RESUMO
OBJECTIVE: This narrative review explores alternative non-antibiotic antimicrobial agents for CRS management in adults. METHODS: Alternative antimicrobial agents using EPOS 2020 guidelines as reference were selected, and articles dated from 2003 to 2022 in English, Portuguese, or Spanish using PubMed and EMBASE databases. The parameters analyzed included study design, evidence level, population characteristics, CRS characteristics, interventions, outcomes, sample size, randomization, blinding, and side effects. Reviews, unrelated contexts,in vitro experiments, and duplicates were excluded. RESULTS: 148 articles were screened; 19 articles were selected for analysis. Randomized controlled trials and cohort studies assessing non-antibiotic antimicrobial treatments for CRS were included. Xylitol demonstrated effectiveness in reducing CRS symptoms, particularly SNOT-22 scores, surpassing saline irrigation benefits. Manuka honey showed potential microbiological benefits in recalcitrant CRS, but symptomatic and endoscopic improvements remained inconclusive. Baby shampoo irrigation improved nasal mucociliary clearance and postoperative outcomes. Colloidal silver nasal irrigation showed limited efficacy in reducing CRS symptoms or endoscopic scores. Povidone-Iodine (PI) nasal irrigation yielded mixed results, with varying effects on culture negativity and SNOT-20 scores. Bacteriophage treatment exhibited promise in decreasing specific bacterial strains and cytokine levels. CONCLUSION: Non-antibiotic antimicrobial therapies, including xylitol, manuka honey, baby shampoo, colloidal silver, PI, bacteriophages, lactoferrin, and carrageenan offer potential alternatives for CRS in adult patients. Xylitol, baby shampoo, and PI presented benefits in improving symptoms and nasal endoscopic scores, however, the number of studies is limited for conclusive recommendations and safety assessments. CRS management should adopt a comprehensive approach, particularly for non-infectious or immune-related cases, moving beyond antibiotics. Antibiotics should be reserved for confirmed bacterial infections. Overall, this review shows the importance of exploring non-antibiotic therapies to enhance the management of CRS.
Assuntos
Rinite , Sinusite , Humanos , Rinite/tratamento farmacológico , Rinite/microbiologia , Doença Crônica , Sinusite/tratamento farmacológico , Sinusite/microbiologia , Anti-Infecciosos/uso terapêutico , Mel , Xilitol/uso terapêutico , RinossinusiteRESUMO
INTRODUCTION AND HYPOTHESIS: Dysuria is a common symptom present in several urological and gynecological conditions. Management relies on the underlying disease but may require additional symptomatic treatment. This study evaluated the combination of methenamine 250 mg and methylthioninium chloride 20 mg in the treatment of dysuria versus phenazopyridine. METHODS: This was a multicenter, single-blind, randomized, superiority clinical trial, including individuals over 18 with dysuria and a score ≥ 5 points on the pre-treatment categorical scale for pain. The primary outcome was the proportion of participants presenting excellent clinical response within 24 h after treatment. Improvement up to 72 h, time to reach improvement, sustained healing, investigators' opinion, and safety were also evaluated. RESULTS: Three hundred and fifteen participants were evaluated. Demographic characteristics and symptoms of dysuria were comparable between groups at baseline. The difference in the excellent response rate between treatments within 24 h was 12.7% (95% CI 6.16, 19.21) for pain, 9.4% (95% CI 3.32, 15.39) for burning, and 12.7% (95% CI 6.37, 18.99) for burning on urination, all in favor of the test drug, which was also superior from 36 to 48 h. Treatments were similar concerning time to reach the absence of symptoms and in the percentage of participants with sustained healing after 72 h. CONCLUSIONS: The association of methenamine with methylthioninium is superior to phenazopyridine in the treatment of dysuria.
