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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2007  |  Volume : 18  |  Issue : 2  |  Page : 239-247
Successful Prevention of Tunneled, Central Catheter Infection by Antibiotic Lock Therapy Using Vancomycin and Gentamycin

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

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Tunneled, cuffed central vein catheters (TCC) are widely used for delivering hemodialysis (HD). Among the complications associated with central vein catheters in HD patients, infection is the principal cause of morbidity and mortality. The optimal strategy for management of TCC infections is unclear. This prospective study was aimed at assessing the efficacy of antibiotic-lock therapy using vancomycin and gentamycin in preventing catheter­related blood stream bacterial infection in patients on HD. A total of 63 HD patients with 81 TCC were enrolled at the time of catheter insertion. Patients were randomized into two groups: Group I (33 patients, 37 insertions) included TCC with antibiotic lock therapy, and Group II (30 patients, 44 insertions) with routine TCC management. Infection-free catheter survival of both groups was evaluated and compared at the end of the 12-month study period. A total of 57 TCC infections were encountered with an incidence rate of 8.95 infections per 1000 dialysis sessions (DS). The rate of infection was significantly lower in Group I (4.54 per 1000 DS) as compared to Group II (13.11 per 1000 DS), p < 0.001. The incidence rates of bacteremia as well as clinical sepsis were also significantly lower in Group I than in Group II (p < 0.001). There was no statistically significant difference between the rates 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, Abdul-Rahman IS. Successful Prevention of Tunneled, Central Catheter Infection by Antibiotic Lock Therapy Using Vancomycin and Gentamycin. Saudi J Kidney Dis Transpl 2007;18:239-47

How to cite this URL:
Al-Hwiesh AK, Abdul-Rahman IS. Successful Prevention of Tunneled, Central Catheter Infection by Antibiotic Lock Therapy Using Vancomycin and Gentamycin. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2019 Nov 14];18:239-47. Available from: http://www.sjkdt.org/text.asp?2007/18/2/239/32317

   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 arterio-venous fistula or graft, as well as 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 13-44%) of episodes of TCC­associated bacteremia. These are associated with substantial morbidity, mortality, and additional cost per infective episode.

The appropriate strategy for TCC manage­ment is controversial. Immediate TCC removal with delayed re-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 72 hours 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 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 being 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. Antibiotic-bonded catheters show a reduced incidence of colonization, but have yet to be sufficiently studied in the HD population. Silver coating has not been shown to confer any 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 TCC­related bacterial infection in patients on HD.

   Patients and Methods Top

Study Design

We prospectively studied all HD patients who had TCC at the King Fahd Hospital of the University, Al-Khobar, Saudi Arabia for TCC­related infections over a 12-month period (February 2005-January 2006). The total number of dialysis sessions was recorded on a daily basis and the study patients were rando­mized into two Groups: Group I (33 patients, 37 TCC insertions) which received the anti­biotic-lock protocol, and Group II (30patients, 44 TCC insertions) which received routine TCC placement and management. Our anti­biotic-lock 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 to1.75 ml of this cocktail was instilled in the venous side and 1.25 to 1.5 ml in the arterial side of the TCC at the end of each dialysis session, and withdrawn immedia­tely before the next dialysis session. Heparin at this concentration was chemically compatible with our antibiotic mixture. At each dialysis session, the 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 the 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 levels of vancomycin and gentamycin in the blood were also measured.

Case Definitions

The Center for Diseases Control (CDC) definition of infections with or without bacteremia was 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 as reported daily by the clinical microbiology laboratory.

Microbiological Tests

Swabs from the TCC site were inoculated into 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.

TCC Care

Catheter insertions were always performed by a designated team. The site of insertion was, in order of preference, the right internal jugular vein, followed by the left internal jugular vein and then the femoral veins, when­ever internal jugular veins were inaccessible. The catheter exit-site was cleaned with a 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 conditions.

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 analyses were performed with Epi Info, 2000, USD, Snellville, USA).

