during the first month following an episode of SAB. The risk declined over time, but remained at a threefold increased level compared to control subjects, suggesting that there are shared risk factors for SAB and VTE. Patients with SAB and well-documented risk factors for VTE may benefit from thromboprophylaxis.

Staphylococcus aureus skin and soft tissue infections in primary healthcare in Denmark: a 12-year population-based study.

A rise in community-onset Staphylococcus aureus infections has been observed in European countries. To ascertain secular trends of S. aureus infections in primary healthcare in Denmark, we conducted this register-based study in the North Denmark region, during the period 1997-2008. We identified all skin and mucosa specimens obtained by general practitioners and all prescriptions for the preferred oral anti-staphylococcal antibiotic, dicloxacillin. Repeat observations within a 12-month period were excluded prior to the calculation of age and gender standardised incidence rates per 100,000 person-years. We included 108,758 specimens, of which 42,778 (39%) yielded S. aureus. The annual incidence rate of specimens doubled during the study period, reaching 2,399 in 2008. The overall rate of S. aureus isolates increased 2-fold to a stable rate at about 850, but for isolates from children and for impetigo specimens, the increase was steeper, with a peak in 2002. A total of 156,462 dicloxacillin prescriptions had been redeemed and the annual prescription rate increased 2.5-fold, peaking at 3,714 in 2007. In conclusion, the annual rates of specimens, S. aureus infections and dicloxacillin prescriptions more than doubled in primary healthcare during the 12-year study period. A major impetigo epidemic and calls for antibiotic stewardship with increased utilisation of specimens were contributing factors.

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.

Changes in blood culture methodology have an impact on time trends of bacteraemia: a 26-year regional study.

The incidence of bacteraemia has increased considerably during the last decades. This may be related to population ageing, increased use of invasive procedures, and increased ascertainment of bacteraemia. Generalized additive and generalized linear models were used to analyse the impact of four successive improvements in blood culture methodology on the recovery of prevalent blood culture isolates while simultaneously controlling for underlying time trend and seasonal variation. Between 1981 and 2006, 20 091 bacteraemias comprising 22 800 blood culture isolates were diagnosed. The changes in methodology increased the recovery of some bacterial groups; the greatest impact was observed for Enterobacteriaceae, pneumococci and Staphylococcus aureus whereas recovery of ß-haemolytic streptococci, Pseudomonas aeruginosa, other Gram-negative aerobes, and fungi was not affected. Changes in blood culture methodology should be taken into account when assessing time trends of bacteraemia.

Bacteraemia with Campylobacter jejuni: no association with the virulence genes iam, cdtB, capA or virB.

The role of bacterial genes in the determination of the clinical spectrum of Campylobacter jejuni infection is unclear. We compared clinical isolates from invasive blood-stream infection with stool isolates from gastroenteritis and found no association of the putative virulence genes iam, capA, virB and cdtB with clinical presentation.

Examining secular trends and seasonality in count data using dynamic generalized linear modelling: a new methodological approach illustrated with hospital discharge data on myocardial infarction.

Time series of incidence counts often show secular trends and seasonal patterns. We present a model for incidence counts capable of handling a possible gradual change in growth rates and seasonal patterns, serial correlation, and overdispersion. The model resembles an ordinary time series regression model for Poisson counts. It differs in allowing the regression coefficients to vary gradually over time in a random fashion. During the 1983-1999 period, 17,989 incidents of acute myocardial infarction were recorded in the Hospital Discharge Registry for the county of North Jutland, Denmark. Records were updated daily. A dynamic model with a seasonal pattern and an approximately linear trend was fitted to the data, and diagnostic plots indicated a good model fit. The analysis conducted with the dynamic model revealed peaks coinciding with above-average influenza A activity. On average the dynamic model estimated a higher peak-to-trough ratio than traditional models, and showed gradual changes in seasonal patterns. Analyses conducted with this model provide insights not available from more traditional approaches.

Challenging the six-hour recommendation for reprocessing sterilizable medical equipment.

