Effect of ethanol/trisodium citrate lock on microorganisms causing hemodialysis catheter-related infections.

PURPOSE: This in vitro study tested the effectiveness of a novel 30% ethanol/4% trisodium citrate (TSC) lock solution against the most common pathogens causing hemodialysis catheter-related infections. METHODS: Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (n = 4), methicillin-sensitive S. aureus (MSSA) (n = 8), methicillin-resistant Staphylococcus epidermidis (MRSE) (n = 8), Pseudomonas aeruginosa (n = 4) and Escherichia coli (n = 4) were tested in duplicate. Bacterial suspensions of each isolate were made in a control solution of normal saline and Mueller-Hinton broth (MHB), and in a lock solution of ethanol 30%, TSC 4% and MHB. Suspensions were incubated at 37 degrees C for 48 h. Colony counts were determined from samples collected at t = 0 h (before exposure to the ethanol/TSC lock), t = 1 h (one hour after exposure to the ethanol/TSC lock), t = 24 h and t = 48 h. To confirm the absence of viable organisms in the lock solution, the remaining volume at 48 h was filtered through a 0.45 microm filter. The filter was rinsed with 15 mL sterile water and plated on tryptic soy agar (TSA). RESULTS: All controls demonstrated significant growth over 48 h. In the lock solutions, initial inocula were reduced to 0 viable colonies by t = 1 h (6-log kill), and there was no growth at t = 24 and 48 h. Filtering of lock solutions also showed no growth. These results were consistent among duplicates of all isolates. CONCLUSIONS: The 30% ethanol/4% TSC lock solution consistently eradicated MRSA, MSSA, MRSE, P. aeruginosa and E. coli within 1 h of exposure. Experiments are currently underway to test this novel lock solution on preventing biofilm production by these pathogens.

Effect of ethanol/trisodium citrate lock on the mechanical properties of carbothane hemodialysis catheters.

AIMS: The objective of this study was to investigate the effect of three locking solutions on the mechanical properties of carbothane hemodialysis catheters. METHODS: Catheters were exposed in vitro to one of three locking solutions (heparin 5000 U/ml; 4% trisodium citrate (TSC) or 30% ethanol/4% TSC). Each solution was locked in six catheters and bathed at 37 degrees C for 9 weeks. Changes in the mechanical properties namely, force at break, elongation at break and elastic modulus of the catheters were determined by tensile testing. RESULTS: The ethanol/TSC lock has an effect on the properties of carbothane hemodialysis catheters. The force at break was significantly lower in the ethanol/TSC group compared to the heparin and TSC groups (113.26 N, 191.97 N and 229.72 N, respectively, p < 0.01). Similarly, elongation at break was lower in the ethanol/TSC group, compared to the heparin and TSC groups (stretched 21.97, 38.29, and 42.42 times original length respectively, p < 0.01). The elastic modulus was not significantly different. CONCLUSIONS: The effect of the ethanol/TSC lock on the catheters is unlikely to prohibit clinical use. After 9 weeks of exposure to the solution, the catheter segments could still be stretched to 22 times their length and withstand 11.5 kg (113 N) of force. Clinically produced forces during dialysis are many times smaller than the force required to break the catheters examined in this study. Therefore, the ethanol/TSC lock shows promise as a new catheter locking solution for the treatment of catheter-related infections. Further clinical studies are required.

Ethanol/trisodium citrate for hemodialysis catheter lock.

AIMS: The objective of this study was to confirm the compatibility of ethanol and 4% trisodium citrate (TSC) for potential use as a catheter locking solution. METHODS: Increasing concentrations of ethanol were combined with 4% TSC in glass test tubes and stored at 37 degrees C over 72 hours. Each tube was visually inspected to determine the highest compatible concentration. To confirm visual compatibility, HPLC analysis was used to compare the concentration of TSC in control solutions (n = 6) to solutions containing both TSC and the highest concentration of ethanol that was visually compatible (n = 6). Compatibility in carbothane hemodialysis catheters was then confirmed in vitro. RESULTS: Results of the compatibility tests indicated that 30% ethanol was the maximum concentration visually compatible with 4% TSC. Ethanol concentrations of 35% or above form a crystalline precipitate in the glass test tubes within 72 hours. HPLC analysis showed no difference in the concentration of TSC in the control solutions compared to the TSC/ethanol solutions when incubated in glass test tubes. A slight, but statistically significant increase in the TSC concentration (1.27%; p < 0.0001) was observed when the ethanol/TSC solution was incubated in carbothane hemodialysis catheters. This slight increase may be due to ethanol absorption into the catheter polymer. Further studies are underway to determine if an ethanol/TSC lock affects the mechanical properties of these carbothane hemodialysis catheters. CONCLUSIONS: We conclude that 30% ethanol is compatible with 4% trisodium citrate in carbothane hemodialysis catheters in vitro. Until the lock's affect on carbothane hemodialysis catheters is known, it cannot yet be recommended for clinical use.

