Triclosen and Its Alternatives in Antibacterial Soaps.

BACKGROUND: In 2017, the Food and Drug Administration banned the marketing of triclosan and triclocarban in antibacterial soaps, citing inefficacy and concerns of systemic absorption and antibacterial resistance. As a result, there is an anticipated decrease in the number of triclosan-containing products on the market with an associated increase in antibacterial alternatives (eg, benzalkonium chloride, benzethonium chloride, chloroxylenol, chlorhexidine) and cases of allergic and irritant contact dermatitis. OBJECTIVES: The aims of the study were to determine the extent that triclosan and triclocarban are being used in the consumer and medical industries after the Food and Drug Administration marketing ban and to appraise the risk of allergic contact dermatitis to triclosan alternatives. METHODS: The National Drug Code Directory (NDCD), Google, Amazon, Target, Walgreens, Walmart, CVS, and Colorado hospitals were surveyed for antibacterial soap use. Antibiotics surveyed include triclosan, triclocarban, benzalkonium chloride, benzethonium chloride, chloroxylenol, and chlorhexidine. RESULTS: The most common antibiotics reported by the NDCD, consumer sites, and Colorado hospitals were benzalkonium chloride, chloroxylenol, and triclosan, respectively. Triclosan accounted for the second most prevalent antibacterial in the NDCD- and consumer site-surveyed products. CONCLUSIONS: The triclosan marketing ban may instigate increased exposure to triclosan alternatives. The addition of antibacterial products to hand soaps does not improve soap effectiveness and may cause harm by contributing to antibiotic resistance and the development of allergic conditions. Additional studies are needed to elucidate the benefits and harms of antibacterial soaps.

Clinical pearl: benzethonium chloride for habit-tic nail deformity.

Treatment of habit-tic nail deformity is challenging, as it often requires both patient awareness and behavioral changes that may be long-standing. Many treatment options have been suggested, but limitations include inadequate supporting evidence and potential adverse effects. Herein, we describe the use of benzethonium chloride as a safe and effective treatment of habit-tic nail deformity.

Ototoxicity of aluminum acetate/benzethonium chloride otic solution in the chinchilla animal model.

OBJECTIVES/HYPOTHESIS: To determine the ototoxic potential of aluminum acetate (0.5%)/benzethonium chloride (0.03%) otic solution in the chinchilla animal model. STUDY DESIGN: A randomized, prospective, controlled study was conducted in the chinchilla animal model. METHODS: Fourteen female chinchillas were used. After an incision was made in each tympanic membrane, baseline auditory brainstem response measurements were performed at 16, 20, and 25 kHz. One ear was randomized to receive aluminum acetate (0.5%)/benzethonium chloride (0.03%), whereas the other ear served as the control and received 0.9% NaCl. Solutions were applied transtympanically once a day for 3 consecutive days. Postapplication auditory brainstem response measurements were done at day 7 and day 30. In half of the animals, scanning electron microscopy was done following the last auditory brainstem response measurement. RESULTS: A statistically significant difference was found between the mean threshold shifts in the experimental and control ears at all frequencies on both 7 and 30 days postapplication (P < .02). Increased ossification of the cochleae was seen in experimental ears (n = 12). Scanning electron microscopy study demonstrated outer hair cell damage and/or loss in the experimental ears. No significant morphological changes were detected on scanning electron microscopy obtained from the control ears. CONCLUSIONS: Application of aluminum acetate (0.5%)/benzethonium chloride (0.03%) otic solution causes hearing loss in chinchillas when a tympanic membrane perforation exists. Further studies are needed to test the effect of this otic solution on hearing. LEVEL OF EVIDENCE: 4.

Sensitization prevalence for benzalkonium chloride and benzethonium chloride.

