Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

A ocorrência de produtos farmacêuticos e de cuidados pessoais no meio ambiente tem levado a preocupações sobre seu impacto ambiental e à saúde pública. O sulfametoxazol (SMX) é um fármaco que tem sido encontrado amplamente no ambiente. Neste estudo foi verificada a eficácia de vários processos, a saber eletroquímico, eletroquímico foto assistido, fotoquímico, Fenton e foto-Fenton, para a degradação de SMX em solução aquosa. A degradação eletroquímica e eletroquímica foto assistida foram realizadas em uma célula de fluxo do tipo filtro-prensa, usando um ânodo dimensionalmente estável comercial com composição nominal Ti/Ru0,3Ti0,7O2. Durante ambos os processos, efeitos de diferentes parâmetros foram analisados, como a natureza do eletrólito, a concentração de eletrólito suporte (NaCl) e a densidade de corrente aplicada. Os experimentos fotoquímicos, Fenton e foto-Fenton foram realizados em um reator de vidro cilíndrico de compartimento único. O efeito das concentrações inicias de Fe2+ e de H2O2 foram estudados para os processos Fenton e foto-Fenton. Similarmente, o efeito do pH inicial, a concentração inicial do SMX e a temperatura foram investigados para todos os processos. A variação da concentração de SMX foi determinada por cromatografia líquida de alta eficiência (CLAE) e a quantidade de matéria orgânica foi monitorada por análise de carbono orgânico total (COT). Os resultados obtidos indicaram que o SMX foi completamente degradado, porém, o COT foi apenas parcialmente removido em todos os processos. No período de tempo de ensaio estabelecido o aumento da densidade de corrente e da concentração de NaCl mais eficiente para a degradação e remoção de COT nos processos eletroquímicos. A quantidade de Fe2+ e H2O2 aumenta a eficiência do processo Fenton e foto-Fenton, e meio ácido foi favorável para todos os processos. O consumo de energia elétrica, baseado no parâmetro EEO (energia por ordem) mostrou que os processos eletroquímicos são energeticamente mais eficientes do que os fotoquímicos. As degradações acompanhadas por CLAE acoplado à espectrometria de massas, permitiu que vários intermediários fossem identificados, sendo então proposta uma sequência reacional para a degradação do SMX. O radical hidroxila e o cloro ativo atacam os anéis benzílico e isoxazólico, tendo sido demonstrado que os compostos iniciais formados foram os compostos hidrolisados e clorados. Os íons inorgânicos, tais como: NO3-, NH4+ e SO42-, também foram identificados durante os processos de degradação. / The occurrence of pharmaceuticals and personal care products in the environment has raised concerns about their impact upon environmental and public health. Sulfamethoxazole (SMX) is a pharmaceutical that has been found widely in the environment. This study investigated the effectiveness of various processes such as electrochemical, photo assisted electrochemical, photochemical, Fenton photo-Fenton to SMX degradation in aqueous solution. The electrochemical and photo-assisted electrochemical degradations were performed in a filter press type flow cell using a dimensionally stable anode with nominal composition of Ti/Ru0.3Ti0.7O2. During both these processes the effects of different parameters were analyzed, such as, nature of the electrolyte concentration of the supporting electrolyte (NaCl) and the applied current density. The photochemical, Fenton and photo - Fenton experiments were carried out in a single compartment cylindrical glass reactor. The effects initial iron concentrations and H2O2 were studied for Fenton and photo-Fenton processes. Similarly the effect of initial pH, initial concentration of SMX and temperature were investigated for all processes. The variation of SMX concentration was determined by high performance liquid chromatography (HPLC) and the amount of organic matter was monitored by analysis of total organic carbon (TOC). The results indicated that SMX was completely degraded, but TOC was partially removed in all processes studied, during experimental period the increase of the current density and NaCl concentration enhanced the degradation and TOC removal in the electrochemical processes. The amount of iron and H2O2 increases the efficiency of Fenton and photo-Fenton processes and acidic media was favorable for all processes. The electrical energy consumption parameter based on EEO (energy per order) was also evaluated and it was observed that the electrochemical processes are more energetically efficient than the photochemical. The degradations followed by HPLC coupled with mass spectrometry, in which several intermediates were identified and proposed a reaction sequence for the degradation of SMX. The hydroxyl radical and active chlorine attack benzene and isoxazólico rings, and has been demonstrated that the initial compounds formed were hydrolyzed and chlorinated compounds. Inorganic ions such NO3-, NH4+ and SO42- were also identified during degradation processes.