Review of macrolides and ketolides: focus on respiratory tract infections.

The first macrolide, erythromycin A, demonstrated broad-spectrum antimicrobial activity and was used primarily for respiratory and skin and soft tissue infections. Newer 14-, 15- and 16-membered ring macrolides such as clarithromycin and the azalide, azithromycin, have been developed to address the limitations of erythromycin. The main structural component of the macrolides is a large lactone ring that varies in size from 12 to 16 atoms. A new group of 14-membered macrolides known as the ketolides have recently been developed which have a 3-keto in place of the L-cladinose moiety. Macrolides reversibly bind to the 23S rRNA and thus, inhibit protein synthesis by blocking elongation. The ketolides have also been reported to bind to 23S rRNA and their mechanism of action is similar to that of macrolides. Macrolide resistance mechanisms include target site alteration, alteration in antibiotic transport and modification of the antibiotic. The macrolides and ketolides exhibit good activity against gram-positive aerobes and some gram-negative aerobes. Ketolides have excellent activity versus macrolide-resistant Streptococcus spp. Including mefA and ermB producing Streptococcus pneumoniae. The newer macrolides, such as azithromycin and clarithromycin, and the ketolides exhibit greater activity against Haemophilus influenzae than erythromycin. The bioavailability of macrolides ranges from 25 to 85%, with corresponding serum concentrations ranging from 0.4 to 12 mg/L and area under the concentration-time curves from 3 to 115 mg/L x h. Half-lives range from short for erythromycin to medium for clarithromycin, roxithromycin and ketolides, to very long for dirithromycin and azithromycin. All of these agents display large volumes of distribution with excellent uptake into respiratory tissues and fluids relative to serum. The majority of the agents are hepatically metabolised and excretion in the urine is limited, with the exception of clarithromycin. Clinical trials involving the macrolides are available for various respiratory infections. In general, macrolides are the preferred treatment for community-acquired pneumonia and alternative treatment for other respiratory infections. These agents are frequently used in patients with penicillin allergies. The macrolides are well-tolerated agents. Macrolides are divided into 3 groups for likely occurrence of drug-drug interactions: group 1 (e.g. erythromycin) are frequently involved, group 2 (e.g. clarithromycin, roxithromycin) are less commonly involved, whereas drug interactions have not been described for group 3 (e.g. azithromycin, dirithromycin). Few pharmacoeconomic studies involving macrolides are presently available. The ketolides are being developed in an attempt to address the increasingly prevalent problems of macrolide-resistant and multiresistant organisms.

A critical review of oxazolidinones: an alternative or replacement for glycopeptides and streptogramins?

OBJECTIVE: To review the available data on the oxazolidinones linezolid and eperezolid. DATA SELECTION: Published reports were obtained by searching MEDLINE for articles published between 1992 and 2000, inclusive. References of published papers were also obtained and reviewed. Abstracts from scientific proceedings were reviewed. DATA EXTRACTION: Due to the limited data available regarding these agents, the criteria for study inclusion were not restrictive. DATA SYNTHESIS: The oxazolidinones (eg, linezolid) are a new antimicrobial class with a unique mechanism of action. They are active against resistant Gram-positive cocci including methicillin-susceptible and -resistant Staphylococcus aureus (MRSA), methicillin-susceptible and -resistant Staphylococccus epidermidis, vancomycin-resistant enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP). Linezolid is active against anaerobes and displays modest activity against fastidious Gram-negative pathogens such as Haemophilus influenzae, but is not active against Enterobacteriaceae. Linezolid is available both orally and parenterally, and has a bioavailability of 100%. Clinical trials comparing linezolid with standard therapy have demonstrated similar bacteriological and clinical cures rates to standard therapy in community- and hospital-acquired pneumonia, uncomplicated and complicated skin and soft tissue infections, and infections caused by MRSA and VRE. Adverse effects have been minor and infrequent; however, platelets should be monitored in patients who have received more than two weeks of linezolid therapy. It is expected that these agents will have a bright future due to their excellent spectrum of activity against antibiotic-resistant Gram-positive organisms, such as MRSA, VRE and PRSP, and their excellent bioavailability. CONCLUSION: The oxazolidinones represent a new class of antimicrobials with a unique mechanism of action. They have excellent activity against susceptible and resistant Gram-positive organisms such as MRSA, methicillin-susceptible S epidermidis, VRE and PRSP, and a good adverse effect profile; they can be administered both intravenously and orally. Their potential use in Canada may be as an intravenous and oral alternative to glycopeptides and streptogramins.

