Intestinal failure occurs when intestinal absorption is inadequate such that macronutrients and/or water and electrolytes supplementation is required to maintain fluid balance, growth and health . Short bowel syndrome (SBS) is the most common cause of intestinal failure in children often secondary to necrotizing enterocolitis, gastroschisis, volvulus or congenital intestinal atresias . A Canadian population-based study estimated the incidence of neonatal SBS to be approximately 24.5 per 100 000 live births and as high as 354 per 100 000 live births in babies born before 37 weeks gestation , therefore, accounting for a significant healthcare problem in the pediatric population. Children with intestinal failure are all initially dependent on central venous catheters (CVCs) for delivery of parenteral nutrition. Although approximately 62% of children with SBS eventually achieve sufficient intestinal adaptation to absorb all of their nutrients enterally , adaptation can take months to years during which time the patients require parenteral nutrition.
Although parenteral nutrition has allowed many patients to live healthy and productive lives, it is not without consequences. Complications from long-term parenteral nutrition are numerous and include those associated with the components of the parenteral nutrition, and those associated with its delivery, specifically CVC infections and associated venous thrombosis. Loss of long-term venous access secondary to these complications can lead to significant morbidity and ultimately mortality [5,6]. Preventing catheter-related bloodstream infections (CRBSIs) is of utmost importance for patients with intestinal failure. Not only can infections lead to catheter loss, they can also worsen intestinal failure-associated liver disease (IFALD). IFALD is often the most fatal complication in infants with intestinal failure. Healthcare providers must, therefore, be proactive in preventing CRBSI in these patients.
CATHETER RELATED BLOOD STREAM INFECTIONS: DEFINITION AND ETIOLOGY
A CVC is defined as any catheter with the tip located in a large central vein, namely the superior or inferior vena cava. Access can be obtained via the femoral, iliac, subclavian, jugular or more peripheral veins. CRBSIs occur when there is verification of the same pathogen on the catheter surface and in the peripheral bloodstream. It is important to confirm the pathogen in both locations because the CVC may grow organisms that have colonized the line but are not causing a bloodstream infection , and peripheral cultures alone cannot distinguish between a transient bacteremia and a true CRBSI . CRBSIs typically arise from bacterial colonization of the internal surface of the intravascular catheter [9,10], often from migration of skin flora . However, children with intestinal failure have additional sources of bacteria that can result in catheter infection including gastrostomy tubes and enterostomies . These patients may also have intestinal dilation with bacterial overgrowth that can predispose to CRBSI . In addition, daily access for parenteral nutrition or fluid administration increases the chance of the catheter serving as a portal for infection.
A review of the pediatric literature reports the incidence of CRBSI to be between 1.1 and 14 infections per 1000 catheter days, depending on patient and catheter variables [4,8,14–19]. In children with intestinal failure the range is very similar (0.9–11 per 1000 catheter days) [20▪,21,22,23▪]. Despite several novel therapies proposed to reduce CRBSI, it continues to be a significant problem for patients with intestinal failure , as well as, a financial burden on the healthcare system . Prevention is essential and begins with basic principles.
CATHETER INSERTION AND MAINTENANCE
One of the most basic, yet crucial factors in preventing CRBSI is meticulous sterile technique during catheter insertion. The most current guidelines from the Centers for Disease Control and Prevention published in 2011 [25▪▪] outline the following steps for central catheter insertion: proper hand hygiene, the use of a mask, cap, sterile gown, sterile gloves, full body drape and cleansing the patient's skin with at least 0.5% chlorhexidine. With the guidelines in mind, many institutions have implemented care ‘bundles’ for CVC insertion. These bundles include a sterile pack containing the necessary equipment for line insertion and/or maintenance, as well as, a checklist for inserting or accessing the line. They may also include routine education sessions and posters for teaching proper sterile technique. A recent multi-institutional collaborative study implemented care bundles in 26 pediatric ICUs. The rate of CRBSIs decreased from 6.3 to 4.3 per 1000 catheter days  and most sites sustained the reduced rate over the following 12 months [27▪▪]. Several additional studies in adult ICUs demonstrated similar reductions in CRBSIs with the implementation of CVC bundles [28–30]. Although there is nothing particularly novel about these interventions, the fact that many hospitals have seen a reduction in the incidence of infections emphasizes the importance of these details. The bundles are probably most valuable when there is a high baseline CRBSI rate. For children with intestinal failure, having protocols for both line insertion and maintenance is ideal considering the prolonged duration of therapy, the high likelihood of multiple care providers, and the importance of preserving venous access.
