Efficacy of ampicillin plus ceftriaxone in the treatment of experimental endocarditis due Enterococcus faecalis highly-resistant to aminoglycosides.

  1. Gavaldà, J. 13
  2. Torres, C. 4
  3. Tenorio, C. 4
  4. López, P. 1
  5. Zaragoza, M. 4
  6. Capdevila, Josep Antón. 1
  7. Almirante, B. 1
  8. Ruiz, F. 4
  9. Borrell, N. 1
  10. Gomis, X. 1
  11. Pigrau, C. 1
  12. Baquero, F. 2
  13. Pahissa, A. 1
  1. 1 Universitat Autònoma de Barcelona
    info

    Universitat Autònoma de Barcelona

    Barcelona, España

    ROR https://ror.org/052g8jq94

  2. 2 Hospital Ramón y Cajal
    info

    Hospital Ramón y Cajal

    Madrid, España

    ROR https://ror.org/050eq1942

  3. 3 Hospital Vall d'Hebron
    info

    Hospital Vall d'Hebron

    Barcelona, España

    ROR https://ror.org/03ba28x55

  4. 4 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

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Revista:
Antimicrobial Agents and Chemotherapy

ISSN: 0066-4804

Año de publicación: 1999

Volumen: 43

Número: 3

Páginas: 639-646

Tipo: Artículo

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PMID: 10049280 SCOPUS: 2-s2.0-0032979084 WoS: WOS:000078843700033 GOOGLE SCHOLAR

Otras publicaciones en: Antimicrobial Agents and Chemotherapy

Resumen

The purpose of this work was to evaluate the in vitro possibilities of ampicillin-ceftriaxone combinations for 10 Enterococcus faecalis strains with high-level resistance to aminoglycosides (HLRAg) and to assess the efficacy of ampicillin plus ceftriaxone, both administered with humanlike pharmacokinetics, for the treatment of experimental endocarditis due to HLRAg E. faecalis. A reduction of 1 to 4 dilutions in MICs of ampicillin was obtained when ampicillin was combined with a fixed subinhibitory ceftriaxone concentration of 4 μg/ml. This potentiating effect was also observed by the double disk method with all 10 strains. Time-kill studies performed with 1 and 2 μg of ampicillin alone per ml or in combination with 5, 10, 20, 40, and 60 μg of ceftriaxone per ml showed a ≥2 log 10 reduction in CFU per milliliter with respect to ampicillin alone and to the initial inoculum for all 10 E. faecalis strains studied. This effect was obtained for seven strains with the combination of 2 μg of ampicillin per ml plus 10 μg of ceftriaxone per ml and for six strains with 5 μg of ceftriaxone per ml. Animals with catheter-induced endocarditis were infected intravenously with 10 8 CFU of E. faecalis V48 or 10 5 CFU of E. faecalis V45 and were treated for 3 days with humanlike pharmacokinetics of 2 g of ampicillin every 4 h, alone or combined with 2 g of ceftriaxone every 12 h. The levels in serum and the pharmacokinetic parameters of the humanlike pharmacokinetics of ampicillin or ceftriaxone in rabbits were similar to those found in humans treated with 2 g of ampicillin or ceftriaxone intravenously. Results of the therapy for experimental endocarditis caused by E. faecalis V48 or V45 showed that the residual bacterial titers in aortic valve vegetations were significantly lower in the animals treated with the combinations of ampicillin plus ceftriaxone than in those treated with ampicillin alone (P < 0.001). The combination of ampicillin and ceftriaxone showed in vitro and in vivo synergism against HLRAg E. faecalis.