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Background: Chronic hemodialysis is a risk factor for invasive bacterial infections. We conducted a nationwide study of risk and mortality of infective endocarditis (IE) among patients undergoing chronic hemodialysis., Methods: In this observational cohort study, patients with end-stage renal disease who initiated hemodialysis in Denmark during 1990 to 2010 were matched on age, gender, and municipality with up to 19 population controls. We extracted information on first admissions with IE, comorbidity, and arteriovenous fistula surgery from medical administrative databases. Incidence rates (IRs) of IE were compared between patients undergoing hemodialysis and population controls using Poisson regression. Risk factors for IE were assessed by Cox regression., Results: IE was diagnosed in 150 of 9392 patients undergoing hemodialysis (IR: 6.83 per 1000 person-years, 95% confidence interval [CI]; 5.82-8.01) and 250 of 176,369 population controls (IR: 0.18 per 1000 person-years, 95% CI; 0.16-0.20) yielding an incidence rate-ratio of 38.1 (95% CI; 31.2-46.7). Among patients undergoing hemodialysis, absence of arteriovenous fistula surgery was associated with increased risk of IE (hazard ratio [HR] = 1.57; 95% CI; 1.09-2.27) after adjusting for age, sex, valvular disease, diabetes and period of first hemodialysis. Age ≥70 years was associated with a lower risk of IE (HR = 0.59; 95% CI 0.37-0.93). The 90-day all-cause mortality following diagnose of IE was 27% (95% CI; 20-35) for patients undergoing hemodialysis and 23% (95% CI; 18-29) for controls., Conclusions: Patients undergoing hemodialysis have markedly elevated risk of IE compared to the general population. Future challenges will be to develop strategies to prevent IE, to reduce IE-related morbidity and mortality in this vulnerable population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge., (Copyright © 2016, American Association for the Advancement of Science.)

Background: Urinary tract infection is the most common infectious disease requiring hospitalisation following renal transplantation. However, the risk and outcome of post-transplant pyelonephritis remains unclear., Methods: This population-based cohort study was conducted from 1 January 1990 to 31 December 2009. Each member of a Danish population-based, nationwide cohort of first-time renal transplant recipients was matched by age and gender with up to 19 population controls. Information on hospital discharge diagnosis, emigration, and mortality was obtained from nationwide administrative databases. Individuals were observed from the date of first renal transplantation and until graft loss, emigration, or death. Risk factors were assessed by Poisson regression., Results: The incidence rate (IR) of first-time hospitalisation for pyelonephritis was 18.5 (95 % confidence interval [CI]: 16.4-20.9) per 1,000 person-years of follow-up (PYFU) among renal transplant recipients (N = 2,656) and 0.26 (CI: 0.21-0.31) per 1,000 PYFU among population controls (N = 49,226) yielding an incidence rate-ratio (IRR) of 72.0 (95 % CI: 57.8-89.7). Among renal transplant recipients, the risk of pyelonephritis decreased during the entire study period and was lowest in 2005-09 (IRR = 0.46, CI: 0.31-0.68). The highest risk of pyelonephritis was observed within the first six months post-transplantation (IR = 69.9 per 1,000 PYFU; CI: 56.4-86.7). Other risk factors for post-transplant pyelonephritis included female gender, high Charlson comorbidity index score, HLA-DR mismatch, cause of renal failure, and calendar period. Interestingly, we found that the combined risk of graft loss and death was 45 %, (CI: 19-77 %) higher in renal transplant recipients following post-transplant pyelonephritis compared to those who had no admission due to pyelonephritis., Conclusions: The risk of first-time hospitalisation for pyelonephritis among renal transplant recipients is high. Further, post-transplant pyelonephritis was associated with excess risk of graft loss and death; this indicates that strategies aimed at reducing upper urinary tract infections are likely to enhance renal graft survival.

♦ BACKGROUND: The incidence of bacteremia and fungemia (BAF) is largely unknown in end-stage renal disease (ESRD) patients initiating peritoneal dialysis (PD). ♦ OBJECTIVE: The main objective was to estimate and compare incidence rates of first episodes of BAF in incident PD patients and a comparison cohort. A secondary objective was to compare causative agents and 30-day post-BAF mortality between PD patients and the comparison cohort. ♦ METHODS: Design: Observational cohort study., Setting: Central and North Denmark regions., Participants: patients who initiated PD during 1995 - 2010. For each patient we sampled up to 10 controls from the general population matched on age, sex, and municipality. ♦ MAIN OUTCOME: Data on positive blood cultures were retrieved from electronic microbiology databases covering the 2 regions. We calculated incidence rates (IRs) of first-time BAF for PD patients and population controls. Incidence-rate ratios (IRRs) were calculated to compare these rates. Thirty-day mortality was estimated by Kaplan-Meier analysis. ♦ RESULTS: Among 1,024 PD patients and 10,215 population controls, we identified 75 and 282 episodes of BAF, respectively. Incidence rates of BAF were 4.7 (95% confidence interval [CI], 3.8 - 5.9) per 100 person-years of follow-up (PYFU) in PD patients and 0.5 (95% CI, 0.4 - 0.5) per 100 PYFU in population controls (IRR = 10.4; 95% CI, 8.1 - 13.5). In PD patients, the most frequent microorganisms were Escherichia coli (18.7%) and Staphylococcus aureus (13.3%). Escherichia coli (27.3%) also ranked first among population controls. Thirty-day mortality following BAF was 20.8% (95% CI, 12.6 - 31.0) and 20.7% (95% CI, 16.3 - 25.9) among PD patients and population controls, respectively. ♦ CONCLUSIONS: Peritoneal dialysis patients are at markedly higher risk of BAF than population controls. Causative agents and the 30-day post-BAF mortality were similar in the 2 cohorts., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Background: To determine complications during outpatient parenteral antimicrobial therapy (OPAT) administrated through a peripheral venous line, PICC-line or PORT-A-CATH (PAC)., Methods: Catheter related complications in patients with cystic fibrosis during OPAT were identified through a retrospective review of patient files supplemented by an interview., Results: In 64 treatment episodes with a peripheral venous line, 51 (79.7 %) used bolus injection and 13 (20.3 %) used infusion pump. 27 out of 51 (53.0 %) bolus injection episodes experienced complications, which required removal. None were observed for infusion pump treatments. The infectious complications requiring removal of peripheral venous line were 9 out of 23 (39.1 %) for the PICC line and 11 out of 26 (42.3 %) for the PAC. No anaphylaxis was observed during the OPAT treatments., Conclusions: Our data indicate that using an infusion pump to administer the antibiotic treatment minimized peripheral venous line complications. The frequency of complications leading to removal of the catheter is about the same for PICC-lines and PACs, but the average life-time of the latter is much longer. Allergic reactions are not a major problem.

