A Quarterly Publication by Cepheid

Volume 02, Issue 01

The Decolonization Decision
In A New Healthcare Paradigm

Converging Pressures Encourage Rapid MRSA/SA Testing


		Ellen Jo Baron, PH. D.
		Director, Clinical Microbiology Lab, SHC Professor, Dept. of Pathology, Stanford Med School

Hospitals are experiencing a new paradigm in which they will receive no reimbursement for healthcare-associated infections (HAI) whether the patient is a carrier at admission or not, and in which their rates of HAI will be available for public scrutiny without the opportunity to justify high rates based on risk factors among patient populations.

At the same time, an ever-increasing number of patients carry methicillin-resistant Staphylococcus aureus (MRSA). These patients not only have an increased risk of infection, but they may also transmit infection to others. In this new healthcare environment, economic considerations will drive the implementation of the most effective infection prevention strategies.

As discussed in previous On-Demand issues, limiting the opportunity for transmission time by using the fastest test for MRSA and S. aureus colonization has been shown to dramatically reduce transmission events and infection rates. Last year, Espinoza reported that one hospital saved an estimated $576,000 per year by performing MRSA testing once a day, using a molecular test for patients in the ICU, followed by strict isolation for colonized patients.¹ The cost reduction was a result of decreased transmission and infections, even without invoking decolonization.

Decolonization: Early Days

As long ago as 1980, prescient physicians such as Victor Yu (Univ. of Pittsburgh) were experimenting with decolonization of hemodialysis patients carrying Staphylococcus aureus in their noses to prevent subsequent S. aureus infections.² S. aureus-colonized patients were much more likely to develop an infection, and 93% of the infecting organisms were the same strain as the colonizer in the patient’s nares. Hemodialysis patients were known to be at greatly increased risk of such infections, given the presence of a constantly manipulated permanent venous access shunt and their relatively compromised immune status.

Dr. Yu and colleagues did not have the benefit of topical preparations available today, so they used oral rifampin, the effects of which were usually only temporary. Despite the inefficient prophylactic regimen, patients given rifampin developed significantly fewer infections than did patients given a placebo. The results of their study were published in the New England Journal of Medicine in 1986.

Three years later, Dr. Boelaert and colleagues from Belgium evaluated nasal mupirocin ointment versus placebo for decolonization in a cohort of hemodialysis patients. During the therapy period, only one of 16 patients receiving mupirocin over a nine-month period was colonized with S. aureus, whereas 10 out 18 of the placebo group patients harbored S. aureus in their nares (highly significant difference).

Most impressively, the placebo group had six S. aureus infections and the mupirocin-treated group only had one (a different strain from the one originally colonizing that patient).³ The data were indisputable even then; but it has taken the healthcare community a long time to embrace the inevitable conclusion: prophylactic treatment of Staphylococcus aureus-colonized patients reduces morbidity and mortality.

Today: A Greater Challenge

Now, 23 years later, we have a more serious adversary, methicillin-resistant S. aureus, and the increased risk of infection among colonized patients is still a threat. In fact, patients carrying MRSA in their noses are even more likely to develop an infection with their own strain of Staphylococcus than those harboring the more benign methicillin-susceptible S. aureus (MSSA).

Keene and colleagues reported that critically ill S. aureus-colonized patients had a 27-fold higher risk of developing a S. aureus infection within 16-19 days after hospital admission than did non-colonized patients.⁴ To quantify the increased risk associated with MRSA, 36% of those carrying MRSA developed infection in contrast to 19% of those carrying MSSA. Only 2% of non-colonized patients subsequently developed a staphylococcal infection.

In another study, 204 liver transplant unit and ICU patients were tested to determine sites of S. aureus carriage.⁵ Of these patients, 26% carried S. aureus in the nares only, 3% were rectal carriers only, and 25% had the organism in both sites. A whopping 40% of those positive for both nasal and rectal carriage developed a Staphylococcus aureus infection, compared with only 18% among nasal carriers and none of the rectal-only carriers.

