Polymeric Biguanide Research Articles

Comparative antimicrobial efficacy of 4 surgical hand-preparation procedures prior to application of an alcohol-based hand rub in veterinary students.

To determine the influence of skin preparations before application of an alcohol-based hand rub (ABHR) on bacterial counts before and after elective surgery. Clinical prospective study. Veterinary students (n = 103) performing ovariohysterectomies on 140 dogs. Participants were randomly assigned to 1 initial surgical preparation on the day of surgery: A - hand preparation with medicated solution (4% w/v chlorhexidine bigluconate followed by an ABHR; B - application of a medication solution (benzalkonium chloride 0.1%-1% and polymeric biguanide hydrochloride 0.01%-0.1%) followed by an ABHR; C - nonmedicated pH-neutral soap hand wash followed by ABHR, and D - direct application of an ABHR. Samples were taken by pressing the distal finger tips to an agar plate before the hand preparation, after the hand preparation (n=3), after ABHR application, and 120 minutes later. Colony-forming units (CFUs) for samples were determined. Total log CFU and CFU log10 reduction were calculated and used for comparison with P < .05. Two hours after surgery commenced, the participants of groups that performed a hand preparation had lower total CFUs than those that did not perform a hand preparation (P= .001). In particular, the number of CFUs was lower when ABHR was performed after application of pHN compared to direct ABHR (P= .001). In this population, performing a hand preparation with pHN prior to applying an ABHR had better antimicrobial effect for the duration of surgery than not performing a hand preparation. Surgeons should wash their hands prior to ABHR before starting their first surgery of the day, even when hands appear clean.

Genomic elements located in the accessory repertoire drive the adaptation to biocides in Listeria monocytogenes strains from different ecological niches

In response to the massive use of biocides for controlling Listeria monocytogenes (hereafter Lm) contaminations along the food chain, strains showing biocide tolerance emerged. Here, accessory genomic elements were associated with biocide tolerance through pangenome-wide associations performed on 197 Lm strains from different lineages, ecological, geographical and temporal origins. Mobile elements, including prophage-related loci, the Tn6188_qacH transposon and pLMST6_emrC plasmid, were widespread across lineage I and II food strains and associated with tolerance to benzalkonium-chloride (BC), a quaternary ammonium compound (QAC) widely used in food processing. The pLMST6_emrC was also associated with tolerance to another QAC, the didecyldimethylammonium-chloride, displaying a pleiotropic effect. While no associations were detected for chemically reactive biocides (alcohols and chlorines), genes encoding for cell-surface proteins were associated with BC or polymeric biguanide tolerance. The latter was restricted to lineage I strains from animal and the environment. In conclusion, different genetic markers, with polygenic nature or not, appear to have driven the Lm adaptation to biocide, especially in food strains but also from animal and the environment. These markers could aid to monitor and predict the spread of biocide tolerant Lm genotypes across different ecological niches, finally reducing the risk of such strains in food industrial settings.

Comparative efficacy study of brimonidine tartrate 0.15% and timolol maleate 0.5% ophthalmic solution (benzalkonium chloride free) versus Brimolol® (with benzalkonium chloride) following single ocular instillation in New Zealand white rabbits

Background: Benzalkonium chloride (BKC) is the most used preservative in topical eye drops but it causes effects such as dry eye and trabecular meshwork degeneration. Polyhexamethylene biguanide (PHMB) is a polymeric biguanide is a less harmful preservative used in ophthalmic solutions. The objective of this study to com-pare the efficacy of PHMB preserved versus BKC preserved ophthalmic solutions containing brimonidine tartrate and timolol maleate on intraocular pressure (IOP) following single ocular instillation in New Zealand white (NZW) rabbits.Methods: This study was conducted on 12 normotensive male NZW rabbits (2.9-3.6 kg) between 6-9 months of age. Animals received single ocular instillation of 35 µl ophthalmic solution containing brimonidine tartrate 0.15 %w/v and timolol maleate 0.5% w/v with PHMB as preservative (n=6, test) or BKC as preservative (n=6, reference) as per the randomization. Intraocular pressure (IOP) was measured before and 2, 4, 6, 8 and 24 hours after instillation using a pneumatonometer. Percentage change in IOP from pre-instillation values were calculated. Changes in IOP were analysed using the repeated-measures analysis of variance followed by Bonferroni post-test.Results: Single ocular instillation of PHMB and BKC formulations show significant IOP reduction up to 6 hours as compared with baseline (p&lt;0.05). Reduction in IOP was 35.8% and 32.0% at 2 hours with PHMB and BKC formulations respectively. No differences were observed between the test and reference groups for change in IOP from baseline.Conclusions: PHMB preserved brimonidine tartrate 0.15% w/v and timolol maleate 0.5% w/v ophthalmic solution was comparable to BKC preserved solution in normotensive NZW rabbits.