Background and Objectives: Infections are common complications among patients on chronic hemodialysis. This population-based cohort study aims to estimate risk and case fatality of bloodstream infection among chronic hemodialysis patients., Methods: In this population-based cohort study we identified residents with end-stage renal disease in Central and North Jutland, Denmark who had hemodialysis as first renal replacement therapy (hemodialysis patients) during 1995-2010. For each hemodialysis patient, we sampled 19 persons from the general population matched on age, gender, and municipality. Information on positive blood cultures was obtained from regional microbiology databases. All persons were observed from cohort entry until first episode of bloodstream infection, emigration, death, or end of hemodialysis treatment, whichever came first. Incidence-rates and incidence-rate ratios were computed and risk factors for bloodstream infection assessed by Poisson regression. Case fatality was compared by Cox regression., Results: Among 1792 hemodialysis patients and 33 618 matched population controls, we identified 461 and 1126 first episodes of bloodstream infection, respectively. Incidence rates of first episode of bloodstream infection were 13.7 (95% confidence interval (CI), 12.5-15.0) per 100 person-years among hemodialysis patients and 0.53 (95% CI, 0.50-0.56) per 100 person-years among population controls. In hemodialysis patients, the most common causative microorganisms were Staphylococcus aureus (43.8%) and Escherichia coli (12.6%). The 30-day case fatality was similar among hemodialysis patients and population controls 16% (95% CI, 13%-20%) vs. 18% (95% CI, 15%-20%)., Conclusions: Hemodialysis patients have extraordinary high risk of bloodstream infection while short-term case fatality following is similar to that of population controls.

When antimicrobials are used empirically, pathogen MICs equal to clinical breakpoints or epidemiological cutoff values must be considered. This is to ensure that the most resistant pathogen subpopulation is appropriately targeted to prevent emergence of resistance. Accordingly, we determined the pharmacokinetic (PK) profile of moxifloxacin at 400 mg/day in 18 patients treated empirically for community-acquired pneumonia. We developed a population pharmacokinetic model to assess the potential efficacy of moxifloxacin and to simulate the maximal MICs for which recommended pharmacokinetic-pharmacodynamic (PK-PD) estimates are obtained. Moxifloxacin plasma concentrations were determined the day after therapy initiation using ultra-high-performance liquid chromatography. Peak drug concentrations (Cmax) and area under the free drug concentration-time curve from 0 to 24 h (fAUC0-24) values predicted for each patient were evaluated against epidemiological cutoff MIC values for Streptococcus pneumoniae, Haemophilus influenzae, and Legionella pneumophila. PK-PD targets adopted were a Cmax/MIC of ≥12.2 for all pathogens, an fAUC0-24/MIC of >34 for S. pneumoniae, and an fAUC0-24/MIC of >75 for H. influenzae and L. pneumophila. Individual predicted estimates for Cmax/MIC and fAUC0-24/MIC as well as simulated maximal MICs resulting in target attainment for oral and intravenous administration of the drug were suitable for S. pneumoniae and H. influenzae but not for L. pneumophila. These results indicate that caution must be taken when moxifloxacin is used as monotherapy to treat community-acquired pneumonia caused by L. pneumophila. In conclusion, this report reveals key information relevant to the empirical treatment of community-acquired pneumonia while highlighting the robust and flexible nature of this population pharmacokinetic model to predict therapeutic success. (Clinical Trials Registration no. NCT01983839.)., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Staphylococcus aureus is a leading cause of bloodstream infections among hemodialysis patients and of exit-site infections among peritoneal dialysis patients. However, the risk and prognosis of Staphylococcus aureus bacteremia among end-stage renal disease patients have not been delineated., Methods: In this Danish nationwide, population-based cohort study patients with end-stage renal disease and matched population controls were observed from end-stage renal disease diagnosis/sampling until first episode of Staphylococcus aureus bacteremia, death, or end of study period. Staphylococcus aureus positive blood cultures, hospitalization, comorbidity, and case fatality were obtained from nationwide microbiological, clinical, and administrative databases. Incidence rates and risk factors were assessed by regression analysis., Results: The incidence rate of Staphylococcus aureus bacteremia was very high for end-stage renal disease patients (35.7 per 1,000 person-years; 95% CI, 33.8-37.6) compared to population controls (0.5 per 1,000 person-years; 95% CI, 0.5-0.6), yielding a relative risk of 65.1 (95% CI, 59.6-71.2) which fell to 28.6 (95% CI, 23.3-35.3) after adjustment for sex, age, and comorbidity. After stratification for type of renal replacement therapy, we found the highest incidence rate of Staphylococcus aureus bacteremia among hemodialysis patients (46.3 per 1,000 person-years) compared to peritoneal dialysis patients (22.0 per 1,000 person-years) and renal transplant recipients (8.9 per 1,000 person-years). In persons with Staphylococcus aureus bacteremia, ninety-day case fatality was 18.2% (95% CI, 16.2%-20.3%) for end-stage renal disease patients and 33.7% (95% CI, 30.3-37.3) for population controls., Conclusions: Patients with end-stage renal disease, and hemodialysis patients in particular, have greatly increased risk of Staphylococcus aureus bacteremia compared to population controls. Future challenges will be to develop strategies to reduce Staphylococcus aureus bacteremia-related morbidity and death in this high-risk population.

