Catheter Lock Solution Research Articles

Exit of catheter lock solutions from double lumen acute haemodialysis catheters an in vitro study

Double lumen dialysis catheters are routinely heparin or citrate 'locked' to maintain patency. Heparin lock-related bleeding episodes and antibiotic lock-related toxicity have been reported. The aim of this study is to quantify the amount of leak during 'lock' procedures and to compare leakage for different double lumen dialysis catheters. In an experimental, in vitro study at a University research laboratory, five different double lumen dialysis catheters were tested using three different lock volumes. Using the catheter flush volume, leak ratios for Flexxicon II 15 cm and 20 cm catheters were greater than that seen in the Arrow 16 cm catheter (P < 0.05). Using 20% less than the catheter flush volume, the Flexxicon II 20 cm catheter had greater leak than the Duo-flow 15 and 20 cm catheters and Arrow 16 cm catheter (P < 0.05). The Flexxicon II 15 cm catheter had greater leak than the Duo-flow 15 cm and Duo-flow 20 cm catheters with 20% less locking volume (P < 0.05). Using 20% greater than the catheter flush volume, the Duo-flow 20 cm catheter had significantly less leak ratio than the Flexxicon II 20 cm catheter (P < 0.05). There were no other significant differences in leak ratios between the catheters. All double lumen dialysis catheters we tested have a substantial amount of leak even when the catheter 'lock' volumes were used, and leak ratio increases significantly with 20% overfill. There is a leak even when using 20% less 'lock' volume. The amount of leak can be clinically important and may explain the reports of bleeding episodes after heparin lock and antibiotic toxicity after antibiotic and anticoagulant combination lock. Some devices have lower leak ratios than others, likely related to catheter design.

Use of Antimicrobial Catheter Lock Solutions to Prevent Catheter-Related Bacteremia

Catheter-related bacteremia is an important source of morbidity and mortality in hemodialysis patients. A number of well-designed, controlled, prospective trials using antimicrobial catheter lock solutions to prevent catheter-related bacteremia have shown a dramatic, statistically significant decrease in not only infection but also mortality related to catheter-related bacteremia. Despite evidence of significant benefit, these locks are not routinely used in the United States. This review describes the epidemic problem of catheter-related bacteremia, reviews recent clinical trials with antimicrobial catheter lock solutions, and discusses current options and potential indications for catheter lock solutions in the hemodialysis population.

Concentrated Heparin Lock Is Associated with Major Bleeding Complications after Tunneled Hemodialysis Catheter Placement

Vascular access complications, including thrombosis, are associated with significant patient morbidity and mortality. Currently, up to 60% of new patients and 30% of prevalent patients are using a catheter for dialysis. To prevent interdialytic catheter thrombosis, these devices are routinely locked with concentrated heparin solutions. Several recent studies have elucidated the potential for abnormal coagulation markers (aPTT) that may arise from this practice. This abnormal elevation in aPTT may be explained by significant early and late leakage from the catheter that occurs after performing a catheter lock. To date no study has evaluated the impact of this practice, or the elevation in aPTT that may result from it, on bleeding complication rates. We conducted a retrospective analysis comparing bleeding rates in subjects who received concentrated heparin catheter lock (5000 u/cc) [group 1, n = 52] to those who received citrate or dilute heparin catheter lock (1000 u/cc) [group 2, n = 91] immediately after tunneled hemodialysis catheter insertion. Baseline characteristics did not differ between the groups except for the preprocedure INR, which was higher in the postpolicy group compared with the prepolicy group (1.29 vs. 1.21, p = 0.04). Results from logistic regression analyses revealed that the likelihood of a composite bleeding event in group 1 was 11.9 times that of a composite bleeding event in group 2, p = 0.04. Concentrated heparin (5000 u/ml) is associated with increased major bleeding complications posttunneled catheter placement compared with low-dose heparin (1000 u/ml) or citrate catheter lock solution, p = 0.02. Given the findings of this study, a randomized controlled trial comparing the safety and efficacy of common anticoagulation lock solutions is warranted.

