What are the concepts related to methicillin resistant Staphylococcus aureus (MRSA) and the control and prevention of MRSA infections in healthcare facilities?
S. aureus, the most virulent staphylococcal species, causes infections ranging from relatively minor superficial skin infections to severe conditions such as bacteremia. S. aureus is an opportunistic pathogen that often colonizes body surfaces such as the nares, skin, or perineum without causing symptoms of infection. Approximately 30 percent of the United States (US) population is colonized with S. aureus.
Previous studies have found that patients colonized with S. aureus were more likely to acquire healthcare-associated (HA) S. aureus infections, compared with patients who were not colonized. However, a study by Wertheim et al., demonstrated that all cause and bacteremia-related deaths were significantly higher among patients who were not colonized compared with those who were colonized before their bacteremias, even though colonization was a strong risk-factor for bacteremia. This finding was possibly due to up-regulated immune responses in colonized patients or to lower virulence of colonizing strains compared with infecting strains. Thus colonization, while increasing infection risk, may actually protect patients who become infected from dying.
Today, 39 to 60 percent of S. aureus clinical isolates in US hospitals are methicillin resistant. MRSA bacteremia is associated with higher mortality rates than is methicillin-susceptible S. aureus (MSSA) bacteremia. Several hypotheses may explain this association:
1) Patients infected with MRSA may be more likely to receive inadequate or inappropriate antimicrobial therapy compared with patients infected with MSSA
2) Appropriate antimicrobial treatment for MRSA bacteremia, which until recently has been limited to vancomycin, may not be as effective as the β-lactam agents used to treat MSSA infections
3) MRSA-infected patients may be more likely to have comorbidities and more severe acute underlying illness compared with MSSA-infected patients or
4) MRSA may possess virulence genes that MSSA does not have.
Risk factors for acquisition of MRSA include: comorbidities such as HIV and renal failure, dialysis, severe illness, intensive care unit (ICU) admission, previous admission to a hospital, injection drug use, and residence in a long-term-care facility, incarceration, living in crowded conditions, and poor hygiene.
Currently, vancomycin is the most frequently prescribed antimicrobial therapy for MRSA bacteremia. However, rare cases of vancomycin resistance among S. aureus have made vancomycin a less appealing option. Since 1997, both vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA), and the fully resistant vancomycin-resistant S. aureus (VRSA) have emerged around the world.
VRSA is defined as an MRSA isolate that carries the VanA gene. VISA is defined as a S. aureus isolate with a vancomycin minimum inhibitory concentration greater than the Clinical and Laboratory Standards Institute (CLSI) break point of 4 μg/ml and hVISA is defined as a S. aureus isolate that has one subpopulation that is vancomycin susceptible according to current CLSI breakpoints and a subpopulation that grows in the presence of vancomycin. The molecular mechanism of intermediate vancomycin resistance is not fully understood. Some investigators have hypothesized that thick S. aureus cell walls trap vancomycin before it reaches the cytoplasmic membrane of S. aureus, thereby rendering the vancomycin inactive.
Prevention and control of methicillin resistant Staphylococcus aureus
Given this background information, what are the key concepts regarding prevention and control of MRSA transmission and infection? First, the reservoir for MRSA is primarily colonized or infected patients. In addition, colonized or infected healthcare workers (HCWs) and contaminated items in the environment can also serve as reservoirs for MRSA. Second, the fact that there are relatively few clones of MRSA worldwide suggests that person-to-person spread, not antimicrobial use, is the most important factor in the spread of MRSA. However, antimicrobial use may predispose patients to acquiring MRSA colonization or infection if they are exposed to the organism. Thus, breaking transmission from these reservoirs and appropriate use of antimicrobial agents are both essential steps in preventing MRSA colonization and infection among patients in healthcare facilities.
What are the conclusions of clinical trials and meta-analyses regarding infection control and Gram positive bacteria – Staphylococcus aureus?
Results of studies have conflicted and the quality of many studies about MRSA control has been poor. Thus, it is difficult to make definitive conclusions based on the results of clinical trials and systematic literature reviews. For example, a cluster randomized trial in 18 ICUs compared surveillance for MRSA and VRE colonization and expanded use of barrier precautions to existing practice and found no difference in the two arms with respect to mean ICU-level incidence of colonization or infection with MRSA or VRE. Investigators for the two meta-analyses of active detection and isolation (ADI) concluded that evidence may favor the use of ADI, but the evidence is of poor quality and the studies had major methodological weaknesses. Thus, they felt that they could not make definitive recommendations.
