Ethanol-lock technique in the treatment of bloodstream infections in pediatric oncology patients with broviac catheter. Routine changing of intravenous administration sets does not reduce colonization or infection in central venous catheters. A prospective randomized trial of urokinase as an adjuvant in the treatment of proven Hickman catheter sepsis. A prospective double-blind randomized trial of urokinase flushes to prevent bacteremia resulting from luminal colonization of subcutaneous central venous catheters. Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial. No difference in catheter sepsis between standard and antiseptic central venous catheters. A prospective randomized trial. Prophylactic urokinase in the management of long-term venous access devices in children: a Children's Oncology Group study. What really affects the incidence of central venous catheter-related infections for short-term catheterization? Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial.
To assess the ethanol-lock technique as a means of treating central venous line infections. Bloodstream infections in patients with tunneled central venous catheters can lead to removal of the lines.
                Twenty-eight children and adolescents aged 2 to 18 years, with different types of cancer, had Broviac catheters and presented with positive blood culture and clinical signs of infection between January 2000 and December 2001. The ethanol-lock technique was performed 24 times in 18 patients in addition to empiric (initially) and specific (after antibiogram) intravenous antibiotic treatment. In another 15 cases, 13 children were treated with systemic antibiotics alone.
                Sixty-seven percent of the patients treated with ethanol locks had no infectious relapse of any kind within 4 weeks of treatment or during subsequent aplasia, compared with 47% treated with systemic antibiotics alone. In one boy the catheter infection could not be cleared with systemic antibiotics alone, but after one course of ethanol locks no more blood culture-positive infectious episodes were observed. No severe clinical side effects of ethanol flush were observed. Mild symptoms that occurred were tiredness, headaches, dizziness, nausea, and light-headedness.
                The ethanol-lock technique appears to be a safe, well tolerated, and effective way to treat central venous line infections, even in small children. A prospective randomized study should be designed to compare antibiotic-lock, ethanol-lock technique, and systemic antibiotics alone in the treatment of device-associated bloodstream infection. To determine the effect of routine intravenous (IV) administration set changes on central venous catheter (CVC) colonization and catheter-related bacteremia.
                Prospective, randomized, controlled trial.
                Eighteen-bed intensive care unit (ICU) in a large metropolitan hospital.
                Two hundred fifty-one patients with 404 chlorhexidine gluconate and silver sulfadiazine-coated multi-lumen CVCs.
                CVCs inserted in the ICU and in situ on day 4 were randomized to have their IV administration sets changed on day 4 (n = 203) or not at all (n = 201). Use of fluid containers and blood product administration sets was limited to 24 hours. CVCs were removed when not required, infection was suspected, or in place on day 7. Catheter cultures were performed on removal by blinded laboratory staff. Catheter-related bacteremia was diagnosed by a blinded intensivist using strict definitions. Data were collected regarding catheter duration, site, Acute Physiology and Chronic Health Evaluation (APACHE) II score, patient age, diagnosis, hyperglycemia, hypoalbuminemia, immune status, number of fluid containers and IV injections, and administration of propofol, blood, total parenteral nutrition, or lipid infusion.
                There were 10 colonized CVCs in the group receiving a set change and 19 in the group not receiving one. This difference was not statistically significant on Kaplan-Meier survival analysis. There were 3 cases of catheter-related bacteremia per group. Logistic regression found that burns diagnosis and increased ICU stay significantly predicted colonization.
                IV administration sets can be used for 7 days in patients with short-term, antiseptic-coated CVCs. Chronic vascular access catheters have become an important adjunct to the treatment of children with complex medical diseases, particularly malignancy. One of the major complications of chronic venous access devices is bacterial infection of the catheter site and bloodstream. Infusion of systemic antibiotics directly into the catheter has been the standard initial therapy with failure leading to catheter removal and replacement. It has been suggested by a number of investigators that the addition of urokinase as a thrombolytic agent to lyse any accumulated thrombus or fibrin would increase the successful catheter clearance by antibiotics. This study was designed as a prospective, randomized trial to compare treatment of children with positive catheter blood cultures with either antibiotics alone or in combination with urokinase 5,000 U boluses 12 and 24 hours after study entry.
                A total of 63 patients were entered in the study. Thirty-three received antibiotics and urokinase, and 30 received antibiotics alone.
                A total of 45 catheters (71%) were cleared of infection and salvaged. Treatment failures leading to catheter removal occurred in 9 of 33 in the experimental group and 9 of 30 in the control population (no significant difference).
