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1.
Sci Rep ; 14(1): 11423, 2024 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-38763922

RESUMO

Negative pressure wound therapy with instillation and dwell time (NPWTi-d) is increasingly used for a diverse range of wounds. Meanwhile, the topical wound irrigation solution consisting of polyhexamethylene biguanide and betaine (PHMB-B) has shown efficacy in managing wound infections. However, the effectiveness of this solution as a topical instillation solution for NPWTi-d in patients with diabetic foot infections (DFIs) has not been thoroughly studied. The objective of this retrospective study was to evaluate the impact of using PHMB-B as the instillation solution during NPWTi-d on reducing bioburden and improving clinical outcomes in patients with DFIs. Between January 2017 and December 2022, a series of patients with DFIs received treatment with NPWTi-d, using either PHMB-B or normal saline as the instillation solution. Data collected retrospectively included demographic information, baseline wound characteristics, and treatment outcomes. The study included 61 patients in the PHMB-B group and 73 patients in the normal saline group, all diagnosed with DFIs. In comparison to patients treated with normal saline, patients with PHMB-B exhibited no significant differences in terms of wound bed preparation time (P = 0.5034), length of hospital stay (P = 0.6783), NPWTi-d application times (P = 0.1458), duration of systematic antimicrobial administration (P = 0.3567), or overall cost of hospitalization (P = 0.6713). The findings of the study suggest that the use of either PHMB-B or normal saline as an instillation solution in NPWTi-d for DFIs shows promise and effectiveness, yet no clinical distinction was observed between the two solutions.


Assuntos
Anti-Infecciosos Locais , Biguanidas , Pé Diabético , Tratamento de Ferimentos com Pressão Negativa , Solução Salina , Cicatrização , Humanos , Pé Diabético/terapia , Pé Diabético/tratamento farmacológico , Masculino , Feminino , Tratamento de Ferimentos com Pressão Negativa/métodos , Pessoa de Meia-Idade , Solução Salina/administração & dosagem , Solução Salina/uso terapêutico , Estudos Retrospectivos , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/uso terapêutico , Idoso , Biguanidas/uso terapêutico , Biguanidas/administração & dosagem , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/terapia , Irrigação Terapêutica/métodos , Betaína/administração & dosagem , Betaína/uso terapêutico , Resultado do Tratamento
2.
JAMA Surg ; 159(5): 484-492, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38381428

RESUMO

Importance: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking. Objective: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution. Design, Setting, and Participants: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11 700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis. Interventions: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure. Main Outcome and Measures: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition. Results: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups. Conclusions and Relevance: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting. Trial Registration: drks.de Identifier: DRKS00012251.


Assuntos
Biguanidas , Laparotomia , Infecção da Ferida Cirúrgica , Irrigação Terapêutica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Masculino , Feminino , Laparotomia/efeitos adversos , Pessoa de Meia-Idade , Biguanidas/uso terapêutico , Biguanidas/administração & dosagem , Idoso , Cuidados Intraoperatórios/métodos , Adulto
3.
Biol Pharm Bull ; 45(2): 220-225, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34819410

RESUMO

Olanexidine gluconate-containing preoperative antiseptic (OLG-C) is colorless, which makes it difficult to determine its area of application. To overcome this drawback, we realized a stable orange-tinted antiseptic (OLG-T) by adding new additives to OLG-C and investigated its pharmaceutical properties compared with OLG-C and povidone iodine (PVP-I). We evaluated the influence of the additives on the antimicrobial activity and adhesiveness of medical adhesives to OLG-T-applied skin by in vitro time-kill/ex vivo micropig skin assays and a peel test using excised micropig skin, respectively. In the in vitro time-kill assay, the bactericidal/fungicidal activity of OLG-T and OLG-C were equivalent. In the ex vivo micropig skin assay, their fast-acting and persistent bactericidal activities against vancomycin-resistant Enterococcus faecalis were higher than that of PVP-I. In the peel test, the adhesion force of the incise drape and the amount of stripped corneocytes on the peeled drape were comparable between OLG-T- and OLG-C-applied skin, but both were less than those of PVP-I-applied skin. The drapes for OLG-T- and OLG-C-applied skin had moderate adhesion force, and the drape-related injuries were expected to be weak. These results suggest that OLG-T performs no worse than OLG-C in terms of its antimicrobial activity and medical adhesive compatibility. Therefore, we expect OLG-T to lead to more convenient preoperative skin preparation and further contribute to lowering surgical site infection rates.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Compostos Azo/administração & dosagem , Bactérias/efeitos dos fármacos , Biguanidas/administração & dosagem , Corantes de Alimentos/administração & dosagem , Glucuronatos/administração & dosagem , Pele/efeitos dos fármacos , Adesividade , Animais , Bactérias/crescimento & desenvolvimento , Composição de Medicamentos , Feminino , Pele/microbiologia , Suínos
4.
Plast Reconstr Surg ; 148(4): 601e-614e, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34415884

