What is the evidence for intraluminal colonization of hemodialysis catheters?
2014; Elsevier BV; Volume: 86; Issue: 1 Linguagem: Inglês
10.1038/ki.2013.527
ISSN1523-1755
Autores Tópico(s)Bacterial biofilms and quorum sensing
ResumoHemodialysis catheter–related bloodstream infections are potentially devastating, leading to increased morbidity, mortality, and cost of care. Prospective studies published over the past 15 years shed light on the pathogenesis of these infections. The data suggest that the intraluminal microbial colonization of hemodialysis catheters often precedes bloodstream infection. This finding supports strategies aimed at preventing or eradicating intraluminal colonization. Hemodialysis catheter–related bloodstream infections are potentially devastating, leading to increased morbidity, mortality, and cost of care. Prospective studies published over the past 15 years shed light on the pathogenesis of these infections. The data suggest that the intraluminal microbial colonization of hemodialysis catheters often precedes bloodstream infection. This finding supports strategies aimed at preventing or eradicating intraluminal colonization. During the initial stages of intravascular catheter colonization, a biofilm is formed that is made up of host proteins and microbes (Figure 1). Bacteria and fungi survive and proliferate within the biofilm, despite host immune defenses and therapeutic doses of antimicrobial agents.1.Dasgupta M.K. Biofilms and infection in dialysis patients.Semin Dial. 2002; 15: 338-346Crossref PubMed Scopus (81) Google Scholar, 2.Marcus R.J. Post J.C. Stoodley P. et al.Biofilms in nephrology.Expert Opin Biol Ther. 2008; 8: 1159-1166Crossref PubMed Scopus (19) Google Scholar, 3.Stewart P.S. Costerton J.W. Antibiotic resistance of bacteria in biofilms.Lancet. 2001; 358: 135-138Abstract Full Text Full Text PDF PubMed Scopus (3310) Google Scholar Catheter-related bloodstream infections (CRBSIs) most commonly emanate from microorganisms colonizing the catheter insertion site migrating distally along the extraluminal surface of the catheter into the bloodstream or from microorganisms that migrate intraluminally into the bloodstream from a colonized catheter hub, connector, or less often from microorganisms in contaminated infusate.4.Mermel L.A. What is the predominant source of intravascular catheter infections?.Clin Infect Dis. 2011; 52: 211-212Crossref PubMed Scopus (121) Google Scholar Some investigators found that when hemodialysis catheters were routinely removed 1 month after insertion, all of the catheters had intraluminal surface biofilm and 'ultrastructural colonization' detected using scanning electron microscopy.5.Bosma J.W. Siegert C.E. Peerbooms P.G. et al.Reduction of biofilm formation with trisodium citrate in haemodialysis catheters: a randomized controlled trial.Nephrol Dial Transplant. 2010; 25: 1213-1217Crossref PubMed Scopus (51) Google Scholar Other investigators have identified bacteria within the biofilm on the luminal surface of hemodialysis catheters using scanning electron microscopy.6.Kanaa M. Wright M.J. Sandoe J.A. Examination of tunnelled haemodialysis catheters using scanning electron microscopy.Clin Microbiol Infect. 2010; 16: 780-786Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar On the other hand, another study found that the outer surface of hemodialysis catheters removed after 138±141 days in bacteremic patients had a thicker biofilm and more microbial colonization than the luminal catheter surface.7.Ramanathan V. Riosa S. Al-Sharif A.H. et al.Characteristics of biofilm on tunneled cuffed hemodialysis catheters in the presence and absence of clinical infection.Am J Kidney Dis. 2012; 60: 976-982Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar In addition, thicker biofilm on hemodialysis catheters has been associated with positive blood cultures drawn through the catheter compared with those with negative blood cultures drawn through the catheter.8.Jones S.M. Ravani P. Hemmelgarn B.R. et al.Morphometric and biological characterization of biofilm in tunneled hemodialysis catheters.Am J Kidney Dis. 2011; 57: 449-455Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Eventually, planktonic bacteria or fungi break off from the biofilm and seed the bloodstream, causing bacteremia or fungemia, which may lead to metastatic infection.9.Olson M.E. Lam K. Bodey G.P. et al.Evaluation of strategies for central venous catheter replacement.Crit Care Med. 1992; 20: 797-804Crossref PubMed Scopus (31) Google Scholar, 10.Fux C.A. Wilson S. Stoodley P. Detachment characteristics and oxacillin resistance of Staphyloccocus aureus biofilm emboli in an in vitro catheter infection model.J Bacteriol. 