                Urokinase could not be shown to act as an adjuvant in the clearance of infection from chronic central venous access catheters that had no evidence of clot or thrombus. This study required the performance of a dye study and excluded any patient with a known thrombus. This conclusion must therefore be limited to patients with no evidence of a clot or fibrin sheath. This study was undertaken to determine if central venous catheter (CVC)-related infection in children with cancer could be prevented by monthly flushing of the catheter with urokinase.
                Between August 1994 and July 1998, 103 patients with cancer were randomized at the time of subcutaneous CVC placement to receive monthly flushing of their catheters with either 5000 IU of urokinase-heparin or heparin alone. Patients subsequently had blood cultures taken from their CVCs during an episode of fever.
                Seventy-four of the 103 patients (72%) enrolled in the study received at least 6 catheter flushes: 40 with urokinase-heparin and 34 with heparin. The median number of flushes was 9.5 in the urokinase-heparin group and 10.2 in the heparin-only group (P = 0.62). There were 5 positive blood cultures in the urokinase-heparin group and seven in patients receiving heparin alone (P = 0.27). Staphylococcus epidermidis was isolated from the blood of 3 patients receiving urokinase-heparin and 6 in those receiving heparin alone (P = 0.17).
                Prophylactic monthly catheter flushes with 5000 IU urokinase did not significantly decrease the number of documented bacteremic events in children with cancer who have CVCs. We did a randomised, double-blind, controlled clinical trial to prospectively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria.
                251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic susceptibility tests using multiple combination bactericidal antibiotic testing (MCBT). Patients who developed an exacerbation of pulmonary disease were randomised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT. The primary outcome was time from randomisation until the patient's next pulmonary exacerbation. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN60187870.
                132 patients had a pulmonary exacerbation and were randomised during the 4.5-year study period. The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group (hazard ratio 0.86 in favour of the conventionally-treated group, 95% CI 0.60-1.23, p=0.40). There was no difference between the groups in treatment failure rate. After 14 days of intravenous antibiotic therapy, changes in lung function, dyspnoea, and sputum bacterial density were similar in both groups.
                Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by standard culture and sensitivity techniques. The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations. To determine the efficacy of antiseptic compared with standard triple lumen central venous catheters (CVCs) in reducing the incidence of catheter sepsis and catheter site infection in patients with CVCs for total parenteral nutrition.
                A prospective, randomized, controlled trial.
                Truman Medical Center, the public teaching hospital for University of Missouri, Kansas City, School of Medicine.
                Seventy-two inpatients on the Metabolic Support Service received a CVC for the infusion of total parenteral nutrition. Diagnoses included pancreatic disease, cancer, bowel obstruction, and intestinal surgery, among others. Patients who had a higher risk for contamination during insertion, such as those with a catheter placed through an introducer, inserted in the emergency department, or changed over a guidewire were excluded from the study.
                The control group received a standard CVC without antiseptics. The treatment group received a CVC with a coating of silver sulfadiazine and chlorhexidine gluconate. Each CVC was inspected for infection or malfunction by the Metabolic Support Service 5 times per week. A transparent occlusive dressing was changed every 7 days or more often if there were signs of infection or nonocclusion. When the CVC was removed, the catheter tip, the blood, and the insertion site were cultured.
                Although 88 catheters were inserted, only 72 catheters were evaluable. There were 40 patients in the standard group and 32 in the antiseptic group. There were no statistically significant differences between the 2 groups for diagnosis, sex, age, length of stay, days with a CVC, or catheter location. The catheter sepsis rate in the standard group was 8% and in the antiseptic group it was 6%. There were no statistically significant differences between the 2 groups in frequency of site infections or catheter sepsis.
                In this study, there were no statistically significant differences in the incidence of catheter-related sepsis or catheter site infections between the standard and antiseptic groups. Future prospective, randomized controlled trials with a larger number of antiseptic catheters are encouraged to confirm or refute these results. Infection and thrombosis are serious complications of long-term vascular access devices in children undergoing chemotherapy. Since routine fibrinolytic therapy may decrease these complications, the purpose of this study was to compare the efficacy of an every-2-week administration of urokinase with standard heparin flushes in reducing the incidence of device-related infections and occlusions.
                This study was a prospective, randomized phase III multicenter trial conducted by the Children's Cancer Group, in which patients with implantable ports or tunneled catheters received either urokinase or heparin every 2 weeks for 12 months. Study end points were time to first occlusion or time to first device-related infection.