Davis and colleagues reported that either MRSA colonization detected at hospital admission or acquisition in the healthcare institution resulted in a ten times higher incidence of MRSA infection than for patients colonized with MSSA or not colonized.⁶ Even long-term (>1 year) carriers of MRSA are at relatively higher risk of morbidity and mortality from a subsequent MRSA infection⁷. An 18 month follow up study of colonized patients after they leave the hospital⁸ revealed a 20-30% risk of serious infection following soft tissue or respiratory tract acquisition and a 40-50% risk of serious infection if the initial isolate came from bone, joint fluid, or nares (as detected on a surveillance test). Clearly, being a carrier of SA or MRSA is a significant risk factor—a sort of “horizontally acquired” genetic risk factor for developing an infection.

MRSA Rates Increasing in the U.S.

More people in the United States are colonized with MRSA now than ever before, and the rate is increasing despite the fact that overall Staphylococcus aureus colonization rates are dropping.⁹ Around 30% of the general U.S. population carries MSSA in their nares, but only around 1.5% carry MRSA (the MRSA rate has almost doubled since the previous survey).

Certain populations are at relatively much higher risk. In addition to hemodialysis patients, HIV/AIDS patients, men who have sex with men, intravenous drug users, obese patients, those with type 1 diabetes, those with conditions that damage the integrity of the skin, and even veterinarians¹⁰ harbor MRSA at rates much higher than the general population. Large animal veterinary personnel had a carriage rate of >15%, compared with around 4% for small animal personnel. The connection here is likely to be the fact that horses and pigs are potential reservoirs of MRSA.

In the healthcare setting, long-term care facility residents are often colonized with MSSA and MRSA. One study found 62% of nursing home patients colonized with S. aureus; 40% overall were colonized with MRSA.¹¹ Interestingly, bacterial loads of nasal MRSA actually increase significantly when patients are treated with beta-lactams or fluoroquinolones for other medical conditions,¹² suggesting that elimination of other mucosal flora by these common antibiotics may put patients at increased risk for becoming carriers. Not surprisingly, the environment surrounding patients taking these antibiotics was more heavily contaminated with MRSA than the environment of control patients.

Consequences are additive and extend beyond the immediate patient. Patients can spread MRSA to their family members. Healthcare workers are more likely to transmit the strain to someone else if the environment is contaminated, and then pass it on to their families.¹³ Patients who enter a room previously occupied by an MRSA-colonized patient have a small but significant increased risk of acquiring the organism themselves.¹⁴

Preventing Infections in MSSA and MRSA-colonized Patients

With the advent of molecular methods for detection of MRSA, we are now armed with the optimal diagnostic tools for recognition of nasal carriers. We can now isolate patients quickly to prevent patient-to-patient transmission. But for individual patients who are carriers, can anything be done to prevent infections in MSSA and MRSA-colonized patients?

Newer studies are showing that indeed, case recognition followed by selective decolonization is highly beneficial to patients who are carriers. A study published several years ago showed a highly statistically significant reduction (67%) in post-surgical sternal wound infections in a group of 854 open heart surgery patients given intranasal mupirocin compared with the initial untreated cohort of 992 similar patients.¹⁵

Thoracic surgeons have jumped on these and other published results, even though the study was not blinded and randomized, and now recommend use of mupirocin prophylaxis for cardiac surgery unless a surveillance test has yielded a negative result for staphylococci.¹⁶ The American Thoracic Society (ATS) has classified the evidence for this recommendation as “A,” representing the best supported in the literature. However, a few skeptics have criticized these studies because they were not placebo-controlled, double-blinded interventional trials, and other factors (such as changes in infection control techniques) could have happened in the interim.

