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Pharmacodynamic parameters of gentamicin and their effect on biological properties of gram-negative bacteria
1Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic.
Abstract:
The in vitro postantibiotic effect (PAE) and the postantibiotic effect of subinhibitory concentrations (PA SME) of gentamicin were investigated on clinical isolates of Salmonella typhimurium, Salmonella enteritidis and Pseudomonas aeruginosa. The PAE was induced by 2 x MIC and 4 x MIC of gentamicin for 0.5 h. The PA SME were studied by the addition of 0.1, 0.2 and 0.3 x MIC during the postantibiotic phase of the bacteria. The S. enteritidis strain did no regrow after affecting of supra-subinhibitory concentrations for 24 h with exception of the concentration 2 x MIC + 0.1 x MIC. The PAEs against P. aeruginosa were nearly identical for all the suprainhibitory concentrations tested (4.4-4.6 h) and no regrowth after PA SME was observed. The studied pharmacodynamic parameters decreased the surface hydrophobicity of Salmonella sp., mainly of S. enteritidis, evaluated by the ability to bind Congo red and by the aggregation in solutions of ammonium sulphate (SAT). Gentamicin in suprainhibitory concentrations expressively decreased the phospholipase C production--an important virulence factor of P. aeruginosa.
Insights
Gentamicin exposure reduced bacterial regrowth and virulence in Salmonella and Pseudomonas aeruginosa. This study explored gentamicin
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Gentamicin is a crucial antibiotic for treating Gram-negative bacterial infections.
- Understanding its postantibiotic effects (PAE) and postantibiotic subinhibitory effect (PA SME) is vital for optimizing treatment strategies.
- Salmonella and Pseudomonas aeruginosa are significant human pathogens with varying antibiotic resistance profiles.
Purpose of the Study:
- To investigate the in vitro PAE and PA SME of gentamicin against clinical isolates of Salmonella typhimurium, Salmonella enteritidis, and Pseudomonas aeruginosa.
- To evaluate the impact of gentamicin on bacterial surface hydrophobicity and virulence factor production.
Main Methods:
- Bacterial isolates were exposed to gentamicin at 2x and 4x minimum inhibitory concentrations (MIC) for 0.5 hours to induce PAE.
- PA SME was assessed by adding 0.1, 0.2, and 0.3x MIC gentamicin during the postantibiotic phase.
- Surface hydrophobicity was measured using Congo red binding and ammonium sulphate aggregation tests.
- Phospholipase C production was quantified as a measure of virulence.
Main Results:
- Salmonella enteritidis showed no regrowth after 24h exposure to supra-subinhibitory concentrations, except at 2x MIC + 0.1x MIC.
- Pseudomonas aeruginosa exhibited consistent PAEs (4.4-4.6h) across tested concentrations with no regrowth observed after PA SME.
- Gentamicin treatment reduced surface hydrophobicity in Salmonella species, particularly S. enteritidis.
- Supra-subinhibitory gentamicin concentrations significantly decreased phospholipase C production in P. aeruginosa.
Conclusions:
- Gentamicin demonstrates significant postantibiotic effects and PA SME against Salmonella and P. aeruginosa.
- These effects are associated with reduced bacterial surface hydrophobicity and decreased production of key virulence factors.
- The findings support the potential for optimized gentamicin dosing regimens to enhance therapeutic outcomes.