JAC Advance Access originally published online on April 5, 2006
Journal of Antimicrobial Chemotherapy 2006 57(6):1172-1180; doi:10.1093/jac/dkl103
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Antibiotic-lock therapy for long-term intravascular catheter-related bacteraemia: results of an open, non-comparative study
1 Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Medicine Department Barcelona, Spain 2 Microbiology Department, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona Barcelona, Spain
*Corresponding author. Tel: +34-93-274-60-90; Fax: +34-93-428-27-62; E-mail: nufernan{at}gmail.com
Received 19 February 2006; accepted 6 March 2006
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Abstract |
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Background: Infection is one of the main problems associated with long-term central venous catheters. This study assesses the effectiveness of antibiotic-lock therapy (ALT) for treating catheter-related bacteraemia (CRB).
Methods: CRB was defined as quantitative blood culture counts through any catheter lumen 5-fold greater than concurrent peripheral blood culture, and qualitative blood culture positive for the same microorganism in all samples. Systemic treatment and ALT were started simultaneously using vancomycin (2000 mg/L) for Gram-positive organisms, and ciprofloxacin or amikacin (2000 mg/L) for Gram-negative bacilli. Heparin was added to ALT. Effectiveness was assessed by clinical and microbiological criteria. Cure was defined as negative blood cultures at both sites without catheter removal at 1 month after the completion of therapy.
Results: A total of 115 episodes of CRB in 98 patients were analysed. Catheters were used for chemotherapy (50 episodes), haemodialysis (37), total parenteral nutrition (24) and combined chemotherapy and nutrition (4). Median time from catheter placement to CRB onset was 105 days (IQ range 26–210). Aetiologies included Gram-positive organisms [56 coagulase-negative staphylococci (CoNS), 20 Staphylococcus aureus and 5 other organisms] in 81 episodes (70%), Gram-negative bacilli (11 Escherichia coli, 5 Pseudomonas aeruginosa and 10 other organisms) in 26 (23%) and polymicrobial in 8 (7%). A total of 94 episodes were cured (82%). There were 21 therapeutic failures: 9 S. aureus (1 related death), 9 CoNS, 1 P. aeruginosa, 1 Proteus vulgaris and 1 polymicrobial. Median catheter follow-up in therapeutic success was 168 days (range 7–2740).
Conclusions: ALT combined with systemic antibiotics seems to be effective for treating CRB, especially in Gram-negative and CoNS episodes. S. aureus CRB had an elevated rate of therapeutic failure.
Keywords: long-term central venous catheters , conservative treatment , outcome
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Introduction |
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An increasing number of patients require long-term central venous catheters (LTCVCs), particularly for haemodialysis, total parenteral nutrition and chemotherapy. However, catheters are not exempt from complications, the most important being thrombosis and infection. The incidence of long-term catheter-related bacteraemia (CRB) is estimated at 2.8–14 episodes/1000 catheter-days.1–4
CRB usually requires systemic antimicrobial therapy and catheter removal. However, the loss of an access vein, the need for a new procedure to replace the catheter and the cost of catheter replacement all argue in favour of attempting to salvage the infected lines when the clinical situation allows it.
Various approaches have been used for this purpose. Some studies focus on preventive actions involving the use of tunnelled catheters5 and Segur-lock® devices,6 or elimination of intraluminal colonization before bacteraemia develops.7–12 Another strategy, once catheter-related sepsis is established, is a combination of antibiotic-lock therapy (ALT) and systemic antimicrobial therapy. The first step in this last conservative approach is to diagnose CRB without removing the line. This is now possible using peripheral and endoluminal quantitative blood cultures (QNBCs), as was established in a recent meta-analysis,13 or the difference in time-to-positivity between central and peripheral blood samples.14
The most common route of bacterial contamination in long-term catheters is through the hub,14–16 and this supports ALT as a suitable treatment method. Originally described by Messing et al.,17 antibiotic-lock consists of closing the catheter and exposing its internal surface to a high concentration of appropriate antibiotic to eradicate the colonizing organism.
Antibiotic-lock has shown success in sterilizing infected central lines in various clinical situations,12,17–24 although only one of these studies was a randomized, placebo-controlled trial.24 Some aspects of this conservative approach still remain to be clarified: microorganisms allowing ALT, optimal antimicrobial agents and doses, use of heparin and the length of treatment.
