JSTOR

Clinical Effectiveness of Active Surveillance Cultures and Isolation

Much of the original evidence supporting use of active surveillance cultures as an effective means to prevent infections caused by antimicrobial‐resistant bacteria emerged from experience with hospital outbreaks. When used during an outbreak, active surveillance cultures have been convincingly demonstrated to interrupt the spread of both VRE ^37,41‐49 and MRSA.^50‐55 The evidence supporting the use of active surveillance cultures for the control of antimicrobial‐resistant bacteria in circumstances other than during an outbreak is more limited.^36,56‐67 Most of the available reports describe surveillance programs applied to high‐risk units (such as ICUs and dedicated wards for immunocompromised patients) or specific populations of high‐risk hospital patients (such as long‐term care facility residents or hemodialysis patients). As a result, the findings of these studies are not easily extrapolated to patients and circumstances in which the risk of transmission of antimicrobial‐resistant bacteria might be lower.

Fewer published reports have examined application of active surveillance cultures to all hospitalized patients, the strategy mandated by the proposed legislation. Further, many of the available studies were not designed to assess the effectiveness of an active surveillance culture program in reducing transmission or infection, but rather were undertaken to determine how colonized or infected patients could be most efficiently and affordably detected.^68‐70 In each case, the investigators concluded that targeted surveillance of high‐risk patients, such as is advocated by the previous SHEA and HICPAC guidelines, offers the optimum strategy to detect colonized and infected patients.

One especially important study that examined the performance of active surveillance cultures to control endemic infection is that of Ostrowsky and colleagues.⁷¹ Testing a strategy to reduce VRE transmission in more than 30 long term and acute care facilities in Iowa, Nebraska, and South Dakota, the investigators demonstrated that the proportion of patients identified as VRE carriers fell from 2.2% to 0.5% in the participating facilities during the 3 years of the study.⁷¹ Although based on periodic screening rather than a continuous active surveillance culture program, the study demonstrates that health system–wide reduction in VRE colonization is possible.

Well‐designed comparator trials represent the “gold standard” for reliably quantifying the performance of active surveillance cultures for the control of antimicrobial resistant pathogens in circumstances other than during an outbreak. However, such investigations have been, thus far, only infrequently undertaken. In one nonrandomized study, Price and colleagues⁷² found that the rate of VRE bacteremia was 2.1 times higher in a hospital that did not screen patients, compared with a second hospital in which high‐risk patients were routinely screened by means of surveillance cultures at admission and periodically during the hospital stay.

A large, multicenter, randomized study incorporating use of active surveillance cultures to screen for both VRE and MRSA is currently underway under the auspices of the Bacteriology and Mycology Study Group and supported by the National Institute for Allergy and Infectious Diseases.⁷³ In this study, 19 ICUs have been randomly assigned to implementation of either routine infection control practices or a more intensive infection prevention strategy, including use of active surveillance cultures to screen for both MRSA and VRE. The primary outcome is the incidence of new colonization or infection events with MRSA and VRE during the ICU stay. The results of this study should be available within the next 12 months and are likely to add considerably to the discussion of use of active surveillance cultures for high‐risk populations.

While awaiting the results of rigorous, prospective, and well‐controlled studies, mathematical models have been employed to help predict the potential effect of using active surveillance cultures to reduce transmission of antimicrobial‐resistant bacteria in lower‐risk patients. Cooper and colleagues⁷⁴ found that “a policy of screening newly admitted patients for MRSA coupled with rapid and effective isolation and treatment could make a major contribution to controlling its spread.”^74(p10228) Bootsma and colleagues⁷⁵ modeled the potential effectiveness of a strategy of rapid diagnostic testing, compared with use of surveillance cultures and isolation, to dramatically reduce the prevalence of MRSA colonization and infection over time. Similar mathematical models are available for VRE transmission.⁷⁶ Although the potential value and importance of theoretical mathematical models are recognized, epidemiological assumptions incorporated in models require validation in a wide variety of settings and circumstances. Careful interpretation of models, recognizing all the limitations and assumptions, is essential.

Any overview of the clinical performance of active surveillance culture programs must acknowledge the ongoing experience with related strategies in Denmark, The Netherlands, and several other European countries, since these efforts have not only informed the studies previously discussed but have likely influenced the current US legislative initiatives. In most of these countries, “search and destroy” methods have been employed to reduce MRSA to the status of an uncommon nonendemic pathogen in recent years. This long‐standing, intensive, coordinated campaign relies on targeted screening of high‐risk patients. If multiple cases of MRSA colonization or infection are detected, entire units may be closed for comprehensive screening and cleaning.^77‐80 In addition, healthcare workers may be screened for MRSA carriage and, if colonized, not allowed to work until successfully decolonized.

