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Effect of clavulanic acid and/or polymorphonuclear neutrophils on amoxicillin bactericidal activity against
M Martín1, M L Gómez-Lus, L Aguilar
1Microbiology Department, School of Medicine, Universidad Complutense, Madrid, Spain.
Abstract:
The effects of polymorphonuclear neutrophils (PMNs) and/or clavulanic acid on the bactericidal activity of amoxicillin (at human serum achievable concentrations) against a serotype 3 penicillin-susceptible Streptococcus pneumoniae strain [minimal inhibitory concentration/minimal bactericidal concentration (MIC/MBC) values of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1) = 0.01/0.01 microgram/ml] and a serotype 9 penicillin-resistant strain [MIC/MBC of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1) = 1/2 microgram/ml] were studied. Against the penicillin-resistant strain, subinhibitory concentrations of amoxicillin reduced the growth rate; this effect was increased by the addition of clavulanic acid. A reduction of the penicillin-resistant initial inocula (3 x 10(6) cfu/ml) at subinhibitory concentrations was obtained only with amoxicillin plus clavulanic acid and PMNs. At suprainhibitory concentrations, both clavulanic acid and PMNs increased the bactericidal activity of amoxicillin, as evidenced by an increased reduction in the penicillin-resistant initial inocula. The combined effect of these antibiotics and immune defenses may help explain the maintenance of their clinical efficacy in respiratory tract infections, despite the increase in the incidence of penicillin-resistant pneumococci.
Insights
The combination of amoxicillin with clavulanic acid and polymorphonuclear neutrophils (PMNs) enhances bacterial killing of penicillin-resistant Streptococcus pneumoniae. This synergistic effect may explain amoxicillin
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Penicillin-resistant Streptococcus pneumoniae poses a significant challenge in treating respiratory tract infections.
- Amoxicillin is a common antibiotic, but its efficacy can be limited by bacterial resistance mechanisms.
Purpose of the Study:
- To investigate the combined effects of amoxicillin, clavulanic acid, and polymorphonuclear neutrophils (PMNs) on the bactericidal activity against Streptococcus pneumoniae.
- To evaluate these effects on both penicillin-susceptible and penicillin-resistant strains.
Main Methods:
- Determining minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) for amoxicillin, penicillin, and amoxicillin/clavulanic acid.
- Assessing the impact of subinhibitory and suprainhibitory concentrations of amoxicillin, with and without clavulanic acid and PMNs, on bacterial growth and survival.
Main Results:
- Subinhibitory amoxicillin reduced growth of the resistant strain, an effect amplified by clavulanic acid.
- Significant reduction of resistant pneumococci inocula at subinhibitory concentrations was achieved only with amoxicillin, clavulanic acid, and PMNs.
- Both clavulanic acid and PMNs boosted amoxicillin's bactericidal activity against the resistant strain at suprainhibitory concentrations.
Conclusions:
- Amoxicillin combined with clavulanic acid and host immune factors (PMNs) demonstrates enhanced bactericidal activity against penicillin-resistant Streptococcus pneumoniae.
- This synergistic action likely contributes to the sustained clinical effectiveness of amoxicillin-based therapies in respiratory infections, despite rising antibiotic resistance.