The aim of this study was to evaluate the effectiveness of combining ALT with systemic therapy to treat CRB in patients with LTCVCs and to determine which microorganisms are more effectively treated with this technique.
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Patients and methods |
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Study location and patients
All consecutive adult patients bearing an LTCVC, who developed CRB between January 1997 and January 2006, and having none of the exclusion criteria were treated conservatively. The study was conducted at Hospital Universitari Vall d'Hebron, a 1000 bed teaching hospital in Barcelona, Spain.
Study design and data collection
A retrospective study of clinical records was conducted for cases between January 1997 and March 2003. Episodes were identified from our nosocomial bacteraemia database. The study was prospective between April 2003 and January 2006. All cases without exception were prospectively evaluated by a staff member of the Infectious Diseases Department. Demographic, clinical, diagnostic, treatment and follow-up data were obtained by detailed chart abstraction using standardized reporting forms. Data were entered into a database [Microsoft® Access 2000 (9.0.3821SR-1)].
Exclusion criteria
Patients with any of the following factors were excluded from ALT: pocket, tunnel or exit-site infection; complicated CRB (endocarditis, osteomyelitis or septic thrombophlebitis); candidaemia; or haemodynamic instability at the moment of diagnosis. In the prospective study, patients with Staphylococcus aureus CRB were excluded, except when there was not an alternative venous access and when the patients did not meet any other exclusion criterion. Excluded patients were treated with systemic antimicrobials and by catheter removal.
Definitions
Only LTCVC-associated episodes of bacteraemia were studied. LTCVC was defined as a permanent or temporary jugular, subclavian or femoral catheter placed for chemotherapy, total parenteral nutrition or haemodialysis.
LTCVCs were classified as follows: (i) non-tunnelled: radiopaque, single or multi-lumen polyurethane catheter percutaneously inserted into a central vein (subclavian, internal jugular or femoral); (ii) tunnelled: radiopaque, single or double-lumen silicone catheter inserted into the internal jugular vein by a subcutaneous distal route; (iii) totally implantable: radiopaque, tunnelled beneath skin, catheter inserted into the subclavian or internal jugular veins with a subcutaneous port accessed with a needle.
Microbiological studies
CRB was suspected when a patient with an LTCVC developed unexplained fever (temperature >37.5°C) and/or clinical signs of sepsis in the absence of documented infection. Microbiological studies included two blood cultures peripherally drawn 15 min apart, a quantitative culture obtained from a peripheral vein by standard venipuncture and a quantitative blood culture (QNBC) obtained through each catheter lumen.
For qualitative blood cultures (QLBCs) 8–10 mL of blood was drawn and placed in aerobic and anaerobic media. Two methods were used for the blood culture: in the first period (1997–1999) the BACTEC 9240 system (Becton Dickinson, San Jose, CA, USA), with two vials for each culture (PLUS aerobic/F and PLUS anaerobic/F media), and in the second period (2000–2006) the BACT/ALERT® system (BioMerieux, Durham, NC, USA), also with a pair of vials (FAN aerobic and FAN anaerobic media).
For QNBCs 1–3 mL of blood was obtained by venipuncture and through each lumen, and was inoculated into sterile tubes containing sodium polyanetholesulphonate as the anticoagulant (Diagnolab, Barcelona, Spain). Blood was mixed with 20 mL of brain heart infusion agar, poured into Petri plates, incubated at 35°C for 5 days, and examined daily. Colony-forming units (cfu) were counted. The number of cfu/mL was calculated by a simple rule of three.25
Presumptive identification of the microorganism was made by Gram staining of a positive culture. Definitive identification was performed with standard procedures on an automatic system (AMS-Vitek; McDonell Douglas Health Systems Company, St Louis, MO, USA) or API System (BioMerieux, Durham, NC, USA).
Antimicrobial susceptibility was assessed according to Clinical and Laboratory Standards Institute (CLSI) recommendations, using Mueller–Hinton agar (Kirby Bauer diffusion method) and Rosco discs (Neo-Sensilab, Rosco Diagnostica, Trastrup, Denmark).
Catheter-related bacteraemia
CRB was established with all three of the following conditions: (i) the same organism isolated from one or more peripheral blood samples and one or more catheter lumen samples; (ii) 5-fold or more increase in cfu/mL between QNBCs obtained through the catheter and the peripheral vein;25 and (iii) no primary source of infection other than the LTCVC identified clinically or bacteriologically.
