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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 4  |  Page : 593-602
Tunneled Catheter-Antibiotic Lock Therapy for Prevention of Dialysis Catheter-Related Infections: A Single Center Experience


Department of Internal Medicine, Nephrology Division, King Fahd Hospital of the University, King Faisal University, Al-Khobar, Saudi Arabia

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   Abstract 

Tunneled cuffed central vein catheters (TCC) are widely used for delivering hemodialysis (HD). Infection is the principal cause of morbidity and mortality associated with central vein catheters in patients on HD. The optimal strategy to combat TCC infec­tion is controversial. This prospective study assesses the efficacy of antibiotic-lock therapy using vancomycin and gentamycin in preventing catheter-related blood stream bacterial infection in patients on HD. A total of 86 TCC in 69 HD patients were enrolled at the time of catheter insertion for delivering HD. Patients were randomized into two groups: Group I (36 patients-39 insertions) included TCC with antibiotic-lock therapy and Group II (33 patients-47 insertions) with routine TCC management. Infection-free catheter survi­val of both groups was evaluated and compared at the end of the 18-month study period. A total of 72 TCC infections were detected with an incidence rate of 6.78 infections/1000 dialysis sessions. The rate of infection was significantly lower in Group I (4.39/1000 dialysis sessions) compared to Group II (11.69/1000 dialysis sessions), p< 0.001. The bacteremia rate, as well as rate of clinical sepsis were also significantly lower in Group I than in Group II (p< 0.001). There was no statistically significant difference in the rate of access site infec­tion in the two groups (p> 0.05). Our study suggests that antibiotic-lock therapy using a combination of vancomycin and gentamycin is useful in preventing catheter-related blood stream infection in patients on HD.

How to cite this article:
Al-Hwiesh AK. Tunneled Catheter-Antibiotic Lock Therapy for Prevention of Dialysis Catheter-Related Infections: A Single Center Experience. Saudi J Kidney Dis Transpl 2008;19:593-602

How to cite this URL:
Al-Hwiesh AK. Tunneled Catheter-Antibiotic Lock Therapy for Prevention of Dialysis Catheter-Related Infections: A Single Center Experience. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Jul 17];19:593-602. Available from: http://www.sjkdt.org/text.asp?2008/19/4/593/41320

   Introduction Top


Tunneled, cuffed central vein catheters (TCC) are an important means of delive­ring hemodialysis (HD) to patients who require immediate initiation of dialysis but are without a mature, functioning arterio­venous fistula or graft and in patients in whom a more desirable vascular access is not feasible. [1],[2] Bacteremia associated with TCC is a major complication and the inci­dence is an average of 3.13 episodes per 1000 catheter days. [3],[4],[5],[6],[7],[8] Serious metastatic infections occur in about 30% (range 13­44%) of episodes of TCC-associated bac­teremia. These are associated with a subs­tantial morbidity, mortality, and additional cost per infective episode. The appropriate strategy for TCC management is controver­sial. Immediate TCC removal with delayed insertion is recommended when TCC-bac­teremia is associated with severe symptoms, such as clinical signs of sepsis, TCC-tunnel tract involvement or persistent fever. [5],[6],[9],[10],[11] However, in patients with minimal or no symptoms, who remain afebrile after 72­hours of antibiotic therapy, three strategies have been proposed for catheter manage­ment. These include TCC salvage, exchange of TCC over a guide wire, or immediate removal with delayed reinsertion when blood cultures are negative. [4],[5],[10],[11][12],[13],[14],[15] All these mea­sures and techniques are expensive, and not free of complications including increased morbidity and mortality. [4],[15] Moreover, TCC salvage has been associated with a high treatment failure rate, [5],[6] the guide wire ex­change approach has the major disadvantage of the necessity of an invasive procedure, which is a cause of patient inconvenience and higher immediate cost. Also, TCC re­moval means loss of vascular access, ad­ded immediate costs and a high degree of patient and physician inconvenience due to the need for multiple procedures, including temporary femoral vein cannulation.