BACKGROUND: At present, reprocessing of sterilizable medical equipment is recommended to be initiated within 6 h after completion of surgery, to ensure that the quality of the instruments does not deteriorate. A literature search showed a lack of evidence for consequences that may occur if medical personnel deviate from the standard 6 h sterilization protocol. AIM: To evaluate the 6 h recommendation for reprocessing sterilizable medical equipment by determining whether residual protein increased proportional to holding time before reprocessing was initiated, and likewise whether an increase in corrosion was present on surgical scissors proportional to holding time. METHODS: Residual protein was identified on surgical instruments contaminated with human blood after different holding times and before washes using the o-phthaldialdehyde (OPA) method. Corrosion was identified on surgical scissors contaminated with human blood after different holding times and after reprocessing using light stereomicroscopy and scanning electron microscopy. FINDINGS: Protein residues ranged between 14.0 and 51.9 µg and thus below the accepted threshold of 100 µg per instrument surface. Corrosion corresponding to 0.05% of the surface was identified on 22 of 30 scissors. Pitting corrosion was seen on four of 30 scissors. CONCLUSION: No association was identified between residual protein and holding time, nor between incidence of corrosion and holding time. The study thereby challenges the relevance of upholding the recommendation of a maximum wait of 6 h prior to reprocessing. The findings will potentially have an impact on the organization of reprocessing of surgical instruments in Denmark and internationally.

An untapped potential for imaging of peripheral osteomyelitis in paediatrics using [18F]FDG PET/CT -the inference from a juvenile porcine model.

PURPOSE: To examine parameters affecting the detection of osteomyelitis (OM) by [18F]FDG PET/CT and to reduce tracer activity in a pig model. BACKGROUND: [18F]FDG PET/CT is recommended for the diagnosis of OM in the axial skeleton of adults. In children, OM has a tendency to become chronic or recurrent, especially in low-income countries. Early diagnosis and initiation of therapy are therefore essential. We have previously demonstrated that [18F]FDG PET/CT is promising in juvenile Staphylococcus aureus (S. aureus) OM of peripheral bones in a pig model, not failing even small lesions. When using imaging in children, radiation exposure should be balanced against fast diagnostics in the individual case. METHODS: Twenty juvenile pigs were inoculated with S. aureus. One week after inoculation, the pigs were [18F]FDG PET/CT scanned. PET list-mode acquired data of a subgroup were retrospectively processed in order to simulate and examine the image quality obtainable with an injected activity of 132 MBq, 44 MBq, 13.2 MBq, and 4.4 MBq, respectively. RESULTS: All lesions were detected by [18F]FDG PET and CT. Some lesions were very small (0.01 cm3), and others were larger (4.18 cm3). SUVmax was higher when sequesters (p = 0.023) and fistulas were formed (p < 0.0001). The simulated data demonstrated that it was possible to reduce the activity to 4.4 MBq without compromising image quality in pigs. CONCLUSIONS: [18F]FDG PET/CT localized even small OM lesions in peripheral bones. It was possible to reduce the injected activity considerably without compromising image quality, impacting the applicability of PET/CT in peripheral OM in children.

Microbiological diagnostics of bloodstream infections in Europe-an ESGBIES survey.

OBJECTIVES: High-quality diagnosis of bloodstream infections (BSI) is important for successful patient management. As knowledge on current practices of microbiological BSI diagnostics is limited, this project aimed to assess its current state in European microbiological laboratories. METHODS: We performed an online questionnaire-based cross-sectional survey comprising 34 questions on practices of microbiological BSI diagnostics. The ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis (ESGBIES) was the primary platform to engage national coordinators who recruited laboratories within their countries. RESULTS: Responses were received from 209 laboratories in 25 European countries. Although 32.5% (68/209) of laboratories only used the classical processing of positive blood cultures (BC), two-thirds applied rapid technologies. Of laboratories that provided data, 42.2% (78/185) were able to start incubating BC in automated BC incubators around-the-clock, and only 13% (25/192) had established a 24-h service to start immediate processing of positive BC. Only 4.7% (9/190) of laboratories validated and transmitted the results of identification and antimicrobial susceptibility testing (AST) of BC pathogens to clinicians 24 h/day. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry from briefly incubated sub-cultures on solid media was the most commonly used approach to rapid pathogen identification from positive BC, and direct disc diffusion was the most common rapid AST method from positive BC. CONCLUSIONS: Laboratories have started to implement novel technologies for rapid identification and AST for positive BC. However, progress is severely compromised by limited operating hours such that current practice of BC diagnostics in Europe complies only partly with the requirements for optimal BSI management.