Systemic antimicrobial treatment and ALT
After drawing of blood, patients who appeared to have CRB were empirically treated with local and systemic vancomycin, or with ciprofloxacin if there was a previous medical history of CRB due to Gram-negative bacilli. In the absence of subsequent bacteriological confirmation, antibiotics were discontinued or modified according to the patient's clinical course.
Patients in whom long-term CRB was demonstrated and all exclusion criteria ruled out received specific systemic antimicrobial treatment combined with ALT from the first day to the end of therapy, a minimum of 3 days in the retrospective study. For the prospective study we established a standard length of therapy of 10–14 days. The antimicrobials and dosage used for ALT were as follows: vancomycin (2000 mg/L) for Gram-positive organisms and ciprofloxacin (2000 mg/L) for Gram-negative bacilli. In case of resistance to ciprofloxacin, we used amikacin at the same doses. In each lumen of non-tunnelled and tunnelled LTCVCs 2 mL was inoculated, and 3 mL was inoculated in totally implantable LTCVCs. For infections due to both Gram-positive and Gram-negative organisms, we used a mixture of vancomycin and ciprofloxacin for ALT. Sodium heparin (20 IU/mL) was added to the antibiotic-lock preparation. The concentrations of antibiotics and heparin used were based on available data on stability and duration of antibacterial effectiveness at these concentrations for room and body temperature up to 10 days.26 Infected LTCVCs were not used during treatment except for haemodialysis, and the first QNBC control was performed 72 h after starting the treatment. When QNBC was positive, a new QNBC was performed 72 h later followed by ALT. When QNBC was negative, a new control was performed every 7 days until the end of therapy, and then 72 h later. ALT was replaced after each QNBC control and after each session in patients with haemodialysis catheters. Antibiotic-lock solution was not flushed into the bloodstream but removed before fresh re-instillation of a new ALT.
Treatment was explained to the patients. However, there was no written informed consert from them and the study did not require ethics approval.
Clinical course
Patients were clinically assessed every day for the first 2 weeks. Criteria for catheter removal under antibiotic treatment included phlebitis and/or purulent exudate at the catheter insertion site, catheter thrombosis, deterioration of the patient's clinical course (e.g. septic shock, respiratory failure or disseminated intravascular coagulation), suspected pulmonary thromboembolism and/or bacterial endocarditis, and persistent fever and/or bacteraemia after 72 h of antibiotic therapy.
Follow-up was done with the catheter in place in all patients until death, until catheter removal for any reason or until last visit at the end of the study (February 2006). A first visit was performed 2 weeks after the end of therapy, and thereafter follow-up was done through clinical records.
Endpoints
Related mortality and effectiveness were the primary endpoints. Cure, treatment failure and relapse were defined as follows: (i) cure: QNBC and QLBC both negative without catheter removal at 1 month after the completion of antimicrobial therapy; (ii) treatment failure: fever or positive QLBC persisting 72 h after the start of ALT and systemic treatment, catheter thrombosis, subcutaneous tunnel infection, metastatic focus or septic shock after the start of treatment; and (iii) relapse: new episode with the same organism (identical genus, species, biotype and antibiotype) in less than 30 days after the completion of treatment for the first episode. Relapse was considered failure in all cases.
Secondary end-points included a description of the aetiologies, determination of organisms most susceptible to treatment with this technique, length of treatment and follow-up.
Statistical analysis
Statistical analyses were performed using Microsoft SPSS-PC+, version 12.0 (SPSS, Chicago, IL, USA). Quantitative variables were described as median and range, or median and 25th–75th percentile values (IQ range). The 
2 test (or Fisher's exact test) was used to compare the distribution of categorical variables, and Student's t-test was used for continuous variables. Differences were considered significant at P < 0.05.
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Results |
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Table 1 shows demographics, description of catheters, overall aetiology, length of treatment, outcome, and follow-up characteristics of both the retrospective and prospective episodes. Both subgroups were quite similar and this fact allowed a further overall analysis. The only differences between them were the length of systemic treatment (but not the length of ALT), absence of non-tunnelled catheters in the prospective study and length of follow-up. Table 2 specifies the aetiology of all 115 episodes.
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Patients with more than one episode of long-term CRB
Ten patients (10%) presented more than one episode of CRB without catheter-removal, as described in Table 3. One patient had four different episodes, one patient three episodes and the remaining eight patients two different episodes each. Episodes of CRB caused by coagulase-negative staphylococci (CoNS) in patients 1, 2, 11, 66 and 85 had isolates of the same species with different antibiotypes.