RESUMO

SUMMARY: The relationship between wound irrigation and healing has been recognized for centuries. However, there is little evidence and no official recommendations from any health care organization regarding best wound irrigation practices. This is the first review of wound irrigation that systematically summarizes the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and distills the evidence into a practical format. In this comprehensive review, the authors outline the irrigation fluids and delivery methods used in the identified studies, analyze reported treatment outcomes, summarize irrigation effectiveness, and propose evidence-based guidelines to improve wound healing outcomes and enhance the consistency of wound irrigation. Thirty-one high-quality studies with a combined total of 61,808 patients were included. Based on the current evidence provided by this review, the authors propose the following guidelines: (1) acute soft-tissue wounds should receive continuous gravity flow irrigation with polyhexanide; (2) complex wounds should receive continuous negative-pressure wound therapy with instillation with polyhexanide; (3) infected wounds should receive continuous negative-pressure wound therapy with instillation with silver nitrate, polyhexanide, acetic acid, or povidone-iodine; (4) breast implant wounds should receive gravity lavage with povidone-iodine or antibiotics; and (5) surgical-site infection rates can be reduced with intraoperative povidone-iodine irrigation.


Assuntos
Medicina Baseada em Evidências/normas , Guias de Prática Clínica como Assunto , Lesões dos Tecidos Moles/terapia , Infecção da Ferida Cirúrgica/prevenção & controle , Irrigação Terapêutica/normas , Biguanidas/administração & dosagem , Medicina Baseada em Evidências/métodos , Humanos , Cuidados Intraoperatórios/métodos , Cuidados Intraoperatórios/normas , Tratamento de Ferimentos com Pressão Negativa/métodos , Tratamento de Ferimentos com Pressão Negativa/normas , Povidona-Iodo/administração & dosagem , Infecção da Ferida Cirúrgica/epidemiologia , Irrigação Terapêutica/métodos , Resultado do Tratamento , Cicatrização
5.
Adv Wound Care (New Rochelle) ; 10(10): 535-543, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33860686

RESUMO

Objective: To analyze long-term outcomes following inpatient treatment of infected wounds with antimicrobial or normal saline instillation during negative pressure wound therapy (NPWT). Approach: This was a single-center retrospective study analyzing the course of patients receiving 0.9% normal saline or 0.1% polyhexanide plus 0.1% betaine as instillation for wounds requiring surgery. Measured outcomes included rates of dehiscence, new wounds, re-operations, amputations, and mortality over 5 years. The article adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Results: Forty-two patients received normal saline instillation and 41 the antiseptic solution. Rates of dehiscence, wound recurrence, and re-operations in the saline and antiseptic cohorts were 6.3% and 5.6%, 9.4% and 5.6%, and 14.3% and 9.8%, respectively (p > 0.05). In patients requiring further surgery, time to wound closure averaged 104 and 130 days in the saline and antiseptic cohorts, respectively (p = 0.81). Five-year amputation and mortality rates were 14.3% and 22% (p = 0.36) and 24% and 17% (p = 0.45) in the saline and antiseptic cohorts, respectively. Innovation: To compare clinical outcomes associated with two fundamentally different instillation solutions over the full wound care episode and elucidate the potential impact of these results for future applications. Conclusion: This is the first evaluation of nonsurrogate outcomes of different instillations for NPWT in infected wounds. The results indicate that normal saline instillation outcomes are comparable to those of 0.1% polyhexanide plus 0.1% betaine. The clinical success, cost benefit, and accessibility of normal saline can expand the utilization of this therapeutic approach for larger patient populations.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Tratamento de Ferimentos com Pressão Negativa/métodos , Solução Salina/uso terapêutico , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Betaína/administração & dosagem , Biguanidas/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Cicatrização/fisiologia
6.
BMC Urol ; 21(1): 58, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836738