Recent efforts have focused on designing catheters with a lower infection rate. These include antibiotic- or antiseptic-bonded ca­theters, and silver-coated catheters. The antibiotic-bonded catheters, although sho­wing reduced incidence of colonization, have not yet been sufficiently studied in the HD population, nor have they been studied as cuffed silastic catheters. Silver coating does not confer benefit against clinical infection or colonization. [16],[17],[18],[19] Catheter-restricted filling with antibiotics as a prophylaxis against infection has recently emerged as a pro­mising option, but evidence in the form of prospective randomized trials are lacking. The aim of the current study is to evaluate the efficacy of antibiotic-lock therapy using a combination of vancomycin and gentamy­cin as a prophylaxis against TCC-related bacterial infection in HD patients.


   Patients and Methods Top


Study Design

We prospectively studied all patients on HD who had TCC at the King Fahd Hos­pital of the University, Al-Khobar, Saudi Arabia for TCC-related infections over an 18-month period (February 2005-July 2006). The total number of dialysis sessions was recorded on a daily basis and the patients were randomized into two groups: Group I, (36 patients/39 TCC insertions) who had antibiotic-lock protocol, and Group II, (33 patients/47 TCC insertions) with routine TCC placement and management. Our antibiotic­lock protocol consisted of a mixture of vancomycin hydrochloride 25 mg/ml, genta­mycin sulphate 40 mg/ml, and heparin 5000 U/ml; a total of 1.5-1.75 ml was instilled in the venous side and 1.25-1.5 ml in the arte­rial side of the TCC at the end of each dialysis session. The medication was with­drawn immediately before the next dialysis session. Heparin at this concentration was compatible with our antibiotic mixture. At each dialysis session, patients were evalua­ted by a nephrologist and a trained HD nurse for evidence of TCC-related infec­tion. Cultures were obtained from the ca­theter exit-site and from patients' blood each time. The presence of infection was recor­ded and tabulated by a trained nurse under the supervision of the nephrologist. Blood samples were collected from a peripheral vein at the beginning of each dialysis ses­sion, and both vancomycin and genta­mycin blood levels were measured.

Case Definitions

The CDC definitions for infections with or without bacteremia were used. [20] Blood for cultures was obtained from the TCC arterial and venous lines as well as peri­pheral blood samples. Staff from the hos­pital's Infection Control Unit reviewed po­sitive cultures reported by the clinical mic­robiology laboratory daily.

Microbiological Tests

Swabs from TCC site were inoculated onto agar media using standard techniques. [21] Blood cultures were performed for aerobic and anaerobic organisms according to esta­blished methods. [22] Bacteria were identified using Microscan (Microscan system, Renton, WA, USA) system.

Catheter Care

One team inserted the catheters in all stu­dy patients, preferentially in the right inter­nal jugular vein followed by the left internal jugular vein and then the femoral veins, when the internal jugular veins were inac­cessible. The catheter exit-site was cleaned with topical iodine solution at the initiation and termination of each dialysis session, and covered by dry sterile gauze during the inter­dialytic period. No topical or systemic anti­biotic prophylaxis was used in the catheter­dependent dialysis patients. Surgical and ra­diological procedures were carried out under complete aseptic precautions.

Data Analysis

Infection rates were calculated in both groups for total, blood stream, clinical sepsis, and TCC-exit-site infection. Data analysis was performed according to the CDC Na­tional Infection Surveillance System. [23] Sta­tistical analysis was performed with Epi Info, 2000, USD, Snellville, USA.