Background: Nontuberculous mycobacteria (NTM) are an emerging threat to cystic fibrosis (CF) patients but their epidemiology is not well described., Methods: In this retrospective observational study we identified all Scandinavian CF patients with a positive NTM culture from airway secretions from 2000 to the end of 2012 and used national CF databases to describe microbiological and clinical characteristics., Results: During the 13-year period 157 (11%) CF patients were culture positive for NTM at least once. Mycobacterium abscessus complex (MABSC) (45%) and Mycobacterium avium complex (MAC) (32%) were the predominant species with geographical differences in distribution. Younger patients were more prone to MABSC (p<0.01). Despite treatment, less than one-third of MABSC patients with repeated positive cultures cleared their infection and a quarter had a lung transplant or died., Conclusion: NTM are significant CF pathogens and are becoming more prevalent in Scandinavia. MABSC and MAC appear to target distinct patient groups. Having multiple positive cultures despite treatment conveys a poor outcome., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Women living with HIV (WLWH) are reportedly at increased risk of invasive cervical cancer (ICC). WLWH in Denmark attend the National ICC screening program less often than women in the general population. We aimed to estimate the incidence of cervical dysplasia and ICC in WLWH in Denmark., Methods: We studied a nationwide cohort of WLWH and a cohort of age-matched females from the general population in the period 1999-2010. Pathology samples were obtained from The Danish Pathology Data Bank containing nationwide records of all pathology specimens. The cumulative incidence and hazard ratios (HRs) for time from inclusion to first cervical intraepithelial neoplasia (CIN)/ICC and time from first normal cervical cytology to first CIN/ICC were estimated. Sensitivity analyses were performed to include prior screening outcome, screening intensity and treatment of CIN/ICC in the interpretation of results., Results: We followed 1,143 WLWH and 17,145 controls with no prior history of ICC for 9,509 and 157,362 person-years. Compared to controls, the overall incidence of CIN1 or worse (CIN1+), CIN2+ and CIN3+ was higher in WLWH and predicted by young age and CD4 count <200 cells/µL. In women with normal baseline cytology, incidences of CIN1+ and CIN2+ were higher in WLWH. However, incidences were comparable between WLWH and controls adherent to the National ICC screening program., Conclusions: Overall, WLWH develop more cervical disease than controls. However, incidences of CIN are comparable amongst WLWH and controls adherent to the National ICC screening program and with a normal baseline cytology.

Background: Data on occurrence and risk factors for pneumocystis pneumonia (PCP) in patients with end-stage renal disease (ESRD) are sparse., Methods: This was a nationwide population-based study assessing occurrence and risk factors for PCP among patients with ESRD and population controls over a 21-year period (1/1 1990 to 31/12 2010). Using Danish registry data, first-time diagnoses of PCP were identified., Results: We identified 13 296 adult patients with ESRD and 244 255 controls, yielding 63 560 and 2 223 660 person-years of follow-up (PYFU), respectively. Fifty-eight first-time diagnoses of PCP were recorded in the ESRD group. Forty-six episodes occurred among renal transplant recipients (RTx) and 12 among haemodialysis patients (HD), yielding incidence rates of 181 (136-242) and 43.1 (24.5-75.9) per 100 000 PYFU. Compared to population controls, we found incidence rate-ratios of 125.9 (78.4-204) among RTx and 29.9 (14.1-59.7) among HD patients. Risk factors for PCP in RTx were age 50-65 years, age > 65 years, diabetes, polycystic kidney disease and hypertensive kidney disease/nephrosclerosis with an IRR of 2.22 (1.14-4.31), 3.12 (1.35-7.21), 3.44 (1.16-10.2), 4.25 (1.55-11.7) and 3.87 (1.49-10.0), respectively, and more than 36 months of dialysis before transplantation with an IRR of 1.99 (1.03-3.84). Among RTx the risk of PCP was highest during the first 6 months post-transplantation and increased from the beginning (IR1990-94 = 111 (46.3-267) per 100 000 PYFU) towards the end of the study period (IR2005-10 = 299 (203-439))., Conclusion: The PCP risk is substantial in RTx within the first 6 months of transplantation, emphasizing the potential benefit of prophylactic treatment in the early post-transplant period. Importantly, we identified subgroups within the RTx group that require more attention.

Background: Patients infected with hepatitis C virus (HCV) and co-infected with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) are at increased risk for progression of liver disease. The aim of this study was to assess HBV and HIV screening performance and outcome in HCV patients followed at a Danish university hospital and affiliated regional outpatient clinics., Methods: HBV and HIV serology data were extracted from a quality assurance database for the assessment of screening performance in patients diagnosed with chronic HCV infection during the period 1 January 1996 to 31 December 2011. Patients with incomplete and missing serology data had complementary serology tests performed to assess the prevalence of HBV and HIV co-infection and HBV immune status., Results: Among 624 HCV patients, 10 (2%) were co-infected with chronic HBV and 32 (5%) with HIV. Approximately half of the cohort were non-immune to HBV or had an unknown HBV serology status. Serology results consistent with resolved infection and HBV vaccination were found in 209 (33%) and 65 (10%) patients, respectively. During the 16-y observation period, HBV and HIV screening coverage at HCV diagnosis increased from 23% to 92% and from 38% to 80%, respectively., Conclusion: Despite improvements throughout the study period, HBV and HIV serology screening remained incomplete. The majority of patients were either HBV non-immune or had an unknown HBV serology status. These findings thus call for a more proactive screening approach as well as an improved HBV vaccination strategy for patients with chronic HCV infection.