The skeptics are about to be proven wrong, however. Very recently, a group from the Netherlands¹⁷ randomized patients found to be colonized with S. aureus by a real-time PCR on hospital admission to receive either intranasal mupirocin and chlorhexidine baths (decolonization treatment) or placebo. The patients who received placebo developed staphylococcal infections twice as often as did the patients who did not receive the decolonization treatment. In patients who developed deep surgical site infections, the difference was even more striking: infections occurred in 1.1% of the decolonization treatment patients and in 4.9% of those given placebo. This study is important for two reasons:

It showed benefit for patients whose decolonization regimens were started after admission, once the PCR test was positive
It showed benefit for both surgical and non-surgical patients.

While the ATS recommendation was targeted to elective surgeries in which there was time to decolonize patients before hospital admission, the Netherlands study showed that in-hospital decolonization after admission would benefit all surgery patients, including those having emergency or non-elective surgery.

Testing and Decolonization Works: Three Examples

Similar findings are being reported elsewhere in other healthcare settings. A recently reported interventional trial in an Israeli hospital targeted returning patients and residents of long term healthcare facilities for surveillance at admission, contact isolation, and decolonization of MRSA-carrying patients.¹⁸ Following the intervention, MRSA bacteremia rates dropped from 32.7% to 10.3% over 3 years.

Surveillance cultures for intensive care unit patients at admission and weekly thereafter followed by contact isolation and decolonization procedures for the patients found to be colonized resulted in an amazing 67% hospital-wide reduction in MRSA infections in a prestigious East coast hospital.¹⁹

Importantly, these authors had evaluated previous interventions, such as barrier precautions during central venous catheter placement, introduction of alcohol gel hand rubs, a house-wide hand hygiene campaign, as well as the MRSA detection and decolonization protocol. None of these other strategies had an impact. The drop in MRSA infections is directly a result of the surveillance and decolonization of MRSA carriers, as proved by the fact that MSSA infection prevalence remained stable throughout the implementation.

Robicsek and colleagues were among the first in the U.S. to adopt a modification of the Search and Destroy strategy used in Europe. As reported last year, they lowered their hospital-associated MRSA disease prevalence by more than a third (from an already low level) using rapid PCR-based initial screening of patients and then isolating and decolonizing MRSA positive patients with nasal mupirocin and chlorhexidine body washes.²⁰

Recognition is Spreading

Finally, another physician specialty, Ear, Nose and Throat (otolaryngologists) is just discovering the benefits of identifying and treating Staphylococcus carriers in order to reduce their risk of infections. In an article published just this year, researchers at the Massachusetts Ear & Eye Infirmary were the first otolaryngologists to evaluate pre-operative treatment for its effects on post-surgical infections, for patients found positive during pre-screening. Pre-screening was performed using a real-time PCR method (Gene-Ohm, Becton-Dickinson) for MRSA, and cultures for MSSA.²¹

Of 420 adult patients evaluated who were undergoing head and neck invasive procedures for cancer or other reason, 241 received surgery before screening was initiated. Of 179 patients presenting for surgery after implementation of the assay, 97 patients were pre-screened. S. aureus, was carried by 25%, but only two strains (2%) were MRSA. The patients colonized with MRSA were treated with 5 days of mupirocin ointment and chlorhexidine baths every other day over 6 days.

Before screening was initiated, 3 of 241 patients developed staphylococcal infections, two of which were MRSA. After screening and intervention, there were no MRSA infections. The study also points out the issues involved in assuring that all eligible patients actually do get screened within an appropriate timeframe, and suggested that the ideal time for screening would be at the pre-operative visit in the doctor’s office.

Convergence of Pressure and Technology

Clearly, there is a strong and growing collection of studies demonstrating the effectiveness of rapid identification and intervention strategies for MRSA and Staphylococcus aureus colonization. There are also pressures encouraging the adoption of these strategies:

Increasing number of people colonized with MRSA
Hospitals bearing costs for HAI
Public scrutiny of hospitals’ HAI rates

In this demanding healthcare environment, on-demand molecular testing is proving essential, with economic considerations driving the implementation of the most effective tests and interventions.

The next article in this issue will highlight the benefits of using a rapid test for diagnostic purposes, which also cuts costs while enhancing patient care.

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