Barriers to implementation of rapid identification and antimicrobial susceptibility testing technologies in the clinical microbiology laboratory: an American perspective

Abstract

Clinical microbiology laboratories are responsible for confirming the aetiology of infectious diseases and providing antimicrobial susceptibility testing results. Traditional culture-based testing can be augmented by more rapid testing modalities to provide clinically actionable information as quickly as possible. Despite improvements in patient outcomes, many clinical microbiology laboratories are facing challenges to in-sourcing these technologies. Depending on a multitude of factors, including size, location and patient population served, these barriers may affect some laboratories and hospital systems to greater or lesser extents than others. It will be up to each individual facility to ascertain its ability to overcome barriers. To aid in this self-assessment, we present for thoughtful consideration a discussion of the barriers to implementation of rapid identification and antimicrobial susceptibility testing technologies, with specific attention to matters of financial cost, staff expertise, operational issues and stakeholder buy-in.

Introduction

The identification of pathogens from clinical specimens, along with antibiotic susceptibility testing (AST) results, are two of the most important tasks performed in clinical microbiology laboratories, as provision of this information enables clinical teams to make informed decisions regarding management of patients with infections. Traditionally, pathogens were identified based on a variety of phenotypic characteristics. The Gram stain, colonial morphology and any haemolysis patterns observed on solid media all provided a presumptive identification for most bacterial pathogens. Definitive identification came from analysis of biochemical testing.^1–3 This process generally yielded a definitive identification in ∼2 to 5 days, depending on the growth rate of the bacteria, and the need for pure subcultures for testing. AST would add at least one more day before fully clinically meaningful information would be reported. Numerous technological advances have standardized this process and improved laboratory workflow. Automated identification and AST systems are now commercially available and provide streamlined workflows, which have decreased the overall time to result.⁴ Total laboratory automation (TLA) further improved workflow by allowing the microbiologist to read cultures as soon as they are ready. Rather than batching culture plates to be read according to source, TLA allows culture reading immediately after appropriate incubation time has been reached. This paradigm shifting technological advance has decreased the overall time between inoculation of media and the first read of the culture, ultimately resulting in faster identification of pathogens from culture. Molecular testing strategies have also improved time to pathogen identification. Single-plex, as well as multi-plex syndromic molecular testing panels, provide an identification directly from a clinical specimen. The time to pathogen identification with these tests is on the order of hours rather than days, providing the clinical team with the pathogen identification more rapidly than traditional culture and allowing more targeted empiric treatment decisions to be made before AST results. These technologies have contributed to meaningful improvements to both patient care^5–7 and laboratory workflow,^8–10 begging the question: why have not more laboratories adopted them? This paper will describe some of the barriers to implementation of rapid ID and AST systems in the clinical microbiology laboratory and provide a potential solution to overcoming these barriers.

Cost

Compared to traditional culture-based testing methods, which generally cost a few dollars per test, rapid ID/AST methods are considerably more expensive. Additionally, implementation of these technologies is an additive process in that the new system does not eliminate any current testing, so a laboratory would not see a financial savings in implementing these tests. Replacement of a VITEK2 card, MicroScan panel or Phoenix panel with a MALDI-ToF mass spectrometry system decreases the cost per isolate for pathogen identification from tens of dollars down to significantly less than one dollar; however, MALDI-ToF systems require a significant up-front capital expenditure, generally on the order of hundreds of thousands of dollars. The process to justify such a large capital expense can be difficult to navigate compared to the justification process for lower-cost instrumentation or instruments obtained via reagent-rental agreements. Likewise, molecular-based rapid testing increases the laboratory expenditure compared to traditional methods. Multiplex molecular syndromic panels provide results for up to 43 targets in ∼1 hour from set up. Acquisition of these systems is associated with both large up-front expenses to purchase the instrument, as well as high costs per test for reagents. Finally, the frequency of quality control testing that must be performed as part of the laboratory Quality Assurance programme, whether or not to deploy rapid test systems at the point-of-care, and the expertise needed to successfully operationalize these test systems, are additional costs that must be considered and understood by healthcare systems as they look to in-source rapid ID/AST technologies.

