Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide‐susceptible and macrolide‐resistant Rhodococcus equi isolates

Abstract

The objectives of this study were to determine the serum and pulmonary disposition of telithromycin in foals and to determine the minimum inhibitory concentration (MIC) of telithromycin against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. A single dose of telithromycin (15 mg/kg of body weight) was administered to six healthy 6-10-week-old foals by the intragastric route. Activity of telithromycin was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells using a microbiological assay. The broth macrodilution method was used to determine the MIC of telithromycin, azithromycin, clarithromycin and erythromycin against R. equi. Following intragastric administration, mean +/- SD time to peak serum telithromycin activity (T(max)) was 1.75 +/- 0.76 h, maximum serum activity (C(max)) was 1.43 +/- 0.37 microg/mL, and terminal half-life (t(1/2)) was 3.81 +/- 0.40 h. Telithromycin activity, 4 h postadministration was significantly higher in BAL cells (50.9 +/- 14.5 microg/mL) than in PELF (5.07 +/- 2.64 microg/mL), and plasma (0.84 +/- 0.25 microg/mL). The MIC(90) of telithromycin for macrolide-resistant R. equi isolates (8 microg/mL) was significantly higher than that of macrolide-susceptible isolates (0.25 microg/mL). The MIC of telithromycin for macrolide-resistant isolates (MIC(50)=4.0 microg/mL) was significantly lower than that of clarithromycin (MIC(50)=24.0 microg/mL), azithromycin (MIC(50)=256 microg/mL) and erythromycin (MIC(50)=24 microg/mL).

Perfil de suscetibilidade antimicrobiana e presença do gene vapA em Rhodococcus equi de origem humana, ambiental e equina

“…O crescimento no núme-ro de isolados apresentando resistência a rifampicina e eritromicina foi descrito em um estudo com cepas de R. equi isoladas durante 10 anos, onde foi possível verificar que 4% destas apresentaram resistência a estes antimicrobianos (Giguére et al 2010). Desta forma, ressalta-se a importância de estudos que avaliem a ação de diferentes agentes antimicrobianos como alternativa em casos de resistência a esses fármacos (Javsicas et al 2010).…”

Pharmacokinetics of macrolides in foals

“…The concentrations of azithromycin, clarithromycin, gamithromycin, tulathromycin, and tilmicosin were higher in PELF than in plasma (Table ; Jacks et al ., ; Womble et al ., ,b; Suarez‐Mier et al ., ; Javsicas et al ., ; Berghaus et al ., ; Peters et al ., ). The large concentration of macrolides in these lung compartments may be relevant from the antimicrobial effect standpoint.…”

“…The pharmacokinetic profiles of erythromycin, clarithromycin, and azithromycin have been previously characterized (Jacks et al ., , ; Davis et al ., ; Womble et al ., ; Suarez‐Mier et al ., ). Several recent studies have expanded the pharmacokinetic knowledge about macrolides, including telithromycin, tulathromycin, tilmicosin, and gamithromycin, in foals (Womble et al ., ; Scheuch et al ., ; Javsicas et al ., ; Venner et al ., ; Berghaus et al ., ). The purpose of this article is to review the PK of these macrolides in foals.…”

Rhodococcus equi Parte 1: epidemiologia, manifestações clínicas, diagnóstico e tratamento

“…A limitação do sucesso da terapia antimicrobiana contra o R. equi, principalmente em isolados resistentes aos antibióticos de eleição, tem estimulado o investimento em estudos de novas alternativas de tratamento da doença, através do teste de novas drogas, como a telitromicina (JAVSICAS et al, 2010).…”