Magister Pharmaceuticae - MPharm / The objective was to prepare new solid phases, i.e. co-crystal forms, of two sulfa antibiotic drugs (sulfamethoxazole and sulfasalazine) with trimethoprim and fourteen potential co-formers with GRAS status. Trimethoprim was chosen for its synergistic effects with both sulfa drugs and the other co-formers were selected in an attempt to improve the physicochemical properties of the antibiotics. A variety of co-crystallization techniques, including solvent assisted grinding, slow evaporation, slurry method and solidification of the melt were used to obtain these results. From these methods, three new solid phases were successfully isolated for the sulfamethoxazole antibiotic, viz. sulfamethoxazole-benzoic anhydride (SMZ-BAN) co-crystal by the slurry method, amorphous sulfamethoxazole-trimethoprim (SMZ-TMP) form by solidification of the melt and amorphous sulfamethoxazole-oxalic acid (SMZ-OA) by slow evaporation. For the sulfasalazine antibiotic, co-crystallization experimentation produced, sulfasalazine-trimethoprim salt (SSZ-TMPs) by slow evaporation, sulfasalazine-trimethoprim co-crystal (SSZ-TMP) by solvent assisted grinding and sulfasalazine-nicotinamide co-crystal (SSZ-NC) by solidification of the melt. Of these six compounds subjected to single crystal X-ray analysis, only one of their structures was elucidated i.e. the salt, SSZ-TMPs. Different techniques that were used to assess the thermal behaviour of the products included hot stage microscopy, differential scanning calorimetry and thermogravimetric analysis. FTIR provided information on the purity of the compounds and the suggested host-guest interaction sites. X-ray powder diffraction supported the determination of the new phase comparative to the parent compounds. Finally dissolution testing was carried out for successful candidates with encouraging recommendations for future work.

Vancomycin has been considered first-line treatment for bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) despite treatment failures in up to 20% of patients with MRSA bacteremia secondary to endocarditis. However, trimethoprim-sulfamethoxazole (TMP-SMX) is as effective as vancomycin for the management of MRSA bacteremia. secondary to endocarditis in injection drug users. We report the successful management of a left ventricular assist device-related MRSA infection with persistent MRSA bacteremia that failed to respond to vancomycin, linezolid, and quinupristin/dalfopristin but did respond to TMP-SMX.

Pharmaceuticals and personal care products (PPCPs) are widely used throughout the world. PPCPs are emerging as pollutants of concern and may pose a risk in the future to drinking water supplies. Two such compounds are sulfamethoxazole (SMXL) and fluoxetine (FLX). These ionizable compounds are not readily removed from water by conventional water treatment technologies. Powdered activated carbon (PAC) is a useful material for removing contaminants from water and is currently used in many water treatment applications. PACs may carry either a net positive or negative surface charge depending on the pH of solution. This study examined the hypothesis that the electrostatic interactions between three PACs’ surface charges and the charges of sulfamethoxazole’s and fluoxetine’s ionizable functional groups would lead to greater sorption efficiency than non-electrostatic interactions alone. Samples containing SMXL or FLX, were treated with varying doses of PAC, and mixed for three hours. The pH of samples were adjusted between experiments to determine if interaction between the polar contaminants and charged surface of PAC significantly impacted removal of the contaminant from solution. Analysis of the treated samples showed the effects of pH and varying PACs on the removal of SMXL and FLX from solution. It was observed that pH of the solution did play a significant role in the removal of contaminant in a number of the experiments, but that under other conditions where greater removal was anticipated based on predicted electrostatic interactions, it did not. These conditions included pH conditions where the contaminant existed predominantly in a negatively charged form. While not the initial focus of this study, it was observed that pore size distribution of the PACs may play a more significant role in the removal of ionizable compounds, especially in the case of fluoxetine, than electrostatic interactions.

No description available.

