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Game changer: Clinical trial sets new standard of care for preventing surgical-site infections
National move to chlorhexidine-alcohol patient prep expected
(Editor's note: In this issue of Hospital Infection Control & Prevention, we continue our focus on infection prevention advances in the surgical suite, following our report on blunt suture needles last month with this special report on a new standard care emerging for skin cleaning of the patient surgical site.)
A landmark clinical trial demonstrating the striking efficacy of chlorhexidine-alcohol as a preoperative patient scrub is expected to change the standard of care and slash surgical-site infection (SSI) rates in hospitals, HIC has learned.
The clear conclusion of the recently published study is that preoperative cleansing of the patient's skin with chlorhexidine-alcohol is far superior to povidone-iodine in terms of preventing surgical-site infections.1 Now it gets interesting. For starters, povidone-iodine is currently used as the skin prep in almost three-quarters of all surgeries, with chlorhexidine alcohol the choice for only about 10% of operations to cleanse patient skin. Costs — for the solutions and materials, not for the later SSIs — are a clear factor in that unbalanced proportion. However, the nature of the clinical trial means the results can be widely extrapolated to other settings, says lead author Rabih O. Darouiche, MD, director of the Center for Prostheses Infection, Baylor College of Medicine in Houston. In short, it's a game changer.
"Overall, we saw a 41% reduction [in SSIs]," he tells HIC. "I cannot think of any confounding variable that essentially would change the potential efficacy of a certain antiseptic preparation in one city vs. another or one hospital vs. another. This is a really easy — a practical, quick and very powerful approach. I really see no barriers that could limit the implementation of this approach on a national basis."
Since 2002, the Centers for Disease Control and Prevention has recommended chlorhexidine-alcohol for skin cleansing of the insertion site for vascular catheters. However, the CDC has not issued a similar recommendation for skin cleansing at surgical sites, citing a lack of clinical evidence. Until now. Published in the prestigious New England Journal of Medicine, Daroiche's study is expected to lead to new CDC recommendations for surgical site prep to prevent endogenous infections from patient flora.
Talking to HIC the day the clinical trial results were published, Darouiche observed, "As of yesterday, povidone-iodine was still the standard of care, but I think that will now change. I anticipate and I am optimistic for the sake of better patient care that this will become national policy. I believe that a number of governmental agencies and professional associations that focus on quality of health care will adopt this approach. Many experts in the field think these results should be able to switch the standard of care from povidone-iodine to chlorhexidine alcohol for preoperative skin cleaning."
One of them is veteran health care epidemiologist Richard Wenzel, MD, professor and chairman of the department of internal medicine at the Medical College of Virginia in Richmond, who wrote an accompanying editorial on the study.2
"I think the weight of evidence is [sufficient] now to change from iodophors to chlorhexidine-alcohol," Wenzel tells HIC. "It's been proven in a number of studies of bathing patients with chlorhexidine, with IV lines compared to povidone-iodine around the lines, and now we have this large multicenter study. The switch to a different skin prep would be at some additional cost, but it is very small compared with preventing 40% of surgical-site infections. And this is not an extra procedure. There is no opportunity costs for the surgeon, he or she is already going to do a prep and they are just changing the materials. It's absolutely remarkable."
The cost of the applicator that contains the chlorhexidine and alcohol is about $6 — roughly twice as much as the iodophor product, Darouiche explains.
"On average, we applied two applicators that contained chlorhexidine-alcohol on the skin of an individual patient in the study; so for each patient who received chlorhexidine-alcohol an additional cost of $9 was incurred," he adds. "This study showed that you would have to apply chlorhexidine-alcohol rather that povidone-iodine in 17 patients in order to prevent one case of surgical-site infection," he says.
"So, 17 patients times $9 is $153. That pales in comparison to how much money you can save by preventing the onset of surgical-site infection, which we know can cost anywhere from a few thousands of dollars to tens of thousands of dollars."
Indeed, the latest analysis of the economic burden of SSIs by researchers at Duke University found that a single surgical infection due to methicillin-resistant Staphylococcus aureus (MRSA) could lead to charges in the $60,000 range.
The Darouiche clinical trial randomly assigned adults undergoing clean-contaminated surgery in six hospitals to preoperative skin preparation with either chlorhexidine-alcohol scrub or povidone-iodine scrub and paint. Enrolled patients were randomly assigned in a 1:1 ratio to have the skin at the surgical site either preoperatively scrubbed with an applicator that contained 2% chlorhexidine gluconate and 70% isopropyl alcohol or preoperatively scrubbed and then painted with an aqueous solution of 10% povidone-iodine. The primary outcome was any surgical-site infection within 30 days after surgery.