Three systematic literature reviews have assessed the effectiveness of antimicrobial agents for treating MRSA colonization. Investigators for two of the three reviews concluded that mupirocin might be effective at reducing nasal carriage. Investigators also disagree about the effectiveness of decolonization. The results of randomized controlled trials of decolonization agents (e.g., mupirocin, chlorhexidine gluconate) to reduce the number of MRSA healthcare-associated infections (HAIs) have varied. The investigators who conducted the only meta-analysis assessing these studies stated that the currently available evidence did not support routine use of topical intranasal mupirocin for infection prophylaxis.
Another meta-analysis found that perioperative mupirocin may prevent surgical site infections (SSI) among patients undergoing cardiothoracic surgery, orthopedic surgery or neurosurgery but not among patients undergoing general surgery because the former procedures were often complicated by Gram-positive surgical site infections but general surgical procedures could be complicated by Gram-negative or by Gram-positive SSIs.
What are the consequences of ignoring control of Gram positive bacteria – Staphylococcus aureus?
The consequences of ignoring the key principles and concepts of Gram positive bacteria-S. aureus control are the continued spread of MRSA within healthcare facilities and continued harm to patients who acquire healthcare-associated infections caused by MRSA. In addition, the cost of healthcare will be increased by the MRSA infections and some or all of these costs may not be reimbursed.
What information supports the research on Gram positive bacteria – Staphylococcus aureus, e.g., case-control studies and case series?
Multiple cohort studies have been performed in a variety of patient populations with the goal of establishing a rule to predict which patients are at high risk for MRSA colonization. A prediction rule would help infection prevention staff determine which patients are likely to carry MRSA and, thus, could transmit MRSA to other patients or could acquire an MRSA infection. Ideally, screening the patients identified as high risk of carrying MRSA would be more cost-effective and take less time than testing all patients for MRSA.
Many prediction rules include recent admission to the hospital and this variable has been a strong predictor of MRSA colonization, with sensitivities ranging from 50% to 70% and specificities ranging from 46% to 88%. Prediction rules have also included risk factors for colonization such as prior operation, antimicrobial use during the past year, and a current wound. These prediction rules had varying success. If these prediction rules were applied, the proportion of MRSA or VRE colonized patients who would be missed ranged from 15% to 43%.
Summary of current controversies regarding Gram positive bacteria – Staphylococcus aureus.
One of the major controversies with respect to prevention and control of MRSA is whether active surveillance (detection) for patients who are colonized but not infected with MRSA is essential for preventing spread of this pathogen within hospitals. Both sides in this debate argue strongly for their position. Proponents of active surveillance for MRSA argue that active surveillance and isolation, which has prevented spread of other nosocomial pathogens such as smallpox and severe acute respiratory syndrome, can also be used to contain endemic MRSA.
Active surveillance for MRSA, which is a vertical approach because it focuses only on one organism, has been credited with the low rates of morbidity and mortality from MRSA in northern Europe and in Western Australia. Proponents of active surveillance acknowledge that a single-pathogen approach is not ideal; however, they argue that current horizontal approaches such as hand hygiene have not decreased MRSA HAI rates significantly. Proponents state that MRSA may have a selective advantage compared with MSSA, may be associated with higher mortality rates than MSSA, and be more virulent compared with other pathogens. Furthermore, ADI for asymptomatic MRSA carriers could prevent transmission of MRSA through multiple routes such as directly from one patient to another, via healthcare workers’ contaminated hands or clothing, and via the environment. Studies have also shown that ADI of MRSA-colonized patients are cost effective.
In contrast, proponents of a horizontal approach argue that hospitals should implement interventions that will decrease spread of any pathogens, including other antimicrobial-resistant pathogens such as enterococci resistant to vancomycin, Acinetobacter baumannii resistant to imipenem, and Pseudomonas aeruginosa resistant to imipenem, because these interventions (e.g., the central-line-associated bloodstream infection [CLABSI] prevention bundle, universal contact precautions, or improved hand hygiene), would decrease the overall rate of healthcare-associated infections more than ADI. (Proponents of a horizontal approach also argue that strategies focusing on active surveillance for patients colonized with MRSA and use of contact precautions for patients with MRSA will not prevent spread of MSSA, spread of other resistant organisms, or infections in patients colonized with MRSA.