BACKGROUND: Benzalkonium chloride (BAK) and benzethonium chloride (BEC) are well-characterized skin irritants and rare sensitizers, but optimal testing for allergic contact dermatitis (ACD) is not established. OBJECTIVE: Sensitization prevalence was sought, and several patch testing concentrations and vehicles were compared. METHODS: One hundred forty-two patients tested to the standard screening series for evaluation of dermatitis consented to additional tests including BAK 0.15% aqueous (aq), BAK 0.15% petrolatum (pet), BEC 0.15% aq, and BEC 0.5% aq. Follow-up to assess clinical relevancy included early and late patch test reads, 1-month clinical follow-up, and long-term phone calls. Patients were categorized as definite, possible, or unlikely to have ACD to BAK and/or BEC. RESULTS: Atopy was not associated with patch test reactions (P = 0.154). Seventy-five percent (6/8) of the patients with possible ACD to BAK had coreactions with BEC. Testing to both BAK 0.15% pet and 0.15% aq would have identified 91% of those with possible ACD to BAK, twice as many than if only BAK 0.1% aq from the standard series was used. CONCLUSION: Sensitization to BAK and BEC, although rare, does occur. Weak and morphologically irritant reactions at day 7 reading can be relevant. We recommend testing to BAK 0.15% aq and 0.15% pet to increase sensitivity and having patients undergo long-term follow-up.

Adverse effects by artificial grapefruit seed extract products in patients on warfarin therapy.

OBJECTIVE: Grapefruit seed extract (GSE) is promoted as a natural product with antibacterial and antiviral properties. The aim of this study was to investigate the composition of some commercially available GSE products and evaluate their effect in vitro on two cytochrome P450 enzymes, CYP2C9 and CYP3A4. METHODS: A couple on lifelong treatment with warfarin and continuous regular follow-ups took some drops of a GSE product for 3 days. The female patient experienced a minor subcutaneous haematoma 3 days later, and her international normalised ratio (INR) value was 7.9. This was reported to the Swedish Medical Products Agency (MPA) as a spontaneous post-marketing report concerning adverse drug reactions/interactions. The composition of the GSE products was determined by proton and carbon-13 nuclear magnetic resonance spectroscopy (NMR). The inhibitory effect of the GSE products on the cytochrome P450 enzymes was tested in an in vitro baculosome assay. RESULTS: The NMR analysis showed that all three investigated GSE products contained the synthetic preservative benzethonium chloride (BTC) in addition to glycerol and water. No authentic GSE extract was found in any of the three GSE products analysed. Furthermore, BTC was found to be a potent inhibitor of CYP3A4 and CYP2C9 activity in vitro. CONCLUSION: Our results suggest that BTC in the GSE products is responsible for the increase in the INR value in a patient on warfarin treatment.

A toxicity index of skin and wound cleansers used on in vitro fibroblasts and keratinocytes.

OBJECTIVE: To determine toxicity indexes of commercially available skin, wound, and skin/wound cleansers on in vitro fibroblasts and keratinocytes. DESIGN: Seventeen cleansers and 3 liquid bath soaps were evaluated for cytotoxic effect on human infant dermal fibroblasts and epidermal keratinocytes. Both skin cell types were exposed to serial 10-fold dilutions of each cleanser until treated cell viability was comparable to untreated controls. RESULTS: The experimental design allowed calculation of relative toxicity indexes ranging from 0 to 100,000. Shur-Clens, SAF-Clens, and saline were found to be the least toxic to fibroblasts (toxicity index 0); Dial Antibacterial Soap and Ivory Liqui-Gel were the most toxic (toxicity index 100,000). Biolex, Shur-Clens, and Techni-Care were the least toxic to keratinocytes (toxicity index 0); hydrogen peroxide, modified Dakin's solution, and povidone (10%) were found to be the most toxic (toxicity index 100,000). CONCLUSIONS: Successful cutaneous tissue repair depends on the viability of the principal cell types involved (fibroblasts and keratinocytes). Toxicity indexes provide helpful guidelines for subsequent in vivo evaluations and clinical applications. The study findings also suggest that judicious use of these supposedly innocuous agents should be considered in a clinical setting.

In vitro evaluation of skin sensitivity of povidone-iodine and other antiseptics using a three-dimensional human skin model.

Povidone-iodine (PVP-I) is an antiseptic which has been widely used in various fields. It was reported to have a weaker skin irritancy than other antiseptics in the Draize skin irritation test using rabbits. Recent increased concern for animal welfare requires us to use skin models in the tests as an alternative to animal testing. Actually, there are some skin models already commercialized, which are available to evaluate skin irritancy caused by e.g. chemical reagents, cosmetics or medicines. In this study, we evaluated the potential of a PVP-I solution and other antiseptics to cause irritation using a cultured human skin model (three-dimensional skin model) under conditions similar to clinical use. This skin model has two layers like a real skin, such as the dermis and epidermis which includes the cornified layer. For the evaluation of skin irritancy in this model, cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay as an endpoint. Antiseptic formulations such as benzalkonium chloride (BAC), benzethonium chloride (BEC), chlorhexidine gluconate (CHG) and alkyldiaminoethylglycine hydrochloride (AEG) were used in this study. As a result, PVP-I showed a significantly weaker skin irritancy compared to the other antiseptics. The present in vitro study results revealed a correlation with the results of previously conducted in vivo skin irritancy tests using rabbits.

Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala.

A double-blind, randomized trial was undertaken in Guatemala to determine the therapeutic efficacy of an ointment for the treatment of cutaneous leishmaniasis that contained 15% paromomycin and 12% methylbenzethonium chloride and that was applied twice a day for 20 days. The treatment group included 35 patients, and the placebo group included 33 patients. The initial clinical response rate (13 weeks after completing the treatment) was 91.4% in the treatment group and 39.4% in the placebo group. The final clinical response rate at the 12-month follow-up examination was 85.7% (31 of 35) in the treatment group and 39.4% (13 of 33) in the placebo group (P < or = 0.001). In general, the treatment was well tolerated and was never interrupted because of adverse effects. The number of adverse effects reported in the placebo group was lower than in the treatment group (16 events versus 30 events). All adverse effects reported by patients disappeared within 1 week of completing the treatment. Our findings show that the combination of paromomycin with methylbenzethonium chloride for 20 days is a good alternative for antimonial treatments of cutaneous leishmaniasis in Guatemala.

Inhibition of acetylcholine esterase and choline esterase by benzethonium chloride and avoidance of the benzethonium chloride carry-over inhibitory effect.

It has been shown that benzethonium chloride produces linear mixed-type inhibition of choline esterase and acetylcholine esterase. These enzymes also show-reagent-carry-over inhibition if the enzyme activities are measured in plastic cuvettes in which previously protein has been determined by the alkaline benzethonium chloride method. Choline esterase is about 10-fold more sensitive to benzethonium chloride than acetylcholine esterase. With acetylthiocholine as substrate Michaelis-Menten constants for choline esterase and acetylcholine esterase are 85 mumol/l and 102 mumol/l, respectively. Carry-over inhibitory effect of benzethonium chloride can be avoided by washing the cuvettes, after protein determination by the benzethonium chloride method, with 5 ml/l Triton X-100, 5 ml/l Tween 20 or 10 g/l sodium dodecyl sulphate. The latter has a disadvantage in that it precipitates out at low temperatures. The dry slide method (Johnson & Johnson) for serum choline esterase is free of the inhibitory effect until the concentration of benzethonium chloride in the sample reaches about 200 mumol/l.

Successful treatment of New World cutaneous leishmaniasis with a combination of topical paromomycin/methylbenzethonium chloride and injectable meglumine antimonate.

Colombian patients with New World cutaneous leishmaniasis were treated with a combination of a topical formulation (15% paromomycin sulfate/5% methylbenzethonium chloride, twice a day) and parenteral meglumine antimonate (20 mg of antimony [Sb]/kg.d]). Cohort 1 received topical therapy for 10 days and Sb for 7 days; 18 (90%) of the 20 patients were cured (follow-up, 12 months). Other clinical data suggested that neither the topical formulation alone nor the 7-day regimen of Sb alone would have cured many patients. In a subsequent cohort, which received topical therapy for 10 days and Sb for 3 days, the cure rate was 42% (eight of 19 patients). In Colombian cohorts (historical controls) treated with Sb alone for 10-15 days, the cure rate was 31%-36%. Side effects in cohort 1 patients consisted of local reactions to the topical formulation: burning and pruritus in 25% of patients and vesicle formation in 15% of patients. This is the first report that a regimen partially composed of topical antimicrobial agents can be highly effective for treatment of New World cutaneous leishmaniasis.

[Successful topical treatment of chronic cutaneous leishmaniasis with paromomycin sulfate (15%) and methylbenzethonium chloride (12%)]. / Erfolgreiche topische Behandlung der chronisch kutanen Leishmaniose mit Paromomycinsulfat (15%) und Methylbenzethoniumchlorid (12%).

