Catheter removal versus retention in the management of catheter-associated enterococcal bloodstream infections

BACKgrounD: Enterococci are an important cause of central venous catheter (CVC)-associated bloodstream infections (CA-BSI). It is unclear whether CVC removal is necessary to successfully manage enterococcal CA-BSI. MEthoDs: A 12-month retrospective cohort study of adults with enterococcal CA-BSI was conducted at a tertiary care hospital; clinical, microbiological and outcome data were collected. rEsuLts: A total of 111 patients had an enterococcal CA-BSI. The median age was 58.2 years (range 21 to 94 years). There were 45 (40.5%) infections caused by Entercoccus faecalis (among which 10 [22%] were vancomycin resistant), 61 (55%) by Enterococcus faecium (57 [93%] vancomycin resistant) and five (4.5%) by other Enterococcus species. Patients were treated with linezolid (n=51 [46%]), vancomycin (n=37 [33%]), daptomycin (n=11 [10%]), ampicillin (n=2 [2%]) or quinupristin/dalfopristin (n=2 [2%]); seven (n=6%) patients did not receive adequate enterococcal treatment. Additionally, 24 (22%) patients received adjunctive gentamicin treatment. The CVC was retained in 29 (26.1%) patients. Patients with removed CVCs showed lower rates of in-hospital mortality (15 [18.3%] versus 11 [37.9]; P=0.03), but similar rates of recurrent bacteremia (nine [11.0%] versus two (7.0%); P=0.7) and a similar post-BSI length of hospital stay (median days [range]) (11.1 [1.7 to 63.1 days] versus 9.3 [1.9 to 31.8 days]; P=0.3). Catheter retention was an independent predictor of mortality (OR 3.34 [95% CI 1.21 to 9.26]). ConCLusIons: To the authors’ knowledge, the present article describes the largest enterococcal CA-BSI series to date. Mortality was increased among patients who had their catheter retained. Additional prospective studies are necessary to determine the optimal management of enterococcal CA-BSI.


Catheter removal versus retention in the management of catheter-associated enterococcal bloodstream infections
The aim of the present study was to examine the epidemiology, treatment and subsequent outcomes of patients with enterococcal CA-BSI, comparing patients with retained versus removed catheters.Our hypothesis was that catheter management does not affect patient outcomes.

MEthoDs setting
Barnes-Jewish Hospital (BJH), a 1250-bed teaching hospital, is the largest hospital in Missouri (USA), and has a referral base that includes the St Louis Metropolitan area, eastern Missouri and western Illinois.It houses all medical specialties, including a stem cell transplantation unit.BJH is affiliated with the Washington University School of Medicine (St Louis, Missiouri, USA).

study design
A retrospective cohort study of patients with enterococcal CA-BSIs during their hospital stay was performed.CA-BSI was defined as enterococcal bacteremia in a patient with a central venous catheter (CVC) in place for at least 48 h and no alternative source of infection.The hospital's medical informatics database was queried for blood cultures positive for any Enterococcus species; this dataset was merged with a manually collected dataset of CVC usage in the hospital, which is part of the hospital infection control database.

Inclusion and exclusion criteria
Adult patients admitted to BJH between January 1, 2006 and December 31, 2006, who presented with, or developed, an enterococcal bloodstream infection and had a CVC present at the time of detection of this infection were included.All types and locations of CVCs were included.Blood cultures were obtained during routine care either peripherally and/or from the CVC.Patients who presented to the hospital with a CVC already in place were included.Patient history and physical examination as well as admitting diagnosis and microbiology results were reviewed to determine whether the catheter was the primary focus of the bacteremia.Patients with a primary focus of bacteremia other than the catheter, patients with a CVC in place for <48 h, and patients who died on the day of the positive blood culture were excluded.Polymicrobial infections were included except concurrent Staphylococcus aureus bacteremia or candidemia within ±3 days of the enterococcal bacteremia (n=20) because both entities are established indications for catheter removal.

