The Effect of Chronic Dosing of Probenecid on Cefazolin Serum Concentrations

Context

Probenecid can increase the serum concentrations of drugs that are eliminated principally by renal secretion such as cefazolin. The use of probenecid concurrently with cefazolin could result in elevated cefazolin levels above the minimum inhibitory concentration (MIC) and longer dosage intervals.

Objectives

Compare the serum levels produced by dosing cefazolin 2000mg IV Q8H to the levels produced by dosing cefazolin 2000mg IV OD plus probenecid 500mg PO QID.

Setting

Inpatients with infections requiring cefazolin treatment in a Community-based Teaching Hospital and outpatients presenting to the Emergency Department of the same hospital for the treatment of cellulitis.

Design

Patients in this prospective, non-randomized, unblinded study, were identified after an order was written for cefazolin 2000mg IV Q8H or 2000mg IV daily plus probenecid 500mg PO QID. For both study arms, a peak cefazolin level was drawn an hour after the infusion was started. Likewise, a cefazolin level was drawn 23 hours later prior to that next scheduled dose. Doses of cefazolin for days 2 through 4 were then administered as ordered. On day 5, peak and trough levels were drawn an hour after the infusion started and 23 hours later respectively.

Main Outcome Measures

Peak and trough cefazolin serum levels on days one and five. Treatment success. Treatment side effects.

Results

A total of 19 patients were prospectively assessed from April 2000 to February 2001. Sample # Daily cefazolin (n=14)(mg/L) Q8H cefazolin (n=5)(mg/L) Day #1 peakday #1 troughday #5 peakday #5 trough 151.50 +/- 41.832.00 +/- 1.86160.38 +/- 26.961.95 +/- 1.73 122.15 +/- 45.3118.65 +/- 13.90136.51 +/- 52.5216.98 +/- 6.67 There were 12 (86%) treatment successes in the once daily arm and 4 (80%) treatment successes in the three times daily arm.

Conclusions

Probenecid 500mg PO QID was effective in maintaining cefazolin serum levels above the MIC90 for Staphylococcus aureus for the duration of the 24 hour dosing interval. First dose effects of probenecid were not enhanced by repeated doses of probenecid and finally, once daily cefazolin plus probenecid was an effective treatment for cellulitis through an outpatient parenteral antibiotic therapy (OPAT) setting, producing acceptable side effects.

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