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Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO. Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM. Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.
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ABSTRACT Purpose: To compare viscotrabeculotomy with anterior chamber irrigation to Ahmed glaucoma valve implantation for secondary glaucoma following silicone oil removal. Methods: A prospective study was conducted on 43 vitrectomized pseudophakic eyes with persistent glaucoma after silicone oil removal. Patients were randomized to either viscotrabeculotomy with anterior chamber irrigation or Ahmed glaucoma valve implantation. All patients were examined on day 1, week 1, and months 1, 3, 6, 9, 12, 18, and 24 postoperatively. Postoperative complications were noted. Success was defined as an intraocular pressure between 6 and 20 mmHg and with an intraocular pressure reduction of >30% compared with the preoperative intraocular pressure. Results: There were 22 eyes in the viscotrabeculotomy with anterior chamber irrigation and 21 eyes in the Ahmed glaucoma valve implantation group. The mean preoperative and postoperative intraocular pressure in the viscotrabeculotomy with anterior chamber irrigation and Ahmed glaucoma valve implantation groups were 35.5 ± 2.6 mmHg and 35.5 ± 2.4 mmHg and 16.9 ± 0.7 mmHg and 17.9 ± 0.9 mmHg respectively (p˂0.0001). There was a statistically significant intraocular pressure reduction at all follow-up time points compared to preoperative values (p˂0.0001) in both groups. The unqualified success rate in the viscotrabeculotomy with anterior chamber irrigation and Ahmed glaucoma valve implantation groups were 72.73% and 61.9%, respectively. A minimal self-limited hyphema was the most common complication. Conclusions: Both viscotrabeculotomy with anterior chamber irrigation and Ahmed glaucoma valve implantation are effective in lowering the intraocular pressure in glaucoma after silicone oil removal with viscotrabeculotomy with anterior chamber irrigation providing greater reduction, higher success rates, and minimal complications.
RESUMO Objetivo: Comparar a viscotrabeculotomia com irrigação da câmara anterior com o implante de válvula de glaucoma de Ahmed para glaucoma secundário após remoção de óleo de silicone. Métodos: Foi realizado um estudo prospectivo de 43 olhos pseudofácicos vitrectomizados com glaucoma persistente após a remoção de óleo de silicone. Os pacientes foram randomizados para viscotrabeculotomia com irrigação da câmara anterior ou implante de válvula de Ahmed. Todos os pacientes foram examinados no primeiro dia, na primeira semana e 1, 3, 6, 9, 12, 18 e 24 meses após a cirurgia. Observaram-se complicações pós-operatórias. O sucesso foi definido como uma pressão intraocular entre 6 e 20 mmHg e uma redução da pressão intraocular >30% em comparação com a pressão intraocular pré-operatória. Resultados: Foram designados 22 olhos para o grupo da viscotrabeculotomia com irrigação da câmara anterior e 21 olhos para o grupo do implante de válvula de Ahmed. A pressão intraocular média pré-operatória foi de 35,5 ± 2,6 mmHg para o grupo da viscotrabeculotomia com irrigação da câmara anterior e pós- e de 35,5 ± 2,4 mmHg no grupo do implante de válvula de Ahmed. e Os valores pós-operatórios foram de 16,9 ± 0,7 mmHg e 17,9 ± 0,9 mmHg para esses mesmos grupos, respectivamente (p<0,0001). Ambos os grupos tiveram uma redução estatisticamente significativa da pressão intraocular em relação aos valores pré-operatórios (p<0,0001) em todos os momentos do acompanhamento. A taxa de sucesso não qualificado nos grupos da viscotrabeculotomia com irrigação da câmara anterior e do implante de válvula de Ahmed foi de 72,73% e 61,9%, respectivamente. A complicação mais comum foi o hifema, autolimitado e mínimo. Conclusões: Tanto a viscotrabeculotomia com irrigação da câmara anterior quanto o implante de válvula de Ahmed são eficazes na redução da pressão intraocular no glaucoma após injeção de óleo de silicone, mas a viscotrabeculotomia com irrigação em câmara anterior proporcionou maior redução da pressão intraocular e maiores taxas de sucesso, com complicações mínimas.
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Leprosy is a Neglected Tropical Disease (NTDs) caused by Mycobacterium leprae (M. leprae). The treatment is considered effective, however, the high dose Multidrug Therapy (MDT) for a long period and its adverse effects result in the abandonment of the treatment by patients. Indeed, antimicrobial resistance is still an obstacle that must be overcome in the treatment of leprosy. In the present article, we reviewed the WHO guidelines for the chemotherapy of leprosy and the methods of synthesis of these drugs.
