Blood Culture Contamination and Diagnostic Stewardship: From a Clinical Laboratory Quality Monitor to a National Patient Safety Measure

Abstract

Laboratory analysis of blood cultures is vital to the accurate and timely diagnosis of bloodstream infections. However, the reliability of the test depends on clinical compliance with standard operating procedures that limit the risk of inconclusive or incorrect results. False-negative blood culture results due to inadequate volumes of blood can result in misdiagnosis, delay therapy, and increase patients’ risk of developing or dying from bloodstream infections. Likewise, commonly occurring bacteria or fungi on human skin (i.e., commensal organisms) can contaminate the blood culture during collection and increase the risk of false positives, compromising care and leading to unnecessary antibiotic therapy and prolonged hospitalization.

In December 2022, a Centers for Medicare & Medicaid Services (CMS) consensus-based entity (CBE) endorsed the Centers for Disease Control and Prevention’s (CDC) proposal for a new patient safety measure to address these concerns. CDC developed this quality measure to promote the standardization of blood culture best practices and improve laboratory diagnosis of bloodstream infections nationally. This special report will emphasize the importance of standardizing blood culture collection and describe the need for a national patient safety measure, new quality tools, and next steps.

INTRODUCTION

Blood cultures are the gold standard of bloodstream infection diagnosis and are based on the detection of viable microorganisms present in blood. The process begins when a blood culture test request is entered by the clinical care team. The clinical or laboratory staff then draw blood from the patient and inoculate the blood into blood culture bottles. These bottles are then incubated for a predetermined period, usually 5 days. If a viable microorganism is present in the bottles, the laboratory will detect it and will use gram stain to perform initial organism identification.

A positive gram stain from a blood culture is considered a panic or alert value also known as a critical value (1). Panic values are test results that a laboratory must immediately alert to the individual or entity requesting the test when any test result indicates an imminently life-threatening condition. Timely reporting of panic values is required by the Clinical Laboratory Improvement Amendments of 1988 (CLIA) (2). Once the clinical care team notification is complete and documented on the test report, the laboratory will use its institutional standard operating procedures (SOPs) to continue the identification process of the organism present and antimicrobial susceptibility testing for the organism identified is also performed when indicated (1, 3).

When performed effectively, blood culture testing provides accurate and reliable results that the clinical care team can use to appropriately treat patients. Clinical decision-making relies on the laboratory correctly identifying the organism causing disease, performing the appropriate antimicrobial susceptibility testing based on organism identification, and identifying antimicrobial resistance genes when indicated. The clinical staff uses laboratory results to promptly tailor and administer patient treatment for the organism causing the illness.

However, improperly collected blood cultures can lead to adverse patient safety events. False-negative blood culture results due to inadequate volumes of blood collected can result in misdiagnosis, delay therapy, and put patients at heightened risk of morbidity and mortality from bacteremia. Likewise, the presence of commonly occurring bacteria or fungi on human skin (i.e., commensal organisms) contaminating the blood culture during specimen collection can increase the risk of false positives, compromising care by leading to inappropriate treatment of patients due to unnecessary or incorrect antibiotic therapy and prolonged hospitalization (4).

In late 2019, the American Society for Microbiology published a clinical microbiology review that provided a comprehensive overview of the problems associated with blood culture contamination (BCC) and solutions to address these issues and avert potential patient safety events. The review covers interventions a hospital or healthcare system can incorporate to reduce or eliminate these events. It also provides a list of questions requiring further research and specifically identifies CDC as a federal agency that should work to address BCC nationally (5).

DEFINING THE CURRENT STATE OF BLOOD CULTURE QUALITY MONITORING

CDC’s Division of Laboratory Systems (DLS) works to improve public health, patient outcomes, and health equity by advancing laboratory systems (6). In pursuit of this mission, DLS investigated the patient safety events that can be associated with poor blood culture collection to define the current state of blood culture quality monitoring.

Clinical laboratories in the United States are regulated and must be certified under CLIA. Among the requirements laboratories must meet for CLIA certification, clinical microbiology laboratories are responsible for the laboratory diagnosis of infectious diseases. This includes the selection, collection, and transportation of specimens (7). These preanalytic testing responsibilities require the clinical laboratory to be involved in collecting blood cultures and providing instructions for preventing contamination.

CLIA also states that clinical laboratories must establish and maintain written policies and procedures to monitor all phases of the total testing process including the preanalytic, analytic, and postanalytic testing phases and correct any identified problems as necessary (8). Professional guidance defines several commonly used metrics to monitor blood culture quality, which helps to support this effort (9–11). Clinical laboratories can use laboratory information management systems to generate and report the BCC rate to determine how many blood cultures were contaminated over a specific time. Monitoring the BCC rate serves as a proxy measurement of the effectiveness of the institution’s SOP for blood culture collection, as it provides metrics that can be used to evaluate the preanalytic testing phase. The Clinical and Laboratory Standards Institute (CLSI) states laboratories should be able to achieve BCC rates substantially below 3%, and when best practices are followed a target contamination rate of 1% is achievable (10).

