11 |
EFFECT OF COMBINATION EXPOSURE TO ZIDOVUDINE AND SULFAMETHOXAZOLE-TRIMETHOPRIM ON IMMUNE RESPONSE IN MICE AND HUMANSFeola, David James 01 January 2005 (has links)
The drug-drug interaction involving zidovudine and sulfamethoxazole-trimethoprim was investigated using an in vitro culture system, an in vivo mouse model, and a clinical trial in HIV-infected patients. We hypothesized that combination exposure causes immune cell populations in the bone marrow to undergo apoptotic cell death, and that the toxicity would affect the host response to an infectious stimulus. Mice were dosed with zidovudine, sulfamethoxazole-trimethoprim, the combination of both drugs, or vehicle only control via oral gavage. Focusing on B-lineage cells in the bone marrow, we determined that cells of the rapidly cycling, early pre-B cell subset are targeted, as well as pro-B cells earlier in development. This toxicity was found to be cell cycle dependent, with an increase in percentage of cells in the S/G2/M phases of the cycle. In vitro experiments using the drugs in a bone marrow culture system demonstrated that the effect of cytotoxicity with combination exposure is synergistic and concentration-dependent. The mechanism of apoptosis that is induced appears to be caspase-independent. To measure host response in mice, animals treated with zidovudine plus sulfamethoxazole-trimethoprim were infected with Pneumocystis murina pneumonia, and the group that received the combination of agents had a blunted antigen-specific IgG response, possibly due to a decreased number of B cells and activated B cells in the draining lymph nodes of the lungs. A clinical trial was conducted in HIV-infected patients, dividing subjects into groups receiving zidovudine, sulfamethoxazole-trimethoprim, the combination of both, or neither agent. Upon vaccination with the influenza vaccine, the combination treatment group had a blunted humoral response, with reduced antigen-specific serum IgG titers as compared to the control group. We conclude that the drug-drug interaction involving zidovudine and sulfamethoxazole-trimethoprim is clinically-significant, and clinicians must consider this toxicity when treating patients with these agents concurrently.
|
12 |
A crystal engineering study of selected sulfa drugs and trimethoprimElbakush, Rasha Elmheidi January 2014 (has links)
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.
|
13 |
The Use of Trimethoprim-Sulfamethoxazole for Serious MRSA InfectionsShams, Wael E., McCormick, Malkanthie, Rapp, Robert P., Evans, Martin E. 01 October 2005 (has links)
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.
|
14 |
Homologous and heterologous stress adaptation in Listeria monocytogenes after sublethal exposure to quaternary ammonium compoundKode, Divya Satish 30 April 2021 (has links) (PDF)
Listeria monocytogenes is an important foodborne pathogen that can adapt to stress conditions to persist in food processing environments. Our findings show that there was a development of low-level tolerance to quaternary ammonium compound (QAC) and antibiotics ciprofloxacin and trimethoprim in L. monocytogenes after sublethal adaptation to QAC. Using eight L. monocytogenes strains, we determined the changes in MIC, growth rate, and surviving CFU for homologous and heterologous stress-response after sublethal exposure to daily cycles of fixed or gradually increasing concentration of QAC. Three main findings were observed: (1) Short-range MIC of QAC, ciprofloxacin, and trimethoprim increased by 1.6 to 2.3, 1.5 to 2.9, and 1.7 to 2.5 fold against QAC-adapted phenotypes of L. monocytogenes as compared to the non-adapted cells; (2) QAC-adapted phenotypes of L. monocytogenes exhibited a significant increase in growth rate by 2.5 to 7.1, 2.1 to 6.8, or 1.4 to 4.8 fold in the broth model containing QAC, ciprofloxacin, or trimethoprim respectively, as compared to non-adapted cells; and (3) QAC-adapted phenotypes of L. monocytogenes exhibited a significant increase in survival by 1.5 to 4, 2.2 to 4.3, or 1.3 to 3.2 log CFU/ml in the agar model containing QAC, ciprofloxacin, or trimethoprim respectively, as compared to non-adapted cells (P < 0.05). There were strain differences in QAC-adapted phenotypes of L. monocytogenes for both homologous and heterologous stress-response with some strains exhibiting a significant increase in short-range MIC, growth rate, and survival while others exhibiting no changes as compared to non-adapted cells. These findings suggest the potential formation of low-level QAC-tolerant and antibiotic-tolerant phenotypes in some L. monocytogenes strains under residual QAC concentrations (where QAC may be used widely) and such cells if not inactivated may survive longer to increase food safety risk.
|
15 |
Topická a systémová léčba acne vulgaris / Topical and systemic treatment of acne vulgarisAckermannová, Veronika January 2020 (has links)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Veronika Ackermannová Supervisor: prof. Radomír Hrdina, MD, CSc. Title of diploma thesis: Topic and systemic treatment of acne vulgaris Acne vulgaris is a skin disease affecting the hair follicles and sebaceous glands. The disease manifests itself by increased sebum production, non-inflammatory (comedones) and inflammatory lesions (papules, pustules, nodules, cysts). It occurs predominantly in adolescents, but may persist into adulthood. It is a multifactorial disease, which is caused by several factors (internal and external stimuli). The major pathogenetic factors include increased sebum production, hyperkeratosis, P. acnes colonization and inflammation present. First, it is necessary to diagnose the type of acne in order to choose the right and effective therapy, because there is not only one type of acne. There are many types and variants of acne, and although they show similar symptoms (affecting the follicles of sebaceous glands), their cause often differs. There is no uniform classification system for acne vulgaris and it varies between authors. Some authors classify acne vulgaris according to severity into mild, moderate and severe, others into comedonic, papulopustular, nodulocystic...
