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* From the Pulmonary and Critical Care Division (Drs. Beutz and Kollef) and Division of Infectious Diseases (Dr. Fraser), Washington University School of Medicine; and Departments of Nursing (Ms. Sherman) and Infection Control (Ms. Mayfield), Barnes-Jewish Hospital, St. Louis, MO.
Correspondence to: Marin H. Kollef, MD, FCCP, Pulmonary and Critical Care Division, Washington University School of Medicine, Box 8052, 660 South Euclid Ave, St. Louis, MO 63110; e-mail: kollefm{at}msnotes.wustl.edu
| Abstract |
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Design: Prospective cohort study.
Setting: A medical ICU (19 beds) from a university-affiliated urban teaching hospital.
Patients: Between February 2001 and October 2001, 300 paired blood culture specimens were obtained from 119 patients (2.52 paired cultures per patient).
Intervention: Prospective patient surveillance and data collection.
Measurements and main results: Thirty-four paired culture results (11.3%; 95% confidence interval, 7.8 to 14.8%) were accepted as true-positives representing a true bacteremia. The sensitivity of catheter-drawn and peripheral venipuncture samples was 82.4% and 64.7%, respectively, and specificity was 92.5% and 95.9%. The positive predictive value was 58.3% for catheter-drawn samples and 66.7% for peripheral venipuncture samples, and the respective negative predictive values were 97.6% and 95.5%.
Conclusions: In critically ill medical patients, the negative predictive value of blood samples obtained by catheter draw or peripheral venipuncture for suspected bloodstream infection is good. However, the sensitivity of blood samples obtained by either catheter draw or peripheral venipuncture alone is not adequate to recommend the elimination of blood samples obtained from the other site. Clinicians should also be aware that additional blood samples may be necessary when interpreting positive blood culture results for common skin or central vein catheter contaminants.
Key Words: antibiotics bacteremia critical care infection intensive care
| Introduction |
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We performed a study with two main goals. The first goal was to determine the overall yield of blood samples for true bacteremia obtained in medical patients admitted to an ICU. The second goal was to compare the performance of blood samples drawn from a central vein catheter and peripheral venipuncture. This investigation was undertaken to provide data that might improve the overall management of critically ill medical patients with suspected bloodstream infection.
| Materials and Methods |
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Outcome Measures
The main outcome measures were the sensitivity, specificity, and positive and negative predictive values of blood samples obtained with catheter draws and peripheral venipuncture for the presence of true bacteremia. The medical ICU has a standing protocol that directs the nursing staff to obtain blood culture specimens at least once daily when any patients temperature exceeds 38.3°C, and as ordered by the patients treating physician. Blood culture specimens can be drawn more than once daily if the patient has repeated temperatures exceeding 38.3°C. However, these additional blood culture specimens require approval from the patients treating physician.
Definitions
A paired culture was defined as at least one blood sample clearly labeled as drawn from a central vein catheter and at least one blood sample drawn by peripheral venipuncture. Blood samples had to be drawn within 4 h of each other as recorded by the patients ICU nurse in the bedside computer (EMTEK Health Care Systems; Tempe, AZ). Reasons for excluding blood samples from analysis included the following: only one blood sample was drawn (no paired cultures available), samples were drawn > 4 h apart, or when the source where the blood sample was drawn from was not clearly identified. Multiple blood sample pairs from the same patient were allowed if they were drawn at least 24 h apart from one another.
The diagnostic criteria used for establishing the presence of a true bacteremia were adapted from previous investigations.7 8 Two of the study physicians blinded to the site of blood collection classified paired cultures with at least one positive result as true bacteremia (or fungemia) if the following criteria were met: (1) certain pathogens, such as Staphylococcus aureus, Gram-negative bacilli, and Candida species isolated from any culture sample represented true bacteremia or fungemia; or (2) common skin contaminants (coagulase-negative staphylococci, diptheroids, Propionobacterium species, Bacillus species, or Micrococcus species) or viridans streptococci isolated from two or more culture samples from different sites and associated with fever (body temperature > 38.3°C), rigors, or hypotension (systolic BP < 90 mm Hg) were considered true bacteremias. Polymicrobial infection with the same organisms in more than one culture sample were also considered to represent true bacteremia if associated with fever (body temperature > 38.3°C), rigors, or hypotension (systolic BP < 90 mm Hg). When the above-mentioned criteria were not applicable, two study physicians reviewed available clinical data including all other culture results, antibiotic utilization, and the patients clinical course to make a determination as to the presence or absence of true bacteremia. All other paired specimens with a positive culture finding were classified as representing contamination. The definition used for sepsis was established by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference.9
Fecal culture specimens for vancomycin-resistant enterococci (VRE) are routinely obtained in all patients admitted to the medical ICU at admission, every 7 days, and at the time of transfer out of the unit. Patients with a fecal culture result positive for VRE were classified as being "VRE positive." Acute renal failure was defined as a twofold increase in baseline creatinine or an absolute increase in creatinine by 176.8 mol/L (2.0 mg/dL). Acute respiratory failure was defined by the requirement for mechanical ventilation for a diagnosis of COPD or a PaO2 < 60 mm Hg while receiving a fraction of inspired oxygen
0.50, or the use of
10 cm H2O of positive end-expiratory pressure.