One of the CLIA certification requirements is that clinical laboratories accept direct inspection by CMS or a CLIA-approved Accreditation Organization (AO) (12). Although some clinical laboratories have generated and reported their BCC rate and assessed adult blood culture volume as a quality measure for years, a 2022 CDC review of AO accreditation checklists for the National Quality Forum measure endorsement application found that these metrics were not universally recognized as quality monitors. Only the College of American Pathologists laboratories listed BCC rate and adult blood culture volume as quality standards (9).

Despite these metrics being absent from most AO checklists, the issues they work to mitigate are familiar. A CDC library literature review found that opportunities to improve blood culture collection are well-studied. In 1986, Blood Cultures: Issues and Controversies, by Dr. John A. Washington II, became one of the first scientific articles discussing the topic and covering the author’s early studies on quality improvement in blood culture collection, handling, and result reporting (13). Since then, there have been many publications discussing blood culture quality monitoring including BCC and blood culture volume (14–16).

In 2021, the US Department of Health and Human Services received correspondence from Congress that urged CMS to take meaningful action to reduce BCC (17). After that, in 2022, a Military Construction, Veterans Affairs, and Related Agencies Appropriations Act was passed in 2022, directing the US Department of Veterans Affairs to prioritize the development and implementation of SOPs to decrease BCC rates to a recommended rate of <1% (18).

These federal actions demonstrate a recognized need to standardize blood culture collection and establish quality monitors across the United States to ensure every patient has equal, local access to quality healthcare. Another need is to be able to compare blood culture quality monitoring studies and data among institutions involved in the blood culture collection total testing process from the initial patient encounter and indication for testing through clinical interpretation and follow-up (19).

STANDARDIZING THE PROCESS NATIONALLY

Once reducing BCC and improving the collection of blood cultures became recognized priorities of the federal government, it fell to CDC, as the scientific arm of the CLIA tri-agency, to promote these crucial goals and practices among the clinical laboratory community. To this end, CDC leveraged the CMS CBE measure endorsement process to establish the BCC rate as a national patient safety measure. CMS CBE endorses quality measures through a transparent, consensus-based process incorporating diverse group feedback to foster healthcare quality improvement (20).

BCC rate became the first clinical laboratory-based national patient safety measure when it was endorsed in December 2022, representing a new approach to addressing patient safety opportunities using laboratory technologies and laboratory information management systems data. Quality and patient safety measures do not replace clinical decision-making. Instead, they serve as a means to inform and improve decision-making, with documentation and established metrics that indicate where processes break down. This measure aims to optimize the clinical laboratory’s approach to handling BCC by increasing communication with clinicians and pharmacists, introducing standardized methods to monitor and reduce BCC, and improving the collection of blood cultures. The measure is part of a CDC continuous improvement project that begins with patients at least 18 years old with an ultimate goal of expanding to include all age groups.

The measurement endorsement process includes a Congressional statutory requirement that a government contractor serves as the CBE for measure endorsement and maintenance. The National Quality Forum served in this role during the development of the BCC measure. Battelle is the current contractor for measure endorsement and maintenance and will oversee the measure. CDC will serve as the measure steward throughout the life of the measure (21).

The initial step in creating a measure is to define its specifications and the data elements needed for calculation. To establish the specifications of the primary measure (BCC rate), CDC used the definition of BCC as described in professional guidance (10, 22). The guidance defines BCC as a commensal organism (i.e., bacteria or fungi that commonly colonize human skin without causing disease) isolated from only one blood culture set out of 2 or more sets collected within 24 h. Such occurrences can lead to false positive test results due to contamination, primarily during specimen collection in the preanalytic testing phase.

Professional guidance also describes the optimal volume of blood to draw from adult patients with a suspicion of bloodstream infection as 2 to 3 blood culture sets obtained in the evaluation of each septic episode, defined as a 24-h period. A target volume of 40–60 mL of blood should be collected. When only one blood culture set is collected, instead of the 2 or more recommended sets, this is called a “single-set” blood culture. A single-set blood culture collected in a 24-h period is an inadequate volume of blood to reliably diagnose bacteremia and may lead to false negatives. Furthermore, a single-set blood culture is insufficient to determine BCC because the professional guidance definition of BCC requires the collection of at least 2 separate blood culture sets. To address blood volume and ensure an appropriate number of blood culture sets are collected, CDC included a submeasure to encourage institutions to assess their rate of single-set blood cultures.

