Patients with ESRD on maintenance hemodialysis are at a greater risk for bacterial infection, particularly Staphylococcus aureus infection (1–7). The annual incidence of S. aureus bacteremia in patients on hemodialysis ranges from 6 to 27% (3,8,9). Complications of S. aureus bacteremia include meningitis, endocarditis, osteomyelitis, and metastatic abscesses (10–12). Patients with ESRD who acquire S. aureus bacteremia are at greater risk of death than patients in whom bacteremia is attributable to other organisms (13).
Recently, a large, multicenter, randomized clinical trial was conducted to evaluate the efficacy and safety of a vaccine intended to reduce the incidence of S. aureus infection in adults with ESRD undergoing hemodialysis with a native-vessel fistula or synthetic or heterologous tissue graft. The trial incorporated a prospective economic evaluation. Although the vaccine was not efficacious in the study, the availability of clinical and economic data from numerous sites in the United States provided a unique opportunity to accurately examine patient characteristics associated with S. aureus infection, as well as inpatient costs, inpatient days, and mortality for patients hospitalized with S. aureus bacteremia and other types of S. aureus infection.
Materials and Methods
Patients and Settings
The randomized, placebo-controlled, double-blind, phase 3 clinical trial was conducted at 164 study sites in the United States to evaluate the efficacy and safety of a vaccine intended to reduce the incidence of S. aureus infection in adult patients with ESRD on hemodialysis (ClinicalTrials.gov identifier: NCT00071214). Eligible patients were 18 yr or older and receiving hemodialysis continuously for at least 8 wk before enrollment using a native-vessel fistula or synthetic or heterologous tissue graft. Patients were excluded if they had S. aureus infection within 3 mo of study entry, recurrent S. aureus infection with current graft, other severe viral or bacterial infection, HIV infection, current use of immunosuppressive or immunomodulatory drugs, or malignant disease in the previous 6 wk. All enrolled patients provided written informed consent to participate in the trial, including consent for the collection of hospital bills.
The clinical trial case report form was designed to collect detailed information on clinically significant infections and cultured organisms. An event notification form was used throughout the trial to report serious adverse events, including hospitalizations for S. aureus infections. This form was designed to collect hospital admission and discharge dates and information about the hospitals where patients were admitted. The form was also used to document whether patients were rehospitalized during the 12-wk period after the initial S. aureus infection for another infection or sequelae resulting from the initial infection. We used information provided in the event notification form and each patient's consent form to request hospital bills from institutions where patients were hospitalized.
On the basis of the sources of positive S. aureus cultures documented for the initial hospitalization, we categorized patients into two groups: (1) patients with S. aureus bacteremia defined as at least one positive blood culture, and (2) patients with other S. aureus infections defined as at least one positive S. aureus culture from a non-blood source and no positive blood cultures. Other S. aureus infections included osteomyelitis; septic arthritis; soft tissue abscess, cellulitis, or fasciitis; sterile space infection; and other infections; but excluded cases of pneumonia and urinary tract infection due to the greater probability of false-positive test results caused by frequent contamination (14,15). We also categorized patients with S. aureus bacteremia according to whether they also had documented S. aureus infections at other sites.
Infection episodes were defined as beginning on the date of the initial hospitalization with a positive culture for S. aureus and continuing for 12 wk. Thus, if patients were rehospitalized during the 12-wk period, these events were considered part of the infection episode. To meet the statistical assumption that all observations were independent, only the initial episode of S. aureus infection for each patient was included in the analysis.
The hospital billing data represent charges. To convert charges to costs, we derived department-level cost-to-charge ratios from each hospital's annual Medicare cost report and multiplied the ratios by department-specific inpatient charges. We adjusted costs from previous years to 2005 U.S. dollars using the Consumer Price Index for Medical Care (16). We assigned physician costs to inpatient procedures reported in the hospital bills based on the corresponding Current Procedural Terminology (CPT) codes. In addition, we assigned costs for physician rounding services for each day patients were hospitalized. We based costs for physician services on average 2005 Medicare reimbursement rates available from the Centers for Medicare and Medicaid Services (17). We summed hospital costs and physician fees to compute total inpatient costs.