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Hansenostáticos , Hanseníase , Humanos , Quimioterapia Combinada , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Hanseníase/etiologia , Hanseníase/microbiologia , Mycobacterium leprae , Guias como AssuntoRESUMO
Abstract Introduction Traumatic large tympanic membrane perforations usually fail to heal and require longer healing times. Few studies have compared the healing and hearing outcomes between gelatin sponge patching and ofloxacin otic solution. Objectives To compare the healing outcomes of large traumatic tympanic membrane perforations treated with gelatin sponge, ofloxacin otic solution, and spontaneous healing. Methods Traumatic tympanic membrane perforations >50% of the entire eardrum were randomly divided into three groups: ofloxacin otic solution, gelatin sponge patch and spontaneous healing groups. The healing outcome and hearing gain were compared between the three groups at 6 months. Results A total of 136 patients with large traumatic tympanic membrane perforations were included in analyses. The closure rates were 97.6% (40/41), 87.2% (41/47), and 79.2% (38/48) in the ofloxacin otic solution, gelatin sponge patch, and spontaneous healing groups, respectively (p = 0.041). The mean times to closure were 13.12 ± 4.61, 16.47 ± 6.24, and 49.51 ± 18.22 days in these groups, respectively (p < 0.001). Conclusions Gelatin sponge patch and ofloxacin otic solution may serve as effective and inexpensive treatment strategies for traumatic large tympanic membrane perforations. However, ofloxacin otic solution must be self-applied daily to keep the perforation edge moist, while gelatin sponge patching requires periodic removal and re-patching.
Resumo Introdução As grandes perfurações traumáticas da membrana timpânica geralmente apresentam falha de cicatrização e requerem tempos de cicatrização mais longos; poucos estudos compararam os resultados de cicatrização e a audição dessas perfurações obtidos com curativo de Gelfoam® e solução otológica de ofloxacina. Objetivo Comparar os resultados de cicatrização de grandes perfurações traumáticas da membrana timpânica tratadas com Gelfoam®, solução otológica de ofloxacina e cicatrização espontânea. Método Perfurações traumáticas de > 50% de todo o tímpano foram divididas aleatoriamente em três grupos: tratamento com solução otológica de ofloxacina, com curativo de Gelfoam® e grupo de cicatrização espontânea. O resultado da cicatrização e o ganho auditivo foram comparados entre os três grupos após 6 meses. Resultados Foram incluídos nas análises 136 pacientes com grandes perfurações traumáticas de membrana timpânica. As taxas de cicatrização foram de 97,6% (40/41), 87,2% (41/47) e 79,2% (38/48) com a solução otológica de ofloxacina, curativo de Gelfoam® e grupos de cicatrização espontânea, respectivamente (p = 0,041). O tempo médio de cicatrização foi de 13,12 ± 4,61, 16,47 ± 6,24 e 49,51 ± 18,22 dias nesses grupos, respectivamente (p < 0,001). Conclusões O curativo de Gelfoam® e a solução otológica de ofloxacina podem servir como estratégias de tratamento eficazes e de baixo custo para grandes perfurações traumáticas de membrana timpânica. Entretanto, a solução otológica de ofloxacina deve ser autoaplicada diariamente para manter a borda da perfuração úmida, enquanto o curativo de Gelfoam® requer sua remoção e reaplicação periódicas.
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INTRODUCTION: Traumatic large tympanic membrane perforations usually fail to heal and require longer healing times. Few studies have compared the healing and hearing outcomes between gelatin sponge patching and ofloxacin otic solution. OBJECTIVES: To compare the healing outcomes of large traumatic tympanic membrane perforations treated with gelatin sponge, ofloxacin otic solution, and spontaneous healing. METHODS: Traumatic tympanic membrane perforations >50% of the entire eardrum were randomly divided into three groups: ofloxacin otic solution, gelatin sponge patch and spontaneous healing groups. The healing outcome and hearing gain were compared between the three groups at 6 months. RESULTS: A total of 136 patients with large traumatic tympanic membrane perforations were included in analyses. The closure rates were 97.6% (40/41), 87.2% (41/47), and 79.2% (38/48) in the ofloxacin otic solution, gelatin sponge patch, and spontaneous healing groups, respectively (p=0.041). The mean times to closure were 13.12±4.61, 16.47±6.24, and 49.51±18.22 days in these groups, respectively (p<0.001). CONCLUSIONS: Gelatin sponge patch and ofloxacin otic solution may serve as effective and inexpensive treatment strategies for traumatic large tympanic membrane perforations. However, ofloxacin otic solution must be self-applied daily to keep the perforation edge moist, while gelatin sponge patching requires periodic removal and re-patching.
