[Case studies: efficacy of a hydrofiber dressing with ionic silver, ethylenediaminetetraacetic acid and benzethonium chloride]. / Efectividad de un apósito de hidrofibra reforzada, con plata iónica al 1,2%, potenciado con EDTA y cloruro de bencetonio: casos de estudio.

SINOPSIS: Objetivo: Se realizó un estudio prospectivo, observacional, de seguimiento de casos en el servicio de cirugía plástica del hospital El Tunal, Bogotá, Colombia, para evaluar la efectividad de un apósito de hidrofibra reforzada, con plata iónica al 1,2%, potenciado con ácido etilendiaminotetraacético (EDTA) y cloruro de bencetonio en pacientes con heridas de difícil cicatrización. Método: Se incluyeron 23 pacientes con heridas de diferentes etiologías, signos locales de infección, presencia de exudado e indicadores visuales o indirectos de biofilm. Los pacientes fueron divididos en tres grupos: heridas que requerían cicatrización por segunda intención (n=10) (grupo 1), heridas con absceso (n=4) (grupo 2) y heridas en las que se requería preparar el lecho para cobertura quirúrgica (n=9) (grupo 3). El seguimiento de cada caso duró tres meses. Resultados: El grupo 1 demostró una disminución de exudado, infección y signos indirectos de biofilm, así como una reducción significativa de la superficie de la herida con cierre total en ocho de los 10 casos pertenecientes a este grupo. El grupo 2 logró el control de exudado y cierre de la cavidad en un promedio de 21 días. El grupo 3 obtuvo adecuada preparación del lecho de la herida y alcanzó una cobertura quirúrgica en 15 días, en promedio. No se encontraron efectos adversos en los pacientes tratados. Conclusión: Los resultados muestran que el apósito estudiado es efectivo para controlar exudado, infección y signos indirectos de biofilm, así como para disminuir el tamaño de la herida, lograr el cierre de heridas con absceso y preparar el lecho para una cobertura quirúrgica definitiva. ABSTRACT: Objective: A prospective, observational, case-series study evaluated the efficacy of a hydrofiber dressing with ionic silver, ethylenediaminetetraacetic acid and benzethonium chloride in patients with hard-to-heal wounds at El Tunal hospital in Bogota, Colombia. Method: A total of 23 patients with wounds of different aetiologies, local signs of infection, exudate and biofilm were recruited. Patients were divided into three groups: wounds for secondary intention healing (group 1), abscesses (group 2) and wounds for surgical coverage (group 3). Patients were followed up for 3 months. Results: Group 1 showed a reduction in exudate and infection levels, and a decrease in indirect signs of biofilm. There was also a significant reduction in wound surface, with eight out of 10 patients in this group achieving complete wound closure. Group 2 obtained exudate control and wound closure in 21 days, on average. Group 3 demonstrated an adequate wound bed preparation for surgical coverage in 15 days, on average. No side effects were observed. Conclusion: The results showed that the hydrofiber dressing could be effective in controlling exudate and infection levels, and managing the indirect signs of biofilm, as well as reducing the wound surface, achieving wound closure in abscesses and performing wound bed preparation for surgical coverage.

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.

[Povidone-iodine versus the benzethonium chloride wipe for penile skin disinfection before semen collection from sperm donors].

