Carsten T. Larsen

Severity of Gentamicin's Nephrotoxic Effect on Patients with Infective Endocarditis: A Prospective Observational Cohort Study of 373 Patients

BACKGROUND Gentamicin is often used to treat infective endocarditis (IE). Gentamicin is highly effective, but its applicability is reduced by its nephrotoxic effect. The aim of this study was to quantify the nephrotoxic effect of gentamicin and the association between the nephrotoxic effect and mortality in patients with IE. METHODS A prospective observational cohort study was performed at 2 tertiary university hospitals in Copenhagen from October 2002 through October 2007; 373 consecutive patients with IE were included. A total of 287 (77%) of the patients received gentamicin treatment (median duration, 14 days); dosage was adjusted according to daily serum creatinine and trough serum gentamicin levels. Kidney function was determined by estimated endogenous creatinine clearance (EECC). Statistical correlation between gentamicin and EECC change was analyzed, and the association between mortality and nephrotoxicity was investigated. RESULTS The primary bacteriological etiologies were as follows: Streptococcus species (37.1%), Staphylococcus aureus (18.2%), and Enterococcus species (16.1%). In the gentamicin group, the mean EECC change was an 8.6% decrease, but in the no-gentamicin group, the mean change was an increase of 2.3% (P = .05). The decrease in EECC was significantly correlated with the duration of gentamicin treatment: a 0.5% EECC decrease per day of gentamicin treatment (P = .002). The decrease in EECC during hospitalization was not related to postdischarge mortality. The mean duration of follow-up was 562 days. CONCLUSIONS The nephrotoxic effect of gentamicin is directly related to treatment duration, with a decrease in EECC of 0.5% per day of gentamicin treatment. In patients treated with gentamicin, the in-hospital decrease in EECC was not related to postdischarge mortality. Consequently, this study does not support abolishment of gentamicin in treatment of IE.

Major Cerebral Events in Staphylococcus Aureus Infective Endocarditis: Is Anticoagulant Therapy Safe?

Objectives: To study the impact of anticoagulation on major cerebral events in patients with left-sided Staphylococcus aureus infective endocarditis (IE). Methods: A prospective cohort study; the use of anticoagulation and the relation to major cerebral events was evaluated separately at onset of admission and during hospitalization. Results: Overall, 70 out of 175 patients (40%; 95% CI: 33–47%) experienced major cerebral events during the course of the disease, cerebral ischaemic stroke occured in 59 patients (34%; 95% CI: 27–41%), cerebral infection in 23 patients (14%; 95% CI: 9–19%), and cerebral haemorrhage in 5 patients (3%; 95% CI: 0.5–6%). Patients receiving anticoagulation were less likely to have experienced a major cerebral event at the time of admission (15%) compared with those without anticoagulation (37%, p = 0.009; adjusted OR: 0.27; 95% CI: 0.075–0.96; p = 0.04). In-hospital mortality was 23% (95% CI: 17–29%), and there was no significant difference between those with or without anticoagulation. Conclusions: We found no increased risk of cerebral haemorrhage in S. aureus IE patients receiving anticoagulation. Anticoagulation was associated with a reduced risk of cerebral events before initiation of antibiotics. Data support the continuance of anticoagulation in S. aureus IE patients when indicated.

The impact of cardiac surgery in native valve infective endocarditis: Can euroSCORE guide patient selection?

BACKGROUND Decision making regarding surgical intervention in native valve endocarditis (NVE) is often complex and surgery is withheld in a number of patients either because medical treatment is considered the best treatment or because the risk of operation is considered too high. The objective of this study was to investigate the outcome of surgical treatment and to validate the ability of euroSCORE to predict operative mortality in NVE patients. METHODS Prospective cohort study including 323 consecutive NVE patients. Patients were divided into 3 groups based on treatment strategy and indication/contraindication for surgery. The additive and logistic euroSCORE was calculated and the observed and predicted mortality was compared. RESULTS Cardiac surgery was associated with a good prognosis, in-hospital and after 12months, compared to conservative treatment. After adjustment for confounders surgery was associated with a survival benefit (hazard ratio (HR) 0.45, 95% CI: 0.27-0.76%; p=0.003). When propensity score was used in regression adjustment, cardiac surgery was still associated with a better outcome after 12months (HR 0.41, 95% CI: 0.25-0.68; p<0.001). Observed mortality for patients receiving surgical treatment was 11% compared to a mean logistic euroSCORE mortality of 16% (NS). The discriminating ability of euroSCORE was good, area under the ROC curve 0.74 (95% CI: 0.64-0.84; p<0.001) logistic model and 0.75 (95% CI: 0.65-0.86; p<0.001) additive model. CONCLUSIONS Cardiac surgery was associated with a good prognosis when indicated regardless of euroSCORE, and surgery should only be withheld after thorough consideration. EuroSCORE remains a valuable tool to identify high-risk IE patients when surgery is considered.

