Prospective Randomized Trial of 3 Antiseptic Solutions for Prevention of Catheter Colonization in an Intensive Care Unit for Adult Patients Author(s): By J. Vallés , MD; I. Fernández , RN; D. Alcaraz , RN; E. Chacón , RN; A. Cazorla , RN; M. Canals , RN; D. Mariscal , MD; D. Fontanals , PharmD; A. Morón , PharmD Source: Infection Control and Hospital Epidemiology, Vol. 29, No. 9 (September 2008), pp. 847853 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/590259 . Accessed: 30/09/2013 10:14
Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at . http://www.jstor.org/page/info/about/policies/terms.jsp

.
JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.

.

The University of Chicago Press and The Society for Healthcare Epidemiology of America are collaborating with JSTOR to digitize, preserve and extend access to Infection Control and Hospital Epidemiology.

http://www.jstor.org

This content downloaded from 115.165.210.196 on Mon, 30 Sep 2013 10:14:09 AM All use subject to JSTOR Terms and Conditions

infection control and hospital epidemiology

september 2008, vol. 29, no. 9

original article

Prospective Randomized Trial of 3 Antiseptic Solutions for Prevention of Catheter Colonization in an Intensive Care Unit for Adult Patients
J. Vallés, MD; I. Fernández, RN; D. Alcaraz, RN; E. Chacón, RN; A. Cazorla, RN; M. Canals, RN; D. Mariscal, MD; D. Fontanals, PharmD; A. Morón, PharmD

objective. To compare the effectiveness for prevention of central venous and arterial catheter colonization of 3 skin antisepsis with 1 of 3 antiseptic solutions: 10% aqueous povidone iodine (aqueous PI), 2% aqueous chlorhexidine gluconate (aqueous CG), and 0.5% alcoholic chlorhexidine gluconate (alcoholic CG). design. setting. Prospective, randomized controlled trial. Intensive care unit in a teaching hospital.

methods. Patients were randomly assigned to 1 of the 3 skin antisepsis groups. The distal tips of catheters were semiquantitatively cultured when the catheters were no longer necessary or if there was a suspicion of catheter-related infection. Rates of catheter colonization, catheterrelated sepsis, and catheter-related bacteremia were compared among the 3 groups. results. A total of 631 catheters were included in the study (194 from the aqueous PI group, 211 from the aqueous CG group, and 226 from the alcoholic CG group). The incidence of catheter colonization was significantly lower in the alcoholic CG than in the aqueous PI group (14.2% vs 24.7%; relative risk, 0.5 [95% confidence interval, 0.3– 0.8; P .01]); it was also significantly lower in the aqueous CG group than in the aqueous PI group (16.1% vs 24.7%; relative risk, 0.6 [95% confidence interval, 0.4 – 0.9; P .03]). There were no significant differences between the aqueous CG and the alcoholic CG groups. Incidences of catheter-related bacteremia were similar for all 3 groups. The aqueous and alcoholic CG solutions were superior to the aqueous PI solution in preventing catheter colonization due to gram-positive bacteria. conclusions. The aqueous and alcoholic CG solutions for cutaneous antisepsis were similarly effective in preventing colonization of central venous catheters and arterial catheters. Both had significantly lower incidences of colonization than did the aqueous PI solution; this effect seems to be related to the CG solutions’ more efficacious prevention of colonization with gram-positive bacteria. Infect Control Hosp Epidemiol 2008; 29:847– 853

Intravascular catheters are indispensable in the management of critically ill patients admitted to intensive care units (ICUs). Although such catheters provide necessary vascular access, their use puts patients at risk for local and systemic infectious complications.1 Bacteremia is the most serious complication related to the use of intravascular catheters.2-4 Rates of catheter-related bacteremia in ICUs range from 2.1 to 30.2 cases per 1,000 catheter-days, depending on the type of ICU.5 Catheter-related infection is associated with an increase in morbidity, mortality, length of hospitalization, and medical costs.3,6,7 Use of an antiseptic solution for skin disinfection at the catheter insertion site helps prevent catheter-related infections.8 A povidone-iodine solution is the most commonly used agent for this purpose. However, different studies have found that the incidence of catheter-related infection is significantly

