Efficacy of ampicillin combined with ceftriaxone and gentamicin in the treatment of experimental endocarditis due to Enterococcus faecalis with no high-level resistance to aminoglycosides.
OBJECTIVE
This study tests the usefulness of ceftriaxone combined with ampicillin as an alternative to ampicillin plus gentamicin for the treatment of experimental endocarditis due to Enterococcus faecalis without high-level resistance to aminoglycosides. It also determines whether adding ceftriaxone to ampicillin and gentamicin increases the effectiveness against experimental enterococcal endocarditis resulting from E. faecalis.


METHODS
Animals with catheter-induced endocarditis were infected intravenously with 108 cfu of the EF91 strain of E. faecalis and were treated for 3 days with ampicillin 2 g every 4 h administered as 'human-like' (H-L) pharmacokinetics, plus gentamicin 1 mg/kg every 8 h H-L, or ceftriaxone 2 g every 12 h H-L alone or combined with gentamicin 6 mg/kg every 24 h administered subcutaneously.


RESULTS
The results of therapy for experimental endocarditis resulting from EF91 showed that the combination of ampicillin plus ceftriaxone was as effective as ampicillin plus gentamicin. The triple combination did not improve on the overall efficacies of the two-drug combinations.


CONCLUSIONS
Because of its lower nephrotoxicity, ampicillin plus ceftriaxone may be a useful alternative therapy for E. faecalis endocarditis in selected patients.
Gavaldá
Joan
J
Infectious Diseases Research Laboratory, Infectious Diseases Division, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Avda. Vall d'Hebron, 119-129, 08035 Barcelona, Spain. gavalda@hg.vhebron.es
Onrubia
Pedro López
PL
Gómez
Mariá Teresa Martín
MT
Gomis
Xavier
X
Ramírez
José Luis
JL
Len
Oscar
O
Rodríguez
Dolors
D
Crespo
Manuel
M
Ruíz
Isabel
I
Pahissa
Albert
A
D000617:Aminoglycosides / Q000494:pharmacology*; D000667:Ampicillin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002443:Ceftriaxone / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D013293:Enterococcus faecalis / Q000187:drug effects*; D005839:Gentamicins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005839:Gentamicins; D010406:Penicillins; D002443:Ceftriaxone; D000667:Ampicillin