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Four patients (4%), in whom the LTCVC was removed because of CRB treatment failure, presented another episode of CRB with the new LTCVC.
Outcome
Overall, treatment was successful in 94 episodes (82%). Cure was documented in 63/81 (78%) episodes caused by Gram-positive organisms, 24/26 (92%) episodes caused by Gram-negative bacilli and 7/8 (88%) polymicrobial episodes.
QNBC performed 72 h after the start of ALT was negative in 62 out of 73 episodes (85%). At 120 h, 75 out of 79 QNBCs (95%) were negative and at day 7 all 83 QNBCs were negative (100%). However, positive or negative status at the first control QNBC did not predict the outcome, as all relapses had a first negative control QNBC, and all the episodes with a first positive control QNBC had a successful outcome.
Table 4 describes all 21 episodes (18%) of CRB with unsuccessful treatment outcome (13 treatment failures, 7 relapses, and 1 related death). Treatment failed in 13 episodes (12%): 8 S. aureus CRB (persistent fever with negative QLBC in 7, persistent fever with positive QLBC in 1), 4 CoNS CRB (1 subcutaneous tunnel infection in Staphylococcus epidermidis CRB, 1 persistent fever in Staphylococcus warneri CRB, 1 persistent fever in unidentified CoNS CRB and 1 catheter thrombosis in unidentified CoNS CRB) and 1 Pseudomonas aeruginosa CRB (subcutaneous tunnel infection). Seven episodes relapsed (6%). Initially, patients received a median of 11 days of systemic treatment and ALT (range 8–20 days), and relapses occurred with a median of 23 days (range 14–30 days) from the start of antimicrobial therapy. Six were cured (three S. epidermidis infections, one Staphylococcus haemolyticus, one Proteus vulgaris, and one S. epidermidis plus Pseudomonas picketti infection) after a median of 12 days of additional systemic treatment and a second course of ALT (range 8–15 days). The remaining patient (S. epidermidis) failed secondary to catheter thrombosis after 5 days of treatment. There was one related death due to septic shock in one episode (1%) of S. aureus CRB.
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Only 3 of the 20 episodes of S. aureus were recorded in the prospective study, and 16 of the 20 episodes had an echocardiogram that ruled out infectious endocarditis in all cases.
Overall, according to aetiology, therapy failed in 9/56 (16%) episodes of CoNS CRB, 9/20 (45%) S. aureus CRB, 1/5 (20%) P. aeruginosa CRB and 1/8 (12%) polymicrobialCRB.
Patients with amikacin-lock
Seven episodes due to Gram-negative bacilli resistant to ciprofloxacin (three Escherichia coli, three P. aeruginosa, and one Acinetobacter baumannii) were locally treated with amikacin. All of them were cured.
Patients with less than 7 days of antibiotic-lock therapy
Eight patients received <7 days of ALT: 6 days in four episodes of CoNS CRB; 5 days in one P. aeruginosa, one E. coli and one Streptococcus oralis CRB and 3 days in one E. coli CRB. This last patient was treated with ciprofloxacin. All eight patients pertained to the retrospective study and were cured.
Follow-up
Median length of catheter follow-up in patients with successful therapy was 168 days (range 7–2740 days). Nine patients had <30 days of follow-up: two non-functional catheters without thrombosis, three unrelated deaths (one urinary septic shock, one terminal haematological condition, one terminal renal failure) and four catheter removals (three end of chemotherapy, one catheter-unrelated bacteraemia).
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Discussion |
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This is the largest published series investigating ALT in long-term CRB. The study included patients from medical and surgical wards and except for yeast, and S. aureus in the prospective study, the aetiology was not an exclusion criterion. Hence, a wide variety of organisms were isolated. Because of these factors, the results may better reflect the epidemiology and importance of this infection than most previous studies, which are mainly restricted to a single medical department and exclude CRB secondary to yeasts, S. aureus and Gram-negative bacilli. It is not surprising that 7% of the episodes in our series were caused by more than one organism, since a similar (8%)27 or even higher percentage (14%)21 has been described.