RESUMO

BACKGROUND: Long-term use of urethral catheters is associated with high risk of urinary tract infection (UTI) and blockage. Microbial biofilms are a common cause of catheter blockage, reducing their lifetime and significantly increasing morbidity of UTIs. A 0.02% polyhexanide irrigation solution developed for routine mechanical rinsing shows potential for bacterial decolonization of urethral catheters and has the potential to reduce or prevent biofilm formation. METHODS: Using an in vitro assay with standard market-leading types of catheters artificially contaminated with clinically relevant bacteria, assays were carried out to evaluate the biofilm reduction and prevention potential of a 0.02% polyhexanide solution versus no intervention (standard approach) and irrigation with saline solution (NaCl 0.9%). The efficiency of decolonization was measured through microbial plate count and membrane filtration. RESULTS: Irrigation using a 0.02% polyhexanide solution is suitable for the decolonization of a variety of transurethral catheters. The effect observed is significant compared to irrigation with 0.9% saline solution (p = 0.002) or no treatment (p = 0.011). No significant difference was found between irrigation with 0.9% saline solution and no treatment (p = 0.74). CONCLUSIONS: A 0.02% polyhexanide solution is able to reduce bacterial biofilm from catheters artificially contaminated with clinically relevant bacteria in vitro. The data shows a reduction of the viability of thick bacterial biofilms in a variety of commercially available urinary catheters made from silicone, latex-free silicone, hydrogel-coated silicone and PVC. Further research is required to evaluate the long-term tolerability and efficacy of polyhexanide in clinical practice.


Assuntos
Biguanidas/farmacologia , Biofilmes/efeitos dos fármacos , Desinfetantes/farmacologia , Contaminação de Equipamentos/prevenção & controle , Cateteres Urinários/microbiologia , Biguanidas/administração & dosagem , Desinfetantes/administração & dosagem , Humanos , Irrigação Terapêutica
7.
J Clin Endocrinol Metab ; 106(2): e696-e710, 2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-33247590

RESUMO

CONTEXT: Prostate cancer (PCa) is one of the leading causes of cancer-related death among the male population worldwide. Unfortunately, current medical treatments fail to prevent PCa progression in a high percentage of cases; therefore, new therapeutic tools to tackle PCa are urgently needed. Biguanides and statins have emerged as antitumor agents for several endocrine-related cancers. OBJECTIVE: To evaluate: (1) the putative in vivo association between metformin and/or statins treatment and key tumor and clinical parameters and (2) the direct effects of different biguanides (metformin/buformin/phenformin), statins (atorvastatin/simvastatin/lovastatin), and their combination, on key functional endpoints and associated signalling mechanisms. METHODS: An exploratory/observational retrospective cohort of patients with PCa (n = 75) was analyzed. Moreover, normal and tumor prostate cells (normal [RWPE-cells/primary prostate cell cultures]; tumor [LNCaP/22RV1/PC3/DU145 cell lines]) were used to measure proliferation/migration/tumorsphere-formation/signalling pathways. RESULTS: The combination of metformin+statins in vivo was associated to lower Gleason score and longer biochemical recurrence-free survival. Moreover, biguanides and statins exerted strong antitumor actions (ie, inhibition of proliferation/migration/tumorsphere formation) on PCa cells, and that their combination further decreased; in addition, these functional parameters compared with the individual treatments. These actions were mediated through modulation of key oncogenic and metabolic signalling pathways (ie, AR/mTOR/AMPK/AKT/ERK) and molecular mediators (MKI67/cMYC/androgen receptor/cell-cycle inhibitors). CONCLUSIONS: Biguanides and statins significantly reduced tumor aggressiveness in PCa, with this effect being more potent (in vitro and in vivo) when both compounds are combined. Therefore, given the demonstrated clinical safety of biguanides and statins, our results suggest a potential therapeutic role of these compounds, especially their combination, for the treatment of PCa.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biguanidas/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Biguanidas/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quimioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Estudos Transversais , Sinergismo Farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Pessoa de Meia-Idade , Células PC-3 , Projetos Piloto , Prostatectomia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Transdução de Sinais/efeitos dos fármacos , Espanha , Resultado do Tratamento
8.
Neuropharmacology ; 184: 108415, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33275959

RESUMO

Several studies have shown that ethanol (EtOH) can enhance the activity of GABAergic synapses via presynaptic mechanisms, including in hippocampal CA1 neurons. The serotonin type 3 receptor (5-HT3-R) has been implicated in the neural actions of ethanol (EtOH) and in modulation of GABA release from presynaptic terminals. In the present study, we investigated EtOH modulation of GABA release induced by 5-HT3-R activation using the mechanically isolated neuron/bouton preparation from the rat CA1 hippocampal subregion. EtOH application before and during exposure to the selective 5-HT3 receptor agonist, m-chlorophenylbiguanide (mCPBG) potentiated the mCPBG-induced increases in the peak frequency and charge transfer of spontaneous GABAergic inhibitory postsynaptic currents. Interestingly, the potentiation was maintained even after EtOH was removed from the preparation. A protein kinase A inhibitor reduced the magnitude of EtOH potentiation. Fluorescent Ca2+ imaging showed that Ca2+ transients in the presynaptic terminals increased during EtOH exposure. These findings indicate that EtOH produces long-lasting potentiation of 5-HT3-induced GABA release by modulating calcium levels, via a process involving cAMP-mediated signaling in presynaptic terminals.


