Differential Time to Positivity: A Useful Method for Diagnosing Catheter-Related Bloodstream Infections

Context Diagnosing central venous catheterrelated bloodstream infections may be difficult. Contribution This prospective study from a tertiary care cancer center examined 191 infections with the same organism detected from simultaneously drawn central and peripheral blood cultures. Catheter-tip colonization or quantitative blood cultures defined catheter-related bloodstream infection. When the culture drawn from the catheter became positive at least 120 minutes earlier than the peripherally drawn culture, the odds of catheter-related bloodstream infection increased by a factor of 5.9. Implications Differential time to positivity of at least 120 minutes between centrally and peripherally drawn blood cultures helps diagnose catheter-related bloodstream infection. The Editors Catheter-related bloodstream infections are a common type of nosocomial bloodstream infections and are associated with the use of central venous catheters (1, 2). Kluger and Maki (3) estimated that more than 200 000 cases of catheter-related bloodstream infections occur annually in the United States, with an attributable mortality rate of 12% to 25% (3). However, despite their high frequency of occurrence and seriousness, such infections are often difficult to diagnose. Clinical manifestations of this type of infection, such as fever and chills, are sensitive but not specific for a diagnosis, whereas other manifestations, suchas catheter-site inflammation, are specific but not sensitive. For the past 25 years, semiquantitative (for example, the roll-plate technique) and quantitative (for example, sonication) methods of catheter culture have been used to establish the diagnosis of catheter-related bloodstream infection (4-6). However, because taking catheter cultures requires the removal or exchange of the catheter, it only minimally affects management of the infection (7). To avoid unnecessary removal of the central venous catheter, some researchers have suggested taking simultaneous quantitative blood cultures from the catheter and the peripheral vein (8, 9). This method has been limited because quantitative blood cultures are labor intensive and costly and therefore are not widely used in clinical microbiology laboratories. Recently, Blot and colleagues (10, 11) reported that the measurement of differential time to positivity between blood cultures drawn through the central venous catheter and those drawn from the peripheral vein is highly diagnostic of catheter-related bloodstream infection in patients with long-term catheters. The differential time to positivity was defined as the difference in the time it took for a blood culture drawn through the central venous catheter and a culture drawn from a peripheral vein to become positive. Other investigators did not show that this method is highly diagnostic of catheter-related bloodstream infection in patients with short-term (<30 days of dwell time) catheters. However, all of the studies reported so far have included a very small number of evaluable patients who had positive simultaneous blood cultures from both the central venous catheter and the peripheral vein (12-14). To investigate the diagnostic usefulness of differential time to positivity, we decided a priori to follow for a year patients who grew the same organism from blood cultures drawn simultaneously through the central venous catheter and peripheral vein. We hypothesized that the diagnostic utility of differential time to positivity would differ between patients who had short-term catheters and those who had long-term catheters. Methods Patients The study took place at the University of Texas M.D. Anderson Cancer Center, in Houston, Texas, between 1 September 1999 and 1 November 2000. We evaluated the results of all blood cultures drawn simultaneously from the central venous catheter and peripheral vein and prospectively followed patients who had positive simultaneous blood cultures that grew the same organisms. Information obtained on these patients included age, sex, underlying disease, duration of hospitalization, duration of stay in the intensive care unit, history of bone marrow transplantation, type of catheter, number of catheter lumen, catheter insertion site, and duration of catheterization. We also evaluated patients for neutropenia, thrombocytopenia, concomitant infections, therapy with antimicrobial agents, and outcome of infections. Definitions and Diagnosis We defined differential time to positivity as the difference in time needed for blood cultures drawn simultaneously through the central venous catheter and from a peripheral vein to become positive. As in previous studies, differential time to positivity was considered positive (that is, suggestive of catheter-related bloodstream infection) if the blood culture drawn through the central venous catheter became positive at least 120 minutes earlier than a positive culture drawn simultaneously from a peripheral