Comparative evaluation of substantivity of two biguanides - 0.2% polyhexanide and 2% chlorhexidine on human dentin.

Background:Substantivity is one of the desirable characteristics of root canal irrigants. Among conventional endodontic irrigants, only chlorhexidine (CHX) is known to exert significant substantivity on root canal dentin. This study explored the substantivity activity of a polymeric biguanide-poly hexamethylene biguanide (PHMB).Aim:The aim of this study was to determine the substantivity of a polymeric biguanide - 0.2% PHMB and compare it with that of 2% CHX.Materials and Methods:To evaluate and compare the substantivity of 0.2% PHMB and 2% CHX on root canal dentin, dentin disks were prepared and substantivity after 1 h, 24 h, 7 days and 21 days was measured using spectrophotometry.Statistical Analysis Used:The data so obtained were analyzed, and the intergroup comparison was made using unpaired t-test.Results:The results of this study indicated that 0.2%. PHMB exerts significantly greater substantivity than 2% CHX on human dentin.Conclusion:Within the limitations, this study supports the use of 0.2% polyhexanide as an endodontic irrigant based on its property of substantivity.

Potential use of germicides in vase solutions for gladiolus ‘White Friendship’

Gladiolus (Gladiolus x hortulanus) is one of the most important crops for cut flowers worldwide, however having a short longevity. Usually, stems are harvested at the bud stage and need water and carbohydrates to support inflorescence development and to ensure flower quality. Vase solutions can supply these elements. However, sugars may benefit bacterial proliferation, which eventually can block xylem vessels. Bactericides potentially inhibit microorganism proliferation and new compounds are being tested constantly. This experiment was conducted to evaluate ‘White Friendship’ cut gladiolus performance in vase solutions with sodium dichloroisocyanurate dihydrate (Na-DCC), 8-hydroxyquinoline (8-HQ) or polymeric biguanide (PB). Inflorescences harvested at commercial maturity were placed in distilled water with 4% w/v of sucrose plus the germicides and kept under ambient conditions. Vase life, inflorescence postharvest development, fresh mass, membrane stability index and water relations were evaluated. There were no visual symptoms of toxicity in the treatments. The highest values of vase life, fully-open flowers, fresh mass and water balance were obtained with the Na-DCC treatment. Inflorescences treated with 8-HQ exhibited the highest values of solution uptake and wilting flowers. PB had a limited effect in gladiolus postharvest since the obtained results were similar to the sucrose alone. There was no effect of germicides on membrane stability index and its reduction was due to flower senescence progress only. Vase solution with Na-DCC plus sucrose improved water balance, increased open flowers, reduced wilting of flowers and fresh mass loss. Therefore, vase solutions with sucrose 4% w/v and Na-DCC enhance postharvest quality of cut gladiolus inflorescences.

Electrospun fibrous mats from a l-phenylalanine based poly(ester amide): Drug delivery and accelerated degradation by loading enzymes

Fibrous mats from an α-amino acid based poly(ester amide) have been prepared due to the potential applications of this kind of polymers in the biomedical field thanks to the expected non-toxicity of their degradation products. Specifically, the electrospinning technique has been applied and both solution properties and operational parameters have been optimized to get continuous fibers in the micrometer range. Furthermore, fibrous mats have been loaded with biguanide compounds differing on molecular size but having a well-proved bactericide activity (i.e., chlorhexidine, CHX and polyhexamethylenebiguanide, PHMB). The high solubility of the poly(ester amide) constituted by l-phenylalanine, adipic acid and 1,4-butanediol also allowed getting appropriate electrospinning conditions to incorporate degrading enzymes like α-chymotrypsin without significant denaturation.Degradability of fibrous mats has been evaluated in distinct enzymatic media (lipase, proteinase K and α-chymotrypsin) being found a similar behavior that contrasts with the significant differences detected when film samples were employed. An accelerated degradation was clearly found for fibrous mats loaded with α-chymotrypsin even when they were exposed to a non-enzymatic aqueous medium.Release of bactericide agents was evaluated and a specific delay was determined when the polymeric biguanide was employed. Nevertheless, PHMB showed a clearly enhanced activity. Biocompatibility of the new fibrous mats was verified being also determined an increase on the cell adhesion with respect to film samples as a consequence of the increased porosity.