Active surveillance also will not prevent MRSA transmission from colonized healthcare workers or from healthcare workers who transiently carry the organism on their hands to un-colonized patients. Additionally, active surveillance programs that only assess nasal carriage will miss colonization of the throat and perineum, which is quite common. Moreover, the isolation component of ADI has been associated with potential harms because contact precautions have been associated with fewer physician visits, (Saint) depression, and decreased patient satisfaction. Furthermore, the costs for active surveillance may decrease the funds available to implement other important infection prevention interventions.
Four large studies have assessed the effectiveness of active surveillance plus contact precautions for preventing spread of MRSA. Robicsek et al., performed a three-phase quasi-experimental study in three hospitals in which they compared baseline (phase 1) to ICU-based universal surveillance for MRSA and contact precautions for patients who carried MRSA (phase 2) and whole-hospital universal surveillance for MRSA, contact precautions for carriers, and decolonization of MRSA carriers (phase 3). These investigators found a significant decrease in MRSA infections over the course of the study.
Similarly, investigators in the Veterans Health Administration performed a quasi-experimental study to assess their nationwide MRSA Prevention Initiative, which included universal ADI. They found that the rates of HA MRSA infections declined by 45% in non-ICUs and by 62% in ICUs after the Initiative was implemented. In contrast, Harbarth et al., implemented ADI plus decolonization for MRSA carriers in half of the surgical wards while the remaining wards served as a control. After a washout period, the intervention and control wards were switched. This study did not find a significant decrease in MRSA infections. Finally, the STAR*ICU Trial was a cluster-randomized ICU trial comparing standard of care to a bundle that included universal surveillance for MRSA, contact precautions for MRSA positive patients, and universal gloving until surveillance culture results were reported to be negative for all other ICU patients. That study found no difference between the intervention and control groups in terms of mean ICU-level incidence of colonization or infection with MRSA.
Decolonizing patients colonized with methicillin resistant Staphylococcus aureus
Experts also disagree about the importance of decolonizing patients colonized with MRSA. Some studies have shown that nasal decolonization with the topical agent mupirocin decreases the incidence of MRSA healthcare-associated infections. Unlike other infection prevention and control interventions, such as ADI, the colonized patient can benefit from MRSA decolonization. Patients colonized with S. aureus have three times higher odds of acquiring a S. aureus infection (ventilator-associated pneumonia, catheter-related infection, bacteremia, urinary infection, wound infection or sinusitis) compared with uncolonized patients. Thus, decolonization may prevent infection with endogenous MRSA. However, mupirocin resistance, the cost of decolonization, the difficulty of decolonizing patients who carry MRSA at sites other than the nares, and recurrent colonization with the same MRSA strain have led some to argue against nasal decolonization.
What is the impact of controlling methicillin resistant Staphylococcus aureus colonization and the implications for infection control?
Infection prevention staff seeks to prevent spread of all pathogens, including MRSA, within healthcare settings. Thus, preventing spread of MRSA and preventing MRSA infections is a major function of all infection prevention programs. However, proponents of ADI (a vertical approach) and proponents of horizontal infection prevention approaches disagree about the extent to which infection prevention programs should focus their attention on MRSA specific interventions and on general prevention interventions. Regardless of which approach an infection prevention program takes, there are substantial adverse effects if MRSA spread in a healthcare setting and if patients acquire MRSA infections.
Klevens et al., estimated that overall in the US, about 18,650 people died during 2005 with invasive MRSA infections, which is greater than the number of persons who died due to HIV during the same time period. Noskin et al., used AHRQ National Inpatient Sample (NIS) data to determine that the marginal impact of S. aureus infection increased: 1) total charges per stay by US $28,526, 2) length of stay by 8.84 days, and 3) mortality per stay by 1.81%. Cosgrove et al., found that MRSA bacteremia was associated with significantly higher mortality rates, lengths of stay, and costs compared with MSSA bacteremia.
Numerous studies have documented that patients who carry MRSA are at increased risk of MRSA infection. For example, Garrouste-Orgeas et al., found that nasal carriage was associated with a three times higher odds of acquiring a S. aureus infection (ventilator-associated pneumonia, catheter-related infection, bacteremia, urinary tract infection, wound infection, or sinusitis) compared with uncolonized patients. Gupta et al., found that preoperative nasal carriage of MRSA was associated with a significantly increased risk of MRSA postoperative infection (relative risk [RR] =8.46; 95% confidence interval [CI]: 1.70, 42.04).
Overview of important clinical trials, meta-analyses, case control studies, case series, and case reports related to infection control and Gram positive bacteria – Staphylococcus aureus.