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Gelatina , Perfuração da Membrana Timpânica , Humanos , Ofloxacino , Membrana Timpânica , Perfuração da Membrana Timpânica/tratamento farmacológico , CicatrizaçãoRESUMO
OBJECTIVE: To determine at two distinct time points the prevalence of resistance to ofloxacin (OFX), the representative class drug of fluoroquinolones (FQs), in M. tuberculosis isolates susceptible to first-line drugs. RESULTS: There were 279 M. tuberculosis isolates from the two cohorts (2004-2005: 238 isolates; 2017: 41 isolates) that underwent OFX drug-susceptibility testing (critical concentration: 2 µg/ml). Of 238 isolates in Cohort 1, no resistance to OFX was detected (95% CI 0-0.016); likewise, in Cohort 2, no resistance to OFX was detected in 41 isolates (95% CI 0-0.086). Our findings suggest that FQ use remains a viable option for the treatment of first-line drug-susceptible TB in Peru.
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Mycobacterium tuberculosis , Preparações Farmacêuticas , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Antituberculosos/farmacologia , Farmacorresistência Bacteriana , Fluoroquinolonas/farmacologia , Humanos , Levofloxacino , Testes de Sensibilidade Microbiana , Moxifloxacina , Peru/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
In the global context of an imminent emergence of multidrug-resistant microorganisms, the present work combined the use of nanotechnology and the therapeutic benefits of natural compounds as a strategy to potentiate antimicrobial action of the wide-spectrum antibiotic Ofloxacin (Ofx). Hybrid solid lipid nanoparticles (SLN) were synthesized by incorporation of chitosan (Chi, a cationic biopolymer with antimicrobial activity) and eugenol (Eu, a phenolic compound that interferes with bacterial quorum sensing) into a lipid matrix by hot homogenization/ultrasonication method. The developed SLN/Chi/Eu sustainably released the encapsulated Ofx for 24â¯h. Characterization by DLS, TEM, DSC, TGA and XRD revealed the presence of positively charged spherical nanoparticles with diameters around 300â¯nm and Ofx entrapped in amorphous state. The SLN exhibited an enhanced bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) for free and nanoencapsulated Ofx formulations was below 1.0⯵g/ml. The MIC values decreased by 6.1- to 16.1-fold when Ofx was encapsulated in SLN/Chi/Eu. Fluorescent-labeled nanoparticles had the ability to interact with the bacterial cell membrane. Selective toxicity of SLN/Chi/Eu-Ofx was tested in the range of 0.3-30.0⯵g/ml and showed no toxicity up to 3.0⯵g/ml Ofx in human cell models (A549 and Wi-38) at 24â¯h and 48â¯h exposure. It was proved that the administration of hybrid SLN to mice by dry powder inhalation reached therapeutic Ofx levels in lungs.
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Anti-Infecciosos , Portadores de Fármacos , Eugenol , Nanopartículas , Ofloxacino , Células A549 , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Eugenol/administração & dosagem , Eugenol/química , Eugenol/farmacocinética , Humanos , Lipídeos/administração & dosagem , Lipídeos/química , Lipídeos/farmacocinética , Pulmão/metabolismo , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Ofloxacino/administração & dosagem , Ofloxacino/química , Ofloxacino/farmacocinética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation, resulting in low ocular bioavailability. Mucoadhesive chitosan (CS)/ tripolyphosphatesodium (TPP) and chitosan (CS)/ tripolyphosphatesodium (TPP)-alginate (ALG) nanoparticles were investigated for the prolonged topical ophthalmic delivery of ofloxacin. A modified ionotropic gelation method was used to produce ofloxacin-loaded nanoreservoir systems. The ofloxacin-loaded CS/TPP and CS/TPP-ALG nanoparticles were characterized for particle size, morphology, zeta potential, encapsulation efficiency, subsequent release and corneal penetration study. The designed nanoparticles have a particle size from 113.8 nm to 509 nm and zeta potential from 16.2 mV to 40.3 mV and encapsulation efficiency values ranging from 19.7% to 33.1%. Nanoparticles revealed a release during the first hours, followed by a more gradual drug release. The ofloxacin-loading CS/TPP or CS/TPP-ALG NPs developed are pronounced penetration enhancing effect as compared to OFX solution (5-6.5 times). Thus, these nanoparticles have a strong potential for ocular drug delivery.
