The role of the clinical laboratory in infection prevention and antimicrobial stewardship

Abstract

Background

The clinical laboratory occupies an important role in enabling effective infection prevention and control (IPC) and antimicrobial stewardship program (ASP) interventions. Indeed, the clinical laboratory generates the microbiologic data to guide clinical practice and recognize new trends that may signal nascent outbreaks and provides timely and accurate testing results that have the potential to impact patient care. In addition, the IPC and ASP groups offer key expertise in clinical care and facility operations that help the laboratory prioritize implementation of clinically relevant technologies. These groups serve as important liaisons between the laboratory and frontline clinicians, ensuring that results are interpreted correctly and translated into meaningful changes in health care delivery.

Content

In this chapter, we present key areas of opportunity within the clinical laboratory to produce high-quality testing results that will guide IPC and ASP decision-making. Data are briefly summarized for each category, with a focus on rapid diagnostic methods, detection of resistant organisms, and biomarker-based management. Recent developments in rapid diagnostic platforms and other diagnostic areas are described and are expected to continue to expand in the near future. Strategies on outcome-based assessment are also addressed. Finally, a framework for effective collaboration between the three respective groups is presented with the goal of enhancing patient care and clinical outcomes.

Introduction

Beyond its direct clinical care role, the clinical laboratory resides at the strategic interface between microbiological testing and actionable results used by infection prevention and control (IPC) and the antimicrobial stewardship program (ASP) within an institution. Indeed, the clinical laboratory generates key microbiological data that allow the IPC department and ASP to function effectively and leads the selection and validation of assays that hold potential to impact patient care. Lack of local data would severely impair the ability of IPC and ASP to plan and optimize detailed interventions that are tailored to local epidemiologic trends. This is not a one-way relationship, however, as IPC and ASP provide the laboratory with essential input regarding the need and implementation of new tests and result reporting and interpretation that enable the laboratory to produce clinically actionable results that translate to real impact on antimicrobial prescribing, institutional costs, and patient outcomes. These three separate but interdependent entities work best with open collaboration, communication, and shared goals. This chapter will serve as an introduction to the roles and objectives of these key programs and present specific areas of opportunity for the clinical laboratory to enhance clinical impact and successfully collaborate with the IPC and ASP groups.

Roles and objectives of key stakeholders

Clinical laboratory

The clinical microbiology and virology laboratories are at the forefront of optimal patient care given their capacity for early identification of organisms including unusual or unsuspected pathogens, timely detection of antimicrobial resistance, emergence of potential outbreaks, and recognition of potential bioterrorism organisms. To do so, they require the appropriate tools, staffing, and resources to fill their mandate to provide highly accurate and reproducible results. In many settings, the current context of the clinical laboratory practice has been challenged by diversion of financial resources resulting from payment restructuring, increasingly complex and expensive assays, gradual loss of conventional microbiology and virology expertise, and large-scale laboratory consolidation. ^, However, this is also a world of tremendous opportunity with the recent revolutionary introduction of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for organism identification, greater importance of molecular testing, and implementation of laboratory automation. ^, Clinical laboratories must carefully decide which assays to adopt, implement cost-effective workflows, and efficiently collaborate with key clinical groups. Among these, the IPC and ASP groups are two key partners with whom the clinical laboratory has the potential to establish mutually beneficial relationships to enhance patient care (At a Glance 83.1).

AT A GLANCE

Shared Activities

Shared activities between the clinical microbiology laboratory, antimicrobial stewardship program (ASP), and infection prevention and control (IPC)

In North America, clinical laboratories are led by MD- or PhD-trained microbiologists and are staffed by clinical laboratory scientists and laboratory assistants. This model may vary in other settings. The clinical laboratory serves many roles that span the full spectrum of testing, from the preanalytical to the postanalytical components.

Preanalytical

Despite significant technological improvements in microbiology, there is still no substitute for high-quality specimen submission. Indeed, the quality of test results and interpretation directly depend on the quality of the sample received in the laboratory. As such, all individuals involved should strive to maintain optimal quality along the spectrum of testing. The laboratory can optimize this process by providing guidance on optimal test selection, test ordering, sample collection, sample transport, and sample processing. The preanalytical phase is also important as it is the most error-prone, with approximately 70% of laboratory errors occurring in this phase. These preanalytical components need to be considered when discussing testing strategy between the clinical laboratory, IPC, and ASP. For example, the accuracy of ruling out tuberculosis from respiratory samples depends on the quality of the sample submitted. As such, the clinical laboratory and the IPC group can work together to ensure optimal sample collection takes place, and that criteria and procedures are followed at the laboratory to optimize organism recovery.