Most studies evaluating organization-level strategies to prevent MRSA colonization and infection are poorly-controlled quasi-experimental studies. These studies typically have very low internal validity due to selection bias, regression to the mean and temporal biases. Most quasi-experimental studies also have limited external validity because factors such as the prevalence of MRSA on admission and hospital characteristics (e.g., ICU size and ICU length of stay) vary among healthcare facilities and, thus, the effectiveness of many organization-level strategies may also vary among healthcare facilities.
See Table I, Table II and Table III for a summary of clinical work.
What national and international guidelines exist related to Gram positive bacteria – Staphylococcus aureus?
Table IV describes five guidelines, a Dutch guideline, a British guideline, an Australian guideline, and two guidelines written by organizations based in the US, the Society for Healthcare Epidemiology of America (SHEA) and the Centers for Disease Control and Prevention’s Healthcare Infection Control Practices Advisory Committee (CDC HICPAC), on prevention of MRSA transmission in healthcare facilities. All of these guidelines recommend similar control measures, however the recommendations for implementation of these measures varies from guideline to guideline. For instance, the SHEA, Dutch, and British guidelines recommend routinely screening high-risk patients for MRSA but the CDC HICPAC and Australian guidelines recommend active surveillance as a targeted measure to be implemented when the incidence or prevalence of MRSA is not decreasing despite other infection control strategies. None of these guidelines recommend active surveillance of all admitted patients.
The recommendations regarding MRSA decolonization strategies also differ. The Dutch guideline is the only guideline that recommends decolonization for all patients colonized with MRSA. The SHEA and Australian guidelines recommend decolonization as an adjunctive measure when the MRSA incidence or prevalence is not decreasing despite implementation of other strategies. CDC HICPAC recommends decolonization for patients who are epidemiologically linked to outbreaks, and the British guidelines recommend decolonization of patients in specific situations such as during outbreaks or before surgical procedures.
Additionally, the CDC HICPAC and Australian guidelines recommend that HCW be screened and decolonized only if they are linked epidemiologically to an MRSA outbreak. The British guidelines state that healthcare workers with skin lesions who were exposed to an MRSA carrier should be treated. The SHEA guideline recommends decolonizing HCWs only if other strategies do not reduce the incidence or prevalence of MRSA. In contrast, the Dutch guideline recommends the “Search and Destroy” approach for MRSA. Thus, the Dutch guideline defines situations in which HCWs should be screened for MRSA (e.g., treated in a foreign hospital) and recommends decolonization of all HCWs found to carry MRSAs.
Finally, all of the guidelines promote some form of contact or barrier precautions for patients colonized or infected with MRSA; however the recommendations for implementation of the precautions differ. Both the SHEA and Dutch guidelines recommend that HCWs wear a mask when treating MRSA carriers, while the British guideline recommends that HCWs wear masks only when they perform procedures that may generate staphylococcal aerosols (e.g., suctioning respiratory secretions).
The CDC HICPAC and Australian guidelines do not recommend that HCWs use masks when implementing contact precautions for MRSA. All of the guidelines recommend that HCWs wear gowns and gloves and that they do hand hygiene after removing the personal protective equipment. However, the Dutch and Australian guidelines state that gloves and gowns must be worn whenever HCWs enter the contact precaution patient-care area, while the SHEA, CDC HICPAC, and British guidelines make exceptions to this rule. For example, when HCWs enter a patient’s room but do touch the patient or the environmental surfaces.
See Table IV and Table V for the strategies and guidelines for controlling MRSA.
Nasal carriage of Staphylococcus aureus
Kenner J, O’Connor T, Piantanida N,et al. Rates of carriage of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in an outpatient population. Infect Control Hosp Epidemiol 2003;24:439-44.
Graham PL,3rd, Lin SX, Larson EL. A U.S. population-based survey of Staphylococcus aureus colonization. Ann Intern Med 2006;144:318-25.
Patel M, Weinheimer JD, Waites KB, Baddley JW. Active surveillance to determine the impact of methicillin-resistant Staphylococcus aureus colonization on patients in intensive care units of a Veterans Affairs medical center. Infect Control Hosp Epidemiol. 2008;29:503-9.
Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: Epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev 1997;10:505-20.
von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med 2001;344:11-6.
Wertheim HF, Vos MC, Ott A, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet 2004;364(9435):703-5.
Lucet JC, Chevret S, Durand-Zaleski I, Chastang C, Regnier B, Multicenter Study Group. Prevalence and risk factors for carriage of methicillin-resistant Staphylococcus aureus at admission to the intensive care unit: Results of a multicenter study. Arch Intern Med 2003;163:181-8.
