Antimicrobial Locks: Putting the Lock on Catheter Infections
2006; Elsevier BV; Volume: 13; Issue: 3 Linguagem: Inglês
10.1053/j.ackd.2006.04.003
ISSN1548-5609
AutoresC. Manierski, Anatole Besarab,
Tópico(s)Acute Kidney Injury Research
ResumoInfectious complications resulting from catheter use in the hemodialysis population remain as the significant cause of morbidity and mortality in this patient population. Because conservation of vascular access sites remains a therapeutic mainstay for chronic hemodialysis patients, clinical investigators have evaluated the safety and efficacy of catheter preservation with antimicrobial lock solutions instilled into the lumens of catheters to treat and prevent infectious complications. The recommended treatment of catheter-related bacteremia includes administration of systemic antibiotics with catheter removal. To date, 4 studies in the hemodialysis population have evaluated the use of systemic antibiotics with an antimicrobial lock solution for treatment of catheter-related bacteremias to amplify the success of catheter salvage. The use of antimicrobial lock solutions for the treatment of catheter-related bacteremia has resulted in successful catheter salvage in approximately 69% of patients, with the remainder requiring catheter removal following a lack of clinical improvement after 48 hours. The antimicrobial lock has also been studied as a prophylactic measure to prevent catheter-related bacteremia. Six studies in the hemodialysis population have evaluated the use of an antimicrobial lock for the prevention of catheter-related bacteremia with an overall 64%-100% reduction in the frequency of catheter-related bacteremia. Although the use of antimicrobial lock for prophylaxis has demonstrated efficacy in clinical trials, its long-term consequences, including potential impact on antimicrobial resistance, are unknown. The objectives of this review are to evaluate the current body of evidence espousing the utilization of an antimicrobial lock solution in tunneled cuffed and uncuffed catheters that are utilized during chronic intermittent hemodialysis. Infectious complications resulting from catheter use in the hemodialysis population remain as the significant cause of morbidity and mortality in this patient population. Because conservation of vascular access sites remains a therapeutic mainstay for chronic hemodialysis patients, clinical investigators have evaluated the safety and efficacy of catheter preservation with antimicrobial lock solutions instilled into the lumens of catheters to treat and prevent infectious complications. The recommended treatment of catheter-related bacteremia includes administration of systemic antibiotics with catheter removal. To date, 4 studies in the hemodialysis population have evaluated the use of systemic antibiotics with an antimicrobial lock solution for treatment of catheter-related bacteremias to amplify the success of catheter salvage. The use of antimicrobial lock solutions for the treatment of catheter-related bacteremia has resulted in successful catheter salvage in approximately 69% of patients, with the remainder requiring catheter removal following a lack of clinical improvement after 48 hours. The antimicrobial lock has also been studied as a prophylactic measure to prevent catheter-related bacteremia. Six studies in the hemodialysis population have evaluated the use of an antimicrobial lock for the prevention of catheter-related bacteremia with an overall 64%-100% reduction in the frequency of catheter-related bacteremia. Although the use of antimicrobial lock for prophylaxis has demonstrated efficacy in clinical trials, its long-term consequences, including potential impact on antimicrobial resistance, are unknown. The objectives of this review are to evaluate the current body of evidence espousing the utilization of an antimicrobial lock solution in tunneled cuffed and uncuffed catheters that are utilized during chronic intermittent hemodialysis. Widespread use of hemodialysis (HD) catheters exposes patients to markedly increased risk of catheter-related complications.1Blankestijn P.J. Treatment and prevention of catheter-related infections in haemodialysis patients.Nephrol Dial Transplant. 