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PubMed1981

The noncovalent bonding of antibiotics to a polytetrafluoroethylene-benzalkonium graft.

This study evaluates the noncovalent bonding of anionic antibiotics to polytetrafluoroethylene grafts using benzalkonium chloride as a cationic anchor. The binding of radiolabeled surfactants and antibiotics was evaluated by liquid scintillation and in an in vitro microbiologic assay against Staphylococcus aureus. Significant quantities of antibiotic were bound when the grafts were pretreated with benzalkonium in ethanol or aqueous solution at elevated temperature. Bound antibiotic is stable in aqueous salt solutions, but slowly dissociates in the presence of blood or serum. The ionic nature of the bonding process is clarified by the use of a variety of antibiotics and surfactants with complementary charges. The ability of the benzalkonium treated grafts to adsorb antibiotic from blood is, likewise, demonstrated and the possibility of concomitantly binding heparin and antibiotic simultaneously is evaluated. These studies support the ability to noncovalently bond antibiotics to polytetrafluoroethylene surfaces and form the basis of eventually utilizing these surfaces in the prevention of vascular prosthetic infections.

Benzalkonium Compounds↗
PubMed1982

The role of antibiotic bonding in the prevention of vascular prosthetic infections.

Oxacillin, a negatively charged antibiotic, was bonded to polytetrafluoroethylene (PTFE) grafts using the cationic surfactant, benzalkonium chloride. Control PTFE grafts and bonded grafts prepared at room temperature and at 90 C were placed in the infrarenal aorta of dogs and challenged by local contamination with Staphylococcus aureus. Bonded grafts were superior to controls in negative cultures, patency, and survival. The possible role of antibiotic bonding in the prevention of vascular prosthetic infection is discussed.

Animals↗
PubMedDate not supplied

Methemoglobinemia: an unusual complication of topical anesthesia.

Allergic reactions tend to be easily recognized and treated, but methemoglobinemia is a rare, life-threatening complication of topical anesthesia of which our staff was unaware until recently. Team work prevented a patient fatality. Directives to alert the staff to suspect methemoglobinemia in patients who develop cyanosis and decreased oxygen saturation levels after administration of topical anesthesia despite administration of oxygen will prevent fatalities in the future.

4-Aminobenzoic Acid↗
PubMed1996

Disinfecting agents for removing adherent bacteria from orthopaedic hardware.

This investigation seeks to determine whether surfactants or detergents can be used to clean and disinfect orthopaedic wounds with implanted hardware. Thus, a stepwise investigation of biocompatible surfactants and detergents was performed to identify an irrigation agent for disinfecting orthopaedic wounds. Bacterial adhesions assays, irrigation studies, and bactericidal assays determined that benzalkonium chloride showed the greatest efficacy. Testing involved stainless steel screws colonized with a preformed biofilm of Staphylococcus epidermidis, Staphylococcus aureus, or Pseudomonas aeruginosa, which were immersed in benzalkonium chloride solutions for various time intervals under static conditions. After 10 minutes, benzalkonium chloride achieved a minimum 4 log kill (10,000-fold) for all 3 strains of bacteria. Additional studies demonstrated that the high mechanical energy of jet irrigation improved the disinfecting properties of this agent. With jet lavage, both 1:1000 and 1:5000 concentrations of benzalkonium chloride achieved a minimum 2 log kill (100-fold) for all 3 bacteria. The results or this study suggest that at tissue compatible concentrations, benzalkonium chloride has significant disinfection properties for in vitro colonized orthopaedic devices, and these properties may be enhanced via jet lavage.

Anti-Infective Agents, Local↗
PubMed1993

Artificial tear composition and promotion of recovery of the damaged corneal epithelium.

In severe dry eye syndromes the corneal epithelium is compromised with development of punctate erosions and increased permeability. In the present study the ability of artificial tear solutions to promote recovery of the corneal epithelial barrier was determined by measurement of corneal uptake of 5,6 carboxyfluorescein (CF). Corneas of anesthetized rabbits were exposed to 0.01% benzalkonium for 5 min to increase epithelial permeability. The cornea was then exposed to an artificial tear solution for 1.5 h followed by measurement of CF uptake. During exposure to three commercial isotonic, nonpreserved solutions and a solution preserved with polyquaternium-1, CF uptake decreased significantly but did not return to control. No recovery of the epithelial barrier occurred during exposure of corneas to nonpreserved hypotonic solutions. During exposure to an experimental tear solution with an electrolyte composition similar to human tears, buffered with bicarbonate, CF uptake returned to control levels. Bicarbonate is an essential component of this solution because the same formula buffered with borate or without buffer was ineffective in promoting recovery of the damaged corneal epithelium.