Trends in Staphylococcus aureus infections, particularly bloodstream infections
Styers D, Sheehan DJ, Hogan P, Sahm DF. Laboratory-based surveillance of current antimicrobial resistance patterns and trends among Staphylococcus aureus: 2005 status in the United States. Ann Clin Microbiol Antimicrob 2006;5:2.
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004;39:309-17.
Biedenbach DJ, Moet GJ, Jones RN. Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY antimicrobial surveillance program (1997-2002). Diagn Microbiol Infect Dis. 2004;50:59-69.
Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: A meta-analysis. Clin Infect Dis 2003;36:53-9.
Cosgrove SE, Qi Y, Kaye KS, Harbarth S, Karchmer AW, Carmeli Y. The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: Mortality, length of stay, and hospital charges. Infect Control Hosp Epidemiol 2005;26):166-74.
Deresinski S. Counterpoint: Vancomycin and Staphylococcus aureus – an antibiotic enters obsolescence. Clin Infect Dis 2007;44:1543-8.
Stryjewski ME, Szczech LA, Benjamin DK Jr, et al. Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia. Clin Infect Dis 2007;44:190-6.
Chang FY, Peacock JE Jr, Musher DM, Triplett P, MacDonald BB, Mylotte JM, et al. Staphylococcus aureus bacteremia: Recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 2003;82:333-9.
Marra AR, Edmond MB, Forbes BA, Wenzel RP, Bearman GM. Time to blood culture positivity as a predictor of clinical outcome of Staphylococcus aureus bloodstream infection. J Clin Microbiol 266.
Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, et al. Invasive methicillin-resistant Staphylococcus aureus infections in the united states. JAMA 2007;298:1763-71.
Bancroft EA. Antimicrobial resistance: It’s not just for hospitals. JAMA 2007;298:1803-4.006;44:1342-6.
Barrett FF, McGehee RF Jr, Finland M. Methicillin-resistant Staphylococcus aureus at Boston city hospital. Bacteriologic and epidemiologic observations. N Engl J Med 1968;279:441-8.
Antimicrobial Resistant Staphylococcus aureus
Geisel R, Schmitz FJ, Fluit AC, Labischinski H. Emergence, mechanism, and clinical implications of reduced glycopeptide susceptibility in Staphylococcus aureus. Eur J Clin Microbiol Infect Dis 2001;20:685-97.
Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: Efficacy and toxicity. Arch Intern Med 2006 166:2138-44.
Centers for Disease Control and Prevention (CDC). Staphylococcus aureus resistant to vancomycin – United States, 2002. MMWR Morb Mortal Wkly Rep 2002;51:565-7.
Srinivasan A, Dick JD, Perl TM. Vancomycin resistance in staphylococci. Clin Microbiol Rev 2002;15:430-8.
Smith TL, Pearson ML, Wilcox KR, Cruz C, Lancaster MV, Robinson-Dunn B, et al. Emergence of vancomycin resistance in Staphylococcus aureus. glycopeptide-intermediate staphylococcus aureus working group. N Engl J Med 1999;340:493-501.
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. In: CLSI document. Nineteenth Informational Supplement ed. ; 2008. p. M100-S19.
Appelbaum PC. Microbiology of antibiotic resistance in Staphylococcus aureus. Clin Infect Dis 2007;45 Suppl 3:S165-70.
Falagas ME, Makris GC, Dimopoulos G, Matthaiou DK. Heteroresistance: A concern of increasing clinical significance? Clin Microbiol Infect 2008;14:101-4.
Jevons M. “Celbenin”-resistant staphylococci. BMJ 1961;(1):124-125.
Interventions to Reduce the Risk of Staphylococcus aureus Infections and Transmission of this Organism
Huskins WC, Huckabee CM, O’Grady NP, Murray P, Kopetskie H, Zimmer L, et al. Intervention to reduce transmission of resistant bacteria in intensive care. N Engl J Med 2011;364:1407-18.
McGinigle KL, Gourlay ML, Buchanan IB. The use of active surveillance cultures in adult intensive care units to reduce methicillin-resistant Staphylococcus aureus-related morbidity, mortality, and costs: A systematic review. Clin Infect Dis 2008;46:1717-25.
Cooper BS, Stone SP, Kibbler CC, et al. Systematic review of isolation policies in the hospital management of methicillin-resistant Staphylococcus aureus: A review of the literature with epidemiological and economic modelling. Health Technol Assess 2003;7):1-194.