Antibiotic-heparin lock: in vitro antibiotic stability combined with heparin in a central venous catheter.

Long-term hemodialysis frequently requires vascular access through central venous catheters (CVCs). Infection related to these catheters is a significant complication. The use of an antibiotic-heparin lock could decrease the risks associated with infected permanent catheters. As an initial step in developing an antibiotic-heparin lock, we investigated the in vitro stability of antibiotic-heparin combinations in CVCs. Initially, cefazolin, vancomycin, ceftazidime, ciprofloxacin 10 mg/ml each, and gentamicin 5 mg/ml were incubated separately in glass test tubes in the dark at 37 degrees C for 72 hours. Samples were analyzed spectrophotometrically for stability at 24-hour intervals. The procedure was repeated with the addition of heparin (final concentration 5000 U/ml in glass test tubes), and the combination was also examined in CVCs. High-performance liquid chromatography analysis was conducted on the antibiotic-heparin combinations at 72 hours to confirm the spectrophotometric results. Ciprofloxacin produced an immediate precipitate with the addition of heparin and was not analyzed further. Absorbance values decreased for all antibiotics, with the greatest decreases at 72 hours for cefazolin (27.4%), vancomycin (29.7%), ceftazidime (40.2%), and gentamicin (8%) when combined with heparin. These decreases were postulated to be secondary to adsorption of the antibiotics to the luminal surface of the catheters because submitting the catheters to ultrasound with 1% sodium bicarbonate and analyzing the resulting solution for absorbance revealed that some of the drug was recovered. Although free antibiotic in CVC solution was reduced, the concentration should be sufficient (approximately 5 mg/ml) to decrease the frequency of infections associated with CVCs. We conclude that the concentrations of vancomycin, ceftazidime, cefazolin, or gentamicin used in our study should be sufficient for an antibiotic-heparin lock.

Prevalence of antimicrobial resistance in respiratory tract isolates of Streptococcus pneumoniae: results of a Canadian national surveillance study. The Canadian Respiratory Infection Study Group.

From October 1997 to November 1998, 1,180 respiratory tract isolates of Streptococcus pneumoniae were collected from 18 medical centers in 9 of the 10 Canadian provinces. Penicillin-intermediate and -resistant isolates occurred at rates of 14.8 and 6.4%, respectively, and these rates varied considerably by geographic region. Trimethoprim-sulfamethoxazole, tetracycline, and macrolide rates of nonsusceptibility were 12.2, 10.6, and 8.0 to 9.3%, respectively. The most potent agents studied were newer fluoroquinolones.

An overview of levodopa in the management of restless legs syndrome in a dialysis population: pharmacokinetics, clinical trials, and complications of therapy.

OBJECTIVE: To review published literature investigating the efficacy and safety of levodopa in the management of restless legs syndrome (RLS), with emphasis on the hemodialysis population. DATA SOURCES: An English-language literature search using MEDLINE was conducted from 1966 to 1997 (key terms: restless legs syndrome, levodopa, hemodialysis). The bibliographies of all identified published articles were reviewed and cross-referenced to ensure that all possible references were identified. STUDY SELECTION AND DATA EXTRACTION: All identified human studies investigating the use of levodopa for the management of RLS in uremic and nonuremic patients were analyzed. RESULTS: The prevalence of RLS is 20-40% in patients with endstage renal disease (ESRD) and approximately 5% in the general population. Although the benefits of levodopa/(carbidopa/benserazide) in reducing the signs and symptoms of RLS are documented in nonuremic patients, evidence in patients with ESRD is less readily available. Three small (< 30 subjects) clinical trials in uremic patients provide preliminary evidence for the usefulness of levodopa/(carbidopa/benserazide) in this population. CONCLUSIONS: In general, the small amount of published literature supports the empirical use of levodopa/carbidopa as a safe and effective therapy to manage the distressing symptoms of RLS in a hemodialysis population. We also report personal observations over a 4-year period in our hemodialysis unit that support levodopa as an effective first-line therapy. We have averted suicidal ideation in two patients and frequently modified symptoms of severe sleep deprivation. The dose of levodopa/carbidopa must be individually titrated to each patient's symptomatology, and morning rebound and afternoon augmentation should be monitored.

The new fluoroquinolones: A critical review.