Background: Women living with HIV (WLWH) are at increased risk of invasive cervical cancer (ICC). International HIV guidelines suggest cervical screening twice the first year after HIV diagnosis and thereafter annually. Adherence to the HIV cervical screening program in Denmark is unknown., Methods: We studied women from a population-based, nationwide HIV cohort in Denmark and a cohort of age-matched females from the general population. Screening behaviour was assessed from 1999-2010. Adjusted odds ratios (OR's) for screening attendance in the two cohorts and potential predictors of attendance to guidelines were estimated. Pathology specimens were identified from The Danish Pathology Data Bank., Results: We followed 1143 WLWH and 17,145 controls with no prior history of ICC for 9,509 and 157,362 person-years. The first year after HIV diagnosis 2.6% of WLWH obtained the recommended two cervical cytologies. During the different calendar intervals throughout the study period between 29-46% of WLWH followed the HIV cervical screening guidelines. Adjusted OR's of attendance to the general population screening program for WLWH aged 30, 40 and 50 years, compared to controls, were 0.69 (95% CI: 0.56-0.87), 0.67 (0.55-0.80) and 0.84 (0.61-1.15). Predictors of attendance to the HIV cervical screening program were a CD4 count > 350 cells/μL and HIV RNA < 500 copies/mL. Calendar period after 2002 and HIV RNA < 500 copies/mL predicted attendance to the general population cervical screening program., Conclusions: The majority of WLWH do not follow the HIV guidelines for cervical screening. We support the idea of cytology as part of an annual review and integration of HIV care and cervical screening in a single clinic setting.

A 65-year-old man with HIV infection presented with acute severe abdominal pain radiating to the back. A CT scan revealed an infrarenal abdominal aortic aneurysm, and an aortobifemoral bypass was undertaken. Subsequently, tissue specimens from the aortic wall grew Listeria monocytogenes. The patient received 8 weeks of intravenous antibiotic treatment followed by oral sulfotrim as secondary prophylaxis and made an uneventful recovery.

Background: We aimed to describe travel patterns, extent of professional pre-travel advice and health problems encountered during travel among HIV-infected individuals., Methods: During a six-month period a questionnaire was handed out to 2821 adult HIV-infected individuals attending any of the eight Danish medical HIV care centers., Results: A total of 763 individuals responded. During the previous two years 49% had travelled outside Europe; 18% had travelled less and 30% were more cautious when choosing travel destination than before the HIV diagnosis. Pre-travel advice was sought by only 38%, and travel insurance was taken out by 86%. However, 29%/74% did not inform the advisor/the insurance company about their HIV status. Nearly all patients on highly active antiretroviral therapy (HAART) were adherent, but 58% worried about carrying HIV-medicine and 19% tried to hide it. Only 19% experienced health problems during travel, 6% sought medical assistance and 0.5% was hospitalized., Conclusions: Danish HIV-infected patients travel frequently outside Denmark. Health and adherence to HAART were not major problems during travel. The main problems were failure to seek pre-travel advice, lack of disclosure of HIV status when seeking pre-travel advice or getting a travel insurance., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Individuals with end-stage renal disease (ESRD) have excess risk of various cancer types. However, the total burden of human papillomavirus-related cancers remains unknown., Methods: We performed a nationwide observational cohort study during 1994-2010.For each person with ESRD, we sampled 19 population controls (without ESRD) matched on age, gender and municipality. Participants were followed until first diagnosis of human papillomavirus-related cancer, death, emigration, or 31 December 2010, whichever came first.Human papillomavirus-related cancers were extracted from Danish medical administrative databases. We considered cancers of the cervix, vulva, vagina, penis, anus, and subsets of head and neck cancers as human papillomavirus-related. We calculated incidence rates of human papillomavirus-related cancer and used Poisson regression to identify risk factors for human papillomavirus-related cancer., Results: Among 12,293 persons with ESRD and 229,524 population controls we identified 62 and 798 human papillomavirus-related cancers, respectively. Incidence rates of human papillomavirus-related- cancer were 102 per 100,000 person-years (95% confidence interval [CI]; 79.5-131) among persons with ESRD and 40.8 per 100,000 person-years (95% CI; 38.1-43.7) among population controls. ESRD patients had 4.54 (95% CI, 2.48-8.31) fold increased risk of anal cancer and 5.81 fold (95% CI; 3.36-10.1) increased risk of vulvovaginal cancer. Adjusted for age, comorbidity, and sex, ESRD patients had 2.41 (95% CI; 1.83-3.16) fold increased risk of any human papillomavirus-related cancer compared with population controls. Compared with dialysis patients renal transplant recipients had an age-adjusted non-significant 1.53 (95% CI, 0.91-2.58) fold higher risk of human papillomavirus-related cancer., Conclusions: Persons with ESRD have excess risk of potentially vaccine-preventable human papillomavirus-related cancers.

Objectives: Individuals with immunodeficiencies are at increased risk of central nervous system (CNS) infections. Data are limited on the risk of CNS infections in patients with end-stage renal disease (ESRD)., Methods: We conducted a population-based, nationwide cohort study among ESRD patients from 1990 to 2009. Data on ESRD patients was obtained from the Danish Nephrology Registry database. Each ESRD patient was matched with up to 19 population controls. Using the National Hospital Registry we identified hospital admissions with CNS infection as primary discharge diagnosis., Results: The study included 13,374 ESRD patients and 245,397 population controls, providing 67,012 person-years and 2,237,237 person-years of observation, respectively. The overall incidence rate (IR) of first-time hospitalisation for CNS infection was 149 per 100,000 person-years (95%-confidence interval [CI], 123-181) among ESRD patients. The IR of CNS infection was comparable among dialysis and transplant patients. Compared to population controls, the incidence rate-ratio of first CNS infection was 5.58 (95%-CI, 4.47-6.91) for ESRD patients in general. The 30-day mortality following hospitalisation for CNS infections was 21% (95%-CI, 14-30) among ESRD patients and 13% (95%-CI, 10-16) among population controls., Conclusions: ESRD patients have considerable excess risk and mortality from CNS infections, which is of great clinical and public health concern., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

The immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral treatment for HIV infection can be caused by a great variety of pathogens. Among these are non-tuberculous mycobacteria (NTM), with Mycobacterium avium complex being the most commonly described finding. Antimycobacterial treatment of NTM in cases of IRIS is controversial. We report the case of a 39-year-old man diagnosed with HIV-1 infection during admission to hospital with Pneumocystis jirovecii pneumonia (PCP) and a CD4 cell count of 60/μl. The patient started antiretroviral treatment and made an uneventful recovery from the PCP diagnosis, but was readmitted after 2.5 months with a purulent infrapatellar bursitis on the left knee. A surgical procedure was performed and Mycobacterium malmoense was grown from the pus from the bursa. The patient recovered without supplemental antimycobacterial treatment. To our knowledge, this is the first report on IRIS caused by M malmoense.