CATHETER LOCATION AND CATHETER TYPE
There are no recent studies investigating the impact of catheter location on CRBSI rates. Previously published reports demonstrated a higher infection rate with femoral catheters compared to other sites in adults [31–34]. This relationship has not been shown in children, even when considering high-risk patients such as burn victims and neonates [19,35]. Children with intestinal failure, however, frequently have chronic stomas with high outputs predisposing to bag leakage and spillage. A CVC in close proximity, therefore, has a higher likelihood of becoming infected. For these reasons, it is preferential to avoid the femoral veins as initial sites in children with intestinal failure.
Similarly, there are no recent data comparing the incidence of CRBSIs among different types of catheters including nontunneled central catheters, tunneled central catheters and peripherally inserted central catheters (PICCs). Most children with intestinal failure require long-term central access and are, therefore, best served by a tunneled CVC or a PICC. Risk factors associated with an increased rate of CRBSI include prematurity, previous abdominal surgery, presence of an enterostomy and using the catheter for parenteral nutrition, but not the specific type of catheter [36,37,38▪,39,40].
CATHETER LOCK SOLUTIONS
Traditionally, a catheter lock solution is used to prevent a thrombus from forming within the catheter when not in use. Heparin, because of its anticoagulant properties, is the standard lock solution; however, there is recent interest in broadening the function of the lock to include infection prevention. Multiple antibiotics have been used, but the more common agents include vancomycin and or gentamicin combined with heparin or citrate. The majority of studies have been conducted in adult patients on hemodialysis or receiving chemotherapy. It is difficult to draw clear conclusions from these trials because of variability among studies including the lock solution, the patient population, the baseline incidence of CRBSI, the type of central catheter and the duration of therapy. However, a recent meta-analysis summarized 16 randomized controlled trials and found a small overall benefit to using an antibiotic lock solution . Nine of the studies were conducted in patients on hemodialysis and seven of the nine demonstrated a statistically significant reduction in infections when an antibiotic was added to the lock. Six of the trials were in patients receiving chemotherapy, and five of these were in children. The pooled results from all six studies showed a slight benefit with the antibiotic lock. Finally, there was one study in critically ill neonates. This study showed a significant reduction in CRBSI from 15.4 to 13.1 per 1000 catheter days with the use of vancomycin and heparin compared to heparin alone .
When specifically considering children with intestinal failure, there is only one recent retrospective study in this population. The study evaluated five children with intestinal failure, who had undergone multivisceral transplantation and were then treated prophylactically with tobramycin-tissue plasminogen activator locks . The lines were locked 4 h each day, for 6 weeks and each patient served as his or her own control. They found significantly fewer bloodstream infections during the study period compared to the control period (46 vs. 74%, P < 0.05). The most recent guidelines published in 2011 by the Centers for Disease Control and Prevention [25▪▪] recommend the use of antibiotic locks in patients with long-term catheters who have multiple line infections despite adherence to basic principles of infection prevention. There is no recommendation regarding what type of antibiotic or the duration of therapy. As a general rule the antibiotic should be chosen to cover the most common organisms cultured from bloodstream infections within the particular institution.
One of the main concerns with the routine use of antibiotic locks is the development of resistant strains of bacteria. Although this has not yet been reported, there are few data available. However, alternative antimicrobial locks are becoming more popular in pediatric patients with CVCs. A randomized controlled trial was conducted in pediatric patients in the last year comparing taurolidine citrate to heparin locks in children receiving chemotherapy [44▪▪]. Taurolidine is derived from the amino acid taurine and is effective against a wide range of microorganisms. A total of 71 patients were included in the study (35 in the intervention group and 36 in the control group) and the incidence of CRBSI was 1.3 per 1000 catheter days in the heparin group compared to 0.3 per 1000 catheter days in the taurolidine/citrate group, which was a statistically significant difference.
