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A 20-year-old soldier caught an eczematous contact dermatitis on the left ear after the protection of hearing "Selektone" had been adapted. The protection of hearing had been disinfected before in a Zephirol solution 1% aqueous. Zephirol contains the quaternary ammonium compound Benzalkonium chloride. The problems of patch testing with Benzalkontium chloride are discussed.
A method for the specific determination of three quaternary ammonium compounds, benzalkonium chloride, cetylpyridinium chloride and dequalinium chloride, used as antibacterial agents in candy-based lozenges, is described based on capillary zone electrophoresis. It is shown that, following optimisation of buffer composition with respect to organic modifier concentration. pH and buffer concentration together with the inclusion of sodium dodecylsulphate as an ion-pairing agent in the case of dequalinium chloride, these analytes migrate in less than 5 min. The resultant electrophoretic peaks are sharp and readily quantified. The individual alkyl components of benzalkonium chloride can be resolved as can related impurities in dequalinium chloride lozenges. The quantitative characteristics of the assay method, based on peak areas normalised with respect to migration times, are reported and the method is compared with a previously published method based on liquid chromatography.
BACKGROUND: Quaternary ammonium compounds constitute a large group of antibacterial chemicals with a potential for inhibiting plaque and gingivitis. One compound, benzalkonium chloride (BC), may be of value, although there is a dearth of evidence to support efficacy. The aim of this study was to measure the ability of 2 BC mouthrinses (0.05% and 0.1%) to inhibit de novo plaque reformation. METHOD: A 4-day plaque regrowth model. For comparative purposes, a commercial mouthrinse containing cetyl pyridinium chloride (CPC) and a positive control chlorhexidine (CX) mouthrinse were also evaluated. RESULTS: Compared to water control, a reduction in plaque scores of 52% was noted for the CX mouthrinse, 22.5% for CPC and 5% and 6% for the 2 BC rinses. For plaque area, reductions of 84%, 47%, 16% and 15% were found for CX, CPC, and the 2 BC rinses, respectively. Significant reductions in plaque area compared to the water rinse were also seen with the 2 BC rinses (p<0.05). However, for both plaque score and plaque area, the CX and CPC rinses significantly reduced plaque compared to the BC rinses (p<0.0001). CONCLUSIONS: These findings would suggest that the 2 benzalkonium rinses would only have a limited value at inhibiting plaque formation.
A highly reproducible and specific method for the analysis of the quaternary ammonium compound, benzalkonium chloride, in effluents from European hospitals is presented. Benzalkonium chloride was extracted with end-capped RP-18 solid-phase cartridges and was selectively eluted. The resulting solution was analyzed by high-performance liquid chromatography (HPLC). After elution from the analytical column of the HPLC system, 9,10-dimethoxyanthracene-2-sulfonate was added continuously as a fluorescence marker, forming a hydrophobic ion-pair with benzalkonium chloride. The ion-pair was analyzed by fluorescence detection. The method was applied to highly complex effluent samples from different sized European hospitals. The measured concentrations were between 0.05 and 6.03 mg/l. The amounts emitted per bed and year were 4.5-362 g and did not correlate with the size of the hospital. The total amounts were 2.6-909 kg/year.
Resistant cells of Pseudomonas aeruginosa and a waterborne Pseudomonas sp. (strain Z-R) were able to multiply in nitrogen-free minimal salts solution containing various concentrations of commercially prepared, ammonium acetate-buffered benzalkonium chloride (CBC), a potent antimicrobial agent. As the CBC concentration increased, growth increased until a point was reached at which the extent of growth leveled off or was completely depressed. Minimal salts solutions of pure benzalkonium chloride (PBC) containing no ammonium acetate did not support bacterial growth. When ammonium acetate was added to PBC solutions in the same concentrations found in CBC solutions, growth patterns developed that were comparable to those found with CBC. Likewise, (NH(4))(2)SO(4) added to PBC solutions supported growth of both organisms. P. aeruginosa was initially resistant to CBC levels of 0.02% and it was adapted to tolerate levels as high as 0.36%. Strain Z-R was naturally resistant to 0.4% CBC. Since ammonium acetate, carried over by the CBC used in drug formulations and disinfectant solutions, has the potential to support the growth of resistant bacteria and thus make possible the risk of serious infection, it is suggested that regulations allowing the presence of ammonium acetate in CBC solution be reconsidered.
The retention behavior of the quaternary ammonium compounds benzalkonium chloride, cetylpyridinium chloride and dequalinium chloride on a 100 x 4.6 mm id cyanopropyl stationary phase column is reported as a function of organic modifier and ionic hydrophobic mobile phase additive concentrations. Optimum liquid chromatographic mobile phases using different mobile phase additives are reported which are suitable for the determination of cetylpyridinium chloride and dequalinium chloride in a variety of candy-based lozenge formulations. The quantitative aspects of assays based on the separation of active ingredients and formulation excipients were established. The generality of application of the assay methods was evaluated by determining the quaternary ammonium content of different lozenges and comparing the values obtained with the stated dose.
