AbstractCatheter-related infections pose a significant risk to critically ill patients, making it crucial to select an appropriate sterilization solution. However, there is currently no consensus on the use of chlorhexidine-containing solutions or povidone-iodine (PVI) and the auxiliary ingredients in solutions. Meta-analysis. PubMed, EMBASE, OVID, Web of Science, and Cochrane Library databases. Two reviewers independently performed study screening and data extraction and used the Cochrane risk-of-bias tool 2.0 (RoB 2.0) for quality assessment. We included 10 fully published RCTs with 12 pairs of comparisons, which included a total of 9,689 catheters. The analysis revealed that chlorhexidine gluconate (CHG)-containing solutions were significantly more effective than PVI in preventing CRBSI (RR = 0.460, 95% CI 0.323–0.654, P < 0.001), catheter-related sepsis (RR = 0.419, 95% CI 0.206–0.853, P = 0.016), and catheter colonization (RR = 0.409, 95% CI 0.266–0.630, P < 0.001). Further subgroup analysis demonstrated that, regardless of the concentration of CHG (≤ 1% or > 1%), it was superior to PVI in preventing CRBSI and catheter colonization (RR = 0.271 ~ 0.585, 95% CI 0.110 ~ 0.400‒0.590‒0.926). CHG-alcohol is most effective at preventing catheter-related infections, especially those caused by 70% alcohol. Compared to PVI, CHG-70% alcohol is the most effective disinfectant for preventing catheter-related infections, as it combines the rapid disinfection and evaporation properties of alcohol with the prolonged antimicrobial effects of chlorhexidine.PROSPERO registration number: CRD42024507163.
IntroductionVenous and arterial catheters, often referred to as ‘lifelines’, are essential for delivering medicines, fluids, and nutrients, as well as monitoring patients. This is particularly crucial for patients residing in intensive care units or emergency departments. However, there is a risk of catheter-related infections during the time the catheter is in place. Catheter-related infection refers to an infection that occurs while the catheter is indwelling and within 48 h after its removal, and it is not associated with infections at other sites1. This includes catheter-related bloodstream infection (CRBSI), catheter-related sepsis or local infection, and catheter colonization. The incidence rates of CRBSIs range from 0.4–4.78 per 1000 catheter-days2,3,4. However, once catheter-related infection occurs, it may lead to interruption of treatment, increased treatment costs, prolonged hospital stays, and even death in severe cases5,6.Catheter-related infections can be prevented by selecting a robust and durable skin sterilization solution during catheter placement and maintenance. This measure is widely recognized as effective in reducing CRBSI7. However, the choice of disinfectant—chlorhexidine gluconate (CHG) or povidone iodine (PVI)—and its ability to prevent catheter-related infections are controversial8,9. Although the Centers for Disease Control and Prevention (CDC) guidelines of the United States of America recommend the use of agents with > 0.5% CHG-alcohol to prevent intravascular-catheter-related infections10,11, CHG-containing solutions are not consistently used for skin disinfection to prevent catheter-related infections12,13. For evidence-based medical practice, obtaining sufficient samples for a single randomized controlled study is challenging due to the low incidence of CRBSIs and catheter-related local infections14. In previous meta-analyses on the effects of CHG-containing solutions and PVI as skin disinfectants in preventing catheter-related infections, several nonfull-text conference abstracts without trial details were included15,16 or the total number of included full-text articles was relatively small (only 4 and 5 articles)14,17. Therefore, an updated comprehensive analysis of the literature that can synthesize the results of multiple similar studies is needed to solve this problem. Moreover, to the best of our knowledge, no studies have analyzed the different disinfection effects of different CHG auxiliary ingredients and alcohol concentrations. However, different auxiliary ingredients and alcohol concentrations have different characteristics, and combining with CHG may lead to great differences in disinfection effects. In the current meta-analysis, we included 10 full-text articles with 12 pairs of comparisons on the effects of CHG-containing solutions versus PVI as skin disinfectants for preventing catheter-related infections and analyzed the differences in the effects of different auxiliary ingredients and alcohol concentrations. The total number of catheters was 9,689, which is the largest among all related meta-analyses to date.MethodsLiterature searchWe searched online for original articles published until July 20, 2023, in English databases, including PubMed, EMBASE, Web of Science, OVID, and the Cochrane Library, using combinations of the following theme words: chlorhexidine, infection or colonization or colonization, randomized or randomized or randomization or random or random or prospective