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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.
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.
Benzalkonium chloride (BAC) is a mixture of quaternary benzyldimethylalkylammonium chlorides which was found to inhibit histamine release induced by polyamines (48/80, ATP, bradykinin, curare, guanethidine, polylysine, polymyxin B, poly-THIQ, protamine, stilbamidine or substance P), but not that caused by antigens, concanavalin A, dextran, lonophores (A23187 or X-537A), enzymes (chymotrypsin or phospholipase C), monoamines (dextromethorphan, meperidine or chlorpromazine) or detergents (decylamine, Triton X-100 or a fire ant venom alkylpiperidine). Inhibition by 1.5 and 3 microgram of BAC per ml caused parallel shifts of the 48/80 dose-response curves to the right with no loss of efficacy, indicating that the antagonism was surmountable. Phospholipase C was partially inhibited by BAC, but Triton X-100 also inhibited phospholipase C (but not 48/80), indicating that the inhibition of phospholipase C by BAC was probably a nonspecific, detergent effect. BAC caused histamine release by itself at concentrations over 5 microgram/ml. Heat inactivation (50 degrees C for 15 min) of the mast cells did not prevent this release, suggesting a lytic mechanism for this action. Structure-activity relations studies on various members of the BAC family for their ability to inhibit 48/80-induced histamine release indicated that benzyldimethyltridecylammonium chloride was the most potent.
A semiautomated method has been developed for quantitatively assaying the activity of detergent disinfectants. Automation permitted a high level of reproducibility, which in turn allowed a meaningful comparison between the activities of some types of quaternary ammonium compounds.
Determinations of the minimum inhibitory concentrations for various antimicrobial surfactants with reference to the bacteria P. acnes, P. granulosum, and St. epidermidis are reported. The results show that quaternary ammonium compounds can display minimum inhibitory concentrations corresponding to those of relevant antibiotics. With the especially effective substance fractionated dimethylcocobenzalkoniumchloride )ARQUAD DMMCD-B), it could be further shown that with in vivo application in 70% isopropanol or in an ethanol-containing film mask ointment suppression can be obtained of P. acnes, all propionibacteria added, and all pilosebaceous duct bacteria which can be cultured under anaerobic conditions. The studies may point out a way of replacing antibiotics in the antimicrobial therapy of acne by quaternary ammonium compounds.
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Fifty-two (52) compounds were tested for spermicidal activity by titration against human spermatozoa. The gradual decrease in mean sperm size was measured against increasing concentration of spermicide and the end-point was taken as the point at which all the peripheral cytoplasm had been removed and only the sperm core of nucleus and tail fibres remained. There were 14 compounds that produced this total effect. All were detergents, of various types, and the effect was purely physical. The most potent compounds caused complete stripping at 0.5-50 pmol/cell and most are already used in spermicidal preparations. A further 11 compounds, including sodium hypochlorite and some phenols, caused partial stripping, while 4 compounds caused sperm swelling. The test was not suitable for assessment of metabolic cell poisons.
Two similar calici agents, San Miguel sea lion virus (SMSV) and vesicular exanthema of swine virus (VESV) are susceptible to the virucidal activity of disinfectants of differing formulation. Ten of 12 compounds were effective against six log10 plaque forming units (PFU) of SMSV in a 2-min exposure at 4, 25 and 37 degrees C. However, only seven of these 10 SMSV-positive compounds inactivated VESV under the same conditions of temperature and time. Two compounds were not effective against SMSV in a 20-min exposure at 4 and 25 degrees C, but were effective at 37 degrees C. Two of the three compounds not effective against VESV in a 20-min exposure at 4 and 25 degrees C were also effective at 37 degrees C. The test iodophor compound inactivated SMSV completely but had only minimal inactivating activity against VESV at the three temperatures tested.
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S-alkylthiuroniumhalides according to formula I (table 1) have been tested under standardized conditions with respect to their antimicrobial activity against bacteria, yeasts and fungi. In table 2 the bacteriostatic and fungistatic efficiency and in table 3 the microbicidal efficiency of 8 different S-alkylthiuronium compounds are compared with the efficiency of N,N-dimethyl-coconutoilalkyl-benzyl-ammonium-chloride. The germ inhibitory effect of the quaternary ammonium compound has been superior to the S-alkylthiuronium salts in almost all respects. The germicidal effect of the S-alkylthiuroniumhalides depends on the alkyl chain length bound to the S-atom and gets the optimum with S-dodecylthiuronium-chloride. Already a 0.0005% concentration is sufficient to kill all test germs within 30 minutes. S-dodecylthiuroniumchloride proved to be just as effective as the known well effective quaternary ammonium compounds. It seems to be possible to increase the microbicidal efficiency by additional alkylating - specially methylating - of both nitrogen atoms.
The antibacterial activities of a homologous series (C8-C18) of alkylbenzyldimethylammonium cholorides (ABDAC) against Pseudomonas aeruginosa have been measured using both a minimum inhibitory concentration (MIC) procedure and a sterilization kinetics test carried out in deionized water. There was a log-linear relationship between activity measured by kinetics and carbon number. With MIC there was a log-linear relationship up to C14, when there was a turndown in activity. Consideration of the colloidal association of ABDAC in deionized water and in a simple salts growth media leads us to suggest that use of high concentrations of nutrient salts in MIC tests will lower the effective concentration of the surface active agents. This change may be responsible for the turndown in activity observed in MIC tests, and that in such circumstances the MIC test does not give a true reflection of the intrinsic activity of the compounds. Literature reports of parabolic relationships between ABDAC alkyl chain length and antimicrobial activity are reinterpreted on this basis.