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Ofloxacino/análise , Quitosana/análise , Nanopartículas/análise , Administração Oftálmica , Fenômenos Fisiológicos Oculares , Infecções Oculares/classificação , Cromatografia Líquida de Alta Pressão/métodos , CórneaRESUMO
OBJECTIVES: Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network. METHODS: From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA. RESULTS: Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases. CONCLUSIONS: This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy.
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Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Hanseníase/epidemiologia , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/genética , Antibacterianos/efeitos adversos , Proteínas de Bactérias/genética , Biópsia por Agulha , Brasil/epidemiologia , Colômbia/epidemiologia , DNA Girase/genética , Dapsona/uso terapêutico , Doenças Endêmicas/estatística & dados numéricos , Monitoramento Epidemiológico , Saúde Global , Humanos , Índia/epidemiologia , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/microbiologia , Testes de Sensibilidade Microbiana , Mutação , Ofloxacino/uso terapêutico , Reação em Cadeia da Polimerase , Estudos Prospectivos , Recidiva , Rifampina/uso terapêutico , Vigilância de Evento Sentinela , Pele/microbiologia , Pele/patologia , Inquéritos e Questionários , Organização Mundial da SaúdeRESUMO
Antimicrobials are continuously detected in environmental waters and their removal is important to avoid health and microorganisms damage. In this work, the peroxidation assisted by ultraviolet radiation (UV/H2O2) was studied to verify if the process was able to degrade sulfaquinoxaline and ofloxacin antimicrobials and to remove the toxicity and the antimicrobial activity of the solution. This process was effective on degradation of the antimicrobials, despite the antimicrobial activity removal, the toxicity of the solution increased throughout the reaction time.
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Fotólise , Raios Ultravioleta , Anti-Infecciosos , Peróxido de Hidrogênio , Oxirredução , Poluentes Químicos da Água/toxicidadeRESUMO
We aimed to quantify the penetration of ciprofloxacin, ofloxacin, and moxifloxacin into the cornea and aqueous humor of cadaver eyes. A total of 60 enucleated eyes, not eligible for corneal transplantation, were divided into three groups and immersed in commercial solutions of 0.3% ciprofloxacin, 0.3% ofloxacin, or 0.5% moxifloxacin for 10 min. Whole corneas and samples of aqueous humor were then harvested and frozen, and drug concentrations analyzed by liquid chromatography tandem mass spectrometry. The mean corneal concentration of moxifloxacin was twice as high as ofloxacin, and the latter was twice as high as ciprofloxacin. The mean concentration of moxifloxacin in the aqueous humor was four times higher than the other antibiotics, and the mean concentrations of ciprofloxacin and ofloxacin were statistically similar. The amount of drug that penetrated the anterior chamber after a 10-min immersion was far below the safe limit of endothelial toxicity of each preparation. Moxifloxacin demonstrated far superior penetration into the cornea and anterior chamber of cadaver eyes compared to ciprofloxacin and ofloxacin. One should not expect endothelial toxicity with the commercial eye drops of ciprofloxacin, ofloxacin, and moxifloxacin that reach the anterior chamber through the cornea.
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Humanos , Humor Aquoso/efeitos dos fármacos , Ofloxacino/farmacocinética , Ciprofloxacina/farmacocinética , Córnea/efeitos dos fármacos , Fluoroquinolonas/farmacocinética , Cadáver , Enucleação Ocular , Teorema de Bayes , MoxifloxacinaRESUMO
New insights into the design of highly sensitive, carbon-based electrochemical sensors are presented in this work by exploring the interesting properties of graphene oxide (GO) and ionic liquids (ILs). An electrochemical sensor based on the carbon paste electrode (CPE) modified with GO and IL was developed for the sensitive detection of ofloxacin using square-wave adsorptive anodic stripping voltammetry (SWAdASV). GO sheets were obtained from the acid treatment of graphene and characterized by scanning and transmission electronic microscopy (SEM and TEM) and selected area electron diffraction (SAED), and the electrochemical behavior of the modified GO-IL/CPE was explored by electrochemical impedance spectroscopy studies. The CPE modification with GO and IL allowed an 8.2 fold increase in the analytical sensitivity for ofloxacin sensing compared to the unmodified CPE. Under the optimized experimental conditions using the SWAdASV technique, the GO-IL/CPE sensor provided an analytical curve for ofloxacin in the concentration range of 7.0×10-9 to 7.0×10-7molL-1, with a sensitivity of 7.7×106µALmol-1 and limit of detection of 2.8×10-10molL-1 (0.28nmolL-1). The proposed sensor was successfully applied for the ofloxacin determination in human urine and ophthalmic samples, with recoveries near 100%. The results were similar those obtained by a spectrophotometric comparative method.
