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Synergistic post-antibiotic effect of amikacin and beta-lactam antibiotics on Enterococcus faecalis
B Isaksson1, H Hanberger, R Maller
1Department of Infectious Diseases, University Hospital, Linköping, Sweden.
Abstract:
The in-vitro post-antibiotic effect (PAE) of amikacin alone and in combination with ceftazidime, ceftriaxone and piperacillin was studied for two strains of Enterococcus faecalis using a bioluminescent assay of bacterial ATP. The two strains of E. faecalis were resistant to amikacin, ceftazidime and ceftriaxone but sensitive to piperacillin. The bacterial cultures were incubated with the beta-lactam antibiotics for 1 h and concentrations of amikacin between 2-64 mg/l were then added. Thereafter, incubation continued with the combinations for one more hour. After dilution, regrowth was monitored by measuring bacterial ATP every hour. Increasing concentrations of amikacin (2-64 mg/l), ceftazidime (8-32 mg/l) and ceftriaxone (32-128 mg/l) resulted in little or no PAE (0-0.3 h) on these strains. PAEs of 0.5 to 1.6 h resulted from exposure to piperacillin (4-32 mg/l). In combination amikacin and piperacillin increased the PAE to 5.5 h. A synergistic PAE was also seen when the enterococci were exposed to amikacin combined with ceftazidime or ceftriaxone in concentrations close to the MICs of the latter antibiotics.
Insights
The post-antibiotic effect (PAE) of amikacin and beta-lactam antibiotics on Enterococcus faecalis was investigated. Amikacin combined with piperacillin showed a synergistic PAE, enhancing bacterial inhibition.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Enterococcus faecalis exhibits resistance to common antibiotics.
- Understanding antibiotic interactions is crucial for effective treatment strategies.
Purpose of the Study:
- To evaluate the in-vitro post-antibiotic effect (PAE) of amikacin alone and in combination with beta-lactam antibiotics against Enterococcus faecalis.
- To assess the synergistic effects of antibiotic combinations on bacterial regrowth.
Main Methods:
- Utilized a bioluminescent assay measuring bacterial ATP to determine PAE.
- Exposed two amikacin-resistant Enterococcus faecalis strains to amikacin, ceftazidime, ceftriaxone, and piperacillin, both individually and in combination.
- Monitored bacterial regrowth hourly after antibiotic exposure and dilution.
Main Results:
- Amikacin, ceftazidime, and ceftriaxone showed minimal PAE on the tested strains.
- Piperacillin demonstrated a moderate PAE (0.5-1.6 h).
- The combination of amikacin and piperacillin significantly increased PAE to 5.5 h, indicating synergy.
Conclusions:
- Amikacin combined with piperacillin exhibits a synergistic post-antibiotic effect against Enterococcus faecalis.
- Combinations of amikacin with ceftazidime or ceftriaxone also showed synergistic PAE near their minimum inhibitory concentrations.
- These findings suggest potential for enhanced therapeutic strategies using specific antibiotic combinations.