In infectious endocarditis patients mortality is highly related to kidney function at time of diagnosis: A prospective observational cohort study of 231 cases☆

BACKGROUND Infective endocarditis is a serious disease with a high mortality even with optimal treatment and care. A number of complicating conditions are known to be of importance for the outcome. But only few data are available in IE patients on the independent prognostic value of kidney function at the time of admittance. METHODS In a prospective observational cohort study data from 235 consecutive IE patients were collected at 2 tertiary heart centres in Copenhagen. Kidney function was evaluated as Estimated Endogenous Creatinine Clearance (EECC) calculated at the time of admission. Patients were divided into 4 groups according to their EECC: 1) >90 ml/min, 2) 60-90 ml/min, 3) 30-60 ml/min and 4) <30 ml/min. Mortality statistical analysis was then applied. RESULTS >Gender: 70.2% male, mean age: 61.3+/-SD 15.0. The most common pathogens were streptococcus species (32.9%) and Staphylococcus aureus (21.8%). Mean follow-up time was 453 days (SD 350). A total number of 76 patients died (32%), with an in-hospital mortality of 14%, and a post discharge mortality of 18%. In 64.9% EECC was decreased at time of admission, and a highly significant relationship between EECC and mortality was demonstrated, P<0.001. For every decrease of 10 ml/min in EECC we found an increase in Hazard Ratio for mortality of 23.1% (CI 13.2-33.8), P<0.001. CONCLUSION Decreased kidney function is prevalent in patients with endocarditis. Calculated EECC at the time of admission is easily obtained in all IE patients and has a high and independent predictive prognostic value for mortality.

Once versus Twice Daily Gentamicin Dosing for Infective Endocarditis: A Randomized Clinical Trial

Objectives: The aim of this randomized study was to investigate the effects of once versus twice daily gentamicin dosing on renal function and measures of infectious disease in a population with infective endocarditis (IE). Methods: Seventy-one IE patients needing gentamicin treatment according to guidelines were randomized to either once (n = 37) or twice daily (n = 34) doses of gentamicin. Kidney function (glomerular filtration rate, GFR) was measured with an isotope method (51Cr-EDTA) at the beginning of treatment and at discharge. Treatment efficacy was assessed by C-reactive protein (CRP) time to half-life, mean CRP and leukocytes. Results: Baseline GFR was similar in the two groups. Both groups displayed a significant fall in GFR from admission to discharge. The mean decrease in GFR was as follows: with once daily gentamicin, 17.0% (95% confidence interval 7.5–26.5), and with twice daily gentamicin, 20.4% (95% confidence interval 12.0–28.8). However, there was no significant difference in the GFR decrease between the once and twice daily regimens (p = 0.573). No difference in infection parameters was demonstrated between the two dosing regimens. Conclusions: A twice daily gentamicin dosing regimen is neither less nephrotoxic nor more efficient than a once daily regimen in the treatment of IE patients. When indicated, gentamicin may therefore also be administered as a single-dose regimen in the treatment of IE patients.

Infective endocarditis: Long-term reversibility of kidney function impairment. A 1-y post-discharge follow-up study

Abstract The aim of this study was to quantify the long-term reversibility of kidney function decrease occurring during hospitalization and treatment for infective endocarditis (IE). A prospective observational cohort study was performed at a tertiary university hospital in Copenhagen from October 2002 through May 2008; 223 consecutive IE patients were included. Forty patients died in hospital and 38 within 1 y of discharge. Of the 145 patients called in for the 1-y follow-up, 111 accepted. Kidney function was assessed by estimated endogenous creatinine clearance (EECC). Statistical correlation between EECC at admission, discharge and follow-up, as well as correlations between gentamicin and EECC changes, were analyzed. In the 111 follow-up patients, the bacteriological aetiologies were: Streptococcus species (47.7%), Enterococcus (16.2%) and Staphylococcus aureus (11.7%). The mean EECC decrease from admission to discharge was 8.4% (95% confidence interval 1.6–15.2; p < 0.001). However this kidney function impairment was reversed at the 1-y follow-up. When divided into subgroups, a full kidney function restitution was seen in only 35.1% of patients with an EECC decrease of >22%. In conclusion, kidney function impairment occurring during hospitalization for IE is potentially reversible within the first y post-discharge.