Laupland KB, Conly JM. Treatment of Staphylococcus aureus colonization and prophylaxis for infection with topical intranasal mupirocin: An evidence-based review. Clin Infect Dis 2003;37:933-8.
Loeb M, Main C, Walker-Dilks C, Eady A. Antimicrobial drugs for treating methicillin-resistant Staphylococcus aureus colonization. Cochrane Database Syst Rev. 2003;(4)(4):CD003340.
Ammerlaan HS, Kluytmans JA, Wertheim HF, Nouwen JL, Bonten MJ. Eradication of methicillin-resistant Staphylococcus aureus carriage: A systematic review. Clin Infect Dis 2009;48:922-30.
Kallen AJ, Wilson CT, Larson RJ. Perioperative intranasal mupirocin for the prevention of surgical-site infections: Systematic review of the literature and meta-analysis. Infect Control Hosp Epidemiol 2005;26):916-22.
Morgan DJ, Day HR, Furuno JP, et al. Improving efficiency in active surveillance for methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus at hospital admission. Infect Control Hosp Epidemiol 2010;31:1230-5.
Harris AD, Furuno JP, Roghmann MC, et al. Targeted surveillance of methicillin-resistant Staphylococcus aureus and its potential use to guide empiric antibiotic therapy. Antimicrob Agents Chemother 2010;54:3143-8.
Riedel S, Von Stein D, Richardson K, Page J, Miller S, Winokur P, et al. Development of a prediction rule for methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus carriage in a Veterans Affairs Medical Center population. Infect Control Hosp Epidemiol 2008;29:969-71.
Robicsek A, Beaumont JL, Wright MO, Thomson RB Jr, Kaul KL, Peterson LR. Electronic prediction rules for methicillin-resistant Staphylococcus aureus colonization. Infect Control Hosp Epidemiol 2011 32:9-19.
Wibbenmeyer L, Appelgate D, Williams I, et al. Effectiveness of universal screening for vancomycin-resistant Enterococcus and methicillin-resistant Staphylococcus aureus on admission to a burn-trauma step-down unit. J Burn Care Res 2009;30:648-56.
Furuno JP, McGregor JC, Harris AD, et al. Identifying groups at high risk for carriage of antibiotic-resistant bacteria. Arch Intern Med 2006;166:580-5.
Harbarth S, Sax H, Fankhauser-Rodriguez C, Schrenzel J, Agostinho A, Pittet D. Evaluating the probability of previously unknown carriage of MRSA at hospital admission. Am J Med 2006;119:275.e15,275.e23.
Jain R, Kralovic SM, Evans ME, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med 2011;364:1419-30.
West TE, Guerry C, Hiott M, Morrow N, Ward K, Salgado CD. Effect of targeted surveillance for control of methicillin-resistant Staphylococcus aureus in a community hospital system. Infect Control Hosp Epidemiol 2006;27:233-8.
Robicsek A, Beaumont JL, Paule SM, et al. Universal surveillance for methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals. Ann Intern Med 2008 18;148:409-18.
Harbarth S, Fankhauser C, Schrenzel J, et al. Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients. JAMA 2008 299:1149-57.
Perl TM, Cullen JJ, Wenzel RP, Zimmerman MB, Pfaller MA, Sheppard D, et al. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. N Engl J Med 2002;346:1871-7.
Kluytmans JA, Manders MJ, van Bommel E, Verbrugh H. Elimination of nasal carriage of Staphylococcus aureus in hemodialysis patients. Infect Control Hosp Epidemiol 1996;17:793-7.
Nicholson MR, Huesman LA. Controlling the usage of intranasal mupirocin does impact the rate of Staphylococcus aureus deep sternal wound infections in cardiac surgery patients Am J Infect Control 2006;34:44-8.
Cimochowski GE, Harostock MD, Brown R, Bernardi M, Alonzo N, Coyle K. Intranasal mupirocin reduces sternal wound infection after open heart surgery in diabetics and nondiabetics. Ann Thorac Surg 2001;71:1572,8.
Garrouste-Orgeas M, Timsit JF, Kallel H, et al. Colonization with methicillin-resistant Staphylococcus aureus in ICU patients: Morbidity, mortality, and glycopeptide use. Infect Control Hosp Epidemiol 2001;22:687-92.
Lee AS, Macedo-Vinas M, Francois P, et al. Impact of combined low-level mupirocin and genotypic chlorhexidine resistance on persistent methicillin-resistant Staphylococcus aureus carriage after decolonization therapy: A case-control study. Clin Infect Dis 2011;52:1422-30.