or prospective, and catheter. We also searched for articles from other sources, including references in related published articles.Inclusion and exclusion criteriaPatients: We included studies involving patients ≥ 16 years of age who received central venous, peripheral venous, hemodialysis, or arterial catheters in hospital settings. Studies involving neonates were excluded because the types of catheters used, insertion techniques, and possible complication factors are different from those of older or adult patients.Intervention: A CHG-containing solution was used for skin disinfection around the catheter insertion site.Comparison: A PVI-containing solution was used for skin disinfection around the catheter insertion site.The outcome measures were as follows: (1) catheter-related bloodstream infection (CRBSI) or its synonym “catheter-related septicemia” or “catheter-associated bacteremia”, which is defined as the isolation of the same microorganism from the cultured blood sample as from the colonized catheter and no other apparent infection source except the catheter; (2) catheter tip culture positive for a microorganism with fever of ≥ 38.5 °C and a reduction in body temperature for at least 1 °C within 48 h. after catheter removal without other apparent causes of fever18,19; (3) catheter colonization, which is defined as ≥ 15 colony-forming units (CFUs) in a semiquantitative catheter tip culture20,21.Type of studies: We included full-text articles on randomized controlled trials (RCTs) comparing CHG-containing solutions with PVI-containing solutions for skin disinfection around the catheter insertion site. Crossover studies were excluded because of the possible contamination of intervention effects. We also excluded conference abstracts that did not provide the details of the trial methods.Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)22 were followed. Two reviewers independently reviewed each of the included articles and extracted the following information: authors, year of publication, study design, participants, sample size, intervention, comparison, definition of outcome measures, setting, and outcomes. Two reviewers independently evaluated the quality of each included study by using the Cochrane risk-of-bias tool 2.0 (RoB 2.0) for randomized controlled trials23. If there was any disagreement on the extracted information in a study, it was resolved by discussion or re-evaluated by another reviewer until a consensus was reached. The protocol of this systematic review has been registered on the PROSPERO website (CRD42024507163), and more information can be found in Supplement 1.Statistical analysisThe outcomes in the studies included in this meta-analysis were categorical data, which were synthesized as risk ratios (RRs) with 95% confidence intervals (CIs). The heterogeneity of the included studies was evaluated through X2 and I2 tests. If statistically high heterogeneity was identified (I2 ≥ 50%; P ≤ 0.10), we used a random effects model. In contrast, if low heterogeneity was identified (I2 < 50% and P > 0.10), a fixed effects model was used. Owing to differences in the composition of disinfectants, we conducted subgroup analyses according to different concentrations of CHG. We also perform sensitivity analysis to test the robustness of the findings. For risk ratios, P < 0.05 was regarded as statistically significant. R language software (R version 4.2.2, https://cran.r-project.org/) was used for data analysis.ResultsStudy selection and characteristicsWe first retrieved 715 articles from various databases and other sources. After excluding duplicate articles, this number was reduced to 327. After review according to the inclusion and exclusion criteria, we ultimately included 10 RCTs (Fig. 1). The characteristics of the included studies are shown in Table 1.Fig. 1Flow diagram of the literature search and study selection.Full size imageTable 1 Characteristics and results of RCT comparing chlorhexidine-containing solutions with povidone-iodine solutions for skin disinfection to prevent vascular catheter colonization and infection.Full size tableAssessment of risk of bias in the included studiesOverall, there was wide variation in the risk of bias for the included studies. One of these studies was assessed to have a high risk of bias28. Four studies were judged to have a lower risk of bias9,26,30. Seven studies were considered to have some concerns8,24,25,27,29,31. Atahan (2012)28 was determined to have a high risk of bias because of the lack of clarity regarding the method of randomization. Four studies employed a blinded block randomization schedule8,24,27, whereas two studies29,31 used computer-generated random numbers for grouping. However, the process of randomization was not adequately described in these two studies, resulting in a low risk of bias. All studies had a low risk of bias in deviations from the intended interventions and measurement of the outcome. In the assessment of missing outcome data, 1 study was deemed to have a certain risk25. Two studies were considered to be at risk of