Laboratories must also be aware of the reimbursement rates for these tests. Given the currently evolving landscape for reimbursement of testing in the United States, there are several factors that require investigation. Reimbursement rules differ depending on whether the intention of the test is to supplement the current laboratory report, to confirm a result or to serve as the preliminary result with confirmation by traditional ID/AST methods. It is important to note that billing of identical results from two different instruments can be considered inappropriate duplication of charges. Billing for reimbursement of confirmatory testing must be carefully done to ensure alignment with regulations of the Centers for Medicare & Medicaid Services. Reimbursement rates vary depending on the geographical location where testing is performed, but in recent years several payers have shown a general trend away from full reimbursement, especially for large, molecular multiplex panels. There are mechanisms to justify the clinical value of rapid testing, including submission of documentation to demonstrate that management of the patient is directly associated with the result of the rapid test. This adds a layer of complexity to the adoption of rapid ID/AST systems that healthcare systems need to be aware of.

Human capital expenses do not show a savings to the laboratory landscape. Rapid testing platforms promote a decrease in technologist time to set up and complete the testing; however, these instruments are random access, with results becoming available continuously. Furthermore, staffing expertise needed to perform clinical and quality control testing and maintain the instrumentation does not allow for reduction of personnel.

Technical expertise

In deciding whether to implement rapid ID/AST testing, the clinical microbiology laboratory must ensure that the appropriate level of expertise is present to both perform the test and to provide expert consultation on the results. Rapid ID/AST tests are typically FDA-cleared in the United States as either waived or non-waived. The Clinical Laboratory Improvement Amendments (CLIA), the US federal regulatory standards that apply to all US facilities that test human specimens for assessment or to diagnose disease, define waived tests as simple tests with a low risk for an incorrect result.¹¹ One example of such a test is a real-time PCR assay that detects Streptococcus pyogenes directly from the throat swab of a patient with signs and symptoms of pharyngitis. Laboratories that perform waived testing require a CLIA certificate, and the test must be performed according to the manufacturer’s instructions. Non-waived tests are defined as those that are moderately complex or highly complex, such as multiplex, real-time PCR assays that detect and identify bloodstream pathogens. Non-waived testing requires additional CLIA requirements be met by the performing laboratory. Laboratories that perform non-waived testing must hold a CLIA certificate and are subject to inspection. These laboratories must also meet certain CLIA quality system standards, including proficiency testing, quality control, quality assessment and personnel requirements.

Maintaining a licensed, well-trained microbiology staff is paramount to successful implementation of rapid ID/AST systems, as these platforms require an understanding of bacterial growth, an ability to correlate the results with conventional methods and a knowledge of intrinsic antimicrobial resistance. Several laboratory professional societies recently conducted surveys to assess the capacity of US laboratories to respond to COVID-19 pandemic testing demands,¹² which confirmed a shortage of trained personnel to perform testing in the clinical microbiology laboratory. Automation can help to alleviate some of the issues that stem from workforce shortages,¹³ but medical laboratory scientists are needed to perform rapid ID/AST testing. Potential solutions to the workforce crisis have been proposed¹⁴; however, when considering the opportunity to implement rapid testing to enhance patient care, laboratories must critically assess their workforce and ensure appropriate staff are in place.

Rapid ID/AST systems represent a paradigm shift in providing clinically actionable information within a much faster time frame than that achieved by traditional culture-based methods. This has yielded a change in the expertise required for the laboratory staff on the evening and night shifts, which have historically been trained to perform Gram stains and set up cultures, but have largely not been required to have expertise in identifying organisms and AST patterns. In-sourcing these platforms requires historic processes to evolve: there is a need to hire medical laboratory scientists with experience in reading and reporting culture results from all specimen types.

Successful implementation of rapid testing requires skilled laboratorians at the bench level, but expertise at the leadership level is also required. An experienced microbiologist with proven skills in operational oversight and personnel management needs to be available to facilitate testing and drive managerial success. Additionally, a certified microbiology specialist at the Director level would be an important asset that could provide vision for the laboratory, guidance on rapid ID/AST system selection and expertise through consultation with clinical teams.¹⁵ Given the significant shift in process described here for bench-level medical laboratory scientists, consultative services by laboratory leadership must also be available on all shifts on which testing is performed.

Operational issues

Multiple logistical and operational issues are involved in successfully implementing rapid ID/AST systems, and each must be thoughtfully considered and planned out. These include: laboratory space (including instrument placement and reagent storage), specimen transport, turnaround time expectations and result communication, among others. Operational constraints may be limiting factors in the successful implementation of rapid ID/AST systems, but overcoming them could lead to improved patient care and higher physician satisfaction with laboratory services.