2001; 16: 1975-1978Crossref PubMed Scopus (33) Google Scholar The risk of death attributable to sepsis in HD patients is 100 times that of the general population,2Sarnak M.J. Jaber B.L. Mortality caused by sepsis in patients with end-stage renal disease compared with the general population.Kidney Int. 2000; 58: 1758-1764Crossref PubMed Scopus (0) Google Scholar and HD central venous catheters (CVCs) are the primary source of bacteremia.3Tokars J.I. Miller E.R. Stein G. New national surveillance system for hemodialysis-associated infections Initial results.Am J Infect Control. 2002; 30: 288-295Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar As a result, CVCs are associated with a greater risk of death compared with other access types, such as grafts and arteriovenous fistulas.4Dhingra R.K. Young E.W. Hulbert-Shearon T.E. et al.Type of vascular access and mortality in U.S. hemodialysis patients.Kidney Int. 2001; 60: 1443-1451Crossref PubMed Scopus (645) Google Scholar, 5Ishani A. Collins A.J. Herzog C.A. et al.Septicemia, access and cardiovascular disease in dialysis patients The USRDS Wave 2 study.Kidney Int. 2005; 68: 311-318Crossref PubMed Scopus (259) Google Scholar Various means have been used to quantitate the rate of infection. Some authors have used the time to infection; a reported 48% of tunneled CVCs become infected by 6 months after their insertion.6Lee T. Barker J. Allon M. Tunneled catheters in hemodialysis patients Reasons and subsequent outcomes.Am J Kidney Dis. 2005; 46: 501-508Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar Other authors have used the fraction of patients with a CVC who develop bacteremia, which has been reported as 30%.5Ishani A. Collins A.J. Herzog C.A. et al.Septicemia, access and cardiovascular disease in dialysis patients The USRDS Wave 2 study.Kidney Int. 2005; 68: 311-318Crossref PubMed Scopus (259) Google Scholar Infection rate has also been expressed as a rate/per time at risk. Published rates for the latter are usually expressed per catheter days at risk and vary significantly. The variation in rates reflects variation in practice. More than 300,000 patients are on maintenance HD in the United States.7USRDS data. http://www.usrds.org/atlas.htmGoogle Scholar Of these patients, almost 30% have a catheter as their vascular access.8Rayner H.C. Besarab A. Brown W.W. et al.Vascular access results from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Performance against Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines.Am J Kidney Dis. 2004; 44: 22-26Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar The reported incidence of catheter-related bacteremia (CRB) varies from 1.6 to 8.6 episodes per 1,000 catheter-days at risk.9Taylor G. Gravel D. Johnston L. et al.Prospective surveillance for primary bloodstream infections occurring in Canadian hemodialysis units.Infect Control Hosp Epidemiol. 2002; 23: 716-720Crossref PubMed Scopus (107) Google Scholar, 10Jean G. Charra B. Chazot C. et al.Risk factor analysis for long-term tunneled dialysis catheter-related bacteremias.Nephron. 2002; 91: 399-405Crossref PubMed Scopus (101) Google Scholar, 11Zaleski G.X. Funaki B. Lorenz J.M. et al.Experience with tunneled femoral hemodialysis catheters.Am J Roentgenol. 1999; 172: 493-496Crossref PubMed Scopus (76) Google Scholar, 12Saxena A.K. Panhorota B.R. Al-Mulhim A.S. Vascular Access related infections in hemodialysis patients.Saudi J Kidney Dis Transplant. 2005; 16: 46-71PubMed Google Scholar A median rate of 3 to 4 episodes per 1,000 catheter-days, or 1.1 to 1.5 episodes per catheter-year at risk, is frequently noted.12Saxena A.K. Panhorota B.R. Al-Mulhim A.S. Vascular Access related infections in hemodialysis patients.Saudi J Kidney Dis Transplant. 2005; 16: 46-71PubMed Google Scholar, 13Beathard G.A. Posen G.A. Initial clinical results with the lifesite hemodialysis access system.Kidney Int. 2000; 58: 2221-2227Crossref PubMed Google Scholar, 14Dogra G.K. Herson H. Hutchison B. et al.Prevention of tunneled hemodialysis catheter-related infections using catheter-restricted filling with gentamicin and citrate A randomized controlled study.J Am Soc Nephrol. 