In this study we compare the ability of nitrifying activated sludge (NAS) and nitrifying trickling filter (NTF) wastewater treatment to remove the following contaminants: acetaminophen, caffeine, 1,7-dimethylxanthine, cotinine, ibuprofen, sulfamethoxazole, triclosan, and trimethoprim. Removal of acetaminophen, cotinine and caffeine was greater than 99% and removal 1,7-dimethylxanthine, ibuprofen, and triclosan was greater than 90% using NAS and NTF treatment. Sulfamethoxazole and trimethoprim were inadequately removed in both NAS and NTF treatments. The horizontal, subsurface flow treatment wetland showed removals of 45-89% for sulfamethoxazole and greater than 96% for trimethoprim. There was no statistical difference (P>0.05) between aeration, temperature and vegetation in the treatment wetland for the removal of sulfamethoxazole and trimethoprim.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The bacterial deposition on surface and also the biofilm form occurring widely in the nature as a protection strategy developed for the bacteria against the harmful external factors. Microorganism, when was in biofilm form was able to generate several problems for the public heath justly for showed a higher resistance from the action of antibacterial agents when compared with the planktonic form. Bacteria are the microorganism more involved with the biofilm production in the presence of beneficial environmental conditions. In this way, Escherichia coli were the strain more involved with the process of adhesion in the surfaces. Few studies were developed to found new antimicrobial drugs precisely because the researches presented more interest to improve the known drugs. Thus, the present study was evaluated the antibiofilm capability of sulfamethoxazole (SMTZ) alone and when complexed with metals as mercury, copper, cadmium and silver. The compounds were tested against Escherichia coli (ATCC 25922). For evaluated the inhibition of the biofilm formation we were used microplates of polystyrene to observe the turbidity through the 570 nm in an ELISA plate reader. The results presented that the sulfamethoxazole compounds had an excellent antibiofilm activity and also that the complex SMTZ-Ag showed the best inhibitory activity against E. coli biofilm formation. Therefore, we conclude that these sulfamethoxazole complexed compounds require more researches in order to expand their antimicrobial activity. / A deposição de bactérias em uma superfície e a sucessiva formação de biofilmes são fenômenos que ocorrem naturalmente na natureza, servem como estratégia de proteção frente a fatores agressivos externos. Os micro-organismos, quando em biofilme, geram grande impacto à saúde pública, pois possuem maior resistência à ação de agentes antibacterianos e métodos de desinfecção quando comparados aos micro-organismos na forma planctônica. As bactérias são os agentes microbianos que mais comumente produzem biofilmes em condições favoráveis. Neste contexto, Escherichia coli inclui-se como uma das bactérias com maior participação nos processos de adesão. Pesquisas visando a descoberta de novos antibacterianos são escassas, uma vez que os esforços estão mais direcionados no aprimoramento da das drogas já existentes. Dessa forma, o presente trabalho se propôs avaliar a capacidade antibiofilme do sulfametoxazol complexado com os metais mercúrio, cobre, cádmio e prata. Esses foram testados frente a bactéria Escherichia coli (ATCC 25922). Para avaliar o grau de inibição da formação do biofilme foram utilizadas microplacas de poliestireno e a leitura da turvação bacteriana foi realizada em densidade óptica de 570nm em leitor de ELISA. Os resultados obtidos demonstram que os compostos de sulfametoxazol apresentaram uma excelente atividade antibiofilme, sendo que o complexo SMTZ-Ag foi o que exibiu melhor atividade contra a formação do biofilme de E. coli. Em vista disso torna-se válido investir em pesquisas no sentido de ampliar as atividades desses compostos.

A derivatization reaction, based on a copulation reaction of diazonium salt of an analyte with a reagent (1-aminonaphthalene or NEDA) producing colour, spectrophotometrically detectable product, has been used for determination of two analytes (procain hydrochloride, sulfamethoxazole) containing amino group in the molecule. The conditions of batch spectrophotometric determination were studied. It was found, that the batch determination is applicable only for procain hydrochloride analysis, because sulfamethoxazole gives time-unstable colour product. FIA arrangement was proposed and effects of selected parameters were optimized using two levels factorial design. The calibration dependences were measured for both analysis with both reagents, and subsequently were applied on determination of analytes in medical forms. Key words: diazotization, flow injection analysis, procaine, spectrophotometry, sulfamethoxazole

A recent systematic literature and meta-analysis reported relative efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of toxoplasmic encephalitis (TE) in HIV-infected adults. Here, we estimated relapse rates during secondary prophylaxis with TMP-SMX, and further explored differences in relapse rates prior to introduction of highly active antiretroviral therapy (HAART) and the widespread adoption of HAART. A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials yielded 707 studies whereby 663 were excluded after abstract screening, and 38 were excluded after full review leaving 6 studies for extraction. We performed double data extraction with a third-party adjudicator. Study designs varied with only one randomized study, four prospective cohorts and one retrospective cohort. Relapse rates were transformed using the Freeman-Tukey method and pooled using both fixed-effect and random-effects meta-analysis models. The TMP-SMX relapse rate was 16.4% (95% CI = 6.2% to 30.3%) based on random-effects models. When the disaggregated pre-HAART studies (n = 4) were included, the relapse rate was 14.9% (random effects; 95% CI = 3.7% to 31.9%). Analysis of two post-HAART studies indicated a relapse rate of 19.2% (random effects; 95% CI = 2.8% to 45.6%). Comparing the relapse rates between pre- and post-HAART studies were contrary to what might be expected based on known benefits of HAART therapy in this population. Nevertheless, cautious interpretation is necessary considering the heterogeneity of the included studies and a limited number of subjects receiving TMP-SMX reported in the post-HAART era.