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Contamination of central venous catheters in immunocompromised patients: a comparison between two different types of central venous catheters
Journal of Hospital Infection (2002) 50: 202±206 doi:10.1053/jhin.2001.1095, available online at http://www.idealibrary.com on
Contamination of central venous catheters in immunocompromised patients: a comparison between two different types of central venous catheters B. Stoiser*, J. Koflery, T. Staudingerz, A. Georgopoulos*, S. Lugauerx, J. P. Guggenbichlerx, H. Burgmann* and M. Frassz *Department of Internal Medicine I (Division of Infectious Diseases and Chemotherapy), yDepartment of Emergency Medicine, zDepartment of Internal Medicine (Division of Intensive Care Unit), University of Vienna, and xClinic for Children and Adolescent, University of Erlangen-Nuernberg, Austria Summary: Catheters impregnated with silver have been proposed as a means of reducing catheter-related infection. We therefore performed a prospective randomized study to compare a new silver-impregnated central venous catheter (CVC) with a commercially available CVC in a cohort of immunocompromised patients. We studied 157 patients of whom 97 could be analysed. The median indwelling time in the study group (SC) was 10.5 days and 11 days in the control group (CC). The incidence of contamination in the SC group was 15.6 vs 24.6 in the CC group referring to 1000 catheter days. In both groups, we found 6% of catheter-related infections according to the definitions of a published scoring system. The differences between the two groups were not significant. We conclude that the SC decrease the incidence of catheter contamination and may have a positive effect on the reduction of CVC-related infections. & 2002 The Hospital Infection Society
Keywords: Impregnated central venous catheter; catheter-related infection; immunosuppression.
Introduction Transcutaneous implantation of central venous catheters (CVC) plays an important role in the care of critically ill patients. CVCs are essential for efficient fluid supply, intravenous chemotherapy and parenteral nutrition. Furthermore, CVCs are valuable tools for monitoring central venous pressures. However, the implantation of CVCs may be associated with Received 2 May 2001; revised manuscript accepted 18 September 2001; published online 18 February 2002. Author for correspondence: Dr B. Stoiser, Department of Internal Medicine I, Div. of Infectious Diseases and Chemotherapy, WaÈhringer GuÈrtel 18-20, A-1090 Vienna. Fax: 43 1 40400/4418; E-mail: [email protected]
0195-6701/02/0302021 05 $35.00/0
severe complications such as (haemo)pneumothorax, arterial puncture, haemorrhage or catheter dislocation.1 The main problem, however, remains catheterrelated infection. Several trials with the aim of reducing the risk of catheter-related infections have been conducted. Antibiotic- or silver-coated catheters have undergone examination,2,3 and special attention has been given to disinfection at the site of catheter insertion,4 and the handling with the catheter hubs.5 Despite these improvements, catheter-related bloodstream infections are still a common cause of patient morbidity and among the most frequent nosocomial infections. Recently,aspeciallydevelopedtechnicalprocedure has been used to disperse small particles of metallic & 2002 The Hospital Infection Society
CVC and contamination
silver into the material of polyurethane catheters, thereby facilitating gradual release of silver ions from the impregnated catheter. Silver ions are thereby incorporated into all areas of the catheter. This results in a stable antimicrobial activity in the tissues surrounding the catheter over a prolonged period of time.6,7 Preliminary studies using the new catheter in surgical patients were encouraging in respect of reduced contamination and resulting catheter-related bloodstream infections.8 The aim of the present study was to assess the possible benefits of a new polyurethane catheter impregnated with dispersed silver ions in immunocompromised patients. Since patients suffering from cancer, haematological malignancies and bone marrow or organ transplantation have an elevated risk for catheter-associated infections,9±11 this prospective, randomized study was conducted in a cohort of immunocompromised patients. Patients and methods One hundred and fifty-four consecutive patients requiring implantation of a CVC were included into this study. Implantation was performed at two intensive care units of the University Hospital of Vienna from April to December 1997. The study was approved by the Institutional Review Board. After giving informed consent, the patients were randomized to receive either a conventional polyurethane catheter (Arrow1, Reading, PA, USA), or a silverimpregnated catheter (ArgenTec1, Fa, City, Country). Both were triple lumen catheters and inserted using a Seldinger technique. Only data of catheters implanted for at least three days were evaluated. Catheter implantation The catheters were inserted by experienced physicians wearing caps, masks, sterile gloves and sterile coats. The insertion site was disinfected with a preparation containing 1 mg hexidine, 314 mg isopropanol and 281 mg n-propanol (corresponding to a 75% solution of alcohol in water, Isozid1-H, Gebro, Fieberbrunn, Austria) and covered by sterile drapes. The catheter was then inserted using the Seldinger technique into either the internal jugular vein or into the subclavian vein by either the infraclavicular or supraclavicular approach. After insertion, catheter entry sites were dressed with sterile gauze and tape. Problems in puncturing the vessel, the number of unsuccessful punctures, ease of insertion, and
