By Rosie D. Lyles, MD, MHA, MSc
Head of Clinical Affairs, Clorox Healthcare
This article originally appeared in the APUA Newsletter, Volume 33, No. 3.
Antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Enterobacteriaceae (CRE) and multi-drug resistant Acinetobacter are increasing in prevalence worldwide, resulting in infections that are difficult and expensive to treat.
Sievert et al¹ describes antimicrobial resistance patterns for hospital-associated infections (HAIs) reported to the National Healthcare Safety Network (NHSN) during 2009-2010. They found S. aureus was the primary pathogen causing overall HAIs, with MRSA being the most common multi-drug resistant organism (MDRO).1
Humans are natural reservoirs for Staphylococcus aureus (S. aureus). Twenty to fifty percent of healthy adults are colonized with S. aureus (10-20 percent are persistent carriers, and approximately 30 percent are intermittent carriers).2 Colonization rates are highest among diabetics, intravenous (IV) drug users, patients on hemodialysis or continuous peritoneal dialysis, and those having dermatologic conditions (eczema and psoriasis) and human immunodeficiency virus (HIV).
Nasal colonization with S. aureus is the single most important determinant of subsequent S. aureus infection. However, colonization— whether presented on admission or hospital-acquired— increases risk of HAIs.(3-5)
Infection control measures to reduce S. aureus HAIs
In recent years, the infection control community has taken two different approaches, vertical and horizontal (Table 1), towards preventing HAIs. Vertical approaches, like decolonization of patients, are an essential practice in reducing MDRO (like MRSA) transmission in hospitals. The two most common decolonization methods are: 1) chlorhexidine gluconate (CHG) bathing and 2) intranasal therapies (mupirocin and povidone-iodine).
Cleansing with CHG has been shown to decrease the bio burden of microorganisms on the patient, the environment, and the hands of healthcare personnel.8 Daily bathing of intensive care unit (ICU) patients with chlorhexidine has been associated with decreased central line-associated blood stream infections (CLABSIs) and decreased acquisition of healthcare pathogens.7 CHG is also commonly used for preoperative bathing to reduce the risk of surgical site infections (SSIs). Lipke et al9 showed the effectiveness of reducing SSIs by bundling multiple risk reduction strategies, i.e., preadmission showers with CHG, and nasal decolonization for MRSA with mupirocin. As a result, overall SSIs were reduced by 63 percent, and SSIs caused by MRSA decreased 78 percent. The facility experienced savings of over $200,000.
Nasal decolonization with mupirocin
For intranasal decolonization, mupirocin (an antibiotic) is commonly applied to the anterior nares two times per day for five days. The reported effectiveness of mupirocin is comparable among methicillin-susceptible S. aureus (MSSA) carriers and MRSA carriers. Recently, Ammerlaan et al10 reviewed 23 clinical trials, including 12 that looked at topically applied antibiotics only. They concluded short-term nasal application of mupirocin is the most effective treatment for eradicating MRSA carriage, with an estimated success rate of 90 percent at one week post treatment and approximately 60 percent after a longer follow-up.10
Mody et al11 published a double blind randomized study looking at the efficacy of intranasal mupirocin versus placebo in reducing colonization and preventing infections in two long-term care centers. Twice-daily treatment was given for two weeks with follow-up to 6 months; after treatment, mupirocin eradicated colonization in 93 percent of residents compared to only 15 percent in the placebo group (p =.001). At 90 days after treatment, 61 percent of residents in the mupirocin group remained decolonized. The authors concluded that mupirocin was effective in decolonizing persistent carriers in long-term care and showed a trend towards reduction of infections.11
Mupirocin has emerged as the topical agent of choice for elimination of S. aureus nasal carriage. However, there is growing evidence of increasing mupirocin resistance to S. aureus and treatment failures, especially with widespread use over long periods of time.12-13 To illustrate how mupirocin resistance has increased, Table 2 provides a summary of mupirocin resistance in several clinical studies, across different regions and decolonization strategies.14
Nasal decolonization with povidone-Iodine: an antibiotic alternative
Due to the increasing demands for antimicrobial stewardship and the need to prevent further spread of resistance across the globe, there is renewed interest in evaluating newer agents and alternative methods for intranasal decolonization. Povidone-iodine (PI) is an excellent alternative for intranasal decolonization because it has a broad activity against gram-positive and gram-negative bacteria.
Hill et al.15 evaluated the in vitro activity of 5% povidone-iodine as a possible alternative to mupirocin for the elimination of nasal carriage of S. aureus. The results suggested povidone iodine may have a role in the prevention of colonization and infection due to MRSA, including mupirocin-resistant strains.
