Efficacy of ampicillin plus arbekacin in experimental rabbit endocarditis caused by an Enterococcus faecalis strain

V Kak1, S M Donabedian, M J Zervos

  • 1Research and Medical Service, John D. Dingell VA Medical Center, and Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

Insights

Ampicillin combined with arbekacin effectively treated experimental Enterococcus faecalis endocarditis. This combination significantly outperformed ampicillin alone or with gentamicin in reducing bacterial burden.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Enterococcus faecalis is a common cause of healthcare-associated infections, including endocarditis.
  • High-level gentamicin resistance (HLGR) in E. faecalis, often mediated by the aac(6 ewer)-Ie-aph(2newer)-Ia gene, complicates treatment.
  • Ampicillin is a standard treatment, but resistance mechanisms necessitate exploring alternative or combination therapies.

Purpose of the Study:

  • To evaluate the in vivo efficacy of ampicillin in combination with arbekacin compared to ampicillin alone or ampicillin plus gentamicin.
  • To assess treatment outcomes in a rabbit model of aortic-valve endocarditis caused by a specific ampicillin-susceptible, HLGR E. faecalis isolate (LC40).

Main Methods:

  • A rabbit model of aortic-valve endocarditis was established using Enterococcus faecalis LC40.
  • Bacterial vegetation counts were determined after treatment with ampicillin alone, ampicillin plus gentamicin, or ampicillin plus arbekacin.

Main Results:

  • The combination of ampicillin plus arbekacin significantly reduced mean bacterial vegetation counts compared to ampicillin alone.
  • Ampicillin plus arbekacin was also significantly more effective than ampicillin plus gentamicin in reducing bacterial vegetation.
  • Enterococcus faecalis LC40 was identified as an ampicillin-susceptible isolate with high-level gentamicin resistance due to the aac(6 ewer)-Ie-aph(2newer)-Ia gene.

Conclusions:

  • Ampicillin combined with arbekacin demonstrates superior efficacy over ampicillin alone and ampicillin plus gentamicin for treating experimental E. faecalis endocarditis.
  • Arbekacin represents a promising therapeutic option in combination with ampicillin for HLGR Enterococcus faecalis infections.

Related Concept Videos

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations01:15

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations

Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...