lower among patients whose catheter insertion sites are disinfected with a chlorhexidine gluconate solution than among patients whose catheter insertion sites are disinfected with a povidone-iodine solution.9-11 For this reason, the Infectious Diseases Society of America guidelines recommend the use of chlorhexidine gluconate as an antiseptic for the prevention of catheter-related infections.12 Several types of chlorhexidine gluconate solutions have been used in different individual trials, including solutions of 0.5% or 1% alcohol chlorhexidine gluconate and solutions of 0.5% or 2% aqueous chlorhexidine gluconate, with the different results compared with a povidone-iodine solution.9-11,13,14 However, commercially available products containing aqueous chlorhexidine are not available in all countries. In July 2000, the US Food and Drug Administration approved a 2% aqueous chlorhexidine gluco-

From the Critical Care Center (J.V., I.F., D.A., E.C., A.C., M.C.), Microbiology Laboratory (D.M., D.F.), and Pharmacy Department (A.M.), Hospital Sabadell, Institut Universitari Parc Taulí, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Sabadell, Spain. Received February 25, 2008; accepted May 20, 2008; electronically published July 29, 2008. © 2008 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2008/2909-0009$15.00. DOI: 10.1086/590259

This content downloaded from 115.165.210.196 on Mon, 30 Sep 2013 10:14:09 AM All use subject to JSTOR Terms and Conditions

848

infection control and hospital epidemiology

september 2008, vol. 29, no. 9

nate solution for skin antisepsis.12 Before 2006, the only antiseptic available in Spain was a 0.5% alcohol chlorhexidine gluconate solution. The aim of this study was to compare the effectiveness of different antiseptic solutions in preventing central venous catheter (CVC) and arterial catheter (AC) colonization. The solutions that we compared were as follows: 0.5% alcohol chlorhexidine gluconate (hereafter referred to as “alcoholic CG”), 2% aqueous chlorhexidine gluconate (hereafter referred to as “aqueous CG”), and 10% aqueous povidone iodine (hereafter referred to as “aqueous PI”).

including erythema and purulent discharge. None of the catheters studied was impregnated with an antimicrobial. Bacteriologic Methods The CVC or AC was removed if it was no longer necessary, and if there was a suspicion of catheter-related infection (eg, fever with a temperature of 38.5°C or higher; leukocitosis, with a leukocyte count greater than14,000 cells/mm3, without any apparent cause; and/or pus, extensive erythema, or tenderness at the catheter insertion site). Before the catheter was removed, the catheter insertion site was cleansed with the antiseptic solution to which the patient had been randomized, to prevent potential contamination by bacteria located on the surface of the site. After removal of the catheter, we performed semiquantitative cultures of a 3– 4-cm segment of the catheter tip.15 All isolates were identified using standard procedures.16 Antimicrobial susceptibility testing was performed using the recommendations of the Clinical and Laboratory Standards Institute.17 The microbiologists who performed the catheter-tip cultures had no knowledge of the antiseptic group to which the catheter had been assigned. Definitions Significant catheter-tip colonization was considered to be present if 15 colony-forming units (cfu) or more grew in a semiquantitative culture of the catheter tip, by use of the rollplate technique (ie, by rolling the catheter segment across a blood agar plate).15 Catheter-related sepsis was considered to be present if a semiquantitative catheter-tip culture was positive for a microorganism, the patient had a temperature of 38.5°C or more, and the patient had a sustained reduction of at least 1°C of body temperature within 48 hours after catheter removal, with no other apparent cause of fever. Catheterrelated bacteremia was considered to be present if the same microorganism (ie, the same species with the same antibiotic susceptibility profile) was recovered from the catheter-tip culture and from blood culture.10 Statistics The study was designed to demonstrate the superiority of the 2 chlorhexidine solutions over the povidone-iodine solution in preventing catheter colonization. On the basis of findings described in the literature,10,13 we hypothesized that there would be a 65% reduction in the rate of catheter colonization for both the aqueous and alcoholic CG groups. To ensure with 80% power and 95% confidence that a percentage reduction of this magnitude would be detected between the 2 chlorhexidine groups and the povidone-iodine group, we needed to evaluate approximately 200 catheters from each of the 3 groups. Results are expressed as the mean values with standard deviations. Statistical analysis was performed using the 2 test or the Fisher exact test, for comparison of proportions, and analysis of variance, for comparison of means. The time to catheter colonization was evaluated by constructing Kaplan-Meier event curves,

