Chlorhexidine gluconate (CHG) is a broad-spectrum topical antiseptic frequently used to prevent healthcare-associated infections. Common uses include antisepsis for central venous catheter (CVC) insertion and maintenance, preoperative bathing, and daily bathing of patients with CVCs.Reference Milstone, Passaretti and Perl ^{1 ,} Reference Marschal, Mermel and Fakih ² In neonates, CHG bathing has been associated with a reduction in central line–associated bloodstream infections.Reference Quach, Milstone, Perpête, Bonenfant, Moore and Perreault ³

A 2009 survey of US neonatal intensive care units (NICUs) with fellowship training programs found that 57% of responding institutions used CHG in the NICU, many restricting use by age or weight.Reference Tamma, Aucott and Milstone ⁴ Respondents cited concerns regarding off-label use, as well as limited availability of safety data in preterm infants. Two other surveys have investigated CHG use in the broader context of infection control practices but did not elicit the full scope of CHG use within NICUs.Reference Hocevar, Lessa, Gallagher, Conover, Gorwitz and Iwamoto ^{5 ,} Reference Klieger, Potter-Bynoe, Quach, Sandora and Coffin ⁶

In May 2012, the US Food and Drug Administration modified the labeled indications for CHG from “do not use in premature or low birthweight infants […] or children less than 2 months of age” to “use with care in premature infants or infants under 2 months of age.” To ascertain trends in CHG use in the setting of this new indication, we resurveyed US NICUs with fellowship training programs to assess several key facets of CHG use.

In 2014, a survey was sent via email to neonatology training program directors in the United States. Follow-up surveys were sent to nonresponding institutions. Study participants completed an online survey about the use of CHG within the NICU, specific infection control practices, associated adverse effects, and concerns regarding the antiseptic’s use in the neonatal population. Data were analyzed using Stata, version 13.0 (StataCorp). This study was approved by the Johns Hopkins Medicine Institutional Review Board.

Of 98 training programs surveyed, 58 (59%) responded (Table 1). Among 46 respondents to the question, there was a mean (SD) of 23 (10.3) years of experience practicing neonatology, and all practiced at level III-IV NICUs. Fifty respondents (86%) reported CHG use within their NICUs, 5 (9%) reported no CHG use, and 3 (5%) did not know whether CHG was used within their NICU. Among NICUs utilizing CHG, the most common uses included skin preparation for CVC insertion, CVC dressing changes, CVC maintenance, and skin preparation for peripheral IV insertion. CHG baths were less frequently utilized, including preoperative baths, decolonization for methicillin-resistant Staphylococcus aureus, and routine bathing. Among 50 NICUs in 2014, 32 restricted CHG use: 21 did so by age, whereas 5 used weight-based criteria and 6 used both age- and weight-based restrictions. Among respondents who provided comments on open-ended questioning, the most common age requirement and weight requirement for CHG use were greater than 28 weeks gestation at birth and weighing more than 1 kg. A variety of CHG concentrations were utilized, ranging from 0.25% to 4.0%; the most common concentration used was 2.0%. Adverse effects of CHG were reported by 24 (53.3%) respondents, all of which were dermatologic. Those who provided specific information on dermatologic adverse events most often described skin irritation or burns. Concerns about CHG use were reported by 27, with common themes from open-ended questions regarding potential skin effects, systemic absorption, and potential neurotoxicity.

TABLE 1 Chlorhexidine Gluconate (CHG) Use by Indication Among Institutions in the Neonatal Intensive Care Unit

NOTE. CVC, central venous catheter; MRSA, methicillin-resistant Staphylococcus aureus; NA, item not queried in 2009 survey; PIV, peripheral intravenous catheter.

Among NICUs with fellowship training programs, CHG use has increased over the past 6 years from 57% to 86%. The benefit of using CHG in hospitalized neonates was investigated in a 2014 study conducted in a tertiary care NICU.Reference Quach, Milstone, Perpête, Bonenfant, Moore and Perreault ³ Among infants with CVCs in place who met age and weight criteria, the rate of central line–associated bloodstream infections decreased from 6.00 cases/1,000 CVC-days to 1.92 cases/1,000 CVC-days after CHG bathing was implemented.Reference Quach, Milstone, Perpête, Bonenfant, Moore and Perreault ³ As evidence of the efficacy of CHG in reducing infection risk in hospitalized neonates continues to emerge, routine CHG use in NICUs is likely to continue to rise.

Despite 86% of sites reporting CHG use, many respondents had ongoing concerns regarding potential side effects of CHG in the neonatal population. CHG use is commonly restricted in neonates by age or weight, though specific restrictions vary considerably among institutions, reflecting a lack of specific guidelines. Practitioners were particularly concerned about potential dermatologic effects. Whether burns associated with CHG use are due to chlorhexidine or due to the alcohol in the preparation remains unclear.

Safety concerns were explored further in a 2013 study, which measured serial serum concentrations of CHG after topical application to preterm infants’ skin for peripherally inserted central catheter placement.Reference Chapman, Aucott, Gilmore, Advani, Clarke and Milstone ⁷ Trace levels of CHG were detectable on serum testing in 10 of 20 enrolled infants, although the clinical significance of this finding was uncertain.Reference Milstone, Bamford, Aucott, Tang, White and Bearer ⁸ Despite in vitro neurotoxicity,Reference Milstone, Bamford, Aucott, Tang, White and Bearer ⁸ it is unknown whether CHG crosses the blood-brain barrier, and no studies have been performed to assess whether trace absorbed levels reach the central nervous system and cause toxicity.

Although overall trends in CHG use can be evaluated, a limitation of this survey-based study is the inability to compare trends for specific institutions given the anonymous nature of the survey. Institutions using CHG may have been more likely to complete the survey, potentially resulting in an overestimate of use.

The heterogeneous practices among responding institutions reflect the lack of specific guidelines for CHG use in neonates. Prospective studies are needed to assess best practices for CHG use in neonates, especially with regard to dosing schedule and efficacy.