203
the catheter position as assessed by chest X-ray were documented. The local appearance was also documented. Clinical follow-up After catheter insertion, C-reactive protein peripheral leukocyte count, temperature, antibiotic therapy and volume substitution and/or parenteral nutrition via the study catheter were documented on a daily basis. When an inflammatory process was suspected, additional examinations such as chest X-rays, blood cultures, wound swabs and urine cultures were performed. The catheter insertion site was inspected by nurses each time the dressing was changed, and patients were asked about discomfort at the site. Microbiological follow-up The decision to remove a catheter was taken by the physicians responsible for the patient's care. Reasons for catheter removal were termination of therapy, catheter dysfunction or suspicion of a catheterrelated infection. The removal was performed by one of the authors of the study according to the following protocol. First a swab from the insertion site was taken, then the insertion site was disinfected with Isozid1-H and the catheter was removed under sterile conditions and was cut at a distance of 5 cm from its tip. Stored in a sterile tube, it was immediately taken for microbiological examination. The catheter segment was examined using a semiquantitative method as described by Maki,2,12 including a roll-plate culture, a selective culture of the lumen, and a culture of the collected fluid. First, the catheter tip was rolled on a blood agar plate. To determine bacterial contamination of the catheter lumen, the catheter was held with sterile forceps and filled using a sterile needle attached to a syringe with 0.5 mL phosphate-buffered saline (PBS) for 5 min, then the lumens were flushed with 5 mL PBS and the fluid was collected in a tube. A separate agar plate was inoculated with 1 mL of this fluid. The catheter segment was then stored in a PBS-filled tube for selective culture of the luminal fluid. The swab of the catheter insertion site was also rolled out on a third agar plate. The two tubes and the three plates were incubated for at least 72 h at a temperature of 37 C. Microbial growth was quantified as colony forming units (cfu). A growth of more than 15 cfu on the blood agar plate was considered positive. Bacterial and fungal species were identified using commercially available tests (API1 bioMeÂrieux, France).
204
Infection criteria To assess catheter-related infections, a score system described by Lugauer et al.13 was used. This scheme evaluates clinical and microbiological parameters to provide a score on which the likelihood of infection is categorized. Statistical analysis For determination of differences between groups, a standard statistical software package was used (SPSS for Windows 6.0). Continuous data are presented as median and range except where indicated. For dichotomous variables, percentages were calculated. Differences between means were calculated by Student's t-test or by Wilcoxon rank-sum test. Percentages were compared by Chi-square test or Fisher's exact test, if appropriate. The cumulative possibility was determined by the Kaplan-Meier method; differences between groups were analysed by the log rank test. All tests were two-tailed. A p-value <0.05 was considered statistically significant. Results Out of 154 catheter insertions, 97 could be analysed with respect to microbiology. Fifty-seven patients had to be excluded from evaluation due to removal of the catheter prior to day 3, accidental removal of the catheter, transfer of the patient to another hospital, or death prior to the end of the study. Of the remaining patients, 50 had been randomized to receive a silver-impregnated catheter (SC group) and 47 patients were randomized to the control group (CC group). There was no statistically significant difference between the groups with respect to age, sex and underlying diseases. The same applied for additional risk factors for infections such as parenteral nutrition, drains or mechanical ventilation. Patient data are shown in Table I. Catheter insertion sites were evenly distributed in both groups, (SC: 26% V. jugularis, 74%: V. subclavia; CC: 32% V. jugularis, 68%: V. subclavia). In the SC group, the mean indwelling time of the catheter was 10.5 days (median, range 3±39) vs. 11.0 days (median, range 4±46) in the CC group. The median antibiotic index (sum of days with antibiotic therapy/sum of days of catheter indwelling time 100) in the SC group was 73.3 vs. 93.0 in the CC group; this was not statistically different. At the time of implantation, 10 patients in the SC group