2004; 186: 4486-4491Crossref PubMed Scopus (200) Google Scholar, 11.Lewis S.L. Sexton D.J. Metastatic complications of bloodstream infections in hemodialysis patients.Semin Dial. 2013; 26: 47-53Crossref Scopus (23) Google Scholar Both intraluminal and extraluminal colonization of hemodialysis catheters are important sources of microbes leading to CRBSI. An intraluminal source may be especially important in those patients with tunneled, cuffed, long-term hemodialysis catheters. This mini review focuses on intraluminal colonization. In a seminal prospective study,12.Cheesbrough J.S. Finch R.G. Burden R.P. A prospective study of the mechanisms of infection associated with hemodialysis catheters.J Infect Dis. 1986; 154: 579-589Crossref PubMed Scopus (166) Google Scholar 13 patients undergoing hemodialysis through central venous catheters developed fever and rigors, 12 of whom had catheter colonization and positive percutaneously drawn blood cultures. Of these 13 patients, their infection emanated from the catheter insertion site, catheter lumen, or both sites in three, eight, and two patients, respectively, suggesting a predominant intraluminal source of infection. Studies of patients receiving hemodialysis through central venous catheters have clearly demonstrated that the catheter lumens often become colonized over time, and in many such cases the same bacteria or fungi can be isolated from percutaneously drawn blood cultures weeks later (Table 1). In another study,13.Dittmer I.D. Sharp D. McNulty C.A.M. et al.Bacterial colonization and peripheral bacteraemia associated with central venous haemodialysis catheters: a cross-sectional study.Nephrology. 1997; 4: 557-561Crossref Scopus (5) Google Scholar investigators performed catheter-drawn blood cultures weekly for 3 weeks just before dialysis. For 15 of 21 patients, catheter-drawn and percutaneously drawn blood cultures grew the same microorganism. All 15 patients were initially asymptomatic and afebrile during dialysis. Eight of the 15 patients subsequently developed evidence of infection manifested by fever and rigors, and in each case the same Gram-positive or Gram-negative microorganism was grown from cultures of the hemodialysis catheter hub, and from catheter-drawn and percutaneously drawn blood cultures. This investigation suggested that patients receiving hemodialysis through catheters may develop intraluminal colonization from a colonized catheter hub, leading to bacteremia, which may occur without associated signs or symptoms. These investigators performed another study in which weekly catheter-drawn blood cultures were obtained from 28 hemodialysis patients just before dialysis.14.Dittmer I.D. Sharp D. McNulty C.A. et al.A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia.Clin Nephrol. 1999; 51: 34-39PubMed Google Scholar When a catheter-drawn blood culture revealed growth, the investigators then obtained percutaneously drawn blood cultures. For 21 of 31 catheters, positive catheter-drawn blood cultures developed at a mean of 27 days after hemodialysis catheter insertion. In 12 of the 21 instances, concordant microbial growth of predominantly coagulase-negative staphylococci from percutaneously drawn blood cultures developed at a mean of 32 days after the first positive catheter-drawn blood cultures were noted. Percutaneously drawn blood cultures revealed growth only after at least 3000 colony forming units/ml of bacteria were detected in intraluminal fluid cultures. These findings suggest that intraluminal catheter colonization, as measured by positive blood cultures drawn through a catheter, occurs in hemodialysis catheters, and if left unchecked this can lead to CRBSI, as defined by growth from percutaneously drawn and catheter-drawn blood cultures.Table 1Studies involving serial intraluminal hemodialysis catheter blood culturesAuthors (reference)No. of catheters/ no. of patients studiedCatheter typeInitial arterial and venous intraluminal fluid discardedBlood culturesIncident (I%); prevalent (P%); both (B)Tunneled (T%); nontunneled (N%); both (B)Yes; discard volume/fluid culture volume/frequency/% colonized catheters/time to colonizationNo; fluid culture volume/frequency/% colonized catheters/time to colonizationVolume (catheter-drawn; percutaneously drawn)/frequency/% colonized catheters develop positive peripheral blood culture with same microorganism/time to peripheral blood culture positivity after intraluminal colonization detected/% of peripheral blood culture positivity preceded by catheter-drawn blood culture positivity with same microorganismDittmer et al.13.Dittmer I.D. Sharp D. McNulty C.A.M. et al.Bacterial colonization and peripheral bacteraemia associated with central venous haemodialysis catheters: a cross-sectional study.Nephrology. 