In vitro activity of daptomycin and vancomycin lock solutions on staphylococcal biofilms in a central venous catheter model

Catheter lock solutions are used for prevention and management of catheter-related bloodstream infections. We investigated the activity of daptomycin and vancomycin lock solutions against Staphylococcus aureus and Staphylococcus epidermidis in an in vitro central venous catheter (CVC) model. Biofilm-producing reference strains of S. aureus and S. epidermidis were evaluated. After 24 h of bacterial growth in a CVC model, daptomycin and vancomycin bactericidal activity (+/- preservative-containing heparin sodium) were separately evaluated as a lock solution using 0.5, 1 and 35 mg/ml. Calcium carbonate (50 mg/l) was added to all lock solutions containing daptomycin. Each CVC was drained, flushed and sonicated at 72 h to assess CFU/ml. After 72 h of exposure in the catheter lock solutions, daptomycin and vancomycin at 0.5, 1 and 5 mg/ml demonstrated bactericidal activity (>3.0 log10 CFU/ml) against S. aureus and S. epidermidis (P <or= 0.001). Heparin lock solution alone produced a non-significant reduction in S. aureus and S. epidermidis (1.92 +/- 0.07 and 1.65 +/- 0.03 log10 CFU/ml, respectively). Daptomycin 5 mg/ml lock solution +/- heparin eradicated (limit of detection 2.0 log10 CFU/ml) S. epidermidis at 72 h as did the vancomycin 5 mg/ml plus heparin. S. aureus was only eradicated from the daptomycin 5 mg/ml catheter lock-solution. Our CVC model demonstrated that 72 h of exposure to 5 mg/ml lock solutions of daptomycin (plus calcium), +/- heparin or 5 mg/ml of vancomycin plus heparin demonstrate promise in treating catheter infections with biofilm-producing S. epidermidis. Similarly, 5 mg/ml of daptomycin (plus calcium) as a lock solution shows great promise in treating S. aureus catheter infections.

Catheter Lock Solutions to Prevent Bloodstream Infections in High-Risk Hemodialysis Patients

Background: Antimicrobial catheter lock solutions (CLS) have been shown to prevent bacteremia in chronic hemodialysis (HD) patients with new HD catheters. However, there is little information regarding the usage of these solutions in patients who have a history of recurrent bacteremia and are at very high risk of infection. The purpose of this investigation was to identify the efficacy of these solutions in such high-risk patients. Methods: A retrospective chart review was performed to identify patients who had a history of recurrent bacteremia and had received prophylaxis with antimicrobial CLS. Results: Nine patients with recurrent bacteremia were identified. These patients had received prophylaxis with minocycline/EDTA, gentamicin/heparin, or vancomycin/heparin solutions. The catheter-related bacteremia rate was 9.13 per 1,000 catheter days prior to the use of CLS, 1.04 during use of solution, and 7.94 after the CLS were discontinued (p < 0.001). Conclusions: These results show a dramatic effect of antimicrobial CLS on the prevention of catheter-related bacteremia.

Activity of sodium metabisulfite against planktonic and biofilm Staphylococcus species

Biofilm-forming staphylococci cause a majority of intravascular catheter-related infections. We evaluated the effect of sodium metabisulfite, a preservative commonly added to intravenously administered pharmaceuticals as an antioxidant and previously used as a catheter lock solution, on planktonic and biofilm staphylococci at clinically encountered concentrations. Sodium metabisulfite exhibited bactericidal activity against planktonic Staphylococcus aureus, Staphylococcus lugdunensis, and Staphylococcus epidermidis at concentrations of 512, 512, and 1024 μg/mL, respectively. A concentration of 720 μg/mL inhibited cell growth by all 3 species in a biofilm formation assay. However, established S. aureus and S. lugdunensis biofilms showed less than 1.5 log 10 decreases in viable cell counts when treated with 720 μg/mL of sodium metabisulfite for 24 h. These in vitro results suggest that the use of sodium metabisulfite as a catheter lock may inhibit staphylococcal colonization of catheters, thereby preventing catheter-related infection.

