• Penicillins And others

  • Beta-lactamase inhibitors

    • Clavulanic Acid

      • Clavulanic Acid

      • Mechanism of Action

        • Clavulanic acid is the prototype "suicide inhibitor" derived from Streptomyces clavuligerus.

          • Clavulanate is then is suicide substrate for many class A beta-lactamases, binding to the enzyme's active site then hydrolyzed the former reactive intermediate which covalently inactivates the enzyme.

          • As result of this inactivation, the beta-lactamase is prevented from destroying co-administered penicillins or cephalosporins.

            • Clavulanic acid itself exhibits very limited intrinsic antibacterial activity, but in combination it extends coverage of companion antibiotics to beta-lactamase producing strains.

            • Some beta-lactamases like AmpC beta-lactamases (cephalosporinases associated with many of the Enterobacteriaceae) are not well inhibited by clavulanate.²

      • Pharmacokinetics

        • Clavulanate is co-formulated most commonly with amoxicillin.

          • Clavulanateis well absorbed orally (especially when taken at the start of a meal) and reaches peak levels usually within 1–2 hours.

          • The drug half-life is ~1 hour, similar to amoxicillin.^3,4 

            • Clavulanate is distributed into tissues such as lung, middle ear fluid, sinuses, and urine, achieving therapeutic concentrations in these sites.⁵

            • The drug combination (amoxicillin/clavulanate)⁶ undergoes partial hepatic metabolism; a significant fraction (25%-40%) is eliminated unchanged renally⁵, and dose adjustments are recommended in severe renal dysfunction.⁶  Current amoxicillin/clavulanic acid formulations use a 4:1 amoxicillin-to-clavulanate ratio.⁶

      • Therapeutic Uses

        • The addition of clavulanic acid to amoxicillin broadens the spectrum by including many ß-lactamase-producing bacteria.

        • The amoxicillin-clavulanate combination is appropriate for many community-acquired infections, including:

          • Respiratory Tract Infections

            • Infections include otitis media, sinusitis, bronchitis, and pneumonia.

            • Causative organisms include H. influenzae or Moraxella catarrhalis producing ß-lactamase.^1,6

              • Haemophilus influenzae (left) and Moraxella catarrhalis (right)

                "This digitally-colorized photomicrographs depicts numerous, Gram-negative, Haemophilus influenzae coccobacilli." Attribution CDC: Public Health Image Library (PHIL) CDC/William B. Cherry, Ph.D. 1964 https://phil.cdc.gov/Details.aspx?pid=23029	"This photomicrographs of the Gram-stained specimen, revealed the presence of numerous, Gram-negative, or Moraxella catarrhalis bacteria. "This bacterium is an aerobic, diplococcal organism, often found inhabiting the human upper respiratory tract as a commensal resident." Attribution CDC: Public Health Image Library (PHIL) CDC/ Dr. W.A. Clark 1977 https://phil.cdc.gov/Details.aspx?pid=15012

          • Skin and Tissue Infections

            • Examples could include infected animal/human bites as well as diabetic foot infections.

            • These concerns apply when staphylococci and anaerobes might be present.¹  

          • Urinary Tract Infections

            • Here the concern centers on those infections resulting from Enterobactericeae including some Extended-Spectrum-Beta-Lactamase (ESBL)-Producing strains under circumstances in which alternative drugs would not be suitable.⁷

              • Enterobactericeae include any number of Gram-negative bacteria including: Klebsiella, Citrobacter, Enterobacter, Salmonella, Escherichia coli, Proteus, Serratia and others.

              • Enterobacteriaceae are part of normal gut bacteria.

                • However they also represented common cause of urinary tract infections with some species responsible for diarrhea.

                • Life-threatening complications may be associated with spread to the bloodstream.

                • Enterobacteriaceae may develop antibacterial resistance including resistance to carbapenem groups of antibiotics.

                  • That is, Enterobactericeae may be producing carbapenemase.⁹

          • Dental Infections and Bite Wound Prophylaxis/Treatment

            • The rationale here has to do with the activity of amoxicillin/clavulanate combination against oral anaerobes.⁸

August, 2025