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ABSTRACT The present research work was envisaged to develop bilayer tablets to improve therapeutic efficacy of antibiotic combination for the treatment of sexually transmitted diseases. The combination of two antibiotics i.e. cefixime trihydrate and ofloxacin were used for the preparation of bilayer tablets which act against genito-urinary infections. The formulations comprise of cefixime trihydrate as immediate release layer formulated using different superdisintegrants and ofloxacin as extended release layer containing HPMC K100M. Evaluation of bilayer tablets were performed for the immediate release cefixime layer and sustain release ofloxacin layer with optimization of excipients. The immediate release layer of cefixime showed complete release within 30 min and ofloxacin release was extended up to 24 hours. The similarity factor value of ofloxacin sustained release layer was found to be 87.01 for initial and 80.35 after 3 months stability when compared with marketed reference product. The present study revealed that cefixime trihydrate and ofloxacin bilayer tablets were successfully developed for the use against sexually transmitted infections.
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Comprimidos/farmacocinética , Infecções Sexualmente Transmissíveis/prevenção & controle , Ofloxacino/farmacocinética , Cefixima/farmacocinética , Derivados da Hipromelose/farmacocinéticaRESUMO
Introduction: There is no information in Colombia on Mycobacterium leprae primary and secondary drug resistance in regards to the WHO-multidrug therapy regime. On the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods. Objective: To determine the prevalence of Mycobacterium leprae drug resistance to rifampicin, ofloxacin and dapsone in untreated and previously treated patients at the Centro Dermatológico Federico Lleras Acosta during the 1985-2004 period. Materials and methods: We conducted a retrospective study which included multibacillary patient biopsies through elective sampling: 381 of them from new patients and 560 from previously treated patients. Using a microtome, we obtained six slides from each skin biopsy preserved in paraffin, and we extracted M. leprae DNA. We amplified three molecular targets through PCR and obtained the patterns of drug resistance to dapsone, rifampicin and ofloxacin by reverse hybridization. Finally, we collected epidemiological, clinical and demographical data for analyses. Results: From 941 samples under study, 4.14% of them were resistant to one or more drugs, and 5.77 and 3.04% had resistant genotypes in new and previously treated patients, respectively. Total resistance for each drug was 0.43% for dapsone, 3.19% for rifampicin and 1.17% for ofloxacin. We found statistically significant differences for rifampicin and for the total population when comparing the results from untreated versus previously treated patients. Two thirds of the resistant samples were resistant to rifampicin alone or combined. Conclusions: The standard multidrug therapy schemes continue being effective for leprosy cases; however, it is necessary to guarantee adherence and regularity. Surveillance to drug resistance in new and previously treated leprosy cases should be established.
Introducción. Colombia no dispone de información sobre farmacorresistencia primaria y secundaria de Mycobacterium leprae al esquema de terapia múltiple de la Organización Mundial de la Salud (OMS) y las autoridades de salud pública del mundo han emitido varias recomendaciones, entre las cuales está organizar de inmediato la vigilancia a la resistencia empleando métodos moleculares simples. Objetivo. Determinar la prevalencia de la resistencia de M. leprae a rifampicina, ofloxacina y dapsona en pacientes del Centro Dermatológico Federico Lleras Acosta con tratamiento previo y sin él durante el período de 1985 a 2004. Materiales y métodos. Se realizó un estudio retrospectivo. Mediante muestreo electivo se incluyeron biopsias de pacientes multibacilares: 381 de pacientes nuevos y 560 de pacientes previamente tratados. Se obtuvieron con micrótomo seis cortes de cada biopsia de piel incluida en parafina, y se realizó la extracción de ADN de M. leprae. Se llevó a cabo la amplificación de tres blancos moleculares mediante PCR y se obtuvieron los patrones de resistencia a los medicamentos dapsona, rifampicina y ofloxacina por hibridación inversa. Se recolectaron datos epidemiológicos, clínicos y demográficos para llevar a cabo los análisis. Resultados. De las 941 muestras estudiadas, 4,14 % era resistente a uno o más fármacos, y se detectaron 5,77 y 3,04 % con genotipos resistentes en pacientes nuevos y previamente tratados, respectivamente. La resistencia total para cada fármaco fue de 0,43 % a dapsona, 3,19 % a rifampicina y 1,17 % a ofloxacina. Se encontró una diferencia estadísticamente significativa para rifampicina y para la población total al comparar los resultados de los pacientes no tratados con los de los pacientes tratados previamente. Dos tercios de las muestras resistentes lo fueron a rifampicina sola o combinada. Conclusiones. Los esquemas de terapia múltiple estándar siguen siendo efectivos para los casos de lepra; sin embargo, es necesario garantizar el cumplimiento y la regularidad y establecer la vigilancia de la farmacorresistencia en pacientes nuevos y previamente tratados.