Optimal Antimicrobial Catheter Lock Solution, Using Different Combinations of Minocycline, EDTA, and 25-Percent Ethanol, Rapidly Eradicates Organisms Embedded in Biofilm

Antimicrobial lock solutions may be needed to salvage indwelling catheters in patients requiring continuous intravenous therapy. We determined the activity of minocycline, EDTA, and 25% ethanol, alone or in combination, against methicillin-resistant Staphylococcus aureus and Candida parapsilosis catheter-related bloodstream infection strains in two established models of biofilm colonization. Biofilm-colonized catheter segments from a modified Robbins device and a silicone disk biofilm colonization model were exposed to these antimicrobial agents for 15 or 60 min, respectively. After exposure, segments were sonicated and cultured. To determine regrowth after incubation at 37 degrees C, following the brief exposure to the antimicrobial agents, an equal number of segments were washed, reincubated for 24 h, and then sonicated and cultured. The triple combination of minocycline-EDTA (M-EDTA) in 25% ethanol was the only antimicrobial lock solution that completely eradicated S. aureus and C. parapsilosis in biofilm of all segments tested in the two models, and it completely prevented regrowth. In addition, M-EDTA in 25% ethanol was significantly more effective in rapidly eradicating the growth or regrowth of methicillin-resistant S. aureus and C. parapsilosis biofilm colonization in the two models than the other solutions--minocycline, EDTA, M-EDTA, 25% ethanol, and EDTA in ethanol. We conclude that M-EDTA in 25% ethanol is highly effective at rapidly eradicating S. aureus and C. parapsilosis embedded in biofilm adhering to catheter segments.

Catheter Lock Solutions: It is Time for a Change

Catheter Lock Solutions: It is Time for a Change

Comparison of Low-Dose Gentamicin With Minocycline as Catheter Lock Solutions in the Prevention of Catheter-Related Bacteremia

Catheter-restricted antibiotic lock solutions were found to be effective in the prevention of catheter-related bacteremia (CRB), but insufficient data are available about the ideal agent and dose. We hypothesized that a low concentration of gentamicin would be as effective as the high doses studied in the past. In this prospective, open-labeled, randomized, clinical trial of patients on long-term hemodialysis therapy, patients were randomly assigned to administration of an antibiotic lock solution of gentamicin/citrate (4 mg/mL), minocycline/EDTA, or the control solution of heparin. Patients were followed up until the study end point of CRB was reached or a censoring event occurred. Interim data analysis was performed after 6 months to assess data safety; efficacy was noted and the study was terminated early. Sixty-two patients were enrolled into the study, evenly distributed in 3 arms, with data from 1 patient excluded from analysis. Seven of 20 patients in the heparin group (4.0 events/1,000 catheter days), 1 of 21 patients in the minocycline group (0.4 events/1,000 catheter days), and none of 20 patients in the gentamicin group developed bacteremia. Results were statistically significant by using 2-tailed Fisher exact test; heparin versus gentamicin, P = 0.008, and heparin versus minocycline, P = 0.020. Antibiotic lock solutions are superior to the standard heparin lock alone in the prevention of CRBs, and low-dose gentamicin solution has efficacy similar to that of greater concentrations used in previous studies.

Sodium citrate 4% locking solution for central venous dialysis catheters--an effective, more cost-efficient alternative to heparin

Thrombosis of the central venous haemodialysis catheter compromises dialysis adequacy and catheter survival. Heparin containing catheter-locking solution has been associated with bleeding, interferes with INR (prothrombin time/international normalized ratio) measurements and is costly. Sodium citrate has been used successfully as a catheter-locking solution, but long-term experience with its use as the exclusive locking solution has not been published. Our haemodialysis unit converted to locking all central venous haemodialysis catheters with sodium citrate 4% instead of heparin 10 000 U/ml. A retrospective analysis compared the outcomes of the year prior and after the conversion. Flow-related catheter exchange rate, prevalence of INR assay interference, tissue plasminogen activator (rt-PA) utilization rate, rate of bacteraemias and annual cost of locking agent were examined. During the study period, 30 925 and 37 139 catheter days were identified during the heparin and citrate years, respectively. The rate of flow-related catheter exchange was not different during the two periods (1.81 vs 1.88 per 1000 catheter days, P = 0.89). Falsely elevated INR values were eliminated with citrate and the rate of rt-PA treatments was similar during the two periods (4.1 vs 3.23 per 1000 catheter days respectively, P = 0.07). The number of bacteraemias was similar during the two periods (0.77 vs 0.94 per 1000 catheter days respectively, P = 0.36) There was an 85% reduction in the costs associated with catheter-locking therapy during the citrate period. The pharmaco-economic benefits of sodium citrate 4% are well supported by this analysis. Furthermore, citrate offers several clinical advantages over concentrated heparin: citrate lock avoids heparin-associated bleeding complications, improves reliability of INR assays and provides an effective alternative for patients with suspected or confirmed heparin-induced thrombocytopenia.