methods
The study was conducted at 16-bed adult medical-surgical ICU in a university medical school–affiliated teaching hospital (Hospital Sabadell, Sabadell, Spain). From January 1, 2005, to June 30, 2006, all consecutive CVCs and ACs inserted into patients in the ICU were included in the study. The following catheters were excluded from the study: catheters inserted into patients before they were admitted to the ICU, catheters inserted with the use of a guidewire, catheters inserted for hemodialysis or for long-term total parenteral nutrition or chemotherapy, pulmonary artery catheters, catheters removed within less than 24 hour of their insertion, catheters inserted into patients who were less than 18 years of age, and catheters that remained in place 72 hours after patients were discharged from the ICU. The decision to insert or remove a catheter was made independently by the physician in charge of the patient. For each catheterization, a form was completed by the physician to prospectively record the characteristics of both patient and catheter. The study was approved by the local ethics committee, and written informed consent was obtained from each patient or from each patient’s surrogate decision maker. Study Design By use of a blinded block randomization schedule, we assigned to each patient to 1 of 3 groups according to the antiseptic solution used for initial and subsequent cutaneous antisepsis: 10% aqueous PI solution (Betadine; Meda Manufacturing), 0.5% alcoholic CG solution (Menalcol; Orraván S.L.), or 2% aqueous CG solution (prepared in the Pharmacy Department of Hospital Sabadell). The site of CVC or AC insertion was prepared with the appropriate agent and was allowed to dry according to a standardized protocol. All catheters were inserted by medical or nursing staff using maximal barrier precautions (ie, using sterile gloves, gowns, masks, and large drapes). Sterile gauze dressings were changed every 72 hours, or sooner if soiled or wet, and the catheter insertion site was cleansed with the agent to which the patient had been randomized. The locations of the CVCs included the internal jugular vein, the subclavian vein, the femoral vein, and the basilica vein. The ACs were placed in either radial or femoral arteries. All catheters were cared for in a similar manner. The insertion site was inspected every 72 hours for evidence of infection,

This content downloaded from 115.165.210.196 on Mon, 30 Sep 2013 10:14:09 AM All use subject to JSTOR Terms and Conditions

use of antiseptics to prevent catheter-related infection

849

figure 1. Flow chart showing inclusion and randomization of catheters evaluated in the study. CG, chlorhexidine gluconate; ICU, intensive care unit.

charged from the ICU. Ultimately, 631 CVCs and ACs inserted into 329 patients were included in the study. Of these 631 catheters, 226 (36%) were in the alcoholic CG group, 211 (33%) were in the aqueous CG group, and 194 (31%) were in the aqueous PI group (Figure 1). Characteristics of patients (Table 1) and of catheters (Table 2) were broadly similar in the 3 groups, with the exception that there were more posttrauma patients in the aqueous PI group, more patients with gastrointestinal disease in the aqueous CG group, and proportionately fewer patients with cardiovascular disease in the aqueous CG group. The reasons for catheter removal and the crude mortality rates in the ICU were similar in the 3 groups. Microbiological Findings Overall, 114 (18.06%) of the 631 catheters became colonized. The incidence of catheter colonization was significantly lower in the alcoholic CG group than in the aqueous PI group (14.2% vs 24.7%; relative risk [RR], 0.5 [95% confidence interval {CI}, 0.3– 0.8; P .01]); it was also significantly lower in the aqueous CG group than in the aqueous PI group (16.1% vs 24.7%; RR, 0.6 [95% CI, 0.4 – 0.9; P .03]). The incidence rate of catheter colonization was also significantly lower in the alcoholic CG than in the aqueous PI group (19.8 vs 31.8 colonized catheters per 1,000 catheter-days; P .02); it was also significantly lower in the aqueous CG group than in the aqueous PI group (21.8 vs 31.8 colonized catheters per 1,000 catheter-days; P .02). As shown in Figure 2, the probability of colonization-free catheter retention was significantly higher in the alcoholic CG and aqueous CG skin antisepsis groups than in the aqueous PI group. There were no significant differences in the incidence of catheter colonization between the alcoholic CG and aqueous CG groups (14.2% vs 16.1% of catheters; RR, 0.8 [95% CI, 0.5–1.3; P .20]). The intention-to-treat analysis included all randomized catheters. Of 998 catheters, 329 (33%) were assigned to the