We compared baseline characteristics between patients who developed S. aureus infection and patients who did not using χ2 tests for categorical variables and t tests for continuous variables. For patients hospitalized for S. aureus infection, we report descriptive statistics to summarize inpatient costs, length of stay, and mortality. We also evaluated these outcomes when stratifying patients by age, sex, race, history of diabetes mellitus, and methicillin sensitivity for the initial S. aureus isolate. We then used generalized linear regression models to identify characteristics associated with 12-wk inpatient costs, inpatient days, and mortality (18). We specified these models using gamma distributions and log links for costs, negative binomial distributions and log links for inpatient days, and binomial distributions and logit links for mortality. In unadjusted analyses, only the characteristic of interest was included in the regression models. In adjusted analyses, the regression models included age, sex, race, history of diabetes mellitus, and methicillin sensitivity for the initial S. aureus isolate. Among patients with S. aureus bacteremia, we also included a covariate representing other documented sites of S. aureus infection. To model the effect of age, we categorized patients into three age groups (<50 yr, 51 to 65 yr, and >65 yr). To model the effect of race, we categorized patients as Caucasian, African American, or other.
We used SAS version 9.1.3 (SAS Institute, Inc., Cary, North Carolina) for all analyses. The institutional review board of the Duke University Health System approved this study.
A total of 3359 patients were enrolled between January 2004 and May 2005; 279 (8.3%) developed S. aureus infection during approximately 1 yr of follow-up (mean, 369 d). Table 1 provides baseline characteristics for patients who did and did not develop S. aureus infection. Across both groups, the mean age was 58 yr, and about one-third of patients were older than 65 yr. Almost half of the patients (45.9%) were African American, not of Hispanic origin, and men comprised approximately 60% of the cohort. Patients who developed S. aureus infection were significantly more likely to have a history of diabetes mellitus, more likely to have had a hemodialysis-related infection in the previous 12 mo, more likely to be nasal carriers of S. aureus, and more likely to have an arteriovenous graft at baseline compared with those who did not develop S. aureus infection.
Among patients with S. aureus infection, 208 were hospitalized for S. aureus infection and 71 (25.4%) were treated on an outpatient basis. We obtained complete hospital billing information for 176 patients from 117 hospitals, representing 208 hospitalizations associated with S. aureus infection. After exclusion of 17 patients hospitalized for pneumonia or urinary tract infection and inclusion of only the initial episode of S. aureus infection for each patient, a total of 176 hospital bills for 159 patients were retained for further analyses of costs, length of stay, and mortality. Of the 159 patients hospitalized with S. aureus infections, 89 (56.0%) had blood cultures positive for S. aureus and 70 (44.0%) had cultures from other sources that were positive for S. aureus.
S. aureus Bacteremia
Table 2 summarizes S. aureus infections documented during initial hospitalizations and rehospitalizations occurring within 12 wk. Among 89 patients with blood cultures positive for S. aureus, the most common type of additional infection site documented during the initial hospitalization was soft tissue abscess, cellulitis, or fasciitis (19.1%). During the initial hospital stay, the average length of stay among patients with S. aureus bacteremia was 10.8 d (Table 3). Eleven patients (12.4%) were rehospitalized during the following 12 wk, and six of those patients (54.5%) continued to have blood cultures positive for S. aureus. Twelve-week mortality was 20.2%. Among the 53 patients with diabetes mellitus, seven (13.2%) died during the 12-wk period.
The mean cost associated with the initial hospitalization for patients with S. aureus bacteremia was $17,969 [95% confidence interval (CI), 14,403 to 21,974], with physician fees comprising 9.8% of the total (Table 3). Over 12 wk, mean inpatient costs increased by approximately $1500 to $19,454 (95% CI, 15,898 to 23,538).
Table 4 reports 12-wk outcomes stratified by age, sex, race, history of diabetes mellitus, methicillin resistance, and additional sites of clinically significant S. aureus infection. In unadjusted comparisons, 12-wk outcomes did not differ significantly across subgroups, with the exception that patients older than 65 yr were more likely to die than patients aged 50 yr or younger (34.5 versus 10.7%; P = 0.04), and patients with a history of diabetes mellitus were less likely to die (13.2 versus 30.6%; P = 0.05). These findings were similar in adjusted analyses, with patients older than 65 yr being more likely to die [odds ratio (OR), 7.84; 95% CI, 1.45 to 42.45; P = 0.02], and patients with a history of diabetes mellitus being less likely to die (OR, 0.21; 95% CI, 0.05 to 0.83; P = 0.03). In adjusted analyses, there was a statistical trend indicating that mean inpatient costs were 1.35 times higher among patients with additional sites of S. aureus infection compared with those without (95% CI, 0.95 to 1.92; P = 0.09).