Data collection
Demographic characteristics, medical history, clinical presentation, diagnostic and therapeutic procedures, antibiotic treatment and key markers of outcome (recurrence of bloodstream infection, length of hospital stay after the bloodstream infection, crude mortality) were abstracted from the medical records.Admission Charlson comorbidity and McCabe severity of illness scores were determined.Duration of catheter retention time after the bacteremia was recorded.Information on antibiotic lock therapy was collected; however, this treatment modality was not used in patients from this cohort.
Postdischarge mortality at both 30 days and three months after bacteremia was obtained from the Social Security Death Index (www.ssdi-search.com).

Definitions
Renal insufficiency was defined by a serum creatinine level >132.6 μmol/L.Sepsis and sepsis-induced hypotension were defined using established criteria (13).Appropriate therapy was defined as pathogen-directed treatment with antibiotics matching susceptibilities.A catheter was considered to be retained if it was present for the duration of the hospitalization after the first positive blood culture.Recurrence of bacteremia (used here synonymously with intermittent bacteremia) was defined as a second positive blood culture after ≥1 negative blood culture and an interval of ≥1 day during their hospitalization.Community-onset enterococcal bloodstream infection was defined as having the first positive blood culture drawn within 48 h of hospital admission.

Data analysis and statistical methods
Data entry was performed using Access and Excel (Microsoft Corporation, USA).Data analysis was performed using SPSS 17 (IBM Corporation, USA).Univariate comparisons among categorical variables and outcome measures were performed using the χ 2 test or Fisher's exact test.A two-sided P <0.05 was considered to be statistically significant.Also calculated was the absolute difference in proportion (∆ p ) of rates of outcome measures including the 95% CI of this difference to describe the precision of this point estimate.Analysis of the difference in proportions and 95% CI enabled the interpretation of statistical significance (if the 95% CI did not cross zero) as well as clinical significance (if the upper limit of the 95% CI exceeded a predefined difference).An absolute difference in recurrence of bacteremia and mortality rates of 15% was considered to represent a clinically significant difference; this estimate was chosen based on previous literature regarding catheter management and clinical experience (14,15).Comparisons among continuous independent variables were performed using the Student's t test or Mann-Whitney U test as appropriate.Variables found to have P<0.1 in univariate testing were considered for entry into a forward, stepwise multivariate logistic regression model.
The study was approved by the Washington University Human Research Protection Office (#07-0690).

Catheter management
The CVC was retained during the hospitalization in 29 (26.1%)patients.In univariate analysis, patients with removed CVCs were similar to patients whose CVC was retained (Table 1).