Analytical

For the analytical phase, the clinical laboratory is involved in many aspects to ensure the testing performed is of high quality. The clinical laboratory oversees quality management procedures that include quality control (QC), or the initial step of controlling a procedure, and quality assurance (QA), which is a broader component that includes proficiency testing, personnel competency testing, monitoring of inventory, and calibration and maintenance of equipment. Importantly, the clinical laboratory actively monitors key QA metrics including test result positivity rates (e.g., proportion of positive blood cultures and molecular assays, blood culture contamination rates), turnaround time of critical test results, and test accuracy. Regular review of these metrics allows identification of irregularities that may require further investigation to address the root cause of the issue and/or communication to other stakeholders including higher levels of management.

Postanalytical

The clinical laboratory also reviews postanalytical performance, including review and approval of test results, proper communication of results, and sample storage conditions. Furthermore, microbiology laboratories take on the task of generating a cumulative antibiogram annually and selecting antimicrobials for susceptibility testing and reporting in collaboration with ASP and other clinical colleagues. Standardized methods for production of a facility-specific antibiogram have been published by the Clinical and Laboratory Standards Institute (CLSI). If a sufficient number of isolates are available, unit-specific antibiograms can be produced in cases where a facility may have a specific unit with unique resistance patterns such as in the intensive care unit(s), and empiric therapy choices may differ based on the location of the patient. These steps require close collaboration with ASP to ensure relevance to local practice and increase their uptake. The clinical laboratory is actively involved as all of the steps outlined require continual review and improvements to achieve consistent quality testing results.

Clinical laboratory role for ASP

For the purpose of ASP, distinct microbiology laboratory roles, of which some may occur in collaboration with other clinical laboratories, have been identified from the Infectious Diseases Society of America (IDSA) ASP guidelines and are presented in Box 83.1 .

BOX 83.1

Microbiology Laboratory Roles in Antimicrobial Stewardship Programs

1.
Stratified cumulative antibiogram susceptibility reporting
2.
Selective or cascade reporting of antimicrobial susceptibility testing
3.
Rapid viral testing for respiratory pathogens
4.
Rapid diagnostic assays for positive blood culture broth
5.
Use of procalcitonin (PCT) testing and algorithms for ICU patients
6.
Use of non–culture-based fungal markers for patients with hematologic malignancies

These examples showcase the potential for clinical laboratory involvement with ASP. However, in practice, this often proves to be a challenge as laboratory input to stewardship programs may be limited. Indeed, surveys from multiple countries have shown varied microbiologist representation in ASP activities ranging from 26% to 89%. It is thus crucial to better understand the respective role of each of these groups and how best to integrate them.

Clinical laboratory role for IPC

For the purpose of infection control (IC), similar roles specific to the microbiology laboratory have been outlined by expert opinion and are included in Box 83.2 . Thus there are multiple areas of opportunity for collaboration between the clinical laboratory, ASP, and IPC, which will be described in further detail in this chapter.

BOX 83.2

Roles of Clinical Microbiology in Infection Prevention and Control

1.
Surveillance and early warning system
- a.
  Notify infection control staff of infection clusters, unusual resistance patterns, possible patient-to-patient transmission
2.
Assist and advise regarding inclusion of laboratory diagnosis in case definition
3.
Perform laboratory confirmation of diagnosis
- a.
  Characterize isolates with high accuracy
- b.
  Store clinically important isolates (e.g., unusual, resistant, and/or outbreak-related)
- c.
  Search the laboratory information system (LIS) for cases
4.
Provide data for use in ongoing surveillance
5.
Perform molecular typing of strains (or send out if testing not offered in-house)
6.
Assess laboratory procedures and adjust as necessary
7.
Maintain surveillance and early warning system

Infection prevention and control

Infection Control and Prevention (IPC; sometimes referred to as IPAC), also known in some locations as Hospital Epidemiology and Infection Control (HEIC) or IC, is a hospital department primarily focused on the prevention of hospital-acquired infections. To this end, IPC is involved in the mitigation of the risk of infection to patients and staff in all aspects of the hospital environment and during the provision of health care. ^, It is led by an IC professional, often a physician hospital epidemiologist or a nurse with IC training, and staffed by infection preventionists, who generally have a background in nursing, though programs in smaller facilities may be structured differently. ^,

