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With treatment complicated by the limited availability of antimicrobials to treat these infections, MDROs are responsible for approximately 23,000 deaths annually from antibiotic-resistant pathogens in the United States alone.64 The CDC states that 10% of individuals screened in healthcare facilities are asymptomatic carriers for a transmissible, “hard-to-treat” microorganism. 65 Drug-resistant organisms are becoming increasingly present in all settings and geographic areas. Carbapenem resistance increased in five European countries from 2008 to 2011. In the United States, infections caused by multidrug- resistant, Gram-negative bacteria have increased over the past decade, and one out of five hospitals reporting invasive infections implicated a carbapenem-resistant K. pneumoniae, one of the most common MDROs. While rates of hospital- onset, MRSA-related bacteremia in the United States have declined, community-onset MRSA- related bacteremia has increased in recent years. The patient safety practices in this report have universal application for reducing the burden of colonization and infection. When differences are significant (e.g., Enterococci in the digestive tract vs. S. aureus on patient skin), we make a note in the findings. The large benefit of these practices, however, comes from this universality: whether the organism is an extremely drug resistant A. baumannii or methicillin-susceptible S. aureus, infection prevention reduces risks and prevents patient harms. Communicating patients’ MDRO status allows facilities to take appropriate infection prevention precautions from the start of the patient encounter. PSP: Chlorhexidine Bathing To Control MDROs Chlorhexidine solutions have broad antimicrobial activity and are already commonly in use as topical disinfectants and antiseptics as part of recommended strategies for MDRO control and infection prevention. Either universal or targeted chlorhexidine bathing can complement other infection control methods of screening, isolation, and eradication. This section examines specific efficacy of chlorhexidine to prevent different infections (by organism, by type of infection), the mode and frequency of successful chlorhexidine bathing for disease prevention, and considerations for or unintended consequences of general chlorhexidine use. “Chlorhexidine bathing” is defined as application of chlorhexidine to the skin or oropharyngeal surfaces to promote decolonization and to prevent infection. As described below, oropharyngeal surfaces represent a reservoir for MDROs in mechanically ventilated patients who cannot perform their own oral care. Since chlorhexidine bathing is recommended for patients at high risk for MDRO- related infections — generally intensive-care patients, many of whom may be mechanically-ventilated as part of their care — we include oral care as part of a chlorhexidine bathing routine.

MRSA Evidence suggests that chlorhexidine bathing in the hospital setting reduces MRSA acquisition and carriage but may not always result in fewer MRSA infections. Three systematic reviews found evidence that chlorhexidine bathing alone reduces MRSA acquisition and carriage. This finding is supported by five strong studies (four experimental, one quasi-experimental) that also found chlorhexidine bathing reduced MRSA carriage and acquisition. While most of these studies found that bathing also reduced MRSA infections, some studies found no significant reduction in infections. One prospective cohort study found no reduction in MRSA colonization rates, specifically, but did find a significant reduction in the rates of infections caused by all MDROs (measured in aggregate, not by specific MDRO). Interpreting these results is made more difficult by the fact that chlorhexidine bathing is recommended as part of a multicomponent strategy that includes nasal mupirocin and, in a few studies, oral antibiotics, as described in general MDRO and MRSA control guidelines. In long-term care facilities, a thorough decolonization protocol that includes chlorhexidine bathing can reduce MRSA colonization without the need for patient isolation. This is an important finding for implementation, because extended patient isolation and gown and glove use may not be feasible or desirable in long- term or residential care settings. VRE Several studies found evidence that chlorhexidine can reduce VRE acquisition and colonization. One rigorous, multicenter study found that chlorhexidine bathing can reduce VRE acquisition. Three systematic reviews found that chlorhexidine can reduce VRE carriage in hospital patients. Finally, two quasi-experimental studies found reduced VRE colonization among patients who were bathed daily with chlorhexidine. CRE Few studies directly addressed chlorhexidine effects on CRE specifically (a number focused on the larger category of MDR-GNB). Of those that did, two observational cohort studies found that chlorhexidine bathing could reduce CRE colonization. HAIs Many studies examined the effect of chlorhexidine bathing on rates of various HAIs, such as catheter- associated urinary tract infection (CAUTI), ventilator-associated pneumonia (VAP) g, and central line- associated blood stream infection (CLABSI). Based on the studies included, chlorhexidine bathing is most effective at reducing colonization by and HAIs from Gram-positive MDROs in patients who have a break in the skin due to a needed medical device (e.g., central line). One review and several studies, including two large studies with more than 10,000 patients and 400,000 patients, respectively, have found

evidence that chlorhexidine bathing can reduce the risk of HAIs, especially in intensive care units. One trial found universal decolonization involving daily chlorhexidine bathing throughout the patient’s entire ICU stay and twice-daily intranasal mupirocin for 5 days was more effective than targeted decolonization or screening and isolation in reducing MRSA-positive clinical cultures and all- cause bloodstream infections. Most studies of chlorhexidine for HAI prevention focused on BSIs, but a few looked at VAP and SSIs. An observation study (found no reduction in intubation-related pneumonia, nor in UTIs, although overall infections and catheter-related infections were significantly lower. 66 Although chlorhexidine is routinely used for preoperative antisepsis in surgical settings, no studies suggest that chlorhexidine bathing reduced SSIs (although some observe a reduction in SSIs among CRE-colonized patients in their study). An important limitation applies to all these studies: because of other HAI prevention initiatives, the absolute number of HAIs is, in some cases, very low. The number needed to treat with chlorhexidine bathing in order to significantly reduce HAIs may be, in some cases, larger than the number of patients enrolled in studies. This finding suggests that chlorhexidine bathing has limited benefit for HAI reduction in settings where HAIs are already well controlled by other means. Application Chlorhexidine bathing, as described in the literature, covers a range in terms of concentration used, mode of application, and frequency. Of those studies that described the frequency of application, almost all described daily chlorhexidine bathing, with a smaller number using multiple applications per day (4 out of 24, of which one was an oropharyngeal- only application of chlorhexidine). In terms of concentration, the vast majority of reviews and studies used a 2% chlorhexidine gluconate solution (either in prepackaged wipes or applied using a soaked washcloth). For otherwise healthy patients outside a hospital setting, daily bathing with 2% chlorhexidine cloths is ineffective in reducing soft skin and tissue infection. Chlorhexidine’s effectiveness includes prolonged residual disinfection, so it is important not to rinse after use. The most common adverse effect in the literature was skin irritation. When use of chlorhexidine wipes was discontinued, pruritus stopped. Oral mucosa lesions were observed in 9.8% percent of the 8,665 mechanically ventilated patients in Wittekamp and colleagues’ chlorhexidine mouthwash study. 67 More serious adverse effects can occur with exposure to sensitive areas (eyes, esophagus, intestinal lining, inner ear). Severe anaphylaxis is possible but rare. Evaluations of Chlorhexidine Resistance The most important unintended consequence of the wide use of chlorhexidine is the development of resistance to chlorhexidine and other biocides.

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