Laboratory space

Many rapid ID/AST systems were designed for placement on a benchtop. Others are larger floor models that take up more laboratory space. In either case, the footprint of the instrument is a key consideration in adopting new technology. Questions to be addressed include does the laboratory have available benchtop space? If not, can an existing instrument be moved to another location in the laboratory to make room for the new system? Note that regulatory agencies such as the College of American Pathologists (CAP) require that instruments be re-validated to confirm continued performance after they have been moved within the laboratory. Do the current benches in the laboratory provide the necessary structural support to accommodate the instrumentation? If the laboratory selects a floor model instrument for rapid ID/AST, is there sufficient space available for the new equipment or will the space need to undergo renovation before installation? The availability of sufficient laboratory space to accommodate the testing being performed is a CAP checklist item that is inspected during a laboratory audit. The microbiology laboratory must be equipped with enough footprint to house the necessary equipment for both conventional and rapid ID/AST systems, along with the personnel to perform the testing. An additional consideration that must be taken into account is that of reagent storage for rapid ID/AST systems. A laboratory that selects a particular test system that requires reagents that are stored at 4°C or below must either currently have enough refrigerator/freezer space to house these reagents, or have the space and be willing to add refrigerators/freezers into the laboratory. Otherwise, the laboratory must adopt a test system that uses reagents that can be stored at room temperature to more easily conform to spatial constraints.

Specimen transport

The clinical utility of rapid ID/AST systems is dependent on the ability to efficiently transport, receive and test the appropriate specimen. In the setting of a centralized laboratory serving multiple outlying locations, the transport time must be seriously considered. Are the specimens being submitted to the central laboratory or are they being plated locally, and then are plates with positive growth submitted to the central laboratory? For rapid ID/AST systems, the laboratory performing this testing would need a pure culture of a pathogen. Submission of a specimen in a conventional transport device, such as the eSwab (Copan Diagnostics, Murrieta, CA, USA), which maintains organism viability for up to 48 h at room temperature,¹⁶ allows for maximum recovery of pathogens in culture and would allow the central laboratory to streamline the entire process, from inoculation to culture reading to set up of rapid ID and AST. The other important logistical issue affecting specimen transport for centralized laboratories is that of the courier system.¹⁷ The selection of an in-house courier versus a contracted third-party courier would probably already have been made by the time the laboratory decides to adopt rapid ID/AST technology; however, it may be necessary to re-evaluate the current schedules and routes to maximize the efficiency of specimen transport from distal locations to the centralized laboratory. In the setting of a hospital-based laboratory serving in-house constituents, the need for efficient transport of the specimen to the laboratory is no less critical.

For example, rapid ID/AST systems for testing positive blood cultures require the positive bottle to be tested within 8 h of signalling as positive. A laboratory system in which blood cultures are incubated locally and then positive bottles are transported to a centralized offsite microbiology laboratory may find this timing requirement difficult to adopt without modifying existing courier routes (and accepting the additional cost that incurs). In this case, consideration must be given to the possibility of de-centralizing the rapid testing to each hospital. Alternatively, testing outside of the 8-hour requirement may be performed, but this would be considered off-label use and would require an internal validation as a laboratory-developed test to demonstrate the accuracy of patient results.

Turnaround time expectations

Conventional culture-based microbiology testing is understood by many healthcare providers to take several days before a definitive result is provided. Implementation of rapid ID/AST technologies can significantly reduce turnaround time (TAT) for clinically meaningful results to be reported to the clinician. However, clinician expectations can be confounded by manufacturer’s sales representatives who colloquially describe these tests as taking ‘only about an hour’ to perform. It is imperative that the laboratory educate the healthcare staff on the use of these new technologies and convey realistic TAT expectations. For example, consider the blood culture, which could take up to 5 days for an inoculated blood culture bottle to turn positive, and then another 2 days for an isolate to be recovered on solid media and identified, with yet another day for the results of conventional antimicrobial susceptibility testing. Most significant positive blood cultures turn positive within 1–2 days, so the conventional testing approach would be expected to provide definitive pathogen identification and AST results within a total of 5 days from receipt of the specimen. With multiplex molecular testing that can be performed directly from a positive blood culture bottle, the TAT for pathogen identification shortens to ∼2.5 days from receipt of the specimen (i.e. up to 2 days for bottle positivity and 1 hour for multiplex testing). The laboratory must convey to its constituents the expected decrease in TAT, which may have an impact on clinician behaviour and overall management of the patient. Likewise, for rapid AST systems, the expected TAT can be decreased from ∼2–3 days from receipt of the (non-blood culture) specimen, to ∼1–2 days from specimen receipt. Future research and outcomes studies will bear out the true impact of these novel rapid AST technologies, but the literature has already shown the impact of rapid identification testing systems.