Overall cure in our study was 82%. Table 5 summarizes the experience with ALT in previous studies. Studies including more than 20 episodes with both Gram-positive and Gram-negative organisms showed cure in 50–93% of cases.12,17,20–24,27,28 The results of Poole et al.23 in 47 cases were very close to ours: 70% overall cure, 75% in S. epidermidis, 40% in S. aureus and 87% in Gram-negative bacilli. Although there is no previous data supporting these statements, the high cure rate in our series could be attributed to three factors: (i) during treatment, the catheter is not used but continuously exposed to antibiotic; (ii) high concentrations of antibiotic are delivered directly to the site of infection, such that the likelihood of sterilizing the lumen surface is enhanced with a lower incidence of toxicity and low risk of drug resistance; and (iii) concurrent systemic antibiotic therapy is always administered.
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The effectiveness of treatment against CoNS CRB without catheter-removal is well established29 and our data confirm this fact. Although we found a relatively high rate of failure in this subgroup of patients, which has been described previously,23 this fact is not of concern because of the low degree of virulence of CoNS. There is no consensus on the need for treatment or the length of therapy for CoNS CRB.29 However, maintenance of a foreign device and the rate of failure in these episodes argue for treating the bacteraemia.
In contrast, it is classically thought that in CRB due to Candida spp., Gram-negative bacilli or S. aureus the catheter should be removed immediately because of the high risk of metastatic infection and increased mortality.30 The benefits of catheter-removal are difficult to assess in Gram-negative infections, since clinical studies are sparse. In keeping with the results of Poole et al.23 we had the best percentage of success in CRB caused by Gram-negative organisms (92%), supporting conservative management of these infections. Although in P. aeruginosa and other non-fermenting Gram-negative bacillus CRBs catheter-removal is the single most important prognostic factor,31,32 we had only a single treatment failure in the eight CRBs caused by these organisms, and it was secondary to subcutaneous tunnel infection, probably not detected at the time of diagnosis. It is much more difficult to decide conservative treatment for S. aureus CRB, since there is substantial evidence that catheter removal is the safest option; some deaths and relapses related to catheter maintenance in S. aureus CRB have been reported.33 Our results are consistent with previous studies, showing one related death and a high failure rate (45%). We believe that conservative management of S. aureus CRB with ALT and systemic treatment should be avoided. However, ALT could be a viable option in selected cases, particularly in non-neutropenic, haemodynamically stable patients with no other vascular access, in whom transoesophageal echocardiography rules out infectious endocarditis,30 and under very close follow-up. Finally, there are too few studies to assess effectiveness in polymicrobial infection. Nonetheless, our results suggest that ALT combined with systemic antimicrobial therapy could be a suitable option in this subgroup of patients.
Sodium heparin combined with ciprofloxacin and vancomycin does not seem to alter the activity of ALT. At 2500 IU/mL this agent has no antimicrobial activity34 and contributes to reduce the risk of central venous thrombosis.35
Our patients received a median of 12 days of systemic treatment and ALT. However, this does not imply that patients must remain in hospital until the end of therapy. Most patients, once afebrile and stabilized, can receive a daily dose of systemic antibiotic and ALT at an outpatient centre.
There is no consensus on the length of ALT. When high concentrations of antibiotic are provided and catheter use avoided, lumen sterilization is probably achieved by 5 days, as demonstrated by negative QNBCs and QLBCs in 95% of successfully treated episodes in which this data was available (75/79). In fact, it seems that a shorter course of ALT does not alter the outcome. All eight patients with <7 days of ALT were cured. The remaining episodes of treatment failure, particularly the relapses, received a median treatment of 11 days, very close to the 12 days of the overall analysis. Prospective studies are necessary to prove that a course of ALT shorter than the 12 days used in the present study is equally effective.
Our study suggests that follow-up of these patients might be done only by clinical assessment, without QNBL controls, since their positive or negative result is not a predictor of success or failure and a cost saving is implicated.