   Results Top


[Table 1] shows a breakdown of the patient population studied. A total of 86 TCC were inserted in 69 patients who had HD during the 18-month study period. The majority were Saudis (91.8%), and 62.4% were male. There were 8854 dialysis sessions [Table 2], with a monthly mean of 509 ± 86. A total of 72 TCC-related infections were detected, with an incidence rate of 6.78/1000 dia­lysis sessions. Out of these infections, 53 occurred in patients in Group II with an incidence rate of 11.69/1000 dialysis ses­sions, and 19 in patients in Group I with an incidence rate of 4.39/1000 dialysis sessions (p< 0.001) [Table 3]. Twenty-one of the 72 TCC infections (29.2%) were complicated by bacteremia. The bacteremia rate was 3.97/1000 dialysis sessions among patients in Group II and only 0.69/1000 dialysis sessions among patients in Group I (p< 0.001). Clinical sepsis occurred in 20 of the 72 TCC infections (27.8%). Clinical sepsis rate was significantly lower among patients in Group I (0.69/1000 dialysis sessions) compared to 3.75/1000 dialysis sessions among Group II patients (p < 0.001). The rate of access site infection was 3.01/1000 dialysis sessions among patients in Group I, compared with 3.97/1000 dialysis sessions in Group II patients; the difference was statistically not significant (p> 0.05). Van­comycin blood levels were undetectable in 89.8% and < 0.5 mcg/ml in 10.2% of pa­tients in Group I, whereas gentamycin blood levels were undetectable in 95.5% and < 1 mcg/ml in 4.5% in patients of the same group. [Table 4] shows the breakdown of organisms isolated from access sites and from blood, and the total number of orga­nisms isolated. Seventy-two percent of the bacteria isolated from blood and vascular access sites were gram-positive cocci, and about 28% of the isolates were gram­negative bacilli. [Figure 1] shows the preva­lence of the infective organisms. Removal of the TCC was followed by eradication of the infection in 94.8% of the patients; in the remaining 5.2%, prolonged administra­tion of intravenous antibiotics was necessary.


   Discussion Top


Patients on HD are known to be at in­creased risk for acquiring infection due to various defects in their immune function, which may be related to the underlying di­ease, the uremic state, or the dialysis pro­cedure itself. Infection associated with HD catheters has emerged as one of the most prominent and serious complications that is encountered in dialysis patients [24] and re­mains a significant cause of morbidity and mortality. Central venous catheters have become an indispensable form of vascular access for HD, but carry a high rate of infection which is approximately double those of all other access types combined. [25] The majority of these catheters become colonized, with consequent peripheral bac­teremia. [26] In fact, patients on dialysis are at a high risk for Staphylococcus aureus Scientific Name Search  bacteremia and have a fourfold higher mortality from TCC-related S. aureus bac­teremia than other patients. [27] Dittmer et al. [26] found that bacterial colonization of central venous catheters often led to bacteremia, and that the risk of subsequent bacteremia was related not only to the duration the catheter was left in situ but also to the degree of colonization. They concluded that surveillance cultures would allow clinicians to detect colonization before bacteremia occurred and thus take preventive mea­sures. Hoen et al. [28] found that long-term implanted catheters was the leading risk factor for bacteremia in chronic HD pa­tients and caused a trend towards re­currence of bacteremia that was not asso­ciated with chronic staphylococcal nasal carriage. TCC were thought to be safer in this respect; however, recent publications have shown that TCC are complicated by frequent systemic infections, and that the treatment of bacteremia associated with in­fected TCC often requires both systemic antibiotic therapy and catheter removal. [15] The incidence of bacteremia associated with TCC is an average of 3.13 episodes per 1000 dialysis sessions in the world­wide publications, [3],[4],[5],[6],[7],[8] whereas it was higher in our patients; this may reflect the need for more strict antiseptic precautions. Serious metastatic infections occur in about 30% (range 13-44%) of episodes of TCC associated bacteremia in the published reports. These included osteomyelitis, septic arthritis, infective endocarditis, epidural and brain abscess, and death. [5],[6][9] When bacteremia occurs, many clinicians feel reluctant to re­move the TCC, because most patients with cuffed tunneled catheters have exhausted all other options for vascular access. Some older, uncontrolled studies have indicated that salvage of the catheter is possible with antibiotics alone. Several recent studies re­lated to this subject need to be discussed in some detail. [29] One study systematically in­vestigated the outcome of catheter-related bacteremia and of the attempted salvage of the catheter. [5] The authors reported that this approach was successful in only 12 of the 38 cases of catheter-related bacteremia and of attempted catheter salvage. In the re­maining two thirds of patients, antibiotic treatment was considered a failure because blood cultures continued to show the initial micro-organism or the patients continued to have fever. In 22% of patients with bacteremia included in that study, serious complications occurred including osteomye­litis, arthritis, and endocarditis. In another study, a different approach was chosen and the outcome of 123 episodes of catheter­related infections was reported. [9] The treat­ment modality was based on clinical symp­toms: minimal symptoms with clean exit-site, change of catheter over guide wire within 48 hours; minimal symptoms with exit-site or tunnel infection, change of catheter over guide wire within 48 hours plus new tun­nel; severe symptoms, catheter removal and delayed replacement. In all cases, a three weeks course of antibiotic administration was applied. In another recent report, a different treatment regimen was presented. [15] It included catheter removal when there was severe sepsis or fever persisting for more than 48 hours of antibiotic treatment.Antibiotic therapy was then continued for approximately three weeks. All these mea­sures and techniques are costly, and not free of complications including increased mor­bidity and mortality. [4],[15] Moreover, TCC salvage has been associated with a high treatment failure rate, [5],[6] the guide wire ex­change approach has the major disadvan­tage of the necessity of an invasive proce­dure, which is a cause of patient incon­venience and higher immediate cost, and TCC removal means loss of vascular ac­cess, added immediate costs and a high degree of patient and physician incon­venience.