1997; 4: 557-561Crossref Scopus (5) Google ScholarNR/21PB (T 67%; N 33%)5ml/10ml/weekly × 3/95%/mean 59d (range 8–233d)10ml; 20–40ml/weekly × 3 and when suspected/76%/NR/100%Dittmer et al.14.Dittmer I.D. Sharp D. McNulty C.A. et al.A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia.Clin Nephrol. 1999; 51: 34-39PubMed Google Scholar31/28B (I% not specified; P% not specified)B (T 35%; N 65%)5ml/10ml/every 7d/68%/mean 27d (range 5–115d) from enrollment10ml; 20ml/weekly after first positive intraluminal culture/52%/mean 32d (range 5–126d)/100%Rodriguez-Aranda et al.15.Rodríguez-Aranda A. Alcazar J.M. Sanz F. et al.Endoluminal colonization as a risk factor for coagulase-negative staphylococcal catheter-related bloodstream infections in haemodialysis patients.Nephrol Dial Transplant. 2011; 26: 948-955Crossref PubMed Scopus (21) Google Scholar64/51B (I 80%; P 20%)T5ml or 0.5 ml/every 15d/25%/mean 391d (±389d) from enrollment~3ml; NR/when suspected or after colonization detected/unknown/median 28d (interquartile range 5–45d)/100%Nielson et al.16.Nielsen J. Kolmos H.J. Rosdahl V.T. Poor value of surveillance cultures for prediction of septicaemia caused by coagulase-negative staphylococci in patients undergoing haemodialysis with central venous catheters.Scand J Infect Dis. 1998; 30: 569-572Crossref PubMed Scopus (22) Google Scholar67/43IB (T 4%; N 96%)NR/every 7d/16% after catheter insertion for coagulase-negative staphylococci/NRNR/when suspected/NR/NR/NRFux et al.17.Fux C.A. Uehlinger D. Bodmer T. et al.Dynamics of hemodialysis catheter colonization by coagulase-negative staphylococci.Infect Control Hosp Epidemiol. 2005; 26: 567-574Crossref PubMed Scopus (30) Google Scholar29/26B (I 93%; P 7%)B (T 17%; N 83%)2ml/10ml/every 7d/2% and 4% at 2 and 4 weeks, respectively, after enrollment for coagulase-negative staphylococciNR/when suspected/no bloodstream infectionsDel Pozo et al.18.Del Pozo J.L. Aguinaga A. Garcia-Fernandez N. et al.Intra-catheter leukocyte culture to monitor hemodialysis catheter colonization. A prospective study to prevent catheter-related bloodstream infections.Int J Artif Organs. 2008; 31: 820-826PubMed Google Scholar37/33ITNR/2ml (blood leukocytes cultured)/every 14d/median 151d (range 0–452d) after enrollmentNR/when suspected or after colonization detected/95% /median 36d (range 2–150d)/100%Wagner et al.19.Wagner J. Schilcher G. Zollner-Schwetz I. et al.Microbiological screening for earlier detection of central venous catheter-related bloodstream infections.Eur J Clin Invest. 2013; 43: 964-969Crossref PubMed Scopus (9) Google ScholarNR/55PT3ml/every 3–4d/NR/NRNR/when suspected/50%/mean 7.5d/50%Abbreviations: d, days; NR, not reported. Open table in a new tab Abbreviations: d, days; NR, not reported. One group of investigators cultured the initial 5ml of fluid drawn from hemodialysis catheter lumens every 15 days just before dialysis.15.Rodríguez-Aranda A. Alcazar J.M. Sanz F. et al.Endoluminal colonization as a risk factor for coagulase-negative staphylococcal catheter-related bloodstream infections in haemodialysis patients.Nephrol Dial Transplant. 2011; 26: 948-955Crossref PubMed Scopus (21) Google Scholar In ~10% of the instances when luminal fluid cultures were obtained, the initial 0.5ml of the heparin catheter lock solution was cultured separately. Overall, the mean time from catheterization to the first positive intraluminal fluid-culture–growing coagulase-negative staphylococci was 378 days ±365 days, in sharp contrast to the findings of one of the above-noted studies.14.Dittmer I.D. Sharp D. McNulty C.A. et al.A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia.Clin Nephrol. 