Phillips et al16 conducted a prospective, open-label trial of twice daily application of nasal mupirocin ointment for 5 days before surgery and compared it to two applications of a 5% PI solution in each nostril within 2 hours of surgical incision in patients undergoing arthroplasty or spine fusion surgery. Both groups also received a bath with 2% CHG impregnated cloths the night before and the morning of surgery. In the analysis, S. aureus deep SSI developed in 5 of 763 surgical procedures in the mupirocin group and in 0 of 776 surgical procedures in the PI group (P=.03).16 Bebko et al17 recently published a preoperative decontamination protocol to reduce SSIs in orthopedic patients undergoing elective hardware implantations.
The study demonstrates that preoperative MRSA decontamination with CHG washcloths and oral rinse, plus intranasal povidone-iodine, decreased the SSI rate by more than 50% among patients undergoing elective orthopedic surgery with hardware implantation. To date, studies have not shown development of resistance to PI antiseptic.18-19 Antiseptics work quickly, are dose independent, and continue working long after they are applied, making it difficult for bacteria to build resistance. Moreover, the cost of using a skin antiseptic is less than the cost of the screening test for S. aureus.20
Consequently, hospitals have less expensive alternatives for decolonizing patients that can complement the benefit of preserving antibiotic efficacy.
- Sievert DM, et al. Antimicrobial-Resistant Pathogens Associated with Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention. Infect Control Hosp Epidemiol 2013:34(1):1-14.
- VandenBergh MF, et al. Follow-up of Staphylococcus aureus nasal carriage after 8 years: redefining the persistent carrier state. J. Clin. Microbiol. 37:3133-3140.
- Kluytmans J, et al. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clinical Microbiology Reviews 1997; 10: 505–520.
- Wertheim HF, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus noncarriers. Lancet 2004; 364: 703–705.
- Davis KA, et al. Methicillin-resistant Staphylococcus aureus (MRSA) nares colonization at hospital admission and its effect on subsequent MRSA infection. Clin Infect Dis. 2004; 39: 776–82.
- Septimus E, et al. Approaches for preventing healthcare associated infections: go long or go wide? Infect Control Hosp Epidemiol July 2014; 35(7): 797-801.
- Supple L, et al. Chlorhexidine only works if applied correctly: use of a simple colorimetric assay to provide monitoring and feedback on effectiveness of chlorhexidine application. Infect. Control Hosp Epidemiol. 2015; 36 (9): 1095-1097
- Vernon MO, et al. Chlorhexidine gluconate to cleanse patients in a medical intensive care unit: the effectiveness of source control to reduce the bioburden of vancomycin-resistant enterococci. Arch Intern Med 2006; 166: 306–312.
- Lipke VL, et al. Reducing surgical site infections by bundling multiple risk reduction strategies and active surveillance. AORN J. 2010; 92(3):288-296.
- Ammerlaan HSM, et al. Eradication of methicillin-resistant Staphylococcus aureus carriage: A systematic review. Clin Infect Dis 2009; 48:922 -930.
- Mody L, et al. Mupirocin-based decolonization of Staphylococcus aureus carriers in residents of 2 long-term care facilities: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2003; 37: 1467–74.
- Pérez-Fontán, M, et al. Mupirocin resistance after longterm use for Staphylococcus aureus colonization in patients undergoing chronic peritoneal dialysis. Am J Kidney Dis. 2002; 39: 337–341.
- Vasquez JE, et al. The epidemiology of mupirocin resistance among methicillin-resistant Staphylococcus aureus at a Veterans’ Affairs hospital. Infect Control Hosp. Epidemiol. 200; 21:459-464.
- Huang, S. Resistance trends against topical antibiotics and antiseptics. Symposium Speaker at 2nd Annual International Conference on Prevention & Infection Control (ICPIC), Geneva, Switzerland: June 17, 2015.
- Hill R, et al. The in-vitro activity of povidone-iodine cream against Staphylococcus aureus and its bioavailability in nasal secretions. J Hosp Infect 2000;45: 198–205.
- Phillips M, et al. Preventing surgical site infections: a randomized, open-label trial of nasal mupirocin ointment and nasal povidone-iodine solution. Infect Control Hosp Epidemiol 2014; 35:826-832.
- Bebko SP, et al. Effect of a preoperative decontamination protocol on surgical site infections in patients undergoing elective orthopedic surgery with hardware implantation. JAMA Surg. 2015; 150 (5):390-395.
- Houang ET, et al. “Absence of bacterial resistance to povidone iodine.” Journal of Clinical Pathology. 1976 Aug; 29 (8):752-5.
- Lanker KB, et al. “Nondevelopment of resistance by bacteria during hospital use of povidone-iodine.” Dermatology. 1997; 195 Suppl 2:10-3.
- Huang SS, et al. Cost savings of universal decolonization to prevent intensive care unit infection: implications of the REDUCE MRSA trial. Infect Control Hosp Epidemiol. 2014 Oct; 35 Suppl 3:S23-31.