Assuntos
Disuria , Metenamina , Humanos , Disuria/tratamento farmacológico , Disuria/etiologia , Azul de Metileno , Dor , Fenazopiridina/uso terapêutico , Método Simples-Cego , AdultoRESUMO
The objective of this study was to evaluate the effect of eubiotics on the intestinal morphology of broilers. For this purpose, 125 birds were divided into six groups with two replicates each (10 birds in each replicate). Group A was given a Basal diet. All groups except group A were challenged with Salmonella enterica serovar Enteritidis. Group B was provided the basal diet, group C was fed a Probiotic-added diet; group D was fed a Prebiotics-based diet; group E was given essential oils plus the basal diet; and group F was provided with organic acids plus the basal diet. Two separate experiments were carried out for Salmonella recovery, checking the cecal tonsils and conducting an intestinal pathomorphic evaluation. Villus length, villus width, villus surface area, and crypt depth were measured by micrometry. There was an overall improvement (p<0.05) in intestinal morphometric parameters for all the treatment groups except for the negative control group, which showed the lowest villus height and villus depth values. Maximum villus height (p<0.05) of the duodenum was achieved by group E, which was fed a diet containing essential oils, whereas a maximum villus surface area index (p<0.05) was recorded for the birds of Group D, which were fed a diet containing prebiotics. Maximum villus height (p<0.05) and surface area index in ileum mucosa was recorded (p<0.05) in the birds of group D (treated with prebiotics). It is concluded that there is an overall increase in the gut histology of broilers fed non-antibiotic based feed.(AU)
Assuntos
Animais , Galinhas/fisiologia , Aditivos Alimentares/efeitos adversos , Salmonella enterica/crescimento & desenvolvimentoRESUMO
Acinetobacter baumannii is an opportunistic pathogen associated with the occurrence of outbreaks in hospital settings, especially in Intensive Care Units (ICUs). Pneumonia, septicemias, urinary tract infections, and recurrent infections associated with the use of hospital devices are some of the most frequent complications. Due to the increase of A. baumannii strains resistant to multiple antimicrobials, associated with their high capacity to form biofilms on biotic and abiotic surfaces, the therapeutic strategies routinely applied have become increasingly restricted and ineffective, resulting in high mortality rates. Many studies have focused on the development of new therapeutic approaches, mainly non-antibiotic-based. Polyclonal (pAb) and monoclonal (mAb) antibodies are increasingly cited in the literature as alternative strategies to the use of antimicrobial drugs and are evaluated for the prevention and treatment of these infections. In this context, this review aimed to synthesize the main strategies based on the use of antibodies that are being evaluated for the control of A. baumannii infections. Here, we describe the main A. baumannii antigenic targets used in studies to assess their potential to induce the formation of antibodies and their possible application in immunotherapy strategies.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Infecções por Acinetobacter/prevenção & controle , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Imunoterapia , Farmacorresistência Bacteriana MúltiplaRESUMO
The global spread of microbial resistance coupled with high costs and slow pace in the discovery of a new antibiotic have made drug repositioning an attractive and promising alternative in the treatment of infections caused by multidrug resistant (MDR) microorganisms. The reuse involves the production of compounds with lower costs and development time, using diversified production technologies. The present systematic review aimed to present a selection of studies published in the last 20 years, which report the antimicrobial activity of non-antibiotic drugs that are candidates for repositioning, which could be used against the current microbial multidrug resistance. A search was performed in the PubMed, SciELO and Google Scholar databases using the following search strategies: [(drug repurposing) OR (drug repositioning) OR (repositioning) AND (non-antibiotic) AND (antibacterial activity) AND (antimicrobial activity)]. Overall, 112 articles were included, which explored the antimicrobial activity in antidepressants, antihypertensives, anti-inflammatories, antineoplastics, hypoglycemic agents, among other drugs. It was concluded that they have significant antimicrobial activity in vitro and in vivo, against standard strain and clinical isolates (Gram-negative and Gram-positive) and fungi. When associated with antibacterials, most of these drugs had their antibacterial activity enhanced. It was also a consensus of the studies included in this review that the presence of aromatic rings in the molecular structure contributes to antimicrobial activity. This review highlights the potential repositioning of several classes of non-antibiotic drugs as promising candidates for repositioning in the treatment of severe bacterial infections of MDR bacteria, extensively resistant (XDR) and pan-resistant (PDR) to drugs.
Assuntos
Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Reposicionamento de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Rumenostomy is a useful procedure commonly performed in cattle for medical treatment of domestic ruminants with forestomach diseases. Methylene blue (MB)-mediated antimicrobial photodynamic therapy (APDT) has been broadly investigated to treat infected wounds. AIM: The aim of the study was to evaluate the effectiveness of MB-mediated APDT (MB-APDT) combined with chlorhexidine and zinc oxide ointment on wound healing process after rumenostomy. METHODS: Fourteen Nelore bulls were subjected to rumenostomy procedure. Animals were randomly divided into MB-APDT (MB associated with a red diode laser performed immediately after surgery and repeated on days 3, 5, 7 and 10) and control groups. Daily care included topical cleaning with chlorhexidine 2% followed by topical zinc oxide ointment. Animals were followed-up until the 28th day. RESULTS: Wounds presented a better post-surgical profile in MB-APDT group when it was compared with the control group. In MB-APDT group, it was also possible to observe less pain on palpation of wounds borders, less edema and inflammatory exudate. Additionally, animals from MB-APDT group were faster discharged from the cattle care facility. CONCLUSION: Our results support the use of MB-APDT for the post-surgical management of rumenostomy. This pilot study ratifies the use of APDT in cattle and also suggests that it could be performed for other surgical procedures as a complementary approach or an alternative for topical administration of antibiotics.
Assuntos
Anti-Infecciosos , Fotoquimioterapia , Ferida Cirúrgica , Animais , Antibacterianos , Bovinos , Masculino , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Projetos Piloto , Ferida Cirúrgica/tratamento farmacológicoRESUMO
Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.