B. Stoiser et al.
Table I Patient characteristics
No. patients Age (range; median) Sex (f/m) Jugular vein insertion Subclavian vein insertion Number of contaminated catheters Underlying diseases Solid tumour Haematological disorder Bone marrow transplantation Organ transplantation Immunosuppression Indwelling time (range/median)
Silver-impregnated catheter
Control catheter
50 20±84/51 27/23 13 37 11
47 24±81/52 21/26 15 32 15
12 10 4 17 6 3±39/10.5
17 7 1 16 6 4±46/11.0
Table II Spectrum of isolates from the catheter segment Coagulase negative Staphylococcus Staphylococcus aureus Streptococcus sp. Klebsiella sp. Enterobacter sp. Candida sp.
68% 12% 4% 4% 4% 8%
(28.6%) received an antistaphylococcal antibiotic compared with 20 in the CC group (62.5%). By the time of removal, 21 (42%) patients in the SC group vs. 20 (40.4%) in the CC group had received antibiotic therapy. Microbiological follow-up revealed 39 sterile cultures in the SC group vs. 32 in the CC group. Ten (SC) vs. 14 (CC) catheters were contaminated, defined as the growth of more than 15 cfu on the blood agar plate. One catheter in each group was culture-positive in the collected fluid only. The contamination rate per 100 catheters was 20 in the SC group vs. 29.8 in the CC group. Contamination episodes per 1000 catheter days in the SC group was 15.6 vs. 24.6 in the CC group. The SC/CC ratio for contamination was therefore 0.630. None of the comparisons between the groups revealed statistical significance. In the SC group, six patients (12%) had clinical signs of infection; three of these infections were attributed to the catheter according to the scoring system used above. In the CC group, 10 patients (21%) showed signs of infection; three of them were considered catheter-related. The spectrum of organisms isolated three is shown in Table II.
CVC and contamination
Discussion Our data revealed a non-significant tendency towards a reduced colonization rate of the silver-impregnated study catheters compared with conventional CVCs in a cohort of immunocompromised patients. The rate of catheter-related systemic infection did not differ between the groups. Median indwelling time was 12 days in both groups, which is considerably longer than in comparable trials.3,14,15 A recently published study comparing a silver-ion-impregnated catheter with conventional catheters found favourable results with respect to the study catheter.8 However, the study population examined consisted mainly of patients undergoing surgery. In our study, patients were immunocompromised and therefore received systemic antibiotic therapy to an extent of 90% during the observation period. Moreover, a tendency towards less antimicrobial medication in the SC group was observed. Most of the patients received antibiotics active against staphylococci. Staphylococci are the most common infectious agents associated with catheter-related infections.16 Bock et al. showed that in patients undergoing immunotherapy, prophylactic use of antibiotics was able to prevent catheter-related infection.17 The high rate of systemic antibiotic therapy, especially in the CC group, may have reduced the catheter-related infection rate. Statistically significant differences might have been found using a larger cohort of patients. Colonization and catheter-related systemic infection rate was low in both groups taking into account a relatively long indwelling time compared with other studies.2,3 Infection rates with multi-lumen catheters have been reported to occur in up to 19%,15,17 and in immunocompromised patients as high as 28%. Silver with its oligodynamic efficacy of the metallic ions is active against the majority of bacterial microorganisms, viruses and fungi. It is stated that silver ions attach to the SH groups of cellular membrane enzymes and so block the metabolism of the microorganisms. This both prevents the adherence of potentially harmful micro-organisms to synthetic materials, and leads to damage of the micro-organisms themselves. For decades, the combination of silver nitrate and silver acetate known as Crede's prophylactics has been used to prevent bacterial eye infection in newborns. The external coating of CVC with clorhexidine plus sulphadiazine silver was found by George et al. to reduce catheter-related infections.18 In these trials, the bactericidal effect was restricted to the catheter surface and did not extend to the lumen.