Recent efforts have focused on designing catheters with a lower infection rate. These include antibiotic- or antiseptic-bonded ca­theters, and silver-coated catheters. The antibiotic-bonded catheters, although sho­wing reduced incidence of colonization, have not yet been sufficiently studied in the HD population, nor have they been studied as cuffed silastic catheters. Silver coating does not confer benefit against clinical infection or colonization. [16],[17],[18],[19] In the face of TCC infections, systemic antibiotics are usually administered but, although ge­nerally effective in eliminating circulating bacteria, they frequently fail to sterilize the line, leaving the patient at continuing risk of complications or recurrence. Studies on patients with HD lines have demonstrated that systemically administered antibiotics do not diffuse back into the catheter lumen in appreciable quantities [30],[31] indicating that the luminal surface is exposed to antibio­tics only for the duration of the injection or infusion. [31],[32] For these reasons, it is not surprising that attention has turned to the antibiotic lock technique, a therapeutic mo­dality that permits the in situ prophylaxis against TCC infections with the twin aims of improving the TCC outcomes and reducing the risk of antibiotic side effects. The technique, also known as intra-luminal therapy, involves the instillation of a con­centrated antibiotic solution into the TCC lumen, in a volume chosen to fill the lumen but not to spill out into the circu­lation. This "antibiotic lock" is then (as in our patients) left in place for a defined period of days (inter-dialytic period) before being removed and, if appropriate, re­placed at the end of each dialysis session. The theoretical advantages of this over sys­temic administration are that higher con­centrations are delivered directly to the site of infection, and for longer duration, such that the likelihood of sterilizing the lumi­nal surface is enhanced. Other proposed benefits include a lower incidence of anti­biotic toxicity, less risk of promoting drug resistance and greater practicality in the outpatient setting. [33],[34],[35] Nevertheless, the trials on "antibiotic lock" technique in HD pa­tients are limited, and almost all of them addressed the use of a single antibiotic protocol; these included ampicillin, amikacin, gentamycin, or vancomycin. Our antibiotic­lock protocol consisted of a mixture of vancomycin 25 mg/ml, gentamycin 40 mg/ ml, and heparin 5000 U/ml. High concen­trations of heparin (3500-10,000 U/ml) are compatible with a broad range of anti­biotics including gentamycin and vanco­mycin. [36] Our results show that the overall TCC-related infections decreased signifi­cantly over the 18-month study period from 12.92/1000 dialysis sessions in patients with the routine TCC care, to 4.51/1000 dialysis sessions in those who received our pro­tocol of the antibiotic lock therapy. The rates of bacteremia as well as clinical sepsis were significantly less in the latter (p< 0.001 in either case). Moreover, our patients were saved from more invasive procedures such as systemic antibiotic therapy, TCC removal, and other surgical maneuvers, which was more convenient to both patients and doc­tors. Although the number of patients is not that large, our study is larger than most previous studies and is the first to address the value of using a combination of vanco­mycin and gentamycin in the antibiotic lock technique as an effective prophylactic mea­sure against TCC-related infections. It is of interest to note that observations derived from the in vitro