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.

Early versus late diagnosis in community-acquired bacterial meningitis: a retrospective cohort study.

OBJECTIVES: To examine clinical characteristics and outcome of patients with late diagnosis of community-acquired bacterial meningitis (CABM). METHODS: We conducted a chart review of all adults with proven CABM in three centres in Denmark from 1998 through to 2014. Patients were categorized as early diagnosis of CABM immediately on admission, or late diagnosis if CABM was not listed in referral or admission records and neither lumbar puncture nor antibiotic therapy for meningitis was considered immediately on admission. We used modified Poisson regression analysis to compute adjusted relative risks with 95% CIs for predictors of late diagnosis and in-hospital mortality. RESULTS: A total of 113/358 (32%) patients were categorized as late diagnosis demonstrating a variety of tentative diagnoses of which 81/113 (72%) were non-infectious. We observed several statistically significant baseline differences (p <0.05) in patients with late versus early diagnosis including age >65 years (56/113, 50% versus 67/245, 27%), neck stiffness (35/97, 36% versus 183/234, 78%), concomitant pneumonia (26/113, 23% versus 26/245, 11%), and meningococcal meningitis (6/113, 5% versus 52/245, 21%). These variables remained statistically significant in multivariate analysis. Moreover, late diagnosis was associated with increased in-hospital mortality (41/113, 36% versus 43/245, 18%; adjusted relative risk 1.7, 95% CI 1.2-2.5). CONCLUSIONS: Late diagnosis of CABM was common and patients were admitted with mostly non-infectious diagnoses. Absence of neck stiffness did not rule out CABM and special attention should be given to patients with pneumonia and the elderly. Late diagnosis was associated with incorrect patient management and increased mortality.

High incidence of candidaemia in a nationwide cohort: Underlying diseases, risk factors and mortality.

BACKGROUND: Denmark has a high incidence rate of candidaemia. A Nordic study suggested a higher Danish prevalence of haematological malignancies as an underlying reason. This nationwide study ascertained clinical characteristics of Danish candidaemia patients and investigated potential factors contributing to the high incidence and mortality. METHODS: Microbiological and clinical data for candidaemia patients in 2010-2011 were retrieved. 30-day mortality was estimated by hazard ratios (HR) with 95% confidence intervals (CI, Cox regression). RESULTS: Data were available for 912/973 candidaemia episodes (93.7%). Intensive care unit (ICU) held the largest share of patients (43.2%). Prevalent host factors were multi-morbidity (≥2 underlying diseases, 74.2%) and gastrointestinal disease (52.5%). Haematological disease was infrequent (7.8%). Risk factors included antibiotic exposure (90.5%), CVC (71.9%) and Candida colonisation (66.7%). 30-day mortality was 43.4%, and 53.6% in ICU. Mortality was lower for patients with recent abdominal surgery (HR 0.70, 95% CI: 0.54-0.92). CONCLUSION: A substantial prevalence of multi-morbidity and a high 30-day mortality was found. We hypothesise, that an increasing population of severely ill patients with prolonged supportive treatment and microbiological testing may in part explain the high candidaemia incidence in Denmark. Nationwide studies are warranted to clarify this issue.

Herpes zoster as a marker of occult cancer: A systematic review and meta-analysis.

OBJECTIVES: Researchers have advocated for an increased awareness of occult cancer among herpes zoster patients, but there are no systematic reviews to support these claims. We therefore conducted a systematic review and meta-analysis of evidence on zoster and risk of occult cancer. METHODS: Through February 18, 2016, we searched PubMed, EMBASE and references of relevant papers for studies on zoster and risk of any cancer. One author screened retrieved papers by title and abstract; included papers were reviewed by two authors for eligibility, data extraction, and potential biases. Despite statistical heterogeneity, associations were consistently in the same direction and we therefore computed pooled relative risks using random-effects models. RESULTS: We identified 46 eligible studies, 10 of which considered all cancer types combined. The pooled relative risk for any cancer was 1.42 (95% confidence interval: 1.18, 1.71) overall and 1.83 (95% confidence interval: 1.17, 2.87) at one year after zoster. Considering cancer subtypes, the highest estimates were generally reported for occult hematological cancer. The absolute risk of any cancer at one year after presentation with zoster was 0.7-1.8%. CONCLUSION: This study supports an association between zoster and occult cancer, but the low absolute risk of cancer limits the clinical implications.