205
However, it has been shown that after an indwelling time of more than 10 days, infection is predominantly intraluminal.16 The average catheter indwelling time in the above cited trials was about seven days in the trials by Maki et al.2 and Darouiche et al.3 and thus considerably shorter than in our study. Therefore, the colonization rates in these studies are not directly comparable to our data. The distribution of the organisms isolated did not differ between the groups, suggesting there was no selection pressure. To exclude the development of resistance towards silver, a longer observation period would be needed. In conclusion, our study revealed no statistically significant benefit of the silver-impregnated CVC. However, in conjunction with a broad-spectrum antibiotic prophylaxis in immunocompromised patients and careful catheter management, they may help to decrease the incidence of catheter contamination and thereby the rate of catheter-related infections. References 1. Yilmazlar A, Bigilin H, Korfali G, Eren A, Ozkan U. Complications of 1303 central venous cannulations. J R Soc Med 1997; 90: 319±321. 2. Maki DG, Stolz SM, Wheeler S, Mermel SL. Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. Ann Intern Med 1997; 127: 257±265. 3. Darouiche RO, Raad I, Heard SO et al. A comparison of two antimicrobial-impregnated central venous catheters. N Engl J Med 1999; 340: 1±8. 4. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of providone-iodine, alcohol, and chlorhexidine for the prevention of infection associated with central venous and arterial catheters. Lancet 1991; 338: 339±343. 5. Tebbs SE, Trend V, Elliott TSJ. The potential reduction of microbial contamination of central venous catheters. J Infect 1995; 30: 107±113. 6. Guggenbichler JP, BoÈswald M, Lugauer S, Krall T. Eine neue Technologie der SilberimpraÈgnierung verleiht Kathetern antimikrobielle Eigenschaften. Infect 1998; 26 (Suppl.) S18±S24. 7. Bechert T, BoÈswald M, Lugauer S, Regenfus A, Greil J, Guggenbichler JP. Der Erlanger Silberkatheter: In-vitro-Ergebnisse zur antimikrobiellen Wirksamkeit. Infect 1998; 26 (Suppl.) S25±S31. 8. BoÈswald M, Lugauer S, Regenfus A et al. Reduktion Katheter-assoziierter Infektionen durch Verwendung eines neuartig impraÈgnierten zentral-venoÈsen Katheters. Infect 1998; 26 (Suppl.) S61±S66. 9. Collignon, Soni N, Pearson I. Sepsis associated with central vein catheters in critically ill patients. Int Care Med 1988; 14: 227±231. 10. Salazar R, Sola C, Maroto P et al. Infectious complications in 126 patients treated with high-dose
206
11.
12.
13.
14.
B. Stoiser et al. chemotherapy and autologous peripheral blood stem cell transplantation. Bone Marrow Transpl 1999; 23: 27±33. Jaeger K, Osthaus A, Heine J et al. Efficacy of a benzalkonium chloride-impregnated central venous catheter to prevent catheter-associated infection in cancer patients. Chemother 2001; 47: 50±55. Maki DG, Weise CE, Sarafin HW. A semiquantitative culture method for identifying intravenouscatheter-related infection. N Engl J Med 1977; 296: 1305±1309. Lugauer S, Regenfus A, BoÈswald M et al. Sicherung der klinischen Diagnose einer Katheter-assoziierten Infektion anhand eines Bewertungsscores. Infect 1998; 26 (Suppl.) S53±S59. Raad I, Darouiche R, Dupuis J et al. Central venous catheter coated with minocycline and rifampicin for the prevention of catheter-related colonization and
15.