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Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Farmacorresistência Bacteriana Múltipla , Hansenostáticos/farmacologia , Hanseníase Multibacilar/microbiologia , Mycobacterium leprae/efeitos dos fármacos , Biópsia , Proteínas de Bactérias/genética , Colômbia/epidemiologia , DNA Bacteriano/genética , Quimioterapia Combinada , Dapsona/farmacologia , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Genótipo , Hansenostáticos/administração & dosagem , Hansenostáticos/uso terapêutico , Hanseníase Multibacilar/epidemiologia , Hanseníase Multibacilar/patologia , Mycobacterium leprae/genética , Mycobacterium leprae/isolamento & purificação , Ofloxacino/farmacologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Rifampina/farmacologiaRESUMO
OBJECTIVE: The objective of the study is to evaluate the physical properties, in vitro release profile, and antibacterial efficiency of chitosan films prepared with ofloxacin. PROCEDURE: Mucoadhesive films were prepared by means of a casting and solvent evaporation technique performed in a 2 wt% acetic acid solution and distilled water. Physical properties were characterized by release and swelling studies, differential scanning calorimetry (DSC) analysis, and attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR) analysis. The in vitro evaluation of the films was performed by inhibiting Staphylococcus aureus and Pseudomonas aeruginosa through activity studies. RESULTS: Circular ofloxacin-loaded chitosan-developed films with 0.3 mg of drug weighed 7 mg were 110 µm thick and 5 mm in diameter. The DSC curve of ofloxacin-loaded chitosan films suggests an amorphous dispersion of ofloxacin within these films. ATR-FTIR analysis showed that ofloxacin is indeed present in the matrix film. The drug was released in vitro over a 1-h period. No statistical difference could be observed between the ofloxacin-loaded chitosan films and sterile disk soaked for 1 min in 0.3% commercial ofloxacin ophthalmic solution for S. aureus and P. aeruginosa (P = 0.1686, P = 0.1172, respectively).The films presented a significantly larger mean bacterial inhibition zone of S. aureus than did the commercial ciprofloxacin control disk (P = 0.0002) and a significantly larger mean bacterial kill zone of P. aeruginosa than did the commercial enrofloxacin control disk (P < 0.0001). CONCLUSIONS: Ofloxacin was successively incorporated onto chitosan films and was not inactivated during the process of manufacturing, thus preserving antibacterial proprieties.
Assuntos
Quitosana/química , Ofloxacino/administração & dosagem , Ofloxacino/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Portadores de Fármacos/química , Membranas ArtificiaisRESUMO
Bitter taste of ofloxacin, a broad spectrum bactericidal agent, is masked and orally disintegrating tablets were formulated. The bitter taste is masked by forming complex between drug and weak cation exchange resins, Tulsion 335 and Indion 204. Effect of pH and drug:resin ratio on the drug loading was studied. Maximum drug loading was observed at pH 6. Ratio of 1:2 of drug:resin masked almost complete bitterness of ofloxacin. Formation of complexes was confirmed by IR spectroscopy. Physical characterization of taste masked complexes was carried out. Present work envisages the taste masking of ofloxacin and development of orally disintegrating tablets. The effect of pH and resin quantities on drug loading were studied to find the optimum conditions of drug loading for complete taste masking. Effect of superdisintegrants like sodium starch glycolate, croscarmellose sodium and polyplasdone XL at varying level on physical parameters of compressed tablets was also assessed. The formulations containing 5 % w/w polyplasdone XL showed about 90 % of drug release within 5 minutes. No significant differences were observed in the physical parameters of resinates as well as tablets prepared from Tulsion 335 and Indion 204.