Extrapolating these experiences to the United States may be difficult. First, there appear to be differences between Europe and North America in the epidemiology of antimicrobial‐resistant bacteria. The high prevalence of MRSA colonization and infection already seen in various regions of the United States represents a particular challenge, as this was not the case in nearly any of the European nations when “search and destroy” programs were initially implemented. Moreover, the impact of community‐associated MRSA colonization and infection on the effectiveness and feasibility of using active surveillance cultures in the United States and other affected nations is unknown.^81,82 Given the rapid spread of community‐associated MRSA strains, it may be particularly challenging to control MRSA with any strategy that focuses exclusively on the hospital. Secondly, it should be noted that the proposed US legislation describes a universal screening program that differs in scope from the targeted “search and destroy” method employed successfully in Europe. Finally, use of active surveillance cultures may be more difficult to implement and sustain because of the size and the heterogeneity of the healthcare environment found in the United States.

Cost‐Effectiveness of Using Active Surveillance Cultures and Isolation

Use of active surveillance cultures has been shown to be cost‐effective during outbreaks in ICUs. Karchmer and colleagues⁸³ demonstrated that weekly surveillance cultures and isolation of infants colonized or infected with MRSA interrupted an epidemic of MRSA infection at one neonatal ICU, and that the cost was 19‐ to 27‐fold less than the attributable cost of excess MRSA bloodstream infections in a comparison hospital where samples for surveillance cultures were not collected. Similarly, Muto and colleagues⁸⁴ found that use of surveillance cultures for high‐risk patients to control an outbreak of VRE infection at a university hospital significantly reduced the incidence of VRE bacteremia and the total costs, compared with those at another hospital where the strategy was not employed.

Use of active surveillance cultures has also been suggested to be cost‐effective in high‐risk settings in the absence of an outbreak. Chaix and colleagues⁸⁵ evaluated the costs and benefits of an active surveillance program to control endemic MRSA in the medical ICU of a French university hospital. Assuming a high risk of infection (greater than 25%) among colonized patients, the authors found that the active surveillance strategy was cost‐effective when the rate of MRSA carriage on admission to the unit was 1%‐7%, even if only a small proportion of MRSA infections were prevented.

Comparable experience with the cost‐effectiveness of using active surveillance cultures for the control of endemic VRE has also been reported. Montecalvo and colleagues⁸⁶ described a multipronged effort to control endemic VRE in an adult oncology unit. They demonstrated that the overall savings attributable to the number of VRE infections prevented by use of active surveillance cultures more than outweighed the added expense of the program itself.

Although these and other studies provide evidence to support the economic benefit of using surveillance cultures to screen for MRSA and VRE among high‐risk patients or during outbreaks, examination of the cost‐effectiveness of screening all patients across all healthcare settings has not yet been performed. Future analyses, especially those that incorporate the results of rigorous epidemiological studies to provide an accurate range of model parameters, are needed.

Effectiveness of Eradication and Suppression of Colonization

Carriers of MRSA or VRE are often colonized for long periods of time.^87,88 During the period that they remain colonized, these patients are at added cumulative risk for infection and can serve as a potential source for transmission to others. To preempt these phenomena, a number of approaches to decolonizing patients have been evaluated for both MRSA^89‐91 and VRE.⁹²

Strategies to eradicate MRSA colonization have included the use of a range of agents applied either topically (generally to the anterior nares) or systemically.^93‐95 The overall utility of decolonization strategies for patients colonized or infected with MRSA was the subject of a recent systematic review.⁹⁶ On the basis of the results of 6 trials that included 384 participants, the authors of the study concluded that the available evidence is inadequate to recommend the use of topical or systemic agents to eliminate MRSA colonization. Unfortunately, aggressive attempts to institute programs to eradicate MRSA have been accompanied by the emergence of MRSA strains that are resistant to mupirocin, the topical antimicrobial agent most commonly used for nasal decolonization.^91,97,98

Attempts to eradicate VRE colonization have primarily focused on eliminating intestinal carriage of the organism, often with nonabsorbable enteral antimicrobial agents. The results of these studies have been variable and somewhat disappointing.^99,100 Limited success has been demonstrated with the nonabsorbable agent ramoplanin.⁹² In one recent study, the rate of VRE acquisition among ICU patients was reduced through the use of chlorhexidine baths to eliminate VRE on the skin.¹⁰¹

Potential Impact on Infection Control Programs and Priorities

In the United States and other countries with established infection prevention and control infrastructure, infection control professionals, managers, and healthcare epidemiologists are responsible for planning and executing a wide array of activities to protect the health of patients, staff and hospital visitors. Included in this broad scope of work are routine surveillance for healthcare‐associated infections, detection and investigation of outbreaks, and ensuring institutional compliance with regulatory mandates from federal agencies and state and local health departments. Increasingly, emphasis has also been placed on the measurement and improvement of performance standards for the prevention of healthcare‐associated infections caused by both antimicrobial‐resistant and antimicrobial‐susceptible bacteria.

