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Published on: October 23, 2016
In vitro activity of ampicillin and ceftriaxone against ampicillin-susceptible Enterococcus faecium
Michael P Lorenzo1, James M Kidd2, Stephen G Jenkins3,4
1Department of Pharmacy, Rhode Island Hospital, Providence, RI, USA.
Objectives:
To assess activity of the combination of ceftriaxone and ampicillin against clinical isolates of ampicillin-susceptible Enterococcus faecium.
Methods:
Ampicillin-susceptible E. faecium (n = 29) and Enterococcus faecalis (n = 10) collected from locations in the USA and France were used for this analysis. Susceptibility testing was performed by gradient diffusion strip (GDS) and broth microdilution (BMD). Synergy with the combination of ceftriaxone and ampicillin was assessed in all isolates using GDS crossing and double disc diffusion methods. Selected isolates (nine E. faecium and three E. faecalis) were assessed for synergy in time-kill studies using ampicillin alone and in combination with ceftriaxone.
Results:
In isolates of E. faecium, the median (range) ampicillin MIC by BMD was 0.5 (0.25-4) mg/L and by GDS it was 2 (1-8) mg/L. In E. faecalis, the median (range) ampicillin MIC by BMD was 0.5 (0.5-1) mg/L and by GDS it was 2 (0.75-3) mg/L. A total of 24/29 (82.8%) isolates of E. faecium displayed synergy by GDS and 22/29 (75.9%) by double disc diffusion. Seven of 10 (70%) isolates of E. faecalis displayed synergy by GDS and 4/10 (40%) by double disc diffusion. Time-kill studies found synergy in 3/9 (33.3%) E. faecium and 3/3 (100%) E. faecalis.
Conclusions:
In contrast to the demonstrated synergy in time-kill models of ceftriaxone and ampicillin for E. faecalis, this combination does not appear to provide uniform synergy in E. faecium. Antagonism was not observed. Clinical correlation is necessary and caution should be used when considering ampicillin and ceftriaxone for the treatment of infections caused by ampicillin-susceptible E. faecium.
Insights
The combination of ceftriaxone and ampicillin showed synergy in some ampicillin-susceptible Enterococcus faecium isolates, but not uniformly. Clinical use requires caution for E. faecium infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Enterococcus faecium and Enterococcus faecalis are common causes of healthcare-associated infections.
- Ampicillin is a standard treatment for susceptible enterococcal infections.
- Ceftriaxone is a third-generation cephalosporin with activity against some Gram-positive bacteria.
Purpose of the Study:
- To evaluate the in vitro activity of the combination of ceftriaxone and ampicillin against clinical isolates of ampicillin-susceptible Enterococcus faecium.
- To compare the synergistic activity of this combination against E. faecium and Enterococcus faecalis.
Main Methods:
- Clinical isolates of ampicillin-susceptible E. faecium (n=29) and E. faecalis (n=10) were tested.
- Susceptibility testing was performed using gradient diffusion strip (GDS) and broth microdilution (BMD).
- Synergy was assessed using GDS crossing, double disc diffusion, and time-kill studies.
Main Results:
- Ampicillin MICs for E. faecium ranged from 0.25-4 mg/L (BMD) and 1-8 mg/L (GDS).
- Synergy between ceftriaxone and ampicillin was observed in 82.8% of E. faecium isolates by GDS and 75.9% by double disc diffusion.
- Time-kill studies showed synergy in 33.3% of E. faecium and 100% of E. faecalis isolates.
Conclusions:
- The combination of ceftriaxone and ampicillin demonstrated variable synergy against ampicillin-susceptible E. faecium.
- While synergy was consistent in E. faecalis, it was not uniform in E. faecium.
- Clinical correlation is needed, and caution is advised when using this combination for E. faecium infections.
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