16. 17.
18.
bloodstream infections. Ann Intern Med 1997; 127: 267±274. Tacconelli E, Tumbarello M, Pittiruti M et al. Central venous catheter-related sepsis in a cohort of 366 hospitalised patients. Eur J Clin Microbial Infect Dis 1997; 16: 203±209. Raad I. Intravascular-catheter-related infections. Lancet 1998; 351: 893±898. Bock SN, Lee RE, Fisher B et al. A prospective randomized trial evaluating prophylactic antibiotics to prevent triple-lumen catheter-related sepsis in patients treated with immunotherapy. J Clin Oncol 8: 161±169. George SJ, Vuddamalay P, Boscoe MJ. Antisepticimpregnated central venous catheters reduce the incidence of bacterial colonization and associated infection in immunocompromised transplant patients. Eur J Anaest 1997; 14: 428±431.
Contamination of central venous catheters in immunocompromised patients: a comparison between two different types of central venous catheters B. Stoiser*, J. Koflery, T. Staudingerz, A. Georgopoulos*, S. Lugauerx, J. P. Guggenbichlerx, H. Burgmann* and M. Frassz *Department of Internal Medicine I (Division of Infectious Diseases and Chemotherapy), yDepartment of Emergency Medicine, zDepartment of Internal Medicine (Division of Intensive Care Unit), University of Vienna, and xClinic for Children and Adolescent, University of Erlangen-Nuernberg, Austria Summary: Catheters impregnated with silver have been proposed as a means of reducing catheter-related infection. We therefore performed a prospective randomized study to compare a new silver-impregnated central venous catheter (CVC) with a commercially available CVC in a cohort of immunocompromised patients. We studied 157 patients of whom 97 could be analysed. The median indwelling time in the study group (SC) was 10.5 days and 11 days in the control group (CC). The incidence of contamination in the SC group was 15.6 vs 24.6 in the CC group referring to 1000 catheter days. In both groups, we found 6% of catheter-related infections according to the definitions of a published scoring system. The differences between the two groups were not significant. We conclude that the SC decrease the incidence of catheter contamination and may have a positive effect on the reduction of CVC-related infections. & 2002 The Hospital Infection Society
Keywords: Impregnated central venous catheter; catheter-related infection; immunosuppression.
Introduction Transcutaneous implantation of central venous catheters (CVC) plays an important role in the care of critically ill patients. CVCs are essential for efficient fluid supply, intravenous chemotherapy and parenteral nutrition. Furthermore, CVCs are valuable tools for monitoring central venous pressures. However, the implantation of CVCs may be associated with Received 2 May 2001; revised manuscript accepted 18 September 2001; published online 18 February 2002. Author for correspondence: Dr B. Stoiser, Department of Internal Medicine I, Div. of Infectious Diseases and Chemotherapy, WaÈhringer GuÈrtel 18-20, A-1090 Vienna. Fax: 43 1 40400/4418; E-mail: [email protected]
0195-6701/02/0302021 05 $35.00/0
severe complications such as (haemo)pneumothorax, arterial puncture, haemorrhage or catheter dislocation.1 The main problem, however, remains catheterrelated infection. Several trials with the aim of reducing the risk of catheter-related infections have been conducted. Antibiotic- or silver-coated catheters have undergone examination,2,3 and special attention has been given to disinfection at the site of catheter insertion,4 and the handling with the catheter hubs.5 Despite these improvements, catheter-related bloodstream infections are still a common cause of patient morbidity and among the most frequent nosocomial infections. Recently,aspeciallydevelopedtechnicalprocedure has been used to disperse small particles of metallic & 2002 The Hospital Infection Society
CVC and contamination
