Hend Hanna

A Comparison of Two Antimicrobial-Impregnated Central Venous Catheters

BACKGROUND The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters. METHODS We conducted a prospective, randomized clinical trial in 12 university-affiliated hospitals. High-risk adult patients in whom central venous catheters were expected to remain in place for three or more days were randomly assigned to undergo insertion of polyurethane, triple-lumen catheters impregnated with either minocycline and rifampin (on both the luminal and external surfaces) or chlorhexidine and silver sulfadiazine (on only the external surface). After their removal, the tips and subcutaneous segments of the catheters were cultured by both the roll-plate and the sonication methods. Peripheral-blood cultures were obtained if clinically indicated. RESULTS Of 865 catheters inserted, 738 (85 percent) produced culture results that could be evaluated. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters impregnated with minocycline and rifampin were 1/3 as likely to be colonized as catheters impregnated with chlorhexidine and silver sulfadiazine (28 of 356 catheters [7.9 percent] vs. 87 of 382 [22.8 percent], P<0.001), and catheter-related bloodstream infection was 1/12 as likely in catheters impregnated with minocycline and rifampin (1 of 356 [0.3 percent], vs. 13 of 382 [3.4 percent] for those impregnated with chlorhexidine and silver sulfadiazine; P<0.002). CONCLUSIONS The use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine.

Intravascular catheter-related infections: advances in diagnosis, prevention, and management

Indwelling vascular catheters are a leading source of bloodstream infections in critically ill patients and cancer patients. Because clinical diagnostic criteria are either insensitive or non-specific, such infections are often overdiagnosed, resulting in unnecessary and wasteful removal of the catheter. Catheter-sparing diagnostic methods, such as differential quantitative blood cultures and time to positivity have emerged as reliable diagnostic techniques. Novel preventive strategies include cutaneous antisepsis, maximum sterile barrier, use of antimicrobial catheters, and antimicrobial catheter lock solution. Management of catheter-related bloodstream infections involves deciding on catheter removal, antimicrobial catheter lock solution, and the type and duration of systemic antimicrobial therapy. Such decisions depend on the identity of the organism causing the bloodstream infection, the clinical and radiographical manifestations suggesting a complicated course, the underlying condition of the host (neutropenia, thrombocytopenia), and the availability of other vascular access sites.

Comparative Activities of Daptomycin, Linezolid, and Tigecycline against Catheter-Related Methicillin-Resistant Staphylococcus Bacteremic Isolates Embedded in Biofilm

ABSTRACT In the setting of catheter-related bloodstream infections, intraluminal antibiotic lock therapy could be useful for the salvage of vascular catheters. In this in vitro study, we investigated the efficacies of the newer antibiotics daptomycin, linezolid, and tigecycline, in comparison with those of vancomycin, minocycline, and rifampin, against methicillin-resistant Staphylococcus aureus (MRSA) embedded in biofilm. We also assessed the emergence of MRSA strains resistant to these antibiotics, alone or in combination with rifampin, after 4-hour daily use for catheter lock therapy. Minocycline, daptomycin, and tigecycline were more efficacious in inhibiting MRSA in biofilm than linezolid, vancomycin, and the negative control (P < 0.001) after the first day of exposure to these antibiotics, with minocycline being the most active, followed by daptomycin and then tigecycline, and with vancomycin and linezolid lacking activity, similar to the negative control. After 3 days of 4-hour daily exposures, daptomycin was the fastest in eradicating MRSA from biofilm, followed by minocycline and tigecycline, which were faster than linezolid, rifampin, and vancomycin (P < 0.001). When rifampin was used alone, it was the least effective in eradicating MRSA from biofilm after 5 days of 4-hour daily exposures, as it was associated with the emergence of rifampin-resistant MRSA. However, when rifampin was used in combination with other antibiotics, the combination was significantly effective in eliminating MRSA colonization in biofilm more rapidly than each of the antibiotics alone. In summary, daptomycin, minocycline, and tigecycline should be considered further for antibiotic lock therapy, and rifampin should be considered for enhanced antistaphylococcal activity but not as a single agent.

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

The changing epidemiology of invasive candidiasis: Candida glabrata and Candida krusei as the leading causes of candidemia in hematologic malignancy.

The objective of the current retrospective study was to compare the epidemiology of candidemia and its risk factors in patients who had hematologic malignancies(HM) with those in patients who had solid tumors (ST).

