Concentração de fluorquinolonas no humor aquoso após instilação tópica de soluções comerciais com ou sem corticosteroides
Arquivos
Data
2017-09-28
Autores
Gomes, Rachel Lopes Rodrigues 
Orientadores
Campos, Mauro Silveira de Queiroz
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivos: comparar a concentração de moxifloxacino ou gatifloxacino no humor aquoso após o uso tópico do moxifloxacino 0.5% ou gatifloxacino 0.3% isolados ou combinados com corticosteroides, e correlacionar a concentração com a concentração inibitória mínima (MIC) para os agentes microbianos mais comumente relacionados à endoftalmites. Métodos: pacientes com indicação de cirurgia de catarata foram selecionados para receber um dos seguintes regimes profiláticos: 1 gota de 6/6h, 1 dia antes da cirurgia (grupos 1 e 2) e 1 gota, 1 hora antes da cirurgia ou 1 gota a cada 15 min, 1 hora antes do procedimento (grupos 3 a 6). Uma das seguintes soluções: moxifloxacino (grupos 2 e 3), moxifloxacino+dexametasona (grupos 1 e 4), gatifloxacino (grupo 5) ou gatifloxacino+prednisolona (grupo 6). Amostras do humor aquoso foram coletadas antes do início da cirurgia. As concentrações do antibiótico nas amostras foram determinadas por meio de cromatografia líquida de alta eficiência acoplada a espectrômetro de massas (LC-MS/MS). Resultados: as concentrações médias de antibiótico nas amostras foram: grupo 1=986.6 ng/mL; grupo 2= 741.3 ng/mL; grupo 3=1280.8 ng/ml; grupo 4=1644.3 ng/ml; grupo 5=433.7 ng/ml; grupo 6=308.1 ng/ml. Entre os grupos 1 e 2 a diferença entre as médias não foi estatisticamente significativa (p=0.13). Por sua vez, entre os grupos 3 e 4 (P=0.01) e entre os grupos 5 e 6 (P=0.008) a diferença foi significativa. Todas as amostras alcançaram MIC para S. epidermidis; 100% das amostras dos grupos 1, 2, 3 e 4, e 97% dos grupos 5 e 6 atingiram o MIC para S. aureus fluoroquinolona-sensível; 100% das amostras dos grupos 1, 3 e 4, 94% do grupo 2, 88% do grupo 5 e 72% do grupo 6 atingiram o MIC para Enterococci (P<0.001); e 100% das amostras dos grupos 1, 2, 3 e 4, 59% do grupo 5 e 36% do grupo 6 atingiram o MIC para S. pneumoniae (P<0.001). Para o S. aureus resistente a fluoroquinolona, 29% do grupo 1, 9% do grupo 2, 23% do grupo 3, 44% do G4, e nenhuma das amostras grupos 5 e 6 atingiram o MIC (P<0.001). Conclusão: moxifloxacino associado à dexametasona demonstrou maior concentração no humor aquoso quando comparada com o moxifloxacino sem associação com corticoide. Gatifloxacino associado à prednisolona demonstrou menor penetração na câmara anterior quando comparado com o a penetração do gatfloxacino isolado. Maior número de amostras do grupo do moxifloxacino atingiu o MIC para Enterocci, S. pneumomiae e S. aureus resistente a fluorquinolonas.
Aims: to compare aqueous humor (AH) concentration of moxifloxacin 0.5% and gatifloxacin 0.3% after the topical administration of the solutions alone or with steroids, and to correlate concentration with the MIC for the most common endophthalmitis-causing organisms. Methods: sixty-eight patients undergoing routine phacoemulsification with intraocular lens implantation received either moxifloxacin 0.5% (G1) alone or moxifloxacin 0.5% combined with dexamethasone (G2). For both groups, one drop of the test solution was instilled four times daily 1 day preoperatively and one drop 1 hour preoperatively. Other 139 patients undergoing phacoemulsification were enrolled to receive 1 drop every 15min, 1h before surgery of one of the solutions: moxifloxacin (G3), moxifloxacin+dexamethasone (G4), gatifloxacin (G5) or gatifloxacin+prednisolone (G6). An aqueous humor sample, obtained immediately before the beginning of the procedure, was submitted to high-performance liquid chromatography-tandem mass spectrometry to determine the moxifloxacin or gatifloxacin concentration. Results: the mean concentrations of moxifloxacin were 986.6 ng/ml in the moxifloxacin with dexamethasone group (G2) and 741.3 ng/ml in the moxifloxacin group (G1) (p = 0.13). Moxifloxacin concentrations of all samples exceeded the MICs for Staphylococcus epidermidis, S. aureus, and Streptococcus pneumoniae. All samples in the moxifloxacin with dexamethasone group and 94% in the moxifloxacin group achieved the MIC for Enterococcus species. For