Effect of low concentrations of clavulanic acid on the in-vitro activity of amoxycillin against beta-lactamase-producing Branhamella catarrhalis and Haemophilus influenzae.
Concentrations of amoxycillin/clavulanic acid achievable in the respiratory tract following oral dosage were assessed for in-vitro activity against beta-lactamase-producing strains of Branhamella catarrhalis and Haemophilus influenzae. In agar-dilution studies, 8 mg amoxycillin/l was required to inhibit 45 strains of beta-lactamase-producing B. catarrhalis, whereas all the strains were inhibited by 0.5 mg amoxycillin/l in the presence of 0.01 mg clavulanic acid/l. Similarly, 0.1 mg amoxycillin plus 0.05 mg clavulanic acid/l were bactericidal against beta-lactamase-producing strain of B. catarrhalis and prevented regrowth within 24 h. In tests against 43 beta-lactamase-producing strains of H. influenzae, concentrations of up to 128 mg amoxycillin/l were required for inhibition, whereas 32 strains (75%) were fully sensitive to amoxycillin (MIC 0.5 mg/l) in the presence of 0.12 mg clavulanic acid/l. These concentrations of amoxycillin/clavulanic acid were also bactericidal for a beta-lactamase-producing strain of H. influenzae. The study therefore showed that amoxycillin/clavulanic acid, at concentrations similar to those likely to be achieved in the respiratory tract following oral dosage, was bactericidal in vitro for beta-lactamase-producing isolates of B.catarrhalis and H. influenzae.
Cooper
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CE
Beecham Pharmaceuticals Research Division, Betchworth, Surrey, UK.
Slocombe
B
B
White
A R
AR
D000658:Amoxicillin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019980:Amoxicillin-Potassium Clavulanate Combination; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004359:Drug Therapy, Combination / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000201:enzymology; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000201:enzymology; D009391:Nephelometry and Turbidimetry / Q000379:methods; D013997:Time Factors; D001618:beta-Lactamases / Q000096:biosynthesis*
D002969:Clavulanic Acids; D019818:Clavulanic Acid; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin; D001618:beta-Lactamases