Over the last few days, I have been treating a significant number of people with machete, bush knife and other significant compound lacerations. For the first 24-36 hours after wound closure these patients are given daily or BD IV Cephazolin with concomitant oral Probenecid.
I thought I'd share the rationale for using a common Gout drug, as a synergistic anti infective agent.
Let's start with Probenicid. This drug is a uricosuric drug that increases Uric Acid yexcretion in the urine. This is why it is primarily used in treating gout and high blood Uric acid.
But originally, Probenecid was developed to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.
Enter intravenous Cephalosporin drugs like Cephazolin.
Cephazolin is a renally excreted first generation Cephalosporin antibiotic which (like Penicillin) is categorised as a Beta-Lactam drug. This group of antibiotics works by inhibiting cell wall synthesis of the bacteria. They stick to special proteins in the bacteria cell wall and cause it to disintegrate and die. They are bactericidal, meaning that they kill the targeted bacteria (as opposed to inhibiting reproduction as other bacteriostatic antibiotics do).
It makes sense then that if these antibiotics are excreted via the kidneys, then their bioavailability would be lessened with healthy renal function. Enter Probenecid. In a patient given probenecid which inhibits antibiotic excretion through the kidneys, the Cephazolin stays in circulation in higher bactericidal concentrations for much longer, effectively increasing the antibiotic's half life, bioavailability and duration of action.
It's like levelling up in the game of Germ Warfare.
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