The impact of MRSA
Despite over a decade of interventions, Methicillin-resistant
Staphylococcus aureus (MRSA) remains a significant and all too common pathogen encountered in the U.S. Healthcare system. Extrapolating data from selected counties from nine states, the Centers for Disease Control and Prevention (CDC) estimated that in the United States MRSA caused over 80,000 “invasive” infections and over 11,000 deaths in 2011 [
1]. This data represents documented severe infections, requiring a positive MRSA culture from a normally sterile site, such as blood cultures associated with bacteremia. Using billing data from U.S. hospitals from 2011, the Agency for Healthcare Research & Quality (AHRQ) found that more than 460,000 hospitalizations had a MRSA diagnosis, with 23,000 deaths associated with these admissions [
2]. MRSA is a leading cause of healthcare associated infections [
1,
3], and patients undergoing a surgical procedure are at an increased risk of acquiring these infections [
1]. Kaye et al. reported that the average immediate economic impact from treating a deep incisional or organ space surgical site infection is $43,970 in patients 65 years and older [
3], not counting possible long term treatment and disability. Unlike other adverse events, eliminating the occurrence of infections cannot be completely controlled and regulated by a single facility, as infection control measures at one facility may well affect and contribute to the MRSA prevalence in other nearby facilities [
4]. Many different types of facilities are at risk, along with their service communities, making the need to control healthcare associated infections even more imperative. Colonization rates of
Staphylococcus aureus (
S. aureus) in the United States are approximately 30% [
5]. The rate of MRSA colonization in patients admitted to hospitals tend to range from 1.3% to 7.6% [
6‐
8], with colonized patients displaying a higher risk of developing a MRSA infection [
9‐
13].
Control of this epidemic is multifactorial, with single interventions unlikely to have a significant impact on attenuating MRSA infection rates. Hand hygiene is of importance, but institutions that only focus on this intervention are unlikely to be successful in controlling MRSA infections. Surgeons performing even simple office procedures using sterile gloves alone know the difficulties in maintaining a sterile field. As observed by Lee et al. [
14], a bundle approach was required and neither active surveillance or hand hygiene alone produced significant reductions in MRSA infections in surgical wards. Using a screening and decolonization protocol, Rao et al. observed that none of the 147 (methicillin-sensitive
Staphylococcus aureus) MSSA and 17 MRSA colonized patients developed an infection post joint arthroplasty [
15].
Active surveillance for MRSA has been studied on a wide range of surgical patients, including surgical intensive care and non-intensive care units; cardiac, vascular, orthopedic, obstetric, head and neck cancer and gastrostomy patients [
14,
16‐
18]. The vast amount of the research has centered on the inpatient setting, of which a combinational or bundled approach has emerged as a superior intervention in preventing the spread of MRSA infections [
14,
18].
Preventative measures for MRSA infections in surgical patients
Surgeons encounter two different scenarios where MRSA preventative measures are needed. The first is for surgery patients admitted to surgical units or intensive care units where universal surveillance testing and isolation vs universal daily decolonization have been advocated. The second is for patients admitted for same-day surgery where preoperative MRSA screening and decolonization can by performed on an outpatient basis, eliminating the need for isolation.
The prevention of the spread of MRSA in surgical units is of critical importance. Prolonged contact with the healthcare setting increases the possibility of patients contracting MRSA from bacteria brought into the facility by other patients. Thus, the longer the contact and the sicker the patient the greater the concern.
One of the factors that may have impeded the adoption of active surveillance protocols [
19] was the highly quoted study published by Harbarth et al. [
20]. This study was referred to in a U.S. Congressional hearing as one of the reasons why the effects of screening are poorly understood [
21,
22] and by The Society for Healthcare Epidemiology of America/Healthcare Infection Control Practices Advisory Committee (SHEA/HIPAC) as a reason why recommendations regarding active surveillance testing cannot be made [
23].
The Harbarth et al., study was well-controlled and produced negative findings in regard to the utilization of active surveillance methods. However, it had methodological limitations [
19] and appeared to have identifiably known deficiencies in implementation: 31% of the patients were identified as MRSA carriers after, not before, the surgery, and only 43% of patients who were known to be carriers before surgery received preoperative antibiotics effective against MRSA [
20]. Of the patients who developed a MRSA infection and were known carriers prior to surgery, only 66% received prophylaxis against MRSA and almost 60% did not receive optimal decolonization of MRSA prior to surgery [
20]. In addition, the study was contradicted by a well-controlled, large multi-national, multi-institutional study published by Lee et al. [
14], (whose corresponding author was Harbarth) which reported surveillance along with hand hygiene and targeted eradication of MRSA to be successful in preventing MRSA surgical infections.
