The Burden of Health Care-Associated Infections
Health care-associated infections (HAIs) are a significant cause of illness, death, and excess costs in all health care settings. They affect 1 out of every 20 hospital patients at any given time.1 Some of the most serious HAIs are those that involve the bloodstream. HAIs also prolong hospitalizations and lead to readmissions.2-4 Finally, patients with HAIs incur large costs, with average direct medical costs of approximately $500-$1,000 per urinary tract infection and $10,000-$20,000 per surgical site infection, central line-associated bloodstream infection, or pneumonia, all of which can be serious enough to incur bloodstream infection.5
Importance of the MRSA Subset of HAIs
MRSA is arguably the most important single pathogen in health care-associated infection when accounting for virulence, prevalence, diversity of disease spectrum, and propensity for widespread transmission.6-9
Among HAIs in 2009-2010, S. aureus was the most common cause of health care-associated infections.10 Also, it is the most common cause of ventilator-associated pneumonia and surgical site infection and the second most common cause of central-line associated bloodstream infections.10 Notably, two-thirds of S. aureus HAIs were due to MRSA.
Pathogenesis and Preventability of Health Care-Associated Infections
The largest fraction of HAIs are caused by bacteria, such as MRSA, that reside on the skin and in the nose and gain access to the bloodstream, lungs, and bladder by way of devices and incisions that breach normal host defenses. These bacteria may be the patient’s normal flora, or they may be new, often antimicrobial-resistant organisms acquired during hospitalization. Current evidence and expert opinion suggests that 65-70 percent of catheter-related bloodstream and urinary tract infections may be preventable.11
Rationale for Universal Decolonization in Intensive Care Units
A recent national survey estimated that 5 percent of inpatients harbor MRSA.9 Other hospital-wide surveys have found estimates of 6-7 percent.10,12 Prevalence is even higher in ICUs.13 Among 12 ICUs in 5 academic hospitals, we found 18 percent of patients carried MRSA14 A worldwide ICU study of infection has shown that 18 percent of patients are infected by MRSA on any given day among 83 North American ICUs.15 Furthermore, studies have shown a high risk of later infection among MRSA carriers, sometimes as high as 33 percent in the year following hospitalization.16-18 These findings led to efforts not only to prevent the spread of MRSA to those who have yet to acquire it, but also to reduce infection among prevalent MRSA carriers.
Chlorhexidine bathing has been previously evaluated in single center and small multicenter studies, which have supported its ability to reduce environmental contamination due to multi-drug resistant organisms (MDROs), MDRO acquisition, and bloodstream infections.19-22 Its use in surgical skin preparation, preoperative bathing, and central line skin preparation, as well as its longstanding use in dental hygiene has further supported the role of chlorhexidine in skin and mucosal antisepsis.
The REDUCE MRSA Trial
The REDUCE MRSA Trial (Randomized Evaluation of Decolonization vs. Universal Clearance to Eliminate Methicillin Resistant Staphylococcus aureus) was undertaken to provide a definitive large-scale ICU trial to establish whether targeted decolonization of MRSA carriers versus universal decolonization of all ICU patients was the most effective intervention.
The REDUCE MRSA Trial was a three-way cluster-randomized trial of 43 hospitals (74 ICUs) in the Hospital Corporation of America health system.23 The three arms included:
- Screening and Isolation: Nasal screening for MRSA followed by isolation if positive.
- Targeted Decolonization: Nasal screening, followed, if positive, by isolation and decolonization with chlorhexidine 2% cloth baths and nasal mupirocin for 5 days.
- Universal Decolonization: Cessation of nasal screening and universal application of mupirocin for 5 days plus daily chlorhexidine 2% cloth baths for the duration of the ICU stay.
The REDUCE MRSA Trial involved nearly 75,000 patients and more than 280,000 patient days in 74 adult ICUs located in 16 States and included predominantly community hospitals.
The materials provided in this enhanced protocol were used by facilities that participated in the REDUCE MRSA Trial.
Effectiveness of Decolonization with Mupirocin and Chlorhexidine
Mupirocin is a prescription drug that was approved by the Food and Drug Administration (FDA) in 2002 for topical treatment of mild wounds due to S. aureus and Streptococcus pyogenes. A nasal formulation is also approved for eradicating nasal carriage of S. aureus. Mupirocin is highly effective in eradicating S. aureus in the short term. Several studies have shown 90 percent efficacy within 2 weeks of a 5-day regimen.24-27 It also significantly reduces short-term hospital-associated MRSA transmission and infections by over 50 percent in observational and cross-over intervention studies.28-30 Importantly, one study suggests that the combination of mupirocin and CHG is better at eradicating MRSA than mupirocin alone.31
Safety of Mupirocin and Chlorhexidine
Both mupirocin and CHG have excellent safety profiles. Systemic absorption of both drugs is minimal.32-36 Of the minimal amount of mupirocin that is absorbed, nearly all is rapidly converted to monic acid, an inactive metabolite.32,34 Multiple observational studies and randomized controlled trials have also shown no systemic absorption of mupirocin following intranasal application.37,38 Safety data for mupirocin from the manufacturer show that less than 1 percent of patients in clinical trials withdrew due to adverse events.
As an over-the-counter skin cleanser used in health care for over 50 years, CHG has an even more extensive safety record.39-44 Several groups have confirmed the absence of systemic absorption following topical use or oral rinsing with CHG.45-48 It is also safe on any superficial wound, including stage 1 and 2 decubitus ulcers, friable skin/rash, and superficial burns. No deleterious effects have been reported with daily use in either long-term ICU patients or outpatient daily bathing for many months. The REDUCE MRSA Trial found negligible rate of skin reactions (<1 percent) from CHG use; two other large scale studies reported the incidence of skin reactions to be no greater than 2 percent.23,49,50