Efficacy and Safety of Weekly Dalbavancin Therapy for Catheter-Related Bloodstream Infection Caused by Gram-Positive Pathogens

BACKGROUND Catheter-related bloodstream infections (CR-BSIs) are associated with substantial mortality, prolongation of hospital stay, and increased cost of care. Dalbavancin, a new glycopeptide antibiotic with unique pharmacokinetic properties that have allowed clinical development of a weekly dosing regimen, possesses excellent activity against clinically important gram-positive bacteria, suggesting utility in the treatment of patients with CR-BSIs. METHODS A phase 2, open-label, randomized, controlled, multicenter study of 75 adult patients with CR-BSIs compared treatment with intravenous dalbavancin, administered as a single 1000-mg dose followed by a 500-mg dose 1 week later, with intravenous vancomycin, administered twice daily for 14 days. Gram-positive bacteria isolated in this study included coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). RESULTS Infected patients who received weekly dalbavancin (n=33) had an overall success rate (87.0%; 95% confidence interval [CI], 73.2%-100.0%) that was significantly higher than that of those who received vancomycin (n=34) (50.0%; 95% CI, 31.5%-68.5%). Adverse events and laboratory abnormalities were generally mild and were comparable for the 2 drugs. CONCLUSIONS Dalbavancin thus appears to be an effective and well-tolerated treatment option for adult patients with CR-BSIs caused by CoNS and S. aureus, including MRSA.

Efficacy of antimicrobial-impregnated bladder catheters in reducing catheter-associated bacteriuria: a prospective, randomized, multicenter clinical trial

OBJECTIVES To examine the efficacy of bladder catheters impregnated with minocycline and rifampin in reducing catheter-associated bacteriuria. METHODS A prospective, randomized clinical trial was conducted at five academic medical centers. Patients undergoing radical prostatectomy were randomized to receive intraoperatively either regular silicone bladder catheters (control catheters) or silicone bladder catheters impregnated with minocycline and rifampin (antimicrobial-impregnated catheters). Catheters remained in place for a mean of 2 weeks. Urine cultures were obtained at about 3, 7, and 14 days after catheter insertion. Bacteriuria was defined as the growth of organism(s) in urine at a concentration of 10(4) colony-forming units per milliliter or greater. RESULTS Kaplan-Meier analysis demonstrated that it took significantly longer for patients (n = 56) who received the antimicrobial-impregnated catheters to develop bacteriuria than those (n = 68) who received the control catheters (P = 0.006 by the log-rank test). Patients who received the antimicrobial-impregnated catheters had significantly lower rates of bacteriuria than those in the control group both at day 7 (15.2% versus 39.7%) and at day 14 (58.5% versus 83.5%) after catheter insertion. Patients who received the antimicrobial-impregnated catheters had significantly lower rates of gram-positive bacteriuria than the control group (7.1% versus 38.2%; P <0.001) but similar rates of gram-negative bacteriuria (46.4% versus 47.1%) and candiduria (3.6% versus 2.9%). The antimicrobial-impregnated catheters provided zones of inhibition against Enterococcus faecalis and Escherichia coli, both at baseline and on removal. CONCLUSIONS Bladder catheters impregnated with minocycline and rifampin significantly reduced the rate of gram-positive catheter-associated bacteriuria up to 2 weeks after catheter insertion.

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.

Management of Central Venous Catheters in Patients with Cancer and Candidemia

To determine the need and appropriate timing of catheter removal in patients with candidemia, the records for 404 patients with cancer and central venous catheters (CVCs) who developed candidemia during the period of 1993-1998 were retrospectively reviewed. Of the total 404 cases of candidemia, 241 (60%) were due to a primary source, 111 (27%) were catheter related, and 52 (13%) were secondary cases of candidemia caused by a source other than the catheter. Multivariate analysis showed that catheter removal < or =72 h after onset improved response to antifungal therapy exclusively in patients with catheter-related candidemia (P=.04). Clinical characteristics that suggested a noncatheter source for the candidemia were disseminated infection (P<.01), previous chemotherapy (P<.01), previous corticosteroid therapy (P=.02), and poor response to antifungal therapy (P<.03). CVC removal < or =72 h after onset should be considered in patients with suspected catheter-related candidemia who have no evidence of dissemination, recent corticosteroid therapy, or chemotherapy.