O gosto amargo de ofloxacina, agente bactericida de largo espectro, é mascarado e formularam-se comprimidos dispersíveis. O sabor amargo é mascarado pela formação de complexo entre o fármaco e resinas de troca catiônica fraca, Tulsion 335 e Indion 204. Efeito do pH e da proporção fármaco: resina sobre a carga de fármaco foi estudada. Carga de fármaco máxima foi observada em pH 6. Proporção 1:2 do fármaco: resina mascarou quase completamente o gosto amargo de ofloxacina. A formação de complexos foi confirmada por espectroscopia no IV. Caracterização física dos complexos de sabor mascarado foi realizada. O presente trabalho preconiza o mascaramento do gosto de ofloxacina e desenvolvimento decomprimidos por via oral, se desintegrando. O efeito do pH e da resina quantidades de carga de fármaco foram estudadas paraencontrar as condições óptimas de carga de fármaco para dissimulação do saborcompleto. Efeito da superdisintegrants como amido glicolato de sódio, croscarmelose sódica e Polyplasdone XL em diferentes níveis de parâmetros físicos de comprimidos também avaliados foi avaliada. As formulações contendo 5 %w/w Polyplasdone XL mostraram cerca de 90% de libertação do fármaco no prazo de 5 minutos. Não foram observadas diferenças significativas nos parâmetros físicos de resinatosbem como comprimidos preparados a partir de Tulsion 335 e Indion 204.
Assuntos
Comprimidos/farmacocinética , Ofloxacino/análise , Resinas de Troca Iônica/farmacocinética , Fator de Crescimento de Hepatócito/classificaçãoRESUMO
One titrimetric and two spectrophotometric methods have been described for the determination of ofloxacin (OFX) in bulk drug and in tablets, employing N-Bromosuccinimide as an analytical reagent. The proposed methods involve the addition of a known excess of NBS to OFX in acid medium, followed by determination of unreacted NBS. In titrimetry, the unreacted NBS is determined iodometrically, and in spectrophotometry, unreacted NBS is determined by reacting with a fixed amount of either indigo carmine (Method A) or metanil yellow (Method B). In all the methods, the amount of NBS reacted corresponds to the amount of OFX. Titrimetry allows the determination of 1-8 mg of OFX and the calculations are based on a 1:5 (OFX:NBS) reaction stoichiometry. In spectrophotometry, Beer's law is obeyed in the concentration ranges 0.5-5.0 µg/mL for method A and 0.3-3.0 µg/mL for method B. The molar absorptivities are calculated to be 5.53x10(4) and 9.24x10(4) L/mol/cm for method A and method B, respectively. The methods developed were applied to the assay of OFX in tablets, and results compared statistically with those of a reference method. The accuracy and reliability of the methods were further ascertained by performing recovery tests via the standard-addition method.
Descrevem-se métodos, um titulométrico e dois espectrofotométricos, para a determinação de ofloxacino (OFX) na matéria-prima e em comprimidos, empregando a N-bromossuccinimida (NBS) como reagente analítico. Os métodos propostos envolvem a adição de excesso conhecido de NBS ao OFX, em meio ácido, seguida de determinação do NBS que não reagiu. Na titulometria, o NBS que não reagiu é determinado iodometricamente e na espectrofotometria, o NBS que não reagiu é determinado pela reação com quantidade fixa de índigo carmim (Método A) ou amarelo de metanila (Método B). Em todos os métodos, a quantidade de NBS que reagiu corresponde à quantidade de OFX. A titulometria permite a determinação de 1-8 mg de OFX e os cálculos se baseiam na estequiometria de reação de 1:5 (OFX:NBS). Na espectrofotometria, a Lei de Beer é obedecida nas faixas de concentração de 0,5-5,0 µg/mL, para o método A, e de 0,3-3,0 µg/mL, para o método B, respectivamente. Os métodos desenvolvidos foram aplicados para o teste de OFX em comprimidos e os resultados foram comparados estatisticamente com aqueles do método de referência. A precisão e a confiabilidade dos métodos foram, posteriormente, verificadas por meio dos testes de recuperação via método de adição de padrão.
Assuntos
Bromosuccinimida/diagnóstico , Espectrofotometria/métodos , Ofloxacino/diagnóstico , Titulometria/métodos , Métodos Analíticos de Preparação de Amostras , Antibacterianos/diagnóstico , Química Farmacêutica/métodosRESUMO
INTRODUÇÃO: Em 1997, após a realização de estudo multicêntrico, duplo cego e randomizado, em nove centros de tratamento de hanseníase na Índia, o Ministério da Saúde adotou o esquema alternativo dose única ROM para casos de lesão única, paucibacilar, sem nervo periférico afetado, índice baciloscópico negativo, em Centros de Referência da doença no Brasil. O estudo se propôs a avaliar a efetividade do esquema ROM em pacientes tratados no período de 1997 a 1999 no Serviço de Dermatologia da Santa Casa de Vitória. MÉTODOS: Foram selecionados e tratados com o esquema ROM, 54 pacientes das formas indeterminada e tuberculóide. Estes pacientes foram convocados de março a outubro de 2006 para reavaliação clínica. RESULTADOS: Vinte e nove pacientes avaliados (85,2 por cento; IC95 por cento: 70-100,4) estavam curados, cinco (14,7 por cento; IC95 por cento: 7,4-22,0) recidivaram e 20 pacientes não retornaram; porém, não havia outra notificação de reingresso ao tratamento no banco de dados da Secretaria Estadual de Saúde. CONCLUSÕES: O estudo evidenciou taxa de cura de 90,8 por cento e taxa bruta de recidiva de 9,2 por cento, após período de sete a nove anos da dose ROM. O tratamento alternativo ROM demonstrou melhor efetividade para lesão única menor que quatro centímetros e aparecimento há menos de cinco anos.