1999; 51: 34-39PubMed Google Scholar All of the patients enrolled in this study had tunneled catheters, whereas two-third of the patients in the above-noted study14.Dittmer I.D. Sharp D. McNulty C.A. et al.A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia.Clin Nephrol. 1999; 51: 34-39PubMed Google Scholar apparently had nontunneled, temporary hemodialysis catheters, which have been demonstrated to become colonized earlier than tunneled hemodialysis catheters.16.Nielsen J. Kolmos H.J. Rosdahl V.T. Poor value of surveillance cultures for prediction of septicaemia caused by coagulase-negative staphylococci in patients undergoing haemodialysis with central venous catheters.Scand J Infect Dis. 1998; 30: 569-572Crossref PubMed Scopus (22) Google Scholar Additional factors may have contributed to this disparity, such as differences in culture methodologies, possible differences in compliance with aseptic technique when handling catheter hubs, different patient populations, and so on. Investigators15.Rodríguez-Aranda A. Alcazar J.M. Sanz F. et al.Endoluminal colonization as a risk factor for coagulase-negative staphylococcal catheter-related bloodstream infections in haemodialysis patients.Nephrol Dial Transplant. 2011; 26: 948-955Crossref PubMed Scopus (21) Google Scholar noted that there was a prior positive luminal fluid culture documented for 14 of 19 catheters (74%) causing CRBSI, compared with 2 of 45 catheters (4%) without CRBSI (P<0.001). The median time from a positive luminal fluid culture to an episode of CRBSI was 32 days (interquartile range, 5–45 days), 32 days (interquartile range, 27–79 days), and 2 days (interquartile range, 2–23 days; P=0.03) for all CRBSI episodes, CRBSI due to Staphylococcus epidermidis, and for non S. epidermidis or polymicrobial CRBSI, respectively. Thus, the virulence of bacteria colonizing the luminal surface of hemodialysis catheters likely has an impact on the time from detection of growth in intraluminal fluid until bacteremia is detected, as measured by percutaneously drawn blood cultures (that is, CRBSI). Molecular fingerprinting confirmed that the bacteria that had grown in luminal fluid cultures were identical to each of the S. epidermidis strains causing CRBSI. In addition, the findings of this study are similar to the mean time of 27 days from a positive catheter-drawn blood culture to an episode of CRBSI in an above-noted study.14.Dittmer I.D. Sharp D. McNulty C.A. et al.A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia.Clin Nephrol. 1999; 51: 34-39PubMed Google Scholar The overall (that is, combining results of the 0.5-ml heparin lock solution cultures with the culture results of the 5ml of fluid containing heparin and blood) sensitivity, specificity, and positive and negative predictive values for luminal fluid cultures to predict CRBSI were 95%, 86%, 83%, and 96%, respectively. The sensitivity and specificity of the 5-ml intraluminal fluid (that is, blood and heparin) cultures was 80% and 100%, respectively, and 100% and 100%, respectively, for 0.5-ml intraluminal heparin cultures. The predictive value of cultures from arterial and venous lumens was similar. Another study found that 16% of incident hemodialysis catheter-drawn blood cultures obtained just before dialysis had the growth of coagulase-negative staphylococci after a median of 24 and 138 days of nontunneled and tunneled catheter use, respectively.16.Nielsen J. Kolmos H.J. Rosdahl V.T. Poor value of surveillance cultures for prediction of septicaemia caused by coagulase-negative staphylococci in patients undergoing haemodialysis with central venous catheters.Scand J Infect Dis. 1998; 30: 569-572Crossref PubMed Scopus (22) Google Scholar Most (73%) 'catheter septicemia' episodes were preceded by positive catheter-drawn blood cultures. In a study that performed weekly hemodialysis catheter-drawn blood cultures immediately before dialysis,17.Fux C.A. Uehlinger D. Bodmer T. et al.Dynamics of hemodialysis catheter colonization by coagulase-negative staphylococci.Infect Control Hosp Epidemiol. 2005; 26: 567-574Crossref PubMed Scopus (30) Google Scholar only 4% of catheter-drawn blood cultures had growth of coagulase-negative staphylococci by 4 weeks of study. These findings are in contrast to some of the above-noted studies,10.Fux C.A. Wilson S. Stoodley P. Detachment characteristics and oxacillin resistance of Staphyloccocus aureus biofilm emboli in an in vitro catheter infection model.J Bacteriol. 