Current Issue
FEBRUARY 2000 - VOLUME 20 - NUMBER 1
INFECTION CONTROL
Use of Blood Cultures in Critically Ill Patients
Richard Henker
About the Author
Richard Henker, RN, PhD, is an assistant professor in the acute tertiary care department in the school of nursing at the University of Pittsburgh, Pittsburgh, Pa.
This article originally appeared in the February 2000 issue of Critical Care Nurse, Vol 20, No. 1, pp45-49. Reprint requests: InnoVision Communications, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 899-1712 or (949) 362-2050 (ext 515); fax, (949) 362-2022; e-mail, ivcReprint@aol.com.
Blood cultures are often used to identify pathogenic organisms that cause bacteremia and sepsis in critically ill patients. Bacteremia and sepsis occur more often in critically ill patients than in other patients1 (see sidebar below). In a multicenter prospective study,3 9% of 11 828 patients admitted to 170 intensive care units during an 8-week period had sepsis. The mortality rate 60 days after diagnosis of sepsis was 60%.3 Because bacteremia is associated with a higher prevalence of mortality in patients with sepsis, determination of the cause of the bacteremia is essential so that patients can be treated with appropriate antibiotics. This article presents clinically relevant questions and reviews current literature related to the most effective use of blood cultures for the identification of pathogens.
When Blood Samples Should Be Obtained for Culture
Body Temperature Threshold
The point at which blood samples for culture are obtained from a patient depends primarily on the assessment of the patient’s fever. A task force of the American College of Critical Care Medicine of the Society of Critical Care Medicine in collaboration with the Infectious Disease Society of America recently recommended that blood samples be obtained for culture if a patient’s body temperature exceeds 38.3°C at any site.4
Although this criterion will help clinicians decide when to obtain blood samples, other factors (eg, the patient’s medical history, findings at physical examination, and leukocyte counts) should be considered when deciding whether or not to collect blood samples for culture.5 In addition, the method of measuring body temperature and the circadian rhythms in body temperature must be considered. Some measures of body temperature are more accurate than others, and body temperature measured at the rectal site is typically higher than core temperature measured in the pulmonary artery.6,7 Hypothermia associated with sepsis (see sidebar) may be an indication for collecting blood samples for culture.
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Effects of Circadian Rhythms on Body Temperature
Time of day affects the sensitivity of body temperature as an indicator of infection. Detection
of fever (ie, body temperature >38.3°C) in a patient is more likely when the patient’s circadian temperature level is highest. Mackowiak et al8 found that in healthy human subjects, the lowest average body temperature (36.4°C) occurs at 6 am and the highest average body temperature (36.9°C) between 4 pm and 6 pm.
Therefore, persons with a normal circadian rhythm are more likely to have fever detected in the evening if a value such as 38.4°C is used to define fever. Because fever is an elevation of body temperature above set-point, which depends on circadian rhythm, it seems reasonable that the threshold temperature for obtaining blood samples for culture varies depending on the difference between measured body temperature and baseline body temperature at a particular time of day.9
Circadian rhythms are altered in critically ill patients. Tweedie et al10 found that peak body temperature was often shifted to times between midnight and 6 am in critically ill patients. This time of day is typically when the lowest body temperatures occur in healthy adults. Felver11 found that in some critically ill patients, rhythm cycles were 6 hours instead of 24 hours. Therefore, elevations in body temperature due to altered circadian variation in critically ill patients may be difficult to determine, a situation that makes detection of fever more difficult.
Factors That Affect Thermoregulation and Generation of Fever
Because of changes that occur in thermoregulation with age, elderly persons are less likely to have fever detected. Average body temperature and the amplitude of circadian variation in body temperature decrease in elderly persons.12,13 These changes in thermoregulation may contribute to a phenomenon termed afebrile bacteremia. Elderly persons have bacteremia without fever more often than do younger persons.14
Fever may not be the best indicator for obtaining blood samples for culture to detect patho-
gens in patients with chronic diseases such as diabetes mellitus and chronic renal failure. The function of the autonomic nervous system is altered in patients with diabetes mellitus. Control of blood flow in the skin is impaired, a condition that alters the ability to conserve heat and decreases the ability to generate a fever.15 Generation of fever is also less likely in patients with uremia than in patients without uremia.