Publications on the subject of conjunctiva in 1991 have been reviewed. Clinical relevant topics have been stressed. In the field of conjunctival affections caused by microorganisms a spectrum of bilateral squamous conjunctival tumors associated with human papillomavirus type 16 were first documented. Chlamydial antibodies cause proliferation of lymphocytes. The peripheral lymphocyte proliferative response to whole chlamydial elementary bodies seems to have a strong correlation between the responses to the Chlamydia trachomatis serotypes B and L1. In the field of impression cytology of the conjunctiva the topographical distribution of ocular surface cells was described. In patients with glaucoma using long-term topical medication, there seem to be significant degrees of conjunctival metaplasia associated with the number of glaucoma medications. These changes in the conjunctival surface may be related to the preservatives in the preparations (benzalkonium compounds). An ultrastructural defect in conjunctiva in recessive dystrophic epidermolysis bullosa may increase the susceptibility of the conjunctiva to minor mechanical trauma. Thus resulting in the bullous and cicatrical changes seen clinically.
The complete nucleotide sequence of the 2.8 kb plasmid pST827 involved in resistance to the quaternary ammonium compound (QAC) benzalkonium chloride in meat-associated staphylococci was determined. An open reading frame (ORF) similar to the QAC resistance genes qacC, ebr and smr previously reported from clinical staphylococcal strains was identified (qacC'). In addition an ORF coding for a protein (Rep827) showing extensive homology to reported replication proteins of Gram-positive organisms was found. The occurrence of known QAC resistance gene (qacA-C) among staphylococcal strains isolated from food processing plants was studied by hybridization analysis. Of 191 isolates, 25 were resistant to benzalkonium chloride. Five of these gave no hybridization signals to probes specific for qacA-C. Further hybridization analysis indicated that pST827 or closely related plasmids are widespread among QAC-resistant staphylococcal strains. The finding of resistant staphylococci in different areas of the food processing industry indicates that QAC resistance is a potential problem in the food processing industry.
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An intracerebral assay technique in mice is described for testing chemical disinfectants acting on the rabies virus. The assay determines whether more than 99% of 10 000 mouse intracerebral LD(50) of virus are inactivated within 1-2(1/2) minutes. By this test, several substances usually available for the treatment of animal bite wounds were found to be effective. They are: 1%-20% soap solutions; 43%-70% alcohol; 1:1000 (0.1%) or lower dilutions of two quaternary ammonium compounds, benzalkonium chloride and cetrimonium bromide; 1:10 000 or lower dilutions of iodine; acetone; and ether.Several other substances tested for possible use in environmental disinfection were also found to be virucidal. They were: 3% caustic soda and commercial preparations of organic phenols, iodine, and a mixture of trisodium phosphate and sodium hypochlorite. No virucidal effect was exerted by a 2% aqueous solution of mercurochrome, a 1:1000 aqueous solution of thiomersal, or 3% formalin (1% formaldehyde).A number of substances that inactivate rabies virus have thus become available for local treatment of bite wounds and for environmental disinfection. The assay procedure described may be useful in testing other disinfectants and chemical substances.
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Benzalkonium chloride, benzethonium chloride, and chlorhexidine gluconate were assayed quantitatively by a direct spectrophotometric method with bromthymol blue buffered at pH 7.5. The method shows good results at concentrations of 0--300 microgram/ml and in the presence of epinephrine bitartrate, phenylephrine hydrochloride, pilocarpine hydrochloride, and polyvinyl alcohol.
A mixture of benzalkonium chloride, Triton X100, and citric acid (Resiguard F) had a marked virucidal effect on lipid-containing deoxyribonucleic and ribonucleic acid viruses, such as vaccinia virus, herpesvirus, and influenza virus. Adenoviruses and picornaviruses were more resistant to inactivation. Electron microscopy showed that influenza particles became aggregated in the presence of Resiguard F and that the outer fringe of hemagglutinin and neuraminidase spikes seen in control virus preparations became indistinct. The mixture had no detectable antiviral activity in mice infected with influenza AO/PR/8/34 virus, and this was attributed to the reduced virucidal effect of Resiguard F in the presence of serum proteins.
A novel microbial sensor system that uses luminous bacteria was developed for the determination of both glucose and toxic compounds. The sensor system consisted of a membrane with luminous bacteria immobilized upon it and a photomultiplier. Measurements were based on the in vivo intensity of the light emitted by the bacteria, as this is affected by their environment. A linear relationship was observed between increased luminescence and concentrations of glucose between 0.05 mM and 0.55 mM. The relative standard deviation was 10% for 0.55 mM glucose (n = 10). Toxic compounds such as benzalkonium chloride, sodium dodecyl sulphate and chromium(VI) were also detected by measuring the decrease in luminescence in their presence.