silver into the material of polyurethane catheters, thereby facilitating gradual release of silver ions from the impregnated catheter. Silver ions are thereby incorporated into all areas of the catheter. This results in a stable antimicrobial activity in the tissues surrounding the catheter over a prolonged period of time.6,7 Preliminary studies using the new catheter in surgical patients were encouraging in respect of reduced contamination and resulting catheter-related bloodstream infections.8 The aim of the present study was to assess the possible benefits of a new polyurethane catheter impregnated with dispersed silver ions in immunocompromised patients. Since patients suffering from cancer, haematological malignancies and bone marrow or organ transplantation have an elevated risk for catheter-associated infections,9±11 this prospective, randomized study was conducted in a cohort of immunocompromised patients. Patients and methods One hundred and fifty-four consecutive patients requiring implantation of a CVC were included into this study. Implantation was performed at two intensive care units of the University Hospital of Vienna from April to December 1997. The study was approved by the Institutional Review Board. After giving informed consent, the patients were randomized to receive either a conventional polyurethane catheter (Arrow1, Reading, PA, USA), or a silverimpregnated catheter (ArgenTec1, Fa, City, Country). Both were triple lumen catheters and inserted using a Seldinger technique. Only data of catheters implanted for at least three days were evaluated. Catheter implantation The catheters were inserted by experienced physicians wearing caps, masks, sterile gloves and sterile coats. The insertion site was disinfected with a preparation containing 1 mg hexidine, 314 mg isopropanol and 281 mg n-propanol (corresponding to a 75% solution of alcohol in water, Isozid1-H, Gebro, Fieberbrunn, Austria) and covered by sterile drapes. The catheter was then inserted using the Seldinger technique into either the internal jugular vein or into the subclavian vein by either the infraclavicular or supraclavicular approach. After insertion, catheter entry sites were dressed with sterile gauze and tape. Problems in puncturing the vessel, the number of unsuccessful punctures, ease of insertion, and
203
the catheter position as assessed by chest X-ray were documented. The local appearance was also documented. Clinical follow-up After catheter insertion, C-reactive protein peripheral leukocyte count, temperature, antibiotic therapy and volume substitution and/or parenteral nutrition via the study catheter were documented on a daily basis. When an inflammatory process was suspected, additional examinations such as chest X-rays, blood cultures, wound swabs and urine cultures were performed. The catheter insertion site was inspected by nurses each time the dressing was changed, and patients were asked about discomfort at the site. Microbiological follow-up The decision to remove a catheter was taken by the physicians responsible for the patient's care. Reasons for catheter removal were termination of therapy, catheter dysfunction or suspicion of a catheterrelated infection. The removal was performed by one of the authors of the study according to the following protocol. First a swab from the insertion site was taken, then the insertion site was disinfected with Isozid1-H and the catheter was removed under sterile conditions and was cut at a distance of 5 cm from its tip. Stored in a sterile tube, it was immediately taken for microbiological examination. The catheter segment was examined using a semiquantitative method as described by Maki,2,12 including a roll-plate culture, a selective culture of the lumen, and a culture of the collected fluid. First, the catheter tip was rolled on a blood agar plate. To determine bacterial contamination of the catheter lumen, the catheter was held with sterile forceps and filled using a sterile needle attached to a syringe with 0.5 mL phosphate-buffered saline (PBS) for 5 min, then the lumens were flushed with 5 mL PBS and the fluid was collected in a tube. A separate agar plate was inoculated with 1 mL of this fluid. The catheter segment was then stored in a PBS-filled tube for selective culture of the luminal fluid. The swab of the catheter insertion site was also rolled out on a third agar plate. The two tubes and the three plates were incubated for at least 72 h at a temperature of 37 C. Microbial growth was quantified as colony forming units (cfu). A growth of more than 15 cfu on the blood agar plate was considered positive. Bacterial and fungal species were identified using commercially available tests (API1 bioMeÂrieux, France).