A total of 849 subjects (409 in the chlorhexidine-alcohol group and 440 in the povidone-iodine group) qualified for the intention-to-treat analysis. The overall rate of surgical-site infection was significantly lower in the chlorhexidine-alcohol group than in the povidone-iodine group (9.5% vs. 16.1%). Chlorhexidine-alcohol was significantly more protective than povidone-iodine against both superficial incisional infections (4.2% vs. 8.6%) and deep incisional infections (1% vs. 3%) — but not against organ-space infections (4.4% vs. 4.5%).
"Actually, we never anticipated that this would reduce the rate of organ-space infection," Darouiche explains. "Most incision infections are caused by organisms that reside on the patient's skin. That's why we anticipated that the chlorhexidine alcohol would significantly reduce the rate of incisional infections, but the skin antiseptics are not expected to find the way below the incisional area and prevent infection in deep organs and spaces."
Moreover, efficacy of infection prevention was not dependent on the organism, meaning MRSA — and all its attendant costs — is as likely to die on the patient's skin as any other bug. Culture of the surgical site in 60 of 61 infected patients yielded growth of organisms (a total of 107 isolates) and similar proportions of infected patients in the two study groups. Gram-positive aerobic bacteria (63 isolates) outnumbered gram negative aerobic bacteria (25 isolates) by a factor of 2.5, with 38% of cultures polymicrobial.
"The protection by chlorhexidine-alcohol was essentially the same across different groups of organisms," he emphasizes.
The 41% reduction in SSI risk is comparable to a 49% reduction in the risk of vascular catheter-related bloodstream infection in a meta-analysis that showed the superiority of skin disinfection with chlorhexidine-based solutions vs. 10% povidone-iodine.3 Although both the antiseptic preparations studied possess broad-spectrum antimicrobial activity, the superior clinical protection provided by chlorhexidine-alcohol is probably related to its more rapid action, persistent activity despite exposure to bodily fluids, and residual effect, Darouiche hypothesizes. As a result, some infections that may have been seeded from the patients' flora during the procedure are prevented. Since two-thirds of surgical-site infections are confined to the incision, optimizing skin antisepsis before surgery could result in a significant clinical benefit and immense cost savings, he stresses.
"Personally, I think better patient care is the primary outcome, and everything else is secondary to that," Darouiche says.
Another encouraging approach to preventing endogenous infections is nasal decolonization of patients prior to surgery. Knowing that nasal carriers of S. aureus are at increased risk for health care associated infections with the organism, researchers in the Netherlands found that temporarily decolonizing patients could sharply reduce infection rates.4 Given the country's highly publicized success in eradicating MRSA, the study was statistically relevant for only susceptible staph strains (MSSA). However, the results should apply in general to MRSA and the clinical situation currently faced by infection preventionists in America, the lead author told HIC in an interview via e-mail.
"There are, as far as we know, no comparative data dealing with MRSA," says Lonneke Bode, MD, a clinician in the department of medical microbiology and infectious diseases at Erasmus University Medical Center in Rotterdam. "Biologically however, it is plausible that this strategy works for MRSA as well as for MSSA, as long as the MRSA strain is mupirocin-susceptible. Please note that this is not a long-term treatment; it only eradicates the bacterium from the skin and nose for a relatively short period of time. Recolonization frequently occurs, but the purpose of this strategy is to be free of the organism during the period with the highest risk of acquiring an infection — during the hospital stay."
In the randomized, double-blind, placebo-controlled, multicenter trial, Bode and colleagues assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase chain reaction (PCR) assay, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection.
From October 2005 through June 2007, a total of 6,771 patients were screened on admission. A total of 1,270 nasal swabs from 1,251 patients were positive for S. aureus. The researchers enrolled 917 of the patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. In the mupirocin-chlorhexidine group, nasal ointment was applied twice daily, and the soap was used daily for a total-body wash. The duration of the study treatment was five days, irrespective of the timing of any interventions.
The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group. The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission, Bode concludes. The intervention also significantly reduced the mean hospital stay by almost two days.
"We think that this strategy not only works for high-risk surgical patients, but also for other patients at high risk for infection," she says, "for example, a nonsurgical patient that will get a central venous catheter. Unfortunately, we enrolled only 109 nonsurgical patients, and were thus underpowered to test our hypothesis. Probably there is also an effect in nonsurgical, high-risk patients, but we weren't able to measure the size of it."
There are other issues to consider, including the possibility of spurring mupirocin resistance in staph. "The more we use it, the more we will have that concern," Wenzel says. "I wish we knew the answer to how much of the contribution to their 60% reduction in Staph aureus was due to the mupirocin and how much was due to the chlorhexidine baths. We don't know that; they used both. But I would recommend this approach for high-risk patients."
Taken together, the two studies — which were unrelated but published in tandem — could represent landmark new gains against SSIs.
"Conservatively, even if you say for example, there are 30 million operations a year, if only 1% to 2% get infected that's 300,000 to 600,000 people," Wenzel says. "Imagine, if you use this single switch [in surgical-site skin cleansings] plus selected use of elimination of Staph aureus nasal carriage — the second study — you could get close to reducing half of surgical-site infections."