Catheter lock solutions: it's time for a change

In recent years, the number of patients on hemodialysis (HD) with central vascular catheters (CVCs) has grown. However, CVC use is often associated with an important risk for catheter related bloodstream infections (CR-BI) and inadequate dialysis due to flow problems. In this study, we reviewed alternative solutions to heparin for locking HD CVCs. Several experiences have demonstrated that trisodium citrate (TSC) (30-47%), citrate (4%) and taurolidine (1.35%) solutions are effective and safe for the prevention of CRBI, while heparin stimulates biofilm formation. High citrate (47%) concentrations can also provide significant advantages in reducing catheter clotting, but controlled studies with larger populations are necessary to confirm and to extend the use of such solutions in clinical practice. Side effects with high sodium citrate concentrations have been reported only immediately after locking, the symptoms are probably caused by a temporary drop in ionized calcium and magnesium, but it is evident that these solutions should only be used by skilled and authorized personnel, with a rigorous protocol.

Comparative In Vitro Efficacies of Various Catheter Lock Solutions

MEDTA (minocycline-edetate calcium disodium), taurolidine (2%)-polyvinylpyrolidine (5%) (T/PVP), and ethanol as potential catheter lock solutions have a unique mechanism of action, broad-spectrum activity, and anticoagulant properties. Traditional lock solutions minocycline (M), rifampin (R), ciprofloxacin (C), and vancomycin, except pharmacologic concentrations of C and R and of M and R, were less effective than MEDTA and T/PVP.

Catheter lock solutions influence staphylococcal biofilm formation on abiotic surfaces

Microbial biofilms form on central venous catheters and may be associated with systemic infections as well as decreased dialysis efficiency due to catheter thrombosis. The most widely used anticoagulant catheter lock solution in the US is sodium heparin. We have previously shown that sodium heparin in clinically relevant concentrations enhances Staphylococcus aureus biofilm formation. In the present study, we examine the effect of several alternative catheter lock solutions on in vitro biofilm formation by laboratory and clinical isolates of S. aureus and coagulase-negative staphylococci (CNS). Lepirudin, low molecular weight heparin, tissue plasminogen activator, sodium citrate, sodium citrate with gentamicin and sodium ethylene diamine tetra-acetic acid (EDTA) were assessed for their effect on biofilm formation on polystyrene, polyurethane and silicon elastomer. Sodium citrate at concentrations above 0.5% efficiently inhibits biofilm formation and cell growth of S. aureus and Staphylococcus epidermidis. Subinhibitory concentrations of sodium citrate significantly stimulate biofilm formation in most tested S. aureus strains, but not in CNS strains. Sodium EDTA was effective in prevention of biofilm formation as was a combination of sodium citrate and gentamicin. Low molecular weight heparin stimulated biofilm formation of S. aureus, while lepirudin and tissue plasminogen activator had little effect on S. aureus biofilm formation. This in vitro study demonstrates that heparin alternatives, sodium citrate and sodium EDTA, can prevent the formation of S. aureus biofilms, suggesting that they may reduce the risk of biofilm-associated complications in indwelling catheters. This finding suggests a biological mechanism for the observed improvement in catheter-related outcomes in recent clinical comparisons of heparin and trisodium citrate as catheter locking solutions. A novel and potential clinically relevant finding of the present study is the observation that citrate at low levels strongly stimulates biofilm formation by S. aureus.

MICROBIAL INACTIVATION PROPERTIES OF METHYLENE BLUE - CITRATE SOLUTION

Background. A practical antimicrobial catheter lock solution should have a wide safety margin, broad and rapid antimicrobial properties, and should not induce microbial resistance. Methods. A solution of 0.05% methylene blue (MB) and 7% sodium citrate at pH 6.2 with a preservative was tested against gram positive and gram negative bacteria and fungi from hospital isolates and ATCC. Some of the tested organisms were: E. coli, P. aeruginosa, E. feacalis, S. aureus (also MRSA), S. epidermidis, C. albicans, A. niger, and the halophilic bacterium V. vulnificus. The initial concentration of challenge suspensions was >106 CFU/mL bacteria, or >104 CFU/mL fungi. A study was also performed to evaluate the anti-biofilm properties of lock solution. The challenge organism was S. aureus (clinical isolate) perfused in plasma over polycarbonate strips alternating with lock solution. Results. For most tested strains a 99.99% reduction was obtained after 2 minutes of exposure to antibacterial solution, and in others this reduction was obtained in less than 1 hour. In control saline solution, concentration of microorganisms remained unchanged for 3 days. Studies of various components demonstrated synergistic rather than additive effects. The lock solution reduces CFU in biofilm from 105 CFU/mL to zero, even after repeated exposure to S. aureus in plasma. Conclusion. MB/citrate solution is microbicidal against all organisms tested. A randomized prospective multi-center trial is now beginning to compare CRBSI in CVC for dialysis, comparing the lock solution and heparin.