in which a positive catheter-tip culture result was considered as failure of antisepsis. The log-rank test was used to compare these estimations of the 3 antiseptic groups. The analysis was carried out on evaluable catheters according to the exclusion criteria. As a sensitivity analysis, an intention-to-treat analysis was also performed on all the catheters in our study, by imputing the worst outcome (ie, catheter colonization) for the excluded catheters. Statistical tests were 2 tailed, and a P value of .05 or less was considered statistically significant.

results
Patients and Catheters During the 18-month study period, 998 catheters were inserted in 420 patients. Of these 998 catheters, 279 did not meet the inclusion criteria and were excluded from the analysis. In addition, 88 CVCs (29 in alcoholic CG group, 32 in the aqueous CG group, and 27 in aqueous PI group; P .20) were also excluded because they were used more than 72 hours after the patient was dis-

table 1. Characteristics of 329 Patients Included in the Trial of 3 Antiseptic Solutions for Prevention of Catheter Colonization in an Intensive Care Unit (ICU), January 1, 2005, to June 30, 2006 Characteristic Age, mean SD, years APACHE II score, mean SD Reason for ICU admission Respiratory failure Cardiovascular failure Neurologic disease Gastrointestinal disease Trauma Surgical intervention Cardiac arrest Renal failure or drug overdose Mortality note. Alcoholic CG group (n 116) 61 19 17 6 Aqueous CG group (n 107) 60 20 16 7 Aqueous PI group (n 106) 61 18 17 9 P .20 .20 .20 .02 .20 .006 .04 .20 .20 .20 .20

57 (25.2) 48 (21.2) 25 (11.0) 15 (6.6) 37 (16.3) 23 (10.1) 12 (5.3) 9 (3.9) 22 (19)

57 (27.0) 25 (11.8) 28 (13.2) 31 (14.6) 34 (16.1) 17 (8.0) 9 (4.2) 10 (4.6) 29 (27.1)

44 (22.6) 39 (20.1) 20 (10.3) 14 (7.2) 48 (24.7) 14 (7.2) 11 (5.6) 4 (2.0) 25 (23.6)

Data are no. (%) of patients, unless otherwise indicated. APACHE, Acute Physiology and Chronic Health Evaluation; CG, chlorhexidine gluconate; PI, povidone iodine; SD, standard deviation.

This content downloaded from 115.165.210.196 on Mon, 30 Sep 2013 10:14:09 AM All use subject to JSTOR Terms and Conditions

850

infection control and hospital epidemiology

september 2008, vol. 29, no. 9

table 2. Characteristics of the 631 Catheters Inserted Into Patients Included in the Trail of 3 Antiseptic Solutions for Prevention of Catheter Colonization in an Intensive Care Unit, January 1, 2005, to June 30, 2006 Characteristic Duration of catheterization, mean Central venous catheters No. used (% of total) Insertion site Internal jugular vein Basilica vein Suvclavian vein Femoral vein Arterial catheters No. used (% of total) Insertion site Radial artery Femoral artery Reason for catheter removal End of treatment or death Infection suspected Catheter dysfunction Accidental removal note. deviation. Alcoholic CG group (n 226) SD 7.1 4.1