Holton DL, Nicolle LE, Diley D, Bernstein K. Efficacy of mupirocin nasal ointment in eradicating Staphylococcus aureus nasal carriage in chronic haemodialysis patients. J Hosp Infect 1991;17:133-7.
Gupta K, Strymish J, Abi-Haidar Y, Williams SA, Itani KM. Preoperative nasal methicillin-resistant Staphylococcus aureus status, surgical prophylaxis, and risk-adjusted postoperative outcomes in veterans. Infect Control Hosp Epidemiol 2011;32:791-6.
Simor AE, Phillips E, McGeer A, Konvalinka A, Loeb M, Devlin HR, et al. Randomized controlled trial of chlorhexidine gluconate for washing, intranasal mupirocin, and rifampin and doxycycline versus no treatment for the eradication of methicillin-resistant Staphylococcus aureus colonization. Clin Infect Dis 2007;44:178-85.
Konvalinka A, Errett L, Fong IW. Impact of treating Staphylococcus aureus nasal carriers on wound infections in cardiac surgery. J Hosp Infect 2006;64:162-8.
Bode LG, Kluytmans JA, Wertheim HF, Bogaers D, Vandenbroucke-Grauls CM, Roosendaal R, et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med 2010;362:9-17.
Darouiche RO, Wall MJ Jr, Itani KM, Otterson MF, Webb AL, Carrick MM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med 2010;362:18-26.
Controversy Regarding Control of Staphylococcus aureus, particularly MRSA
Wenzel RP, Edmond MB. Infection control: The case for horizontal rather than vertical interventional programs. Int J Infect Dis 2010;14(Suppl 4):S3-5.
Wenzel RP, Bearman G, Edmond MB. Screening for MRSA: A flawed hospital infection control intervention. Infect Control Hosp Epidemiol 2008;29:1012-8.
Farr BM. Doing the right thing (and figuring out what that is). Infect Control Hosp Epidemiol 2006;27:999-1003.
Farr BM, Jarvis WR. What works and what doesn’t for the control of methicillin-resistant Staphylococcus aureus infection: Dogma and data. Clin Infect Dis 2009;49:987-8.
Vriens MR, Fluit AC, Troelstra A, Verhoef J, van der Werken C. Is methicillin-resistant Staphylococcus aureus more contagious than methicillin-susceptible S. aureus in a surgical intensive care unit? Infect Control Hosp Epidemiol 200223:491-4.
Farr BM, Jarvis WR. Why we disagree with the analysis of Wenzel et al. Infect Control Hosp Epidemiol 2009;30:497-9.
Cost, Cost-Benefit, and Savings associated with Control Programs
Bjorholt I, Haglind E. Cost-savings achieved by eradication of epidemic methicillin-resistant Staphylococcus aureus (EMRSA)-16 from a large teaching hospital. Eur J Clin Microbiol Infect Dis 2004;23:688-95.
Vriens M, Blok H, Fluit A, Troelstra A, Van Der Werken C, Verhoef J. Costs associated with a strict policy to eradicate methicillin-resistant Staphylococcus aureus in a Dutch university medical center: A 10-year survey. Eur J Clin Microbiol Infect Dis 2002;21:782-6.
Karchmer TB, Durbin LJ, Simonton BM, Farr BM. Cost-effectiveness of active surveillance cultures and contact/droplet precautions for control of methicillin-resistant Staphylococcus aureus. J Hosp Infect 2002;51:126-32.
Papia G, Louie M, Tralla A, Johnson C, Collins V, Simor AE. Screening high-risk patients for methicillin-resistant Staphylococcus aureus on admission to the hospital: Is it cost effective? Infect Control Hosp Epidemiol 1999;20:473-7.
Chaix C, Durand-Zaleski I, Alberti C, Brun-Buisson C. Control of endemic methicillin-resistant Staphylococcus aureus: A cost-benefit analysis in an intensive care unit. JAMA 1999;282:1745-51.
Jernigan JA, Clemence MA, Stott GA, et al. Control of methicillin-resistant Staphylococcus aureus at a university hospital: One decade later. Infect Control Hosp Epidemiol 1995;16:686-96.
Noskin GA, Rubin RJ, Schentag JJ, Kluytmans J, Hedblom EC, Jacobson C, et al. Budget impact analysis of rapid screening for Staphylococcus aureus colonization among patients undergoing elective surgery in US hospitals. Infect Control Hosp Epidemiol 2008;29:16-24.