|
16 |
Trimethoprim/sulfamethoxazole Induced Liver Injury in Treatment of Pneumocystis Jiroveci Pneumonia in an Oncology PatientWaldroup, C., Bossaer, John B. 01 December 2016 (has links)
No description available.
|
17 |
Comparative removal of pharmaceuticals and antimicrobials in conventional and constructed wetland wastewater treatment in cold climateGorsalitz, Emily Kristine 01 July 2012 (has links)
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.
|
18 |
Antibiotic associated diarrhea in horses : with special reference to Clostridium difficile /Gustafsson, Agneta, January 2004 (has links) (PDF)
Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2004. / Härtill 4 uppsatser.
|
19 |
Estudo físico-químico do complexo de inclusão do fármaco Trimetoprim com a β ciclodextrina aleatoriamente metilada / STUDY OF PHYSICAL-CHEMICAL INCLUSION COMPLEX DRUG TRIMETHOPRIM WITH RANDOM METHYL Β CYCLODEXTRINKubota, Daniela 16 March 2010 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Cyclodextrins are well-known as good solubilizers for many drug molecules, since they are capable of increasing the solubility of the drugs by the formation of inclusion complexes, which in turn can be used in pharmaceutical formulations. In this work we aimed to prepare and characterize inclusion complexes of the randomly methylated β-cyclodextrin (RAMEB) and the antibiotic drug trimethoprim (TMP). The inclusion complex has been prepared by the suspension method and a kinetic study of the inclusion process allowed us to determine that a contact time of 24 hours is necessary for the equilibrium establishment. The inclusion complex in the solid state has been characterized by TG, DSC, FTIR, XRD, uni- and bidimensional 1H NMR spectroscopy (ROESY). Three different media were chosen for the study of the solution behavior: water, acid (pH 4.0) and basic (pH 9.0). The occurrence of inclusion has been evidenced primarily by the increase of the solubility of TMP in the presence of RAMEB according to the phase-solubility diagrams. The phase-solubility diagram obtained in acid medium, water and basic medium exhibited respectively the characteristic AL, BS, AN profiles. The AL profile is related to linear increasing in the solubility with increasing CD concentration, in contrast to the other profiles. The phase-solubility diagrams also provide a means of determining the values of association constants, in the case of linear behavior. Here a value of 754,9 L.mol-1 has been found for the formation in acid medium, indicating that formation of the complex is favored in this medium. A 1:1 stoichiometry was found for the inclusion complex both from the phase-solubility and from the Job Plot, as known as continuous variation method. Additional evidences of complexation were provided by TG analysis which showed an increasing of TMP stability when complexed to RAMEB. From NMR spectroscopy it was possible to evaluate the orientation adopted by drug molecules inside the RAMEB cavity. From this result, it became clear that TMP is included in the cavity through the trimethoxyphenyl ring, according to cross-peaks that indicate proximity in space between protons from this ring and protons from the RAMEB cavity. / Ciclodextrinas são conhecidas como bons solubilizantes para vários fármacos, pois aumentam a solubilidade dos mesmos, sendo por isso, incorporadas em formulações farmacêuticas. O presente trabalho teve por objetivo preparar e caracterizar complexos de inclusão entre um derivado metilado de ciclodextrina, a β-ciclodextrina aleatoriamente metilada (RAMEB) (randomly methylated β-cyclodextrin) e o fármaco Trimetoprim (TMP). Os complexos foram preparados pelo método da suspensão, sendo que o estudo da cinética de complexação do TMP na RAMEB foi importante para identificar o tempo necessário de formação deste complexo. Sendo este tempo de vinte quatro horas até o estabelecimento do equilíbrio. O complexo de inclusão no estado sólido foi caracterizado por TG, DSC, FTIR, DRX e espectroscopia de RMN 1H, bidimensional (ROESY). Foram estabelecidos três meios para o estudo em solução: em água, em um meio ácido (pH 4) e um meio básico (pH 9). A ocorrência de inclusão nos estudos em solução foi evidenciada através do aumento da solubilidade do TMP em presença da RAMEB, descritos pelo do diagrama de solubilidade de fases. Nestes, obteve-se um perfil do tipo AL para o meio ácido, BS em água e AN para o meio básico, sendo que um perfil do tipo AL demonstra um aumento da solubilidade do TMP em concentrações crescentes de RAMEB, fato que não ocorre para os outros perfis. Ainda, a partir destes estudos, um valor de 754,9L.mol-1 para a constante de associação do complexo em meio ácido foi obtido. Isso confirma que formação do complexo é mais pronunciada em meio ácido. A estequiometria de 1:1 para o complexo foi sugerida tanto a partir do diagrama de solubilidades quanto pelo método das variações contínuas. Evidências adicionais da inclusão foram propiciadas por análises termogravimétricas (TGA), onde foi observado um aumento de estabilidade térmica do fármaco quando encapsulado na ciclodextrina. Por espectroscopia de ressonância magnética nuclear (RMN), foi possível determinar o modo de inclusão envolvido na formação do complexo, através da orientação do fármaco na cavidade da ciclodextrina. Por esse estudo fica evidenciado que o fármaco trimetoprim entra na cavidade maior da ciclodextrina e sua orientação é pelo o anel trimetoxifenil, pois foram encontradas correlações que indicam proximidade espacial dos átomos de hidrogênios deste grupo com átomos do interior da cavidade da CD.
|
20 |
Systematic review and meta-analysis of secondary prophylaxis for prevention of HIV-related toxoplasmic encephalitis relapse using trimethoprim-sulfamethoxazoleConnolly, Mark P., Haitsma, Gertruud, Hernández, Adrián V., Vidal, José E. 20 October 2017 (has links)
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.
|
Page generated in 0.0679 seconds