study of organisms in op­timal growth conditions should be applied with great care. For example, the concen­tration of an antibiotic within a lock may exceed its MIC for the colonizing orga­nism by 1000-fold or more, yet it is clear that organisms within biofilms can survive much higher concentrations. [37],[38], It should also be remembered that the concepts of "susceptible" and "resistant" as defined by published breakpoints are not directly ap­plicable to antibiotic locks. However, it seems sensible to prefer bactericidal over bacteriostatic agents, and at least to be guided by the results of conventional sus­ceptibility testing. Many authors who have investigated access-related infections in HD patients have reported S. aureus as the lea­ding cause of bacteremia in this setting. Kurt et al. [39] reported a prevalence of 82%, while other studies reported a prevalence between 52 and 67%. [40],[41] Our findings differ from the reported pattern of infection, be­cause about half of the organisms isolated from the blood were S. epidermis rather than S. aureus . We addressed in a previous study published by our center [25] the possi­bility of the emergence of more virulent strains of S. epidermis among these patients. Moreover, gram negative bacteremia was considered to be uncommon among HD patients, and 11% prevalence was consi­dered as an outbreak of gram-negative bac­teremia by some authors. [42] The 27.8% rate of gram negative bacteria in our study is higher than previously quoted figures. [40],[43],[44] However, we must notice that these figures have been reported with other HD access options; namely arteriovenous fistulae and grafts. With the wide use of TCC in HD, and the few reports addressing the new era of organisms in this setting, accurate epi­demiological data for TCC-associated or­ganisms are difficult to find. It seems ap­propriate for now to use the combination of vancomycin and gentamycin in the above­mentioned concentrations to guard against both staphylococcal and gram-negative bac­terial infections in TCC.


   Conclusion Top


TCC lock with vancomycin, gentamycin and heparin appears to be highly effective strategy for the reduction of morbidity, and potentially mortality and costs, associated with TCC-related bacterial infections in HD patients. In this study, this protocol was free of side effects. The implications of our study extend beyond renal units, as tun­neled central catheters are now widely used in other specialties. Many other antibiotics have yet to be tested with this modality, and it is to be hoped that antibiotic locks will be subject to randomized controlled trials of sufficient power to confirm or refute their use.


   Acknowledgment Top


The authors would like to thank all the staff in the Hemodialysis Unit at the King Fahd Hospital of the University for their valuable help and cooperation. The authors also thank the workers in the Microbiology Department and the staff of Hospital's Infection Control Unit for their support.

 
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Correspondence Address:
Abdulla Khalaf Al-Hwiesh
Department of Internal Medicine, Nephrology Division, King Fahd Hospital of the University, P.O. Box 40246, Al-Khobar 31952
Saudi Arabia
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3 Recent advances in intestinal failure
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    Abstract
    Introduction
    Patients and Methods
    Results
    Discussion
    Conclusion
    Acknowledgment
    References
    Article Figures
    Article Tables
 

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