IDENTIFYING GAPS IN CARE

As part of the measure submission process, CDC analyzed blood culture data from 259 facilities nationwide to determine any gaps in care and health equity concerns. The analysis leveraged the Premier Healthcare Database and Cerner Health Facts, 2 large electronic healthcare databases containing data from both private and academic US hospitals. This analysis revealed higher rates of bacterial contamination at facilities with <300 beds compared to facilities with >300 beds (OR = 1.38, P = 0.0055) and higher rates in the summer than the spring (OR = 0.95, P < 0.0001) or fall (OR = 0.97, P = 0.0087).

In addition, patient characteristics were assessed from >5.2 million blood culture episodes. The data revealed a significantly increased incidence of BCC among patients who identified as Black (OR = 1.21, P = <0.0001), non-Hispanic (OR = 1.04, P = 0.0156), unmarried (OR = 0.9, P = <0.0001), and male (OR = 0.94, P = <0.0001). When compared to patients aged 18–39 (OR = 0.71, P = <0.0001) and 40–59 years (OR = 0.87, P = <0.0001), patients 60 years or older were more likely to have contaminated blood cultures. These findings are supported by other studies that identified equity issues in care during the analysis of patient-specific factors associated with BCC, such as increasing age, Black race, increasing BMI, presence of specific comorbidities, activation of code sepsis, and sepsis plus shock on presentation (23).

Although US hospital and healthcare systems are unique, regardless of the population served or where a patient or caregiver chooses to seek medical care, all patients and caregivers should be able to expect equal quality healthcare across the United States (24). However, these data suggest that what should be the case has yet to be, and action is needed to address these inequities CDC identified these gaps in equitable care using laboratory data from laboratory information management systems not typically leveraged to improve patient outcomes. These data further support the need to empower healthcare systems to work with their clinical laboratories to standardize blood culture collection, quality monitoring, and reporting to root out any existing inequities and close these gaps in care.

USING TOOLS TO IMPLEMENT THE MEASURE

With the measures in place, the next step was to determine how to address these gaps in care. Preanalytic errors account for most BCC events. Even though most of these errors will occur outside of the laboratory, CLIA states that the clinical laboratory is responsible for all phases of testing (8). There is a collaboration platform within hospitals, the antibiotic stewardship team, which CMS requires (25). This team is suited to champion a team-based approach to improve antimicrobial therapy as it is ideally composed of infection disease clinicians, infection preventionists, nursing managers, pharmacists, laboratory professionals, and other healthcare professionals. This multidisciplinary group has the tools and expertise to closely examine the BCC and single-set rates, and take a collaborative team-based approach to implementing interventions to improve blood culture collection (26, 27).

Given that diagnostic stewardship (DS) is an approach to reduce diagnostic errors, it is integral to antibiotic stewardship. DS can also be incorporated with antibiotic stewardship efforts to ensure the proper test is performed for the right patient at the right time (28). DS aims not just to ensure the correct test is done but also to ensure the right test is done correctly. Hospitals and healthcare systems can ensure that everyone involved is aligned and focused on effective value-added processes and optimal patient outcomes by including the clinical laboratory in continuous improvement projects led by these stewardship teams (29).

To promote DS, the CDC published Blood Culture Contamination: An Overview for Infection Control and Antibiotic Stewardship Programs Working with the Clinical Laboratory in 2022. This quality improvement tool was designed to support infection control and antibiotic stewardship programs as they work with the clinical laboratory to improve the blood culture total testing process (30). In 2023, DLS published another quality improvement tool, Preventing Adult Blood Culture Contamination: A Quality Tool for Clinical Laboratory Professionals, to provide clinical laboratories with an overview of the primary and submeasures and encourage co-operation and collaboration with antibiotic stewardship teams (31). Both tools promote DS by emphasizing the importance of working together to achieve optimal results.

Included in the DLS tool, available to the public as a webpage and downloadable PDF, is an overview of the measure’s purpose, applicable regulations such as the CLIA standards for quality assessment, specimen submission, handling, and referral, and specimen integrity and identification (8, 32, 33). The tool also outlines critical steps that could be included in institutional SOPs. These process steps do not account for all potential considerations that may be included in every hospital laboratory’s unique institutional policies. Instead, the goal was to outline the critical steps identified by the CLSI and the Infectious Disease Society of America.

The DLS tool provides calculations for determining an institution’s BCC and single-set rates and instructions for categorizing commensal organisms using CDC’s National Healthcare Safety Network (NHSN) common commensal organism list (34). The NHSN common commensal list is controlled and maintained by CDC and is updated annually based on feedback from a panel of experts. It is a publicly available resource that can be downloaded as a searchable Excel spreadsheet and provides contact information for guidance on appropriate reporting procedures. If the laboratory identifies a NHSN common commensal organism in one set out of 2 or more sets collected, BCC can be considered and communicated to the clinical care team for the opportunity to follow-up appropriately.