Risk factors for extended-spectrum ß-lactamase-producing Escherichia coli urinary tract infection in the community in Denmark: a case-control study.

OBJECTIVE: To verify the role of proton pump inhibitors (PPI) and nitrofurantoin, which have appeared as novel risk factors for carriage of extended-spectrum ß-lactamase (ESBL) -producing Escherichia coli, as risk factors for ESBL E. coli urinary tract infection (UTI). We included known risk factors to ascertain whether our findings are comparable with those of previous studies. METHODS: Population-based case-control study including 339 cases with community-onset ESBL E. coli UTI in 2007-2012, 3390 non-ESBL E. coli UTI controls and 3390 population controls. We investigated potential risk factors by estimating ORs and 95% CIs adjusting for sex, age and co-morbidity. RESULTS: Comparing cases with non-ESBL E. coli UTI, PPI use yielded an OR of 1.6 (95% CI 1.2-2.0) and antibiotic exposure gave an OR of 1.4 (95% CI 1.1-1.8); these were driven by nitrofurantoin (OR 1.8; 95% CI 1.3-2.6) and macrolides (OR 1.7; 95% CI 1.2-2.3). Other risk factors included previous hospitalization with one or two and more than two hospitalizations versus none yielding ORs of 1.9 (95% CI 1.4-2.5) and 4.6 (95% CI 3.2-6.8), recent surgery (OR 2.0; 95% CI 1.5-2.8), renal disease (OR 2.2; 95% CI 1.4-3.4), chronic pulmonary disease (OR 1.4; 95% CI 1.0-2.0) and cancer (OR 1.5; 95% CI 1.1-2.1). Comparing cases with population controls, we found that most risk factors were also risk factors for non-ESBL UTI. CONCLUSIONS: ESBL E. coli UTI were associated with previous hospitalization and surgery. Nitrofurantoin and macrolides augmented the risk. PPIs had a moderate effect but may be important facilitators of ESBL carriage due to their widespread use.

Gender differences in the outcome of community-acquired Staphylococcus aureus bacteraemia: a historical population-based cohort study.

OBJECTIVES: Female gender has been suggested to be associated with poor outcome in patients with Staphylococcus aureus bacteraemia (SAB), but existing data remain sparse and conflicting. We investigated clinical outcomes in female and male patients with community-acquired (CA-) SAB. METHODS: Population-based medical registers were used to conduct a cohort study of all adult patients with CA-SAB in northern Denmark, 2000-2011. Thirty-day mortality after CA-SAB for female and male patients was estimated by the Kaplan-Meier method. Using Cox proportional hazards regression, we computed hazard ratios (HRs) of death according to gender, overall and stratified by age groups, co-morbidity level, and selected major diseases while adjusting for potential confounders. Moreover, we estimated 30-day prevalence proportions for SAB-associated infective endocarditis and osteomyelitis by gender. RESULTS: Among 2638 patients with CA-SAB, 1022 (39%) were female. Thirty-day mortality was 29% (n = 297) in female patients and 22% (n = 355) in male patients, yielding an adjusted HR (aHR) of 1.30 (95% CI, 1.11-1.53). This association appeared robust across age groups, whereas no consistent pattern was observed according to co-morbidity level. Compared with male patients, the prognostic impact of gender was most pronounced among female patients with diabetes (aHR 1.52; 95% CI 1.04-2.21)), and among female patients with cancer (aHR 1.40; 95% CI 1.04-1.90). The 30-day prevalence of infective endocarditis or osteomyelitis did not differ according to gender. CONCLUSION: Female patients with CA-SAB experienced increased 30-day mortality compared with male patients. Gender should be considered in the triage and risk stratification of CA-SAB patients.