Our study has four major limitations. The first is selection bias. Some episodes of CRB could have been unintentionally lost in the retrospective analysis. Furthermore, only 3 of the 20 episodes of S. aureus CRB were recorded in the prospective study, suggesting that physicians had a more conservative attitude based on previous experience with this subgroup,36 supported by the fact that a new exclusion criterion was added to the prospective study. Second, data were not prospectively collected in all cases. However, although the first 51 episodes were retrospectively recorded, Table 1 shows that the only differences between the retrospective and the prospective groups were the absence of non-tunnelled catheters in the prospective study, the length of systemic therapy (but not the length of ALT) and obviously the length of follow-up. However, all cases without exception were prospectively evaluated by a staff member of the Infectious Diseases Department. These facts give the series sufficient homogeneity to permit a consistent overall analysis. Another limitation was the absence of a control group. However, Marr et al.1 reported cure in only 32% of patients with systemically treated CRB (without catheter-removal or ALT), making a control group ethically unfeasible. Finally, genotype study of the isolated organisms was not performed in all cases. However, patients with more than one episode due to the same species had different antibiotypes, making it improbable that the second episode was a relapse. If we consider that the five patients with more than one episode due to CoNS actually had a relapse, overall failure would be 26/108 (24%), and 14/49 (29%) in CoNS CRB. That would represent a higher rate of failure in CoNS CRB (although safe) without altering overall ALT effectiveness.
In recent sporadic studies, ALT has been used to treat CRB with new antimicrobials such as linezolid, dalbavancin and taurolidine, with good results.37–39 Further prospective studies will establish the effectiveness of these new agents for conservative management of CRB.
In conclusion, our study suggests that ALT combined with a conventional systemic antibiotic seems to be an effective treatment for long-term CRB, particularly in Gram-negative and CoNS episodes. It is also possible to treat polymicrobial CRB, although studies including more episodes of these aetiologies are necessary to establish effectiveness and safety. Although a conservative management of S. aureus CRB with ALT and a systemic antibiotic must be avoided, in certain selected patients (non-neutropenic, haemodynamically stable from the beginning, with no alternative vascular access, infectious endocarditis ruled out and with close follow-up) ALT combined with systemic antibiotics could be a therapeutic option. During treatment it is probably not necessary to perform a control QNBC if the patient has a good outcome. Further investigation will elucidate the length of ALT. Molecular analysis is necessary to establish the true rate of relapses.
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None to declare.
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Acknowledgements |
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We thank Celine Cavallo for the language support.
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References |
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1 Marr KA, Sexton DJ, Conlon PJ, et al. (1997) Catheter-related bacteremia and outcome of attempted catheter salvage in patients undergoing haemodialysis. Ann Intern Med 127:275–80.
2 NNIS System. (2003) National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2003, issued August 2003. Am J Infect Control 31:481–98.[CrossRef][ISI][Medline]
3 Rotsein C, Brock L, Roberts RS. (1995) The incidence of first Hickman catheter-related infection and predictors of catheter removal in cancer patients. Infect Control Hosp Epidemiol 16:451–8.[ISI][Medline]
4 Stevenson KB, Adcos MJ, Mallea MC, et al. (2000) Standardized surveillance of hemodialysis vascular access infections: 18-month experience at an outpatient, multifacility hemodialysis center. Infect Control Hosp Epidemiol 21:200–3.[CrossRef][ISI][Medline]
5 Mueller BU, Skelton J, Callender DPE, et al. (1992) A prospective randomized trial comparing the infectious and non infectious complications of an externalized catheter versus a subcutaneous implanted device in cancer patients. J Clin Oncol 10:1943–58.[Abstract]
6 Segura M, Franch G, Alia C, et al. (1991) Pathogénie et prévention des septicémies liées au cathéter: études bactériologiques in vitro et in vivo d'un nouveau modèle de connecteur. Nutr Clin Metabol 5:81–6.
7 Andris DA, Krzywda EA, Edmiston CE, et al. (1998) Elimination of intraluminal colonization by antibiotic lock in silicone vascular catheters. Nutrition 14:427–32.[CrossRef][ISI][Medline]
8
Carratala J, Niubo J, Fernandez-Sevilla A, et al. (1999) Randomized, double-blind trial of an antibiotic-lock technique for prevention of gram-positive central venous catheter-related infection in neutropenic patients with cancer. Antimicrob Agents Chemother 43:2200–4.
9
Berrington A and Gould FK. (2001) Use of antibiotic locks to treat colonized central venous catheters. J Antimicrob Chemother 48:597–603.
10 Crnich CJ and Maki DG. (2002) The promise of novel technology for the prevention of intravascular device-related bloodstream infection. II. Long-term devices. Clin Infect Dis 34:1362–8.[CrossRef][ISI][Medline]
11 Oncu S, Oncu S, Ozturk B, et al. (2004) Elimination of intraluminal colonization by antibiotic lock in catheters. Tohoku J Exp Med 203:1–8.[Medline]
12 Santarpia L, Pasanisi F, Alfonsi L, et al. (2002) Prevention and treatment of implanted central venous catheter (CVC)-related sepsis: a report after six years of home parenteral nutrition (HPN). Clin Nutr 21:207–11.[CrossRef][ISI][Medline]
13
Safdar N, Fine JP, Maki DG. (2005) Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection. Ann Intern Med 142:451–66.