In addition to local and institutional efforts, infection prevention and control activities have increasingly been promoted and coordinated on a broader scale, emphasizing interinstitutional collaboration for the transfer of knowledge and the sharing of best practices. Such initiatives have included national and regional collaborations aimed at reducing central line–associated bloodstream infections and ventilator‐associated pneumonia, pay‐for‐performance programs to enhance the appropriate delivery of perioperative antimicrobial prophylaxis, and public health interventions to promote more‐uniform infection control approaches.¹⁰² These efforts have resulted in substantial numbers of infections prevented and, ultimately, lives saved.

The allocation of infection control resources for these manifold tasks has traditionally been the responsibility of healthcare epidemiologists and infection control and prevention professionals, with the support of hospital administrators. Through careful risk assessment based on the available local data, and with sensitivity to the clinical priorities of the institution, these experts must allocate an increasingly limited pool of personnel and resources. Priority is typically given to the most critical needs of patients, while the flexibility is retained to respond swiftly to both unexpected changes in local epidemiological trends, as well as the most up‐to‐date scientific evidence.

Legislation mandating use of active surveillance cultures or any other infection control strategy neither recognizes the need for flexible allocation of resources to the most critical hospital‐specific challenges nor allows for a timely response when significant new information becomes available. In addition, legislation mandating any single infection control and prevention strategy that exclusively targets specific antimicrobial‐resistant pathogens may be counterproductive, compared with integrated infection prevention and control strategies that result in a greater overall reduction in the number of healthcare‐associated infections caused not only by MRSA and VRE but by all antimicrobial‐resistant and antimicrobial‐susceptible pathogens. For example, improvement in hand hygiene compliance and prevention of surgical site infections, ventilator‐associated pneumonia, and central venous access device–associated infection are clinically efficacious against nearly all pathogens responsible for healthcare‐associated infections. The relative emphasis placed on these initiatives, as well as use of active surveillance cultures, is best determined by risk assessment at the level of the individual institution.

The dilemmas posed by legislation mandating use of active surveillance cultures will be especially problematic if no additional resources are made available for implementation. Without additional support, healthcare epidemiologists and infection control and prevention professionals will be necessarily compelled to dedicate themselves to performance of active surveillance cultures at the expense of established and effective strategies that may be more appropriate to the local situation. In this manner, mandating use of active surveillance cultures could lead to worsening rates of other potentially devastating healthcare‐associated infections—including Clostridium difficile–associated disease,¹⁰³ healthcare‐associated infections caused by antimicrobial‐susceptible and other antimicrobial‐resistant bacteria, and even pandemic influenza or other as‐yet‐unrecognized emerging pathogens. Legislation mandating use of one particular infection control strategy is no different than legislation insisting on use of one specific operative approach by cardiovascular surgeons, one pain regimen by palliative care specialists, or one particular chemotherapy agent by oncologists.

Requirements for Data Management and Validation, Monitoring Compliance, and Enforcement

The success of any active surveillance program depends on the quality, timeliness, and reliability of the data generated. The results must be presented in a manner that is familiar and easy to understand. Simultaneously, to allow meaningful benchmarking and comparisons across institutions, an active surveillance culture program must conform to standards recognized by accreditation bodies, professional societies, and public health authorities. Nevertheless, numerous questions remain about the epidemiological, biological, clinical, and logistical implications of active surveillance. How are rates of MRSA and VRE colonization and infection most appropriately quantified? How should patients who acquire colonization with MRSA or VRE during one hospitalization but return with infection at a subsequent admission be counted and managed? What is the optimal body site from which to obtain specimens for surveillance, and is this site the same for all patient populations and situations? Does the same hold true for novel or emerging strains of MRSA or VRE? What is the most appropriate microbiological assay to use for surveillance? Is there a role for more‐sensitive molecular assays? Resolution of the questions and controversies regarding these standards must be established as a prerequisite for the application of active surveillance cultures to lower‐risk and high‐risk patients. Rational and evidence‐based standards must be developed with input from experts in healthcare epidemiology and in infection control and prevention to ensure that the design, conduct, analysis, and interpretation of surveillance programs are appropriate.