Animals↗
PubMed2000

Antibacterial activity of anesthetic solutions and preservatives: an in vitro comparative study.

PURPOSE: To investigate the antibacterial activity of topical anesthetic solutions and their preservatives individually in vitro, to determine involvement with bacterial growth inhibition. MATERIAL AND METHODS: Proparacaine and tetracaine (in concentrations of 0.125%, 0.25%, and 0.50%), edetate disodium (EDTA), benzalkonium chloride, EDTA + benzalkonium chloride, and sterile saline solution were used. Five microliters of each solution were applied to standard filter paper disks and placed in Mueller-Hinton agar previously inoculated with known strains of Pseudomonas aeruginosa and Staphylococcus aureus. Zones of growth inhibition were measured 24 hours later and analyzed. RESULTS: There were no zones of inhibition in the agar inoculated with P. aeruginosa to all tested solutions. Benzalkonium chloride alone and associated with EDTA inhibited growth of S. aureus. All other solutions did not inhibit S. aureus. CONCLUSION: Preservative-free anesthetic solutions seemed not to interfere with bacterial development in culture media. Benzalkonium chloride alone and associated with EDTA inhibited development of gram positive bacteria, S. aureus, but did not inhibit P. aeruginosa.

Anesthetics, Local↗
PubMed2001

Effects of three penetration enhancers on transcorneal permeation of cyclosporine.

PURPOSE: To investigate the permeation of cyclosporin A (CsA) through fresh and frozen human corneas in the presence and absence of three penetration enhancers: benzalkonium chloride (BZCl), dimethylsulfoxide (DMSO), and Cremophor-EL. METHODS: Human corneas, unsuitable for transplantation, were either freshly used for permeability experiments or snap-frozen in liquid nitrogen and stored at -85 degrees C. CsA permeation through either fresh or thawed frozen corneal tissue was determined using a flow-through diffusion apparatus (20 degrees C for 24 hours). Flux rates for CsA were determined in the presence and absence of the penetration enhancers 0.01% BZCl, 20% DMSO, and Cremophor-EL (10% and 20%). Analysis of variance and Duncan's multiple-range test were used to test for steady state, and an unpaired Student t test with Welch's correction was used to test for differences between the mean flux values at each time point. A significance level of 5% was used for all of the statistical tests. RESULTS: No statistically significant differences in flux values of CsA could be detected between fresh and frozen corneas. In the presence of Cremophor-EL (10% and 20%) and 0.01% BZCl, statistically significant increases in flux values of CsA before 16 hours and after 16 hours, respectively, could be observed. In the presence of 20% DMSO, no statistically significant increases in flux values could be detected. CONCLUSIONS: The permeation of CsA through human corneas appeared to be enhanced by the presence of BZCl and Cremophor-EL. Additionally, it was shown that the flux rate of CsA across fresh and frozen corneas was not significantly different.

Adolescent↗
PubMed2004

In vitro transcorneal penetration of metronidazole and its potential use as adjunct therapy in Acanthamoeba keratitis.

PURPOSE: To investigate the in vitro permeation of metronidazole through rabbit and human corneas in the presence and absence of 0.01% benzalkonium chloride and to suggest its use as adjunct therapy in the treatment of Acanthamoeba keratitis. METHODS: Metronidazole permeation through rabbit and human corneas, the latter being unsuitable for transplantation, were used for all permeability experiments. Flux rates for metronidazole from 0.5% and 1.0% aqueous solutions in the presence and absence of 0.01% benzalkonium chloride (BZCL) were determined. ANOVA and the Duncan multiple range test were used to test for steady state and an unpaired t test with the Welch correction was used to test for differences between the mean flux values at each time point. A significance level of 5% was used for all the statistical tests. In the clinical cases described, 0.5% aqueous solution was used. RESULTS: Steady-state flux rates for metronidazole from 0.5% and 1.0% solutions across both rabbit and human corneas were achieved after 6 and 4 hours, respectively. No statistically significant differences were obtained in the presence and absence of 0.01% BZCl (P < 0.05) between the steady state flux values at both concentrations of metronidazole of human and rabbit corneas, except for 0.5% metronidazole across rabbit corneas. Flux rates of metronidazole across human corneas were 12%-33% higher than those across rabbit corneas. For both rabbit and human corneas, flux rates of metronidazole from 0.5% and 1.0% solutions were reduced by between 4% and 11%, respectively, in the presence of 0.01% benzalkonium chloride. CONCLUSIONS: Although statistically significant differences in flux values were obtained between human and rabbit corneas, the study supports the suitability of the in vitro rabbit cornea as a model for investigating permeation of drugs through human corneas. However, direct extrapolation of animal data to humans must be approached cautiously. The metronidazole from a 1% solution had a steady-state flux rate approximately double that from the 0.5% solution. Higher concentrations of up to 1% may be considered for clinical use for treating Acanthamoeba keratitis infections. It would appear to be prudent to omit benzalkonium chloride as a preservative from preparations of metronidazole formulated for topical ophthalmologic use. Early clinical experience with the topical solution as adjunct therapy in the treatment of Acanthamoeba keratitis is encouraging.