                Five hundred seventy-seven patients from 29 institutions were enrolled, of whom 51% had external catheters and 49% had ports. Urokinase administration resulted in fewer occlusive events than heparin (23% v 31%; P =.02), a longer time to first occlusive event (log-rank analysis, P =.006), and a 1.6-fold difference in the rate of occlusive events (Poisson regression, P =.003). Similar results were noted when comparing ports and tunneled catheters. The urokinase group also had a 1.4-fold difference in the rate of infection (Poisson regression, P =.05) and longer time to first infection (log-rank, P =.07), but the difference was significant only in tunneled catheters.
                Urokinase administration every 2 weeks significantly affects the rate of occlusive events in ports and tunneled catheters and of infectious events in external catheters compared with heparin administration. Central venous catheterization is one of the important sepsis reasons in surgical patients. In this randomized controlled study, the effect of the frequency and type of catheter site care, as well as age, coexisting malignancy or diabetes mellitus, total parenteral nutrition administration and antibiotics use, on central venous catheter infection was investigated. Seventy-two single-lumen polyurethane catheters were included. In group I (n: 33), a transparent occlusive dressing was applied to the insertion site and not removed for 7 days unless there were signs of local infection. In group II (n: 39), daily site care was done with povidone-iodine 10% solution and a new sterile gauze was applied. Chi-square, linear correlation and multiple regression tests were used for statistical analysis. Mean duration of catheters was 8 +/- 4 days. There was no catheter-related sepsis. Ten (13.9%) patients had positive catheter tip cultures of whom three had site infection as well. The incidence of site and tip infections were not significantly different in group I and II (p > 0.05). Site infection and age younger than 60 years significantly increased the rate of tip infection (p: 0.004 and p: 0.02 respectively). Total parenteral nutrition administration was associated with higher rate of tip infection (p: 0.06). Coexisting malignancy or diabetes mellitus, duration of catheter and antibiotics use did not have any significant effect on the rate of central venous catheter infections (p > 0.05). In conclusion, we observed that the frequency of insertion site care and the type of dressing applied to the site had no significant effect on the rate of CVC infection. Insertion site infection was the most significant factor increasing the incidence of catheter tip infection. The use of the CVC for total parenteral nutrition facilitated tip infection as well. Bacterial infection may adversely affect the hemostasis of patients with gastroesophageal variceal bleeding (GEVB). Antibiotic prophylaxis can prevent bacterial infection in such patients, but its role in preventing rebleeding is unclear. Over a 25-month period, patients with acute GEVB but without evidence of bacterial infection were randomized to receive prophylactic antibiotics (ofloxacin 200 mg i.v. q12h for 2 days followed by oral ofloxacin 200 mg q12h for 5 days) or receive antibiotics only when infection became evident (on-demand group). Endoscopic therapy for the GEVB was performed immediately after infection work-up and randomization. Fifty-nine patients in the prophylactic group and 61 patients in the on-demand group were analyzed. Clinical and endoscopic characteristics of the gastroesophageal varices, time to endoscopic treatment, and period of follow-up were not different between the two groups. Antibiotic prophylaxis decreased infections (2/59 vs. 16/61; P <.002). The actuarial probability of rebleeding was higher in patients without prophylactic antibiotics (P =.0029). The difference of rebleeding was mostly due to early rebleeding within 7 days (4/12 vs. 21/27, P =.0221). The relative hazard of rebleeding within 7 days was 5.078 (95% CI: 1.854-13.908, P <.0001). The multivariate Cox regression indicated bacterial infection (relative hazard: 3.85, 95% CI: 1.85-13.90) and association with hepatocellular carcinoma (relative hazard: 2.46, 95% CI: 1.30-4.63) as independent factors predictive of rebleeding. Blood transfusion for rebleeding was also reduced in the prophylactic group (1.40 +/- 0.89 vs. 2.81 +/- 2.29 units, P <.05). There was no difference in survival between the two groups. In conclusion, antibiotic prophylaxis can prevent infection and rebleeding as well as decrease the amount of blood transfused for patients with acute GEVB following endoscopic treatment.
No significant effect of urokinase or ethanol lock in addition to systemic antibiotics was found. However, this could be due to low power or a too-short follow-up. The cohort studies identified no adverse events; some cohort studies reported CVC malfunctioning. No RCTs or CCTs were published on antibiotic lock treatment alone. More well-designed RCTs are needed to further explore the effect of antibiotic or other lock treatments in the treatment of CVC-related infections in children with cancer.