The mitigation of infectious risks is achieved through multiple avenues and activities. This includes compliance with industry standards and regulations regarding the built environment of the hospital, which involves oversight of diverse systems and processes, as well as surveillance of clinical care to ensure best practices for infection prevention are implemented ( Table 83.1 ). IPC is also tasked with the critical task of active surveillance for classical hospital- or health care–acquired infections, including surgical site infections (SSIs), device-associated infections such as catheter-associated urinary tract infections (CAUTIs) and central line-associated bloodstream infections (CLABSIs), ventilator-associated pneumonias (VAPs), and Clostridioides difficile infection (CDI). ^, The results of longitudinal surveillance for these infections are publicly reported as quality measures and form the basis for ongoing quality improvement projects within IC. IPC also identifies and investigates clusters of infections that may be transmitted through the health care environment, oversees data-driven interventions to prevent further transmission or occurrence of infection, and plays a key role in emergency preparedness for management of outbreaks of novel pathogens and bioterrorism events. ^,

TABLE 83.1

Infection Prevention and Control Areas of Involvement to Mitigate Infectious Risk

Hospital building	Water distribution
	Heating, ventilation, air conditioning (HVAC)
	Renovation and construction projects
	Monitoring of surveillance cultures from air, water, and surfaces, especially in high-risk areas
Hospital services	Food services
	In-facility laundry
	Environmental Cleaning
Disinfection	Disinfection and sterilization of reusable medical equipment
Surveillance	Active surveillance for hospital- and health care–associated infections
Best clinical practice	Contact and isolation precautions
	Hand hygiene
	Infection prevention processes for surgical procedures
	Risk reduction for infection with use of medical devices

Especially in the surveillance aspect, IPC is heavily dependent on the clinical laboratory for the identification of individual hospital-acquired infections, as well as clusters or changes in the rates over time, in order to evaluate for lapses in IC procedures or areas where practice improvement is needed. In outbreak settings where epidemiologic links can be identified between infections caused by the same species of organism, the clinical laboratory may also be needed to provide additional information on the relatedness of the causative organisms in each infection. This can be performed by molecular typing methods including next-generation sequencing (NGS) to determine if the outbreak is associated with general lapses in IC procedures, which would be suggested by the presence of unrelated organisms, or is more specific in origin, emanating from a single source or through cross-transmission. Such testing can guide the eventual recommendations to general reinforcement of proper IC procedures or more directed interventions to interrupt transmission channels. ^,

Antimicrobial stewardship

Antimicrobial stewardship can be defined by both goals and practices. As a general concept, antimicrobial stewardship is “a coherent set of actions which promote using antimicrobials responsibly [to ensure] sustainable access to all who need them,” as antimicrobials are a class of drugs with potential clinical impact on both the treated individual and the community. In practice, antimicrobial stewardship can be defined as “coordinated interventions designed to improve and measure the appropriate use of antimicrobial agents by promoting the selection of the optimal antimicrobial drug regimen including dose, duration of therapy, and route of administration,” or, more simply, as optimization of the use of antimicrobial agents in the treatment of patients with infections. This involves more than ensuring that patients are receiving appropriate antibiotics for identified infections and also encompasses concordance with published guidelines for empiric therapy, optimization of antibiotic choice and dosing for identified infections, ^, treatment of infection for the shortest effective duration, ^, preferential use of antibiotics with lower risks of CDI or other serious side effects, proper choice and duration of surgical antimicrobial prophylaxis, ^, and avoidance of antibiotic use in conditions where they are not indicated, such as viral upper respiratory syndromes and asymptomatic bacteriuria. ^,

In the United States, ASPs are organized around seven core elements as defined by the Centers for Disease Control and Prevention (CDC). Similar core elements for antimicrobial stewardship in other regions have been described elsewhere. The CDC core elements are presented in Box 83.3 .