A 19-year-old male patient with chronic cutaneous leishmania is was treated topically with paromomycin sulphate (15%) and methylbenzethonium chloride (12%) in petrolatum album. After application twice daily for two periods of 32 and 44 days the lesions were completely healed. Previous treatment for 9 months with ketoconazole (400 mg/day) together with the topical application of thiabendazole (2.5%) in base had been unsuccessful. No major side effects were observed after paromomycin sulphate application.

Toxicity of ototopical drugs: animal modeling.

It is important to be aware of the potential ototoxicity of any drug, vehicle, or antiseptic that is used in the middle ear. Frequently used ear drops (Cortisporin otic suspension, Coly-Mycin S Otic, and VoSoL otic solution) were studied for their ototoxicity. Compound action potentials were measured before and at 1, 2, and 24 hours following drug application on the round window membranes of chinchillas. Each drug was applied for 10 minutes and then was removed by rinsing. The sound pressure in decibels sound pressure level that produced a compound action potential amplitude of 10 microV was defined as the threshold. The change in threshold was interpreted as hearing loss. On the basis of the short-term results at 24 hours following drug application, the ototoxicity of Coly-Mycin was calculated to be twice that of Cortisporin, and the ototoxicity of VoSoL four times that of Cortisporin.

A clinical trial of Neo Sampoon vaginal tablets and Emko foam in Alexandria, Egypt.

Results are reported for a comparative 12-month study of Neo Sampoon foaming vaginal tablets containing 60 mg of the spermicide, menfegol, and Emko vaginal foam containing an 8.0% concentration of the spermicide, nonoxynol-9. Conducted in cooperation with the Family Planning Association in Alexandria, Egypt, the trial included 349 women who were randomly allocated to use one of the two contraceptive products. The twelve-month cumulative life-table rate for accidental pregnancy (per 100 women) was 2.8 for Neo Sampoon tablet users and 2.1 for Emko foam users. The 12-month continuation rates were 77.6 and 77.2 per 100 women for the tablet and foam groups, respectively. In both groups, the majority of discontinuations from the study were for personal reasons, including lack of confidence in the method, messiness, partner's objection and a burning sensation. Few women reported a product-related complaint while using their assigned contraceptive method. The most commonly reported complaint for both methods was that use of the product led to an uncomfortable burning sensation for the woman and/or her partner. This complaint, however, was cited by less than 5% of the women in each group. Thus, a combination of low pregnancy rates, few complications and complaints and high continuation rates confirm the relative acceptability, effectiveness and short-term safety of these methods of contraception among this sample of Egyptian women.

PIP: Results are reported for a 12-month study of Neo Sampoon foaming vaginal tablets containing 60mg of the spermicide, menfegol, and EMKO vaginal foam containing an 8.0% concentration of the spermicide, nonoxynol-9. Conducted in cooperation with the Family Planning Association in Alexandria, Egypt, the trial included 349 women randomly allocated to use 1 of 2 contraceptive products. The 12-month cumulative life-table rate for accidental pregnancy (per 100 women) was 2.8 for Neo Sampoon tablet users and 2.1 for Emko foam users. The 12-month continuation rates were 77.6 and 77.2/100 women for the tablet and foam groups, respectively. In both the majority of discontinuations from the study were for personal reasons, including lack of confidence in the method, messiness, partner's objection and a burning sensation. Few women reported a product-related complaint while using their assigned contraceptive method. The most commonly reported complaint for both methods was that use of the product led to an uncomfortable burning sensation for the woman and/or her partner. This complaint, however, was cited by 5% of the women in each group. Thus, a combination of low pregnancy rates, few complications and complaints and high continuation rates confirm the relative acceptability, effectiveness and short-term safety of these methods of contraception among this sample of Egyptian women.

Evaluation of extrinsic tooth discoloration.

Extrinsic brown tooth discolorations are frequently detected in connection with antibacterial agents used for chemical plaque control. The present investigation confirmed the staining ability of an antibacterial quarternary ammonium salt, benzethoniumchloride, used as a 2% additive to a dentifrice. A weak chelator did not alter the discoloration tendency. Extrinsic discoloration was evaluated both by direct inspection, from color photographs and by using a microphotometric technique. The discoloration tendency was well demonstrated by all three techniques. Evaluation from the color photographs, however, may be preferable in epidemiological surveys while the microphotometric technique may possess certain advantages in detailed experimental discoloration studies.