selective reporting of results24,27. The risk of bias in the included studies is shown in Fig. 2.Fig. 2Risk of bias of RCT comparing chlorhexidine-containing solutions with povidone-iodine solutions for skin disinfection to prevent vascular catheter colonization and infection.Full size imageOutcomesIn this meta-analysis, we first analyzed and compared the differences in the effects of CHG-containing solutions and PVI-containing solutions in preventing CRBSI, catheter-related sepsis, and catheter colonization. Considering the different skin irritation and disinfection effects of different concentrations of CHG, we then divided the analysis into two subgroups according to CHG concentration (CHG ≤ 1%, CHG > 1%), and compared the difference in effect with PVI again32. Finally, another subgroup analysis was conducted on the basis of the main excipients and alcohol concentration of the CHG disinfectant.Catheter-related bloodstream infectionsWe conducted a comprehensive analysis of 12 pairs of comparisons from 10 RCTs, which included a total of 9,689 catheters. Among these, 4,879 catheters were in the intervention group, and 4,810 catheters were in the control group. After performing a heterogeneity test, we found that the studies had low heterogeneity (I2 = 11%), so we used the common effect model for analysis. The results of our analysis revealed that CHG-containing solutions were more effective than PVI-containing solutions in preventing CRBSI (RR = 0.460, 95% CI 0.323–0.654, P < 0.001). We also conducted a sensitivity analysis by eliminating each study one by one, and the results remained consistent. The publication bias test indicated that all the included studies had a low risk of bias (Begg’s P = 0.312), confirming the stability and reliability of our meta-analysis results (Supplemental Fig. 1). The subgroup analysis also yielded consistent results. For CHG > 1%, the RR was 0.337, with a 95% CI of 0.193–0.590. For CHG ≤ 1%, the RR was 0.585, with a 95% CI of 0.369–0.926. No differences were observed in the subgroup analysis (test for subgroup differences: P = 0.136) (Figs. 3 and 4).Fig. 3(a) Forest map of RCT comparing chlorhexidine-containing solutions with povidone-iodine solutions for catheter-related bloodstream infections, catheter-related sepsis and catheter colonization. (b) Sensitive analysis of RCT comparing chlorhexidine-containing solutions with povidone-iodine solutions for catheter-related bloodstream infections, catheter-related sepsis and catheter colonization.Full size imageCatheter-related sepsisFive studies, involving a total of 7288 catheters, examined the occurrence of catheter-related sepsis. The intervention group consisted of 3650 catheters, whereas the control group had 3638 catheters. A heterogeneity test revealed significant heterogeneity (I2 = 67% > 50%), which led to the utilization of a random effects model. The findings indicated that CHG-containing solutions were more effective than PVI-containing solutions in preventing catheter-related sepsis or local infection (RR = 0.419, 95% CI 0.206–0.853, P = 0.016). However, sensitivity analysis revealed that the removal of the Mimoz25 1996 study altered the research outcomes (RR = 0.396, 95% CI 0.152–1.031; P = 0.058). In the subgroup analysis, regardless of the concentration of CHG, its effect was not statistically significant compared with that of PVI (CHG ≤ 1%: RR = 0.585, 95% CI 0.342–1.001; CHG > 1%: RR = 0.290, 95% CI 0.072–1.166), and no differences were observed in the subgroup analysis (test for subgroup differences: P = 0.335) (Fig. 4). The risk of publication bias analysis indicated a low risk of bias in the five included studies (Begg’s P = 0.142) (Supplemental Fig. 1).Catheter colonizationTwelve pairs of comparisons were analyzed, involving a total of 9,458 catheters, with 4,755 in the intervention group and 4,703 in the control group. After a heterogeneity test was conducted, it was determined that the included articles exhibited significant heterogeneity (I2 = 88% > 50%). Therefore, a random effects model was selected for analysis. The comprehensive analysis results indicated that CHG-containing solutions were more effective at preventing catheter colonization than were PVI-containing solutions (RR = 0.409, 95% CI 0.266–0.630, P < 0.001) (Fig. 3). Subgroup analysis also yielded consistent results (CHG ≥ 1%: RR = 0.271, 95% CI 0.110–0.668; CHG ≤ 1%: RR = 0.566, 95% CI 0.400–0.801) (Fig. 3). The analysis of publication bias revealed a low risk among the included studies (Begg’s P = 0.075) (Supplemental Fig. 1). Furthermore, when the influence of each individual study was systematically excluded, the results of this study remained stable and consistent without apparent fluctuations (Fig. 3).Fig. 4Subgroup besed on different (a) concentrations, (b) excipients or (c) alcohol concentrations of CHG.Full size imageSubgroup analysis based on different excipients and alcohol concentrations of CHGThe main ingredients of CHG-containing solutions are alcohol, benzyl alcohol, and water. Subgroup analysis was performed according to different