Nelson RE, Samore MH, Smith KJ, Harbarth S, Rubin MA. Cost-effectiveness of adding decolonization to a surveillance strategy of screening and isolation for methicillin-resistant Staphylococcus aureus carriers. Clin Microbiol Infect. 2010;16:1740-6.
Contact Precautions and Possible Adverse Effects of Contact Precautions
Snyder GM, Thom KA, Furuno JP, Perencevich EN, Roghmann MC, Strauss SM, et al. Detection of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci on the gowns and gloves of healthcare workers. Infect Control Hosp Epidemiol2008;29:583-9.53. Kirkland KB. Taking off the gloves: Toward a less dogmatic approach to the use of contact isolation. Clin Infect Dis 2009;48:766-
Day HR, Perencevich EN, Harris AD,et al. Do contact precautions cause depression? A two-year study at a tertiary care medical centre. J Hosp Infect 2011;78:1-4.
Saint S, Higgins LA, Nallamothu BK, Chenoweth C. Do physicians examine patients in contact isolation less frequently? A brief report. Am J Infect Control 2003;31:354-6.
Morgan DJ, Diekema DJ, Sepkowitz K, Perencevich EN. Adverse outcomes associated with contact precautions: A review of the literature. Am J Infect Control 2009;37:85-93.
Shardell M, Harris AD, El-Kamary SS, Furuno JP, Miller RR, Perencevich EN. Statistical analysis and application of quasi experiments to antimicrobial resistance intervention studies. Clin Infect Dis 2007;45:901-7.
Harris AD, Lautenbach E, Perencevich E. A systematic review of quasi-experimental study designs in the fields of infection control and antibiotic resistance. Clin Infect Dis 2005;41:77-82.
Harris AD, Bradham DD, Baumgarten M, Zuckerman IH, Fink JC, Perencevich EN. The use and interpretation of quasi-experimental studies in infectious diseases. Clin Infect Dis 2004;38:1586-91.
Popovich KJ, Weinstein RA, Hota B. Are community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains replacing traditional nosocomial MRSA strains? Clin Infect Dis 2008;46:787-94.
Saravolatz LD, Markowitz N, Arking L, Pohlod D, Fisher E. Methicillin-resistant Staphylococcus aureus. epidemiologic observations during a community-acquired outbreak. Ann Intern Med 1982;96:11-6.
Herold BC, Immergluck LC, Maranan MC, Lauderdale DS, Gaskin RE, Boyle-Vavra S, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA 1998;279:593-8.
From the Centers For Disease Control and Prevention. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus – Minnesota and North Dakota, 1997-1999. JAMA 1999;282):1123-5.
Centers for Disease Control and Prevention (CDC). Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus – Minnesota and North Dakota, 1997-1999. MMWR Morb Mortal Wkly Rep 1999;48:707-10.
Wassenberg MW, Bootsma MC, Troelstra A, Kluytmans JA, Bonten MJ. Transmissibility of livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch hospitals. Clin Microbiol Infect 2011;17:316-9.
Guidelines for Controlling Resistant Staphylococcus aureus
Muto CA, Jernigan JA, Ostrowsky BE, et al. SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and Enterococcus. Infect Control Hosp Epidemiol 2003;24:362-86.
Siegel JD, Rhinehart E, Jackson M, Chiarello L, Healthcare Infection Control Practices Advisory Committee. Management of multidrug-resistant organisms in health care settings, 2006. Am J Infect Control 2007;35(Suppl 2):S165-93.
Siegel JD, Rhinehart E, Jackson M, Chiarello L, Health Care Infection Control Practices Advisory Committee. 2007 guideline for isolation precautions: Preventing transmission of infectious agents in health care settings. Am J Infect Control 2007;35(Suppl 2):S65-164.
Wertheim HF, Ammerlaan HS, Bonten MJ, et al. Optimisation of the antibiotic policy in the Netherlands. XII. The SWAB guideline for antimicrobial eradication of MRSA in carriers. Ned Tijdschr Geneeskd 2008;152:2667-71.
Infection Prevention Working Party (WIP). MRSA hospital guideline [Internet]; 2007.
Coia JE, Duckworth GJ, Edwards DI, Farrington M, Fry C, Humphreys H, et al. Guidelines for the control and prevention of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities. J Hosp Infect 2006;63(Suppl 1):S1-44.
National Health and Medical Research Council. Australian Commission on Safety and Quality in Healthcare, Australian guidelines for the prevention and control of infection in healthcare. Commonwealth of Australia [Internet]; 2010.
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