Assuntos
Região CA1 Hipocampal/metabolismo , Etanol/administração & dosagem , Neurônios/metabolismo , Receptores 5-HT3 de Serotonina/metabolismo , Sinapses/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Animais Recém-Nascidos , Biguanidas/administração & dosagem , Região CA1 Hipocampal/efeitos dos fármacos , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Masculino , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor de Serotonina/administração & dosagem , Sinapses/efeitos dos fármacos
9.
Exp Parasitol ; 218: 108008, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32979343

RESUMO

Acanthamoeba sp. is a free living amoeba that causes severe, painful and fatal infections, viz. Acanthamoeba keratitis and granulomatous amoebic encephalitis among humans. Antimicrobial chemotherapy used against Acanthamoeba is toxic to human cells and show side effects as well. Infections due to Acanthamoeba also pose challenges towards currently used antimicrobial treatment including resistance and transformation of trophozoites to resistant cyst forms that can lead to recurrence of infection. Therapeutic agents targeting central nervous system infections caused by Acanthamoeba should be able to cross blood-brain barrier. Nanoparticles based drug delivery put forth an effective therapeutic method to overcome the limitations of currently used antimicrobial chemotherapy. In recent years, various researchers investigated the effectiveness of nanoparticles conjugated drug and/or naturally occurring plant compounds against both trophozoites and cyst form of Acanthamoeba. In the current review, a reasonable effort has been made to provide a comprehensive overview of various nanoparticles tested for their efficacy against Acanthamoeba. This review summarizes the noteworthy details of research performed to elucidate the effect of nanoparticles conjugated drugs against Acanthamoeba.


Assuntos
Acanthamoeba/efeitos dos fármacos , Amebicidas/administração & dosagem , Nanopartículas/administração & dosagem , Acanthamoeba/crescimento & desenvolvimento , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Amebíase/tratamento farmacológico , Amebíase/mortalidade , Amebíase/parasitologia , Amebicidas/farmacologia , Amebicidas/uso terapêutico , Biguanidas/administração & dosagem , Biguanidas/farmacologia , Biguanidas/uso terapêutico , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Infecções Protozoárias do Sistema Nervoso Central/mortalidade , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Clorexidina/administração & dosagem , Clorexidina/farmacologia , Clorexidina/uso terapêutico , Sistemas de Liberação de Medicamentos , Imunocompetência , Hospedeiro Imunocomprometido , Encefalite Infecciosa/tratamento farmacológico , Encefalite Infecciosa/mortalidade , Encefalite Infecciosa/parasitologia , Nanopartículas/classificação , Nanopartículas/uso terapêutico , Trofozoítos/efeitos dos fármacos
10.
Wounds ; 32(8): 208-216, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32804659

RESUMO

INTRODUCTION: Biofilm in chronic wounds impedes the wound healing process. Each biofilm has differing characteristics requiring a multifaceted approach for removal while maintaining a surrounding environment conducive to wound healing. OBJECTIVE: In this study, 3 of the components in a wound cleanser are tested to determine synergy in eradicating biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in vitro. MATERIALS AND METHODS: The 3 components assessed for synergy were ethylenediamine tetraacetic acid sodium salts (EDTA), vicinal diols (VD; ethylhexylglycerin and octane-1,2-diol), and polyhexamethylene biguanide (PHMB). Each component was assessed individually and in combination while dissolved in a base solution. The Calgary assay method was used for biofilm growth and treatment. Kull Equation analysis for synergy was conducted using viable count results. RESULTS: Synergy is defined as the interaction of components to produce a combined effect greater than the sum of their separate effects. The base solution containing all 3 components (EDTA, VD, and PHMB) reduced biofilm viability by more than 5 logs, demonstrating statistically significant synergy. The 3 components tested individually in the base solution resulted in the following: EDTA did not reduce bacteria viability; VD reduced viability by about 1 log; and PHMB reduced P aeruginosa viability by about 2.5 logs and MRSA viability by about 4 logs. Of importance, the MRSA biofilm failed to regrow in the recovery plates after combined treatment, indicating complete elimination of the biofilm bacteria. CONCLUSIONS: The experimental and calculated results indicate the 3 components (VD, EDTA, and PHMB) when used together act synergistically to eradicate MRSA and P aeruginosa biofilms in vitro.


