Therapy of Rhodococcus equi disseminated infections in nude mice

Abstract

Rhodococcus equi is a facultative, intracellular, gram-positive coccobacillus increasingly reported as an opportunistic pathogen in human immunodeficiency virus-positive patients. However, the optimal drug regimen for treating R. equi pulmonary or systemic infections is not yet known. Therefore, a model of intravenously infected nude mice with disseminated infection was created to study the efficacy of antibiotics alone or in combination as determined by the reduction of bacterial CPU per gram in the lungs and spleen after 4 and 11 days of treatment. The studied antibiotics possessing low MICs against R. equi strains were amikacin, ciprofloxacin, erythromycin, imipenem, minocycline, rifampin, and vancomycin. Vancomycin, imipenem, and rifampin were the most effective agents in monotherapy. On the other hand, amikacin, ciprofloxacin, erythromycin, and minocycline alone were not active in this model. The most active drug combinations were those including vancomycin. No antibiotic-resistant mutants were selected in vivo with treatment involving any drugs used alone or in combination. Although the treatment recommended until now for R. equi infections is rifamnpin plus erythromycin, this study suggests that antibiotic combinations which include vancomycin may be the most effective in vivo.

Neumonía cavitada por Rhodococcus equi en paciente inmunocomprometido no infectado por virus de inmunodeficiencia humana: Caso clínico y revisión

“…Algunos estudios han reportado susceptibilidad in vitro a ampicilina/sulbactam y amoxicilina/ácido clavulánico 27 . Nordmann, estudió la susceptibilidad de R. equi a antimicrobianos en ratas demostrando que vancomicina, imipenem y rifampicina eran las más efectivas, y que las combinaciones de antimicrobianos más activas incluían vancomicina 28 . Existen algunos reportes de resistencia a rifampicina 29 , imipenem 30 , y vancomicina 31 , por lo que es recomendable realizar estudio de susceptibilidad in vitro, a pesar de que no están estandarizados 2 .…”

Characterization of Mutations in the rpoB Gene Associated with Rifampin Resistance in Rhodococcus equi Isolated from Foals

“…Replacement of His526 by an aspartic acid led to low-level resistance (MIC, 8 g/ml), as did replacement of Asp516 by a valine (MIC, 2 g/ml) and Ser531 by a leucine (MIC, 8 g/ml) ( Table 1). Low-level resistance conferred in R. equi by replacement of Ser531 by a leucine is surprising since this high-frequency change is always associated with highlevel resistance in M. tuberculosis, S. aureus, and E. coli (12,13). In our study, only one strain harbored this mutation, and this result should be confirmed.…”

The medically important aerobic actinomycetes: epidemiology and microbiology

“…The combinations of imipenem and vancomycin and of imipenem and teicoplanin (another glycopeptide) were recently used successfully in the treatment of R. equi infections (107,491). Nordmann et al considered that trimethoprim-sulfamethoxazole and clarithromycin, which were not included in their study, may be interesting to study with this nude mouse model (419). These antimicrobial agents have low MICs against R. equi and antimicrobial activity against other pulmonary opportunistic pathogens (P. carinii and rapidly growing mycobacteria) that may coexist with R equi in AIDS patients.…”

“…In 1992, Nordmann et al (419) investigated the in vivo activity of several antimicrobial agents and antimicrobial combinations against R equi inoculated intravenously into nude mice that were congenitally T-lymphocyte deficient. The efficacy of the antimicrobial agents was determined on the basis of the reduction of bacterial CFU per gram in the lungs and spleen after 4 and 11 days of therapy.…”