The DLS quality tool also includes guidance on educating clinicians during the laboratory reporting and interpretation phase of testing with comments on laboratory reports to serve as postanalytic nudges to educate clinicians on what is discovered in the laboratory. This step is critical because clear communication from the clinical laboratory regarding microorganisms present in a patient specimen is essential for the clinician’s approach to patient care. It is best practice to inform those caring for the patient and responsible for clinical decision-making to report possible contamination or inadequate volume to allow the clinical team to make clinical decisions such as adjusting antibiotic therapy or obtaining additional cultures.

In 2023, CDC published the Hospital Sepsis Program Core Elements (35). This resource lists BCC and single-set rate metrics as examples for tracking sepsis, epidemiology, management, and outcomes. It also includes microbiology, laboratory medicine, and phlebotomists, among those who should be part of the antibiotic stewardship team when working to improve the diagnosis of sepsis.

PROMOTING THE BCC MEASURE NATIONALLY

CDC has been working with AOs, professional organizations, hospitals, laboratories, patient advocates, and other interested parties to promote the adoption of the quality measure and tools nationally. Partnering with and getting feedback from these groups is crucial to standardizing these processes, as they are actively involved in implementing the measures.

For example, in 2023, the Indiana Hospital Association (IHA) launched a state-wide learning collaborative to reduce BCC, using CDC’s quality improvement tools as a guiding resource (30, 31). Approaches include bite-sized learning grounded in evidence-based practices to improve the collection of blood cultures. With an advisory team of multidisciplinary experts, IHA reviewed the available evidence, shared best practices, and co-designed practical resources. Additionally, IHA supported the voluntary collection of blood culture data from hospital members to determine the current state of the state and identify improvement opportunities (36).

CDC is also connected with the US Veterans Health Administration (VHA), which has an ongoing initiative to reduce BCC among the nation’s veterans and dependents. VHA developed and validated a BCC dashboard based on automated data queries. Twelve facilities compared the data from the automated query against their own locally derived BCC data. This dashboard standardized the definition of BCC throughout the organization. Other successful VHA practices include development of a standard work tool and standardized education, dedicated teams involving infection prevention, utilization of continuous improvement initiatives, focused sustainment practices, quality data, and leadership sponsorship. These efforts by the VHA demonstrates optimal collaboration and an articulate systems focus on how best to approach these opportunities at a national level (37).

CDC presented the BCC national patient safety measure at the Fall 2023 Clinical Laboratory Improvement Advisory Committee (CLIAC) session on “The Role of the Laboratory in Diagnostic and Antimicrobial Stewardship.” This presentation and subsequent discussions during the session led CLIAC to submit a recommendation to Health and Human Services to update the CLIA regulations to include BCC rate monitoring within the laboratory quality management system (38).

CDC is currently prioritizing the development of training materials for public use. The goal is to integrate laboratory and clinical care considerations and provide detailed explanations for each process step, aiming to comprehensively explain the reasoning, or “the why,” behind each step. CDC also works to establish data collection structures for blood culture quality monitoring through NHSN. This type of data is required to track improvement, determine needs, and support the continual endorsement of the measure in the future.

CONCLUSION

Blood cultures are a valuable tool for diagnosing infections, but they have unintended consequences and impact patient safety if they are not collected and handled appropriately. Healthcare professionals have spent decades working to eliminate these impacts using educational approaches, data collection and interpretation, and drafting laboratory guidelines. Meaningful improvement will require the hospital administration to commit to supporting resources to implement and maintain processes and procedures for measurement and data sharing, as well as a means to act on the results.

Clinical laboratory professionals are well-versed in maintaining quality monitors required by regulatory standards. They can play a crucial role in measuring success and identifying gaps in care and processes using laboratory expertise, technologies, and information systems. By implementing this laboratory-based national patient safety measure all healthcare teams can share knowledge and work together as one to ensure not only the best diagnostic testing occurs for the right patient at the right time but also the best outcomes are afforded to our patients and caregivers every time no matter where they choose to seek out medical care. The CDC recommends clinical laboratories incorporate blood culture quality monitors into their quality management systems and commit to continuous improvement of processes to capture and address any opportunities for value-added advancement of laboratory services and patient outcomes.

Nonstandard Abbreviations:

CMS

Centers for Medicare & Medicaid Services

CBE

consensus-based entity

SOPs

standard operating procedures

BCC

blood culture contamination

DLS

Division of Laboratory Systems

AO

Accreditation Organization

DS

diagnostic stewardship

NHSN

National Healthcare Safety Network

IHA

Indiana Hospital Association

VHA

US Veterans Health Administration

CLIAC

Clinical Laboratory Improvement Advisory Committee