Can we trust our blood culture results?

Key Takeaways:

• Blood cultures are the gold standard for diagnosing bloodstream infections and informing treatment decisions.
• ‘Contaminants’ refer to microorganisms that are not the primary cause of the infection but may be present in the blood sample due to external factors. For instance, common contaminants include Staphylococcus epidermidis, a bacterium that is part of the normal skin flora. True pathogens typically grow faster than these contaminants.
• Despite their importance in providing a diagnosis and the resultant patient therapy, blood culture results can be affected by various factors. These include the quality of the blood sample collected, antimicrobial substances in the blood, and the laboratory’s handling and processing techniques. The importance of blood volume in the blood culture bottle is another important factor in getting an accurate blood culture.
• Understanding the limitations and potential sources of error is crucial for accurately interpreting blood culture results.
• Accurate and timely blood culture results are not mere numbers on a report; they are the key to diagnosing and effectively treating bloodstream infections, and their accuracy can be the difference between a successful intervention and a potentially tragic outcome.

Why are blood cultures important?

When patients present with a fever, not all of them have signs of chills or rigor. Septicemia can develop rapidly and without warning, and progress to sepsis and septic shock. Hypotension, decreased urine output, and altered mental status can lead to acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Blood cultures offer essential information on what organisms, if any, are growing in the bloodstream, enabling targeted antimicrobial therapy rather than keeping the patient on broad-spectrum therapy. The organism identification and the targeted therapy give us the best chance at quality patient outcomes.
on how to proceed with patient treatment and management.

Blood cultures are a critical tool in diagnosing and treating infections that invade the bloodstream. The process involves several steps. First, a sample of the patient’s blood is drawn, usually from a vein in the arm. The blood is then transferred to a culture medium, which provides the necessary nutrients for the growth of microorganisms. The culture medium is then incubated at a specific temperature, usually around 37 degrees Celsius, which is the optimal temperature for most pathogens. This allows any present bacteria or fungi to grow, which can be identified under a microscope. This testing is particularly important for infections progressing to septicemia, as early identification is critical.

The factors that influence blood culture accuracy, including sources of contamination and the ability to interpret blood culture results, are crucial. Physicians, as the frontline in patient care, play a vital role in enhancing blood culture methodology and interpretation by adhering to best practices in clinical correlation and highlighting ongoing research and advances.

What is the impact of potential contamination?

Many factors, such as geographic location, patient population, drug resistance, and local healthcare institution practices can drive the causative organism. Most hospital-acquired and community-based septicemia is caused by gram-negative bacilli, a group of bacteria that do not retain the crystal violet stain used in the Gram-staining method of bacterial differentiation. These include Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Gram-positive aerobic bacteria, which retain the crystal violet stain, are oftentimes responsible for infections in the elderly and infections due to device-related procedures. These include Staphylococcus aureus and Streptococcus pneumoniae.

Blood cultures play a pivotal role in identifying and presuming the source of infection, enabling proper patient treatment and management. They are a vital diagnostic test that physicians utilize daily, but because of contamination, blood cultures have long been subject to critical interpretation and use.

The ramifications of blood culture contamination extend beyond potential financial losses to laboratories and hospitals. Inaccurate or misleading blood culture results can lead to misdiagnosis, improper use of antibiotics, drug resistance, c. difficile, and acute kidney injury (AKI), as well as the false-positive diagnosis of CLABSI and MRSA, and an unnecessarily extended length of stay for patients. All of which lead to poor patient outcomes. Vigilance in preventing contamination is not just important, it is paramount.

Contamination can occur during the blood collection process, in the laboratory, or during the interpretation of results. When a blood culture is contaminated, it can lead to a false positive result, indicating an infection where there is none, or a false negative result, failing to detect an actual infection. Many studies report high contamination rates among positive blood culture results, ranging from 3.9% to one-third to one-half.^1,2

The magnitude of false positive or false negative results on blood culture results demands action. Blood culture results have improved our understanding of the limitations of blood culture testing sources of error, including contamination and improper handling of samples.

Factors Affecting Blood Culture Accuracy

The essential elements for reducing blood culture contamination also play critical roles in optimizing blood culture results. True positive blood culture results aim to obtain a single isolate of a known pathogen responsible for infection rather than multiple isolates or nonpathogenic bacteria. Patient selection, clinical scenarios, and pre-analytical and analytical methods also matter.