There are at least 19 studies over the last decade that observed a beneficial effect of active surveillance in the prevention of MRSA infections [
14‐
16]. Seventeen of these studies were reviewed in a recent AHRQ publication [
16]. We reviewed these 19 studies and found that in 14, observed benefits of active surveillance reached statistical significance. However, with the exception of Lee et al. [
14], the studies that demonstrated a statistically significant effect on MRSA have been criticized for deficiencies in design, not controlling confounding variables and/or secular trends [
16,
19]. In other words, the majority of the studies were a before and after design and there is a possibility that an unknown factor may have been present or introduced as these studies were conducted. Confounding factors may vary results in either direction. For example, the implementation of another seemingly unrelated protocol might produce an unexpected augmentation of the intervention’s positive results or the increase in the rates of MRSA in the community might produce an unexpected mitigation of the observed results. However, dominant impacting factors causing positive results across so many studies is unlikely.
A review of the literature regarding MRSA active surveillance in surgical patients was published by AHRQ in 2013 and failed to make recommendations, despite multiple studies observing that active surveillance reduces MRSA infections [
16]. Taken together, the negative study published by Harbarth et al. [
20], and the lack of control for unknown possible confounding factors in the remaining studies, appeared to be reasons that prevented AHRQ from making recommendations.
If the studies with known unadjusted confounding factors (the factor that biased the results is evident) are disregarded and the myriad of positive studies with a possible unknown confounding factor are then considered, the case for the use of active surveillance would be strengthened.
This is not to say that as new treatments emerge protocols should not be changed, but not implementing or having the best practice protocols in place during a rampant epidemic may be a leading cause for the inability to control multi-resistant organisms in the United States. This problem was outlined in a 2008 report from the Government Accountability Office (GAO), which found a need for the U.S. Department of Health and Human Services to prioritize the almost 1200 recommended prevention practices, of which over 500 are strongly recommended [
24]. Recently, Drees et al. [
25] found highly variable definitions and management protocols for Multidrug resistant gram-negative bacilli and concluded that this variation might contribute to the emergence of these bacteria.
Different prevention protocols are indicated for patients admitted the day of surgery. In this setting, emphasis can be placed on eradication of the carrier state before surgery. A common protocol was the use of intranasal mupirocin and a daily bathing with either chlorhexidine [
14,
15,
26,
27] or triclosan [
6,
28,
29] for 5 days. Several studies required three consecutive negative swabs before MRSA eradication was confirmed and the patient could proceed for elective surgery [
6,
30]. Many of these patients would not have to be isolated, but one could argue that they were effectively isolated from the treatment facility during outpatient decolonization.
There is ample evidence for the beneficial effect of active surveillance and eradication prior to surgery. Why not then subject all patients to the decolonization/eradication protocols and not perform surveillance? There are three concerns with this approach. The first is regarding the selection of antibiotics for preoperative prophylaxis, the second is the promotion of bacterial resistance on the targeted bacteria, and the third is the effect on the microbiome of both the patient and facility.
Selection of antibiotics for preoperative prophylaxis
All studies on surgical patients analyzed by AHRQ and those published by Lee et al. [
14], and Rao et al. [
15], were reviewed. At least five of these studies varied the type of preoperative antibiotic depending upon MRSA surveillance results [
14,
15,
27,
29,
31]. The antibiotic was either ‘modified’ [
14], switched to vancomycin [
15,
27,
31] or combined with teicoplanin [
29]. This is important, because as observed by Gupta et al. [
11], vancomycin is associated with an increase in surgical site infections in non-MRSA carriers but not in MRSA carriers. An extensive review of this subject was conducted by Crawford et al. [
32], who observed that “…the suspected weaker activity against MSSA” has been one of the factors in preventing the routine use of vancomycin for preoperative prophylaxis.
Even though MRSA has been observed to have a higher mortality and a longer length of treatment than MSSA [
32], MSSA is an important pathogen and has been observed to be an important causative organism in hip and knee arthroplasty [
15]. If MSSA is detected preoperatively, eradication prior to elective surgery has been observed to reduce surgical site infections [
33].
Several authors also used decolonization protocols on all preoperative patients, but used surveillance to determine the duration of the decolonization. For example: In MRSA carriers, Jog et al. [
29], used surveillance to extend the decolonization period with mupirocin and triclosan to five days, (United Kingdom’s National Health Services recommends five days of decolonization for newly identified carriers [
34]), and to substitute preoperative antibiotics gentamicin and teicoplanin for gentamicin and flucloxacillin. The authors observed a significant reduction in MRSA infections.
However, these protocols also relate to the second concern, the promotion of bacterial resistance, which may take years or decades to emerge [
35]. Of increased concern is the eradication protocols that are performed on all patients every day, regardless of colonization status, in an inpatient setting or unit. Many decolonization protocols use both an intranasal antibiotic and an antiseptic body wash. This results in a repeated and prolonged exposure of both the patient’s and facility’s microbiome to the antimicrobial agents.