Aqueous CG group (n 211) 7.5 4.5

Aqueous PI group (n 194) 7.7 4.8

P .20 .20 .20

139 (61.5) 52 (37.4) 47 (33.8) 25 (17.9) 15 (10.7) 87 (38.5) 78 (89.6) 9 (10.4) 156 (69.1) 67 (29.6) 3 (1.3) 0

129 (61.1) 56 (43.4) 31 (24) 22 (17) 20 (15.5) 82 (38.9) 69 (84.1) 13 (15.8) 123 (58.3) 79 (37.4) 7 (3.3) 1 (0.5)

112 (57.7) 43 (38.4) 32 (28.5) 23 (20.5) 14 (12.5) 82 (42.3) 67 (81.7) 15 (18.2) 125 (64.4) 61 (31.4) 5 (2.5) 2 (1)

.20

.16

Data are no. (%) of catheters, unless otherwise indicated. CG, chlorhexidine gluconate; PI, povidone iodine; SD, standard

alcoholic CG solution, 339 (34%) were assigned to the aqueous CG solution, and 329 (33%) were assigned to the aqueous PI solution. The incidence of catheter colonization was significantly lower in the alcoholic CG group than in the aqueous PI group (35.1% vs 48% of catheters; RR, 0.7 [95% CI, 0.6 – 0.8; P .01]); it was also signficantly lower in the aqueous CG group than in the aqueous PI group (39.5% vs 48% of catheters; RR,

figure 2. Probability of catheter colonization in the 0.5% alcoholic chlorhexidine gluconate (CG), 2% aqueous CG, and 10% povidone-iodine (PI) groups.

0.8 [95% CI, 0.7– 0.9; P .03]). Overall, the results of the intention-to-treat analysis were highly consistent with the perprotocol analysis. The microorganisms isolated from catheter tips associated with colonization are indicated in Table 3. The percentage of catheters colonized by gram-positive bacteria was higher in the aqueous aqueous PI group than in the alcoholic and aqueous CG groups (19.6%, 11.9%, and 11.3% of catheters, respectively; P .03). The percentage of catheter-tip cultures with negative results was lower in the aqueous PI group than in the alcoholic and aqueous CG groups (75.2%, 84.9%, and 81.9% of catheter-tip cultures, respectively; P .03). The incidence of catheter-related sepsis was lower in the alcoholic and aqueous CG groups than in the aqueous PI group (6.6%, 8%, and 10% of catheters, respectively; P .20). There were no significant differences in the incidence of catheter-related bacteremia in the 3 groups: it was 3.98% in the alcoholic CG group, 4.26% in the aqueous CG group, and 4.63% in the aqueous PI group, which correspond to incidence rates of catheter-related bacteremia of 4.3 cases per 1,000 catheter-days in the alcoholic CG group, 4.3 cases per 1,000 catheter-days in the aqueous CG group, and 5.3 cases per 1,000 catheter-days in the aqueous PI group (P .20). The incidences of skin inflammation at catheter insertion sites were similar in the 3 groups: 15.6% in the aqueous PI group, 17% in the alcoholic CG group, and 16.8% in the aqueous CG (P .20). There were no local or systemic hypersensitive reactions associated with the use of any of the 3 antiseptic solutions.

This content downloaded from 115.165.210.196 on Mon, 30 Sep 2013 10:14:09 AM All use subject to JSTOR Terms and Conditions