Patient Factors

The clinical decision to obtain blood cultures weighs on several patient characteristics. Clinical evaluation begins with patient history and detailed physical exam, which can be age-dependent and may include:

• Duration of fever–often important but unreliable in clinically identifying occult bacteremia
• History that indicates a specific illness, such as meningococcal infections during known outbreaks
• Risk of occult bacteremia
• Underlying medical conditions such as invasive pneumococcal infections may lead to a significant risk of increased mortality.
• History of prematurity in infants is a factor since prematurity is associated with higher risks.
• History of gastroenteritis–increases the clinical suspicion of Salmonella infections.
• Epidemiology–exposure to apparent viral syndromes and upper respiratory infections.
• Risk factors for invasive pneumococcal disease and other underlying illnesses such as sickle cell anemia and acquired immunodeficiency syndrome (AIDS).

Patient factors such as prior antibiotic use, patient immune function, the severity and stage of infection, and the presence of fastidious or slow-growing organisms may affect blood culture sensitivity and specificity. For instance, if a patient has recently taken antibiotics, it may affect the growth of bacteria in the blood culture, leading to a false negative result. Blood culture results, while important, are never a substitute for a thorough clinical evaluation, including lactate levels, C-reactive protein, procalcitonin, CBC, Creatinine, glucose, bilirubin, radiologic imaging such as CT or MRI, urinalysis with culture, wound cultures, sputum cultures, and venous or hemodialysis catheter or port line and tip cultures.

Sample Collection: preanalytical and analytical methods

The proper body site selection may depend on the clinical situation and patient age. Meticulous preparation of the venipuncture site involves proper skin disinfection technique, hand hygiene, sterile technique with sterile gloves, and selective use of sterile drapes. Blood culture bottle top disinfection that is maintained throughout the collection process as well as ANTT (aseptic non touch technique) are of paramount importance. Masking of the patient and the health care worker are important in maintaining a contaminant free environment. Blood cultures should always be drawn first prior to other blood tests and should be avoided through central or peripheral lines; proper phlebotomy training and experience are mandatory. The appropriate amount of blood volume should be obtained, usually 8-10 ml of blood per bottle (aerobic and anaerobic bottles) or 20-30 ml per venipuncture in adults with a minimum of two separate draws from two separate sites within a short period of time. Completely filling the aerobic bottle with required volume is of utmost importance as more than 90% of the organisms that cause BSI will grow out in the aerobic bottle.

The transport time to the laboratory must be timely and efficient. Blood culture samples should be kept at room temperature and handled according to the manufacturer’s guidelines.

Blood culture analysis typically includes continuously monitored blood culture systems that reduce overall turnaround time. These systems use automated detection methods to identify the presence of microorganisms in the blood sample. Most analyses offer rapid diagnostics for faster identification of contaminants and true pathogens. The results are then interpreted by trained laboratory personnel, who consider the clinical context and the characteristics of the microorganisms detected.

Laboratory techniques and protocols that may affect blood culture accuracy include:

• Incubation time and conditions
• Media selection and supplementation
• Identification and susceptibility testing methods
• Quality control and proficiency testing

Future technologies may aim for ultrasensitive molecular methods. These techniques may be particularly valuable if the organism recovered in the blood culture is clinically significant. Depending on the particular antibiotic treatment, these ultrasensitive results may also aid the physician in measuring the patient’s response to infection.

Interpreting Blood Culture Results

When and how to treat the patient depends heavily on clinical judgment, the process by which physicians use their experience and knowledge to make decisions about patient care. Blood culture results may be relayed to physicians, but most hospitals have established institutional critical action value policies that must be followed. Ultimately, physicians must decide on the type, dose, and method of antibiotic administration, but they must exercise caution due to local hospital and community trends.

Concise reporting of blood culture results must consider transparency in contaminant organisms that meet certain standards and highlight specific pathogens. According to the local hospital formularies, possible antibiotic resistance must be correlated with blood culture results and what antibiotics are appropriate. Many critical care physicians seek advice from their infectious disease colleagues before deciding on antibiotic dosing, timing, and possible drug-drug interactions.

Bacteremia should be treated urgently with appropriate antibiotics since any delay may be associated with increased morbidity and mortality. Debate continues regarding whether empiric antibiotics may play a universal role in treatment. “Shotgun” or overly aggressive antibiotic therapy remains controversial, but in some cases, it also saves lives.

Most physicians compare the patient’s clinical picture, which may vary by the hour, with blood culture results to determine appropriate antibiotic therapy. Even then, broad-spectrum antibiotics are used if the patient is at high risk of morbidity or mortality. The consequences may be dire no matter what.

The best analogy is to compare blood culture results to tornado warnings. Accuracy and timing can make the difference. Minutes count. No one knows why a tornado may strike one house and skip the one next door. The same is true for bacteremia; no one knows why some patients develop septicemia, and some don’t.

