Plasma concentration of orally administered amoxicillin and clindamycin in patients receiving haemodialysis.

OBJECTIVES: In the randomized controlled trial PANTHEM, the prophylactic effect of oral amoxicillin or clindamycin is investigated in patients receiving chronic haemodialysis (HD). However, data on plasma concentrations of these antibiotics during HD are sparse. This study aims to determine if the plasma concentration of amoxicillin and clindamycin is sufficient during HD after oral administration of amoxicillin and clindamycin at three different time intervals prior to the HD procedure. METHODS: Adult patients receiving chronic HD were investigated twice with an interval of at least 7 days starting with either a tablet of 500/125 mg amoxicillin/clavulanic acid or a tablet of 600 mg clindamycin. Patients were randomized to take the antibiotics either 30, 60 or 120 min prior to the HD procedure. Plasma antibiotic concentrations were measured at start, midway and at the end of HD. A lower threshold was set at 2.0 mg/L for amoxicillin and at 1.0 mg/L for clindamycin. In addition, a population pharmacokinetic (PK) analysis was performed, assessing PTA. RESULTS: In the amoxicillin cohort (n = 37), 84% of patients and 95% of all plasma amoxicillin concentrations were above or at the threshold throughout the dialysis procedure. In the clindamycin cohort (n = 33), all concentrations were above the threshold throughout the dialysis procedure. Further, in all patients, the mean plasma concentration of both amoxicillin and clindamycin across the HD period was well above the threshold. Finally, the PK model predicted a high PTA in the majority of patients. DISCUSSION: In patients on chronic HD, oral administration of amoxicillin/clavulanic acid (500/125 mg) or clindamycin (600 mg) within 30-120 min prior to HD leads to a sufficient prophylactic plasma concentration across the HD period.

Temporal changes in cardiovascular disease and infections in dialysis across a 22-year period: a nationwide study.

BACKGROUND: Cardiovascular diseases (CVD) and infections are recognized as serious complications in patients with end stage kidney disease. However, little is known about the change over time in incidence of these complications. This study aimed to investigate temporal changes in CVD and infective diseases across more than two decades in chronic dialysis patients. METHODS: All patients that initiated peritoneal dialysis (PD) or hemodialysis (HD) between 1996 and 2017 were identified and followed until outcome (CVD, pneumonia, infective endocarditis (IE) or sepsis), recovery of kidney function, end of dialysis treatment, death or end of study (December 31st, 2017). The calendar time was divided into 5 periods with period 1 (1996-2000) being the reference period. Adjusted rate ratios were assessed using Poisson regression. RESULTS: In 4285 patients with PD (63.7% males) the median age increased across the calendar periods from 65 [57-73] in 1996-2000 to 69 [55-76] in 2014-2017, (p <  0.0001). In 9952 patients with HD (69.2% males), the overall median age was 71 [61-78] without any changes over time. Among PD, an overall non-significant decreasing trend in rate ratios (RR) of CVD was found, (p = 0,071). RR of pneumonia increased significantly throughout the calendar with an almost two-fold increase of the RR in 2014-2017 (RR 1.71; 95% CI 1.46-2.0), (p <  0.001), as compared to the reference period. The RR of IE decreased significantly until 2009 (RR 0.43; 95% CI 0.21-0.87), followed by a return to the reference level in 2010-2013 (RR 0.87; 95% CI 0.47-1.60 and 2014-2017 (RR 1.1; 95% CI 0.59-2.04). A highly significant (p <  0.001) increase in sepsis was revealed across the calendar periods with an almost 5-fold increase in 2014-2017 (RR 4.69 95% CI 3.69-5.96). In HD, the RR of CVD decreased significantly (p <  0.001) from 2006 to 2017 (RR 0.85; 95% CI 0.79-0.92). Compared to the reference period, the RR for pneumonia was high during all calendar periods (p <  0.05). The RR of IE was initially unchanged (p = 0.4) but increased in 2010-2013 (RR 2.02; 95% CI 1.43-2.85) and 2014-2017 (RR 3.39; 95% CI 2.42-4.75). No significant changes in sepsis were seen. CONCLUSION: Across the two last decades the RR of CVD has shown a decreasing trend in HD and PD patients, while RR of pneumonia increased significantly, both in PD and in HD. Temporal trends of IE in HD, and particularly of sepsis in PD were upwards across the last decades.