Other Non-Bloodstream S. aureus Infection
Among the 70 patients initially hospitalized with a clinically significant non-bloodstream S. aureus infection, 68.6% had soft tissue abscess, cellulitis, or fasciitis, and 7.1% had osteomyelitis. Mean length of stay during the initial hospitalization was 9.8 d. Five patients (7.1%) were readmitted during the following 12 wk. Twelve-week mortality was 15.7%. Among the 47 patients with diabetes mellitus, seven (14.9%) died during the 12-wk period.
For patients with non-bloodstream S. aureus infections, the mean cost for the initial hospitalization was $17,056 (95% CI, 13,478 to 21,046), with physician services representing 8.0% of the total. Twelve-week costs were about $2200 higher at $19,222 (95% CI, 14,436 to 25,551).
As shown in Table 4, when stratified by patient characteristics, patients in both of the older age groups incurred inpatient costs that were approximately twice the mean cost for patients aged 50 yr or younger. In adjusted analyses, patients aged 51 to 65 yr incurred costs 1.76 times higher (95% CI, 1.04 to 2.98; P < 0.04), and patients older than 65 yr incurred costs 2.10 times higher (95% CI, 1.25 to 3.53; P < 0.01) than patients aged 50 yr or younger. Inpatient days showed similar patterns, with patients aged 51 to 65 yr incurring an average of 1.57 times more inpatient days (95% CI, 1.03 to 2.39; P = 0.04), and patients older than 65 yr incurring an average 2.11 times more inpatient days (95% CI, 1.41 to 3.16; P < 0.01) than patients aged 50 yr or younger. In unadjusted analyses, patients with a history of diabetes mellitus incurred significantly higher mean inpatient costs (means ratio, 1.85; 95% CI, 1.21 to 2.82; P < 0.01). However, after adjustment for age, sex, race/ethnicity, and sensitivity to methicillin, the significant association did not remain (means ratio, 1.32; 95% CI, 0.84 to 2.08; P = 0.23). Relative to Caucasian patients, patients who were Asian, Hispanic, or American Indian/Alaska native incurred higher costs (adjusted means ratio, 1.66; 95% CI, 0.98 to 2.79; P = 0.06). There was also a statistical trend indicating that patients with methicillin-resistant S. aureus infection incurred higher mean costs compared with patients with methicillin-sensitive S. aureus infection (adjusted means ratio, 1.39; 95% CI, 0.95 to 2.05; P = 0.09), but days in the hospital were similar at 12 wk. Among patients with non-bloodstream S. aureus infections, 12-wk mortality did not significantly differ across subgroups in unadjusted or adjusted analyses.
Despite catheter access being a primary risk factor for infection among patients on hemodialysis (19), our analyses revealed that approximately one in 12 patients receiving dialysis via arteriovenous fistula or synthetic or heterologous tissue graft developed S. aureus infection during a 1-yr period. Consistent with the published literature (2), patients with diabetes mellitus and patients with nasal carriage of S. aureus upon study entry were at a higher risk of infection. The high prevalence of both risk factors at baseline underscore their importance for patients with ESRD (20,21). This study is also consistent with previous studies showing that patients with synthetic or heterologous tissue grafts are at higher risk of S. aureus infection than patients with arteriovenous fistulas (22).
Hospitalizations for S. aureus bloodstream or non-bloodstream infections in patients undergoing hemodialysis impose considerable economic costs on the health care system. We found that, on average, patients with either type of infection were hospitalized 11 to 12 d and incurred inpatient costs of approximately $20,000 during the 12 wk after hospitalization with S. aureus infection. All-cause mortality at 12 wk was 20.2% for patients hospitalized with S. aureus bacteremia and 15.7% for patients with other types of S. aureus infection.