Blood Culture Technique
Blood samples were obtained by critical care nurses caring for the patient. Before collecting the blood sample, skin was disinfected with 70% isopropyl alcohol followed by 2% iodine tincture. The antecubital fossa was the preferred sampling site using a sterile needle and syringe. The blood samples from central vein catheters were obtained from needleless caps that were disinfected with 70% isopropyl alcohol, allowed to dry, and wiped with a Betadine pad (Cepti-seal; Blood Culture Prep Kit II; Medi-Flex Hospital Products; Overland Park, KS) for 30 s. The excess Betadine was wiped off with sterile gauze prior to obtaining the sample. Three milliliters of blood were aspirated and discarded from both the central vein catheter and peripheral venipuncture. A new syringe was used to aspirate an additional 20 mL of blood. A blood volume of 10 mL was injected into each of two blood culture bottles. Injection of
5 mL of blood into a blood culture bottle was not permitted to avoid false-negative results.10
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All blood samples were inoculated into aerobic and anaerobic media and processed using the Bactec Blood Culture system (Bactec; Becton Dickinson; Sparks, MD).
Statistical Analysis
All values are expressed as mean ± SD (continuous variables) or as a percentage of the group from which they were derived (categorical variables). Continuous variables were compared using the Student t test. The
2 test was used to compare categorical variables. All p values were two tailed, and p
0.05 was considered to indicate statistical significance.
The influence of prevalence of true bacteremia on the operating characteristics of blood cultures obtained with peripheral venipuncture and through a central vein catheter was assessed using a range of prevalence values that could be expected to occur in clinical practice. This modeling method was used to estimate the changes in the predictive accuracy of the two blood culture techniques over this range of prevalence values.7 8
To identify variables independently associated with the presence of true bacteremia (dependent variable), a multiple logistic regression model was used to control for the effects of confounding variables.12 13 A stepwise approach was used to enter new terms into the logistic regression model, where 0.05 was set as the limit for the acceptance or removal of new terms. Variables entered into the logistic regression model were required a priori to have a plausible biological relationship to the dependent outcome variable in order to avoid spurious associations.14 Model overfitting was examined by evaluating the ratio of outcome events to the total number of independent variables in the final model, and specific testing for interactions between the independent variables was included in our analysis.14 Results of the logistic regression analyses are reported as adjusted odds ratios with 95% confidence intervals (CIs).
| Results |
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Thirty-four paired culture results (11.3%; 95% CI, 7.8 to 14.8%) were accepted as true-positives representing a true bacteremia. This represented the occurrence of at least one episode of true bacteremia in 25 patients (1.36 episodes of true bacteremia per patient). Two of these (5.9%) were specimens that did not meet the preset criteria for true bacteremia and required confirmation from two study physicians. Each of these was a single positive blood culture result of a common skin contaminant in patients with evidence of sepsis and no other source of identifiable infection. In one of these cases, the central line was removed and the culture of the catheter tip grew the same organism identified in the single blood culture. Among the 34 paired culture results representing true bacteremia, 8 were classified as secondary bacteremias (23.5%). The infections associated with secondary bacteremia included pneumonia (n = 5), soft tissue/wound (n = 2), and urinary tract (n = 1).
The patient characteristics associated with blood specimens representing a true bacteremia and those negative for bacteremia are shown in Table 1 . The absence of IV antibiotics administered through the central vein catheter at the time blood samples were drawn was statistically more common among patients with a true bacteremia. Table 2 compares the characteristics of the central vein catheters through which the catheter drawn blood samples were obtained. Patients with a true bacteremia had their central vein catheters placed statistically later during their ICU stays, and the line day blood culture samples were drawn was statistically greater compared to patients negative for true bacteremia. In addition to patient and central vein catheter characteristics, patients with multiple pairs of blood samples were statistically more likely to have true bacteremia compared to patients having a single blood sample pair (20 true bacteremias among 70 patients [28.6%] vs 5 true bacteremias among 49 patients [10.2%]; p = 0.015).
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All 235 catheter-negative/venipuncture-negative paired culture results were accepted as true-negatives. All 16 catheter-positive/venipuncture-positive paired culture results were classified as true bacteremia or fungemia. True bacteremia was determined to be present in 6 of 17 catheter-negative/venipuncture-positive pairs (35.3%), and in 12 of 32 catheter-positive/venipuncture-negative pairs (37.5%). The pathogens isolated from the paired cultures for each category are shown in Table 3 .
