Nancy A. Melville

January 22, 2015

PHOENIX — Bathing patients in the intensive care unit daily with the antimicrobial agent chlorhexidine to prevent hospital-acquired infections might not be effective and could even increase the risk for resistance, according to a randomized clinical trial.

"We do think that this study should make ICU clinicians rethink the practice of using chlorhexidine bathing routinely in their ICUs," said Todd Rice, MD, from the Vanderbilt University School of Medicine in Nashville, Tennessee.

"The benefit is uncertain at best, and the risk for increasing resistance and the prevalence of more resistant organisms is an important consideration," he told Medscape Medical News.

The study, published online January 20 in JAMA to coincide with its presentation here at the Society of Critical Care Medicine 44th Critical Care Congress, challenges the practice.

However, a smaller study of chlorhexidine use in a surgical ICU, also presented at the meeting, did find a reduction in infections.

These findings do not support daily bathing of critically ill patients with chlorhexidine.

"We found chlorhexidine to be very effective, with a relative risk reduction of 44% for developing multiple infection types," said study investigator Joshua Swan, PharmD, from the Department of Pharmacy Services at Houston Methodist Hospital.

The larger of the two trials was a randomized crossover study of 9340 patients at five ICUs. Study investigators evaluated once-daily bathing of all patients with either 2% chlorhexidine or with nonantimicrobial disposable cloths for 10 weeks, which was followed by a 2-week washout period.

Patients then crossed over, and were bathed with the alternate method for another 10 weeks.

No Significant Difference

Dr Todd Rice

There was no significant difference in the primary outcome — a composite of central-line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and Clostridium difficile infections — between the chlorhexidine and the nonantimicrobial cloth groups (2.86 vs 2.90 per 1000 patient-days; P = .95).

There were also no significant differences between the groups in the secondary outcomes of hospital-acquired bloodstream infections, blood culture contamination, and clinical cultures yielding multidrug-resistant organisms.

"These findings do not support daily bathing of critically ill patients with chlorhexidine," Dr Rice and colleagues conclude.

In the second study, 325 patients in the surgical ICU at Houston Methodist Hospital were randomized to bathing every 48 hours with either with a 2% chlorhexidine solution (n = 161) or with soap and water (n = 164) for up to 28 days.

The study looked at surgical site infections, primary bloodstream infections, catheter-associated urinary tract infections, and ventilator-associated pneumonia.

Patients and practitioners were aware of the treatment group, but the investigators who determined the infection outcomes were blinded.

Of the 53 hospital-acquired infections detected, 18 were in the chlorhexidine group and 35 were in the soap-and-water group. There was a 44% reduction in the risk for the four hospital-acquired infections with chlorhexidine, compared with soap and water (hazard ratio [HR], 0.555; 95% confidence interval [CI], 0.309 - 0.998; P = .049).

Table. Infection Rates per 1000 Days at Risk

Infection Chlorhexidine Group, Days Soap-and-Water Group, Days P Value
Catheter-associated urinary tract 12.5 22.2 .21
Surgical site 5.9 12.4 .29
Ventilator-associated 25.8 40.0 .33
Bloodstream 0.0 2.0 .99


Because of concerns about an increased risk for skin effects, including rashes or ulcers, Dr Swan and colleagues looked at safety end points. However, they found no significant difference between the chlorhexidine and soap-and-water groups for one or more skin occurrences (19% vs 19%).

Chlorhexidine bathing involved covering the patient with the solution and allowing it to air dry.

"The air-drying is a very important component," Dr Swan explained, "because you want to create a barrier on the skin to provide full-body antisepsis."

"For every 11 patients bathed with chlorhexidine, we prevented one infection. That has a tremendous impact for clinicians taking care of surgical ICU patients," he said.

After this study, Houston Methodist adopted the chlorhexidine regimen, Dr Swan told Medscape Medical News.

"Based on the results of the other published random clinical trials and the experiences from our own study, all of the ICUs in our hospital adopted daily bathing with a chlorhexidine cloth as the standard of care," he said.

Dr Swan reported that the use of chlorhexidine helped the surgical ICU patients in this study to reach national goals set by the US Health and Human Services action plan to prevent hospital-acquired infection, which included goals to reduce central-line-associated bloodstream infections by 50%, surgical site infections and catheter-associated urinary tract infections by 25%, and ventilator-associated pneumonia by any amount.

"By applying this intervention to our surgical ICU population, we were able to meet these goals, so we were very excited about that," he said.

Contradicting Results

Dr Rice noted that even in the one surgical ICU his team assessed, no effect of chlorhexidine bathing was seen. He added that the differences between the two studies in comparison methods could be important.

Dr Swan's team compared chlorhexidine with soap and water, "which has been shown in previous studies to be inferior to bathing cloths with just soap," Dr Rice explained.

"Their control arm may very well have been an inferior method of bathing, compared with our control arm, which used nonantimicrobial bathing cloths. This might have led to higher infection rates in the control arm," he said.

What might be most important, however, is that the rates of infection in the patients enrolled in that study were considerably higher than in our study, Dr Rice noted.

Chlorhexidine bathing appears to have the greatest benefit in settings where the baseline prevalence of drug-resistant organisms is high, write Didier Pittet, MD, from the World Health Organization in Geneva, and Derek Angus, MD, from the University of Pittsburgh School of Medicine, in an editorial also published online in JAMA.

"In these settings, the same benefits may potentially be gained through other approaches, such as improved hand hygiene, which may be safer and less likely to affect the ecology of bacterial resistance in the ICU," Dr Rice said.

The Vanderbilt study was supported by grants from the National Institutes of Health and through the Vanderbilt Institute for Clinical and Translational Research. Dr Swan and Dr Rice have disclosed no relevant financial relationships.

Society of Critical Care Medicine (SCCM) 44th Critical Care Congress: Abstract 4. Presented January 18, 2015.


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