Background: Gender differences in the risk of AIDS-defining illness (ADI) and mortality have been reported in the HIV-1-infected (HIV-positive) population, with conflicting findings. We aimed to assess the impact of gender on the risk of ADI and death in HIV-positive patients infected sexually., Methods: This was a population-based, nationwide cohort study of incident Danish HIV-positive individuals infected by sexual contact. Outcomes were progression to AIDS and death. We used Cox proportional hazards models and Poisson regression analyses to calculate the risk of progression to AIDS and mortality rate ratios (MRR) between risk groups and compared these with the general Danish population., Results: We identified 587 heterosexually infected women, 583 men who have sex with women (MSW), and 1089 men who have sex with men (MSM). The total follow-up time was 13,708 person-y. At the time of HIV diagnosis MSM had a lower prevalence of AIDS compared to MSW. Women and MSW presented more often with tuberculosis and less often with AIDS-defining cancers compared to MSM. In the adjusted analyses we observed no differences in progression to AIDS. In the adjusted analyses of risk of death, there were no differences between the 3 risk groups, although we saw a trend towards a higher risk of death in older MSW. MSM had a lower risk of death compared to the background population than women and MSW., Conclusions: In the Danish HIV population, gender has no major impact on progression to AIDS or mortality. Differences in these factors between women, MSW, and MSM are mainly due to confounding from race and CD4 + cell count at diagnosis.

Background: Pneumonia is commonly diagnosed in immunosuppressed individuals. The risk and attributable morbidity of first hospitalization for pneumonia among renal transplant candidates and recipients were compared to those of population controls., Methods: This population-based cohort study was conducted from 1 January 1990 to 31 December 2009. Each member of a Danish population-based, nationwide cohort of first-time renal transplant recipients was matched by age and sex with up to 19 population controls. Information on hospital discharge diagnosis, emigration, and mortality was obtained from nationwide administrative databases. Individuals were observed from diagnosis of end-stage renal disease until first hospitalization for pneumonia. Risk factors were assessed by Poisson regression., Results: The study included 4729 renal transplant candidates and recipients and 81 757 controls, providing 25 546 and 704 329 person-years of observation, respectively. Compared with population controls, the incidence rate ratio of first hospitalization for pneumonia was 10.2 (95% confidence interval [CI], 8.74-11.8) for renal transplant candidates, 8.02 (95% CI, 7.29-8.83) for renal transplant recipients, and 13.7 (95% CI, 11.5-16.3) for patients with graft loss. Among renal transplant recipients, risk factors included male sex, age ≥50 years, diabetes, chronic interstitial nephritis, polycystic kidney disease, and 1-3 years of prior dialysis. Patients with pneumonia had a 78% (95% CI, 1.52-2.10) increased risk of graft loss. Thirty-day mortality of patients was comparable to that of the background population., Conclusions: The risk of first-time hospitalization for pneumonia remains high among renal transplant candidates and recipients. The attributable morbidity and mortality are of great clinical and public health concern and preventive measures are warranted.

Background: The software program InfCare HIV is a combined clinical decision support tool and database. This study investigated the usefulness of InfCare HIV for identifying and characterizing suboptimally treated HIV-infected patients at a Danish HIV clinic., Methods: This cross-sectional cohort study included data on all HIV-infected patients treated at the Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark on a specific date. InfCare HIV was used to identify and characterize suboptimally treated patients defined as patients with virological failure (VF) or untreated patients with a CD4 + count below 350 cells/μl. Patient characteristics were analyzed (i.e. age, sex, ethnicity, and nadir and latest CD4 + cell count). Treatment history and reasons for suboptimal treatment were also investigated., Results: Among all 530 patients, 421 were receiving highly active antiretroviral therapy (HAART) and had undergone at least 48 weeks of treatment on 29 October 2010. Of these, 27 (6.4%) had ongoing VF. Four were untreated despite a CD4 + count below 350 cells/μl. Among patients on HAART, patients with VF were younger and had lower median nadir CD4 + cell counts than patients without VF. Further, 33.3% (6/18) of African Black men but only 4.1% (10/244) of Caucasian men on HAART had VF (p < 0.001). The primary reason for VF was non-adherence. Three untreated patients had refused HAART, and 1 was not treated because of concerns of non-adherence., Conclusions: InfCare HIV was successfully used to identify patients with suboptimal treatment. A surprisingly high percentage of African Black men had VF.

Background: An increased incidence of Achromobacter xylosoxidans infections has been observed at the Cystic Fibrosis Centre at Aarhus University Hospital, as the proportion of patients colonised with A. xylosoxidans increased from 6 to 10% from 2005 to 2009., Methods: Pulsed field gel electrophoresis (PFGE) was used to type isolates of A. xylosoxidans., Results: Four patients infected for 2-7 years were part of a larger epidemic spread involving both Danish CF centres, while 11 patients carried strains with unique genotypes. Longitudinal analysis of isolates from ten patients with multiple preserved isolates showed that each patient persistently carried isolates of a single genotype. Following lung transplantation, two patients showed re-colonisation of the lung grafts with the pre-transplant A. xylosoxidans strain., Conclusions: A. xylosoxidans has been transmitted between patients from our clinic, but the recent increase in incidence is not caused by cross infections., (Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to describe the clinical course of severe and complicated pandemic (H1N1)v infection treated with oral oseltamivir and inhaled zanamivir in a series of intensive care patients., Methods: We investigated a case series of patients with respiratory failure and a positive (H1N1)v real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Treatment consisted of oseltamivir tablets 75 mg × 4 daily in a nasogastric tube plus zanamivir intravenous (i.v.) solution 25 mg × 4 daily as inhalation. Ventilator inspiratory plateau airway pressure in the ventilator was kept below 30 cmH₂O, PaO₂ above 8 kPa and pH above 7.30. If this could not be achieved, inhalational nitric oxide (NO) was added or extracorporeal membrane oxygenation (ECMO) was initiated., Results: Twenty-one patients were admitted, with a median age of 50 y (range 6-69 y). Five patients (23.8%) died in the intensive care unit (ICU) and 1 patient died 2 weeks after ICU discharge. Nine patients received ECMO treatment, of whom 3 died during ECMO (33.3%; 3/9) and 1 at 2 weeks after. The mortality in patients not receiving ECMO treatment was 16.6% (2/12). Sixteen patients (76%) were influenza PCR-positive on day 7 after the start of antiviral treatment. Irreversible presumed lung fibrosis complicated with pneumothorax was common. A high Murray score at admission was significantly associated with a fatal outcome., Conclusions: The mortality in these patients was high despite combined antiviral treatment with oseltamivir and zanamivir. Patients shed virus for a long time despite intensive therapy. Optimal management of patients with bilateral pneumonia and respiratory failure caused by (H1N1)v still needs to be determined.