14 Raad I, Costerton JW, Sabharwall U, et al. (1993) Ultrastructural analysis of indwelling vascular catheters: a quantitative relationship between luminal colonization and duration of placement. J Infect Dis 168:400–7.[ISI][Medline]
15 Girvent M and Sitges-Serra A. (1995) Pathogenesis of catheter related sepsis (letter). Ann Surg 221:115.[Medline]
16 Sitges-Serra A, Hernandez R, Maestro S, et al. (1997) Prevention of catheter sepsis: the hub. Nutrition 13:Suppl 4, 30–5.
17 Messing B, Peitra-Cohen S, Debure A, et al. (1988) Antibiotic-lock technique: a new approach to optimal therapy for catheter-related sepsis in home parenteral nutrition patients. JPEN J Parenter Enteral Nutr 12:185–9.[Abstract]
18 Capdevila JA, Segarra A, Planes AM, et al. (1998) Long-term follow-up of patients with catheter-related bacteremia treated without catheter removal. Clin Microbiol Infect 4:472–6.
19
Capdevila JA, Segarra A, Planes AM, et al. (1993) Successful treatment of haemodialysis catheter-related sepsis without catheter removal. Nephrol Dial Transplant 8:231–4.
20 Domingo P, Fontanet A, Sanchez F, et al. (1999) Morbidity associated with long-term use of totally implantable ports in patients with AIDS. Clin Infect Dis 29:346–51.[ISI][Medline]
21 Krzywda EA, Andris DA, Edmiston CE, et al. (1995) Treatment of Hickman catheter sepsis using antibiotic lock technique. Infect Control Hosp Epidemiol 16:596–8.[ISI][Medline]
22 Messing B, Man F, Colimon R, et al. (1990) Antibiotic-lock technique is an effective treatment of bacterial catheter-related sepsis during parenteral nutrition. Clin Nutr 9:220–5.[CrossRef][ISI][Medline]
23
Poole CV, Carlton D, Bimbo L, et al. (2004) Treatment of catheter-related bacteraemia with an antibiotic lock protocol: effect of bacterial pathogen. Nephrol Dial Transplant 19:1237–44.
24
Rijnders BJ, Van Wijngaerden E, Vandecasteele SJ, et al. (2005) Treatment of long-term intravascular catheter-related bacteremia with antibiotic lock: randomized, placebo-controlled trial. J Antimicrob Chemother 55:90–4.
25 Capdevila JA, Planes AM, Palomar M, et al. (1992) Value of differential quantitative blood cultures in the diagnosis of catheter-related sepsis. Eur J Clin Microbiol Infect Dis 11:403–7.[CrossRef][ISI][Medline]
26
Anthony TU and Rubin LG. (1999) Stability of antibiotics used for ‘antibiotic-lock treatment’ of infections of implantable venous devices (ports). Antimicrob Agents Chemother 43:2074–6.
27 Reimund JM, Arondel Y, Finck G, et al. (2002) Catheter-related infection in patients on home parenteral nutrition: results of a prospective survey. Clin Nutr 21:33–8.[CrossRef][ISI][Medline]
28 Krishnasami Z, Carlton D, Bimbo L, et al. (2002) Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic-lock solution. Kidney Int 61:1136–42.[CrossRef][ISI][Medline]
29 Raad I, Davis S, Khan A, et al. (1992) Impact of central venous catheter removal on the recurrence of catheter related coagulase-negative staphylococcal bacteremia. Infect Control Hosp Epidemiol 13:215–21.[ISI][Medline]
30 Mermel LA, Farr BM, Sherertz RJ, et al. (2001) Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 32:1249–72.[CrossRef][Medline]
31 Elting LS and Bodey GP. (1990) Septicemia due to Xanthomonas species and non-aeruginosa Pseudomonas species: increasing incidence of catheter-related infections. Medicine 69:296–306.[Medline]
32 Kuikka A and Valtonen VV. (1998) Factors associated with improved outcome of Pseudomonas aeruginosa bacteremia in a Finnish university hospital. Eur J Clin Microbiol Infect Dis 17:701–8.[CrossRef][ISI][Medline]
33 Dugdale DC and Ramsey PG. (1990) Staphylococcus aureus bacteraemia in patients with Hickman catheters. Am J Med 89:137–41.[CrossRef][ISI][Medline]
34 Capdevila JA, Gavalda J, Fortea J, et al. (2001) Lack of antimicrobial activity of sodium heparin for treating experimental catheter-related infection due to Staphylococcus aureus using the antibiotic-lock technique. Clin Microbiol Infect 7:206–12.[CrossRef][ISI][Medline]
35
Droste JC, Jeraj HA, MacDonald A, et al. (2003) Stability and in vitro efficacy of antibiotic-heparin lock solutions potentially useful for treatment of central venous catheter-related sepsis. J Antimicrob Chemother 51:849–55.