Result communication

The ability of the laboratory to rapidly produce a test result is only one part of the successful implementation of rapid ID/AST systems. The other part is the rapid, proactive communication of that result to the healthcare provider, especially if the reporting is done in collaboration with an active antimicrobial stewardship committee.¹⁸ Laboratories should discuss the expectations with constituent stakeholders, including the Antimicrobial Stewardship Committee and the Infection Prevention Department, to determine how to maximize the impact of rapid test results on patient care. Are the results going to be considered critical values, which must be called to the provider in STAT fashion? Are the results going to be called to the antimicrobial stewardship team, who would then evaluate whether or not antibiotic therapy should be modified? Are the results going to be reported electronically? In one of our laboratories, the results of a rapid blood culture pathogen identification test were called to an on-call antimicrobial stewardship pharmacist. In the United States, this is a specialized member of the clinical team with expertise in optimizing the antimicrobial regimens of patients with infectious diseases. In our setting, the antimicrobial stewardship pharmacist reviewed the rapid test result, as well as the patient’s therapeutic regimen, and contacted the patient’s primary care physician (i.e. general practitioner in much of Europe) if and when a modification to a more appropriate antibiotic was necessary. This decision was made after several conversations with the antimicrobial stewardship team, and after significant education was provided to the various clinical teams in across the healthcare system.

Stakeholder buy-in

The laboratory is responsible for identifying new testing methodologies that will improve laboratory services and patient care and, in so doing, it is incumbent on the laboratory to provide a cost-benefit analysis to justify new technology. This, in turn, requires communication of these findings to laboratory stakeholders to demonstrate its value. Hospital leaders, clinical staff and laboratorians must all understand the value of rapid ID/AST technologies and agree that there is value in implementation for their laboratory and healthcare system. Leadership must understand the rationale for this new, more expensive technology and be willing to provide the necessary financial and personnel resources for its successful implementation. Clinical care staff should be educated about the new technology, including the expected new timeline for results to be reported because rapid ID/AST systems will probably cause adjustments to clinical practice, particularly regarding the implementation of Antimicrobial Stewardship and Infection Prevention practices. As the primary constituents of the clinical microbiology laboratory, Infectious Disease clinicians and pharmacists can be strong advocates for implementation of rapid ID/AST technology, as long as they have a clear understanding of how it will affect patient care. Laboratory staff must understand how the new technology will impact their workflow. Staff must be trained to any changes to specimen receipt, testing setup, reporting of results and making critical value calls to providers, and the value that these changes will bring must be explained and accepted. Finally, as part of a good communication strategy, it is necessary for the laboratory to provide data demonstrating the performance of the new technology. Communication of data including time to identification and time to AST results must be provided to the clinical team to demonstrate successful implementation of the new technology and to build trust in the new process.

Conclusions

Rapid ID/AST technologies have brought about meaningful improvements to both patient care and laboratory workflow; however, many laboratories have not been able to adopt them. In this work we discussed several of the barriers to implementation of rapid ID/AST systems in the clinical microbiology laboratory and provided potential solutions to overcoming these barriers. Issues such as test/equipment costs, personnel costs, staffing expertise, communication needs, specimen transport and stakeholder buy-in were discussed and, where possible, we have provided our own insights into how we successfully overcame those barriers. Some of our solutions may not meet the needs of all readers; however, our goal with this paper was to provide a potential roadmap for readers to consider. Each laboratory must now consider the extent to which these barriers can be overcome locally.

Funding

This paper was published as part of a supplement financially supported by bioMérieux.

Transparency declarations

G.A.C. was an employee of bioMerieux from September 2019 to April 2023. C.C.S. has none to declare.