2002; 13: 2133-2139Crossref PubMed Scopus (242) Google Scholar If the catheter infection rate is combined with the prevalence of catheters, approximately 100,000 episodes of CRB can be estimated to occur in the United States annually. Approximately one-third of these episodes will require in-patient hospitalization.15Tokars J.L. Light P. Anderson J. et al.A prospective study of vascular access infections at seven outpatient hemodialysis centers.Am J Kidney Dis. 2001; 37: 1232-1240Abstract Full Text PDF PubMed Scopus (103) Google Scholar At an average cost of $22,000 16Engemann J.J. Friedman J.Y. Reed S.D. et al.Clinical outcomes and costs due to Staphylococcus aureus bacteremia among patients receiving long-term hemodialysis.Infect Control Hosp Epidemiol. 2005; 26: 534-539Crossref PubMed Scopus (127) Google Scholar per bacteremic episode, the national cost could approach 1 billion dollars and becomes a significant fraction of the total cost of end-stage renal disease (ESRD) care. The cost from disability, rehospitalizations, and delay in eligibility for transplantation is immeasurable. In 1988, Messing et al 17Messing B. Peitra-Cohen S. Beliah M. Bernier J. Antibiotic-lock technique An approach to iptimal therapy for catheter-related sepsis in home parenteral nutrition patients.JPEN J Parenter Enteral Nutr. 1988; 12: 185Crossref PubMed Scopus (258) Google Scholar were the first to report the utility of a new method for treatment of catheter-related sepsis in patients who received total parenteral nutrition (TPN) that resulted in a 91% catheter salvage rate. This method, referred to as antibiotic lock, has since been extrapolated to several patient populations who require long-term intravenous access for various indications. These populations include patients who receive total parenteral nutrition, chemotherapy, and intermittent HD. The technique involves instilling a highly concentrated antimicrobial-anticoagulant solution in a volume sufficient to fill the catheter lumen, which, thus, "locks" the catheter when it is not in use. This lock dwells within the lumen of the catheter for various intervals that range from hours to days. Ultimately, this intraluminal solution is withdrawn and expended upon next use of the catheter. The purpose of utilizing the antimicrobial lock (AML) is to either prevent seeding or promote eradication of the microorganisms that colonize the inner lumen of the catheter and, thus, avert systemic dissemination of the pathogenic organisms. The use of AML in the HD population serves three functions: (1) as an adjunct to systemic antimicrobials for treatment of CRB, (2) to provide primary prophylaxis to prevent CRB in newly inserted catheters, and (3) to provide secondary prophylaxis in already existing catheters. This article aims to evaluate the current body of evidence for use of AML for both tunneled-cuffed catheters and uncuffed catheters employed during intermittent HD. Biofilm formation occurs when planktonic bacteria attach irreversibly to a foreign surface, such as an indwelling HD catheter.18Dasgupta M.K. Biofilms and infection in dialysis patients.Semin Dial. 2002; 15: 338-346Crossref PubMed Scopus (86) Google Scholar All indwelling vascular catheters are colonized by microorganisms within 24 hours after insertion.19Raad I. Costerton W. Sabharwal U. et al.Ultrastructural analysis of indwelling vascular catheters A quantitative relationship between luminal colonization and duration of placement.J Infect Dis. 1993; 168: 400-407Crossref PubMed Scopus (486) Google Scholar Bacteria are introduced to the lumen through the flora of the surrounding skin or the hands of health-care workers during catheter-hub manipulation.19Raad I. Costerton W. Sabharwal U. et al.Ultrastructural analysis of indwelling vascular catheters A quantitative relationship between luminal colonization and duration of placement.J Infect Dis. 1993; 168: 400-407Crossref PubMed Scopus (486) Google Scholar, 20Maar K.A. Sexton D.J. Conlon P.J. et al.Catheter-related bacteraemia and outcome of attempted catheter salvage in patients undergoing haemodialysis.Ann Intern Med. 1998; 15: 275-280Google Scholar Once bacteria attach to the catheter lumen, microcolonies subsequently form and produce a protective glycocalyx, or biofilm, which consists of a mesh of exopolysaccharide, protein, fibrin, fibrinogen, and fibrinonectin.21Mohammad S.F. Enhanced risk of infection with device-associated thrombi.ASAIO J. 2000; 46: S63-S68Crossref PubMed Scopus (13) Google Scholar Coagulase-negative staphylococci have emerged as an important pathogen associated with biofilm, because of their innate ability to adhere to catheter surfaces and produce this exopolysaccharide. Within the biofilm, channels are formed among the microcolonies that carry nutrients that enhance bacterial survival.22Costerton J.W. Stewart P.S. Greenberg E.P. Bacterial biofilms A common cause of persistent infection.Science. 