BOX 83.3

CDC Core Elements of Antimicrobial Stewardship

1.
Hospital leadership commitment: dedication of necessary human, financial, and information technology resources to antimicrobial stewardship
2.
Accountability: appoint a leader or co-leaders responsible for program management
3.
Pharmacy experience: pharmacist with expertise in the pharmacology of antibiotics, ideally as a co-leader of the antimicrobial stewardship program, leads implementation efforts to improve antibiotic use
4.
Action: implement interventions to improve antibiotic use
5.
Tracking: monitor antibiotic prescribing, the impact of interventions, and important outcomes such as Clostridioides difficile infection rates and changes in resistance patterns
6.
Reporting: regularly report antibiotic use and resistance patterns to prescribers, pharmacists, nurses, and hospital leadership
7.
Education: educate prescribers, pharmacists, and nurses about adverse reactions from antibiotics, antibiotic resistance, and optimal prescribing

Implementation of the core elements can vary from facility to facility based on size and complexity of operations. In general, the ASP is run by a physician and pharmacist, ideally with subspecialty training in infectious diseases and antimicrobial stewardship. ^, Recommendations for staffing requirements based on facility size and acuity have been published. ^, While the CDC core elements emphasize the centrality of pharmacy expertise in an ASP, other publications recommend expertise in “infection management” more generally. This more holistic approach recognizes that proper treatment of infections involves much more than simply the correct choice (empiric or directed) of antimicrobial agent. For example, intra-abdominal infections can be treated with antibiotic courses as short as 4 days following achievement of source control via surgical or interventional procedures, which highlights the importance of source control compared to antibiotic therapy in management of these and related types of infections.

The activities performed by a specific ASP will depend on the staffing, with proportionally larger programs often being capable of more intensive interventions. Typical ASP activities range from distribution of national guidelines for the antibiotic course and duration for the treatment of identified infections, development of local guidelines based on local/regional resistance data (i.e., the cumulative antibiogram) and preferential use of antibiotics with fewer side effects or lower risk of CDI, pre-authorization for use of restricted antibiotics, prospective audit and feedback, either for targeted antimicrobials or a more intensive form known as “handshake stewardship” due to the focus on face-to-face feedback and discussion, enforcement of antibiotic timeouts for reappraisal of current antibiotic necessity, pharmacokinetic monitoring for aminoglycosides and vancomycin, and educational interventions. ^, ^, ^, ^, There are many opportunities to utilize information technology for stewardship purposes, either through electronic medical record (EMR) platforms or third-party software, and these may include the construction of order sets and other decision-support tools at the point of ordering, monitoring for appropriateness of target antibiotic usage and bug-drug mismatches, opportunities for conversion from intravenous to oral formulations, and real-time alerts for critical microbiological results. The major outcomes tracked by ASPs include antibiotic utilization, usually normalized as days of therapy per bed-days of care for in-patient units, patient outcomes such as mortality and hospital length-of-stay (LOS), process measures such as the appropriateness of antibiotic prescriptions, as well as key complications of antibiotic use such as CDI. ^, Reporting to leadership may be done within the facility IC committee as a way to formally link the ASP and IPC, and stewardship guidelines also suggest that the hospital epidemiologist be part of the stewardship team. ^, ^,

As with IPC, ASPs are heavily dependent on data generated by the clinical laboratory to direct their interventions, and close collaboration between ASP and the laboratory is critical. Essentially any intervention aside from general education or dissemination of national guideline recommendations, even pre-authorization of the use of restricted antimicrobial agents, requires knowledge of local resistance patterns or specific culture results for an individual patient. As presented above, one of the most common collaborations between ASP and the clinical microbiology laboratory is the production and dissemination of the cumulative antibiogram, which is a cumulative assessment of antimicrobial susceptibility profiles within the facility that can be used to monitor for changes in resistance patterns, optimize decisions on empiric antimicrobial therapy for specific syndromes based on these patterns, and may also help direct IC measures.

ASPs may also work with the clinical microbiology laboratory on the implementation of selective antibiotic susceptibility reporting, or the subset known as cascade reporting, in order to nudge providers to the use of optimal first-line therapies or narrower-spectrum antibiotics and avoid use of formulary-restricted antibiotics or other agents associated with higher rates of toxicities or other complications in the treatment of uncomplicated infections. ASPs can also collaborate with the clinical microbiology laboratory on the implementation of rapid diagnostic platforms, which may allow for earlier switch from empiric to targeted therapy, and studies have shown that diagnostic test or antibiotic susceptibility results, rapid or otherwise, may have a higher effect on management by frontline providers when integrated into clinical care in the context of a stewardship intervention. ^, ^,

POINTS TO REMEMBER

Infection prevention and control (IPC) is dedicated to the prevention of infections in the health care setting.
The core function of the antimicrobial stewardship program (ASP) is to promote the responsible use of antimicrobial agents.
ASPs are organized around seven core elements.
IPC and ASP activities are broad in scope and nature.
Collaboration with the clinical laboratory is essential for IPC and ASP programs.