Outcome of Dialysis-Requiring Acute Kidney Injury in Patients With Infective Endocarditis: A Nationwide Study.

BACKGROUND: Infective endocarditis (IE) may be complicated by acute kidney injury, yet data on the use of dialysis and subsequent reversibility are sparse. METHODS: Using Danish nationwide registries, we identified patients with first-time IE from 2000 to 2017. Dialysis-naïve patients were grouped into: those with and those without dialysis during admission with IE. Continuation of dialysis was followed 1 year postdischarge. Multivariable adjusted Cox proportional hazard analysis was used to examine 1-year mortality for patients surviving IE according to use of dialysis. RESULTS: We included 7307 patients with IE; 416 patients (5.7%) initiated dialysis treatment during admission with IE and these were younger, had more comorbidities and more often underwent cardiac valve surgery compared with nondialysis patients (47.4% vs 20.9%). In patients with both cardiac valve surgery and dialysis treatment (n = 197), 153 (77.7%) initiated dialysis on or after the date of surgery. The in-hospital mortality was 40.4% and 19.0% for patients with and without dialysis, respectively (P < .0001). Of those who started dialysis and survived hospitalization, 21.6% continued dialysis treatment within 1 year after discharge. In multivariable adjusted analysis, dialysis during admission with IE was associated with an increased 1-year mortality from IE discharge, hazard ratio = 1.64 (95% confidence interval, 1.21-2.23). CONCLUSION: In dialysis-naïve patients with IE, approximately 1 in 20 patients initiated dialysis treatment during admission with IE. Dialysis identified a high-risk group with an in-hospital mortality of 40% and an approximate 20% risk of continued dialysis. Those with dialysis during admission with IE showed worse long-term outcomes than those without.

Hypertension, cardiovascular disease and cause of death in Danish living kidney donors: matched cohort study.

OBJECTIVES: We aimed to investigate the long-term absolute risk of hypertension and cardiovascular disease after kidney donation in living kidney donors. DESIGN: Living kidney donors were matched to 10 controls from the general population. SETTING: Multiple Danish national registries were used to identify living kidney donors from 1 January 1996 to 31 December 2017 nationwide. PARTICIPANTS: 1262 living kidney donors and 12 620 controls. MAIN OUTCOME MEASURES: Hypertension, cardiovascular disease and diabetes. RESULTS: The median age of living kidney donors was 52 (men 43%). Hypertension developed in 50 (4%) and 231 (1.8%) with a median follow-up of 7 years (IQR 3.3-12.1 years with a maximum follow-up of 22 years) and 6.9 years (IQR 3.2-11.7 years and maximum follow-up of 22 years) for donors and controls, respectively. The absolute risk of hypertension was 2.3% (95% CI 1.4% to 3.2%) and 1.2% (95% CI 1.0% to 1.4%), 4.2% (95% CI 2.8% to 5.7%) and 2.4% (95% CI 2.1% to 2.8%), 8.6% (95% CI 6.0% to 11.3%) and 3.3% (95% CI 2.8% to 3.8%) within 5, 10, 15 years for donors and controls, respectively. The ratio of the 10-year absolute risks for hypertension was 1.64 (95% CI 1.44 to 1.88) for donors compared with the controls. Two donors and four controls developed renal replacement therapy requiring end-stage renal disease during follow-up. The absolute risk of cardiovascular disease and diabetes was 7.3% (95% CI 5.7% to 9.5%) and 8.3% (95% CI 7.7% to 9.0%), 1.7% (95% CI 0.7% to 2.8%) and 3.2% (95% CI 2.7% to 3.6%) at 10 years for donors and controls, respectively. CONCLUSIONS: Living kidney donors have an increased long-term absolute risk of hypertension compared with controls from the general population.

Increased risk of Staphylococcus aureus bacteremia in hemodialysis-A nationwide study.