This study offers several methodologic advantages over other studies that have examined costs associated with S. aureus bacteremia in patients with ESRD on hemodialysis (23,24). Engemann et al. (18) used data from a single tertiary care medical center and found that the average 12-wk inpatient cost of treating S. aureus bacteremia in patients on hemodialysis was $28,473 (adjusted to 2005 dollars). Nissenson et al. (23) used data from the U.S. Renal Data System and estimated 12-wk costs of $20,915 (adjusted to 2005 dollars). Both of these studies were limited to S. aureus bacteremia, whereas ours also evaluated patients with S. aureus non-bloodstream infections. Compared with the study by Engemann et al. (24), which was limited to a single hospital, our study included patients from more than 100 institutions. Also, the cost estimates reported by Nissenson et al. (23) were based on Medicare Diagnosis-Related Group-based payments, which may not be representative of actual costs incurred by hospitals. Our study used patient-level hospital cost information that reflected care received by individual patients. In addition, we relied on data collected prospectively in a randomized clinical trial designed for regulatory approval of a vaccine and were thus subject to data monitoring and auditing processes to ensure the validity of the data across many study sites. Previous research was based on an analysis of retrospective claims data and thus depended on the accuracy of diagnosis coding (23).
Twelve-week readmission rates were remarkably similar across the three studies at 12 to 13%. Twelve-week mortality was similar in the study presented here (20.2%) and the study by Engemann et al. (24) (19.0%) (Nissenson et al. (23) did not report 12-wk mortality). Thus, in terms of patient outcomes, there is little evidence that the selection of patients into the clinical trial affected the generalizability of the study sample.
Nevertheless, a unique feature of our study was the exclusion of patients receiving hemodialysis via catheter upon entry into the study. Several studies have documented decreased use of catheters and increased use of arteriovenous fistulas in the United States (25,26). From 1998 through 2004, use of fistulas increased from 27.8 to 41.2% (26). Thus, our findings represent the increasingly prevalent use of fistulas. Furthermore, our findings provide evidence that despite the lower risk of infection conferred by the avoidance of catheters, once patients on hemodialysis develop S. aureus infection, their outcomes appear to be similar regardless of vascular access type (27).
In the study presented here, we observed significantly higher inpatient costs and more inpatient days among older patients hospitalized with non-bloodstream S. aureus infection. We did not observe this relationship among patients hospitalized with S. aureus bloodstream infection, but this was likely attributable to the significantly higher mortality rate observed among patients older than 65 yr in this cohort. Across both types of S. aureus infection, we also found evidence that costs were lower among Caucasian patients relative to other racial/ethnic groups. However, this finding may have been more a function of greater proportions of non-white patients being treated in hospitals in urban areas with higher cost structures rather than differences in resource use because inpatient days were similar across groups. An unexpected finding was that patients with diabetes mellitus hospitalized with S. aureus bacteremia were significantly less likely to die, but this finding was not observed among patients hospitalized with non-bloodstream infections. Given that there were only 18 patients with S. aureus bacteremia who died and the inconsistency of the findings across both groups of patients with S. aureus infection, we are uncertain about the prognostic power of diabetes mellitus as a mortality risk factor among patients with ESRD and bacteremia.
Our study has several limitations. First, the analysis is limited to inpatient costs for patients hospitalized with S. aureus infection. Although this is consistent with previous analyses, approximately 25% of patients with a positive culture for S. aureus were treated on an outpatient basis; however, for patients treated on an inpatient basis the exclusion of outpatient costs is unlikely to have a significant effect on the results. In the study by Engemann et al. (24), outpatient costs represented only 0.4% of total costs ($118). Second, the analysis was not limited to admissions due to S. aureus infection. Thus, for patients with nosocomial infections, some proportion of inpatient costs is not attributable to S. aureus infection. Approximately 11% of patients had documentation of a positive culture at least 2 d after admission. Third, for patients hospitalized with S. aureus bacteremia with additional sites of S. aureus infection, we did not have information on the timing of positive cultures; thus, we could not determine whether the additional sites of infection were a potential source or complication of S. aureus bloodstream infection. Fourth, the prevalence of other sites of infection was unexpectedly low among patients hospitalized with S. aureus bacteremia. One possible explanation is that, because S. aureus bacteremia was the primary endpoint in the trial, site investigators may have been less likely to report additional sites of S. aureus infection. Also, the case report form for the trial indicated that documentation of other sites of S. aureus infection should include those that were “clinically significant.”