Workflow and communication between the laboratory, infection prevention and control, and antimicrobial stewardship program

Communication is the bedrock of collaboration between the clinical laboratory, IPC, and ASP and should occur at many levels within the hospital or health care system. More formal areas for communication and collaboration between services include the IC committee, which is generally chaired by the hospital epidemiologist and should include representation from the clinical laboratory in addition to other clinical and ancillary services and is tasked with review of surveillance data, including outbreaks and necessary responses, and approval of IC policies and procedures. Antimicrobial stewardship guidelines recommend that the clinical microbiologist and hospital epidemiologist be included as key members of the stewardship team, which may be structured as a formal committee or a more informal working group. Information must also flow freely from the clinical microbiology laboratory to both IPC and ASP, as the function of each is deeply dependent on data generated in the laboratory.

Results of active surveillance cultures or molecular tests for multidrug-resistant organisms (MDROs) must be rapidly communicated from the laboratory to IC to ensure that the appropriate isolation and contact precautions are used during clinical care to limit transmission within the hospital environment and ensure that any necessary enhanced cleaning procedures are followed. ^, As clinical care, especially in large centers, is fragmented between many teams and services, clinical laboratory personnel may be the first to notice clusters or outbreaks and can alert IC of these concerns.

Collaboration with the clinical laboratory is also essential to the practices of antimicrobial stewardship, as the core functions of ASP depend on knowledge of culture and susceptibility results for individual patients. Antibiograms or local treatment guidelines are updated periodically and are not time-critical products. In contrast, most ASP interventions performed on a daily basis such as prospective audit and feedback, are dependent on culture and susceptibility results, and this is an area where rapid communication of laboratory results to ASPs can make a significant impact on antimicrobial use and patient care. As rapid molecular diagnostic tests for organism identification and antimicrobial susceptibility become more common, these provide new opportunities to shorten the time to appropriate, targeted antimicrobial therapy, which is facilitated by integrated communication from the clinical laboratory to ASP and the primary team. ^,

Laboratory diagnostic methods to support infection prevention and control and antimicrobial stewardship program

Rapid identification of bloodstream infections

Bloodstream infections continue to be associated with significant morbidity and mortality, particularly in septic shock. Early initiation of appropriate antimicrobial therapy in this setting is crucial to achieve favorable clinical outcomes but may be challenging to achieve with current microbiological methods given the lengthy turnaround time required for testing. This is especially important in cases of resistant or unusual microorganisms, where standard empiric therapy may not be active. Thus given the crucial role of the microbiology laboratory in these settings, there has been major interest in technology development to reduce time to organism identification and antimicrobial susceptibility testing (AST). Methods for the rapid identification and AST of organisms causing bloodstream infections have the potential to improve many ASP targets, including shortened time to initiation of appropriate therapy (either antibiotic de-escalation or escalation) and reductions in hospital LOS, mortality, antimicrobial-related side effects, and antibiotic selection pressure. Rapid identification of genetic markers of resistance such as for methicillin-resistant Staphylococcus aureus (MRSA) (gene: mecA ) and vancomycin-resistant enterococcus (VRE) (genes: vanA , vanB , and others) may also quickly guide the implementation of appropriate IC measures including contact precautions and use of single-patient rooms. However, in real-world practice, factors other than timing of organism identification that influence clinical outcomes should also be considered. These include severity of clinical presentation, host factors such as immune compromise, availability of expert ASP advice, baseline clinical education level of providing teams, and effectiveness of communication of results to providers. Moreover, given that new technologies are often significantly more costly than previous traditional methods, thoughtful design and implementation of workflows that optimize communication of actionable results between the microbiology laboratory, ASP, and IPC is necessary to optimize cost-effective practices and maximize the benefits of the resources that are used. Direct communication of results from the clinical laboratory to the ASP and/or treating team have been shown to be effective. ^, ^, Furthermore, as a general principle, the clinical laboratory should be involved in all aspects of result communication implementation.