Medications used in 'Dry Eye' patients are reviewed for their effects on the corneal surface including the overlying tear film. Preservatives are discussed, since they affect the properties of commercial preparations which may be instilled frequently as a substitute for normal tears. The major beneficial effect which a topically applied agent can have on epithelium is to supplement or stabilise the tear film. Thimerosal sometimes triggers a sensitivity reaction, and other mercurial compounds are unstable. Benzalkonium chloride compromises both corneal epithelium and tear film. Some cationic detergents, including chlorhexidine digluconate and polyquat, cause less disruption at prophylactic concentrations. The use of a small drop size is helpful in preventing toxic effects of preservatives. All preservatives should be avoided when unit doses of a sterile tear replacement, such as saline, can be made available. Topical antibiotics should be used only to control known bacterial infections, avoiding high concentrations of bacitracin, gentamicin, and neomycin. Steroids and antibiotic/steroid combinations must be used with great caution, and only when uncontrolled ocular inflammation justifies the risk of possible corneal ulceration.
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Concern has been growing regarding the potential of antibiotic and disinfectant co-resistance in clinically important bacteria. In this study, the susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) to chlorhexidine (CHX), the quaternary ammonium compounds cetylpyridinium chloride (CPC) and benzalkonium chloride (BC), triclosan, dibromopropamidine isethionate (DBPI) and triclocarban were compared. MRSA exhibited low-level resistance to CHX and the QACs, with MICs of 1.5 to 3-fold (CHX), and 2 to 4-fold (QACs) higher than MSSA. However, the MIC values for MRSA ranged between 0.025 (the MIC of MSSA) and 1 microg/mL with triclosan, and between <5 (the MIC of MSSA) and 75 microg/mL with DPBI. Nevertheless, these strains remain relatively sensitive to most of these antimicrobial agents. The bactericidal efficacy of CHX, CPC and DBPI (with the exception of one strain) correlated with their MIC value. This was not observed using triclosan; MRSA and MSSA strains were equally susceptible to its killing effect, regardless of MIC. The permeabilizing agent, ethylenediamine tetraacetic acid (EDTA) was unable to potentiate the antibacterial activities of the biocides against any of the strains tested. Attempts to select for staphylococcal strains with increased resistance to triclosan, CPC or CHX, using disc diffusion, step-wise broth, or repeated exposure/recovery technique, were only partially successful, and resistance was found to be unstable. The susceptibilities of vancomycin-resistant enterococcus (VRE) and vancomycin-sensitive enterococcus (VSE) to the biocides were also compared and found to be similar both in terms of MIC testing and time-kill studies.
The cytotoxic effects of newly synthesized bis-quaternary ammonium compounds (bis-QACs) and benzalkonium chloride were investigated on skin and blood cells, namely normal human epidermal keratinocytes of neonatal foreskin, a normal human skin fibroblast cell line NB1RGB, erythrocytes and a lymphoma cell line JM. The bis-QACs tested were 4, 4'-(1,6-hexamethylenedithio)bis(1-octylpyridinium iodide) (4DTBP-6, 8), N,N'-tetramethylenebis(1-dodecyl-4-carbamoylpyridinium iodide) (4BCAP-4,12), N,N'-hexamethylenebis(1-decyl-4-carbamoylpyridinium iodide) (4BCAP-6,10), 4,4'-(1,4-tetramethylenedicarbonyldiamine) bis (1-decylpyridinium iodide) (4DCABP-4,10), 4,4'-(1, 4-tetramethylenedicarbonyldiamine) bis (1-dodecylpyridinium iodide) (4DCABP-4,12), 4,4'-(1, 4-phenyldicarbonyldiamine)bis(1-dodecylpyridinium iodide) (4DCABP-P, 12), and 4,4'-(1, 6-hexamethylenedioxydicarbonyl)bis(1-dodecylpyridinium iodide) (4DOCBP-6,12). All bis-QACs consisted of two identical alkylpyridinium rings and bridge structure linking rings to each other have a methylene bridge but only 4DCABP-P,12 has a phenyl ring as a bridge. Most of the LD(50) values in acute cytotoxic assays of these bis-QACs tended to be lower than those of benzalkonium chloride. However, the comparison of the antibacterial activity against cytotoxic effects on several human cells revealed that bis-QACs, especially 4DTBP-6,8, have wide concentration ranges showing sufficient antibacterial activity and lower cytotoxic effect on human cells (except for 4DOCBP-6,12), although benzalkonium chloride caused significant human cell damage at the concentrations necessary for antibacterial activity. Moreover, judging from the LD(50) value of 4DTBP-6,8 [67 microM, a 6.7-fold higher concentration than the upper value of MIC] obtained in an artificial human skin model TESTSKIN, 4DTBP-6,8 is thought to be a more effective and safer antiseptic reagent for application to the skin surface than benzalkonium chloride. Taken together, bis-QACs are expected to be a promising new generation of antimicrobial QACs.