Lastly, billing data were not collected for hospitalizations for reasons other than S. aureus infection. Although we were not able to directly compare inpatient costs associated with S. aureusversus other conditions, our estimate of the cost associated with S. aureus infection at approximately $19,000 per episode is higher than the estimate of $13,186 for inpatient costs associated with vascular access placement reported in the U.S. Renal Data System 2007 Annual Data Report (26). These costs are significant given that patients undergoing hemodialysis are hospitalized an average of 2 times per year and approximately one in 20 hospitalizations are due to infectious diseases. Furthermore, the overall mean annual cost of medical care for patients undergoing dialysis was estimated at $65,405 in 2005 (26).
This study using robust data from a large, multicenter, randomized trial confirms that the effect of S. aureus infection on inpatient costs and mortality is significant in patients on hemodialysis. Patients hospitalized with S. aureus bacteremia plus an associated infection incurred higher 12-wk inpatient costs than patients without associated infections. Interventions to reduce the incidence of S. aureus infections in this high-risk population could reduce the overall economic burden associated with ESRD.
Dr. Hohenboken is an employee of Nabi Biopharmaceuticals. Dr. Griffiths is a consultant for Nabi Biopharmaceuticals. Dr. Stryjewski has received research funding from and is a consultant for Theravance, Inc. Dr. Schulman has received research funding from Nabi Biopharmaceuticals and has made available online a detailed listing of financial disclosures (http://www.dcri.duke.edu/research/coi.jsp). Dr. Fowler has received research funding from and is a consultant for Nabi Biopharmaceuticals. Dr. Reed has received research funding from Nabi Biopharmaceuticals and has made available online a detailed listing of financial disclosures (http://www.dcri.duke.edu/research/coi.jsp). Mss. Li, Friedman, and O'Neal and Drs. Middleton and Inrig did not report any financial disclosures.
This study was funded in part by a research agreement between Nabi Biopharmaceuticals and Duke University. We thank Carolyn Cotton, Kate Barr, and Janice Tzeng of Duke University for assistance with data acquisition and research support; and Damon Seils of Duke University for assistance with manuscript preparation.
Published online ahead of print. Publication date available at www.cjasn.org.
1. Sexton DJ: Vascular access infections in patients undergoing dialysis with special emphasis on the role and treatment of Staphylococcus aureus. Infect Dis Clin North Am15 :731– 742,2001
2. Powe NR, Jaar B, Furth SL, Hermann J, Briggs W: Septicemia in dialysis patients: Incidence, risk factors, and prognosis. Kidney Int55 :1081– 1090,1999
3. Quarles LD, Rutsky EA, Rostand SG: Staphylococcus aureus bacteremia in patients on chronic hemodialysis. Am J Kidney Dis6 :412– 419,1985
4. Marr KA, Sexton DJ, Conlon PJ, Corey GR, Schwab SJ, Kirkland KB: Catheter related bacteremia and outcome of attempted catheter salvage in patients undergoing hemodialysis. Ann Intern Med127 :275– 280,1997
5. Kessler M, Hoen B, Mayeux D, Hestin D, Fontenaille C: Bacteremia in patients on chronic hemodialysis. A multicenter prospective survey. Nephron64 :95– 100,1993
6. Marr KA: Staphylococcus aureus bacteremia in patients undergoing hemodialysis. Semin Dial13 :23– 29,2000
7. MMWR Weekly Invasive Methicillin-Resistant Staphylococcus aureus Infections Among Dialysis Patients—United States, 2005. March 9, 2007.56 :197– 199. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5609a3.htm
8. Nielsen J, Kolmos HJJ, Espersen F: Staphylococcus aureus bacteraemia among patients undergoing dialysis—Focus on dialysis catheter-related cases. Nephrol Dial Transplant13 :139– 145,1998
