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[Experimental investigation on various administration methods of gentamicin. Comparison of the effect of gentamicin
Abstract:
We compared the efficacy of intravenously, intramuscularly administered or intravenously infused over 45 minutes gentamicin (GM) by the experimental system in rabbits using diffusion chambers. Serum concentrations of GM obtained with 3 administration methods were different, while the peak values after intramuscular injection and intravenous drip infusion were similar. Similar concentration time curves of GM in the chambers were revealed after intramuscular injection and intravenous infusion. No marked difference in 3 administration methods was showed in the effects on the growth of P. aeruginosa in the chamber. Viable bacterial number in the chambers decreased when the GM concentration in the chamber was 4--5 times of MIC, and thereafter regrowth was observed after the decrease of GM concentration in the chambers to 2--3 times of MIC. About 8 hours were required for growth to the base line value. In the leucocyte containing chambers, viable bacterial number similarly decreased, but the rate of regrowth was slow. About 12 hours were required for growth to the base line value. The regrowth rate in the GM containing chamber was similar to that in the antibiotic free chamber. From this result, it is suggested that, when the antibiotic concentration in the chamber is 1--2 times of MIC, antibiotic does not show the growth suppressive effect and the activating effect on phagocytosis of leucocytes in the environment closed to the practical pathological condition such as this model. For the patients with qualitative or quantitative abnormal changes of phagocyte, short interval of drug administration might be needed. For this purpose, intravenous drip infusion under monitoring of serum concentration is more suitable than intramuscular injection, which might be accompanied with severe pain and contracture of injected muscle.
Insights
Intravenous gentamicin infusion and intramuscular injection showed similar gentamicin (GM) peak serum concentrations. Gentamicin efficacy against P. aeruginosa was comparable across administration methods, with regrowth observed when concentrations fell below therapeutic levels.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Infectious Diseases
- Microbiology
Background:
- Gentamicin (GM) is a crucial antibiotic for treating bacterial infections.
- Optimizing gentamicin administration routes is essential for effective therapeutic outcomes.
- Understanding gentamicin's behavior in vivo, particularly its concentration-time profiles and impact on bacterial growth, is vital.
Purpose of the Study:
- To compare the efficacy of intravenous, intramuscular, and intravenous infused gentamicin in rabbits using a diffusion chamber model.
- To evaluate the pharmacokinetic and pharmacodynamic differences between various gentamicin administration methods.
- To assess the impact of gentamicin concentration on Pseudomonas aeruginosa growth and host immune cell function.
Main Methods:
- Rabbits were administered gentamicin via intravenous injection, intramuscular injection, or 45-minute intravenous infusion.
- Gentamicin concentrations in serum and diffusion chambers were measured.
- Pseudomonas aeruginosa growth and bacterial counts were monitored in chambers with and without leukocytes.
Main Results:
- Serum gentamicin concentrations varied by administration method, with similar peak levels for intramuscular injection and intravenous infusion.
- Similar gentamicin concentration-time curves were observed in diffusion chambers after intramuscular injection and intravenous infusion.
- Gentamicin demonstrated efficacy when concentrations were 4-5 times the minimum inhibitory concentration (MIC), but bacterial regrowth occurred as concentrations decreased to 2-3 times MIC.
Conclusions:
- Gentamicin administration route influences serum concentrations but shows comparable efficacy in this model.
- Antibiotic efficacy is concentration-dependent, with growth suppression and phagocytosis enhancement only occurring at higher concentrations (4-5x MIC).
- Intravenous drip infusion may be preferable to intramuscular injection for maintaining therapeutic gentamicin levels and potentially reducing patient discomfort.