vein. Significant colonization of the catheter tip was defined as a positive semiquantitative catheter culture by the roll-plate method, whereby at least 15 colony-forming units (CFUs) of an organism were cultured from the catheter tip (4). We used 3 definitions of catheter-related bloodstream infection in this study to evaluate the diagnostic accuracy of differential time to positivity. All of the definitions included the presence of clinical signs and symptoms of bacteremia, such as fever and chills, in the absence of sources for the bacteremia other than the catheter. The definitions were as follows: 1. Composite definition of catheter-related bloodstream infection as defined by the recent Infectious Disease Society of America (IDSA) guidelines (15): Positive simultaneous blood cultures from the central venous catheter and peripheral vein yielding the same organism in the presence of either significant catheter-tip colonization with 15 CFUs or more of the same organism (same species and antibiogram) isolated from the blood cultures, or simultaneous quantitative blood cultures in which the number of CFUs isolated from the blood drawn through the central venous catheter was at least 5-fold greater than the number isolated from blood drawn percutaneously. 2. Partial definition based on simultaneous quantitative blood cultures: The presence of at least 5 times the number of CFUs from the central venous catheter blood culture compared with that the number from the peripheral vein blood culture. 3. Partial definition based on semiquantitative catheter culture: Catheter-tip culture with at least 15 CFUs of the same organism isolated from the peripheral vein blood culture. A bloodstream infection originating from a noncatheter source was defined as one with positive blood cultures from the central venous catheter and peripheral vein that did not fulfill any of the criteria of quantitative catheter-related bloodstream infection or tip culturebased bloodstream infection, as defined earlier. Evaluable cases of bloodstream infection were those with positive simultaneous blood cultures of the same organisms from the central venous catheter and peripheral vein, in which it was possible to determine the source of the bloodstream infection (catheter or otherwise) on the basis of the definitions outlined earlier. Short-term central venous catheters were those with a dwell time of less than 30 days, and long-term central venous catheters were those with a dwell time of 30 days or more. The principal investigator determined whether infections were catheter related and had no knowledge of differential time to positivity at the time of adjudication of the reference standard definitions. Culture Techniques After rigorous antiseptic cleansing of the skin and the hub with 70% alcohol, we drew quantitative and qualitative blood cultures from the peripheral vein and central venous catheter hub simultaneously (maximum of 15 minutes apart). From the central venous catheter, we drew 7 to 10 mL of blood and then discarded the sample to avoid contamination with previously administered agents that could have antimicrobial activity. We subsequently drew 20 mL of blood through the central venous catheter and divided the sample into 2 portions. We placed 10 mL in isolator tubes (isolator 10, Wampole, Cranbury, New Jersey) for quantitative culturing by using the lysis centrifugation method, as described elsewhere (16). Another 10 mL of blood was placed in a regular aerobic blood culture bottle (aerobic 26+, Becton Dickinson DIS, Sparks, Maryland). We also drew 20 mL of blood percutaneously and processed the sample in the same manner as the blood culture from the central venous catheter. All blood culture bottles were taken promptly to the microbiology laboratory and placed in an automatic culture detector (Bactec 9240, Bactec Plus Aerobic/F, Becton Dickinson DIS, Sparks, Maryland), which records culture positivity every 15 minutes according to changes in fluorescence related to microbial growth. Catheters were removed aseptically, at the discretion of primary care physicians, if they were no longer needed or if infection was suspected. A 5-cm segment of the removed catheter tip was aseptically cut and delivered to the microbiology laboratory for culture by the semiquantitative roll-plate method (4). Statistical Analysis We divided the study sample into 2 groups, those with catheter-related bloodstream infection and those without, on basis of the composite definition of catheter-related bloodstream infection according to IDSA guidelines (15). We determined the significance of the differences between the 2 study groups using the chi-square test or the Fisher exact test, as appropriate, for categorical variables. The Student t-test or MannWhitney test was used for continuous variables. All P values were based on 2-tailed tests (level of significance, P 0.05). Sensitivity, specificity, and likelihood ratios, along with associated 95% CIs, were determined for differential time to positivity o