INTRODUCTION: Staphylococcus aureus bacteremia (SAB) is a high-risk infection and feared complication related to hemodialysis. This study aimed to investigate incidence and risk factors for SAB depending on hemodialysis access type. METHODS: The Danish National Registry on Regular Dialysis and Transplantation was used to identify patients from January 1, 1996 to December 31, 2011 with end-stage kidney disease. Patients were followed until death, the first episode of SAB, or end of study (December 31, 2011). Independent risk factors were assessed by multivariable Poisson regression with time-updated exposure variables. FINDINGS: Total of 9997 patients were included. The initial modality of renal replacement therapy was hemodialysis in 6826 patients and peritoneal dialysis in 2882 patients; 289 patients had preemptive kidney transplantation. SAB occurred in 1278 patients (12.8%). The incidence rate of SAB declined after 90 days and leveled off after 270 days in hemodialysis, peritoneal dialysis, and kidney transplanted. As compared to peritoneal dialysis, the adjusted rate ratio (RR) for SAB was 7.42 (95% CI 5.63-9.79) in uncuffed central venous catheter (CVC), 5.68 (95% CI 4.39-7.36) in cuffed CVC, 4.43 (95% CI 2.10-9.53) in arteriovenous graft, and 3.40 (95% CI 2.79-4.15) in arteriovenous fistula. SAB risk did not differ between uncuffed and cuffed CVC. The risk of SAB was increased during the first three months of renal replacement therapy especially for CVC (RR 11.37 [95% CI7.09-18.22]) compared with peritoneal dialysis. Diabetes mellitus (RR 1.35 [95% CI 1.20-1.51]) and male sex (RR 1.15 [95% CI 1.03-1.29]) were also associated with SAB. DISCUSSION: Patients on hemodialysis had a high incidence rate of SAB, particularly those undergoing hemodialysis via CVC. SAB risk was comparable for cuffed and uncuffed CVC. Diabetes mellitus, male sex, and the first three months in renal replacement therapy were independently associated with SAB.

The impact of hemodialysis on mortality risk and cause of death in Staphylococcus aureus endocarditis.

BACKGROUND: The risk of infective endocarditis (IE) is markedly increased in patients receiving chronic hemodialysis compared with the general population, but outcome data are sparse. The present study investigated causes and risk factors of mortality in a hemodialysis-treated end-stage kidney disease- (ESKD) and a non-ESKD population with staphylococcus (S.) aureus endocarditis. METHODS: Hemodialysis-treated ESKD patients with S. aureus endocarditis were identified from Danish National Registries and Non-ESKD patients from The East Danish Database on Endocarditis. For establishing the cause of death The Danish Registry of Cause of Death was used. Independent risk factors of outcome were identified in multivariable Cox regression models. RESULTS: One hundred twenty-one hemodialysis patients and 190 non-ESKD patients with S. aureus endocarditis were included during 1996-2012 and 2002-2012, respectively. The all-cause in-hospital mortality was 22.3% in hemodialysis- and 24.7% in non-ESKD patients. One-year mortality, excluding in-hospital mortality, was 26.4% in hemodialysis patients and 15.2% in non-ESKD patients. The hazard ratio of all-cause mortality in hemodialysis was 2.64 (95% CI 1.70-4.10) at > 70 days after admission compared with non-ESKD. Age (HR 1.03 (95% CI 1.02-1.04)) and diabetes mellitus (HR 2.17 (95% CI 1.54-3.10)) were independent risk factors of all-cause mortality. The hazard ratio of cardiovascular death in hemodialysis was 3.20 (95% CI 1.78-5.77) at > 81 days after admission compared with non-ESKD. Age and diabetes mellitus were independently related to cardiovascular death. CONCLUSION: All-cause in-hospital mortality rates were similar in hemodialysis and non-ESKD patients with S. aureus endocarditis whereas one-year mortality rates were significantly increased in the hemodialysis population.

Long-term causes of death in patients with infective endocarditis who undergo medical therapy only or surgical treatment: a nationwide population-based study.

OBJECTIVES: It is known that patients surviving infective endocarditis have a poor long-term prognosis; however, few studies have addressed the long-term causes of death in patients surviving the initial hospitalization. METHODS: Using Danish administrative registries, we identified patients admitted to a hospital with 1st time infective endocarditis in the period from January 1996 to December 2014, who were alive at the time of discharge. The study population was categorized into (i) patients undergoing medical therapy only and (ii) patients undergoing surgical and medical treatment. We examined the cardiovascular and non-cardiovascular causes of death. Using the Cox analysis, we investigated the associated risk of dying from a specific prespecified cause of death (heart failure, infective endocarditis and stroke) within the surgery group when compared with the medically treated group. RESULTS: We identified 5576 patients: 4220 patients belonged to the medically treated group and 1356 patients to the surgery group. At the 10-year follow-up, the mortality rate was 63.1% and 41.6% in the medically treated group and the surgery group, respectively. Cardiovascular disease was the most frequent cause of death in both groups accounting for 52.5% in the medically treated group and 55.2% in the surgery group. Patients undergoing surgery were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients [hazard ratio = 0.66 (95% confidence interval: 0.46-0.94) and hazard ratio = 0.59 (95% confidence interval: 0.37-0.96), respectively]. CONCLUSIONS: No major differences were found in the main causes of death between groups. Patients in the surgical group were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients.