Objective: To study the influence of povidone-iodine (PI) versus that of the benzethonium chloride wipe (BCW) on semen collection and semen quality of sperm donors undergoing penile skin disinfection and provide some evidence for the selection of disinfection methods for semen collection. METHODS: We used PI from August to December 2015 and BCWs from January to July 2016 for penile skin disinfection before semen collection, with two samples from each donor, one collected with and the other without penis skin disinfection (the blank control group). After semen collection, we conducted a questionnaire investigation on the influence of the two disinfection methods on semen collection and compared the semen parameters between the two groups of sperm donors. RESULTS: Totally, 185 sperm donors were included in this study, of whom 63 underwent penile skin disinfection with PI and the other 122 with BCWs before semen collection. Statistically significant differences were found between the PI and BCW groups in the adaptability to the disinfectant and rigid disinfection procedures (P <0.05), but not in the other items of the questionnaire (P >0.05). Compared with the sperm donors of the blank control group, those of the PI group showed statistically significant difference in the percentage of progressively motile sperm (PMS) (ï¼»63.02 ± 3.18ï¼½% vs ï¼»61.45 ± 4.78ï¼½%, P<0.05), but not in the abstinence time (ï¼»4.97 ± 1.79ï¼½ vs ï¼»4.7 ± 0.94ï¼½ d, P >0.05), semen volume (ï¼»4.11 ± 1.54ï¼½ vs ï¼»4.15 ± 1.61ï¼½ ml, P >0.05), sperm concentration (ï¼»110 ± 29.6ï¼½ vs ï¼»107.5 ± 31.79ï¼½ ×106/ml, P >0.05), or total sperm count (ï¼»439.10 ± 170.13ï¼½ vs ï¼»434.02 ± 186.91ï¼½ ×106/ejaculate, P >0.05), while those of the BCW group exhibited no remarkable difference in any of the above parameters (P >0.05). Among the samples with abnormal semen quality, significantly fewer were found with abnormal PMS in the BCW than in the PI group (1.64% ï¼»2/122ï¼½ vs 9.68% ï¼»6/62ï¼½, P <0.05). However, there were no significant differences between the PI and BCW groups in the abnormal semen volume, abnormal sperm concentration, or the rate of semen bacterial contamination (P >0.05). CONCLUSIONS: Before semen collection from donors, penile skin disinfection with povidone-iodine may affect both the semen collection process and the quality of donor sperm, while the benzethonium chloride wipe can reduce the influence on the semen collection process and does not affect the semen parameters.

Co-delivery of chemosensitizing siRNA and an anticancer agent via multiple monocomplexation-induced hydrophobic association.

Synergistic combination of gene targeting and chemotherapy by co-delivering siRNA and anticancer drugs has widely been investigated to develop siRNA-based therapeutics for cancer treatment. Despite clinical potential of this approach, big challenges still remain such as delivery efficiency or stability/biocompatibility of the siRNA delivery system. Here we report a simple and biocompatible co-delivering formulation based on a unique complexation method, i.e., multiple monocomplexation-induced hydrophobic association between Bcl-2 targeting siRNA and a monocationic anticancer agent (benzethonium chloride, BZT). A colloidal formulation of the hydrophobically associated multiple monocomplex (HMplex) composed of siRNA, BZT and Pluronic F-68 was spontaneously constructed by physical mixing of the ternary constituents. In vitro and in vivo studies revealed that the ternary HMplex with a low charge ratio (N/P=4) possesses a tightly complexed stable nanostructure with Pluronic surface and small colloidal size less than 10nm, which allowed for 1) suitable protection of siRNA in serum-rich physiological environment, 2) efficient intracellular transfection into the cytoplasm, and 3) successful peritumoral co-delivery into the tumor tissue with dense interstitial matrix. Compared to non-targeting HMplexes between scrambled siRNA and BZT, Bcl-2 targeting HMplexes enhanced significantly both mRNA down-regulation by siRNA and apoptosis induction by BZT, and thus greatly suppressed the tumor volume when administered to highly aggressive and resistant human breast cancer xenografts (MDA-MB-231) in mice. These results elucidate that the co-complexed siRNA and BZT were liberated by intracellular decomplexation to trigger a synergistically combined therapeutic action. The successful siRNA/chemodrug co-delivery in vivo via peritumoral route and the greatly promoted therapeutic efficacy thereby represent the clinical potential of HMplexes for adjuvant locoregional cancer treatment by gene-targeted combination therapy.

An in vitro test of the efficacy of an anti-biofilm wound dressing.

Broad-spectrum antimicrobial agents, such as silver, are increasingly being formulated into medicated wound dressings in order to control colonization of wounds by opportunistic pathogens. Medicated wound dressings have been shown in-vitro to be effective against planktonic cultures, but in-vivo bacteria are likely to be present in biofilms, which makes their control and eradication more challenging. Recently, a functional wound dressing (AQUACEL(®) Ag+ Extra™ (AAg + E)) has been developed that in addition to silver contains two agents (ethylenediaminetetraacetic acid (EDTA) and benzethonium chloride (BC)) designed to disrupt biofilms. Here, the efficacy of AAg + E is demonstrated using a biofilm model developed in an isothermal microcalorimeter. The biofilm was seen to remain viable in the presence of unmedicated dressing, silver-containing dressing or silver nitrate solution. In the presence of AAg + E, however, the biofilm was eradicated. Control experiments showed that neither EDTA nor BC alone had a bactericidal effect, which means it is the synergistic action of EDTA and BC disrupting the biofilm with silver being bactericidal that leads to the product's efficacy.