MALDI-based methods

Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) technology has completely revolutionized microbial identification in the clinical microbiology laboratory by enabling faster, simpler, and more accurate results in a cost-effective way. ^, This technology was initially developed for use on fresh (16- to 24-hour growth), isolated bacterial colonies. It was subsequently adapted for use from rapid (2- to 6-hour) organism subculture, and from positive blood culture broth after short processing. The direct processing approach accuracy rate is lower than for subculture but allows more rapid organism identification. Different MALDI-TOF MS approaches directly from positive blood culture broth are available: a commercial kit that is CE-marked but not cleared by the US Food and Drug Administration (FDA) (Sepsityper by Bruker Daltonics, Inc., Billerica, MA) and in-house developed protocols.

MALDI-TOF MS-based identification has shown value beyond that of the Gram stain result alone, particularly to guide empiric therapy with identification of organisms with an increased risk of resistance such as AmpC-producing Enterobacterales. In addition, rapid MALDI-TOF MS procedures (either through rapid subculture or direct processing) have been shown to significantly reduce the time to organism identification compared to standard subculture, with a time benefit ranging from 11.7 to 30 hours depending on the protocol and comparator method used. In adults, rapid MALDI-TOF MS identification has been associated with reduced LOS, hospital costs, and mortality, ^, ^, though these studies were implemented as a bundle including rapid AST and/or ASP intervention which may partly explain the observed benefit. In children, the clinical impact of rapid MALDI-TOF MS identification has been associated with reduced time to appropriate antimicrobial treatment in inpatients, reduced infection-related LOS, but not with a mortality benefit. ^, Similarly, these pediatric studies have included an ASP component to their diagnostic intervention, again highlighting the importance of a strong partnership between the laboratory and ASP.

Molecular methods

Multiplexed syndromic panels have emerged over the last few years for organism detection and identification of antimicrobial resistance genes and have been widely adopted in microbiology laboratories across the United States. At the time of chapter preparation, eight FDA-cleared multiplex panels from positive blood culture broth are available based on different technologies: FilmArray BCID (BioFire Diagnostics, LLC, Salt Lake City, UT), Verigene BC-GP and BC-GN (Luminex Corp, Austin, TX), ePlex BCID-GP, BCID-GN, and BCID-FP (GenMark Diagnostics, Carlsbad, CA), and iC-GPC and iC-GNR (iCubate, Huntsville, AL).

These panels include 8 to 29 bacterial and/or fungal targets, and three to nine antimicrobial resistance genes. Detection of antimicrobial resistance genes is of limited utility in settings with low prevalence of resistant organisms. Turnaround time ranges from 1 to 4.5 hours, and studies have demonstrated robust test performance characteristics with sensitivity and specificity greater than 90% for most organisms tested across platforms. However, as with the other multiplexed syndromic molecular assays, false positive results due to contamination may occur, including from the matrix used for testing such as blood culture broth and stool transport media such as Cary-Blair medium. ^,

Of the syndromic multiplex panels for positive blood cultures, the FilmArray BCID and the Verigene BC-GP and BC-GN panels have been available commercially for the longest, with FDA approval in 2013, 2012, and 2014, respectively. These assays have been the most extensively studied so far for their test performance and impact on clinical and economic outcomes. The FilmArray BCID panel in combination with ASP intervention was shown to be associated with reduced turnaround time to organism identification and time to effective or optimal antimicrobial therapy. ^, ^, ^, However, its impact on LOS was mixed, with a beneficial impact seen in one study for coagulase-negative staphylococci, and no effect in others. ^, One of these studies also demonstrated cost-effectiveness of BCID implementation when coupled with ASP intervention for the rapid identification of coagulase-negative staphylococci contaminants. Similarly, the Verigene BC-GP and BC-GN panels have demonstrated favorable impact on turnaround time, but mixed results on LOS and mortality.

These results are promising and support the role of rapid molecular diagnostics for positive blood cultures. However, as for rapid MALDI-TOF MS identification, the findings must be considered carefully as rapid diagnostic methods are often implemented in a bundled fashion with heterogeneous ASP interventions such that it may be difficult to discern the benefit of the diagnostic method alone. Moreover, timely and effective communication of the rapid results to the clinician is critical to produce a favorable clinical impact. The main limitations of the blood culture multiplex panels, high cost and low throughput, may be of greater importance in high-volume laboratories and should be considered.

Other methods

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