Return to the workforce following infective endocarditis-A nationwide cohort study.

BACKGROUND: The ability to return to work after infective endocarditis (IE) holds important socioeconomic consequences for both patients and society, yet data on this issue are sparse. We examined return to the workforce and associated factors in IE patients of working age. METHODS: Using Danish nationwide registries, we identified 1,065 patients aged 18-60 years with a first-time diagnosis of IE (1996-2013) who were part of the workforce prior to admission and alive at discharge. RESULTS: One year after discharge, 765 (71.8%) patients had returned to the workforce, 130 (12.2%) were on paid sick leave, 76 (7.1%) received disability pension, 23 (2.2%) were on early retirement, 65 (6.1%) had died, and 6 (0.6%) had emigrated. Factors associated with return to the workforce were identified using multivariable logistic regression. Younger age (18-40 vs 56-60 years; odds ratio, 2.85; 95% CI, 1.71-4.76) and higher level of education (higher educational level vs basic school; 5.47, 2.05-14.6) and income (highest quartile vs lowest; 3.17, 1.85-5.46) were associated with return to the workforce. Longer length of hospital stay (>90 vs 14-30 days; 0.16, 0.07-0.38); stroke during IE admission (0.38, 0.21-0.71); and a history of chronic kidney disease (0.29, 0.11-0.75), chronic obstructive pulmonary disease (0.31, 0.13-0.71), and malignancy (0.39, 0.22-0.69) were associated with a lower likelihood of returning to the workforce. CONCLUSIONS: Seven of 10 patients who were part of the workforce prior to IE and alive at discharge were part of the workforce 1 year later. Younger age, higher socioeconomic status, and absence of major comorbidities were associated with return to the workforce.

Risk of Infective Endocarditis in Patients with End Stage Renal Disease.

BACKGROUND AND OBJECTIVES: Endocarditis is a serious complication in patients treated with RRT. The study aimed to examine incidence and risk factors of endocarditis in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Danish National Registry on Regular Dialysis and Transplantation contains data on all Danish patients receiving renal replacement (hemodialysis, peritoneal dialysis, or kidney transplantation) for ESRD. Incidence of endocarditis was estimated for each RRT modality. Independent risk factors of endocarditis were identified in multivariable Cox regression models. RESULTS: From January 1st, 1996 to December 31st, 2012, 10,612 patients (mean age 63 years, 36% female) initiated RRT (7233 hemodialysis, 3056 peritoneal dialysis, 323 pre-emptive kidney transplantation). Endocarditis developed in 267 (2.5%); of these 31 (12%) underwent valve surgery. The overall incidence of endocarditis was 627 per 100,000 person-years in patients receiving RRT. Incidence was higher in patients receiving hemodialysis compared with those receiving peritoneal dialysis or kidney transplantation (1092 per 100,000 person-years, 212 per 100,000 person-years, and 85 per 100,000 person-years, respectively). Adjusted hazard ratios for endocarditis in patients receiving hemodialysis were 5.46 (95% confidence interval [95% CI], 3.28 to 9.10) and 0.41 (95% CI, 0.18 to 0.91) for kidney-transplanted recipients, respectively, as compared with patients in peritoneal dialysis. The incidence of endocarditis in hemodialysis recipients with central venous catheters was more than two-fold higher as compared with those with arteriovenous fistulas. Overall mortality, subsequent to endocarditis, was 22% in-hospital and 51% at 1 year. The first 6 months in RRT, aortic valve disease, and previous endocarditis were identified as significant risk factors of endocarditis. CONCLUSIONS: Patients receiving RRT have a high incidence of endocarditis, in particular during hemodialysis treatment using central venous catheters. The first 6 months in RRT, aortic valve disease, and previous endocarditis are significant risk factors for developing endocarditis.