874 infection control & hospital epidemiology july 2017, vol. 38, no. 7


table 1. Number (%) of Staphylococcus aureus Isolates in Each Period at Respective Minimum Inhibitory Concentrations (MICs) of Chlorhexidine (CHX)a


Period A No CHX,


MIC (µg/mL CHX) 0.25


0.5 1 2


Total


Dec 2007–Dec 2008 0 (0)


10 (31) 18 (56) 4 (13)


32


CHX MIC for S. aureus Isolates (% of Total for Period) Period B


CHX Bathing,


Feb 2010–Aug 2010 1 (5)


14 (74) 1 (5)


3 (16) 19


Period C No CHX,


Mar 2011– Sep 2011 0 (0)


9 (56)


97 (44) 0 (0)


16 Period D CHX Bathing


Jul 2014–May 2015 0 (0)


23 (62) 14 (38) 0 (0)


37


Total 1 (1)


56 (54) 40 (38) 7 (7)


104 aMIC for each isolate was the lowest concentration of CHX at which no growth was detected. The maximum MIC detected was 2 µg/ml. discussion


Chlorhexidine is a broadly active antiseptic that has been used in healthcare for more than 50 years. Due to increased concern regarding HAIs, CHX has been more broadly employed. Examples of CHX use include oral rinses to prevent ventilator-associated pneumonia, skin disinfection to prevent catheter-related bloodstream infections, and whole-body bathing to prevent acquisition and transmission of multidrug-resistant organisms.1 The increasing use of CHX has triggered concern regarding the possible emergence of CHX resistance. Low-level CHX resistance, also known as tolerance, is well-


described in staphylococci and is due to the activity of multidrug-efflux pumps mediated by genes qacA and qacB.4 Although the clinical significance of low-level CHX resistance remains debatable, qacA/B-positive S. aureus has been asso- ciated with elevated vancomycin MIC and bacteremia.5 In combination with resistance to mupirocin, qacA/B has been implicated with MRSA decolonization protocol failure.6 The prevalence of qacA/B in MRSA varies widely based on geo- graphy.2 In the United States, most studies examining the emergence and prevalence of CHX-resistant S. aureus have been reassuring. McGann et al7 characterized 5 qacA/B(+) MRSA strains recovered in 2003, but they did not find any qacA/B(+) MRSA among several hundred strains recovered from patients in 2010 and 2011 from an East Coast healthcare network.7 McDanel et al8 noted that low-level chlorohexidine resistance and qacA/B presence in only 0.6% of 829 MRSA isolates obtained from 3,806 nursing home residents in California. Warren et al9 characterized 504 nasal swab MRSA isolates obtained during 2005–2012 after implementa- tion of a daily CHX bathing protocol and found qacA/B in 6.2% of strains in 2005 and 7.7% in 2012. However, a cau- tionary report noted that organisms causing central-line– associated bloodstream infections were more likely to have reduced susceptibility to CHX if the patients were cared for in a unit that utilized daily CHX patient bathing.10 McNeil et al5 noted qacA/B positivity in 22.7% of 247 nosocomial S. aureus strains.


The present study provides reassurance that broad use of


CHX in hospitalized patients does not easily prompt the de novo development of CHX resistance. Several unique features are worthy of emphasis. First, the 2 distinct and prolonged periods of hospital-wide CHX use for patient bathing, preceded and separated by long periods of nonuse, provided a strong natural experiment to test the impact of CHX use on emergence of CHX resistance. Second, only isolates of S. aureus clearly responsible for invasive hospital-associated infection were analyzed. Notably, some of the previous studies on this subject are potentially flawed by broadly testing all S. aureus isolates, including community-associated strains that presumably were not subjected to the pressure of CHX expo- sure. Third, testing for CHX resistance was performed by both phenotypic and genotypic methods. Several limitations of this study should also be noted.


Although observation spanned 7.5 years, this was a single-center study and involved relatively few S. aureus isolates. Although there was no obvious linkage between the patients and no major ongoing MRSA outbreak, molecular epidemiologic testing was not performed to assess for clonality. Finally, no attempt was made to search for cross resistance with other biocides or antibiotics, and no testing for CHX resistance in other bacterial species was performed.Wedid not attempt to detect smr, which also confers decreased susceptibility to chlorhexidine. However, due to the lack of increased chlorhexidine resistance in our population, the presence of this gene is unlikely. The results of this study provide reassurance that CHX can


be used broadly in hospitalized patients without selecting for CHX-resistant S. aureus. However, these results do not exclude the emergence of resistance in the future, and continued surveillance for resistance is warranted. Meanwhile, this institution has strenuous programs to ensure hand hygiene, environmental disinfection, and limitation of fomites, which will hopefully reduce the spread of resistant staphylococci if they are introduced into the hospital environment. We believe that bathing patients with CHX provides additional benefits in the prevention of HAIs and transmission of multidrug resistant organisms, and this measure integrates effectively with our infection prevention program.


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