204
Infection criteria To assess catheter-related infections, a score system described by Lugauer et al.13 was used. This scheme evaluates clinical and microbiological parameters to provide a score on which the likelihood of infection is categorized. Statistical analysis For determination of differences between groups, a standard statistical software package was used (SPSS for Windows 6.0). Continuous data are presented as median and range except where indicated. For dichotomous variables, percentages were calculated. Differences between means were calculated by Student's t-test or by Wilcoxon rank-sum test. Percentages were compared by Chi-square test or Fisher's exact test, if appropriate. The cumulative possibility was determined by the Kaplan-Meier method; differences between groups were analysed by the log rank test. All tests were two-tailed. A p-value <0.05 was considered statistically significant. Results Out of 154 catheter insertions, 97 could be analysed with respect to microbiology. Fifty-seven patients had to be excluded from evaluation due to removal of the catheter prior to day 3, accidental removal of the catheter, transfer of the patient to another hospital, or death prior to the end of the study. Of the remaining patients, 50 had been randomized to receive a silver-impregnated catheter (SC group) and 47 patients were randomized to the control group (CC group). There was no statistically significant difference between the groups with respect to age, sex and underlying diseases. The same applied for additional risk factors for infections such as parenteral nutrition, drains or mechanical ventilation. Patient data are shown in Table I. Catheter insertion sites were evenly distributed in both groups, (SC: 26% V. jugularis, 74%: V. subclavia; CC: 32% V. jugularis, 68%: V. subclavia). In the SC group, the mean indwelling time of the catheter was 10.5 days (median, range 3±39) vs. 11.0 days (median, range 4±46) in the CC group. The median antibiotic index (sum of days with antibiotic therapy/sum of days of catheter indwelling time 100) in the SC group was 73.3 vs. 93.0 in the CC group; this was not statistically different. At the time of implantation, 10 patients in the SC group
B. Stoiser et al.
Table I Patient characteristics
No. patients Age (range; median) Sex (f/m) Jugular vein insertion Subclavian vein insertion Number of contaminated catheters Underlying diseases Solid tumour Haematological disorder Bone marrow transplantation Organ transplantation Immunosuppression Indwelling time (range/median)
Silver-impregnated catheter
Control catheter
50 20±84/51 27/23 13 37 11
47 24±81/52 21/26 15 32 15
12 10 4 17 6 3±39/10.5
17 7 1 16 6 4±46/11.0
Table II Spectrum of isolates from the catheter segment Coagulase negative Staphylococcus Staphylococcus aureus Streptococcus sp. Klebsiella sp. Enterobacter sp. Candida sp.
68% 12% 4% 4% 4% 8%
(28.6%) received an antistaphylococcal antibiotic compared with 20 in the CC group (62.5%). By the time of removal, 21 (42%) patients in the SC group vs. 20 (40.4%) in the CC group had received antibiotic therapy. Microbiological follow-up revealed 39 sterile cultures in the SC group vs. 32 in the CC group. Ten (SC) vs. 14 (CC) catheters were contaminated, defined as the growth of more than 15 cfu on the blood agar plate. One catheter in each group was culture-positive in the collected fluid only. The contamination rate per 100 catheters was 20 in the SC group vs. 29.8 in the CC group. Contamination episodes per 1000 catheter days in the SC group was 15.6 vs. 24.6 in the CC group. The SC/CC ratio for contamination was therefore 0.630. None of the comparisons between the groups revealed statistical significance. In the SC group, six patients (12%) had clinical signs of infection; three of these infections were attributed to the catheter according to the scoring system used above. In the CC group, 10 patients (21%) showed signs of infection; three of them were considered catheter-related. The spectrum of organisms isolated three is shown in Table II.
