416 rates in the group using the cap with a chlorhexi dine rod were significantly lower than rates in the group with the needleless connector/disinfecting cap (0 28 vs 0 75 episodes/1000 HD catheter d[.]
416 rates in the group using the cap with a chlorhexidine rod were significantly lower than rates in the group with the needleless connector/disinfecting cap (0.28 vs 0.75 episodes/1000 HD catheter days) I nnovative HD Catheter Design and Composition There have also been considerations to change the composition or design of HD catheters to try to reduce catheter-related infections Much of this effort has focused on preventing bacterial colonization and biofilm formation in catheters [137, 138] Catheters impregnated with various antibiotics, antimicrobials, or anticoagulants have been designed, most of them for acute care HD catheters since the active agents are limited in potency, often eluting away by 7–10 days [139–145] There is limited data to date as to the broad efficacy of this approach in the chronic dialysis setting, however, with even less data in children with end-stage kidney disease Catheters are also being designed with polymers or additives aimed at maintaining a smooth intraluminal surface over time [51] Since microorganisms find it easier to attach to and then produce biofilm on roughened surfaces, bacterial colonization should be impeded in catheters with smooth intraluminal surfaces that resist developing irregularities [50, 51] Again there is limited data currently as to the clinical efficacy of this approach, though it seems to better address the role of biofilm in catheter-associated infections ntimicrobial Locks as Preventative A Strategy Antimicrobial locks have also been used as a preventative strategy to protect the intraluminal catheter surface from microorganism colonization and biofilm formation, with some reports suggesting more than 50% reduction in CRBSI rates [146–148] A concern about long-term antimicrobial locks is the development of resistant microorganisms, though this seems to have been A M Onder and M J G Somers more problematic when such locks were first being utilized and much higher antibiotic concentrations were used [147, 149] The risk-benefit analysis of preventative locks in any dialysis setting must also take into account the current frequency of CRBSI in that population and the risks that ensue from CRBSI treatment, including the impact of repetitive exposure to systemic antibiotics [150] In a pediatric study of 43 children and over 16,000 HD catheter days, a group of children considered high risk for CRBSI received prophylactic tobramycin-TPA catheter locks after each dialysis session for 6 months and then weekly for an additional 6 months CRBSI rates dropped significantly in these high-risk children to nearly a third of baseline levels There was a trend toward increased infections again when prophylaxis was decreased to weekly Additionally, there was significant decrease in systemic antibiotic exposure and percentage of HD catheters lost to malfunction during the period of prophylaxis More extensive data exists in adult HD patients looking at both the efficacy and potential adverse consequences of prophylactic antibiotic locks Many studies have demonstrated decreased rates of CRBSI using various antimicrobial- anticoagulant mixes [33, 151–153] Table 24.2 lists combinations of antimicrobials and anticoagulants that have been reported effective with both treating infection and in HD catheter prophylaxis Several studies have shown that antibiotic resistance can become problematic with prophylactic locks and contribute to significant drug-resistant infections in these HD patients [33, 154], though other studies have not shown a significant change in antibiotic resistance over time [151–153, 155] Given the results of initiatives like the SCOPE collaborative that reduced HD catheter- associated infections in children by implementing specific bundles of clinical care, it remains to be seen whether antibiotic locks may prove an additional strategy to reduce infections further and whether sequelae like antibiotic resistance will be a relevant issue in the setting of even less frequent prior or ongoing systemic exposure to antibiotics 24 Infectious Complications of Hemodialysis in Children 417 Table 24.2 Antibiotic lock solutions Antibiotic Vancomycin Vancomycin Vancomycin Cefazolin Tobramycin Tobramycin Gentamicin Gentamicin Gentamicin Gentamicin Antibiotic concentration 5 mg/ml 2.5 mg/ml 5 mg/ml 5 mg/ml 5 mg/ml 5 mg/ml 5 mg/ml 4 mg/ml 1 mg/ ml 0.32 mg/ml Anticoagulant Heparin Heparin TPA Heparin TPA Heparin Heparin Trisodium citrate Heparin Trisodium citrate Exit Site and Tunnel Infections An exit site infection usually presents with erythema of the site, often accompanied by tenderness, discharge, and even swelling and induration of the subcutaneous catheter tunnel within 2 cm of the exit site An isolated exit site infection infrequently presents with fever, and most can be diagnosed readily with inspection of the exit site Chronic poor exit site care, a breach of the exit site dressing, issues with immobilization of the catheter at the exit site, and Staphylococcus aureus nasal carriage are all risk factors for HD catheter exit site infections Staphylococcus species are the most likely microorganisms causing HD catheter exit site infections When exit site infections are suspected from external inspection, the immediate subcutaneous catheter tunnel should also be carefully examined for tenderness or induration and to make sure that no discharge can be readily expressed out the exit site Any discharge should be cultured, and there should be a low threshold to consider blood cultures from the HD