[Formulation of benzethonium chloride into gels]. / Formulácia benzetóniumchloridu do gélov.

This study is focused on the preparation of gels with antimicrobial effects. A quaternary ammonium salt, benzethonium chloride, in a concentration of 0.01-0.5% (w/w) was employed as the drug. The humectant employed was propylene glycol in concentrations of 5% and 10% (w/w). Two types of polymers, chitosan and hydroxyethyl cellulose, in the same concentrations of 2.5% (w/w), were used for gel preparation. Finally the flow properties, rheological parameters and pH values of the gels were evaluated. Based on the obtained results, the samples of the gels prepared on the basis of chitosan and hydroxyethyl cellulose, which have the following optimum composition shown below, were found: 2,5% (w/w) CHIT + 0,5% (w/w) BZCl + 10% (w/w) PG; 2,5% (w/w) HEC + 0,5% (w/w) BZCl + 5% (w/w) PG.

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.

Acute otitis externa: an update.

Acute otitis externa is a common condition involving inflammation of the ear canal. The acute form is caused primarily by bacterial infection, with Pseudomonas aeruginosa and Staphylococcus aureus the most common pathogens. Acute otitis externa presents with the rapid onset of ear canal inflammation, resulting in otalgia, itching, canal edema, canal erythema, and otorrhea, and often occurs following swimming or minor trauma from inappropriate cleaning. Tenderness with movement of the tragus or pinna is a classic finding. Topical antimicrobials or antibiotics such as acetic acid, aminoglycosides, polymyxin B, and quinolones are the treatment of choice in uncomplicated cases. These agents come in preparations with or without topical corticosteroids; the addition of corticosteroids may help resolve symptoms more quickly. However, there is no good evidence that any one antimicrobial or antibiotic preparation is clinically superior to another. The choice of treatment is based on a number of factors, including tympanic membrane status, adverse effect profiles, adherence issues, and cost. Neomycin/polymyxin B/hydrocortisone preparations are a reasonable first-line therapy when the tympanic membrane is intact. Oral antibiotics are reserved for cases in which the infection has spread beyond the ear canal or in patients at risk of a rapidly progressing infection. Chronic otitis externa is often caused by allergies or underlying inflammatory dermatologic conditions, and is treated by addressing the underlying causes.

Comparative study on toxic effects induced by oral or intravascular administration of commonly used disinfectants and surfactants in rats.

Accidental ingestion or injection of household products sometimes occurs due to their accessibility, but the toxic manifestations have not been well characterized when they are internally administered. The aim of this study was to investigate the toxic effects induced by ingestion or injection of different ionic surfactants and disinfectants in rats. The test drugs involved benzalkonium and benzethonium (BZK and BZT, both cationic surfactants used as disinfectants), alkyldiaminoethylglycine (AEG, an amphoteric surfactant used as a disinfectant), linear alkylbenzenesulfonate (LAS, an anionic surfactant), polyoxyethylene cetylether (PEC, a nonionic surfactant), chlorhexidine (CHX, not a surfactant but a disinfectant) and saline (control). Male Sprague-Dawley rats were administered one of the test drugs orally (p.o.), intravenously (i.v.) or intraarterially (i.a.). The fatal effects appeared rapidly (<30 min) in i.v.-administered rats, while taking hours (>5 h) in i.a./p.o.-administered rats after a dose of around LD(50) , although the progress and degree of toxic effects varied among the drugs tested. In intravascular administration, BZK and BZT were fatal at doses of 15-20 mg kg(-1) . Higher concentrations in lung and kidney than in blood were determined. CHX showed a high toxic effect compared with cationic surfactants. The rats administered anionic (LAS) or amphoteric (AEG) surfactant died in less than 24 h at doses over 100 mg kg(-1) . In p.o. administration, the toxic effects were concentration/dose-dependent, and all rats administered high doses of surfactants except for PEC died at 5-20 h. The overall toxic ranks could be: cationic surfactant/CHX> anionic/amphoteric surfactant > nonionic surfactant.

Kinetics of 14carbon dioxide excretion from 14C-urea by oral commensal flora.