An endogenous antipyretic, which prevents fever generation, is thought to be more prevalent in patients with renal failure.16 Other factors may affect the ability of critically ill patients to reach a temperature threshold that would indicate that blood samples should be collected for culture. Medications such as paralytic or vasoactive agents may decrease the ability to generate fever. Paralytic agents prevent shivering, and medications that cause vasodilatation promote convective heat loss. Fever can also be masked in patients receiving analgesics (eg, acetaminophen with codeine) because of unintended antipyretic effects.
Corticosteroids and nonsteroidal antiinflammatory medications interfere with enzymes in the arachidonic acid cascade, preventing the development of fever. Extracorporeal devices such as ventricular assist devices and continuous hemodialysis or ultrafiltration systems may increase heat loss and make generation of fever difficult.
Timing the Collection of Blood Samples
Even if blood samples for culture are obtained immediately after a fever is detected, the bacteria or fungi that caused the fever may no longer be present when blood is collected.17 In one study,18 only 7.39% of 8467 cultures of blood samples collected because of fever were suggestive of pathogens. In a controlled study,19 a lag occurred between the time endotoxin was injected into the blood stream and the time fever developed.
Endotoxin injected intravenously into human subjects had little effect on the subjects’ body temperature for the first 40 to 60 minutes after administration. In addition, release of the pathogen from the source may occur on an intermittent basis, making recovery of the pathogen from the blood difficult.5 Although the bacteria or fungi may no longer be in the blood when the fever develops, cultures are more likely to be useful in identifying pathogens if the blood samples are collected as soon after development of fever as possible.
Another consideration in the timing of collection of blood cultures is antibiotic administration. Cultures of blood samples are more likely to show no growth when patients are receiving antibiotics.20 Therefore, if empirical antibiotics are ordered at the same time as blood cultures because fever was detected, the blood samples should be collected before the antibiotics are administered.
The frequency with which blood samples are obtained for culture depends on the patient’s clinical features. After initial blood samples are collected for culture from a patient with a new fever, a second set of blood samples should be collected within the first 24 hours after the generation of fever.4 Decisions to obtain subsequent blood samples for culture depend on whether or not bacteremia or fungemia is suspected.
A common practice used when obtaining blood samples for culture is to let some time elapse between venipunctures. Although intermittent release of bacteria is thought to occur, Li et al21 compared blood samples that were obtained simultaneously with blood samples that were obtained serially and found that leaving any period of time between venipunctures was of no added advantage in detecting bacteremia. The American College of Critical Care Medicine recommends that a second set of blood samples be collected for culture within the first 24 hours after the fever spike. Because of the intermittent nature of some infectious processes, this second set of samples may be useful for detecting pathogens that are released into the blood intermittently.
Where to collect Blood Samples for Culture
Peripheral Sites and Contamination
Two separate peripheral venipunctures with separate culture tubes are recommended for identifying a pathogen,4 so that skin contaminants can be ruled out. If one blood culture shows growth and one does not, the growth on the culture may be suggestive of contamination during venipuncture. Bacterial findings typically indicative of skin contamination include Corynebacterium species and Propionibacterium acnes. Coagulase-negative staphylococci species (eg, Staphylococcus epidermidis, Staphylococcus hominis, and Staphylococcus haemolyticus) can be contaminants, but these species can also be pathogens.22,23
Intravascular Devices
Blood samples are often obtained through an intravascular device when obtaining a second blood sample from a peripheral site is difficult. The disadvantage of using an intravascular device is the increased likelihood of contamination due to bacterial growth on the catheter.24 Bates et al25 found that 6% of blood samples obtained through an intravascular device were contaminated, compared with 3% of samples obtained by using peripheral venipuncture.
If a patient is receiving hyperalimentation, the intravenous catheter for this therapy is not to be used for obtaining blood samples for culture as stated in the guidelines of the Centers for Disease Control and Prevention.26 Although peripheral venipuncture is the best way to avoid contamination when collecting blood samples for culture, that method is not always possible. Clinicians must be aware that the risk of contamination of a blood sample is greater when an intravascular device is used than when peripheral venipuncture is used.