Assuntos
Biguanidas/uso terapêutico , Biofilmes/efeitos dos fármacos , Detergentes/uso terapêutico , Ácido Edético/uso terapêutico , Éteres de Glicerila/uso terapêutico , Octanóis/uso terapêutico , Pele/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Biguanidas/administração & dosagem , Detergentes/administração & dosagem , Sinergismo Farmacológico , Ácido Edético/administração & dosagem , Éteres de Glicerila/administração & dosagem , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Octanóis/administração & dosagem , Pseudomonas aeruginosa/efeitos dos fármacos , Pele/microbiologia , Ferimentos e Lesões/microbiologia
12.
J Wound Care ; 29(7): 380-386, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32654602

RESUMO

OBJECTIVE: The burden of wound care within the NHS is estimated at a cost of £5.3 billion per year and is set to rise annually by 30%. This case series describes the results of using polyhexanide (PHMB) and betaine wound irrigation solution and gels (Prontosan, B.Braun Medical Ltd., UK) across the UK in hard-to-heal (also described as chronic) wounds up to 20 years' duration, with an observation period of greater than one month. Over half of the hard-to-heal wounds were healed and vast improvements to all other wounds were observed. Improvements to wound bed condition were reported as early as two days after commencing initial treatment, with decreases in malodour, exudate, slough and pain reported across the case series. In addition to wound bed improvements, a reduction in dressing change frequency of 55% was observed in hard-to-heal wounds under the new treatment regime.


Assuntos
Betaína/administração & dosagem , Biguanidas/administração & dosagem , Úlcera por Pressão/terapia , Administração Cutânea , Géis , Humanos , Medicina Estatal , Irrigação Terapêutica , Reino Unido , Cicatrização
13.
BMC Urol ; 20(1): 92, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641131

RESUMO

BACKGROUND: In patients with indwelling bladder catheters for > 2 weeks, bacterial colonization is inevitable, leading to urinary tract infections or encrustations with subsequent catheter blockage. Currently, bladder irrigations are the most frequently used prophylactic means, but the best solution remains yet to be determined. In vitro studies demonstrate that polihexanide is a promising option for catheter irrigation, but no data about safety and tolerability exist. METHODS: In a prospective observational study in patients with indwelling bladder catheter for > 2 weeks, a 0.02% polihexanide solution was used to rinse the catheter on five consecutive days. Adverse events, tolerability and vital signs were assessed before, during, after and at the end of the treatment period. RESULTS: There was no serious adverse event in the study. A total of 28 adverse events (AEs) in 15 (46.88%) participants were experienced. Absolute changes in pain scores were not clinically relevant. No incidences of either flushing or sweating were found during instillation. Bladder spasms during instillation were reported in two cases during a single instillation. Mean pulse rates did not change by more than 3 beats per minute. Mean changes in body temperature did not exceed 0.12 °C. Clinically relevant changes in blood pressure were recorded for 3 patients. CONCLUSIONS: This is the first study to demonstrate that a 0.02% polihexanide solution can safely be used for catheter irrigation. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02157415 ), June 6th, 2014.


Assuntos
Biguanidas , Cateteres de Demora , Desinfetantes , Cateteres Urinários , Idoso , Biguanidas/administração & dosagem , Biguanidas/efeitos adversos , Estudos de Coortes , Desinfetantes/administração & dosagem , Desinfetantes/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Soluções , Irrigação Terapêutica/métodos
14.
Lancet Infect Dis ; 20(11): 1281-1289, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32553191