2004; 186: 4486-4491Crossref PubMed Scopus (200) Google Scholar,14.Dittmer I.D. Sharp D. McNulty C.A. et al.A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia.Clin Nephrol. 1999; 51: 34-39PubMed Google Scholar which may reflect differences in the proportion of incident and prevalent catheters in the studies, or possibly for other reasons as specified above. In another study, investigators obtained blood from each incident tunneled catheter lumen every 2 weeks, centrifuged the blood to obtain the buffy-coat–containing leukocytes, and then cultured 50μl of the fluid.18.Del Pozo J.L. Aguinaga A. Garcia-Fernandez N. et al.Intra-catheter leukocyte culture to monitor hemodialysis catheter colonization. A prospective study to prevent catheter-related bloodstream infections.Int J Artif Organs. 2008; 31: 820-826PubMed Google Scholar The median time from catheterization to the first positive intraluminal buffy coat blood culture was 151 days (range 0–452 days). The median time from positive buffy coat blood cultures to CRBSI was 36 days (range 2–150 days) after excluding patients who had a CRBSI without previously positive intraluminal buffy coat blood cultures. Most CRBSI episodes were due to coagulase-negative staphylococci. The latter findings are similar to those of two of the above-noted studies (that is, 27 days14.Dittmer I.D. Sharp D. McNulty C.A. et al.A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia.Clin Nephrol. 1999; 51: 34-39PubMed Google Scholar and 32 days15.Rodríguez-Aranda A. Alcazar J.M. Sanz F. et al.Endoluminal colonization as a risk factor for coagulase-negative staphylococcal catheter-related bloodstream infections in haemodialysis patients.Nephrol Dial Transplant. 2011; 26: 948-955Crossref PubMed Scopus (21) Google Scholar). These authors noted an increased sensitivity of arterial lumen buffy coat blood cultures (data not provided). In a study in which investigators obtained blood from each prevalent tunneled catheter lumen before each hemodialysis session, blood was analyzed with the help of peptide nucleic acid fluorescence in situ hybridization and acridine-orange leucocyte cytospin testing.19.Wagner J. Schilcher G. Zollner-Schwetz I. et al.Microbiological screening for earlier detection of central venous catheter-related bloodstream infections.Eur J Clin Invest. 2013; 43: 964-969Crossref PubMed Scopus (9) Google Scholar The two hemodialysis patients who developed coagulase-negative staphylococcal CRBSI had the identical microorganism identified by testing intraluminal blood samples 7 and 8 days before symptoms of CRBSI developed. The sensitivity, specificity, positive and negative predictive values for peptide nucleic acid fluorescence in situ hybridization or acridine-orange leucocyte cytospin testing were 100%, 96%, 50%, and 100%, respectively. In one study, 15 of 24 (75%) asymptomatic patients with tunneled hemodialysis catheters in place for more than 30 days had intraluminal colonization detected by cultures of intraluminal heparin or an intraluminal brush technique.20.Koch M. Coyne D. Hoppe-Bauer J. et al.Bacterial colonization of chronic hemodialysis catheters: evaluation with endoluminal brushes and heparin aspirate.J Vasc Access. 2002; 3: 38-42PubMed Google Scholar Two-thirds of the bacteria were coagulase-negative staphylococci. As with an above-noted study,18.Del Pozo J.L. Aguinaga A. Garcia-Fernandez N. et al.Intra-catheter leukocyte culture to monitor hemodialysis catheter colonization. A prospective study to prevent catheter-related bloodstream infections.Int J Artif Organs. 2008; 31: 820-826PubMed Google Scholar these investigators also found that arterial lumen cultures were most sensitive. Specifically, 9 of the 11 catheters with positive intraluminal heparin cultures were detected using cultures of the arterial lumen compared with 6 of the 11 detected by venous lumen cultures. Other investigators found that all 26 patients using either temporary or permanent hemodialysis catheters dialyzed for 51±35 days had blood cultures growing predominantly coagulase-negative staphylococci drawn through catheter lumens after discarding heparin-locking solutions.21.Zwiech R. Adelt M. Chrul S. A taurolidine-citrate-heparin lock solution effectively eradicates pathogens from the catheter biofilm in hemodialysis patients.Am J Ther. 2013Crossref Scopus (15) Google Scholar Three of the 26 had concomitant percutaneously drawn blood cultures. A limitation of some of the above-noted studies reflects the fact that some investigators did not perform molecular fingerprinting or additional typing methods to determine whether or not additional episodes of bacteremia were relapses or new infections in those patients who had more than one such event, or to confirm that potential skin contaminants grown from percutaneously drawn and catheter-drawn cultures were truly identical.13.Dittmer I.D. Sharp D. McNulty C.A.M. et al.Bacterial colonization and peripheral bacteraemia associated with central venous haemodialysis catheters: a cross-sectional study.Nephrology. 