quinolone-resistant S. aureus, the MIC was achieved in 29% in the moxifloxacin with dexamethasone group and 9% in the moxifloxacin group (p=0.06). Mean antibiotic concentrations in the AH: G3=1280.8 ng/ml; G4=1644.3 ng/ml; G5=433.7 ng/ml; G6=308.1 ng/ml. Mean concentrations between G3 and 4 (P=0.01), and G5 and 6 (P=0.008). All samples achieved the MIC for S. epidermidis; 100% of samples from G3 and 4, and 97% from G5 and 6 reached the MIC for fluoroquinolone-sensible S. aureus; 100% of the samples from G3 and 4, 88% from group 5 and 72% from group 6 have reached the MIC for Enterococci (P<0.001); and 100% of samples from G3 and 4, 59% from G5 and 36% from G6 reached the MIC S. pneumoniae (P<0.001). For the fluoroquinolone-resistant S. aureus, 23% from G1, 44% from G2, and no samples from G5 and 6 have achieved the MIC (P<0.001). Conclusion: moxifloxacin+dexamethasone demonstrated a higher concentration in the AH compared to the moxifloxacin alone. Gatifloxacin+steroids demonstrated less penetration in the anterior chamber compared to the steroid-free gatifloxacin solution. Moxifloxacin was superior to gatifloxacin considering MIC for Enterococci, S. pneumoniae and fluoroquinolone resistant S. aureus.
Aims: to compare aqueous humor (AH) concentration of moxifloxacin 0.5% and gatifloxacin 0.3% after the topical administration of the solutions alone or with steroids, and to correlate concentration with the MIC for the most common endophthalmitis-causing organisms. Methods: sixty-eight patients undergoing routine phacoemulsification with intraocular lens implantation received either moxifloxacin 0.5% (G1) alone or moxifloxacin 0.5% combined with dexamethasone (G2). For both groups, one drop of the test solution was instilled four times daily 1 day preoperatively and one drop 1 hour preoperatively. Other 139 patients undergoing phacoemulsification were enrolled to receive 1 drop every 15min, 1h before surgery of one of the solutions: moxifloxacin (G3), moxifloxacin+dexamethasone (G4), gatifloxacin (G5) or gatifloxacin+prednisolone (G6). An aqueous humor sample, obtained immediately before the beginning of the procedure, was submitted to high-performance liquid chromatography-tandem mass spectrometry to determine the moxifloxacin or gatifloxacin concentration. Results: the mean concentrations of moxifloxacin were 986.6 ng/ml in the moxifloxacin with dexamethasone group (G2) and 741.3 ng/ml in the moxifloxacin group (G1) (p = 0.13). Moxifloxacin concentrations of all samples exceeded the MICs for Staphylococcus epidermidis, S. aureus, and Streptococcus pneumoniae. All samples in the moxifloxacin with dexamethasone group and 94% in the moxifloxacin group achieved the MIC for Enterococcus species. For quinolone-resistant S. aureus, the MIC was achieved in 29% in the moxifloxacin with dexamethasone group and 9% in the moxifloxacin group (p=0.06). Mean antibiotic concentrations in the AH: G3=1280.8 ng/ml; G4=1644.3 ng/ml; G5=433.7 ng/ml; G6=308.1 ng/ml. Mean concentrations between G3 and 4 (P=0.01), and G5 and 6 (P=0.008). All samples achieved the MIC for S. epidermidis; 100% of samples from G3 and 4, and 97% from G5 and 6 reached the MIC for fluoroquinolone-sensible S. aureus; 100% of the samples from G3 and 4, 88% from group 5 and 72% from group 6 have reached the MIC for Enterococci (P<0.001); and 100% of samples from G3 and 4, 59% from G5 and 36% from G6 reached the MIC S. pneumoniae (P<0.001). For the fluoroquinolone-resistant S. aureus, 23% from G1, 44% from G2, and no samples from G5 and 6 have achieved the MIC (P<0.001). Conclusion: moxifloxacin+dexamethasone demonstrated a higher concentration in the AH compared to the moxifloxacin alone. Gatifloxacin+steroids demonstrated less penetration in the anterior chamber compared to the steroid-free gatifloxacin solution. Moxifloxacin was superior to gatifloxacin considering MIC for Enterococci, S. pneumoniae and fluoroquinolone resistant S. aureus.
Descrição
Citação
GOMES, Rachel Lopes Rodrigues. Concentração de fluorquinolonas no humor aquoso após instilação tópica de soluções comerciais com ou sem corticosteroides. 2017. São Paulo, [68] p. Tese (Doutorado em Oftalmologia e ciências visuais) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, 2017.