BACKGROUND AND AIM: Previous studies have shown that while performing the (14)C-urea breath test ((14)C-UBT) for the detection of Helicobacter pylori (H. pylori), there is possibility of false-positive results due to the other urease producing bacteria present in oropharynx, if breath samples are obtained within 30 min after administration of non-capsulated (14)C-urea. Therefore, we have exclusively evaluated the kinetics of (14)carbon dioxide ((14)CO(2)) excretion by oral commensal flora to theoretically propose optimum breath collection timings for (14)C-UBT. METHODS: Multiple breath samples up to 15 min were collected in 0.25 mmol benzethonium hydroxide from 25 healthy volunteers after they withheld 37 kBq (1 muCi) of (14)C-urea in their mouths for 15 s and then expectorated the tracer. The test was repeated on the same subjects without and with mouth cleansing protocols. Breath (14)CO(2) content was measured by the Liquid Scintillation Counter (1409; Wallac, Turku, Finland) and results were expressed as (14)CO(2) excretion per mmol breath CO(2) (% administered dose). RESULTS: Peak breath radioactivity at 1 min in the former protocol was 3.53 times higher than the latter which declined subsequently with a half time of 1 min and 2.5 min, and reached baseline levels by 15 and 10 min, respectively. The peak radioactivity (100%) at 1 min declined by 94% and 97.8% in the former and later protocols, respectively, at 15 min. Although magnitude of the peak varied in different subjects, the shape of curve remained almost similar in all cases. CONCLUSIONS: Without mouth cleansing, oral micro flora excreted more (14)CO(2) up to 15 min after administration of non-capsulated (14)C-urea. Therefore, it is proposed that two breath samples may be obtained either at 15 and 20 min without or at 10 and 15 min with mouth cleansing protocols for reliable analysis of (14)C-UBT data for H. pylori detection.

Evaluation of an alcohol-based surgical hand disinfectant containing a synergistic combination of farnesol and benzethonium chloride for immediate and persistent activity against resident hand flora of volunteers and with a novel in vitro pig skin model.

OBJECTIVE: To evaluate the immediate, persistent and sustained in vivo activity of an alcohol-based surgical hand disinfectant, consisting of a zinc gel and a preservative system containing a synergistic combination of farnesol and benzethonium chloride (ZBF disinfectant), and to develop a pig skin model for in vitro evaluation of the immediate and persistent efficacy of alcohol-based surgical hand disinfectants against resident hand flora. DESIGN: The in vivo immediate, persistent, and sustained activity of ZBF disinfectant was evaluated using human volunteers and the "glove-juice" method described in the US Food and Drug Administration's Tentative Final Monograph (FDA-TFM) for Healthcare Antiseptic Products. A novel in vitro pig skin model was developed to compare the immediate and persistent activity of alcohol-based surgical hand disinfectants against resident flora using Staphylococcus epidermidis as the test organism. Four alcohol-based surgical hand disinfectants were evaluated using this model. RESULTS: The results for the ZBF disinfectant exceed the FDA-TFM criteria for immediate, persistent, and sustained activity required for surgical hand disinfectants. The reduction factors for the 4 hand disinfectants obtained using the pig skin model show good agreement with the log(10) reductions in concentrations of hand flora obtained using human volunteers to test for immediate and persistent activity. CONCLUSION: The ZBF disinfectant we evaluated met the FDA-TFM criteria for surgical hand disinfectants. The immediate and persistent efficacy of the surgical hand disinfectants evaluated with the novel pig skin model described in this study shows good agreement with the results obtained in vivo.

Otitis externa: Review and clinical update.

Otitis externa can take an acute or a chronic form, with the acute form affecting four in 1,000 persons annually and the chronic form affecting 3 to 5 percent of the population. Acute disease commonly results from bacterial (90 percent of cases) or fungal (10 percent of cases) overgrowth in an ear canal subjected to excess moisture or to local trauma. Chronic disease often is part of a more generalized dermatologic or allergic problem. Symptoms of early acute and most chronic disease include pruritus and local discomfort. If left untreated, acute disease can be followed by canal edema, discharge, and pain, and eventually by extra-canal manifestations. Topical application of an acidifying solution is usually adequate in treating early disease. An antimicrobial-containing ototopical is the preferred treatment for later-stage acute disease, and oral antibiotic therapy is reserved for advanced disease or those who are immunocompromised. Preventive measures reduce recurrences and typically involve minimizing ear canal moisture, trauma, or exposure to materials that incite local irritation or contact dermatitis.