How to collect Blood Samples for Culture
One goal when collecting blood samples for culture is to prevent contamination. False-positive results lead to increased cost due to increased length of stay, additional diagnostic evaluation (eg, radiography), and unnecessary administration of antibiotics.25 If the contamination rate in an institution is greater than 3%, procedures related to collection of blood samples for culture should be evaluated.27
Skin Preparation
Identification of pathogens via cultures of blood samples is more accurate if steps are taken to prevent skin contamination of the samples. Preparation of the skin by using a 2-step process with alcohol and chlorhexidine is as effective as use of alcohol and povidone-iodine in terms of antibacterial activity on the skin before venipuncture for blood samples in neonates.28 Another method that decreases contamination of blood samples is preparation of the skin with a solution containing 2% iodine and 47% ethanol.18
In a study comparing methods of skin preparation, contamination occurred in 6.25% of cases when iodophor pads were used and in 3.74% of cases when 2% tincture of iodine and 47% ethanol pads were used. One of the important procedural points when preparing the skin for venipuncture to obtain blood samples for culture is to allow time for the bacteria to be killed by the iodine. Although most bacterial killing occurs in the first 15 seconds after application of povidone-iodine solutions, free iodine that is left to dry on the skin continues to kill bacteria.29 A 2-step process seems to be most effective in preventing contamination, but further studies that compare methods would provide more support for the best method of preventing contamination of blood cultures.
Amount of Blood Collected
The amount of blood collected affects the sensitivity of blood cultures. Mermel and Maki30 compared results of blood culture when small amounts of blood (ie, 3.5 mL) and larger amounts of blood (ie, 7-10 mL) were collected from adult patients. The number of blood cultures that showed growth of microorganisms was significantly greater in patients when larger volumes of blood were obtained for culture. Although a task force from the American College of Critical Care Medicine recommends that two 10-mL blood culture tubes be used, using even greater amounts of blood (ie, 20 mL) can increase the likelihood of yielding a culture that shows growth of microorganisms.21 The volume of blood recommended for use when obtaining blood samples from children is 1 to 2 mL, and the recommended volume from neonates is 1 mL.31
Type of Culture Tube
The type of media used for blood cultures depends on the patient’s medical history and condition. Routine blood culture systems favor the growth of aerobic bacteria and allow growth of fungi. If specific pathogens are suspected, then other types of blood culture media may be used. Use of culture media for anaerobes was considered routine at one time but has decreased because of the decline in frequency of anaerobic bacterial infections.32,33 The increasing number of immunocompromised patients due to organ transplantation, acquired immunodeficiency syndrome, and the increased survival of patients with malignant neoplasms has led to a greater number of patients with fungal infections.
Use of culture tubes with medium specific for fungi may be appropriate for these populations of patients.34 The increasing frequency of mycobacterial disease (eg, tuber-culosis) has led to more frequent use of culture media specific for mycobacteria.35 Media for detecting viruses may be used in patients at risk for specific viral infections such as cytomegalovirus infection.34 Blood culture systems that remove the effects of antibiotics on bacterial growth have been available since 1980, but studies supporting the effectiveness of these systems are not available.4,36
Switching of Needles
A common practice when using venipuncture to obtain blood samples for culture is to switch the needle used for the venipuncture with a sterile needle for inoculating the culture tubes to prevent contamination of the tubes. In a meta-analysis37 that included 8 studies, switching needles between venipuncture and inoculation of the culture tube decreased contamination from a weighted rate of 3.7% to 2%. The weighted overall difference in contamination rate between switching and not switching needles was 1.25% with a 95% confidence interval of 0.75% to 1.75%.
Although the difference was statistically significant, the 95% confidence interval was small. When the procedure for switching needles for inoculation of culture tubes is being developed, the slight benefit in terms of contamination will have to be weighed against the greater risk of needle-stick injury.
Unnecessary Blood Cultures
An elevation in body temperature in some patients does not always warrant collecting blood samples for culture. Examples of situations in which obtaining blood samples is inappropriate are drug-induced fever, hyperthermia, and inflammatory response. In these patients, expenses associated with blood cultures could be applied to other diagnostic evaluation.
Summary
Infection, bacteremia, and sepsis are frequent complications in critically ill patients. Ideally, the infectious agent is readily identified to facilitate timely treatment to promote the patient’s recovery. Use of blood cultures is one method of identifying the pathogen. Fever is the primary indicator for obtaining blood samples for culture, but other indicators may be considered, depending on the patient’s medical history and condition. Use of appropriate techniques when collecting blood samples for culture will decrease contamination and improve the likelihood of identification of the infectious agent.
One new technique being tested for the identification of pathogens that cause bacteremia in-
volves genetic technology and the polymerase chain reaction.38,39 The polymerase chain reaction is used to identify the DNA of bacteria that are present in the blood. Blood cultures may not always result in identification of the pathogen because the organism may not grow once placed in culture medium. This new method that uses the polymerase chain reaction may be more sensitive than blood cultures because it requires only DNA from bacteria. Although early studies have not been conclusive in terms of the benefits of this new technology, additional research will improve methods for identification of pathogens in critically ill patients.40
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