Positive blood cultures offer time for clinical correlation and distinguish true pathogens from contaminants. The clinical importance of positive blood cultures is to be able to perform antimicrobial susceptibility testing along with options for antibiotic therapy.

Before a Gram stain is final, all patients typically receive broad-spectrum antibiotics covering gram-positive and gram-negative bacteria, including extended-generation cephalosporins or a beta-lactamase inhibitor. Hospital patients should be given coverage for Pseudomonas. Vancomycin should be used to cover resistant gram-positive bacteria, specifically methicillin-resistant Staphylococcus aureus (MRSA). There is no universally accepted duration of antibiotic treatment.

Negative blood cultures are subject to sensitivity and negative predictive value, the impact of prior antibiotic therapy, consideration of alternative clinical evaluation and testing, and the clinical context. That is an additional reason why completely filling the aerobic bottle with required volume is of utmost importance. Empiric antibiotic therapy is without consensus when used for patients with a negative blood culture result.

Optimizing Blood Culture Utility

Physicians collaborate with laboratory personnel and pathologists to optimize all laboratory results, including blood cultures. Blood is normally a sterile body site, so a positive blood culture generally predicts an infection, typically bacteremia.

Clinical assessment and treatment hinge on the judicious balance of the severity of the patient’s illness and whether the blood culture results offer valuable insight into patient management. Instituting antibiotic therapy by dose and type may be as important as timely de-escalation, adjustment, or discontinuance.

Best Practices

There are several guidelines for best practices when collecting a blood culture sample. These guidelines recommend the following strategies for reducing blood culture contaminations.

• Choose the right patient for blood cultures at the right time and in the right clinical setting.
  • Blood cultures are both underutilized and overutilized
  • Judicious use of empiric antibiotics before or after blood cultures can alter patient outcomes
• Adequate skin antisepsis
• Blood cultures should always be drawn first prior to other lab tests
• Blood culture bottle top disinfection and maintained disinfection practices
• Peripheral venipuncture technique
  • Collection of multiple sets from different sites
  • Timely transport, storage, and processing of samples
• Hand hygiene practices and sterile gloves
• Masking of patient and HCW
• Fill bottles to required volumes
• Prioritize filling the aerobic bottle
• Phlebotomy teams and education on proper technique
• Adherence to laboratory protocols and quality control measures
• Surveillance and feedback
  • Contamination rates
  • Antibiotic stewardship, particularly evaluating the impact of unnecessary vancomycin usage.

Diversion Devices

These commercially available devices, like the Steripath® family of products, can significantly reduce or, as in some studies, completely eliminate blood culture contamination. The premise is that the device initially diverts an aliquot of the potentially contaminated blood and then collects the remaining contaminate-free blood into the blood culture bottle.

Despite meticulous topical antisepsis, precise collection, and proven laboratory protocols, it is impossible to ensure the complete eradication of microorganisms from the deep keratin layer of the skin. The latest diversion devices are self-contained, do not require extra collection tubes, and may offer the best prevention of contamination within blood cultures by addressing these events at the source.

Conclusion

Blood cultures have been critical to saving lives for over a century. However, blood culture contamination has caused unintended consequences for patients, ranging from misdiagnosis to improper antibiotic usage, antibiotic resistance, and healthcare financial losses.

Awareness of factors influencing accuracy and limitations is essential. While we may better understand how blood culture contamination occurs through the awareness of factors influencing accuracy, we still need to improve.

Our best practices include adherence to proven methods and clinical correlation to optimize blood culture utility. Ongoing research and advancements aim to improve blood culture methodology and interpretation. Further use of clinically and statistically proven initial diversion devices offers exciting new opportunities to reduce contamination rates to previously unseen levels which can dramatically improve patient outcomes.

References:

¹Weinstein, M. P., Towns, M. L., Quartey, S. M., Mirrett, S., Reimer, L. G., Parmigiani, G., & Reller, L. B. (1997). The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 24(4), 584–602. https://doi.org/10.1093/clind/24.4.584

²Story-Roller, E., & Weinstein, M. P. (2016). Chlorhexidine versus Tincture of Iodine for Reduction of Blood Culture Contamination Rates: a Prospective Randomized Crossover Study. Journal of clinical microbiology, 54(12), 3007–3009. https://doi.org/10.1128/JCM.01457-16

³Oestergaard LB, Christiansen MN, Schmiegelow MD, Skov RL, Andersen PS, Petersen A, et al. Familial Clustering of Staphylococcus aureus Bacteremia in First-Degree Relatives: A Danish Nationwide Cohort Study. Ann Intern Med. 2016 Sep 20. 165 (6):390-8.