Comparative efficacy of hand hygiene agents in the reduction of bacteria and viruses.

BACKGROUND: Health care-associated infections most commonly result from person-to-person transmission via the hands of health care workers. METHODS: We studied the efficacy of hand hygiene agents (n = 14) following 10-second applications to reduce the level of challenge organisms (Serratia marcescens and MS2 bacteriophage) from the hands of healthy volunteers using the ASTM-E-1174-94 test method. RESULTS: The highest log 10 reductions of S marcescens were achieved with agents containing chlorhexidine gluconate (CHG), triclosan, benzethonium chloride, and the controls, tap water alone and nonantimicrobial soap and water (episode 1 of hand hygiene, 1.60-2.01; episode 10, 1.60-3.63). Handwipes but not alcohol-based handrubs were significantly inferior from these agents after a single episode of hand hygiene, but both groups were significantly inferior after 10 episodes. After a single episode of hand hygiene, alcohol/silver iodide, CHG, triclosan, and benzethonium chloride were similar to the controls in reduction of MS2, but, in general, handwipes and alcohol-based handrubs showed significantly lower efficacy. After 10 episodes, only benzethonium chloride (1.33) performed as well as the controls (1.59-1.89) in the reduction of MS2. CONCLUSIONS: Antimicrobial handwashing agents were the most efficacious in bacterial removal, whereas waterless agents showed variable efficacy. Alcohol-based handrubs compared with other products demonstrated better efficacy after a single episode of hand hygiene than after 10 episodes. Effective hand hygiene for high levels of viral contamination with a nonenveloped virus was best achieved by physical removal with a nonantimicrobial soap or tap water alone.

Comparison of the effectiveness of two topical paromomycin treatments versus meglumine antimoniate for New World cutaneous leishmaniasis.

The randomized, controlled study compared the therapeutic efficacy and safety of two paromomycin-containing topical preparations with the gold treatment standard, meglumine antimoniate, and with each other in 120 Ecuadorian patients with ulcerated lesions. The two paromomycin treatment comparisons were double-blinded. Group 1 (n = 14) received 15% paromomycin plus 12% methylbenzonium chloride (PR-MBCL) dissolved in a soft white paraffin base, applied twice daily for 30 days. Group 2 (n = 40) was also treated for 30 days with 15% paromomycin plus 10% urea (PR-U) dissolved in the same paraffin base. Group 3 (n = 40) received 20mg/kg/day of IM meglumine antimoniate (MA) for 10 days as per Ecuadorian Ministry of Public Health recommendations at the time of the study. The 10-day treatment was completed by 90% of the MA group compared to 72.5% of the PR-MBCL (X2 = 4.0, P = 0.045) and 75% of the PM-U (X2 = 3.1, P > 0.05) groups whose treatment regime lasted 20 days longer than the MA treatment. Post-treatment lesion burning, redness, inflammation, and soreness were more common in the two paromomycin groups compared to MA group (P < 0.05). The frequency of treatment-related side effects in the two paromomycin groups was similar. Six weeks after the start of treatment, 80.6% of MA subjects were clinically cured compared to 48.3% in the PR-MBCL (X2 = 6.1, P = 0.014) and 40% in the PM-U groups (X2 = 12.6, P = 0.002). By 12 weeks, the proportion of clinically cured subjects in the MA (91.7%) compared to PM-MBCL (79.3%) or PM-U (70%) groups was not significantly different (P > 0.05). MA-treated subjects clinically cured by 12 weeks had a faster mean healing time (29.5 +/- 12.2 days) compared to those in the PM-MBCL (versus 43.1 +/- 14.4 days, t = -3.7, P = 0.001) or PR-U groups (43.5 +/- 17 days; t = -3.2, P = 0.002). During the 48-week post-treatment follow-up period, infection reactivation was observed in 15.2% of the MA subjects compared to 17.4% in the PM-MBCL and 10.5% PM-U of subjects diagnosed as clinically healed by 12 weeks (P > 0.05). The results suggest that although the time required for the clinical healing of ulcerated lesions takes longer, topical paromomycin may be an acceptable therapeutic alternative in endemic areas where meglumine antimoniate is not available, is too costly or medically contraindicated.