catheter if there is any concern for an associated CRBSI. Ultrasound examination of the area may also be indicated to further delineate tunnel involvement or help define the extent of infection Meticulous exit site care must follow any initial concern for or diagnosis of an exit site infection, with special attention to antisepsis of the skin and application of triple antibiotic ointment or a chlorhexidine patch dressing at the exit site This care should be repeated at every dialysis ses- Anticoagulant concentration 5000 units/ml 2500 units/ml 1 mg/ml 5000 units/ml 1 mg/ml 5000 units/ml 5000 units/ml 3.13% 5000 units/ml 4% Reference [156] [79] [30] [6] [30] [156] [147] [157] [153] [151] sion until there is no longer any acute concern Additionally, antibiotics are usually prescribed, most often oral cefazolin as empiric therapy Culture results of any discharge and clinical response can guide ongoing antibiotic therapy In the setting of concern for CRBSI or a more systemic process, intravenous antibiotic therapy should be used The typical duration of antibiotic treatment for an uncomplicated HD exit site infection is 10–14 days, and symptoms are expected to resolve within the first week Lack of resolution of symptoms or early recurrence after the completion of treatment should prompt re-evaluation MRSA or gram-negative bacterial infection is the usual reason for suboptimal early response to typical measures The more widespread adoption of agents such as >0.5% chlorhexidine with alcohol, 70% alcohol, or povidone-iodine for skin antisepsis near the exit site along with use of triple antibiotic ointment or a chlorhexidine patch should continue to help reduce the frequency with which exit site infections are faced in children on HD In comparison to an exit site infection, a tunnel infection is a more serious complication of HD catheter use Tunnel infections are diagnosed by erythema, induration, or tenderness along the subcutaneous HD catheter tunnel distal to the exit site On occasion, purulent discharge may be milked along the tunnel to the exit site Tunnel infections may occur without a concomitant exit site infection, but their development is always a concern when a child with an HD catheter has an exit site infection Tunnel infections are more dif- 418 ficult to clear than exit site infections given they are not as readily accessible for local care, and there is always concern about involvement of surrounding tissue or hematogenous spread, especially when there is concomitant fever Accordingly, it is typical practice to treat a tunnel infection with intravenous antibiotics Prior to antibiotic administration, any discharge from the exit site or expressed from the tunnel should be cultured, and blood cultures should also be obtained from the HD catheter ports If there is palpation of any collection along the tunnel, tunnel ultrasound should be obtained to look for abscess Generally, most centers begin to treat tunnel infections with the same empiric antibiotics as CRBSI, with narrowing of antibiotic coverage determined by culture results Given the concern for deeper tissues being at risk of infection, the treatment duration is typically 3 weeks If the symptoms exacerbate, not substantially improve during the first week, or recur early after the completion of treatment, the HD catheter should be removed and replaced with the creation of a new exit site and tunnel AVF and AVG Infections An AVF is always the vascular access of choice for any patient on long-term HD. An AVF provides better dialysis efficacy and is much less likely to have issues with infection than a catheter An AVG is considered in those in whom AVF cannot be created Although infections may be seen more often in an AVG than an AVF, their frequency is still dramatically lower than rates seen with HD catheters, with overall incidence estimated at 0.5% chlorhexidine with alcohol, 70% alcohol, or 10% povidone-iodine on the skin over the access reduces the risk of introduction of microorganisms into the access during cannulation As with any skin antisepsis, cleaning the site for an appropriate amount of time and then allowing the site to dry optimize the benefits of such care In the setting of persistent fevers without an apparent source of infection, chronic elevation of inflammatory markers, or erythropoietin-resistant anemia, a prior thrombosed AVG that is still in place may need to be investigated as a source of ongoing clinically significant inflammation or even infection Physical examination and ultrasound of the area may be helpful There is also data to suggest that technetium-labeled leukocyte scans may be able to more precisely assess if there is ongoing infection in an old or unused AVG, with close correlation between positive findings on scan and eventual positive bacterial cultures following surgical excision [159] This potential complication may be especially important for kidney transplant patients with clotted but not resected AVGs [160] 419 Transmissible Infections in the Pediatric Hemodialysis Unit Given the nature of hemodialysis, there is a high risk for blood exposure for both hemodialysis patients and their healthcare providers Of particular concern are blood-borne pathogens such as hepatitis and HIV. With the more widespread adoption of specific guidance regarding infection control in the hemodialysis unit, the number of such infections is quite small, especially considering the ever-increasing number of adult chronic hemodialysis patients Given that children on hemodialysis make up such a tiny fraction of the entire hemodialysis population and are much less likely to spend long periods of time on hemodialysis prior to transplantation, the number of such