CVC and contamination
Discussion Our data revealed a non-significant tendency towards a reduced colonization rate of the silver-impregnated study catheters compared with conventional CVCs in a cohort of immunocompromised patients. The rate of catheter-related systemic infection did not differ between the groups. Median indwelling time was 12 days in both groups, which is considerably longer than in comparable trials.3,14,15 A recently published study comparing a silver-ion-impregnated catheter with conventional catheters found favourable results with respect to the study catheter.8 However, the study population examined consisted mainly of patients undergoing surgery. In our study, patients were immunocompromised and therefore received systemic antibiotic therapy to an extent of 90% during the observation period. Moreover, a tendency towards less antimicrobial medication in the SC group was observed. Most of the patients received antibiotics active against staphylococci. Staphylococci are the most common infectious agents associated with catheter-related infections.16 Bock et al. showed that in patients undergoing immunotherapy, prophylactic use of antibiotics was able to prevent catheter-related infection.17 The high rate of systemic antibiotic therapy, especially in the CC group, may have reduced the catheter-related infection rate. Statistically significant differences might have been found using a larger cohort of patients. Colonization and catheter-related systemic infection rate was low in both groups taking into account a relatively long indwelling time compared with other studies.2,3 Infection rates with multi-lumen catheters have been reported to occur in up to 19%,15,17 and in immunocompromised patients as high as 28%. Silver with its oligodynamic efficacy of the metallic ions is active against the majority of bacterial microorganisms, viruses and fungi. It is stated that silver ions attach to the SH groups of cellular membrane enzymes and so block the metabolism of the microorganisms. This both prevents the adherence of potentially harmful micro-organisms to synthetic materials, and leads to damage of the micro-organisms themselves. For decades, the combination of silver nitrate and silver acetate known as Crede's prophylactics has been used to prevent bacterial eye infection in newborns. The external coating of CVC with clorhexidine plus sulphadiazine silver was found by George et al. to reduce catheter-related infections.18 In these trials, the bactericidal effect was restricted to the catheter surface and did not extend to the lumen.
205
However, it has been shown that after an indwelling time of more than 10 days, infection is predominantly intraluminal.16 The average catheter indwelling time in the above cited trials was about seven days in the trials by Maki et al.2 and Darouiche et al.3 and thus considerably shorter than in our study. Therefore, the colonization rates in these studies are not directly comparable to our data. The distribution of the organisms isolated did not differ between the groups, suggesting there was no selection pressure. To exclude the development of resistance towards silver, a longer observation period would be needed. In conclusion, our study revealed no statistically significant benefit of the silver-impregnated CVC. However, in conjunction with a broad-spectrum antibiotic prophylaxis in immunocompromised patients and careful catheter management, they may help to decrease the incidence of catheter contamination and thereby the rate of catheter-related infections. References 1. Yilmazlar A, Bigilin H, Korfali G, Eren A, Ozkan U. Complications of 1303 central venous cannulations. J R Soc Med 1997; 90: 319±321. 2. Maki DG, Stolz SM, Wheeler S, Mermel SL. Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. Ann Intern Med 1997; 127: 257±265. 3. Darouiche RO, Raad I, Heard SO et al. A comparison of two antimicrobial-impregnated central venous catheters. N Engl J Med 1999; 340: 1±8. 4. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of providone-iodine, alcohol, and chlorhexidine for the prevention of infection associated with central venous and arterial catheters. Lancet 1991; 338: 339±343. 5. Tebbs SE, Trend V, Elliott TSJ. The potential reduction of microbial contamination of central venous catheters. J Infect 1995; 30: 107±113. 6. Guggenbichler JP, BoÈswald M, Lugauer S, Krall T. Eine neue Technologie der SilberimpraÈgnierung verleiht Kathetern antimikrobielle Eigenschaften. Infect 1998; 26 (Suppl.) S18±S24. 7. Bechert T, BoÈswald M, Lugauer S, Regenfus A, Greil J, Guggenbichler JP. Der Erlanger Silberkatheter: In-vitro-Ergebnisse zur antimikrobiellen Wirksamkeit. Infect 1998; 26 (Suppl.) S25±S31. 8. BoÈswald M, Lugauer S, Regenfus A et al. Reduktion Katheter-assoziierter Infektionen durch Verwendung eines neuartig impraÈgnierten zentral-venoÈsen Katheters. Infect 1998; 26 (Suppl.) S61±S66. 9. Collignon, Soni N, Pearson I. Sepsis associated with central vein catheters in critically ill patients. Int Care Med 1988; 14: 227±231. 10. Salazar R, Sola C, Maroto P et al. Infectious complications in 126 patients treated with high-dose
206
11.
12.
13.
14.
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