One-year mortality in coagulase-negative Staphylococcus and Staphylococcus aureus infective endocarditis.

The aim of this study was to investigate in-hospital mortality and 12-month mortality in patients with coagulase-negative Staphylococcus (CoNS) compared to Staphylococcus aureus (S. aureus) infective endocarditis (IE). We used a prospective cohort study of 66 consecutive CoNS and 170 S. aureus IE patients, collected at 2 tertiary university hospitals in Copenhagen (Denmark) and at 1 tertiary university hospital in Gothenburg (Sweden). Median (range) C-reactive protein at admission was higher in patients with S. aureus IE (150 mg/l (1–521) vs 94 mg/l (6–303); p<0.001), which may suggest a more serous infection. CoNS was associated with prosthetic valve IE (49% vs 24%; p<0.001) and median diagnostic delay was longer in CoNS IE patients (20 d (0–232) vs 9 d (0–132); p<0.001). In-hospital mortality was equally high in both groups but 25% of the CoNS IE patients had died after 1 y compared to 39% of patients with S. aureus IE (p =0.05). In conclusion, CoNS IE was associated with a long diagnostic delay and high in-hospital mortality, whereas post-discharge prognosis was better in this group of patients compared to patients with IE due to S. aureus.

Blood pressure level and relation to other cardiovascular risk factors in male hypertensive patients without clinical evidence of ischemic heart disease.

Arterial hypertension is accompanied by increased morbidity and mortality and constitutes a substantial part of medical care. Antihypertensive intervention reduces the cardiovascular morbidity and mortality. The aims of the study were to evaluate the relationship between cardiovascular risk factors and the blood pressure (BP), and to evaluate the percentage of patients who had achieved a BP level as recommended by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). BP was evaluated in relation to age, body mass index, duration of hypertension, cholesterol and triglyceride level, smoking status, information of regular exercise, a family history of ischemic heart disease (IHD) and drug treatment, in 220 men treated for arterial hypertension. In the univariate analyses we found a higher systolic blood pressure (SBP) with older age, higher SBP in smoking patients and lower SBP in patients with regular exercise. In a multivariate model age (p = 0.0004), smoking status (p = 0.01) and regular exercise (p = 0.06) were independently associated with SBP. There was a lower diastolic blood pressure (DBP) with older age, and age was independently associated with DBP. Office SBP was above 140 mmHg in 83% and above 160 mmHg in 44% of patients. During ambulatory blood pressure monitoring (AMBP), SBP was above 135 mmHg in 40% and above 155 mmHg in 15% of patients. In addition to male sex and hypertension there was a high percentage of other cardiovascular risk factors-43% was smoking, 21% had a family history of IHD, 77% had a se-cholesterol above 5.5 mmol/l and 48% had a se-triglyceride above 1.6 mmol/l. In a consecutive group of asymptomatic male treated hypertensive patients SBP is independently associated with age and smoking status, and DBP with age. A high percentage of the patients do not have a well controlled BP, and a high percentage have additional risk factors such as smoking, hypercholesterolaemia, hypertriglyceridaemia and a family history of IHD. This means that there is room for much improvement in the control of hypertension.

Dihydroergotamine and mobilization after major orthopedic surgery

The effects of dihydroergotamine (DHE) on the degree of mobilization and response to orthostatic stress after total hip arthroplasty were studied. In the mobilization study, 78 patients received DHE, 0.5 mg im, twice a day from the day of surgery until full mobilization was achieved. Eighty‐four patients who received placebo served as controls. There was no significant difference in the time until the first day of mobilization or the degree of mobilization. In the orthostatic test condition, subgroups of 61 patients receiving placebo and 55 patients receiving DHE were subjected to orthostatic testing. There were no differences in cardiovascular response to bed rest or in orthostatic stress. We conclude that DHE does not stabilize the cardiovascular reaction to orthostatic stress, nor does it enhance mobilization in patients after total hip arthroplasty.