pediatric infections is even smaller Transmission of hepatitis B infection was of particular concern when chronic hemodialysis first became widespread in the early 1970s, with incidence rates up to 30% being described related to poor infection control practices and the need for repeated blood transfusions in the era before erythropoietin availability [161] With stricter infection control requirements, the advent of erythropoietin, and the development of the hepatitis B vaccine, dialysis-acquired incident hepatitis B infections have dropped to 0.05% in the United States [162], and most patients with hepatitis infections receiving dialysis now acquired their infection prior to their need for dialysis Routine childhood hepatitis B vaccination was begun in 1991 with that recommendation extending to adolescents in 1995 to limit the number of non-immune pediatric patients entering adulthood As a result, almost all children now starting hemodialysis in the United States are already vaccinated against hepatitis B. Nonetheless, any child starting dialysis needs to be screened for hepatitis B infection (HBsAg, HBsAb, HBcAb) before or within 7 days of initiation Until there is confirmation that the child does not have an active hepatitis B infection, the child needs to be kept isolated from other patients while on dialysis and needs to be dialyzed on a dedicated machine In the child who has never been immunized, a primary series of hepatitis B vaccine should be provided, with follow-up serologic testing to con- 420 firm subsequent immunity In the immunized child, with initial serologic evidence of immunity, subsequent periodic serologic assessment while on HD is needed, since children with CKD and on dialysis lose serologic evidence of immunity at an increased rate compared to healthy children [163] With loss of immunity, revaccination is recommended, with reassessment of serologies to confirm if there has been seroconversion once more Similar to hepatitis B, hepatitis C or HIV infection is less of a concern in children on dialysis as well It is rare to find a young child with hepatitis C or HIV infection outside of perinatal transmission The advent of antiretroviral therapy has substantially reduced the likelihood of perinatal HIV transmission Since both of these viruses are primarily transmitted through IV drug abuse or sexual activity, these infections are more of a concern in adolescents, but again their frequency is very low Children initiating hemodialysis should, nonetheless, be screened for both these infections Unlike hepatitis B, infection with hepatitis C or HIV does not require patient isolation, dedicated equipment, or any other special practice during hemodialysis Typical infection control measures for provision of care and procurement and handling of laboratory samples, recommended sanitization and maintenance of dialysis equipment, as well as well-established blood bank practices to screen blood products for these infections should effectively prevent any iatrogenic disease transmission Moreover, ongoing antiviral therapy for HIV and consideration of antiviral therapy for hepatitis C should also help reduce the very low transmission risk during dialysis even further The use of antiviral prophylaxis after needle stick injury can also reduce concern for this route of acquired infection Infection Prevention and Surveillance As alluded to elsewhere in this chapter, embedding strategies to prevent infection into day-to-day dialysis care can play an important role in reducing the number of dialysis-associated infections that occur Strict adherence to practice guidelines for catheter connection and disconnection and for exit A M Onder and M J G Somers site and dressing care is often made difficult by time constraints or varying levels of patient cooperation Moreover, it is important for there to be general awareness that guidelines may change or be revised as new evidence is gained from clinical experience, such as the switch to 0.5% chlorhexidine with alcohol solutions from 10% povidoneiodine solutions for catheter hub and exit site care [120, 121] Concomitant with efforts to optimize the technical aspects of dialysis provision to reduce infection risk, there also needs to be ongoing attention to aspects of a general infection prevention strategy, such as the environment of care, screening for infection in patients and staff, and use of personal protective equipment One of the earliest reports of successful reduction of CRBSI by using standardized catheter care practices was by Eisenstein et al in a pediatric dialysis unit [23] Similar results were achieved in adults with implementation of the CDC Dialysis Bloodstream Infection Prevention Collaborative Interventions [35, 36], with reduction in infection shown to be sustainable over a prolonged period of time [164] Recent data from the Children’s Hospital Association’s Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) collaborative has also shown how the implementation of standardized care practices can affect short-term and long-term dialysis-associated infection rates in children [165] The SCOPE collaborative standardized HD catheter care via implementation of care bundles that were aligned with the preventive practices earlier recommended by the CDC [36, 37] Ongoing adherence to these recommendations was tracked by active surveillance within each participating center During the first years of SCOPE, increasing rates of adherence to recommended bundle practices were demonstrated During this same time, the adjusted CRBSI rate significantly decreased from 3.3/100 patient months in the 12 months prior to implementation of the care bundles to 0.8/100 patient months during the study period (p