1999; 284: 1318-1322Crossref PubMed Scopus (9242) Google Scholar The biofilm protects the underlying bacteria by preventing penetration of antiseptics, antimicrobial agents, or immune cells.23Yasuda H. Ajiki Y. Aoyama J. et al.Interaction between human polymorphonuclear leucocytes and bacteria released from in-vitro bacterial biofilm models.J Med Microbiol. 1994; 41: 359-367Crossref PubMed Scopus (48) Google Scholar Staphylococcus epidermidis, S aureus, and Candida are the predominant organisms that induce biofilm formation in the HD population, although other organisms, including gram-negative bacteria, may also be implicated.18Dasgupta M.K. Biofilms and infection in dialysis patients.Semin Dial. 2002; 15: 338-346Crossref PubMed Scopus (86) Google Scholar The ideal AML would have the following characteristics: sufficient concentration to maximize antimicrobial activity, anticoagulant activity to prevent thrombus formation, stability within the lumen under normal clinical conditions, and lack of exposure to the systemic circulation. The antimicrobials evaluated either alone, or in combination, in the HD population include the antibiotics vancomycin, gentamicin, cefazolin, ceftazidime, and ciprofloxacin. Antiseptics tested have included taurolidine and trisodium citrate; the latter having additional activity as an anticoagulant. The purpose of the AML technique is to decontaminate the intraluminal surface of the catheter to prevent systemic dissemination of the organisms contained within the biofilm. Instillation of high concentrations of antibiotics into the lumen of silicone vascular catheters in vitro eliminates existing biofilm.24Andris D.A. Krzywda E.A. Edmiston C.E. et al.Elimination of intraluminal colonization by antibiotic lock in silicone vascular catheters.Nutrition. 1998; 14: 427-432Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Various antimicrobials have been evaluated in controlled clinical trials in several populations, including patients who utilize a permanent catheter to receive total parenteral nutrition, chemotherapy, and intermittent hemodialysis. Antibiotics can have activity against gram-positive, gram-negative, or anaerobic bacteria. On the other hand, agents with antiseptic activity such as taurolidine, ethylenediaminetetraacetic acid (EDTA), or trisodium citrate have activity against a broad range of bacteria, in addition to yeast, protozoa, and viruses. Antiseptic agents differ somewhat from antibiotics. An antiseptic is a more general agent that kills or suppresses the growth/multiplication of microorganisms. Antiseptics often chelate metals essential for growth or suppress growth through hyperosmolality. By contrast, antibiotics are chemical substances produced by microorganisms that can inhibit the growth of other microbial organisms. Chelating antiseptics such as citrate or EDTA may also augment the action of antibiotics by permeabilizing the bacterial cell wall, which permits the more rapid entry of antibiotics. Both antibiotics and antiseptics have been evaluated in the HD population. Antimicrobial concentrations within the catheter lumen must achieve concentrations 100 to 1,000 times greater to eradicate bacteria within a biofilm, as compared with planktonic organisms.25Gaillard J.L. Merlino R. Pajot N. et al.Conventional and nonconventional modes of vancomycin administration to decontaminate the internal surface of catheters colonized with coagulase-negative staphylococci.JPEN J Parenter Enteral Nutr. 1990; 14: 593-597Crossref PubMed Google Scholar, 26Simon V.C. Simon M. Antibacterial activity of teicoplanin and vancomycin in combination with rifampicin, fusidic acid, or fosfomycin against staphylococci on vein catheters.Scand J Infect Dis. 1990; 72: 14-19Google Scholar, 27Guggenbichler J.P. Berchtold D. Allerberger F.R. et al.In vitro and in vivo effect on antibiotics on catheters colonized by staphylococci.Eur J Clin Microbiol Infect Dis. 1992; 11: 408-415Crossref PubMed Scopus (55) Google Scholar, 28Kropec A. Huebner J. Wursthorn M. et al.In vitro activity of vancomycin and teicoplanin against Staphylococcus epidermidis colonizing catheters.Eur J Clin Microbiol Infect Dis. 1993; 12: 545-548Crossref PubMed Scopus (28) Google Scholar, 29De Arellano E.R. Pascual A. Martinez-Martinez L. et al.Activity of eight antibacterial agents on Staphylococcus epidermidis attached to Teflon catheters.J Med Microbiol. 