In vitro synergistic properties of clavulanic acid, with ampicillin, amoxycillin and ticarcillin

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Abstract
Clavulanic acid (CA) was tested for in vitro synergistic activity with ampicillin, amoxycillin and ticarcillin against a wide range of organisms. Considerable extension of the spectrum of activity of all three antibiotics was seen in the presence of CA. Some strains of bacteria producing known types of β-lactamases were used and the effects of CA with ampicillin and ticarcillin were correlated with the inhibitory activity of CA against the isolated β-lactamases. MIC determinations with amoxycillin showed CA to be an effective synergist at 0.05 to I mg/1 against amoxycillin-resistant Branhamella catarrhalis (6 strains) and Neisseria gonorrhoeae (6 strains). Against amoxycillin-resistant strains of Haemophilus influenzae (15), Staphylococcus aureus (35), Klebsiella aerogenes (45) and Bacteroides fragilis (28), less than 2.5 mg/I of CA rendered amoxycillin active. Against strains of Escherichia coli (100) and K. aerogenes (32) producing a plasmid-mediated β-lactamase and Proteus mirabilis and Pr. vulgaris strains (23), although synergistic effects were seen with low concentrations of CA higher concentrations (2 to 10 mg/1) were required to render the majority of strains susceptible to amoxycillin. CA had low binding to human serum protein and the effect of serum, varying media and pH on the synergistic activity of CA + amoxycillin. was negligible. Slightly improved activity was seen when the inoculum size was reduced.