Central venous catheters increase the risk of nosocomial infection [1,2], with devastating consequences for immunocompromised patients. The incidence of catheter related sepsis ranges from 2.8–17.4% for systemic infection in a surgical intensive care unit (ICU) [3–5]. Previous studies [6,7] have demonstrated the benefit of antiseptic-coated (silver-sulphadiazine/chlorhexidine acetate) catheters and we have attempted to quantify the advantages in the immunocompromised patient.
Patients, undergoing or having undergone transplantation of the heart, heart-lung or lung(s) with concomitant immunosuppression, requiring central venous access, were recruited. After local Ethics Committee approval (DEC625, Hillingdon Health Agency), we studied 86 episodes in consenting patients aged 19–60 years. Patients were randomly allocated, by computer generated random numbers, either to a control group (Group I) in whom a standard multi-lumen polyurethane central venous catheter (Arrow International, Reading, PA, USA), or to a trial group (Group II) in whom a chlorhexidine and silver-sulphadiazine impregnated multi-lumen catheter (ARROWgard Blue™, Arrow International) was inserted. Unfortunately, as the impregnated catheter is manufactured in blue, it was not possible to blind the physicians inserting the catheter or involved in the care. All patients had 2% aqueous chlorhexidine  based skin preparation, following which the attending physician allocated the central venous catheter with a full aseptic technique. The site (internal jugular, subclavian or femoral) and ease of insertion (1–2 attempts, >2 attempts, multiple sites) were noted. The site was then dressed with an transparent bioocclusive dressing. No catheters were inserted by replacement over a guidewire. The dressing was changed daily, and the catheter left in situ. The catheter was removed if there were signs of local infection (erythema, pus), positive blood cultures requiring a change of lines, or a clinical decision was made for catheter removal. The catheter was removed by a standard aseptic non-touch protocol, the tip cut with sterile scissors into a gallipot, and sent for microbiological investigation. Maki's semi-quantitative technique was used , with the tip rolled over a blood agar plate and incubated and the colonies formed at 72h were counted, giving a quantitative number of colony forming units (CFU). Analysis was undertaken by technicians unaware of the difference between the catheters. The concomitant use of antibiotics was recorded, as were other clinical investigations of blood, urine cultures, other catheter tips and swabs of likely infected sites initiated by the clinician. The immunosuppression regime was decided by the clinical team and altered according to clinical and laboratory data.
We regarded colony growth greater than 5 CFU to be significant and defined a colonized catheter as suggested by Collignon et al..
Another site of infection (blood culture, other line or urine) growing the same organism with a similar antibiotic sensitivity profile as the colonized central venous catheter identified associated infection.
Comparison between the groups was with Student's t-test or χ2 analysis where indicated. Fisher's exact test was used where the conditions for χ2 analysis were not present. Significance was accepted at P<0.05.
Eighty-six catheters were studied, of which 79 valid results from 60 patients were obtained. Seven catheters were lost owing to deviation from protocol, contamination of catheter tip and death. Of these 79 catheters, 35 were in the control group (standard catheter) and 44 in the study group (ARROWgard Blue™). Transplantation procedures, mean duration of use, ease of insertion and site of insertion were comparable between the two groups (Tables 1 and 2). No catheters were removed because of overt sepsis or pyrexia. Both groups had prophylaxis of cefotaxime (10–20 mg kg−1 8 hourly) and flucloxacillin (10–15 mg kg−1 6 hourly), with the addition of ofloxacin, ceftazidime and teicoplanin, when indicated.
The results of the catheter tip cultures are summarized in Table 3. Of the 35 catheters removed from the control group, 25 (71%) had positive catheter tip cultures. Of these, 18 (51%) had Coagulase negative staphylococci, 11 (31%) had Enterobacteriaceae and 1 (3%) Pseudomonas aeruginosa. Of the 44 catheters removed from the study group, 10 (25%) had positive catheter tip cultures, of which all 10 had Coagulase negative staphylococci, and 3 (7%) had additional Enterococcus faecalis.