1994; 40: 43-47Crossref PubMed Scopus (43) Google Scholar, 30Pascual A. Arellano E.R. Martinez-Martinez L. et al.Effect of polyurethane catheters and bacterial biofilms on the in-vitro activity of antimicrobials against Staphylococcus epidermidis.J Hosp Infect. 1993; 24: 211-218Abstract Full Text PDF PubMed Scopus (44) Google Scholar The ability for systemic-antibiotic therapy to achieve these high concentrations within the catheter lumen has been studied. Bastani et al 31Bastani B. Minton J. Islam S. Insufficient penetration of systemic vancomycin into the PermCath lumen.Nephrol Dial Transplant. 2000; 15: 1035-1037Crossref PubMed Scopus (27) Google Scholar evaluated the in vivo penetration of systemic vancomycin therapy into the lumen of HD catheters in 24 chronic HD patients. The intraluminal concentration achieved for patients who received systemic vancomycin alone was only 0.2 ± 0.6 μg/mL compared with a concentration of 125.6 μg/mL ±13 μg/mL for those who received a 0.1mg/mL vancomycin lock. This evaluation demonstrated that to attain concentrations sufficient for eradication of intraluminal biofilm, systemic exposure alone is not adequate and requires the higher concentrations attained by catheter-restricted locking. In a similar study, the in vitro antimicrobial effectiveness of vancomycin on intraluminal colonization with S epidermidis was evaluated.32Gaillard J.L. Merlino R. Pajo N. et al.Conventional and nonconventional modes of vancomycin administration to decontaminate the internal surface of catheters colonized with coagulase-negative staphylococci.JPEN J Parenter Enteral Nutr. 1990; 14: 593-597Crossref PubMed Scopus (76) Google Scholar Vancomycin was infused for 1 hour every 8 hours for 3 consecutive days at a dose of 450 mg/d. In addition, continuous infusion of vancomycin at 450 mg/d for 3 days was also studied. Although both of these methods reduced bacterial colonization, they failed to sterilize the intraluminal surface. However, vancomycin instilled as a lock solution at a concentration of 5 mg/mL twice daily completely decontaminated the lumen of the catheter, as demonstrated by quantitative culture. One must always be concerned about the potential for interaction between the antimicrobial and anticoagulant that could lead to decreased antimicrobial activity. Previous studies have suggested that heparin can inactivate the antimicrobial activity of gentamicin, which may be of significance with the AML, as gentamicin is commonly used in this technique.33Regamy C. Schaverg D. Kirby W.M. Inhibitory effect of heparin on gentamicin concentrations in blood.Antimicrob Agents Chemother. 1972; 1: 329-332Crossref PubMed Scopus (19) Google Scholar In 1972, Regamy et al 33Regamy C. Schaverg D. Kirby W.M. Inhibitory effect of heparin on gentamicin concentrations in blood.Antimicrob Agents Chemother. 1972; 1: 329-332Crossref PubMed Scopus (19) Google Scholar reported that the in vitro concentration of gentamicin in human serum was reduced 56% in the presence of heparin (1,000 U/mL). However, the concentration of gentamicin in this study was relatively low (0.001 mg to 0.016 mg/mL), and Krishnasami et al 34Krishnasami Z. Carlton D. Bimbo L. et al.Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution.Kidney Int. 2002; 61: 1136-1142Crossref PubMed Scopus (222) Google Scholar found that this inhibition could be overcome at gentamicin concentrations greater than 1 mg/mL, which is closer to the concentrations typically used in AML. The ability for antiseptics to provide the addition of antifungal activity remains an attractive therapeutic option during AML. Taurolidine, a derivative of the amino acid taurine, has a broad spectrum of antimicrobial activity. The mechanism of action is believed to involve methylol derivatives, which interact with components of bacterial cell walls and result in irreparable injury, similar to an antiseptic. It has been shown in vitro to eradicate catheter biofilm of a variety of gram-positive, gram-negative, and fungal organisms.35Torres-Viera C. Thauvin-Eliopoulos C. Souli M. et al.Activities of taurolidine in vitro and in experimental enterococcal endocarditis.Antimicrob Agents Chemother. 