Objective: To compare the outcome of highly active antiretroviral therapy (HAART) in HIV-infected patients initiating equivalent regimens within and outside a randomized controlled trial (RCT)., Study Design and Setting: The Danish Protease Inhibitor Study (DAPIS) was a national multicenter RCT comparing initial treatment with indinavir, ritonavir, or saquinavir/ritonavir during 96 weeks. From the Danish HIV Cohort Study we identified all patients initiating one of these protease-inhibitor-based HAART regimens: 425 patients within DAPIS and 677 outside the trial. We compared viral load, CD4 count response, and mortality., Results: At weeks 96 and 240, trial participants were more likely than nonparticipants to have undetectable viral load (adjusted odds ratio [adOR] 1.28 [95% CI=0.94-1.74] and 1.70 [95% CI=1.16-2.50]) and a CD4 increase > or =100 cells/microl (adOR 1.37 [95% CI=1.03-1.82] and 1.53 [95% CI=1.04-2.25]). For antiretroviral-experienced, but not for antiretroviral-naïve patients, trial participants had a lower risk of death (mortality rate ratio [MRR]=0.46 [95% CI=0.27-0.77]) than nonparticipants. This effect was moderated in adjusted analyses (MRR=0.60 [0.33-1.07])., Conclusions: Compared to nontrial patients, trial participants had better response to HAART. The differences were small defying the notion that results obtained in RCTs are unachievable in routine clinical practice.

We present the demographic data on HIV-infected children from the Danish Paediatric HIV Cohort Study, an observational database on HIV in Denmark. Up to 1 July 2003 a total of 89 children had been diagnosed with HIV infection before the age of 16 y, of which 12 (13.5%) had died, 2 (2.2%) had emigrated from Denmark, and 13 had reached the age of 16 y. Estimates of prevalence and incidence of HIV infection in the area were 5.77/100,000 and 0.39/100,000 respectively, which are lower than in the adult population. After 1993 the number of newly diagnosed HIV infected children remained quite constant with an average of 4.2 diagnoses per y. Of the enrolled patients only 15.7% had both their parents of Danish origin, while 58.5% had at least 1 of the parents from an African country. Of the entire cohort, 20% were Caucasians, 51% were males and 76% were infected perinatally. There has been a shift in the HIV epidemic in children over recent y, with a higher proportion of newly diagnosed HIV patients having contracted the infection perinatally, a higher proportion being of non-Caucasian race, and the newly diagnosed individuals being younger. Even since 1995, a major part of the newly diagnosed children was born in Denmark by mothers from high-endemic areas and we therefore suggest that HIV-testing should actively be offered to all pregnant women coming from these high-risk areas.

We used a population-based cohort study design to describe the demographic characteristics of the HIV-infected population in Denmark and their variation over time. HIV treatment in Denmark is restricted to 9 centres, and all 3941 HIV-1 infected patients more than 15 y old seen at these centres in 1995-2003 were included. We found an estimated HIV prevalence of 70 per 100,000, and a mean annual incidence rate of 5.1 per 100,000 persons. The number of newly infected individuals was stable with a median of 231 per y (period 1995-2002), whereas the number of deaths decreased from 166 in 1995 to 50 in 2000 (p=0.000) and remained stable thereafter. Of the enrolled patients, 75% were males, 80% were Caucasian, 13% were black African, and the primary risk behaviour was male-to-male sexual contact (44%), heterosexual contact (36%), and injection drug use (11%). During the y 1995-2003 we found an increase in age at diagnosis (p=0.000), and no major changes in gender, race, mode of infection, or baseline CD4+ cell count and viral load, neither overall not within subgroups of patients. In this period 14.5% had AIDS at the time of HIV diagnosis. Our data do not confirm concerns about unmonitored evolution in the HIV epidemic in Denmark.

Background: Mitochondrial toxicity can be induced by reverse-transcriptase inhibitors, and an association between levels of mitochondrial DNA (mtDNA) per cell and lipodystrophy, peripheral neuropathy, and HIV infection per se has been suggested. Studies aimed at increasing the oxidative capacity in HIV-infected patients have been sparse., Methods: Levels of mtDNA in fat and peripheral blood mononuclear cells (PBMCs) from 25 HIV infected patients and 10 healthy control subjects were studied with real-time PCR analysis. A placebo-controlled and double-blind design was used to assign individuals to receive either 100 mg of coenzyme Q twice daily for 3 months or a matching placebo regimen. Levels of mtDNA and other parameters were assessed before and after the intervention period., Results: The mean number of mtDNA copies per cell was lower in fat tissue obtained from patients with peripheral neuropathy (1547 mtDNA copies/cell; P=.045), patients with lipodystrophy (1732 mtDNA copies/cell; P=.003) and in HIV patients with no complications associated with highly active antiretroviral therapy (2935 mtDNA copies/cell; P=.078), compared with healthy control subjects (6198 mtDNA copies/cell). No clear difference was seen in mtDNA content in PBMCs. Coenzyme Q therapy improved the general condition of patients (P=.005) and caused a reversible increase in peripheral neuropathy pain (P=.048). Compared with placebo, treatment with coenzyme Q did not result in changes in mtDNA levels in fat cells or in PBMCs after the treatment period., Conclusions: Levels of mtDNA in fat tissue, but not in PBMCs, were associated with peripheral neuropathy and lipodystrophy. High-dose coenzyme Q therapy increased well-being in asymptomatic HIV-infected patients and those with lipodystrophy, as well as in control subjects, but aggravated pain in patients with peripheral neuropathy.