A more readily available alternative is ethanol. The bactericidal properties of ethanol have been demonstrated in several in-vitro studies [9,45]. The mechanism of action includes nonspecific protein denaturation and diffusion through the polysaccharide matrix of the bacterial biofilm [10,24,46,47]. Biofilms form on implanted medical devices and can result in persistent infection because they are 10–1000 times more resistant to antibiotic therapy . Ethanol lock therapy (ELT) has been utilized for both prevention and treatment of CRBSI at a standard concentration of 70% [14,22,24,47–50]. There have been several studies evaluating ELT for the prevention of CRBSI in children with intestinal failure. A retrospective study by Mouw et al. reviewed 10 children with SBS on home parenteral nutrition. Each child's CVC was treated with 70% ethanol daily for 4–14 h. The infection rate decreased from 11.1 to 2.1 per 1000 catheter days after initiating ethanol lock. A retrospective study by Jones et al. reviewed 23 children with intestinal failure. Each patient received 70% ethanol lock for 3 days each week, 4 h per day, and was compared to his or herself prior to the use of the ethanol lock. The infection rate dropped from 9.9 to 2.1 per 1000 catheter days after initiating ELT. Finally, a recently published study [23▪] reviewed 10 patients with intestinal failure on parenteral nutrition. The patients were treated with ELT daily for at least 4 h per day and the catheter infection rate decreased from 10.2 to 0.9 per 1000 catheter days. The same group published a meta-analysis of four studies comparing the rate of CRBSI in children with intestinal failure who received either ethanol or heparin CVC locks. The analysis found that the use of ethanol significantly reduced the risk of CRBSI by 81% [51▪▪]. The theoretical downside to routinely using ethanol as a lock solution is the potentially increased risk of catheter thrombosis, with published studies reporting a catheter thrombosis rate ranging from 0 to 50% [21,22,23▪,52]. An alternate day ethanol/heparin lock schedule may be superior and is worthy of investigation. In addition, it is becoming more difficult to obtain 95% ethanol, from which 70% ethanol lock is derived, and, therefore, the efficacy of ethanol at a lower concentration is being investigated. Ethanol may prove to be an effective lock solution for children with intestinal failure.
ANTIBIOTIC IMPREGNATED CATHETERS AND DRESSINGS
In addition to antimicrobial lock solutions, there are also catheters impregnated with antibiotics. In theory this could reduce the likelihood of a biofilm forming on the inside surface of the catheter, thereby decreasing the incidence of CRBSI. The majority of the studies have been conducted in adults with short-term catheters impregnated with chlorhexidine/silver sulfadiazine or minocycline/rifampin. Initially, catheters were coated with antibiotic on the outside surface but newer catheters are coated on both external and internal surfaces. The most recent randomized controlled trials in adults using second-generation catheters demonstrated a reduction in catheter colonization, but did not show a reduction in the rate of CRBSI [53–55].
Although there are no randomized pediatric trials, there are two recent studies in critically ill children. Chelliah et al. compared the incidence of CRBSI in children in the ICU with minocycline–rifampin catheters compared to standard noncoated catheters. A total of 225 catheters were included in the analysis (69 coated and 156 noncoated). The overall incidence of CRBSI did not differ significantly between groups (7.53 vs. 8.64 per 1000 catheter days). The second study  looked at a stepwise approach to reducing CRBSIs in children in the ICU. One of the interventions included using minocycline–rifampin catheters. They found that the coated catheters decreased the infection rate from 6.4 to 4.2 per 1000 catheter days, without an increase in antibiotic-resistant organisms. Given that the majority of the available antibiotic impregnated catheters are designed for short-term use, are large (7F and larger) and are not cuffed, these catheters should not be routinely used for infants and children with intestinal failure. However, there is a relatively new minocycline–rifampin coated PICC (Cook Spectrum Turbo-Ject) that could be considered for patients with difficult-to-manage or recurrent infections.
The catheter dressing is another potential mechanism for preventing CRBSIs. Sterile dressings act as the initial barrier to the environment. The chlorhexidine sponge dressing has been the most popular choice due to the effectiveness of chlorhexidine as a skin preparation [11,25▪▪,27▪▪]. A randomized controlled trial by Timsit et al. found that by using chlorhexidine sponge dressings for CVCs in adult patients in the ICU, the incidence of CRBSIs was reduced from 1.3 to 0.3 per 1000 catheter days. Catheters were in situ for a mean of 6 days and there was no evidence of antibiotic resistance in the bacteria found in skin samples when the catheters were removed. The current guidelines recommend the use of chlorhexidine sponge dressings for short-term catheters in patients older than 2 months of age when the CRBSI rate remains elevated despite best efforts [25▪▪]. Applicability to patients with intestinal failure must be approached with caution because many of the patients are neonates and may not tolerate chlorhexidine exposure and most patients require long-term CVCs.
Minimizing CRBSIs in infants and children with intestinal failure is of utmost importance to prevent worsening liver dysfunction and maintain the ability to administer parenteral nutrition. Current strategies for CRBSI prevention in these patients include implementing protocols and checklists for line insertion and maintenance, avoiding femoral veins in patients with enterostomies, considering an antibiotic or ethanol lock and using a chlorhexidine dressing in patients with recurrent infections.
Conflicts of interest
The authors have no conflicts of interest to disclose.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 92).
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