excipients. The results showed that the antibacterial effect of CHG-alcohol was better than that of CHG-benzyl alcohol and CHG-water, but it was statistically significant only in preventing catheter-related sepsis (P = 0.000).The excipient of the CHG-containing solutions used in 7 studies was alcohol, and 5 studies reported the alcohol concentration. The alcohol concentration was 79% in 3 studies and 70% in two studies. Subgroup analysis was performed on the basis of alcohol concentration to compare its effect with that of PVI-containing solutions in preventing CRBSI and catheter colonization (other outcome indicators are unavailable). The results shown the rates of CRBSI and catheter colonization were lower in the CHG-70% alcohol group than in the CHG-79% alcohol group, but a significant difference was shown only in preventing catheter colonization (P = 0.040) (Supplemental Fig. 2).DiscussionThis article offers a comprehensive analysis of the role of CHG-containing solutions and PVI-containing solutions as skin disinfectants in the prevention of intravascular catheter-related infections. The total number of included full-text RCT articles and catheters is the largest among the related meta-analyses thus far. The results of our meta-analysis indicate that CHG-containing solutions are more effective than PVI-containing solutions in preventing catheter-related bloodstream infections (CRBSIs), catheter-related sepsis, and catheter colonization. For preventing catheter-related sepsis, only 5 RCTs were available for this meta-analysis17; when CHG concentrations were divided into two subgroups (≤ 1% CHG or > 1% CHG), no significant effect of CHG-containing solutions was found for either subgroup compared with PVI-containing solutions. Notably, the sensitivity analysis heavily relied on the Mimoz25 1996 study, which utilized a CHG antiseptic solution containing benzalkonium chloride, an ingredient not present in other studies. This additional component is known to synergistically enhance the sterilizing effect of CHG33. Consequently, both the results of that study (RR = 0.3, 95% CI 0.1–1, P = 0.02) and the meta-analysis of 5 RCTs support the notion that CHG-containing solutions are more effective than PVI-containing solutions in preventing catheter-related sepsis or local infection. In addition, prolonged indwelling time of the catheter increases the risk of catheter-related sepsis, emphasizing the importance of the sterilization solution34. In addition, the incidence of catheter-related sepsis is very low. Therefore, many catheters need to be included to achieve an effective sample size10,37. This may be an important reason for the inconsistency between the meta-analysis results of the 5 RCTs and the subgroup analysis results.In the prevention of catheter-related infections, CHG is generally considered superior to PVI, as indicated by various meta-analyses16,17. CHG is a potent and effective antibacterial disinfectant for the skin. Compared with povidone, it has a longer duration of antibacterial activity and has a stronger sterilizing effect on gram-positive bacteria than gram-negative bacteria22. Since gram-positive bacteria are the main cause of central catheter bloodstream infection and associated mortality35, CHG can be recommended as the preferred disinfectant for catheter placement and maintenance care. With respect to the concentration of CHG, this study did not find that a concentration greater than 1% is more effective in reducing the risk of CRBSI than a concentration of 1% or less. However, according to a network meta-analysis conducted by Masuyama17, 1% CHG-alcohol has been shown to be more effective than 0.5% CHG-alcohol and 2% CHG-aqueous in reducing the risk of CRBSI (RR = 0.48, 95% CI 0.32–0.71; RR = 0.49, 95% CI 0.31–0.78). This difference in findings may be attributed to the subgroup analysis in this study, which had limited categorization, and the absence of a direct comparison of the effects of different CHG concentrations on reducing catheter-related infections.There are variations in the sterilization efficacy of CHG when it is combined with different auxiliary ingredients. The performance of CHG-alcohol is superior to that of CHG-benzyl alcohol, followed by CHG-water. When the alcohol concentration is 70%, it is most effective in preventing catheter-related infections. When combined with other biocidal agents, the combination of alcohol and chlorhexidine is beneficial to health, can effectively prevent catheter-related bloodstream infections15,36, and has less antibiotic resistance37. The 70% alcohol concentration can efficiently penetrate bacterial cell walls and deactivate bacteria. Conversely, 79% alcohol may evaporate too quickly due to its high concentration, resulting in less effective disinfection38,39. Benzyl alcohol is capable of killing bacteria, but it notably irritates the skin, particularly in adults, and may increase the likelihood of skin allergies compared with other disinfectants40. And Menyhay et al. compared the disinfection effects of 70% alcohol and CHG-70% alcohol disinfectants