RESUMO

BACKGROUND: Surgical site infection (SSI) is the most common problem after surgery. Although several guidelines have indicated the efficacy of antiseptics, such as chlorhexidine-alcohol and povidone-iodine, in reducing SSI rate, the optimal recommendation is still not established. Olanexidine might have higher bactericidal activity than other antiseptic agents. However, no randomised study has evaluated the efficacy and safety of olanexidine over conventional antiseptics. We compared the effect of aqueous olanexidine and aqueous povidone-iodine on the incidence of SSI following clean-contaminated surgery. METHODS: This was a multicentre, prospective, randomised, blinded-endpoint superiority trial for surgical skin antisepsis in clean-contaminated gastrointestinal and hepatobiliary pancreatic surgeries in four Japanese hospitals. Patients aged 20 years or older who underwent elective clean-contaminated wound surgery were randomly assigned in a 1:1 replacement ratio using a computer-generated block randomisation. Patients were randomly assigned to surgical skin antisepsis with an aqueous formulation of 1·5% olanexidine or surgical skin antisepsis with an aqueous formulation of 10% povidone-iodine before surgery. We used olanexidine in a ready-to-use applicator, and povidone-iodine was administered by a brush or by compression using pliers. Both antiseptics were applied from the papilla with a cranial limit and to the upper thigh with a caudal limit. The antiseptics were allowed to dry for 3 min, and then surgery started. Participants, some investigators, and data analysts were masked to treatment allocation. Participant enrolment was done by non-masked investigators. The primary outcome was 30-day SSI assessed in the intention-to-treat population. The surgical wound site of each participant was observed daily. After discharge, participants underwent at least one outpatient visit within 30 days after surgery. This trial is registered with University hospital Medical Information Network, 000031560. FINDINGS: Between June 10, 2018, and April 18, 2019, 883 patients were assessed for eligibility. 587 patients were eligible and 294 received olanexidine and 293 received aqueous povidone-iodine before surgery. 30-day SSI occurred in 19 (7%) patients in the olanexidine group and 39 patients (13%) patients in the povidone-iodine group (adjusted risk difference -0·069; 90% CI -0·109 to -0·029; adjusted risk ratio [RR] 0·48, 90% CI 0·30 to 0·74; p=0·002). Five patients (2%) in the olanexidine group and five (2%) in the povidone-iodine group developed adverse skin reactions (adjusted RR 0·99, 95% CI 0·29 to 3·40; p=1·00). INTERPRETATION: Olanexidine significantly reduced the occurrence of overall SSI and superficial incisional SSI compared with aqueous povidone-iodine in clean-contaminated surgery. Our results indicate that olanexidine might have a role to prevent SSI in patients who undergo clean-contaminated surgeries. FUNDING: Keio University and Ohyama Health Foundation.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Antissepsia/métodos , Biguanidas/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Povidona-Iodo/administração & dosagem , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
15.
Eur J Med Chem ; 200: 112462, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32464472

RESUMO

Platelet thrombosis is the main pathogeny resulting in the low curability of ischemic stroke, a leading cause of mortality and disability worldwide. Metformin, a biguanide derivative that is the first-line oral medicine for type 2 diabetes, alleviates the severity of ischemic stroke in diabetic patients and suppresses platelet activation in experimental animal model. However, the clinical implementation of commercial biguanide analogs for stroke related to platelet thrombosis remains challenging due to its weak potency, poor pharmacokinetic characteristics and possible hypoglycemia. Here, twenty-three biguanide derivatives were designed and synthesized based on the principles of bioisosteres. These derivatives were evaluated for the activity of antiplatelet thrombosis in vivo. We found that N-trifluoromethanesulfonyl biguanide derivative, compound b10, uniquely prevented cerebral infarction as well as neuronal function injury, and significantly decrease the mortality rate of ischemic stroke in the middle cerebral artery occlusion mice without significant side effects. We verified that b10 directly inhibited platelets thrombus formation and decreased the compactness of stroke thrombi. Particularly, b10 exhibited good potency to inhibit human platelet activation including platelet aggregation, adhesion, pseudopodia formation, integrin GPIIb/IIIa activation, CD62P expression and clot retraction. Meanwhile, the pharmacokinetics assessment showed that b10 had satisfying pharmacological characteristics including a longer duration and a higher oral absorption ratio than its parent compound. In addition, b10 remarkably ameliorated not only stroke related to platelet thrombosis but also carotid artery thrombus formation. It is concluded that the novel potent antiplatelet thrombotic agent derived from biguanide is a promising candidate for stroke treatment.


Assuntos
Biguanidas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Trombose/tratamento farmacológico , Administração Oral , Animais , Biguanidas/administração & dosagem , Biguanidas/química , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/química , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Relação Estrutura-Atividade , Trombose/patologia
16.
Am J Surg ; 220(4): 1076-1082, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32139102

RESUMO

AIM: To compare the efficacy of Negative Pressure Wound Therapy (NPWT) with and without irrigation with 0.1% polyhexanide-betaine. METHODS: We randomized 150 subjects in a 16-week RCT to compare healing in patients with diabetic foot infections. NPWT delivered at 125 mm Hg continuous pressure. NPWT-I were administered at 30 cc per hour. RESULTS: There were no differences clinical treatment or outcomes: wound area after surgery (18.5 ± 19.0 vs. 13.4 ± 11.1 cm2, p = 0.50), duration of antibiotics (39.7 ± 21.0 vs. 38.0 ± 24.6 days, p = 0.40), number of surgeries (2.3 ± 0.67 vs. 2.2 ± 0.59, p = 0.85), duration of NPWT (148.1 ± 170.4 vs. 114.5 ± 135.1 h, p = 0.06), healed wounds (58.7% vs. 60.0%, p = 0.86), time to healing (56.3 ± 31.7 vs. 50.7 ± 27.8, p = 0.53), length of stay (13.8 ± 6.4 vs. 14.5 ± 11.2 days, p = 0.42), re-infection (20.0% vs. 22.7%, p = 0.69, and re-hospitalization (17.3% vs. 18.7, p = 0.83). CONCLUSIONS: The addition of irrigation to NPWT did not change clinical outcomes in patients with diabetic foot infections. CLINICAL TRIAL NUMBER: NCT02463487, ClinicalTrials.gov.