Investigating Hyponatremia, Exit-Site Management and Discharge Planning

Investigating Hyponatremia, Exit-Site Management and Discharge Planning

Inhibition of the anti-staphylococcal activity of the antiseptic polihexanide by mucin.

The antiseptic Lavasept (LS), containing the polymeric biguanide polihexanide (CAS 28757-48-4), possesses microbicidal activity against a broad spectrum of bacteria including Staphylococcus aureus. It is used for antiseptic wound care in concentrations corresponding to 0.2-0.4 mg polihexanide per ml. To obtain basic data on its ability to eradicate S. aureus colonizing the nasal mucosa, the influence of mucin on the anti-staphylococcal activity was investigated. A disk agar-diffusion method was applied. Two reference strains of S. aureus (methicillin-sensitive S. aureus ATCC 29213 and methicillin-resistant S. aureus ATCC 33591) and 20 fresh clinical isolates were used. In the absence of mucin, the growth of all strains was inhibited by polihexanide concentrations of 0.1 mg/ml. In the presence of 0.25% mucin in the test medium, a concentration of 0.4 mg/ml was necessary to inhibit all strains. Mucin concentrations of 0.5% and 1%, that are even lower than the mucin concentrations in healthy nasal secretions, abolished the activity of the therapeutic concentrations of polihexanide. It is concluded that the inactivation of LS by mucin obstructs a reliable clearance of nasal S. aureus carriage.

Efficacy of Contact Lens Multipurpose Solutions Against Serratia Marcescens

To compare the susceptibilities of clinical isolates of Serratia marcescens and the standard ISO ATCC 13880 strain to five contact lens multipurpose disinfection solutions (MPDSs). Five commercially available MPDSs, containing either a polymeric biguanide or polyquaternium, were tested using ISO/CD 14729 stand-alone test for contact lens care products against four ocular isolates of S. marcescens and the strain ATCC 13880. An average log reduction in bacterial numbers at the manufacturer's minimum recommended disinfection time was determined and compared with the criteria for stand-alone disinfection products for each MPDS against each bacterial strain. All the MPDSs tested met the stand-alone criteria of 3-log reduction of viable bacteria against the ATCC strain of S. marcescens. However, there was more variability in their ability to meet disinfection criteria when tested against the clinical isolates. Two of the clinical isolates were significantly more resistant to disinfection than was the recommended ISO strain (p < or = 0.034). Two of the polyquaternium-1-based disinfection solutions (solutions D and E, p < or = 0.005) were less effective overall than the other MPDSs against S. marcescens. The importance of strain selection for the testing of MPDSs is indicated, and the use of a single laboratory strain may be insufficient to provide assurance that the disinfection solution will be effective against clinical isolates. Furthermore, clinical isolates of S. marcescens may show increased resistance to disinfection with polyquaternium.

INFUSÃO UTERINA COM BIGUANIDA POLIMÉRICA SOBRE A COLONIZAÇÃO BACTERIANA DO ÚTERO DE VACAS COM INFECÇÃO PUERPERAL APÓS RETENÇÃO DE ENVOLTÓRIOS FETAIS

Com o objetivo de estudar a viabilidade da utilização de biguanida polimérica, no tratamento tópico de infecções puerperais em fêmeas bovinas após o parto prematuro, 20 fêmeas Girolando pertencentes a um sistema de produção leiteira, que apresentaram retenção de envoltórios fetais e conseqüentemente endometrite puerperal, foram distribuídas aleatoriamente em dois grupos. O Grupo I, foi constituído de animais que receberam três infusões uterinas de biguanida polimérica; e o Grupo 2, animais não tratados. Foram realizadas colheitas de conteúdo uterino na primeira, terceira e quinta semanas pós-parto para realização de cultivos bacteriológicos, ou seja, antes da infusão, aos 14 e 28 dias após tratamento medicamentoso. O resultado dos cultivos bacteriológicos nos dois grupos demonstrou que a utilização da biguanida polimérica não reduziu a colonização bacteriana no útero dos animais tratados, em comparação àqueles não tratados.