9. Neilsen J, Ladefoged SD, Kolmos HJJ: Dialysis catheter-related septicaemia—Focus on Staphylococcus aureus septicaemia. Nephrol Dial Transplant13 :2847– 2852,1998
10. Gonza[Combining Acute Accent]lez C, Rubio M, Romero-Vivas J, Gonza[Combining Acute Accent]lez M, Picazo JJ: Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms. Clin Infect Dis29 :1171– 1177,1999
11. Fowler VG Jr, Miro JM, Hoen B, Cabell CH, Abrutyn E, Rubinstein E, Corey GR, Spelman D, Bradley SF, Barsic B, Pappas PA, Anstrom KJ, Wray D, Fortes CQ, Anguera I, Athan E, Jones P, van der Meer JT, Elliott TS, Levine DP, Bayer AS, ICE Investigators: Staphylococcus aureus endocarditis: A consequence of medical progress. JAMA293 :3012– 3021,2005
12. Mal S, Berendt AR, Peacock SJ: Staphylococcus aureus bone and joint infection. J Infect44 :143– 151,2002
13. Danese MD, Griffiths RI, Dylan M, Yu HT, Dubois R, Nissenson AR: Mortality differences among organisms causing septicemia in hemodialysis patients. Hemodial Int10 :56– 62,2006
14. Ruiz M, Arosio C, Salman P, Bauer TT, Torres A: Diagnosis of pneumonia and monitoring of infection eradication. Drugs60 :1289– 1302,2000
15. Lifshitz E, Kramer L: Outpatient urine culture: Does collection technique matter? Arch Intern Med160 :2537– 2540,2000
16. U.S. Department of Labor, Bureau of Labor Statistics. Available at: http://www.bls.gov/cpi/home.htm
17. Centers for Medicare and Medicaid Services. National Physician Fee Schedule Payment Amount File. Available at: http://www.cms.hhs.gov/PhysicianFeeSched/01_overview.asp
18. McCullagh P, Nelder JA: Generalized Linear Models, 2nd ed., London, Chapman & Hall,1989
19. Combe C, Pisoni RL, Port FK, Young EW, Canaud B, Mapes DL, Held PJ: Dialysis outcomes and practice patterns study (DOPPS) data on the use of central venous catheters in chronic hemodialysis. Nephrologie22 :379– 384,2000
20. Cavanaugh K, Merkin S, Plantinga L, Fink N, Sadler J, Powe N: Accuracy of patients’ reports of comorbid disease and their association with mortality in ESRD. Am J Kidney Dis52 :118– 127,2008
21. Lederer SR, Riedelsdorf G, Schiffl H: Nasal carriage of methicillin resistant Staphylococcus aureus: The prevalence, patients at risk and the effect of elimination on outcomes among outclinic haemodialysis patients. Eur J Med Res12 :284– 288,2007
22. Klevens RM, Edwards JR, Andrus ML, Peterson KD, Dudeck MA, Horan TC: NHSN participants in outpatient dialysis surveillance. Dialysis surveillance report: National Healthcare Safety Network (NHSN)-data summary for 2006. Semin Dial21 :24– 28,2008
23. Nissenson AR, Dylan ML, Griffiths RI, Yu HT, Dean BB, Danese MD, Dubois RW: Clinical and economic outcomes of Staphylococcus aureus septicemia in ESRD patients receiving hemodialysis. Am J Kidney Dis46 :301– 308,2005
24. Engemann JJ, Friedman JY, Reed SD, Griffiths RI, Szczech LA, Kaye KS, Stryjewski ME, Reller LB, Schulman KA, Corey GR, Fowler VG Jr: Clinical outcomes and costs due to Staphylococcus aureus bacteremia among patients receiving long-term hemodialysis. Infect Control Hosp Epidemiol26 :534– 539,2005
25. Rayner HC, Besarab A, Brown WW, Disney A, Saito A, Pisoni RL: Vascular access results from the Dialysis Outcomes and Practice Patterns Study (DOPPS): Performance against Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines. Am J Kidney Dis44[ Suppl 2]:22– 26,2004
26. U.S. Renal Data System. USRDS 2007 Annual Data Report: Atlas of End-Stage, Renal Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD,2007
27. Inrig JK, Reed SD, Szczech LA, Engemann JJ, Friedman JY, Corey GR, Schulman KA, Reller LB, Fowler VG Jr: Relationship between clinical outcomes and vascular access type among hemodialysis patients with Staphylococcus aureus bacteremia. Clin J Am Soc Nephrol1 :518– 524,2006