Furthermore, of the 25 infected catheters in the control group, 11 had an associated infection, positive blood cultures were identified in three of these. Ten of the 35 catheters in the control group were not infected, but 2 (20%) of these had other positive cultures (blood, other line tips, urine). Four of the 10 infected catheters had an associated infection (P<0.03), of which one was a positive blood culture. Thirty-three of the 44 study group catheters were not infected, but 6 (18%) patients had evidence of infection from another source(P=NS). No adverse events including hypersensitivity or toxicity were seen.
The use of central venous lines for monitoring and therapy in the immunocompromised patient is routine. Bacterial contamination may have devastating consequences . Vincent et al., in a survey of the prevalence of infection in general ICUs across Europe, found that the presence of a central venous catheter was associated with a four-fold increased odds ratio for nosocomial infection. Although the population reported here was different, specialist unit against general medical/surgical ICUs, we can reasonably expect a similar if not greater increase in risk of infection in this population. One of the novel approaches used to limit infection, is the use of catheters impregnated with antiseptic materials, chlorhexidine and silver sulphadiazine. The rationale for the use of these agents have been discussed elsewhere [11,12] and includes the effectiveness of these compounds when used as topical agents and a low potential for resistance to develop to these compounds. Studies in animals , have shown a reduction in the colonization of catheter tips. We have studied the impact of using these catheters in an immunosuppressed (transplant) population, during short term use associated with major surgery or acute clinical deterioration. The study catheter contains 0.67 mg of silver sulphadiazine and 1.2 mg of chlorhexidine in a 10 cm length of catheter . The levels of these compounds, measured within blood, are less than 1% of the therapeutic levels required, when systemic treatment is given , and the likelihood of sensitivity or toxicity is low. In clinical use, no episodes of sensitivity to the catheters have been reported (Arrow International, personal communication). Blood levels of silver, sulphadiazine and chlorhexidine have been reported to remain below the detectable limit . Apart from the catheter itself, a number of other factors are known to influence the incidence of catheter related sepsis. These include duration of catheter use, ease of insertion, site of insertion, number of lumens, skin preparation and catheter care . Both groups were comparable with regard to these factors, although the control group had a statitistically non significant higher rate (29% CFU 21%) of femoral catheterization. As suggested by Collignon et al., we routinely accept 5 CFU as significant. The high colonization rates of the standard catheters surprised us, but in the study by Bach et al., 100% of such catheters were colonized, and therefore the rate reported here of 71% (using >5 CFU) is comparable. The use of the antiseptic bonded catheter resulted in the number of catheters colonized being reduced by 68%. This reduction was seen, both in the colonization by Coagulase negative staphylococci and Enterobacteriacaeae. Although Coagulase negative staphylococci are commonly regarded as a contaminant, its significance has been reviewed [13,15–17] and it cannot be regarded as benign. Other organisms that are commonly associated with catheter related sepsis, include Staphylococcus aureus, and Candida. We had no instances of infection with these organisms. We presume that the low incidence of colonization with Staphylococcus aureus was secondary to the routine use of flucloxacillin, and the low incidence of fungal infections as the lines were not used for parenteral nutrition and their relatively short duration of use. Catheter infections associated with other infected sources of the same organism, are highly suggestive of catheter related sepsis and were reduced by 58%.
We conclude that the use of chlorhexidine and silver-sulphadiazine impregnated catheters in the immunocompromised patient, reduces colonization of the catheter tip, and associated infection in blood or other invasive lines. Extrapolation of these results to a reduction in sepsis and death [18,19] would require a larger study.
We thank Arrow International for the supply of 'ARROWgard Blue' catheters at the same unit price as the standard polyurethane catheters normally purchased. No other assistance was received. We also thank P. Dimmer and his team of operating department assistants for their assistance without which this project would have taken considerably longer.
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