Acanthamoeba Keratitis↗
PubMed1988

Evaluation of rapid drying hand disinfectant preparations in the intensive care unit.

MK412A (0.2% chlorhexidine in 70% ethanol) and MK412B (0.2% benzalkonium chloride in 70% ethanol), which are rapid drying and rubbing antiseptic preparations, have been evaluated for hand sterilization over a month by ICU nurses. They have been shown to have effective skin decontaminant efficacy under practical conditions in a busy ICU. There were no adverse reactions except for two cases of mild erythema in the MK412A treatment group. In a comparative in vitro study with Pseudomonas cepacia, 0.2% chlorhexidine solution alone and 0.2% benzalkonium chloride solution alone were less bactericidal than MK412A and MK412B.

Benzalkonium Compounds↗
PubMed1996

Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients.

OBJECTIVES: To compare the efficacy of a newly available antiseptic solution (composed of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzyl alcohol), with 10% povidone iodine, on the prevention of central venous or arterial catheter colonization and infection. DESIGN: Prospective, randomized clinical trial. SETTING: Surgical-trauma intensive care unit (ICU) in a university hospital. PATIENTS: All patients admitted to the ICU and requiring the insertion of a central venous and/or an arterial catheter from July 1, 1992 to October 31, 1993. INTERVENTIONS: Patients were randomly assigned to one of two groups according to the antiseptic solution used for insertion and catheter care. The same solution was used for skin disinfection from the time of catheter insertion to the time of removal of each catheter. MEASUREMENTS AND MAIN RESULTS: Catheter distal tips were quantitatively cultured when catheters were no longer necessary, if there was a suspicion of catheter-related infection, and routinely after 7 days of use for arterial catheters, or after 15 days of use for central venous catheters. The rate of significant catheter colonization (i.e., > or = 10(3) colony-forming units [cfu]/mL by quantitative culture), and catheter-related sepsis (as defined by sepsis abating following catheter removal per 1,000 catheter-days), were significantly lower in the chlorhexidine group (12 vs. 31 [relative risk 0.4, 95% confidence interval 0.1 to 0.9, p < .01] and 6 vs. 16 [relative risk 0.4, 95% confidence interval 0.1 to 1, p = 0.5], respectively). The rate of central venous catheter colonization and central venous catheter-related sepsis per 1,000 catheter-days were also significantly lower in the chlorhexidine group (8 vs. 31 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .03] and 5 vs. 19 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .02], respectively). Finally, the rate of arterial catheter colonization per 1,000 catheter-days was significantly lower in the chlorhexidine group (15 vs. 32 [relative risk 0.5, 95% confidence interval 0.1 to 1, p = .05]), whereas the rate of arterial catheter-related sepsis per 1,000 catheter-days was similar for the two study groups (8 in the chlorhexidine group vs. 10 in the povidone iodine group [relative risk 0.8, 95% confidence interval 0.1 to 2.2, p = .6]). The 0.25% chlorhexidine solution was superior to the 10% povidone iodine solution in preventing catheter colonizations and catheter-related sepsis due to Gram-positive bacteria (5 vs. 20 [p < .001], and 2 vs. 10 [p < .001], respectively), whereas the activity of the 0.25% chlorhexidine solution was nonsignificantly superior in preventing Gram-negative infections (7 vs. 4 [p = .5], and 4 vs. 2 [p = .8], respectively). CONCLUSIONS: The 4% alcohol-based solution of 0.25% chlorhexidine gluconate and 0.025% benzalkonium chloride was more effective than 10% povidone iodine for insertion site care of short-term central venous and arterial catheters. This effect appeared related to a more efficacious prevention of infections with Gram-positive bacteria.

