Combination of Ceftriaxone and Ampicillin for the Treatment of Enterococcal Endocarditis: A Qualitative Systematic Review.
OBJECTIVE
The aim of this systematic review is to review all human trials assessing the efficacy and safety of ampicillin and ceftriaxone for enterococcal endocarditis and to discuss the clinical implications of the findings.


METHODS
MEDLINE (1946-), EMBASE (1974-), CENTRAL, Google Scholar, and the World Health Organization Clinical Trials Registry Platform were searched through January 2017 using the search terms ampicillin, penicillin, ceftriaxone, cephalosporin, enterococ*, and endocarditis. Unpublished studies were eligible for inclusion. Additional references were identified from literature citations.


METHODS
Clinical trials in humans that reported on clinical efficacy or adverse outcomes with ceftriaxone and ampicillin therapy in patients with enterococcal endocarditis were included. Case reports, nonhuman, and non-English studies were excluded.


RESULTS
Four observational clinical studies were identified. One examined the effects of ceftriaxone and ampicillin alone, and 3 compared the therapy to the current standard of care, ampicillin and gentamicin. The studies had small sample sizes and were not adequately designed or powered to establish noninferiority or equivalence to the current standard of care. Rates of clinical cure with ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours were similar to those of ampicillin and gentamicin. Ampicillin and ceftriaxone therapy was well tolerated with low rates of renal failure (0%-33%).


CONCLUSIONS
The evidence to support the use of ampicillin and ceftriaxone for enterococcal endocarditis is not definitive. In the absence of compelling evidence, clinicians may consider ampicillin and ceftriaxone in patients with Enterococcus faecalis infection at high risk for nephrotoxicity or those with aminoglycoside-resistant pathogens.
1 University of British Columbia, Vancouver, BC, Canada.
Shaylee C
SC
Peterson
1 University of British Columbia, Vancouver, BC, Canada.|2 Vancouver General Hospital, Vancouver, BC, Canada.
Tim T Y
TTY
Lau
1 University of British Columbia, Vancouver, BC, Canada.|3 Children's and Women's Health Centre of British Columbia, Vancouver, BC, Canada.
Mary H H
MHH
Ensom
D000667:Ampicillin / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D013293:Enterococcus faecalis / Q000302:isolation & purification; D005839:Gentamicins / Q000627:therapeutic use; D006801:Humans; D051437:Renal Insufficiency / Q000139:chemically induced
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D002443:Ceftriaxone; D000667:Ampicillin
Enterococcus; ampicillin; ceftriaxone; cephalosporin; combination drug therapy; endocarditis; penicillin