Original Investigation 

Infectious Diseases

Chlorhexidine vs Povidone-Iodine and Incidence of Catheter-Related Infections: A Systematic Review and Meta-Analysis

Bertrand Drugeon, Gabor Mihala, Jessica Schults, et al

JAMA Netw Open 2026;9;(2):e2558954. doi:10.1001/jamanetworkopen.2025.58954

Key Points

Question  What concentration and formulation of chlorhexidine or povidone-iodine is associated with the lowest incidence of catheter-related infections (catheter-related bloodstream infections, catheter tip colonization, or local infections)?

Findings  In this network meta-analysis and systematic review including 11 985 catheters from 16 randomized trials, alcohol-based rather than aqueous-based formulations, isopropyl alcohol rather than ethanol, chlorhexidine-based rather than povidone-iodine formulations, and higher (1% or higher) rather than lower concentrations of chlorhexidine for skin preparation were associated with lower infection rates.

Meaning  These findings suggest that high concentration chlorhexidine in isopropyl alcohol should be recommended as the first-line skin antiseptic before intravascular catheter insertion.

Abstract

Importance  Intravascular catheters are essential in health care but remain a major source of health care–associated infections. Optimal skin antisepsis before insertion is key, yet the most effective antiseptic agent, concentration, and formulation remain uncertain.

Objective  To determine the concentration and formulation of chlorhexidine gluconate (CHG) or povidone-iodine (PVI) associated with the lowest incidence of catheter-related infections (CRIs).

Data Sources  PubMed, EMBASE, Cochrane Central, Scopus, Web of Science, and CINAHL were searched through January 7, 2025, without restrictions. Trial registries and reference lists of relevant studies and guidelines were reviewed.

Study Selection  Randomized clinical trials (RCTs) comparing CHG- or PVI-based skin antisepsis before insertion of intravascular catheters were eligible if they reported at least 1 CRI outcome (catheter-related bloodstream infection [CRBSI], catheter tip colonization, or local infection). Two independent reviewers screened titles, abstracts, and full texts.

Data Extraction and Synthesis  Data were extracted independently by 2 reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed with the Cochrane risk of bias 2 tool. A random-effects network meta-analysis (NMA) was performed to estimate relative risks (RRs) with 95% CIs.

Main Outcomes and Measures  The primary outcomes were incidence of CRBSIs, catheter tip colonization, and local infections associated with CHG or PVI formulations.

Results  Sixteen RCTs (7803 patients; 11 985 catheters) met inclusion criteria. When compared with aqueous formulations, alcohol-based formulations were consistently associated with lower infections rates, with isopropyl alcohol being superior to ethanol. Compared with alcoholic PVI, alcoholic CHG was associated with lower CRBSIs (RR, 0.70 [95% CI, 0.45 to 1.08]), catheter tip colonizations (RR, 0.42 [95% CI, 0.37 to 0.48]), and local infections (RR, 0.40 [95% CI, 0.23 to 0.70]). High concentration CHG (1% or higher) further lowered CRBSIs (RR, 0.31 [95% CI, 0.19 to 0.52]) and colonization (RR, 0.36 [95% CI, 0.30 to 0.42]) compared with lower concentrations. Local adverse events were uncommon, slightly more frequent with alcohol-based formulations, and similar between CHG and PVI.

Conclusions and Relevance  In this NMA of RCTs, high concentration CHG in isopropyl alcohol was associated with the lowest incidence of CRIs. These results suggest that alcoholic PVI and aqueous formulations should be reserved for situations in which CHG or alcohol cannot be used.