   Results Top

[Table - 1] shows a breakdown of the patient­population studied. A total of 81 TCC were inserted in 63 patients who were on HD during the 12-month study period. The majority of the study subjects were Saudi Nationals (88.7%), and 60.3% were male. During the study period, a total of 6372 dialysis sessions were per­ormed and included 3091 sessions in Group I patients and 3281 in Group II patients, with a monthly mean of 512 ±74. A total of 57 TCC­related infections were detected, with an incidence rate of 8.95 per 1000 dialysis sessions (DS). Of these infections; 43 occurred in patients in Group II with an incidence rate of 13.11 per 1000 DS, and 14 in patients of Group I with an incidence rate of 4.54 per 1000 DS (p < 0.001) [Table - 2]. Eighteen of the 57 TCC infections (31.6%) were complicated with bacteremia. The bacteremia rate was 4.88 per 1000 DS in patients of Group II and 0.65 per 1000 DS in patients of Group I (p < 0.001). Clinical sepsis occurred in 16 (28.1%) of the 57 TCC infections. The clinical sepsis rate was significantly lower in patients of Group I (0.65 per 1000 DS) as compared with 4.27 per 1000 DS in Group II patients (p < 0.001) For access site infection, the rate was 3.24. per 1000 DA in patients of Group I, and 3.96 per 1000 DS in Group II; the difference was statistically not significant (p > 0.05). Vancomycin blood levels were undetectable in 90.1% and < 0.5 mcg/ml in 9.9% of patients in Group I, whereas gentamycin blood levels were undetectable in 93.94% and < 1 mcg/ml in 6.06% in patients of the same group. [Table - 3] shows the break-down of the 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 28% of the isolates were gram-negative bacilli. [Figure - 1] shows the prevalence of the various infective organisms. Removal of the TCC was followed by eradi­cation of the infection in 94.6% of patients; in the remaining 5.4%, prolonged therapy with intravenous antibiotics was necessary.

   Discussion Top

Infection associated with HD catheters has emerged as one of the most prominent and serious complications in dialysis patients,[24] and remains a significant cause of morbidity and mortality. Central venous catheters have become an indispensable form of HD access; however, the incidence rates of infection with central venous catheters are approximately double those of 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 of Staphylococcus aureus Scientific Name Search  bacteremia and they have a fourfold higher mortality from TCC­related 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 amount of time the catheter was left in situ, but also to the degree of colonization. On the other hand, Hoen et al [28] found that long-term implanted catheters were the leading risk factors for bacteremia in chronic HD patients and also caused a trend towards recurrence of bacteremia that was not associated with chronic staphylococcal nasal carriage.

The incidence of bacteremia associated with TCC is, on an average, 3.13 episodes per 1000 dialysis sessions in various publications, [3],[4],[5],[6],[7],[8] whereas it was 8.95 per 1000 DS in our patients; an incidence which is much higher and 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 published reports. These include 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 salvaging 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 salvaging of the catheter.[5] The authors reported that this approach was successful in only 12 out of 38 cases of catheter-related bacteremia. In the remaining two thirds of patients, antibiotic treatment was considered a failure because blood cultures continued to show a persistence of the initial microorganism or, the patients continued to have fevers. In another study, a different approach was chosen and the outcomes of 123 episodes of catheter-related infections were reported.[9] The treatment modality was based on clinical symptoms: patients with minimal symptoms with a clean exit site received exchange over guidewire within 48 hours; those with minimal symptoms with exit site or tunnel infection had exchange over guidewire within 48 hours plus a new tunnel, while patients with severe symptoms underwent catheter removal and delayed replacement. All cases received a three week course of anti­biotics. 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 after 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] and the guide wire exchange approach is highly invasive and is a cause of patient inconve­nience and higher immediate cost. 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. [9] In the face of TCC infections, systemic antibiotics are usually administered, and although they are generally effective in eliminating circulating bacteria, they frequently fail to sterilize the line, leaving the patient exposed to the risk of complications or recurrence. Studies in 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 aim of improving TCC out­comes and reducing the risks of antibiotic side effects. The technique, also known as intra­luminal 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 time (interdialytic days) 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 for a longer duration of time, 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, trials on the "antibiotic lock" technique in HD patients are limited, and almost all of them addressed the use of a single antibiotic protocol that included ampicillin, amikacin, gentamycin, or vancomycin. Our antibiotic-lock protocol consisted of a mixture of vancomycin, gentamycin and heparin; the high concen­tration of heparin (3500-10,000 U/ml) is compatible with a broad range of antibiotics including gentamycin and vancomycin [36]. Our results show that overall TCC-related infe­ctions decreased significantly over the 12­month study period in patients who received the antibiotic lock therapy. 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 than can the same organism in a dispersed suspension.[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. How-ever, 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. 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 blood were S. epidermis rather than S. aureus. We addressed in a previous study published from our center [25] regarding 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 am 11% prevalence was considered an outbreak of gram-negative bacteremia by some authors.[42] The 28.1% rate of gram negative bacteria in our study is higher than previously quoted figures. [40],[43],[44] However, 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 acombi-nation of vancomycin and gentamycin in the above-mentioned 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 a highly effective strategy for the reduction of morbidity, and potentially mortality and costs associated with TCC-related bacterial infections in HD patients. The use of both antibiotics in this study was free of reported 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 future studies employing randomized controlled trials of sufficient power will confirm or refute their use.