A nonpeptide provides insight into mechanisms that regulate Drosophila melanogaster heart contractions.

Here we report the effect of a nonpeptide, benzethonium chloride (bztc), on Drosophila melanogaster larval, pupal, and adult heart rates in vivo. Benzethonium chloride reduced the frequency of spontaneous contractions in the D. melanogaster pupal heart, but not in the larval heart or the adult heart as measured in noninvasive whole animal preparations. When applied directly to the D. melanogaster heart, in the absence of hemolymph, bztc reduced the frequency of spontaneous contractions in larval, pupal, and adult hearts. These findings are consistent with the conclusion that bztc acts through or is regulated by different mechanisms in these three developmental stages. An alternative explanation is that larval hemolymph and adult hemolymph contain a material that interferes with the effect of the nonpeptide on heart contractions. Bztc mimicked the effect of the peptide dromyosuppressin (DMS) on the heart at an equivalent concentration; in contrast, 103-fold more nonpeptide is required to mimic the effect of DMS on fly gut. These findings are consistent with the presence of tissue-specific myosuppressin receptors or mechanisms.

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.

Subarachnoid ketamine in swine--pathological findings after repeated doses: acute toxicity study.

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate whether 5% ketamine with and without preservative, administered intrathecally to swine, produced a clinical anesthetic effect and caused direct subacute neurotoxicity. METHODS: Twenty pigs were used. Under general anesthesia, a subarachnoid catheter was placed at L5-L6 or L6-S1 spinal interspace. Five animals were used for initial clinical evaluation of the anesthetic effects of subarachnoid ketamine (12.5 and 25.0, and 500 mg). Two animals were excluded because of bloody taps, two served as controls (catheterization without drug administration), four received ketamine racemate (25.0 mg/d), four received ketamine racemate preservative free (25.0 mg/d), and three received benzethonium chloride, the ketamine excipient (0.05 mg/d). All drugs were administered for 7 days. The catheters were withdrawn at the end of the treatment period. After 35 days, the pigs were euthanized and the spinal cord removed and preserved for histopathologic study with hematoxilyn-eosin and luxol-fast blue myelin staining. Histopathologic effects were defined as absent/minimal, mild, or severe by a pathologist, unaware of group allocation, by evaluating the presence and intensity of peripheral and/or central chromatolysis, spongiosis, neuronal loss, perivascular neuroglia, neuronolysis, and myelin degeneration. RESULTS: All doses of ketamine produced immediate cutaneous anesthesia and motor block; benzethonium chloride did not. Histopathologic examination showed no neurotoxic effect of ketamine without preservative; ketamine with preservative showed a discrete neurotoxic effect, and the preservative alone produced a moderate neurotoxic effect. CONCLUSIONS: Clinically, in swine, subarachnoid ketamine without preservative is a safe and effective anesthetic and did not show significant neurotoxic effects. However, ketamine with preservative produces minimal changes, and benzethonium chloride alone produces moderate neurotoxic effects.

Topical paromomycin/methylbenzethonium chloride plus parenteral meglumine antimonate as treatment for American cutaneous leishmaniasis: controlled study.

We determined the efficacy of the combination of the topical formulation 15% paromomycin sulfate/12% methylbenzethonium chloride (MBCL) and a short course (7 days) of parenteral meglumine antimonate (pentavalent antimony [Sb]) as treatment of American cutaneous leishmaniasis in Colombian patients. Patients were randomly assigned in unequal allocation (2:1:1:1) to group 1 (topical paromomycin/MBCL plus injectable Sb for 7 days), group 2 (topical placebo plus injectable Sb for 7 days), group 3 (topical paromomycin/MBCL plus injectable Sb for 3 days), and group 4 (injectable Sb for 20 days). Cure was defined as complete reepithelialization of all lesions without relapse. Cure rates among groups were as follows: 58% (34 of 59), group 1; 53% (16 of 30), group 2; 20% (6 of 30), group 3; and 84% (26 of 31), group 4. Seventy-one percent of the organisms identified to the species level were Leishmania braziliensis panamensis. We conclude that 10 days of therapy with paromomycin/MBCL does not augment the response of cutaneous leishmaniasis (predominately due to L. braziliensis panamensis) to a short course of treatment with meglumine antimonate.