use of antiseptics to prevent catheter-related infection

851

table 3. Microorganisms Recovered From Semiquatitative Catheter-Tip Cultures for Catheters Included in the Trail of 3 Antiseptic Solutions for Prevention of Catheter Colonization in an Intensive Care Unit, January 1, 2005, to June 30, 2006 No. (%) of catheters Group and species of organism recovered Gram-positive bacteria Overall Coagulase-negative Staphylococcus Staphylococcus aureus Enterococcus faecalis Corynebacterium species Gram-negative bacteria Overall Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Pseudomonas aeruginosa Candida species Multiple species None Alcoholic CG group (n 226) 27 (11.9) 22 (81) 4 (15) 1 (4) 0 6 (2.6) 2 (3.3) 2 (3.3) 1 (1.7) 1 (1.7) 0 0 0 1 (0.4) 192 (84.9) Aqueous CG group (n 211) 24 (11.3) 24 (100) 0 0 0 10 (4.7) 2 (0.2) 2 (0.2) 1 (0.1) 2 (0.2) 1 (0.1) 2 (0.2) 1 (0.4) 3 (1.4) 173 (81.9) Aqueous PI group (n 194) 38 (19.6) 32 (84) 3 0 3 9 (4.6) 1 (0.1) 2 (0.2) 1 (0.1) 1 (0.1) 0 4 (0.4) 0 1 (0.5) 146 (75.2) P .03

.20

.20 .20 .03

discussion
Our study demonstrates that alcoholic CG solution is as effective as the aqueous CG solution, and both were more effective than the aqueous PI solution in preventing short-term CVC and AC colonization. The preventive effects of the aqueous and alcoholic CG solutions seems to be related to the CG solutions’ more efficacious prevention of colonization due to grampositive bacteria. The use of the alcoholic and aqueous CG solutions also appeared to be associated with longer durations of time in which catheters were not colonized. The skin surrounding the catheter insertion site is considered one of the major sources from which microorganisms can colonize catheters, leading to the formation of microbial biofilm on the external surface of the catheter. This route was found to be the most common source of catheter colonization for short-term catheters with a mean dwell time of 7–9 days.18 The use of an effective antiseptic solution for skin disinfection during insertion and subsequent care of the catheter insertion site may therefore decrease the occurrence of catheter colonization. The current guidelines for the prevention of intravascular catheter–related infections12 recommend the disinfection of clean skin with an appropriate antiseptic before catheter insertion and during dressing changes. Although use of a 2% chlorhexidine-based preparation is recommended, a tincture of iodine, an iodophor, or 70% alcohol can be used (category IA recommendation) according with these guidelines.12 Despite these guidelines, and despite the fact that several studies have demonstrated the efficacy of chlorhexidine gluconate, and despite the results of a recent meta-analysis suggesting that the incidence of catheter-related infections is significantly re-

duced among patients who received chlorhexidine gluconate, compared with patients who received povidone iodine,11 the povidone-iodine solution is still one of the most commonly used agent for cleaning AC and CVC insertion sites.12 Several types of chlorhexidine gluconate solutions have been used in the individual trials, including a 0.5% or 1% alcoholic chlorhexidine gluconate solution and a 0.5%, 1%, or 2% aqueous chlorhexidine gluconate solution. All of these solutions provide a concentration of chlorhexidine gluconate that is higher than the minimal inhibitory concentration for most nosocomial bacteria and yeasts.9 However, depending on the type and concentration of chlorhexidine gluconate used, controversial results have been found. Maki et al.9 used an antiseptic of CVC and AC insertion sites that was composed of aqueous CG, and they demonstrated that there was a reduction in the incidence of catheter-related bacteremia, compared with site preparation with 10% povidone iodine or 70% alcohol. However, a 0.5% tincture of chlorhexidine solution was no more effective in preventing catheter-related bacteremia or CVC colonization than 10% povidone-iodine solution in a prospective, randomized study.19 Therefore, it remains unclear which antiseptic solution (and at what concentration) is best for reducing the risk of catheter-related infection. In addition, commercially available products containing chlorhexidine have not been available in all countries. Until July 2000, the US Food and Drug Administration did not approve the aqueous CG solution for skin antisepsis.12 In Spain, the alcoholic CG solution was the unique market formulation until 2006 when an aqueous chlorhexidine gluconate solution became available.