   Acknowledgement 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.

   References Top

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Correspondence Address:
Abdulla K Al-Hwiesh
Nephrology Division King Fahd Hospital of the University P.O Box 40246, Al-Khobar 31952
Saudi Arabia
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American Journal of Kidney Diseases. 2010; 56(3): 566-577
10 Antibiotic-based catheter lock solutions for prevention of catheter-related bloodstream infection: a systematic review of randomised controlled trials
Snaterse, M. and Rüger, W. and Scholte op Reimer, W.J.M. and Lucas, C.
Journal of Hospital Infection. 2010; 75(1): 1-11
11 Systematic review of antimicrobials for the prevention of haemodialysis catheter-related infections
Rabindranath, K.S. and Bansal, T. and Adams, J. and Das, R. and Shail, R. and MacLeod, A.M. and Moore, C. and Besarab, A.
Nephrology Dialysis Transplantation. 2009; 24(12): 3763-3774
12 Prevention of catheter-related bacteremia in children on hemodialysis: Time for action
Stefanidis, C.J.
Pediatric Nephrology. 2009; 24(11): 2087-2095
13 Catheter-related bacteremia in hemodialysis patients: The role of the central venous catheter in prevention and therapy
Troidle, L. and Finkelstein, F.O.
International Journal of Artificial Organs. 2008; 31(9): 827-833
14 Antimicrobial lock solutions for the prevention of infections associated with intravascular catheters in patients undergoing hemodialysis: Systematic review and meta-analysis of randomized, controlled trials
Yahav, D. and Rozen-Zvi, B. and Gafter-Gvili, A. and Leibovici, L. and Gafter, U. and Paul, M.
Clinical Infectious Diseases. 2008; 47(1): 83-93
15 Meta-analysis: Antibiotics for prophylaxis against hemodialysis catheter-related infections
James, M.T. and Conley, J. and Tonelli, M. and Manns, B.J. and MacRae, J. and Hemmelgarn, B.R.
Annals of Internal Medicine. 2008; 148(8): 596-605
16 Empiric Therapy for Intravenous Central Line Infections and Nosocomially-Acquired Acute Bacterial Endocarditis
Bouza, E. and Burillo, A. and Munoz, P.
Critical Care Clinics. 2008; 24(2): 293-312
17 New recommendations in the treatment of Gram-positive bacteraemia in dialysis patients
Ponticelli, C.
Nephrology Dialysis Transplantation. 2008; 23(1): 27-32
18 Challenges for randomized controlled trials in nephrology: Illustrations in vascular access science and care
Lok, C.E. and Moist, L.M.
Journal of Nephrology. 2007; 20(6): 632-645


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