Objectives: To assess the mortality in a cohort of HIV-infected patients starting highly active antiretroviral therapy (HAART) compared to the mortality of the general population, focusing on the influence of the CD4 cell count at the time of starting HAART., Methods: Patients in the HIV Cohort Study in Western Denmark starting HAART before 1 January 2002 were identified. For each patient, 100 population controls matched on age and gender were extracted from the Danish Civil Registration System. Mortality rates were compared between the two cohorts overall, and in four groups defined by baseline CD4 cell counts., Results: A total of 647 HIV-infected patients and 64 700 population controls were included, accounting for 53 and 815 deaths during follow-up. In the HIV group, mortality rates were 70.0 per 1000 person-years at risk in the lowest CD4 cell group (< 50 x 10 cells/l), and 3.2 in the highest (> or = 200 x 10 cells/l). Compared with population controls, mortality rate ratios declined with increasing CD4 cell counts, being 15.3 [95% confidence interval (CI), 9.8-23.8], 8.6 (95% CI, 4.3-16.8), 5.9 (95% CI, 3.0-11.4), and 3.6 (95% CI, 2.0-6.5) in the groups with CD4 cell count < 50, 50-99, 100-199, and > or = 200 x 10 cells/l., Conclusion: In comparison with the general population, HIV-infected patients starting HAART with a CD4 cell count above 200 x 10 cells/l had low mortality rates that were comparable with the rates found in other chronic medical diseases. The mortality rates increased considerably when treatment was started at lower baseline CD4 cell counts.

Greenland is a high-income country with free access to human immunodeficiency virus (HIV) care, including highly active antiretroviral therapy (HAART). We aimed to examine the HIV prevalence, age and gender distribution, and the effectiveness of HAART on CD4 positive cell count, viral load (VL), and mortality in the Greenland HIV-infected population. In this population-based cohort study we collected demographic, clinical and biochemical data on all HIV-infected patients followed in health clinics since 1995. For each case, we identified 100 age- and gender-matched population controls. The HIV cohort included 103 patients of whom 91% were Inuit; 81% were infected heterosexually. Only 40% of the patients had a VL <400 copies/ml at 48 weeks after starting HAART, and patients on HAART had a substantial excess relative mortality compared with the general population (mortality rate ratio [MRR]: 10.6; 95% confidence interval [CI]: 6.9-16.4). After the introduction of HAART, the mortality decreased (MRR: 2.5; 95% CI 0.9-6.8), but remained high with a mortality rate of 62 per 1000 person-years (py) (95% CI 29-129). Our findings underline the difficulties of implementing successful HIV treatment even with unlimited economic resources and free access to health care.

Saquinavir hard gel capsule (hgc), the first human immunodeficiency virus (HIV) protease inhibitor (PI) used in clinical practice, has been shown to have insufficient effectiveness. A population-based cohort study assessed the long-term consequences of using saquinavir hgc as initial PI in HIV-infected patients pre-exposed to nucleoside reverse transcriptase inhibitors. 121 patients starting a regimen with saquinavir hgc were compared with 91 starting with non-boosted indinavir (n = 72) or ritonavir (n = 19). Median follow-up time was 4.6 and 4.7 y for the 2 groups. Starting with saquinavir hgc was associated with a lower overall probability of achieving an undetectable viral load [risk ratio (RR) = 0.41, 95%, confidence interval (95% CI) 0.30-0.56]. However, the lower probability of having undetectable viral load during follow-up declined over time with odds ratios (OR) = 0.27 (95%, CI 0.14-0.54), 0.35 (951% CI 0.19-0.66), 0.47 (95% CI 0.24-0.91) and 0.73 (95% CI 0.34-1.55) at 60, 120, 180 and 240 weeks, respectively, after starting HAART. Starting with saquinavir hgc was correlated with a higher risk of having the initial PI discontinued (RR = 1.89, 95% CI 1.39-2.58). The insufficient suppression of viral load in patients starting with saquinavir hgc subsided during follow-up, probably owing to the earlier discontinuation of saquinavir hcg in favour of newer and more potent HAART regimens.

We performed a population-based cohort study to assess the impact of nonwhite origin on the outcome of highly active antiretroviral therapy (HAART) for a Danish cohort of human immunodeficiency virus (HIV)-infected patients. A total of 389 whites and 135 nonwhites started receiving HAART before 1 April 2001. After 1 year of treatment, 78% of nonwhites and 76% of whites achieved a virus load of <500 HIV RNA copies/mL. No major differences were found between the 2 groups with respect to achievement of a virus load of <500 copies/mL (relative risk [RR], 0.94; 95% confidence interval [CI], 0.74-1.18), risk of clinical progression (RR, 0.63; 95% CI, 0.32-1.24), or response measured by total CD4+ cell count. One year after fulfilling Danish recommendations for initiation of HAART, 91% of nonwhites and 93% of whites had started receiving HAART. Race and ethnic origin play no major role in the outcome associated with HAART if access to health care is free.

Introduction: The course of HIV infection has changed since the introduction of highly active anti-retroviral treatment., Material and Methods: We present demographic data from an observational database on HIV and AIDS in the Western part of Denmark, a region representing 2,935,156 individuals, or 55.1% of the population in Denmark (1 January 2000). Five centres in the region treat HIV positive adults; all patients attached to these centres since 1995 are included. Altogether 749 adult HIV-infected individuals were enrolled as of 31 December 1999. Estimates of the prevalence and incidence of HIV infection in the area were 25.8/100,000 and 2.6/100,000 respectively, which are lower than the average for the country., Results: The number of newly diagnosed HIV-infected patients remained constant in the period 1995-1999 with an average of 62 diagnoses per year. The number of HIV-related deaths declined from 43 in 1995 to 15 in 1999., Discussion: There seems to be a shift in the HIV epidemic over the last few years, with a higher proportion of newly diagnosed HIV-patients who have contracted the infection through heterosexual contact, and a higher proportion who are immigrants from less developed countries.