INTRODUCTION: In 1997, after obtaining a combined multi-state double-blind randomly controlled clinical trial study from nine Indian centers involved in the treatment of Hansen's Disease, the Ministry of Health adapted the single dose ROM Therapy approach in those cases involving the treatment of a single skin lesion, paucibacillary leprosy without evidence of peripheral nerve trunk involvement and indication of negative baciloscope, in the Referral Centers in Brazil. The study aimed to evaluate the effectiveness of the single dose ROM Therapy approach in those patients who were treated from the period of 1997 to 1999 in the Ambulatory Dermatologic Unit in the Hospital in Vitória, ES. METHODS: Fifty-four patients with tuberculoid and indeterminate leprosy were selected and treated with the single dose ROM Therapy approach. These patients were contacted from March 2006 up and until October 2006 for further clinical reevaluation. RESULTS: From the studies conducted, the following results were found to exist: 29 patients (85,2 percent; 95 percentCI: 70-100,4) were cured, 5 patients (14,7 percent; 95 percentCI: 7,4-22,0) relapsed, and 20 patients didn't return; however, there are no additional records of any notification of other treatment(s) in the State Department of Health's informational data banks. CONCLUSIONS: The study demonstrated a rate of cure of 90.8 percent and a rate of relapse of 9.2 percent after a period of seven to nine years using the single dose ROM Therapy approach. Additionally, this alternative treatment further demonstrated a better effectiveness for a single skin lesion smaller than four centimeters and with an appearance in less than five years.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Hansenostáticos/administração & dosagem , Hanseníase/tratamento farmacológico , Minociclina/administração & dosagem , Ofloxacino/administração & dosagem , Rifampina/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/métodos , Estudos Longitudinais , Hanseníase Tuberculoide/tratamento farmacológico , Hanseníase Tuberculoide/patologia , Hanseníase/patologia , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
Avaliou-se a concentração de ofloxacina liberada por uma lente de contato de membrana de celulose biossintética, para tratamento de ceratite bacteriana experimental em cães, pela inoculação de Staphylococcus aureus intraestromal. Comparou-se o tratamento com a lente de contato biossintética impregnada com ofloxacina à terapia tópica convencional. Realizou-se avaliação microbiológica e dosagem de ofloxacina no humor aquoso por meio do método de cromatografia líquida de alto rendimento (HPLC). Houve diferença estatística na contagem de colônias bacterianas entre os olhos com ceratite e os demais grupos, no primeiro dia de coleta. O biomaterial, impregnado com ofloxacina, promoveu liberação gradual durante o período de avaliação, aos três e sete dias; no terceiro dia, o grupo tratado com a lente de contato obteve mediana de 3,72μg/mL, enquanto o grupo tratado com colírio resultou em 49,56μg/mL. Apesar do valor inferior, o grupo com lente de contato atingiu a concentração inibitória mínima, sendo eficaz no controle da infecção bacteriana.(AU)
The concentration of ofloxacin released by contact lens made of biosynthetic cellulose membrane was evaluated for the treatment of experimental bacterial keratitis in dogs by intrastromal inoculation of Staphylococcus aureus. The biosynthetic contact lens impregnated with ofloxacin was compared with the conventional topical therapy. The microbiological evaluation and the determination of ofloxacin in aqueous humor were evaluated by high performance liquid chromatography (HPLC). There was not statistical difference in the counting of bacterial colonies among the eyes with keratitis and other groups, on the first day of collection. The biomaterial, impregnated with ofloxacin, promoted gradual release during the evaluation period, at three and seven days; on the third day, the group treated with the contact lens obtained a median of 3.72μg/mL, while the group treated with eye drops resulted in 49.56μg/mL. Despite the lower value, the group with contact lens reached the minimum inhibitory concentration, which was effective in controlling the bacterial infection.(AU)