Ioannis Chatzinikolaou

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

In Vitro and Ex Vivo Activities of Minocycline and EDTA against Microorganisms Embedded in Biofilm on Catheter Surfaces

ABSTRACT Minocycline-EDTA (M-EDTA) flush solution has been shown to prevent catheter-related infection and colonization in a rabbit model and in hemodialysis patients. We undertook this study in order to determine the activities of M-EDTA against organisms embedded in fresh biofilm (in vitro) and mature biofilm (ex vivo). For the experiment with the in vitro model, a modified Robbin’s device (MRD) was used whereby 25 catheter segments were flushed for 18 h with 106 CFU of biofilm-producing Staphylococcus epidermidis, Staphyloccocus aureus, and Candida albicans per ml. Subsequently, each of the catheter segments was incubated in one of the following solutions: (i) streptokinase, (ii) heparin, (iii) broth alone, (iv) vancomycin, (v) vancomycin-heparin, (vi) EDTA, (vii) minocycline (high-dose alternating with low-dose), or (viii) M-EDTA (low-dose minocycline alternating with high-dose minocycline were used to study the additive and synergistic activities of M-EDTA). All segments were cultured quantitatively by scrape sonication. For the experiment with the ex vivo model, 54 catheter tip segments removed from patients and colonized with bacterial organisms by roll plate were longitudinally cut into two equal segments and exposed to either saline, heparin, EDTA, or M-EDTA (with high-dose minocycline). Subsequently, all segments were examined by confocal laser electron microscopy. In the in vitro MRD model, M-EDTA (with a low concentration of minocycline) was significantly more effective than any other agent in reducing colonization of S. epidermidis, S. aureus, and C. albicans (P < 0.01). M-EDTA (with a high concentration of minocycline) eradicated all staphylococcal and C. albicans organisms embedded in the biofilm. In the ex vivo model, M-EDTA (with a high concentration of minocycline) reduced bacterial colonization more frequently than EDTA or heparin (P < 0.01). We concluded that M-EDTA is highly active in eradicating microorganisms embedded in fresh and mature biofilm adhering to catheter surfaces.

Antibiotic-coated hemodialysis catheters for the prevention of vascular catheter–related infections: a prospective, randomized study ☆

PURPOSE To determine the efficacy of minocycline-rifampin-coated hemodialysis catheters in reducing catheter-related infections in patients requiring hemodialysis for acute renal failure. METHODS Between May 2000 and March 2002, 66 patients were randomly assigned to receive a minocycline-rifampin-impregnated central venous catheter and 64 were randomly assigned to receive an unimpregnated catheter. Patients were followed prospectively until the catheter was removed. Catheter-related infection was determined through quantitative catheter cultures, quantitative blood cultures, or both. RESULTS Both groups of patients were similar in age, sex, underlying disease, type of dialysis (continuous vs. intermittent), neutropenia during catheterization and its duration, catheter insertion difficulties, and administration of blood products or medication. The mean (+/- SD) catheter dwell time was the same in both groups (8 +/- 6 days, P = 0.7). There were seven catheter-related infections (11%), all associated with the use of unimpregnated catheters. Kaplan-Meier estimates for the risk of catheter-related infection showed that coated catheters were less likely to be associated with infection (P = 0.006). CONCLUSION The use of polyurethane hemodialysis catheters impregnated with minocycline and rifampin decreases the risk of catheter-related infection in patients with acute renal failure.

Aspergillus terreus: an emerging amphotericin B-resistant opportunistic mold in patients with hematologic malignancies.

Invasive aspergillosis (IA) has emerged as a common cause of morbidity and mortality among immunocompromised patients. At The University of Texas M. D. Anderson Cancer Center (Houston, TX), Aspergillus terreus is second to A. fumigatus as the most common cause of IA. In the current study, the authors compared the risk factors and outcomes associated with IA caused by A. terreus and IA caused by A. fumigatus.

Minocycline-Ethylenediaminetetraacetate Lock Solution for the Prevention of Implantable Port Infections in Children with Cancer

In this prospective cohort study, minocycline-ethylenediaminetetraacetate (M-EDTA) was used as a lock solution in indwelling ports inserted in 14 children with cancer. No port infections, thrombotic events, or other adverse events were observed, compared with 10 port infections that occurred in 48 control patients whose ports were flushed with heparin. M-EDTA is a promising lock solution in long-term catheters.

Clinical experience with minocycline and rifampin-impregnated central venous catheters in bone marrow transplantation recipients: efficacy and low risk of developing staphylococcal resistance.

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Oropharyngeal Candidiasis as a Marker for Esophageal Candidiasis in Patients with Cancer

The present study was designed to determine the frequency of candidal esophagitis in cancer patients with oral thrush. Patients with clinically and microbiologically diagnosed oral candidiasis were evaluated by endoscopy for concurrent esophageal candidiasis. Esophageal involvement was documented by mucosal lesions, microbiological findings of candidal infection in smears of brushing material, positive cultures of brushing material, and histological evidence of mucosal invasion by the yeast. For 21 of the 22 patients studied, there were endoscopic and microbiological findings of candidal esophagitis. Cultures of the brushing material from all 22 patients were positive, while histological evidence was found for 14 patients. Only 10 of the patients had mild esophageal symptoms. It is concluded that oral thrush represents a reliable marker for esophageal candidiasis in patients with cancer. Routine endoscopy is not necessary to confirm the diagnosis; this procedure should be reserved for patients with persistent thrush and symptoms despite antifungal therapy.

Prospective Study of the Value of Quantitative Culture of Organisms from Blood Collected through Central Venous Catheters in Differentiating between Contamination and Bloodstream Infection

ABSTRACT Collection of blood through a central venous catheter for the diagnosis of bacteremia is a debated topic. Quantitative cultures of organisms from blood collected through central venous catheters were found to be highly sensitive, specific, and predictive of bacteremia, especially when a cutoff point of 15 colonies of skin organisms was used.

Prospective evaluation of the impact of amoxicillin, clarithromycin and their combination on human gastrointestinal colonization by Candida species.

Background: Amoxicillin and clarithromycin have been used extensively for the eradication of Helicobacter pylori. However, no study has examined the impact of their combination on the Candida albicans concentration of the gastrointestinal (GI) tract. This is the first study examining and comparing directly the effect of amoxicillin, clarithromycin and their combination on the C. albicans concentration of the human GI tract. Methods: Thirty-three adult patients (11 in each antibiotic group) were studied prospectively. Quantitative stool cultures for Candida were conducted at the beginning, the end and 1 week after the discontinuation of antibiotic treatment. Results: All three regimens increased the GI colonization in patients by Candida. The combination of amoxicillin with clarithromycin caused the highest increase; however, this was not statistically significant. Conclusion: Amoxicillin and clarithromycin used either alone or in combination cause a small to moderate increase in GI colonization by Candida. Hence, these drugs could be safely used in patients at risk for candidiasis originating from the GI tract.

Central Venous Catheter Related Infections: The Role of Antimicrobial Catheters

Intravascular devices are indispensable in modern-day medical practice, especially in the care of critically and chronically ill patients, such as patients in intensive care units (ICU), cancer patients, patients with renal failure requiring chronic hemodialysis, or patients requiring organ or bone marrow transplantation. Additionally surgical patients especially the ones with short bowel syndrome, totally depend on intravenous catheters for their nutritional support. These devices are used to administer intravenous fluids, medications, blood products and total parenteral nutrition (TPN) fluids, as well as for hemodynamic status monitoring of critically ill patients.