Avaliação da eficácia da claritromicina e da amicacina no tratamento da infecção experimental de camundongos BALB/c pelo Mycobacterium massiliense
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2012-08-21
Autores
Colombo, Débora Corona
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Universidade Federal do Espírito Santo
Resumo
Nosocomial infections caused by rapidly growing mycobacteria (RGM) have increased significantly in recent years in developed and developing countries. In Brazil, the occurrence of outbreaks due to RGM was reported since last decade. In most cases, a single strain of M. massiliense, named BRA100, was the causative agent. M. massiliense, as well as other species of the group RGM, is resistant to a broad-spectrum of antimicrobial agents, which limits the therapeutic options for the treatment of patients. Due to the lack of clinical trials to establish appropriate therapeutic regimens, the current guidelines for the treatment of infections caused by these microorganisms are based on in vitro antimicrobial activities and clinical case reports. However, there are variations in the correlation between the in vitro susceptibility tests results and the therapeutic response observed, which creates a controversy about their use to support the pharmacotherapy of infections by RGM. In this context, we conducted a study to evaluate the activities of clarithromycin and amikacin against M. massiliense in BALB/c mice. The Minimal Inhibitory Concentration (MICs) of clarithromycin and amikacin for the M. massiliense isolate obtained from a nosocomial outbreak that occurred in 2007, were determined by the broth microdilution assay using cation-adjusted Mueller–Hinton. For in vivo tests, BALB/c mice were infected intravenously with 1 X 107 to 2 x 107 CFU/mL of M. massiliense. Treatments with amikacin or clarithromycin lactobionate were initiated one day post-infection. The mice received daily by subcutaneous injection, 0.1 ml of clarithromycin lactobionate (50mg/kg/12h) or 0.1 ml of amikacin (100mg/kg/day) for 14 days. The mice were sacrificed 24 to 48h after administration of the last dose. Spleen and liver were aseptically removed for determination of weight and number of CFU (log10) per organ. Our results demonstrated in vitro activities of clarithromycin and amikacin against the M. massiliense isolate. Treatment of BALB/c mice with clarithromycin prevented the development of hepatosplenomegaly, as well as the formation of granulomatous lesions for 15 days of infection with M. massiliense. Nevertheless, the clarithromycin and even amikacin were not effective, inducing no reduction of the bacterial population of M. massiliense in the organs. The in vitro susceptibility for bacteria isolated from organs of the mice demonstrated that there was no development of inducible resistance to clarithromycin and amikacin during 12 the treatment. In conclusion, there was no correlation between the activities in vitro and in vivo of clarithromycin and amikacin against M. massiliense.
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Mycobacterium massiliense
Citação
COLOMBO, Débora Corona. Avaliação da eficácia da claritromicina e da amicacina no tratamento da infecção experimental de camundongos BALB/c pelo Mycobacterium massiliense. 2012. 89 f. Dissertação (Mestrado em Doenças Infecciosas) - Programa de Pós-Graduação em Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, 2012.