Clinical Utility of Blood Cultures Drawn from Indwelling Central Venous Catheters in Hospitalized Patients with Cancer

Long-term, indwelling central venous catheters are indispensable in the management of patients with cancer. Common indications for the placement of these catheters in patients with cancer include poor peripheral access; frequent need to administer blood products or antibiotics or to draw blood; continuous infusion of chemotherapeutic agents; a prolonged treatment course; and use of vesicant drugs (1). The convenience of these catheters makes them an obvious choice for frequent blood draws, and the reliability of routine laboratory data obtained from blood drawn through central venous catheters has been demonstrated (2). However, the American College of Physicians guidelines (3) and expert opinion (4) discourage the use of intravascular devices to obtain blood for culture. Such statements have evolved because of concern that contamination rates will increase (that is, specificity will decrease) when blood cultures are obtained through intravascular devices, leading to prolonged hospitalization and increased cost (5), and concern about possible line contamination. Results from studies supporting (6, 7) or refuting (8-11) such concerns have been inconsistent. Furthermore, none of these studies were blinded, and all lacked a clear gold standard definition of true bacteremia. Because drawing blood through central venous catheters is convenient and prevents trauma to the veins, it is a potentially worthwhile means of obtaining samples for culture. We therefore conducted a retrospective evaluation of paired blood cultures from patients hospitalized on the hematology-oncology ward to determine the sensitivity and specificity of blood for culture drawn through a central venous catheter compared with that for culture samples obtained through peripheral venipuncture, using a predetermined definition for true bacteremia. We also examined antibiotic use and clinical outcomes for patients in whom a paired culture yielded discordant results. Methods We retrospectively screened all blood cultures from patients on an oncology ward at New England Medical Center, a 300-bed tertiary care university-affiliated hospital, between August 1994 and June 1996. Information collected from patient records included diagnosis, type and date of catheter placement, presence of neutropenia, antimicrobial use, other blood culture results, and relevant clinical data (presence of fever, rigors, or hypotension). Definitions A paired culture was defined as at least one blood culture set clearly labeled as drawn from a central venous catheter and at least one blood sample drawn through a peripheral venipuncture. Blood samples had to be drawn within 4 hours of each other. Reasons for excluding cultures from our analysis included the following: only one blood sample was drawn (no paired culture), samples were not drawn within 4 hours of each other, or the source of the draw was not clearly marked. Aside from the presence of a central line, patients whose cultures were excluded did not differ from patients whose cultures were included in the analysis. Guidelines were modified from published articles by Arbo and Snydman (12) and Weinstein and colleagues [13] as follows: 1) Certain pathogens [such as Staphylococcus aureus, gram-negative bacilli, and Candida species] isolated from any culture sample represented true bacteremia or fungemia; 2) common skin contaminants (coagulase-negative staphylococci, diphtheroids, Propionibacterium species, Bacillus species, or Micrococcus species) or viridans streptococci isolated from two or more culture samples drawn from different sites and associated with fever (body temperature>38.3 C), rigors, or hypotension [systolic blood pressure<90 mm Hg] were considered true bacteremias; and 3) polymicrobial infection with the same organisms in more than one culture sample and associated with fever(body temperature>38.3 C), rigors, or hypotension (systolic blood pressure<90 mm Hg) were considered true bacteremias. Analytical Framework True bacteremia (or fungemia) or contamination was determined by two infectious diseases physicians who were blinded to the source from which the blood culture was drawn. The physicians had access to results of all other blood cultures (obtained from 7 days before to 7 days after the paired culture) and clinical data, including other sites of infection, antibiotic use, temperature and laboratory data (obtained from 2 days before until 2 days after the paired culture) to assist in their decisions. Both specialists evaluated the culture pairs together to reach complete agreement. Outcome Measures Sensitivity, specificity, and positive and negative predictive value for catheter draws and peripheral venipunctures were the main outcomes measured against the infectious disease experts' assessment of culture and clinical information. In addition, any catheter draw or peripheral venipuncture that yielded one or more organisms not responsible