Adult↗
PubMed2004

The need for caution with topical anesthesia during endoscopic procedures, as liberal use may result in methemoglobinemia.

During upper gastrointestinal endoscopy, topical oropharyngeal anesthesia with lidocaine and/or benzocaine is used routinely by many endodscopists. Although such a practice is usually safe, there have been a number of reports of methemoglobinemia induced by topical anesthesia. Early treatment is extremely important as the development of methemoglobinemia is potentially fatal. Methemoglobinemia should be considered when oxygen desaturation occurs without another explanation. In this case series, we report 4 cases of methemoglobinemia that followed the liberal application of Cetacaine for ERCP. All patients recovered after appropriate treatment but these cases serve to highlight the potential problem, the importance of early recognition and treatment, and the most appropriate treatment options.

4-Aminobenzoic Acid↗
PubMedDate not supplied

Benzalkonium chloride: a potential disinfecting irrigation solution.

OBJECTIVE: To determine the disinfecting properties of benzalkonium chloride as an irrigation agent. DESIGN: Comparison was made between irrigation of contaminated muscle strips with benzalkonium chloride and normal saline (control). SUMMARY OF BACKGROUND DATA: Benzalkonium chloride is a cationic disinfectant, which has questionable efficacy in an organic environment. However, no previous study has attempted to use high volumes of this cationic solution to overcome the neutralizing effect of organic tissue and thus maintain this detergent's germicidal properties. METHODS: 2.5 cm x 0.5 cm x 0.5 cm pieces of bovine muscle were aseptically cut from the center of freshly harvested beef muscle and incubated with 1.0 x 10(7) colony forming units of bacteria for 15 minutes. The muscle strips were then irrigated with either 100 mL, 1 L, or 10 L of benzalkonium chloride at a 1:2000 concentration in normal saline. Normal saline was used as the control. The muscle strips were sonicated to remove adherent bacteria; the number of living organisms was determined by quantitatively culturing the sonicate. RESULTS: In vitro, benzalkonium chloride was superior to normal saline at disinfecting bovine muscle (p < or = 0.001). When 10 L of benzalkonium chloride irrigation was used, no living bacteria could be recovered (p < or = 0.012). CONCLUSION: In this experimental setting benzalkonium chloride was an effective disinfection agent, with enhanced activity at large volumes.

Animals↗
PubMedDate not supplied

Comparison of castile soap, benzalkonium chloride, and bacitracin as irrigation solutions for complex contaminated orthopaedic wounds.

OBJECTIVE: The purpose of the present study was to determine the effects of cleaning a contaminated orthopaedic wound with different classes of wound irrigation solutions. STUDY DESIGN: Rats with a contaminated orthopaedic wound were randomized into treatment groups: normal saline (NS), castile soap (CS), benzalkonium chloride (BzC), bacitracin (Abx), or sequential irrigation with BzC, CS, and NS. INTERVENTION: Pseudomonas aeruginosa [P. aeruginosa; 1 x 10(6) colony-forming units (CFU)], or Staphylococcus aureus (S. aureus; 1 x 10(6) CFU) were placed into a paravertebral wound (containing a wire implant placed through a spinous process) and allowed to incubate for fifteen minutes. The wound was then irrigated with three liters of either NS, 0.05 percent CS, 0.03 percent BzC, Abx (33,000 units per liter) or underwent a sequential irrigation treatment (one liter each of BzC, CS, NS). MAIN OUTCOME MEASUREMENTS: The animals were observed daily for wound complications for fourteen days and then killed, and cultures of the wound were obtained. RESULTS: Pseudomonas aeruginosa: Both CS and the sequential irrigation treatment significantly lowered the rate of positive wound cultures when compared with NS (p < 0.05). Irrigation with BzC resulted in a higher rate of positive wound cultures and complications. The sequential irrigation treatment prevented the wound complications associated with irrigation with BzC alone. Staphylococcus aureus: Only BzC irrigation significantly lowered the rate of positive wound cultures when compared with NS (p < 0.05). CONCLUSION: The rate of positive wound cultures due to P. aeruginosa is effectively reduced by irrigation with CS alone or by the sequential irrigation treatment. When used alone, the antiseptic BzC results in a higher rate of positive wound cultures and wound complications. The wound complications seen with irrigation with BzC alone are prevented by the sequential irrigation treatment (BzC followed by CS and NS). The rate of positive wound cultures in this model due to S. aureus is not decreased by irrigation with CS; however, the rate of positive wound cultures is safely and effectively decreased with the use of BzC.

Animals↗