Assuntos
Biguanidas/administração & dosagem , Pé Diabético/terapia , Tratamento de Ferimentos com Pressão Negativa/métodos , Irrigação Terapêutica/métodos , Cicatrização , Administração Tópica , Adulto , Desinfetantes/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Ther Apher Dial ; 24(1): 81-84, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31066988

RESUMO

Topical antibiotic and antiseptic agents have been documented to reduce exit-site infection (ESI) and peritonitis in PD. The aim of this randomized controlled study was to evaluate the efficacy of polyhexanide in the prevention of ESI and peritonitis. Patients were excluded if they had active infection, > 18 years of age, ESI and peritonitis within the previous 4 weeks, received PD for less than 3-months and history of allergy to either drug. All patients were followed up until catheter removal, death, switch to dialysis, transplantation or the end of the study. ESI, tunnel infection, peritonitis, catheter removal and microorganism cause of catheter-related infection were recorded prospectively during clinic follow-up. A total of 88 patients (41 povidone-iodine group; 47 polyhexanide group) were enrolled with a total follow-up duration of 480 and 555 patient-months for povidone-iodine and alternating group, respectively. There were no significant differences in the age, sex, BMI, time of PD, rate of DM, and S. aureus carriage state. A total of 8 ESI and 25 peritonitis episodes were detected during the study. ESI and peritonitis rates tended to be lower in polyhexanide group compared with the povidone-iodine group (0.06 episodes/patient-year vs. 0.12 episodes/patient-year; 0.26 episodes/patient-year vs. 0.32 episodes/patient-year, respectively), but were not significant statistically. Moreover, catheter removal was similar in both groups (0.04 / patient-year vs. 0.05 / patient-year). Polyhexanide is efficient and safe for the prevention of ESI and peritonitis and it may be used as an alternative procedure for the care of healthy exit sites.


Assuntos
Biguanidas/administração & dosagem , Infecções Relacionadas a Cateter/prevenção & controle , Peritonite/prevenção & controle , Povidona-Iodo/administração & dosagem , Adulto , Anti-Infecciosos Locais/administração & dosagem , Remoção de Dispositivo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Peritonite/etiologia , Estudos Prospectivos
18.
Cornea ; 39(2): 245-249, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31724982

RESUMO

PURPOSE: The aim of this study was to reduce the cytotoxicity and improve the amoebicidal effect of polyhexamethylene biguanide (PHMB) at low concentrations by combining it with histone deacetylase (HDAC) inhibitors. METHODS: To reduce the cytotoxic effect on human corneal epithelial (HCE) cells, the concentration of PHMB was reduced to 0.0002%. To enhance the amoebicidal effect of PHMB, HDAC inhibitors such as suberoylanilide hydroxamic acid, MS275, or MC1568 were combined with it. Acanthamoeba and HCE cells were treated with 3 combinations to evaluate the amoebicidal and cytotoxic effects. Microscopy and fluorescence-activated cell sorting analysis were performed to investigate the apoptotic cell death of Acanthamoeba by these combinatorial treatments. RESULTS: The low concentration of PHMB (0.0002%) alone demonstrated no cytopathic effects (CPEs) on HCE cells. Three combinatorial treatments using 0.0002% PHMB with 10 µM suberoylanilide hydroxamic acid, 10 µM MS275, or 10 µM MC1568 showed higher amoebicidal effects on A. castellanii trophozoites than PHMB alone. Fluorescence-activated cell sorting analysis confirmed that HDAC inhibitors increased the apoptotic cell death of Acanthamoeba. Mild CPEs were observed from HCE cells cotreated with PHMB and the HDAC inhibitors after 24 hours of exposure. CONCLUSIONS: Combinatorial treatments showed high amoebicidal effects on Acanthamoeba and low CPEs on HCE cells, which suggests their potential application for Acanthamoeba keratitis treatment.