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| Discussion |
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Our investigation is unique in evaluating medical patients in the ICU setting with suspected bloodstream infection. DesJardin et al7 found the negative predictive value for catheter-drawn and peripheral venipuncture cultures to be 99% and 98%, respectively, with little decrement over the prevalence range of positive blood culture results for hospitalized patients with cancer. The same investigators found similar results for critically ill surgical patients.8 Our study uniquely identified the presence of IV antibiotic administration as a potential confounding factor when interpreting blood culture results. Patients receiving IV antibiotics were statistically less likely to have a true bacteremia. Similar findings have been made with regards to BAL and protected specimen brush cultures for the evaluation of ventilator-associated pneumonia.15 16 However, unlike pneumonia, where histology can serve as a "gold standard" for the diagnosis of infection, true bacteremia has no other diagnostic "gold standard." Antibiotic administration has also been shown to interfere with the interpretation of cerebral spinal fluid culture specimens obtained to diagnose bacterial meningitis.17 18
Comparisons of blood cultures obtained by peripheral venipuncture and from central vein catheters for the detection of catheter colonization or catheter-related infection have also been performed. Juste et al19 found that the sensitivity and specificity of peripheral venipunture (41.5% and 77.7%, respectively) were similar to the sensitivity and specificity of culture results obtained from the catheter hubs (50.8% and 78.9%, respectively) for the identification of microorganisms colonizing the catheters. Similarly, Blot et al20 evaluated the accuracy of peripheral venipuncture and central vein catheter cultures for the diagnosis of catheter-associated bacteremia. They identified 28 instances where the same microorganisms were isolated from peripheral venipuncture cultures and catheter-drawn cultures. A definite diagnosis of catheter-related bacteremia was established in 16 of 17 patients whose catheter-drawn culture results were positive at least 2 h earlier than the peripheral venipuncture cultures. These data suggest that paired blood cultures obtained by peripheral venipuncture and from catheter draws can be helpful in the identification of catheter-related infections.
The relatively low positive predictive value of blood samples obtained from catheter draws is concerning for several reasons. First, treating contamination as infection can potentially prolong hospitalization and increase medical care costs.21 22 Second, antibiotic treatment may be needlessly started based on false-positive culture results.6 This increases the possibility that resistant bacteria can emerge resulting in more difficult to treat infections. Bloodstream infections are usually treated with at least 10 to 14 days of antibiotic therapy.23 This duration of treatment has been shown to be an important risk factor for the subsequent emergence of infections with antibiotic-resistant bacteria.24 Although the negative predictive value was relatively good for blood samples drawn through central vein catheters, there are important consequences associated with missing the diagnosis of bloodstream infection. Previous studies have identified a significant association between the administration of inadequate antimicrobial treatment of bloodstream infections and hospital mortality.2 25 26 27 28 29 A more recent study of medical and surgical patients requiring critical care found that individuals with a bloodstream infection who received initially inadequate antibiotic treatment had a significantly greater hospital mortality rate compared to patients receiving an adequate initial antibiotic regimen (61.9% vs 28.4%; p < 0.001).30 These data emphasize the importance of establishing an accurate diagnosis of bloodstream infection among hospitalized patients in order to begin treatment with an adequate antimicrobial regimen as soon as possible.
Our study has several limitations. First, it was conducted at a single hospital. Therefore, the results may not be applicable to ICUs with different patterns of central vein catheter utilization and different rates of bloodstream infection. Second, we allowed the inclusion of multiple blood culture specimens from individual patients. This may have prevented us from identifying additional factors predictive of true bacteremia as a result of the limited number of patients examined. We also could not evaluate the yield of blood cultures from patients having a single pair of culture samples drawn compared to patients having multiple sets of culture samples drawn. This may be an important area for future investigation, as our data suggest that multiple blood cultures are more often associated with patients having true bacteremia. Additionally, no "gold standard," other than a positive blood culture result, exists to define the presence of true bacteremia. As a result, we cannot be completely confident that some of our blood culture results were not misclassified. Finally, we did not routinely culture central vein catheters when they were removed. This prevented us from accurately determining the number of bacteremias due to catheter-associated infection.
In summary, blood culture specimens are commonly obtained in the ICU setting. Clinicians should be aware of the potential limitations of these samples to define the presence or absence of true bacteremia. We recommend that when a central vein catheter is present, one pair of blood samples should be obtained from the central vein catheter and the other via peripheral venipuncture. When the central vein catheter and peripheral venipuncture samples are concordant, then antimicrobial management should be straightforward. The main problem arises when the samples are discordant. Clinicians caring for patients will have to decide if the discordant positive culture represents true bloodstream infection or contamination. This may require obtaining additional cultures, monitoring the patients clinical status closely, and possibly beginning antibiotic treatment with or without the removal of the central vein catheter when catheter-associated bloodstream infection is suspected.31
| Acknowledgements |
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| Footnotes |
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Received for publication March 4, 2002. Accepted for publication July 10, 2002.
| References |
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