The legislation as proposed in both Illinois and Maryland does not specify how the implementation of mandatory active surveillance culture programs would be ensured and monitored, nor is it clear who would bear the costs (hospitals, patients, and/or insurers). Currently, Medicare and most other insurers will not reimburse providers for performance of screening cultures. In addition, the role of the Joint Commission on Accreditation of Healthcare Organizations, the Centers for Disease Control and Prevention, and other agencies with whom healthcare epidemiologists and infection control and prevention professionals have historically collaborated to develop and ensure practice standards also remains to be defined. It would be imprudent to assume that local or state health departments are equipped with the infrastructure, resources, or expertise to oversee mandatory active surveillance culture programs at every healthcare facility in their jurisdiction. In fact, many state health departments do not have staff with infection control expertise. Adding oversight of active surveillance programs to public health departments could unnecessarily strain the capacity of these agencies. The amount and complexity of information to be reported to health departments would be substantial, and management of such information would divert public health personnel away from other important duties, such as oversight of tuberculosis programs; communicable disease surveillance, prevention, and control activities; and investigation of community outbreaks. The result would be not only inconsistent supervision and coordination of institutional active surveillance programs but also a necessary shift of state resources from other important public health efforts.

Safety and Isolation Precautions

Despite the benefit of preventing transmission of bacterial pathogens from patient to patient and the clear negative effects of MRSA and VRE infection, several recent studies have raised concern regarding potential negative aspects of patient isolation. Stelfox et al.¹⁰⁴ found that isolated patients were twice as likely as control patients to experience adverse events, more likely to file a formal complaint with the hospital, more likely not to have vital signs appropriately recorded, and more likely to have more days without a physician progress note. Similar observations have been reported in a number of other studies.^105‐107 Accurately determining the safety of isolation and optimizing practice to ensure the best outcome for patients should be addressed prior to the widespread implementation of active surveillance culture programs.

Logistical Barriers to the Mandatory Implementation of Active Surveillance Culture Programs

In addition to the broader concerns already described, a number of more practical challenges would accompany the widespread implementation of active surveillance culture programs as mandated by the proposed legislation, particularly if additional resources are not made available to support these initiatives. Although each such logistical challenge may individually not be insurmountable, in the context of the greater concerns regarding legislation mandating use of active surveillance cultures, the examples described below and other obstacles must be anticipated and addressed before, not after, any widespread program is implemented.

At least initially, identification of MRSA or VRE carriers by means of active surveillance cultures will be associated with an increase in the number of patients who must be cared for using contact precautions, which ideally includes use of a private room. Estimates based on the experience at hospitals that have performed limited prevalence surveillance at hospital admission indicate that up to 7.9% of all admitted patients would require initial isolation after the adoption of a mandatory active surveillance culture program.^{68,69,108,109} The limited number of single‐patient rooms in many healthcare facilities represents a very real issue that would need to be addressed in the face of legislation mandating use of active surveillance cultures.

Although cohorting of colonized or infected patients together under the care of dedicated providers has been advocated and shown to be practical under special circumstances,⁵⁶ this can be quite difficult on a large scale and could potentially lead to delays in the admission of patients, patient transfers within the hospital, and hospital discharge of colonized or infected patients who require skilled nursing care or rehabilitation. In addition, if use of active surveillance cultures is also mandated in long‐term care facilities, the resultant need for isolation may further limit the availability of beds in such facilities for patients being discharged from the hospital, creating an additional bottleneck in patient flow.¹¹⁰ Although, in the long term, many of these patient‐flow issues will improve if the spread of antimicrobial‐resistant bacteria diminishes and there are fewer patients colonized or infected with MRSA and VRE, the short‐term detriment could be significant, were legislation mandating use of active surveillance cultures to be enacted.

A second practical issue that would accompany legislation mandating use of active surveillance cultures relates to the change in workload that would be faced by clinical microbiology laboratories. At most healthcare facilities, including some large acute care hospitals, the clinical microbiology laboratory is not presently equipped or staffed to manage the collection, processing, analysis, and interpretation of the increased number of specimens and results that would be generated by more widespread use of active surveillance cultures to screen for antimicrobial‐resistant pathogens. Even at centralized laboratories, unless there is advance planning, the addition of the thousands, if not tens of thousands, of cultures generated by active surveillance could overwhelm staff, equipment, and resources. Delays in processing and reporting isolates obtained as part of routine clinical care may occur, with possible risk to patients.