1997; 4: 557-561Crossref Scopus (5) Google Scholar,14.Dittmer I.D. Sharp D. McNulty C.A. et al.A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia.Clin Nephrol. 1999; 51: 34-39PubMed Google Scholar,18.Del Pozo J.L. Aguinaga A. Garcia-Fernandez N. et al.Intra-catheter leukocyte culture to monitor hemodialysis catheter colonization. A prospective study to prevent catheter-related bloodstream infections.Int J Artif Organs. 2008; 31: 820-826PubMed Google Scholar,20.Koch M. Coyne D. Hoppe-Bauer J. et al.Bacterial colonization of chronic hemodialysis catheters: evaluation with endoluminal brushes and heparin aspirate.J Vasc Access. 2002; 3: 38-42PubMed Google Scholar,21.Zwiech R. Adelt M. Chrul S. A taurolidine-citrate-heparin lock solution effectively eradicates pathogens from the catheter biofilm in hemodialysis patients.Am J Ther. 2013Crossref Scopus (15) Google Scholar Finally, in one study,16.Nielsen J. Kolmos H.J. Rosdahl V.T. Poor value of surveillance cultures for prediction of septicaemia caused by coagulase-negative staphylococci in patients undergoing haemodialysis with central venous catheters.Scand J Infect Dis. 1998; 30: 569-572Crossref PubMed Scopus (22) Google Scholar the case definition for CRBSI was met if a catheter-drawn blood culture or a percutaneously drawn blood culture was documented rather than requiring growth in the latter culture to meet the case definition. Nevertheless, data derived from the above-noted studies suggest that intraluminal hemodialysis catheter colonization often precedes CRBSI measured by concomitant growth from percutaneously drawn blood cultures. This insight should direct efforts toward minimizing catheter hub colonization and eventual luminal colonization. In addition, a better understanding of the pathogenesis of hemodialysis CRBSI afforded by these studies should focus prevention strategies on the catheter lumen, such as using antimicrobial lock solutions beginning after hemodialysis catheter insertion, or initiated once luminal colonization is detected. For example, in one study,18.Del Pozo J.L. Aguinaga A. Garcia-Fernandez N. et al.Intra-catheter leukocyte culture to monitor hemodialysis catheter colonization. A prospective study to prevent catheter-related bloodstream infections.Int J Artif Organs. 2008; 31: 820-826PubMed Google Scholar investigators obtained blood cultures in patients whose intraluminal buffy coat blood cultures were found to contain at least 1000 colony forming units/ml of bacteria. Thirteen patients with 28 coagulase-negative staphylococcal catheter colonization episodes met this criterion and had positive catheter-drawn blood cultures, as well as negative percutaneously drawn blood cultures, or the ratio of quantitative blood cultures through the catheter and percutaneously was less than 4:1, respectively. For these patients' catheters, a teichoplanin/heparin catheter lock solution was used after each dialysis session for 21 days. Quantitative blood cultures obtained 1 week later were negative in 25 of the 28 patients. However, 17 of these 28 patients had a relapse of catheter colonization with a median free interval of 70 days (range 2–101 days). In one of the above-noted studies,21.Zwiech R. Adelt M. Chrul S. A taurolidine-citrate-heparin lock solution effectively eradicates pathogens from the catheter biofilm in hemodialysis patients.Am J Ther. 2013Crossref Scopus (15) Google Scholar 23 patients who only had growth from catheter-drawn blood cultures of coagulase-negative staphylococci or Staphylococcus aureus then had their hemodialysis catheters locked once with a combination of taurolidine, citrate, and urokinase and then locked after each dialysis session with a combination of taurolidine, citrate, and heparin. When these patients had repeat catheter-drawn blood cultures after removal of the locking solution 34±8 days later, none of these cultures had