36 Pigrau C, Rodríguez D, Planes AM, et al. (2003) Management of catheter-related Staphylococcus aureus bacteremia: when may sonographic study be unnecessary? Eur J Clin Microbiol Infect Dis 22:713–9.[CrossRef][ISI][Medline]
37
Curtin J, Cormican M, Fleming G, et al. (2003) Linezolid compared with eperezolid, vancomycin, and gentamicin in an in vitro model of antimicrobial lock therapy for Staphylococcus epidermidis central venous catheter-related biofilm infections. Antimicrob Agents Chemother 47:3145–8.
38 Koldehoff M and Zakrzewski JL. (2004) Taurolidine is effective in the treatment of central venous catheter-related bloodstream infections in cancer patients. Int J Antimicrob Agents 24:491–5.[CrossRef][ISI][Medline]
39 Raad I, Darouiche R, Vazquez J, et al. (2005) Efficacy and safety of weekly dalbavancin therapy for catheter-related bloodstream infection caused by gram-positive pathogens. Clin Infect Dis 40:374–80.[CrossRef][ISI][Medline]
40 Rao JS, O'Meara A, Harvey T, et al. (1992) A new approach to the management of Broviac catheter infection. J Hosp Infect 22:109–16.[CrossRef][ISI][Medline]
41 Johnson DC, Johnson FL, Goldman S. (1994) Preliminary results treating persistent central venous catheter infections with the antibiotic lock technique in pediatric patients. Pediatr Infect Dis J 13:930–1.[ISI][Medline]
42 Benoit JL, Carandang G, Sitrin M, et al. (1995) Intraluminal antibiotic treatment of central venous catheter infections in patients receiving parenteral nutrition at home. Clin Infect Dis 21:1286–8.[ISI][Medline]
43 McCarthy A, Byrne M, Breathnach F, et al. (1995) ‘In-situ’ teicoplanin for central venous catheter infection. Irish J Med Sci 164:125–7.[ISI][Medline]
44 Boorgu R, Dubrow AJ, Levin NW, et al. (2000) Adjunctive antibiotic/anticoagulant lock therapy in the treatment of bacteremia associated with the use of a subcutaneously implanted hemodialysis access device. ASAIO J 46:767–70.[CrossRef][Medline]
45 Fourcade J, Mallaval FO, Raffenot D, et al. (2001) Intérêt d'un verron antibiotique pour la prévention des récurrences de bactériémies à point de départ des cathéters centraux en hémodialyse chronique. Nephrologie 22:457–8.[Medline]
46 Longuet P, Douard MC, Arlet G, et al. (2001) Venous access port—related bacteremia in patients with acquired immunodeficiency syndrome or cancer: the reservoir as a diagnostic and therapeutic tool. Clin Infect Dis 32:1776–83.[CrossRef][ISI][Medline]
47
Bailey E, Berry N, Cheesbrough JS. (2002) Antimicrobial lock therapy for catheter-related bacteraemia among patients on maintenance haemodialysis. J Antimicrob Chemother 50:615–7.
48
Guedon C, Nouvellon M, Lalaude O, et al. (2002) Efficacy of antibiotic-lock technique with teicoplanin in Staphylococcus epidermidis catheter-related sepsis during long-term parenteral nutrition. JPEN J Parenter Enteral Nutr 26:109–13.
49 Sanchez-Muñoz A, Aguado JM, Lopez-Martin A, et al. (2005) Usefulness of antibiotic-lock technique in management of oncology patients with uncomplicated bacteremia related to tunneled catheters. Eur J Clin Microbiol Infect Dis 24:291–3.[CrossRef][ISI][Medline]
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