It was shown that ability of developing resistance to QAC by Moraxella ssp. is limited, while marine strains of Pseudomonas sp. are able to develop both homological and heterological resistance to Sterinol and Laurosept. Five months storage in medium without QAC caused partial loss of resistance of strains which previously gained resistance to this compound. None of the tested marine bacteria strains was able to get resistance against Chloramina T. Strains with developed resistance to Laurosept and Sterinol became more sensitive to Chloramina T. On the other hand, as a result of contact of the same bacteria with sublethal doses of Chloramina T increase of sensitivity to QAC was observed.
Four different quaternary ammonium compounds were tested by microtechniques for evaluating their activity against the type species of six viral groups very frequently involved in human and animal pathology. Three disinfectants showed good activity against five of the representative viruses under test, while the fourth proved less effective. Poliovirus type 1 was found to be completely resistant.
Clostridium perfringens spores were injured by ultrahigh-temperature treatment at 105 C for 5 min. Injury was manifested as an increased sensitivity to polymyxin and neomycin. Since many of the survivors could not germinate normally the ultrahigh-temperature-treated spores were sensitized to and germinated by lysozyme. Polymyxin reportedly acts upon the cell membrane. Neomycin may inhibit protein synthesis and has surface-active properties. Injured spores were increasingly sensitive to known surface-active agents, sodium lauryl sulfate, sodium deoxycholate, and Roccal, a quaternary ammonium compound. Injured spores sensitive to polymyxin and neomycin also were osmotically fragile and died during outgrowth in a liquid medium unless the medium was supplemented with 20% sucrose, 10% dextran, or 10% polyvinylpyrrolidone. The results suggested that a spore structure destined to become cell membrane or cell wall was the site of injury. Repair of injury during outgrowth in the presence of protein, deoxyribonucleic acid, ribonucleic acid and cell wall synthesis inhibitors was consistent with this hypothesis.
The endothelial surface of isolated rabbit corneas were perfused for three hours with varying concentrations of benzalkonium chloride and cetylpyridinium chloride. The threshold for physiological and ultrastructural alteration of corneal endothelium is approximately 0.0001% for benzalkonium chloride and 0.01 mM for cetylpyridinium chloride. The effects of the surfactants can be induced with as little as a 15-minute exposure without subsequent recovery. Use of ophthalmic medications or irrigating solutions containing these agents inside the eye is potentially hazardous to the corneal endothelium. Topical administration of 0.133% benzalkonium chloride to the anterior surface of deepithelialized in vivo corneas (five doses, seven minutes apart) caused no alterations of corneal endothelial cell function or ultrastructure.
Pseudomonas cepacia or Enterobacter species or both were isolated from blood cultures of 79 patients in a community hospital between April 1971 and March 1972. No common exposures other than venipuncture correlated with positive blood cultures. Pseudomonas cepacia, Enterobacter, and other Gram-negative enteric bacteria were cultured from aqueous benzalkonium chloride used for skin antisepsis prior to ordinary and blood culture venipuncture. Contamination of blood cultures by organisms from the antiseptic most likely accounted for positive cultures in 35 to 38 patients (92%) with P cepacia. The remaining three patients had repeated blood cultures positive for P cepacia and circumstantial clinical evidence of bacteremia; they may have contracted disease through exposure to the contaminated antiseptic. Substitution of an iodine-alcohol antiseptic abruptly reduced the isolation of P cepacia and Enterobacter.
A number of carboxyl-containing ethylene copolymers have been prepared which exhibit long term antibacterial and antifungal properties. These materials containing antimicrobial agents bound to the copolymer backbone as carboxylate salts, have been tested for their applicability to hospital products as a means of providing "self-sanitizing" articles. Tests have shown that these materials, although not bactericidal, do inhibit microbial growth. Investigations of the compatibility of these polymers with commodity polymers have been made and water emulsions of the polymers have been tested for applicability as components of product protectant coatings.
Electron micrographs of Pseudomonas aeruginosa grown in nutrient broth or broth containing subinhibitory concentrations of benzalkonium chloride indicate that benzalkonium chloride at 50 and 100 mug/ml strips off the outer cell membrane. Cells grown in the presence of edetate disodium, 50-100 mug/ml had convoluted surfaces (wavy in cross section). Cells damaged by growing on nutrient agar containing benzalkonium (200 mug/ml), when subsequently grown for 16 hr in nutrient broth, produced cells with apparently normal outer lavers. Similar cells grown on nutrient agar plus benzalkonium (500 mug/ml) when grown for 16 hr in nutrient broth had normal resistance to edetate disodium lysis, but cells grown overnight in broth plus benzalkonium (500 mug/ml) showed increased sensitivity to edetate disodium lysis. Cells grown on nutrient agar in the presence of benzalkonium (800 mug/ml) grew in broth plus benzalkonium (10 mug/ml) without stripping of their external membrane, but replicate inocula into broth plus benzalkonium (10 mug/ml) and edetate disodium (50 mug/ml) produced cells with structural damage to the outer lavers of the cell envelope.