microbial growth. The data from these studies suggest that some locking regimens may eradicate intraluminal hemodialysis catheter colonization. However, relapses may occur depending on the lock solution used and microbial pathogen involved. In addition, growth from weekly cultures of hemodialysis catheter luminal fluid could alert nephrologists that such patients have an increased risk of CRBSI, and such information should lower the threshold for obtaining percutaneously drawn blood cultures or blood cultures collected during dialysis to detect true bacteremia or fungemia 22.Quittnat Pelletier F. Joarder M. Lok C.E. Accuracy of blood culture results from hemodialysis circulation as compared to the gold standard for diagnosing catheter-related blood stream infections (NKF abstract 211).Am J Kidney Dis. 2012; 59: B67Abstract Full Text Full Text PDF Scopus (33) Google Scholar,23.Quittnat Pelletier F. Joarder M. Lok C.E. Challenges in obtaining peripheral blood cultures on hemodialysis patients during hemodialysis (NKF abstract 212).Am J Kidney Dis. 2012; 59: B67Abstract Full Text Full Text PDF Scopus (73) Google Scholar and consider initiating antimicrobial lock therapy at that point in time. A shortcoming to this approach is extraluminal hemodialysis catheter colonization, which will not be detected by cultures of intraluminal fluid and which will not respond to lock therapy. Bacteria or fungi that infect hemodialysis catheters, similar to other intravascular devices, will form a biofilm that aids in their survival.3.Stewart P.S. Costerton J.W. Antibiotic resistance of bacteria in biofilms.Lancet. 2001; 358: 135-138Abstract Full Text Full Text PDF PubMed Scopus (3310) Google Scholar,24.Dunne Jr., W.M. Bacterial adhesion: seen any good biofilms lately?.Clin Microbiol Rev. 2002; 15: 155-166Crossref PubMed Scopus (1097) Google Scholar As noted above,5.Bosma J.W. Siegert C.E. Peerbooms P.G. et al.Reduction of biofilm formation with trisodium citrate in haemodialysis catheters: a randomized controlled trial.Nephrol Dial Transplant. 2010; 25: 1213-1217Crossref PubMed Scopus (51) Google Scholar, 6.Kanaa M. Wright M.J. Sandoe J.A. Examination of tunnelled haemodialysis catheters using scanning electron microscopy.Clin Microbiol Infect. 2010; 16: 780-786Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 7.Ramanathan V. Riosa S. Al-Sharif A.H. et al.Characteristics of biofilm on tunneled cuffed hemodialysis catheters in the presence and absence of clinical infection.Am J Kidney Dis. 2012; 60: 976-982Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar biofilm has been noted in several studies of ex vivo hemodialysis catheters. Biofilm development on a catheter surface begins with microbial attachment, maturation of the biofilm, and final detachment of microbes from the biofilm surface. Microbes are difficult to eradicate from a mature biofilm, but there are various approaches currently being investigated to do so, which include enzymatic dispersal or breakdown of the biofilm, blocking cell–cell signaling among bacteria or fungi in a biofilm, or use of antimicrobial peptides that have bactericidal activity against dormant microbes within a biofilm.25.Brooks J.L. Jefferson K.K. Staphylococcal biofilms: quest for the magic bullet.Adv Appl Microbiol. 2012; 81: 63-87Crossref Scopus (35) Google Scholar In addition, recent data suggest that altering the surface of catheters can prevent the initial microbial attachment, thereby preventing biofilm formation.26.Desrousseaux C. Sautou V. Descamps S. et al.Modification of the surfaces of medical devices to prevent microbial adhesion and biofilm formation.J Hosp Infect. 2013; 85: 87-93Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar Thus, in the future, modification of hemodialysis catheter composition will inevitably occur, along with the development of novel catheter lock solutions, which will mitigate the risk of catheter infection in vulnerable hemodialysis patients. What are some take-home messages and implications for the practicing nephrologist? Hemodialysis catheters can become colonized with bacteria on the luminal and extraluminal surface. Luminal surface colonization can be detected by cultures of the luminal contents. Some nephrologists may wish to obtain such cultures, particularly in high-risk patients with a history of recurrent catheter infections, on a regular basis and initiate preventative strategies if intraluminal colonization is detected. Alternatively, a nephrologist may wish to initiate preventative strategies starting at the time of catheter insertion. Some of the above-noted studies and others27.Boyce J.M. Prevention of central line-associated bloodstream infections in hemodialysis patients.Infect Control Hosp Epidemiol. 