Aryloxoalcanoic compounds induce resistance to antibiotic therapy in urinary tract infection caused by Escherichia coli.

Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) is administered to enhance diuresis. These compounds are structurally analogous to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), as they have a chlorinated phenoxy moiety. As these agents are mainly excreted by the renal route, they could potentially coexist with Escherichia coli in the urinary tract of infected patients. Induction of the in vitro resistance of E. coli to hydrophilic antibiotics was determined by increasing the values of the minimum inhibitory concentration (2-40-fold). These results correlated with drastically inhibited expression of the hydrophilic bacterial channel OmpF. In vivo assays were performed in ascending urinary tract infection in female BALB/c mice. Treatment with the hydrophilic antibiotic cephalexin 25 mg kg(-1) day(-1) by the oral route diminished renal infection. The CFU mean values in the kidneys were between 75% and 89% lower than those in animals without treatment. Simultaneous exposure to CL (at a therapeutic dose, 28.6 mg kg(-1) day(-1)) did not change the effect of the treatment. In contrast, ET at 2.9 mg kg(-1) day(-1) or 2,4-D at 70 mg kg(-1) day(-1) inhibited the antibiotic therapeutic effect. Moreover, 2,4-D dramatically increased bacterial infection after 9 days of exposure.

Associação de medicamentos: estatinas e fibratos / Combination of drugs: statins and fibrates

Monoterapia para o tratamento das dislipidemias é frequentemente insuficiente para o alcance das metas recomendadas pelas diretrizes. Entretanto, nos últimos anos, o uso de terapia combinada tem se apresentado como uma nova opção em muitos casos. Uma revisão de 36 estudos envolvendo a combinação de estatinas com fibratos apresentou 29 casos de rabdomiólise e uma prevalência geral de miopatia de 0,12 por cento. A combinação de estatinas com o genfibrozil parece causar mais rabdomiólise que com os fibratos de nova geração (especialmente quando comparado com fenofibrato ou bezafibrato). Idade avançada, diabetes, mulheres, medicações concomitantes, disfunção renal, consumo excessivo de álcool, exercícios, traumatismos e cirurgias estão também associados com maior risco de efeitos adversos.

[Drug combinations: statins and fibrates]. / Associação de medicamentos: estatinas e fibratos.

Monotherapy for the treatment of dyslipidemias is commonly insufficient to achieve all lipid targets recommended by current guidelines. Therefore, the use of combined treatment has emerged as a new option in many cases in the last few years. A review of 36 studies in which the combination of statins with fibrates was used revealed 29 cases of rhabdomyolysis with a prevalence of 0.12% in the risk of myopathy. Combination of a statin with genfibrozil appeared to cause more rhabdomyolysis than with newest fibrates (especially when compared with fenofibrate or bezafibrate). Advanced age, diabetes, females, concomitant medications, renal insufficiency, excess in alcohol intake, exercises, trauma and surgery were all associated with higher rates of adverse effects.

Statin and fibrate associated myopathy: study of eight patients.

Lipid-lowering drugs have been occasionally associated with neuromuscular symptoms and muscle biopsy changes. We reported the clinical course and the muscle biopsy in eight patients with hyperlipoproteinemia, treated with lipid -lowering drugs (statins/fibrates). Five patients had myalgias while; in two cases there was proximal muscle weakness. All patients became asymptomatic after the withdrawal of the drug, although creatine kinase remained elevated. We performed muscle biopsy in six cases from three months to two years after suspension of the drug. We found variation in fibers diameters in all cases, with necrosis of fibers in five cases, inflammatory infiltration in one case, the presence of vacuolated fiber in one patient and ragged-red fibers in three subjects. We concluded that although the muscle biopsy findings were not specific, the prolonged use of statins and or fibrates might induce a chronic myopathy even in the absence of symptoms.

Statin and fibrate associed myopathy: study of eight patients

As drogas redutoras de colesterol são ocasionalmente associadas a sintomas neuromusculares e alterações morfológicas observadas na biopsia muscular. Relatamos o curso clínico e achado da biopsia muscular em oito pacientes com hiperlipoproteinemia tratados com drogas redutoras de colesterol (estatinas/fibratos). Cinco pacientes tiveram mialgia e em dois havia fraqueza muscular proximal. Todos os pacientes ficaram assintomáticos após retirada da medicação embora a creatinoquinase permanecesse elevada. Analisamos a biopsia muscular em seis casos realizados entre três meses e dois anos após a suspensão da droga. Encontramos variação no calibre das fibras em todos os casos com necrose de fibras em cinco, infiltrado inflamatório em um caso, presença de vacúolos em um e "ragged red fiber" em três deles. Concluímos que, embora os achados da biopsia muscular não fossem específicos, o uso prolongado de estatinas e/ou fibratos pode induzir a uma miopatia crônica até mesmo na ausência de sintomas.