Assuntos
Acanthamoeba castellanii/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Biguanidas/farmacologia , Desinfetantes/farmacologia , Epitélio Corneano/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Acanthamoeba castellanii/metabolismo , Anexina A5/metabolismo , Benzamidas/farmacologia , Biguanidas/administração & dosagem , Células Cultivadas , Desinfetantes/administração & dosagem , Sinergismo Farmacológico , Epitélio Corneano/metabolismo , Citometria de Fluxo , Fluoresceína-5-Isotiocianato , Humanos , Ácidos Hidroxâmicos/farmacologia , Microscopia de Fluorescência , Piridinas/farmacologia , Pirróis/farmacologia , Vorinostat/farmacologia
19.
Ann Surg ; 272(1): 55-64, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31599810

RESUMO

OBJECTIVE: To evaluate whether intraoperative subcutaneous wound irrigation with 0.04% polyhexanide can reduce surgical site infection (SSI) in elective laparotomies compared to saline. BACKGROUND: SSI is a common complication after gastrointestinal surgery. To date, there is a lack of evidence whether subcutaneous wound irrigation is beneficial in terms of reduction of SSI. METHODS: The RECIPE trial was an investigator initiated single-center, single-blind prospective, randomized controlled trial with 2 parallel treatment groups, comparing wound irrigation with 0.9% saline to antiseptic 0.04% polyhexanide solution in elective laparotomies. Primary endpoint was the rate of SSI within 30 days postoperatively according to Centers for Disease Control and Prevention criteria. RESULTS: Between February 02, 2015, and May 23, 2018, 456 patients were randomly assigned to saline (n = 228) or polyhexanide (n = 228). Final cohort for analysis comprised 393 patients (202 in the saline and 191 in the polyhexanide group). Overall rate of SSI was 28.2%, n = 111. Simple analysis with cross tabulation revealed that significantly fewer SSIs occurred in the polyhexanide group: n = 70 (34.7%) versus n = 41 (21.5%); P = 0.004. In a multiple logistic regression model the factor wound irrigation with polyhexanide [odds ratio (OR) 0.44; 95% confidence interval (CI) 0.27-0.72; P = 0.001) was associated with risk reduction of SSI. Preoperative anemia (OR 2.08; 95% CI 1.27-3.40; P = 0.004) and more than 5 prior abdominal operations compared to none (OR 8.51; 95% CI 2.57-28.21; P < 0.001) were associated with SSI. CONCLUSIONS: Intraoperative subcutaneous wound irrigation with antiseptic 0.04% polyhexanide solution is effective in reducing SSI after elective laparotomies.


Assuntos
Biguanidas/administração & dosagem , Procedimentos Cirúrgicos do Sistema Digestório , Desinfetantes/administração & dosagem , Laparotomia , Infecção da Ferida Cirúrgica/prevenção & controle , Irrigação Terapêutica/métodos , Feminino , Humanos , Cuidados Intraoperatórios , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória , Satisfação do Paciente , Estudos Prospectivos , Método Simples-Cego , Cloreto de Sódio/administração & dosagem
20.
Yakugaku Zasshi ; 139(12): 1569-1581, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787647

RESUMO

To investigate medication adherence to oral antihyperglycemic agents and its associated factors in Japanese type 2 diabetic patients, a questionnaire survey was conducted in 983 adult patients receiving once-daily (QD) or twice-daily (BID) dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitor) or BID biguanides (BG) as monotherapy at 502 pharmacies in Japan. The percentage of patients with good adherence (the proportion of days in which patients took all pills as prescribed in the past 7 days ≥80%) was high (≥90%) in any dosing regimen with no significant difference among the groups. The following factors were identified as associating with good adherence: the longer duration of type 2 diabetes (≥1 year) (p=0.002), "Feeling your disease gets worse if you don't take medications" (p=0.031), "Not forgetting to bring along your medicine when you leave home" (p=0.007), "Feeling anxiety on taking medications for long period of time" (p=0.042), "Neither feeling nor not feeling anxiety on taking medications for a long period of time" (p=0.004), "Never run out of your medicine because you get a refill on time" (p=0.035), and the lower MMAS-4 score (p<0.001). Subgroup analyses revealed that adherence of younger patients (<65 years) with BG (BID) was lower than those with DPP-4 inhibitor (QD) (p=0.021). Additionally, around 60% of patients currently prescribed with QD preferred QD regimen, and ≥80% patients prescribed with BID equally preferred once-weekly or QD regimen, suggesting a large discrepancy exists between their preference and the actual regimen in patients on BID.


Assuntos
Biguanidas/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/psicologia , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Hipoglicemiantes/administração & dosagem , Adesão à Medicação , Administração Oral , Adulto , Idoso , Ansiedade , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem
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