Influence of Mucin on the Activity of the Antiseptic Lavasept® against Staphylococcus aureus

Background: Lavasept^®, containing the polymeric biguanide polyhexanide, may be effective against Staphylococcus aureus colonizing the nasal mucosa. To obtain basic data on its suitability for that purpose, its antimicrobial activity was examined in the presence of mucin. Methods: A disk diffusion test was applied using Mueller-Hinton agar, and disks soaked with a therapeutic and a 10-fold higher concentration of Lavasept. Commercially available mucin preparations from porcine stomach were added to the test system. Reference strains and 20 clinically isolates of S. aureus, and reference strains of Escherichia coli, Pseudomonas aeruginosa, Enterococcusfaecalis, and Candida albicans were tested. Results: Supplementation of the test medium with 1% mucin completely abolished the activity of disks loaded with the therapeutically used concentration of the antiseptic. The neutralizing effect of mucin occurred with all test strains. Conclusions: The inactivation of Lavaseptby mucin may hamper a reliable clearance of nasal S. aureus carriage.

Acanthamoeba castellanii: Growth, encystment, excystment and biocide susceptibility

Stages in the encystment and excystment processes of Acanthamoeba castellanii have been studied. The kinetics of encystment involved measurements of the three phases (pre-encystment, cyst initiation and cyst wall synthesis). Excystment, starting from a mature cyst, involved pre-emergence, penetration outwards of the cyst wall and free trophozoite. The sensitivity to biocides of trophozoites in the exponential growth phase, pre-encystment trophozoites, mature cysts and pre-excystment cysts has been investigated. Some differences in relative sensitivity to a bisbiguanide (chlorhexidine) and a polymeric biguanide (polyhexamethylene biguanide) were observed, but mature cysts were always the most resistant cellular form.

Treatment of Nocardia asteroides Keratitis with Polyhexamethylene Biguanide

Polyhexamethylene biguanide (PHMB) is a polymeric biguanide disinfectant that has been used previously in the treatment of Acanthamoeba keratitis. The authors report the first case of Nocardia asteroides keratitis treated successfully with PHMB. Further studies documenting the efficacy of PHMB against N. asteroides in vitro also are presented. A soft contact lens wearer presented with an infectious keratitis. Cultures from the cornea grew N. asteroides. The infection resolved with the treatment with PHMB 0.02%. Serial dilutions of PHMB were performed against N. asteroides in culture. In vitro dilution studies determined that the minimal inhibitory concentration for PHMB against the tested isolate of N. asteroides was 0.01%. This is a concentration that has been shown to be well tolerated by the cornea in vivo. Polyhexamethylene biguanide is effective against both Acanthamoeba and Nocardia and may have a wider range of usefulness than that currently recognized. Further testing, both in vitro and in vivo, is required.

Polybiguanides: synthesis and characterization of polybiguanides containing hexamethylene groups

A series of polymeric biguanide hydrochlorides containing hexamethylene groups has been synthesized by developing methods for melt and solution polymerization, based on the reaction of cyano groups with amine hydrochlorides. These polymers were characterized by solution viscometry, gel permeation chromatography, 1H n.m.r. and i.r. spectroscopy and thermal analyses (d.s.c. and t.g.a.). The presence of some melamine groups in the polymers made by melt polymerization was noticed and identified based on i.r. spectroscopy. The polymer salts obtained were generally hygroscopic and water soluble and lacked crystallinity. The hygroscopicity of the polymers varied with the hydrocarbon groups contained in the chains and the extent and nature of salt formation. The polybiguanide salts in both aqueous and polar non-aqueous solutions showed typical solution viscosity features of polyelectrolytes. The polybiguanides readily formed coloured complexes with copper ions.