for needleless catheter connectors. They found that 15 connectors that were not disinfected were all infected, and 67% of the connectors that were disinfected with alcohol alone were contaminated with bacteria. However, only 1 (1.6%) of the s joints using CHG-70% alcohol was infected41. Current research supports that CHG-70% alcohol disinfectant has a prominent role in preventing catheter-related infections. This is because this component can not only utilize the rapid and bactericidal properties of alcohol, but also utilize the long-lasting antibacterial effect of chlorhexidine.Catheter-related infections not only increase patient discomfort and adversely affect prognosis, they also prolong hospital stays and increase medical costs and workload for healthcare professionals. The use of disinfectants with potent antiseptic properties during catheter placement and maintenance can significantly reduce the incidence of these infections. The results of this study can help clinicians select effective and less irritating antiseptics.LimitationsNotably, only English-language articles were included in this meta-analysis, which could introduce bias. However, according to relevant research, including only English literature will not affect the conclusion42. Additionally, in our subgroup analysis, we categorized CHG into only two subgroups on the basis of a 1% concentration threshold. Our analysis did not reveal a correlation between higher CHG concentrations and increased effectiveness. Nevertheless, this should not discourage further investigation into comparisons of the effects of various concentrations of CHG and PVI. Future research could delve deeper into this aspect. Finally, when subgroup analysis of different CHG excipients and alcohol concentrations was conducted, relatively few studies could be included, so the results require further exploration.ConclusionThis meta-analysis included a total of 9,689 catheters (the largest number of catheters among the related meta-analyses thus far) and revealed that skin antiseptic solutions containing chlorhexidine gluconate were more effective than povidone-iodine in reducing the risk of catheter-related infections, especially CHG-70% alcohol. Therefore, CHG-70% alcohol solutions are recommended for catheter placement and maintenance.
Data availability
The data and materials used or produced throughout this study have been included in this manuscript.
AbbreviationsCHG:
Chlorhexidine gluconate (CHG)
PVI:
Povidone-iodine
CRBSI:
Catheter-related bloodstream infection
PRISMA:
Preferred reporting items for systematic reviews and meta analyses
RCT:
Randomized controlled trial
CFUs:
Colony-forming units
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Download referencesFundingThis research was supported by the National Natural Science Foundation of China (Nos. 82002967 and 82372660), which promotes cutting-edge scientific endeavors of national significance.Author informationAuthor notesThese authors contributed equally: Aiping Deng and Fangli Xiong.Authors and AffiliationsWest China School of Nursing, Sichuan University, Chengdu, ChinaAiping Deng & Fangli XiongWest China Hospital, Sichuan University, Chengdu, ChinaAiping DengCenter of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, ChinaFangli XiongDivision of Liver Surgery, Department of General Surgery, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, ChinaQiuping RenWest China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaQiuping RenNursing Key Laboratory of Sichuan Province, West China Medical Center, Sichuan Medical Univsersity, Chengdu, ChinaQiuping RenAuthorsAiping DengView author publicationsYou can also search for this author inPubMed Google ScholarFangli XiongView author publicationsYou can also search for this author inPubMed Google ScholarQiuping RenView author publicationsYou can also search for this author inPubMed Google ScholarContributionsAiping Deng and Fangli Xiong contributed equally to this work. Searched and screened the literature: Aiping Deng, Fangli Xiong. Literature data extraction and quality assessment: Aiping Deng, Fangli Xiong. Analyzed the data: Aiping Deng. Wrote the paper: Aiping Deng, Fangli Xiong and Qiuping Ren. Supervised and reviewed the paper: Qingping Ren. All the authors reviewed the manuscript and agreed on the final version.Corresponding authorCorrespondence to
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Reprints and permissionsAbout this articleCite this articleDeng, A., Xiong, F. & Ren, Q. Chlorhexidine solutions are more effective than povidone-iodine solutions as skin disinfectants for the prevention of intravascular catheter-related infections: A meta-analysis.
Sci Rep 15, 10657 (2025). https://doi.org/10.1038/s41598-025-92476-wDownload citationReceived: 07 August 2024Accepted: 27 February 2025Published: 27 March 2025DOI: https://doi.org/10.1038/s41598-025-92476-wShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard
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KeywordsCatheter-related bloodstream infectionsChlorhexidinePovidone-iodine