2012; 33: 936-944Crossref PubMed Scopus (26) Google Scholar, 28.Hemmelgarn B.R. Moist L.M. Lok C.E. et al.Prevention of dialysis catheter malfunction with recombinant tissue plasminogen activator.N Engl J Med. 2011; 364: 303-312Crossref PubMed Scopus (161) Google Scholar, 29.Maki D.G. Ash S.R. Winger R.K. et al.A novel antimicrobial and antithrombotic lock solution for hemodialysis catheters: a multi-center, controlled, randomized trial.Crit Care Med. 2011; 39: 613-620Crossref PubMed Scopus (96) Google Scholar, 30.LaPlante K.L. Mermel L.A. In vitro activity of daptomycin and vancomycin lock solutions on staphylococcal biofilms in a central venous catheter model.Nephrol Dial Transplant. 2007; 22: 2239-2246Crossref PubMed Scopus (78) Google Scholar demonstrate that antimicrobial lock solutions containing either antibiotics, antiseptics, anticoagulants, other novel agents, or combinations of these, can prevent biofilm formation, catheter colonization, and catheter-related bloodstream infection. Some of these studies and more rigorous animal models31.Chauhan A. Lebeaux D. Decante B. et al.A rat model of central venous catheter to study establishment of long-term bacterial biofilm and related acute and chronic infections.PLoS One. 2012; 7: e37281Crossref PubMed Scopus (49) Google Scholar suggest that some antimicrobial lock solutions can eradicate biofilm-containing bacteria. Importantly, some lock solutions such as ethanol have been associated with adverse reactions or can adversely affect the catheter integrity.32.Slobbe L. Doorduijn J.K. Lugtenburg P.J. et al.Prevention of catheter-related bacteremia with a daily ethanol lock in patients with tunnelled catheters: a randomized, placebo-controlled trial.PLoS One. 2010; 5: e10840Crossref PubMed Scopus (91) Google Scholar Some antimicrobial-coated central venous catheters have been demonstrated to reduce the risk of CRBSI in prospective, randomized trials,33.Casey A.L. Mermel L.A. Nightingale P. et al.Antimicrobial central venous catheters in adults: a systematic review and meta-analysis.Lancet Infect Dis. 2008; 8: 763-776Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar but there are few such studies involving hemodialysis catheters, and none have demonstrated a significant reduction in CRBSI.34.Trerotola S.O. Johnson M.S. Shah H. et al.Tunneled hemodialysis catheters: use of a silver-coated catheter for prevention of infection—a randomized study.Radiology. 1998; 207: 491-496Crossref PubMed Scopus (116) Google Scholar, 35.Chatzinikolaou I. Finkel K. Hanna H. et al.Antibiotic-coated hemodialysis catheters for the prevention of vascular catheter-related infections: a prospective, randomized study.Am J Med. 2003; 115: 352-357Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar, 36.Schindler R. Heemann U. Haug U. et al.Bismuth coating of non-tunneled haemodialysis catheters reduces bacterial colonization: a randomized controlled trial.Nephrol Dial Transplant. 2010; 25: 2651-2656Crossref PubMed Scopus (23) Google Scholar Finally, before turning to technologic advances to mitigate the risk of hemodialysis CRBSI, recent collaborative quality improvement efforts focusing on basic infection control interventions have been demonstrated to effectively reduce bloodstream infections in outpatient hemodialysis units.37.Lindberg C. Downham G. Buscell P. et al.Embracing collaboration: a novel strategy for reducing bloodstream infections in outpatient hemodialysis centers.Am J Infect Control. 2013; 41: 513-519Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar,38.Patel P.R. Yi S.H. Booth S. et al.Bloodstream infection rates in outpatient hemodialysis facilities participating in a collaborative prevention effort: a quality improvement report.Am J Kidney Dis. 2013; 62: 322-330Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar In the future, further adoption of such quality improvement efforts and implementation of technologic advances to this vulnerable patient population holds the greatest hope for the prevention of these life-threatening infections.
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