This content downloaded from 115.165.210.196 on Mon, 30 Sep 2013 10:14:09 AM All use subject to JSTOR Terms and Conditions

852

infection control and hospital epidemiology

september 2008, vol. 29, no. 9

To our knowledge, there are no previous studies comparing aqueous chlorhexidine solutions with alcoholic chlorhexidine solutions, and all published studies have compared chlorhexidine solutions with povidone iodine or other antiseptic solutions. Ethanol possesses a potent microbial log reduction factor and is therefore highly antiseptic; combining it with other antiseptic solutions will rapidly reduce the concentration of microflora on the skin and will also have the sustained effect of keeping the number of microorganisms low. In fact, in a metaanalysis of 6 randomized trials comparing several formulations of chlorhexidine gluconate and povidone iodine, only those studies that used alcoholic CG solutions found statistically significant reductions in the rate of catheter colonization, compared with those studies that used povidone-iodine solutions.11 In our study, we found no significant differences between the aqueous and alcoholic CG solutions, but the incidence of catheter colonization was lower in the alcoholic CG group than in the aqueous CG group; it is possible that, with a higher number of catheters, we could assess significant differences. Our study demonstrates that the alcoholic CG solution may be safe to use instead of the aqueous CG solution, and it is an alternative solution in countries where aqueous CG solution is not available. Our findings differ from those of a previously randomized trial by Humar et al.19 comparing a 10% povidone-iodine solution with a 0.5% tincture of chlorhexidine solution as cutaneous antisepsis for prevention of CVC infection. Their study demonstrated no differences between the 2 solutions with respect to incidences of catheter colonization, catheter-related bacteremia, and eradication of gram-positive cocci. In our study, we included ACs and CVCs, and the number of catheters in each arm of the study was higher than in the Humar et al. study.19 We used the same definition of significant local catheter colonization as Humar et al.19 (ie, the growth of 15 cfu or more in a semiquantitative culture of the catheter tip), and the duration of catheterization was similar to that of Humar et al.19 as well. Overall, we found that there were no significant differences between the aqueous and alcoholic CG solutions. There were no significant differences between the aqueous and alcoholic CG groups in the number of CVCs and ACs included, and the 2 groups’ distributions of sites of CVC insertion were also similar. We were not able to demonstrate any clear benefit to using the aqueous CG solution, as opposed to the alcoholic CG solution, to decrease the incidences of infection and colonization. The aqueous CG and alcoholic CG solutions were superior to the aqueous PI solution, mainly in preventing catheter colonization due to gram-positive bacteria. This has been previously shown in a study of the disinfection of insertion sites for peritoneal dialysis catheters that demonstrated that chlorhexidine gluconate reduced the colony counts of coagulasenegative staphylococci, which are the microorganisms causing most catheter-related infections.20 Our study has some potential limitations. Despite randomization at the time of study inclusion, the patients in the 3

groups were not equally distributed with regard some risk factors for catheter colonization. However, we do not believe that they invalidate our results on the comparative efficacy of the 3 antiseptics solutions. The sample size was large enough to demonstrate differences in rates of catheter colonization but was not large enough to demonstrate differences in rates of catheter-related bloodstream infection. However, our results indicate a trend toward lower rates of catheter-related sepsis and catheter-related bacteremia in the aqueous and alcoholic CG groups, compared with the aqueous PI group. Catheter colonization, however, is considered an acceptable first-step surrogate end point for catheter-related bacteremia, because both are highly correlated statistically (r 0.69, r2 0.48, and P .001) and clinically.21 The relatively low rate of catheterrelated bacteremia observed in our study indicates that a much larger sample size of catheters would have been required to show a difference between the activities of the 3 antiseptic solutions, with bacteremia as the major end point. The study was carried out in a single ICU, and therefore this limits our ability to generalize the findings to other hospitals. However, after the results obtained in the ICU, the aqueous PI solution was replaced by the alcoholic CG solution for the cleansing of all CVC insertion sites in all the wards of our hospital. In conclusion, we found that the use the alcoholic or aqueous CG solution, rather than the aqueous PI solution, for cutaneous disinfection before and after insertion of ACs and CVCs significantly reduces the incidence of catheter colonization in an adult ICU.

acknowledgments
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article. Address reprint requests to J. Vallés, MD, Critical Care Center, Hospital Sabadell, Parc Tauli s/n, 08208 Sabadell, Spain (jvalles@cspt.es).