Resumo Introdução: Antibióticos são frequentemente usados para o tratamento de rinossinusite. Questões têm sido levantadas sobre os efeitos adversos dos antibióticos e a resistência crescente. A falta de desenvolvimento de novos compostos antibióticos aumentou a necessidade da exploração de compostos não antibióticos que têm atividade antibacteriana. A amlodipina é um composto não antibiótico com atividade anti-inflamatória. Objetivo: O objetivo desse estudo foi investigar o papel potencial da amlodipina no tratamento da rinossinusite, avaliando seus efeitos sobre o estado oxidativo do tecido, histologia da mucosa e inflamação. Método: Quinze cobaias albinas adultas foram inoculadas com Staphylococcus aureus e tratadas com solução salina, cefazolina ou amlodipina durante sete dias. O grupo controle incluiu cinco cobaias saudáveis. Os animais foram sacrificados após o tratamento. Alterações histopatológicas foram identificadas com a coloração de hematoxilina-eosina. A inflamação foi avaliada pela densidade de infiltração de leucócitos polimorfonucleares. Foram determinados os níveis teciduais de antioxidantes (superóxido dismutase, glutationa) e um produto de oxidação (malondialdeído). Resultados: Em animais com rinossinusite induzida, a amlodipina reduziu a perda dos cílios, edema da lâmina própria e deposição de colágeno em comparação com o grupo placebo (solução salina) e embora não seja superior à cefazolina, a amlodipina diminuiu a infiltração de leucócitos polimorfonucleares. Os níveis de atividade da superóxido dismutase e glutationa foram reduzidos, enquanto os níveis de malondialdeído aumentaram significativamente nos três grupos de tratamento em comparação ao grupo controle. O grupo tratado com amlodipina apresentou aumento significante dos níveis de superóxido dismutase e glutationa e diminuição dos níveis de malondialdeído em comparação com todos os grupos de tratamento. Conclusão: O composto não antibiótico amlodipina pode ter um papel no tratamento da rinossinusite aguda através de mecanismos protetores de tecido, antioxidantes e anti-inflamatórios.
Assuntos
Animais , Sinusite/tratamento farmacológico , Rinite/tratamento farmacológico , Anlodipino/farmacologia , Anti-Inflamatórios/farmacologia , Valores de Referência , Staphylococcus aureus , Superóxido Dismutase/análise , Ensaio de Imunoadsorção Enzimática , Distribuição Aleatória , Cefazolina/uso terapêutico , Cefazolina/farmacologia , Reprodutibilidade dos Testes , Resultado do Tratamento , Anlodipino/uso terapêutico , Glutationa/análise , Glutationa/efeitos dos fármacos , Cobaias , Malondialdeído/análise , Anti-Inflamatórios/uso terapêutico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologiaRESUMO
INTRODUCTION: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. OBJECTIVE: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. METHODS: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. RESULTS: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. CONCLUSION: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.
Assuntos
Anlodipino/farmacologia , Anti-Inflamatórios/farmacologia , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Anlodipino/uso terapêutico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Cefazolina/farmacologia , Cefazolina/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Glutationa/análise , Glutationa/efeitos dos fármacos , Cobaias , Malondialdeído/análise , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Distribuição Aleatória , Valores de Referência , Reprodutibilidade dos Testes , Rinite/microbiologia , Rinite/patologia , Sinusite/microbiologia , Sinusite/patologia , Staphylococcus aureus , Superóxido Dismutase/análise , Superóxido Dismutase/efeitos dos fármacos , Resultado do TratamentoRESUMO
Diclofenac sodium, an antiinflammatory agent, exhibited remarkable inhibitory action against both drug sensitive and drug resistant clinical isolates of Mycobacterium tuberculosis, as well as other mycobacteria. This drug was tested in vitro against 45 different strains of mycobacteria, most of which were inhibited by the drug at 10-25 µg/ml concentration. When tested in vivo, diclofenac, injected at 10 µg/g body weight of a Swiss strain of white mice, could significantly protect them when challenged with 50 median lethal dose of M. tuberculosis H37 Rv 102. According to chi2 test, the in vivo data were highly significant (p 0.01). Diclofenac was further tested for synergism with the conventional antimycobacterial drug streptomycin against M. smegmatis 798. When compared with their individual effects, synergism was found to be statistically significant (p 0.05). By the checkerboard assessment procedure, the fractional inhibitory concentration index of this combination was found to be 0.37, confirming synergism.
Diclofenac sódico, um agente antiinflamatório, mostrou ação inibitória marcante contra isolados clínicos de Mycobacterium tuberculosis sensíveis e resistentes à drogas, bem como contra outras micobactérias. A droga foi testada in vitro contra 45 cepas diferentes de micobactérias, sendo que a maioria foi inibida pela droga na concentração de 10-25 µg/ml. Quando testado in vitro, diclofenac injetado em ratos albinos da linhagem Swiss, na proporção de 10 µg/g de peso corporal, provocou proteção significativa dos animais desafiados com metade da dose letal de M. tuberculosis H37 Rv 102. De acordo com o teste chi2, os dados in vivo foram altamente significativos (p 0,01). Diclofenac foi posteriormente testado quanto ao sinergismo com a droga antimicobacteriana convencional estreptomicina, frente a M. smegmatis 798. Quando comparado aos seus efeitos individuais, o sinergismo foi estatisticamente significativo (p 0,05). Através da análise checkerboard, o índice fracional de concentração inibitória para essa combinação foi 0,37, confirmando o sinergismo.