2000; 44: 1720-1724Crossref PubMed Scopus (69) Google Scholar Use of an anticoagulant in the lock solution is necessary to prevent thrombus formation during the interdialytic period. Although its use has risks and benefits, heparin instillation remains the gold standard for anticoagulation of the catheter lumen during the interdialytic period. It is both readily available and inexpensive and remains the preferred anticoagulant by most hemodialysis centers. However, several considerations are warranted when it is used in the AML technique. Because of potential compatibility issues with certain antibiotics, Capdevila et al 36Capdevila J.A. Gavalda J. Fortea J. et al.Lack of antimicrobials activity of sodium heparin for treating experimental catheter-related infection due to Staphylococcus aureus using the antibiotic-lock technique.Clin Microbiol Infect. 2001; 7: 206-212Crossref PubMed Scopus (50) Google Scholar investigated the activity of heparin alone against S aureus in an experimental catheter-infection model. The authors found that heparin lacked antibacterial activity against S aureus. In another study, Shanks et al 37Shanks R.M.Q. Donegan N.P. Graber M.L. et al.Heparin stimulates Staphylococcus aureus biofilm formation.Infect Immun. 2005; 73: 4596-4606Crossref PubMed Scopus (232) Google Scholar found that heparin, in fact, promoted S aureus biofilm formation. Although the mechanism was not determined, heparin did not seem to promote primary attachment to the catheter surface; rather, it seemed to promote biofilm formation through a protein-synthesis−dependent mechanism. Intraluminal trisodium citrate (TSC) has been evaluated as an anticoagulant during the interdialytic period at various concentrations that ranged from 2.2% to 30%.38Weijmer M.C. Debets-Ossenkopp Y.J. Vondervoort F.J. et al.Superior antimicrobial activity of trisodium citrate over heparin for catheter locking.Nephrol Dial Transplant. 2002; 17: 2189-2195Crossref PubMed Scopus (130) Google Scholar TSC may have several advantages over heparin, including prevention of heparin-induced thrombocytopenia or inadvertent systemic heparinization. At TSC concentrations of 30%, Weijmer et al 38Weijmer M.C. Debets-Ossenkopp Y.J. Vondervoort F.J. et al.Superior antimicrobial activity of trisodium citrate over heparin for catheter locking.Nephrol Dial Transplant. 2002; 17: 2189-2195Crossref PubMed Scopus (130) Google Scholar demonstrated that TSC had antimicrobial activity against Staphylococcus, Escherichia coli, Pseudomonas, and C albicans. Although 30% TSC may have several advantages in encompassing both antimicrobial and anticoagulant activity, the occurrence of one fatal event caused by inadvertent systemic exposure to this high concentration of citrate led to a ban by the Food and Drug Administration on use of TSC at concentrations above 4% in the United States.39FDA News Page. FDA Issues Warning on Tricitrasol. April 14, 2000Google Scholar The antimicrobials evaluated either alone or in combination in the HD population include vancomycin, gentamicin, cefazolin, ceftazidime, ciprofloxacin, and taurolidine. Several in vitro and in vivo studies have demonstrated the compatibility of these antimicrobials with varying concentrations of heparin or citrate (see Table 1). Although many of the in vitro analyses in the clinical trials were based on visual inspection for precipitate, Vercaigne et al 40Vercaigne L.M. Sitar D.S. Penner S.B. et al.Antibiotic-Heparin lock in vitro antibiotic stability combined with heparin in a central venous catheter.Pharmacotherapy. 