Prevention of uncuffed hemodialysis catheter-related bacteremia using an antibiotic lock technique: A prospective, randomized clinical trial

As a result of the high rate of infection, the NKF-K/DOQI guidelines recommended that an uncuffed catheter (UC) should not be used for longer than three weeks. However, the findings of the Dialysis Outcomes and Practice Patterns Study recognized that 48% of new hemodialysis patients in the US and 75% in Europe used UC for temporary access during arteriovenous fistula or graft maturation. The antibiotic lock technique (ALT) has been recommended to prevent catheter-related bacteremia (CRB). Here, we prospectively evaluated the efficacy of catheter-restricted filling using an antibiotic lock solution in preventing CRB. A total of 120 new hemodialysis patients requiring a temporary catheter while waiting for placement and maturation of an arteriovenous fistula or graft were enrolled in this study. Patients with a UC were randomly assigned to receive either an antibiotic-heparin lock solution (antibiotic group: cefazolin 10 mg/ml, gentamicin 5 mg/ml, heparin 1000 U/ml) or a heparin lock solution (no-antibiotic group: heparin 1000 U/ml) as a catheter lock solution during the interdialytic period. The end point of the trial was CRB. CRB developed in seven (11.7%) patients in the no-antibiotic group (Staphylococcus aureus, two; Staphylococcus epidermidis, five) whereas only one patient in the antibiotic group had S. aureus bacteremia. CRB rates per 1000 catheter-days were 0.44 in the antibiotic group versus 3.12 in the no-antibiotic group (P=0.031). Kaplan-Meier analysis also showed that mean CRB-free catheter survival of 59 days (95% CI, 58-61 days) in the antibiotic group was greater than that in the no-antibiotic group (55 days; 95% CI, 50-59 days). The results suggest that ALT may be a beneficial means of reducing the CRB rate in hemodialysis patients with UC.

117 Safety of 70% ethanol as an antiseptic catheter-lock solution for tunneled polyurethane central venous catheters (CVC): Randomized placebo controlled trial

117 Safety of 70% ethanol as an antiseptic catheter-lock solution for tunneled polyurethane central venous catheters (CVC): Randomized placebo controlled trial

Randomized, Clinical Trial Comparison of Trisodium Citrate 30% and Heparin as Catheter-Locking Solution in Hemodialysis Patients

Interdialytic hemodialysis catheter-locking solutions could contribute to a reduction of catheter-related complications, especially infections. However, they can cause side effects because of leakage from the tip of the catheter. Recently, trisodium citrate (TSC) has been advocated because of its antimicrobial properties and local anticoagulation. In a multicenter, double-blind, randomized, controlled trial, TSC 30% was compared with unfractionated heparin 5000 U/ml for prevention of catheter-related infections, thrombosis, and bleeding complications. The study was stopped prematurely because of a difference in catheter-related bacteremia (CRB; P < 0.01). Of 363 eligible patients, 291 could be randomized. The study included 98 tunneled cuffed catheters and 193 untunneled. There were no significant differences in patient and catheter characteristics on inclusion. In the heparin group, 46% of catheters had to be removed because of any complication compared with 28% in the TSC group (P = 0.005). CRB rates were 1.1 per 1000 catheter-days for TSC versus 4.1 in the heparin group (P < 0.001). For tunneled cuffed catheters, the risk reduction for CRB was 87% (P < 0.001) and for untunneled catheters was 64% (P = 0.05). Fewer patients died from CRB in the TSC group (0 versus 5; P = 0.028). There were no differences in catheter flow problems and thrombosis (P = 0.75). No serious adverse events were encountered. Major bleeding episodes were significantly lower in the TSC group (P = 0.010). TSC 30% improves overall patency rates and reduces catheter-related infections and major bleeding episodes for both tunneled and untunneled hemodialysis catheters. Flow problems are not reduced.