New antiretroviral drugs, expanding knowledge of their long-term toxic effects and the large number of patients with treatment failure have increased the demand for new strategies in the antiretroviral treatment of HIV-infected patients. The present study was conducted as part of the HIV Cohort Study in western Denmark to reveal trends in the use of antiretrovirals in the region. The cohort includes all patients attached to those centers treating HIV patients in western Denmark. A total of 537 patients who started highly active antiretroviral therapy (HAART) were included. The number of patients receiving HAART increased dramatically in 1996 and 1997 before leveling off, with 45-75 patients initiating treatment annually thereafter. Median follow-up time after initiation of HAART was 151 weeks. An estimated 45.1% of patients had the initial HAART regimen modified during the first year of follow-up. Side-effects and treatment failure were the main reasons for treatment modifications. Major new strategies implemented in the region in 1999 and 2000 included treatment with boosted protease inhibitors and non-nucleoside reverse transcriptase inhibitors.

The purpose of the current study was to determine the efficacy and safety of nevirapine combined with nelfinavir and two nucleoside reverse transcriptase inhibitors (NRTIs) in patients previously exposed to highly active antiretroviral therapy (HAART). In a prospective, open-label, randomized study, 56 HIV-infected adults who had received HAART, including saquinavir hard gel capsule, ritonavir, or indinavir, were randomly assigned to receive nevirapine in addition to nelfinavir and two NRTIs. The proportion of patients who achieved an undetectable viral load (plasma HIV-RNA <200 copies/ml) at weeks 24 and 36 was significantly higher in the nevirapine group than in the control group (55% and 52% vs. 22% and 22%; p =.015 and p =.047). No differences in CD4 cell count or clinical outcome were observed. In the nevirapine group, 17% of patients discontinued treatment because of rashes. We conclude that the addition of nevirapine, when switching from one protease inhibitor-containing regimen to one containing nelfinavir, has a substantial effect on viral suppression.

Purpose: To assess the effect of changing antiretroviral therapy in patients initially treated with saquinavir hard gel capsule (hgc)., Method: A retrospective cohort study comparing the virological and immunological responses in antiretroviral-naïve patients initially treated with a regimen of saquinavir-hgc, zidovudine, and lamivudine, with patients receiving either ritonavir or indinavir on a background of zidovudine and lamivudine., Results: Twenty-nine patients starting with saquinavir-hgc as the protease inhibitor (PI) component were compared to 58 patients starting with ritonavir (n = 16) or indinavir (n = 42). Median follow-up time was 30 and 33 months, respectively. Twelve, 18, 24, and 30 months after starting a regimen including saquinavir-hgc, 72%, 50%, 4%, and 0% of patients still received this PI. At these time points, 35%, 24%, 59%, and 74% of the patients in the saquinavir group obtained an HIV-RNA <500 copies/mL compared to 76%, 72%, 66%, and 65% in the indinavir/ritonavir group. No significant difference in CD4 count between the two groups was observed., Conclusion: We found that saquinavir-hgc, in combination with nucleoside reverse transcriptase inhibitors, suppressed viral load insufficiently in HIV patients naïve to antiretroviral therapy. However, the suboptimal effect of saquinavir-hgc seems reversible after optimizing the antiretroviral regimen, at least for the short term.

We present demographic data from an observational database of HIV and AIDS in the Western part of Denmark, a region with a population of 2,935,156 individuals (55.1% of the population of Denmark). Five centers in the region treat HIV-positive adults; all patients attached to these centers since 1995 are included in this study. In total, 749 adult HIV-infected individuals were enrolled as of 31 December, 1999. Estimates of prevalence and incidence of HIV infection in the area were 25.9/100,000 and 2.6/100,000, respectively, which are lower than average for the country. The number of newly diagnosed HIV-infected patients remained constant during the period 1995-99, with an average of 62 diagnoses per year. The number of HIV-related deaths declined from 43 in 1995 to 15 in 1999. Of the enrolled patients, 70.9% were of Danish origin, 75% were Caucasians, 69.7% were male and 47.2% had heterosexual contact as their primary risk behavior. There seems to have been a shift in the HIV epidemic in recent years, with a higher proportion of newly diagnosed HIV patients having contracted the infection through heterosexual contact, a higher proportion being immigrants from less developed countries and newly diagnosed individuals getting older.

Until December 31st 1997, 163 HIV/AIDS patients were treated with HAART at the Department of Infectious Diseases, Aarhus University Hospital. The patients mainly received a combination of zidovudine, lamivudine and saquinavir. They were observed for an average period of 375 days. HAART was found to increase the amount of CD4 lymphocytes in peripheral blood and decrease the number of HIV-RNA copies. Both effects were seen to be more pronounced in patients naive to antiretroviral treatment. However, 64 patients had their protease inhibitor changed during the observation period, 53% due to failure of suppression of the viral load, 25% due to adverse events and 22% due to other reasons.

Protease inhibitors are important components in anti-retroviral regimens. In this retrospective study 29 HIV-infected patients treated with a regimen of zidovudine, lamivudine and saquinavir hard gel in 1 centre in Denmark were compared with 58 patients treated with zidovudine, lamivudine and ritonavir or indinavir followed at 5 other centres in Scandinavia. All patients were naive to anti-retroviral therapy prior to institution of the actual anti-retroviral regimen and were followed for a median of 1.3 and 1.4 y respectively. The 2 groups did not differ significantly with respect to age, gender, route of infection, ethnic background, viral load, CD4 count, AIDS at baseline or frequency of clinical controls. Six and 12 months after initiating anti-retroviral therapy, 31% and 34% of the patients on the saquinavir regimen obtained HIV-RNA < or = 500 compared with 76% and 73% in the control group (p < 0.001). In contrast to viral load, the increase in CD4 count did not differ significantly between the 2 groups. In conclusion, we found that with respect to suppression of viral load a regimen of saquinavir, zidovudine and lamivudine seemed to be inferior to a regimen of zidovudine, lamivudine and ritonavir or indinavir.