2000; 20: 394-399Crossref PubMed Scopus (73) Google Scholar utilized high-performance liquid chromatography (HPLC) analysis to evaluate compatibility, both within a test tube and within a dual lumen, polyurethane HD catheters. The authors evaluated a concentration of 10 mg/mL for cefazolin, vancomycin, ceftazidime, and ciprofloxacin and a 5 mg/mL concentration for gentamicin, combined with 5,000 U/mL of heparin. Ciprofloxacin precipitated immediately, whereas the other antibiotic-heparin combinations demonstrated stability. All combinations demonstrated decreased HPLC absorbance from 8% to 40.2% when instilled into the catheter for 72 hours, which could reflect adsorbance onto the catheter surface. However, this finding was not thought to be clinically significant, as remaining concentrations were still several hundred−fold greater than typical minimum-inhibitory concentrations of common biofilm organisms.Table 1In Vitro and In Vivo Evaluations of Stability of Antimicrobial Lock SolutionsStudyAntibiotic ConcentrationAnticoagulant ConcentrationLength of Time and Storage ConditionsCommentsKrishnasami et al24Andris D.A. Krzywda E.A. Edmiston C.E. et al.Elimination of intraluminal colonization by antibiotic lock in silicone vascular catheters.Nutrition. 1998; 14: 427-432Abstract Full Text Full Text PDF PubMed Scopus (59) Google ScholarGentamicin 4 mg/mL Vancomycin 2.5 mg/mL Cefazolin 5 mg/mL Vancomycin (2.5 mg/mL) + gentamicin (1 mg/mL) Cefazolin (5 mg/mL) + gentamicin (1 mg/mL)Heparin 2,500 U/mL72 hours at 37°CEffect of heparin on the bactericidal activity of gentamicin overcome at concentration > 1 mg/mLPoole et al56Poole C.V. Carolton D. Bimbo L. et al.Treatment of catheter-related bacteraemia with an antibiotic lock protocol Effect of bacterial pathogen.Nephrol Dial Transplant. 2004; 19: 1237-1244Crossref PubMed Scopus (168) Google ScholarCeftazidime 5 mg/mLHeparin 2,500 U/mL72 hours at 37°CLocks prepared by dialysis nurses from antibiotic solutions used for systemic administrationCapdevila et al36Capdevila J.A. Gavalda J. Fortea J. et al.Lack of antimicrobials activity of sodium heparin for treating experimental catheter-related infection due to Staphylococcus aureus using the antibiotic-lock technique.Clin Microbiol Infect. 2001; 7: 206-212Crossref PubMed Scopus (50) Google ScholarVancomycin 0.1 mg/mL or ciprofloxacin 0.1 mg/mL5% Sodium heparinBetween hemodialysis sessions in vivoNo in vitro reportedVardhan et al57Vardhan A. Davies J. Daryanani I. et al.Treatment of haemodialysis catheter-related infections.Nephrol Dial Transplant. 2002; 17: 1149-1150Crossref PubMed Google ScholarVancomycin 0.1 mg/mL + gentamicin 0.02 mg/mLHeparin 5,000 U/mLBetween hemodialysis sessions in vivoIn vitro stability verified by pharmacy quality controlDogra et al14Dogra G.K. Herson H. Hutchison B. et al.Prevention of tunneled hemodialysis catheter-related infections using catheter-restricted filling with gentamicin and citrate A randomized controlled study.J Am Soc Nephrol. 2002; 13: 2133-2139Crossref PubMed Scopus (242) Google ScholarGentamicin 40 mg/mLSodium citrate 3.13%Between hemodialysis sessions in vivoNo in vitro reportedAllon58Allon M. Prophylaxis against dialysis catheter-related bacteremia with a novel antimicrobial lock solution.Clin Infect Dis. 2003; 36: 1539-1544Crossref PubMed Scopus (141) Google ScholarTaurolidine 1.35% (13.5 mg/mL)Sodium citrate 4%Between hemodialysis sessions in vivoNo in vitro reportedBetjes and van Agteren59Betjes M.G. van Agteren M. Prevention of dialysis catheter-related sepsis with a citrate-taurolidine-containing lock solution.Nephrol Dial Transplant. 2004; 19: 1546-1551Crossref PubMed Scopus (198) Google ScholarTaurolidine 1.35% (13.5 mg/mL)Sodium citrate 4%Between hemodialysis sessions in vivoNo in vitro reportedMcIntyre et al42McIntyre C.W. Hulme L.J. Taal M. et al.Locking of tunneled hemodialysis catheters with gentamicin and heparin.Kidney Int. 2004; 66: 801-805Crossref PubMed Scopus (138) Google ScholarGentamicin 5 mg/mLHeparin 5,000 U/mLBetween hemodialysis sessions in vivoSolution made up before instillationKim et al60Kim S.H. Song K.I. Chang J.W. et al.Prevention of uncuffed hemodialysis catheter-related bacteremia using an antibiotic lock technique A prospective, randomized clinical trial.Kidney Int. 2006; 69: 161-164Crossref PubMed Scopus (91) Google ScholarCefazolin 10 mg/mL + gentamicin 5 mg/mLHeparin 1,000 U/mLBetween hemodialysis sessions in vivoBastani et al43Bastani B. Amin K. He
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