for true bacteremia or fungemia was counted as a contaminant; these results were used to calculate a contamination rate. Finally, for paired cultures that yielded a discordant result, antibiotic use, length of stay (time from paired blood cultures to discharge), and in-hospital mortality were examined. An additional analysis was done to determine the clinical impact of a culture result in which either a peripheral venipuncture or catheter draw failed to detect a true bacteremia. Two infectious diseases specialists, each blinded to the source of true bacteremia, determined the need for additional antibiotic therapy beyond that which the patient was receiving before or on the same day that the samples for paired culture were obtained. For discordant paired cultures that yielded a contaminant, two infectious diseases physicians, blinded to the source of contaminant, determined how often antibiotic therapy was specifically directed at the contaminant. Because many patients were receiving antibiotic therapy when the paired culture in question was obtained [for example, empirical treatment of neutropenic fever or treatment of a previously diagnosed infection], specific therapy directed at the contaminant was defined as 1) initiation of antibiotics within 72 hours of the paired culture in response to the contaminant or 2) the continuation of specific therapy directed at the contaminant beyond the time when another indication to administer antibiotics had resolved (such as neutropenia or fever). Blood Culture Technique Blood for culture was obtained by using the following general guidelines. For samples drawn through a central venous catheter, a nurse caring for the patient obtained the sample. The port was disinfected with either 70% isopropyl alcohol or a povidone-iodine swab, and 10 mL of blood was drawn. All peripheral venipunctures were performed by housestaff caring for the patient. Ten milliliters of blood was obtained after skin antisepsis with povidone-iodine. Blood samples from each draw were inoculated in aerobic and anaerobic media and processed by using the ESP 384 Blood Culture System (Accumed International, Inc., Westlake, Ohio). Statistical Analysis In this study, multiple blood culture pairs could be drawn from a single person during one or more hospitalizations. To more accurately estimate the confidence intervals for the central catheter (c), peripheral venipuncture (p), and central catheter minus peripheral venipuncture (c p) differences, we used bootstrap methods to adjust for potential clustering around patient, hospital admission, and blood culture (14). To perform the bootstrapped analysis, we drew 2000 samples of size 552 with replacement from the original data set (n=552 pairs). From each sample, we calculated sensitivity, specificity, positive predictive value, and negative predictive value for c, p, and c p. We then ranked these results and found the lower and upper 2.5% values that represent the 95% confidence, or percentile, intervals. Exact two-sided P values were calculated. Differences in length of stay were analyzed by using the Kruskal-Wallis test. All statistical analyses were performed by using the SAS system for Windows, version 6.12 (SAS Institute, Inc., Cary, North Carolina). Role of the Funding Source Support for this study was provided by a training grant from the National Institutes of Health. The decision to undertake the study was made solely by the authors. Results Culture Results and Clinical Characteristics During the period studied, 551 paired blood cultures met our criteria for a paired blood draw from a central venous catheter and peripheral venipuncture. These 551 paired cultures were obtained from 185 patients with 306 admissions to a hematology-oncology service. Catheter-negative/venipuncture-negative results accounted for 469 (85%) of the paired cultures. Eighty-two paired cultures had a positive result; of these, 32 (6%) were catheter-positive/venipuncture-positive, 17 (3%) were catheter-negative/venipuncture-positive, and 33 (6%) were catheter-positive/venipuncture-negative. Eighty-nine percent of the 82 paired cultures with a positive result were drawn from long-term, indwelling Hickman or port catheters (Table 1). Leukemia was the most common diagnosis (47%), and 71% of the paired cultures were taken from patients who had had bone marrow transplantation. Fifty-four percent of patients were neutropenic at the time of blood draw, and 71% of patients were receiving antibiotic therapy at the time of blood draw. Table 1. Demographic and Clinical Characteristics of Patients from Whom 82 Paired Blood Cultures with at Least One Positive Result Were Obtained All 469 catheter-negative/venipuncture-negative paired cultures were accepted as true negatives. All 32 catheter-positive/venipuncture-positive paired cultures showed true bacteremia or fungemia. In one paired culture in this group, S. aureus was isolated from the venipuncture and S. epidermidis was isolated from the catheter. Therefore, the S. aureus infection was inclu