DIsCussIon
Removal of an intravascular catheter is, with few exceptions, considered to be an essential part of managing CA-BSI.However, robust data to support this approach are only available for a limited number of pathogens responsible for these infections.Despite the lack of sufficient data to provide an evidence-based recommendation with regard to CA-BSI caused by Enterococcus species, national guidelines recommend removing the involved catheters (9).To our knowledge, the present study represents the largest investigation into catheter management and outcomes of enterococcal bloodstream infections.
The main finding of the present study was increased mortality in patients whose catheters were retained during the hospitalization.Our findings suggest that catheter removal should be considered to improve patient survival.Also, the difference in the two outcome proportions exceeded the predetermined clinically meaningful difference of 15%, which gives us a quantitative estimate of the impact of catheter removal.The patient groups were very similar with respect to demographic characteristics and comorbidities, including adjunctive antibiotic treatment with the aminoglycoside gentamicin.These findings are congruent with the single study encountered in the scientific literature that scrutinized outcomes of enterococcal CA-BSI and specifically investigated catheter management, albeit in a smaller number of  patients (11).There, the authors retrospectively examined 61 enterococcal CA-BSI, with 82% of the episodes due to E faecalis and polymicrobial infections found in 18% of the study population.Of note, they did not exclude patients with concurrent Staphylococcus aureus or yeast bloodstream infections, although these infections likely guided catheter management significantly more than the detection of enterococci.Sandoe et al (11) evaluated whether successful treatment of a bloodstream infection was possible without removal of the catheter, which was achieved in five of 13 cases (38%).If the catheter was removed, the chance for cure was higher (40 of 48 [83%]).They found a combination of a cell wall-active agent with an aminoglycoside to be significantly more effective than monotherapy when the catheter was retained.The authors concluded that, although the removal of the catheter was performed in the majority of cases, it did not appear to be a necessary part of the management as long as antimicrobial treatment was optimized.In our study, even though we did not set cure as an end point, 67 (81.7%) of 82 patients with catheters removed survived the hospital admission and 61 (74.4%) survived at 30 days postbacteremia.These rates were much lower for patients with retained catheters.In summary, these data suggest that although enterococcal CA-BSI are not an absolute indication for catheter removal, removal should be favoured over catheter retention.Reasons for catheter retention may have been that the treating physicians of patients who were severely ill at the time of enterococcal bloodstream infection were reluctant to remove the catheter because it was essential for nonantibiotic medications; that the patients had limited options for alternative intravenous access; or that their comorbidities increased the risk of catheter removal and replacement.Catheter management may have been driven by reasons other than the infection alone, and removing the catheter could have been a lower priority or higher risk in the patients' overall medical management.Because we collected crude mortality data, it is also conceivable that patients died from causes not related to the CA-BSI.Of note, we did not observe a difference in recurrence of infection depending on catheter management; it is possible that the size of the cohort prevented us from noting a statistically significant difference.
Our patients are notable for a high percentage of comorbid conditions, including metastatic solid tumours (23%) and leukemia (25%); accordingly, the crude in-hospital mortality rate was high in our study population.An independent factor associated with death was the detection of VRE in the stool, which may be a marker for frequent health care exposure.Despite this finding, CA-BSIs with vancomycinresistant E faecium did not result in increased mortality compared with non-VRE infections.This is different from an earlier prospective study and a more recent meta-analysis, in which vancomycin resistance was found to be associated with increased mortality (16,17).Most likely, we could not replicate this association due to the small sample size.However, the association of VRE colonization with mortality has been demonstrated previously in a cohort of bone marrow transplant patients (18).
Limitations of the present study include its retrospective design, the fact that the diagnosis of recurrent infection depended on the treating physician ordering blood cultures and that postdischarge outcomes, including completion of planned antibiotic therapy, follow-up blood cultures, and catheter removal postdischarge, were not studied.In addition, catheter management is potentially influenced by other reasons for retention (difficulty of finding alternative access, bleeding diathesis) and we did not report outcomes for different catheter types.Finally, changes in the usage of daptomycin and linezolid have occurred since the time of the study.Although this was the largest study of enterococcal CA-BSI to date, it is still a relatively small sample to detect rare outcomes.

ConCLusIons
Based on our study findings, catheter removal is preferable to retention in patients with enterococcal CA-BSI.A large prospective or multicentre study should be performed to identify patients at highest risk for mortality and to add strength to our results.DECLArAtIons: None of the following authors has a conflict of interest to declare: J Marschall, ML Piccirillo, J Doherty.VJ Fraser is a consultant for Merck and Member of the Speakers' Bureau for Pfizer, Merck and Cubist Pharmaceuticals.DK Warren is a consultant for 3M Healthcare and Cardinal Health, and receives research funding from Sage Products Inc, Cubist Pharmaceuticals and 3M Healthcare.
Authors' ContrIButIons: JM and DKW devised the study; JAD generated the query based on the Medical Informatics and Infection Control databases; VJF assisted in study design; JM and MLP collected and analyzed the data, and wrote the manuscript; all authors critically reviewed the final draft of the manuscript.ACKnoWLEDgEMEnts: This study itself was performed without external financial support.JM was supported by a CTSA KL2 Career Development Award (5KL2RR024994-03) and a research grant from the Swiss National Science Foundation (PBBSB-113014); he currently receives support from the Building Interdisciplinary Research Careers in Women's Jonas Marschall MD1 , Marilyn L Piccirillo BA 1 , Victoria J Fraser MD 1 , Joshua A Doherty BS 2 , David K Warren MD MPH 1 ; for the CDC Prevention Epicenters Program 1 Division of Infectious Diseases, Washington University School of Medicine; 2 Medical Informatics, BJC Healthcare, St Louis, Missouri, USA Correspondence: Dr Jonas Marschall, Department of Infectious Diseases, Bern University Hospital and University of Bern, Friedbühlstrasse 51, Bern 3010, Switzerland.Telephone 41-31-632-9992, e-mail jonas.marschall@insel.ch