OBJECTIVE: This paper reviews the literature available on the new fluoroquinolones - clinafloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sparfloxacin and trovafloxacin - to compare these agents with each other and contrast them with ciprofloxacin, an older fluoroquinolone. DATA SELECTION: Published papers used were obtained by searching MEDLINE for articles published between 1994 and 1998, inclusive. References of published papers were also obtained and reviewed. Abstracts from scientific proceedings were reviewed. DATA EXTRACTION: Due to the limited data available on several of the agents, criteria for study inclusion in the in vitro, pharmacokinetics and in vivo sections were not restrictive. DATA SYNTHESIS: The new fluoroquinolones offer excellent Gram-negative bacillary activity and improved Gram-positive activity (eg, against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin. Clinafloxacin, gatifloxacin, moxifloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (eg, Bacteriodes fragilis). All of the new fluoroquinolones have a longer serum half-life than ciprofloxacin (allowing for once daily dosing), and several are eliminated predominantly by nonrenal means. No clinical trials are available comparing the new fluoroquinolones with each other. Clinical trials comparing the new fluoroquinolones with standard therapy have demonstrated good efficacy in a variety of infections. Their adverse effect profile is similar to that of ciprofloxacin. Clinafloxacin and sparfloxacin cause a high incidence of phototoxicity (1.5% to 14% and 2% to 11.7%, respectively), grepafloxacin causes a high incidence of taste perversion (9% to 17%) and trovafloxacin causes a high incidence of dizziness (11%). They all interact with metal ion-containing drugs (eg, antacids), and clinafloxacin and grepafloxacin interact with theophylline. The new fluoroquinolones are expensive; however, their use may result in savings in situations where, because of their potent and broad spectrum of activity, they can be used orally in place of intravenous antibiotics. CONCLUSIONS: The new fluoroquinolones offer advantages over ciprofloxacin in terms of improved in vitro activity and pharmacokinetics. Whether these advantages translate into improved clinical outcomes is presently unknown. The new fluoroquinolones have the potential to emerge as important therapeutic agents in the treatment of respiratory tract and genitourinary tract infections.

Imipenem and meropenem: Comparison of in vitro activity, pharmacokinetics, clinical trials and adverse effects.

OBJECTIVE: To compare and contrast imipenem and meropenem in terms of in vitro activity, pharmacokinetics, clinical efficacy and adverse effects. DATA SELECTION: MEDLINE search from 1975 to 1997 and follow-up of references. DATA EXTRACTION: Clinical trials comparing imipenem with meropenem, or either imipenem or meropenem with standard therapy in the treatment of serious infections were selected. DATA SYNTHESIS: Imipenem, the first carbapenem, was first marketed in 1987; meropenem was introduced to the market in 1996. In general, imipenem is more active against Gram-positive cocci while meropenem is more active against Gram-negative bacilli. The agents display similar pharmacokinetics. Clinical studies in patients with serious infections (intra-abdominal infection, respiratory infection, septicemia, febrile neutropenia) report similar bacteriological and clinical cure rates with imipenem and meropenem. Meropenem is approved for the treatment of bacterial meningitis, whereas imipenem is not. Adverse effects are similar. CONCLUSIONS: Current literature supports the use of imipenem at a dose of 500 mg every 6 h and meropenem at 1 g every 8 h for the treatment of severe infections. For the treatment of serious infections, imipenem (500 mg every 6 h or 2 g/day [$98/day]) is more economical than meropenem (1 g every 8 h or 3 g/day [$142/day]) based on acquisition cost.

Recommended treatment for urinary tract infection in pregnancy.

OBJECTIVE: To establish and recommend a therapeutic regimen for the treatment of urinary tract infection (UTI) in pregnancy based on the published studies. DATA SOURCES: An English-language literature search employing MEDLINE, Index Medicus, and bibliographic reviews of the references obtained were searched (key terms: urinary tract infection, UTI, pregnancy, bacteriuria). STUDY SELECTION AND DATA EXTRACTION: All identified human studies dealing with bacteriuria or UTI in pregnancy were analyzed. DATA SYNTHESIS: Limited data are available regarding the appropriate antibiotic management of UTI in pregnancy. Single-dose cure rates with amoxicillin are approximately 80 percent. Trimethoprim/sulfamethoxazole provides cure rates of greater than 80 percent. Cephalosporins and nitrofurantoin produce variable results. CONCLUSIONS: We recommend separating pregnant subjects with UTI into two groups. Those with asymptomatic bacteriuria can be treated with a single dose of an antimicrobial to which the organism is susceptible. For those with symptomatic UTI, we recommend amoxicillin 500 mg tid for three days. Urine cultures should be repeated seven days following therapy to assess cure or failure. Well-designed studies need to be performed, comparing single-dose and three-day therapy for UTI in pregnancy.