Treatment of Acanthamoeba Keratitis with Polyhexamethylene Biguanide

Polyhexamethylene biguanide (PHMB) is a polymeric biguanide disinfectant that has not previously been used in the treatment of infection. Six patients with confirmed Acanthamoeba keratitis were treated with PHMB 0.02%. All patients had uncontrolled keratitis refractory to therapy with multiple conventional antiamebic agents. The rationale for use and the dose of PHMB was determined by in vitro sensitivity testing of the Acanthamoeba corneal isolates to the drugs available for use. Trophozoite forms were sensitive to most agents. Only PHMB was cysticidal at low concentrations in all cases. Sensitivity to the other drugs, including propamidine, showed wide variation. In 5 of 6 cases, complete resolution of inflammation followed the introduction of PHMB. Toxicity to the ocular surface was not evident with PHMB, unlike propamidine or neomycin. The reasons for the treatment failure in one case, despite cyst sensitivity to both PHMB and propamidine, are not clear. PHMB is a promising new treatment for this infection.

Inhibitory and lethal effects of chlorhexidine and a polymeric biguanide on some strains of Providencia stuartii

The effects of chlorhexidine diacetate and vantocil IB on the viability of Providencia stuartii strains are described. Exposure of Prov. stuartii strains to different concentrations of chlorhexidine in broth culture resulted in a decrease in viability over the first 6 h, followed by regrowth. During incubation, bacteria adhered to the surface of the culture vessel and multiplied despite the presence of a bactericidal concentration of the drug in the medium. It is concluded that the phenomenon of ‘regrowth’ results from adhesion to glass containers and the subsequent dispersal of some of these cells into the culture medium.

Interaction of a polymeric biguanide biocide with phospholipid membranes

Differential scanning calorimetry (DSC) and fluorescence polarization methods have been used to study the interactions between phospholipid membranes and a polymeric biocide, poly(hexamethylene biguanide hydrochloride) (PHMB). It was found that PHMB had very little effect on neutral lipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE), whereas it greatly reduced the phase transition temperature of phosphatidylglycerol (PG), an acidic lipid found in bacteria. Although the corresponding monomeric biocide had a similar effect on the PG bilayer, the behaviour towards mixed lipid bilayers of PC and PG has been shown to be completely different for the polymeric and monomeric biocides: viz. the former can induce isothermal phase separation into a PHMB-PG complex domain and a PC-enriched domain, whilst the latter cannot. This may account for the great difference in bactericidal activity between them. It is suggested that PHMB interacts primarily with negatively charged species in the membranes, inducing aggregation of acidic lipids in the vicinity of the adsorption site, where higher fluidity and higher permeability are expected. The results have shown that two factors might be crucial in the cidal activity of such types of cationic disinfectants as biguanides: phase separation and interaction with the hydrocarbon interior of the membranes. Polymeric biocides could be particularly effective by virtue of their ability to combine hydrophobic character and multiple charges within a single molecule.

Evaluation of teat-dipping formulations containing a germicidal polymeric biguanide

Evaluation of teat-dipping formulations containing a germicidal polymeric biguanide

Comparison of the Action of Vantocil, Cetrimide and Chlorhexidine on Escherichia coli and its Spheroplasts and the Protoplasts of Gram Positive Bacteria

SUMMARYThe actions of chlorhexidine, cetrimide and Vantocil (the hydrochloride of a polymeric biguanide) on bacteria and spheroplasts or protoplasts derived therefrom have been compared. Lysis of Escherichia coli spheroplasts by chlorhexidine or cetrimide is due to rupture of the cytoplasmic membrane. Membranes ruptured with cetrimide can reform to give small, empty envelopes. With increasing concentrations of cetrimide or chlorhexidine more and more granules appear in the cytoplasm, increasing in size with increasing concentration, until the structure becomes transformed to a granular body similar in size to the original spheroplast. With chlorhexidine or Vantocil this now electron‐dense body is rigid, but with cetrimide it collapses to a flat disc which does not lyse. The granules appear to consist of coagulated cytoplasm. This effect of excess of these antiseptics not only prevents osmotic lysis of the spheroplast or the collapsed disc but renders them immune to lysis by a variety of chemical agents. In isolated cytoplasm, chlorhexidine or cetrimide causes precipitation over a narrow range of concentrations but greater than those required for lysis. With Vantocil precipitation occurs gradually over a wide range of concentrations, starting at concentrations equal to those which cause a limited amount of lysis of the spheroplast or a relatively small increase in permeability of intact bacteria. Lanthanous and uranyl ions also precipitate cell contents but do not lyse spheroplasts; spheroplasts treated with these ions are protected from lysis by other agents.