references
1. Raad I. Intravascular-catheter-related infections. Lancet 1998;351:893– 898. 2. Smith RL, Meixler SM, Simberkoff MS. Excess mortality in critically ill patients with nosocomial bloodstream infections. Chest 1991;100:164 –167. 3. Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1994;271:1598 –1601. 4. Vallés J, León C, Alvarez-Lerma F; Spanish Collaborative Group for Infections in Intensive Care Units of Sociedad Espanola de Medicina Intensiva y Unidades Coronarias (SEMIUC). Nosocomial bacteremia in critically ill patients: a multicenter study evaluating epidemiology and prognosis. Clin Infect Dis 1997;24:387–395. 5. Jarvis WR, Edwards J, Culver DH, et al. Nosocomial infection rates in adult and pediatric intensive care units in the United States. Am J Med 1991;91(Suppl 3B):185S–191S. 6. Renaud B, Brun-Buisson C; ICU-Bacteremia Study Group. Outcomes of primary and catheter.related bacteremia: a cohort and case-control study in critically ill patients. Am J Respir Crit Care Med 2001;163:1584 –1590. 7. Blot SI, Depuydt P, Annemans L, et al. Clinical and economic outcomes in critically ill patients with nosocomial catheter-related bloodstream infections. Clin Infect Dis 2005;41:1591–1598.

This content downloaded from 115.165.210.196 on Mon, 30 Sep 2013 10:14:09 AM All use subject to JSTOR Terms and Conditions

use of antiseptics to prevent catheter-related infection

853

8. Raad I, Hohn DC, Gillbreath BJ, et al. Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol 1994;15:231–238. 9. Maki DG, Ringer M, Alvarado CJ. Prospective, randomized trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991; 338:339 –343. 10. Mimoz O, Pieroni L, Lawrence C, et al. Prospective, randomized trial of two antiseptic solutions for prevention of central venous and arterial catheter colonization and infection in intensive care patients. Crit Care Med 1996;24:1818 –1823. 11. Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint S. Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: a meta-analysis. Ann Intern Med 2002;136:792– 801. 12. O’Grady NP, Alexander M, Patchen Dellinger E, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis 2002;35:1281–1307. 13. Parienti JJ, du Cheyron D, Ramakers M, et al. Alcoholic povidone-iodine to prevent central venous catheter colonization: a randomized unitcrossover study. Crit Care Med 2004;32:708 –713. 14. Mimoz O, Villeminey S, Ragot S, et al. Chlorhexidine-based antiseptic solution vs alcohol-based povidone-iodine for central venous catheter care. Arch Intern Med 2007;167:2066 –2072.

15. Maki DG, Weise CE, Sarafin HW. A semiquantitative culture method for identifying intravenous catheter related infection. N Engl J Med 1977;296: 1305–1309. 16. Murray PR, Baron EJ, Jorgensen JH, Phaller MA, Yolken RH, eds.Manual of Clinical Microbiology. 8th ed. Washington, DC: ASM Press; 2003. 17. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. 14th and 16th informational supplements. CLSI document. Wayne, PA: CLSI, 2005 and 2006: M100-S15/S16. 18. Safdar N, Maki DG. The pathogenesis of catheter-related bloodstream infection with noncuffed short-term central venous catheters. Intensive Care Med 2004;30:62– 67. 19. Humar A, Ostromecki A, Direnfeld J, et al. Prospective ranzomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of central venous catheter infection. Clin Infect Dis 2000;31:1001–1007. 20. Shelton DM. A comparison of the effects of two antiseptic agents on Staphylococcus epidermidis colony forming units at the peritoneal dialysis catheter exit site. Adv Perit Dial 1991;7:120 –124. 21. Rijnders BJA, Van Wijngaerden E, Peetermans WE. Catheter-tip colonization as a surrogate end point in clinical studies on catheter-related bloodstream infection: how strong is the evidence? Clin Infect Dis 2002;35: 1053–1058.

This content downloaded from 115.165.210.196 on Mon, 30 Sep 2013 10:14:09 AM All use subject to JSTOR Terms and Conditions