Tetrasodium EDTA as a Novel Central Venous Catheter Lock Solution Against Biofilm

Central venous catheter (CVC)-related bloodstream infections (BSIs) are known to increase rates of morbidity and mortality in both inpatients and outpatients, including hematology-oncology patients and those undergoing hemodialysis or home infusion therapy. Biofilm-associated organisms on the lumens of these catheters have reduced susceptibility to antimicrobial chemotherapy. This study tested the efficacy of tetrasodium EDTA as a catheter lock solution on biofilms of several clinically relevant microorganisms. Biofilms of Staphylococcus epidermidis, methicillin-resistant S. aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Candida albicans were grown to levels of approximately 1 x 10(5) colony-forming units (CFU)/cm(-1) on CVC segments in a model system, then subjected to the tetrasodium EDTA lock treatment. Comparisons of biofilms before and after exposure to the 40-mg/mL(-1) tetrasodium EDTA lock for 21 hours showed that the biofilm viable cell counts of all organisms tested were significantly reduced (P < .05) after exposure to the treatment. Antimicrobial lock treatment using 40 mg/mL(-1) of tetrasodium EDTA for at least 21 hours could significantly reduce or potentially eradicate CVC-associated biofilms of clinically relevant microorganisms.

Loss of Catheter Locking Solution Caused by Fluid Density

The avoidance of clotting in catheter lumina between treatments usually entails locking with an anticoagulant solution such as heparin. In a previous work, it was shown that approximately 20% of locking solution flows from the catheter during instillation of the lock equal in volume to the lumen volume. Furthermore, the locking solution may spill into the blood stream under the influence of gravity. This work investigates the influence of density and viscosity of the locking solution on the volume and speed of locking solution loss from the catheter lumen. A large fraction of the catheter locking solution spills under the influence of gravity if the locking solution's density is higher than the fluid it spills to (blood). Locking solution lost is replaced by blood. Viscosity delays this process, but at 90 minutes after injection, the loss is completed even when highly viscous lock solutions are used. Slow administration of the lock has negligible influence upon the dynamics of the loss.

Alteplase as a Catheter Locking Solution: In Vitro Evaluation of Biochemical Stability and Antimicrobial Properties

To reduce potential complications of fibrin deposition to catheter surfaces, there is increasing empiric use of alteplase as a catheter lock solution. The purpose is to evaluate the properties of alteplase when reconstituted in sterile water (SW) or bacteriostatic water (BW) for prolonged periods. Alteplase in glass vials was reconstituted (1 mg/mL) with SW or BW (0.9% benzyl alcohol) in duplicates and stored at 37 degrees C. Biochemical assays were performed at days 0 and 7 and included optical clarity, protein concentration, percent protein monomer, and in vitro clot lysis activity. Microbiologic assays were performed on days 7 through 28 with use of a standardized antimicrobial effectiveness test (pass/fail) and pour-plate methods incubated at 22.5 degrees C (fungus, 3-7 days) or 32.5 degrees C (bacteria, 3-5 days). Organisms tested included Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger. Biochemical assay results were as follows: on day 0, all samples were clear/colorless; protein concentrations were 1.10 mg/mL +/- 0 in SW and 1.11 mg/mL +/- 0 in BW; percent protein monomer was 8.2% +/- 0.07 in SW and 98.6% +/- 0.07 in BW; and in vitro clot lysis activity (in percent of relative activity) was 100% in all samples. On day 7, all samples were clear/colorless, protein concentrations were 1.11 mg/mL +/- 0.07 in SW and 1.11 mg/mL +/- 0.07 in BW; percent protein monomer was 97.4% +/- 0.21 in SW and 96.1% +/- 0.21 in BW; and in vitro clot lysis activity (relative activity compared with day 0) was 91% +/- 2.8 in SW and 90% +/- 2.8 in BW. Microbiologic assays (US Pharmacopeia [USP] antimicrobial effectiveness test) yielded a failing result for alteplase reconstituted in SW and a passing result for alteplase reconstituted in BW. Alteplase reconstituted with SW or BW remains relatively stable with retained bioactivity when stored at 37 degrees C for as long as 7 days. Despite the biochemical similarities of the two solutions, only alteplase in BW met USP criteria as an effective antimicrobial solution. Further clinical evaluation is warranted.